United States Prevention, Pesticides EPA738-R-98-013
Environmental Protection And Toxic Substances December 1998
Agency (7508W)
&EPA Reregistration
Eligibility Decision (RED)
Bromoxynil
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, D.C. 20460
OFFICE OF
PREVENTION, PESTICIDES
AND TOXIC SUBSTANCES
CERTIFIED MAIL
Dear Registrant:
I am pleased to announce that the Environmental Protection Agency has completed its
reregistration eligibility review and decisions on the pesticide chemical case 2070 which includes
the active ingredients bromoxynil phenol and bromoxynil octanoate. The enclosed Reregistration
Eligibility Decision (RED), which was approved on September 23, 1998, contains the Agency's
evaluation of the data base of this chemical, its conclusions of the potential human health and
environmental risks of the current product uses, and its decisions and conditions under which
these uses and products will be eligible for reregistration. The RED includes the data and labeling
requirements for products for reregistration. It also includes requirements for additional data
(generic) on the active ingredient to confirm the risk assessments.
To assist you with a proper response, read the enclosed document entitled "Summary of
Instructions for Responding to the RED." This summary also refers to other enclosed documents
which include further instructions. You must follow all instructions and submit complete and
timely responses. The first set of required responses is due 90 days from the receipt of this
letter. The second set of required responses is due 8 months from the date of this letter.
Complete and timely responses will avoid the Agency taking the enforcement action of suspension
against your products.
Please note that the Food Quality Protection Act of 1996 (FQPA) became effective on
August 3, 1996, amending portions of both pesticide law (FIFRA) and the food and drug law
(FFDCA). This RED takes into account, to the extent currently possible, the new safety standard
set by FQPA for establishing and reassessing tolerances. However, it should be noted that in
continuing to make reregistration determinations during the early stages of FQPA implementation,
EPA recognizes that it will be necessary to make decisions relating to FQPA before the
implementation process is complete. In making these early case-by-case decisions, EPA does not
intend to set broad precedents for the application of FQPA. Rather, these early determinations
will be made on a case-by-case basis and will not bind EPA as it proceeds with further policy
development and any rulemaking that may be required.
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If EPA determines, as a result of this later implementation process, that any of the
determinations described in this RED are no longer appropriate, the Agency will pursue whatever
action may be appropriate, including but not limited to reconsideration of any portion of this
RED.
If you have questions on the product specific data requirements or wish to meet with the
Agency, please contact the Special Review and Reregi strati on Division representative Karen
Jones (703) 308-8047. Address any questions on required generic data to the Special Review and
Reregi strati on Division representative, Linda Werrell (703) 308-8033.
Sincerely,
Lois A. Rossi, Director
Special Review and
Reregi strati on Division
Enclosures
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SUMMARY OF INSTRUCTIONS FOR RESPONDING TO
THE REREGISTRATION ELIGIBILITY DECISION (RED)
1 DATA CALL-IN (PCI) OR "90-DAY RESPONSE"-If generic data are required for
reregi strati on, a DCI letter will be enclosed describing such data. If product specific data are
required, a DCI letter will be enclosed listing such requirements. If both generic and product
specific data are required, a combined Generic and Product Specific DCI letter will be enclosed
describing such data. However, if you are an end-use product registrant only and have been
granted a generic data exemption (GDE) by EPA, you are being sent only the product specific
response forms (2 forms) with the RED. Registrants responsible for generic data are being sent
response forms for both generic and product specific data requirements (4 forms). You must
submit the appropriate response forms (following the instructions provided) within 90 days
of the receipt of this RED/DCI letter; otherwise, your product may be suspended.
2 TIME EXTENSIONS AND DATA WAIVER REOUESTS-No time extension requests
will be granted for the 90-day response. Time extension requests may be submitted only with
respect to actual data submissions. Requests for time extensions for product specific data should
be submitted in the 90-day response. Requests for data waivers must be submitted as part of the
90-day response. All data waiver and time extension requests must be accompanied by a full
justification. All waivers and time extensions must be granted by EPA in order to go into effect.
3 APPLICATION FOR REREGISTRATION OR "8-MONTH RESPONSE"-You must
submit the following items for each product within eight months of the date of this letter
(RED issuance date).
a. Application for Reregistration (EPA Form 8570-1). Use only an original application
form. Mark it "Application for Reregistration." Send your Application for Reregistration (along
with the other forms listed in b-e below) to the address listed in item 5.
b. Five copies of draft labeling which complies with the RED and current regulations
and requirements. Only make labeling changes which are required by the RED and current
regulations (40 CFR 156.10) and policies. Submit any other amendments (such as formulation
changes, or labeling changes not related to reregi strati on) separately. You may, but are not
required to, delete uses which the RED says are ineligible for reregi strati on. For further labeling
guidance, refer to the labeling section of the EPA publication "General Information on Applying
for Registration in the U.S., Second Edition, August 1992" (available from the National Technical
Information Service, publication #PB92-221811; telephone number 703-487-4650).
c. Generic or Product Specific Data Submit all data in a format which complies with
PR Notice 86-5, and/or submit citations of data already submitted and give the EPA identifier
(MRID) numbers. Before citing these studies, you must make sure that they meet the
Agency's acceptance criteria (attached to the DCI).
d Two copies of the Confidential Statement of Formula (CSF) for each basic and
each alternate formulation. The labeling and CSF which you submit for each product must
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comply with P.R. Notice 91-2 by declaring the active ingredient as the nominal concentration.
You have two options for submitting a CSF: (1) accept the standard certified limits (see 40 CFR
§158.175) or (2) provide certified limits that are supported by the analysis of five batches. If you
choose the second option, you must submit or cite the data for the five batches along with a
certification statement as described in 40 CFR §158.175(e). A copy of the CSF is enclosed;
follow the instructions on its back.
e Certification With Respect to Data Compensation Requirements Complete and
sign EPA form 8570-31 for each product.
4 COMMENTS IN RESPONSE TO FEDERAL REGISTER NOTICE-Comments
pertaining to the content of the RED may be submitted to the address shown in the Federal
Register Notice which announces the availability of this RED.
5 WHERE TO SEND PRODUCT SPECIFIC PCI RESPONSES (90-DAY) AND
APPLICATIONS FOR REREGISTRATION (8-MONTH RESPONSES)
By U.S. Mail:
Document Processing Desk (RED-SRRD-PRB)
Office of Pesticide Programs (7504C)
EPA, 401 M St. S.W.
Washington, D.C. 20460-0001
By express:
Document Processing Desk (RED-SRRD-PRB)
Office of Pesticide Programs (7504C)
Room 266A, Crystal Mall 2
1921 Jefferson Davis Hwy.
Arlington, VA 22202
6. EPA'S REVIEWS—EPA will screen all submissions for completeness; those which are not
complete will be returned with a request for corrections. EPA will try to respond to data waiver
and time extension requests within 60 days. EPA will also try to respond to all 8-month
submissions with a final reregi strati on determination within 14 months after the RED has been
issued.
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REREGISTRATION ELIGIBILITY DECISION
Bromoxynil
LISTB
CASE 2070
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TABLE OF CONTENTS
REREGISTRATION ELIGIBILITY DECISION TEAM i
EXECUTIVE SUMMARY v
I. INTRODUCTION 1
II. CASE OVERVIEW 2
A. Chemical Overview 2
B. Use Profile 2
C. Estimated Usage of Pesticide 4
D. Data Requirements 4
E. Regulatory History 4
III. SCIENCE ASSESSMENT 6
A. Physical Chemistry Assessment 6
B. Human Health Assessment 7
1. Toxicology Assessment 7
a. Acute Toxicity 7
b. Subchronic Toxicity 8
c. Chronic Toxicity and Carcinogenicity 12
d. Developmental Toxicity 15
e. Reproductive Toxicity 20
f. Mutagenicity 21
g. Neurotoxicity 26
h. Immunotoxicity 26
i. Metabolism 27
j. Dermal Penetration 27
k. Other Toxic Endpoints 28
1. Toxicity Equivalence 29
m. Dose-Response Assessment 29
n. Toxicological Endpoints for Risk Assessmen 32
2. Exposure Assessment and Risk Assessment 35
a. Dietary Exposure - Food Sources 35
b. Dietary (food sources) Risk Characterization 44
c. Dietary Exposure - Drinking Water 46
d. Aggregate Risk 49
e. Cummulative Risk 50
3. Occupational Exposure and Risk Characterization 51
a. Handler Exposures and Risk 51
b. Postapplication Exposures and Risk 65
c. Epidemiological Information 66
C. Environmental Assessment 67
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1. Ecological Toxicity Data 67
a. Toxicity to Terrestrial Animals 67
b. Mammals 69
c. Insects 69
d. Toxicity to Aquatic Animals 69
e. Toxicity to Plants 71
2. Environmental Fate 73
a. Environmental Fate Assessment 73
b. Environmental Fate and Transport 74
c. Water Resources 78
3. Exposure and Risk Characterization 87
a. Ecological Exposure and Risk Characterization 87
b. Environmental Risk Characterization 102
IV. RISK MANAGEMENT AND REREGISTRATION DECISION 106
A. Determination of Eligibility 106
1. Eligibility Decision 107
2. Eligible and Ineligible Use 107
B. Regulatory Position 107
1. Tolerance Reassessment 107
2. Summary of Risk Management Decisions Ill
a. Human Health Ill
b. Environmental 113
c. Restricted Use Classification 116
d. Reference Dose Exceedance 116
e. Endangered Species Statement 117
f. Labeling Rationale 117
g. Spray Drift Advisory 117
h. Occupational and Residential Labeling Rationale/Risk Mitigation
118
3. Occupational-Use Products (WPS Uses and Non-WPS Uses) 119
4. Post-Application/Entry Restrictions 120
a. Occupational-Use Products (WPS Uses) 120
b. Occupational-Use Products (NonWPS Uses) 122
C. Other Labeling Requirements 123
V. ACTIONS REQUIRED OF REGISTRANTS 123
A. Manufacturing-Use Products 123
1. Additional Generic Data Requirements 123
2. Labeling Requirements for Manufacturing-Use Products 123
a. Formulation Statements 123
b. Plantback Intervals 124
B. End-Use Products 124
1. Additional Product-Specific Data Requirements 124
2. Labeling Requirements for End-Use Products 125
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a. PPE/Engineering Control Requirements for Pesticide Handlers
125
b. Products Intended Primarily for Occupational Use (WPS and
nonWPS) 125
c. Entry Restrictions 126
3. Products Intended Primarily for Occupational Use 127
a. WPS Uses 127
b. Non-WPS Uses 128
4. Labeling for Products Intended Primarily for Occupational Use . . 128
a. Application Restrictions 128
b. Engineering Controls 129
c. User Safety Requirements 129
5. User Safety Recommendations 129
a. Spray Drift Labeling 130
C. Existing Stocks 133
VI. APPENDICES 135
A. Table of Use Patterns Subject to Reregistration 136
B. Table of the Generic Data Requirements and Studies Used to Make the
Reregistration Decision 191
C. Citations Considered to be Part of the Data Base Supporting the Reregistration
Decision 197
D. Generic Data Call-In 217
1. Generic Data Call-In Chemical Status Sheet 233
2. Generic DCI Response Forms Inserts (Insert A) plus Instructions
235
3. Requirements Status and Registrants' Response Forms (Insert B) plus
Instructions 239
E. Product Specific Data Call-In 245
1. Product Specific Chemical Status Sheets 258
2. Data Call-in Response Form for the Product Specific Data(Form A
inserts) Plus Instructions 260
3. Product Specific Requirement Status and Registrant's Response Forms
(Form B inserts) and Instructions 264
4. EPA Batching of End-Use Products for Meeting Data Requirements for
Reregistration 271
5. List of All Registrants Sent This Data Call-In (insert) Notice 274
F. List of Available Related Documents and Electronically Available Forms.
275
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REREGISTRATION ELIGIBILITY DECISION TEAM
Office of Pesticide Programs:
Biological and Economic Analysis Division
Margaret Cogdell
Neil Anderson
Environmental Fate and Effects Division
Renee Costello
William R. Effland
David Wells
R. David Jones
Kevin Poff
Liz Resek
Health Effects Division
Richard Griffin
Ed Budd
Christina Swartz
Brian Steinwand
Olga Odiott
Jane Smith
Alan Nielsen
Barbara Madden
Michelle Centra
Tim Leighton
Registration Division
Tobi Colvin-Snyder
Special Review and Reregistration Division
Linda M. Werrell
Tom Luminello
Office of General Counsel
Jonathan J. Fleuchaus
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GLOSSARY OF TERMS AND ABBREVIATIONS
ADI Acceptable Daily Intake. A now defunct term for reference dose (RfD).
AE Acid Equivalent
a.i. Active Ingredient
ARC Anticipated Residue Contribution
CAS Chemical Abstracts Service
CI Cation
CNS Central Nervous System
CSF Confidential Statement of Formula
DFR Dislodgeable Foliar Residue
ORES Dietary Risk Evaluation System
DWEL Drinking Water Equivalent Level (D WEL) The DWEL represents a medium specific (i.e. drinking
water) lifetime exposure at which adverse, non carcinogenic health effects are not anticipated to
occur.
EEC Estimated Environmental Concentration. The estimated pesticide concentration in an environment,
such as a terrestrial ecosystem.
EP End-Use Product
EPA U.S. Environmental Protection Agency
FAO/WHO Food and Agriculture Organization/World Health 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
GLC Gas Liquid Chromatography
GM Geometric Mean
GRAS Generally Recognized as Safe as Designated by FDA
HA Health Advisory (HA). The HA values are used as informal guidance to municipalities and other
organizations when emergency spills or contamination situations occur.
HOT Highest Dose Tested
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 animal, e.g., mg/kg.
LDlo Lethal Dose-low. Lowest Dose at which lethality occurs.
LEL Lowest Effect Level
LOG Level of Concern
LOD Limit of Detection
LOEL Lowest Observed Effect Level
MAI Multiple Active Ingredient
MATC Maximum Acceptable Toxicant Concentration
MCLG Maximum Contaminant Level Goal (MCLG) The MCLG is used by the Agency to regulate
contaminants in drinking water under the Safe Drinking Water Act.
ug/g Micrograms Per Gram
mg/L Milligrams Per Liter
MOE Margin of Exposure
MP Manufacturing-Use Product
MPI Maximum Permissible Intake
ill
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GLOSSARY OF TERMS AND ABBREVIATIONS
MRID Master Record Identification (number). EPA's system of recording and tracking studies submitted.
N/A Not Applicable
NOEC No effect concentration
NPDES National Pollutant Discharge Elimination System
NOEL No Observed Effect Level
NOAEL No Observed Adverse Effect Level
OP Organophosphate
OPP Office of Pesticide Programs
Pa Pascal, the pressure exerted by a force of one newton acting on an area of one square meter.
PADI Provisional Acceptable Daily Intake
PAG Pesticide Assessment Guideline
PAM Pesticide Analytical Method
PHED Pesticide Handler's Exposure Database
PHI Preharvest Interval
ppb Parts Per Billion
PPE Personal Protective Equipment
ppm Parts Per Million
PRN Pesticide Registration Notice
Q!* The Carcinogenic Potential of a Compound, Quantified by the EPA's Cancer Risk Model
RBC Red Blood Cell
RED Reregistration Eligibility Decision
REI Restricted Entry Interval
RfD Reference Dose
RS Registration Standard
RUP Restricted Use Pesticide
SLN Special Local Need (Registrations Under Section 24 © 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 Layer Chromatography
TMRC Theoretical Maximum Residue Contribution
torr A unit of pressure needed to support a column of mercury 1 mm high under standard conditions.
/j.g/L Micrograms per liter
WP Wettable Powder
WPS Worker Protection Standard
IV
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EXECUTIVE SUMMARY
The U. S. Environmental Protection Agency has completed its reregi strati on eligibility
decision for the pesticide bromoxynil, which includes the active ingredients bromoxynil phenol and
bromoxynil octanoate. The decision includes a comprehensive reassessment of the required target
data and the use patterns of currently registered products. Bromoxynil is a herbicide used mainly on
field corn, wheat and grain crops to control a variety of grasses and broadleaf weeds. The Agency
has concluded that no uses, as prescribed in this document, will cause unreasonable risks to humans
or the environment and therefore, all products are eligible for reregi strati on. Due to deficiencies in
the database, two studies and surface water monitoring are required to confirm the Agency's risk
assessment conclusions.
Background
Bromoxynil is a selective contact foliage applied herbicide used to control variety of
grasses broadleaf weeds. Bromoxynil inhibits photosynthetic electron transport and also uncouples
oxidative phosphorylation in mitochondria, thereby stopping energy production and negatively
affecting plant respiration. Agricultural crop use sites include: food crops (e.g., garlic/onions); food
and feed crops (e.g., mint, flax, spearmint, peppermint, barley, oats, rye, triticale, wheat, sorghum,
cotton, and field, sweet, and pop corn); and feed crops (e.g., fodder/hay, grass, millet (proso), alfalfa,
sudangrass). Non-food uses include: fallow/idleland; outdoor industrial areas; nonagricultural
uncultivated areas/soils; ornamental herbaceous plants; commercial/industrial lawns; ornamental (non-
residential) lawns and turf; golf course turf; and sod farms. Bromoxynil is formulated as an
emulsifiable concentrate, soluble concentrate, and a gel formulation (in water soluble packages). The
application rates for crop uses range from 0.25 Ib ai/acre to 0.5 Ib ai/acre. There are no residential
uses for this herbicide.
Human Health Risk
Bromoxynil phenol has been classified as a Group C, possible human carcinogen. Rapid
conversion of the ester forms of the chemical (heptanoate and octanoate) permit the risk assessment
to be based on exposure to the phenol. The Reference Dose (RfD) for bromoxynil phenol is 0.015
mg/kg/day based on the threshold NOEL/LOEL of 1.5 mg/kg/day in a 12 month-chronic oral toxicity
study in dogs. Chronic dietary risk is estimated to occupy less than one percent (1%) of the chronic
RfD. The aggregate dietary risk of cancer to the general population from residues in food and water,
associated with long-term exposure to bromoxynil was estimated to be 1.7 x 10"6. The estimated
aggregate acute dietary risk, calculated as Margins of Exposure (MOE), all exceed 10,000.
Therefore, significant concerns related with acute dietary exposure are not predicted.
The Agency has determined the aggregate risk from bromoxynil meets the certainly of no
harm standard. EPA believes that the bromoxynil risk is "negligible". Regarding the aggregate
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carcinogenic risk, the Agency does not apply the negligible risk standard as a bright line test because
of the lack of precision in quantitative cancer risk assessment. There are a significant number of
uncertainties in both the toxicological data used to derive the cancer potency of a substance and in
the data used to measure and calculate exposure.
In accordance with the Food Quality Protection Act of 1996, the Agency uses a weight-of-
evidence approach to determine whether to retain, reduce, or remove the 10X safely factor required
for possible enhanced sensitivity to infants and children. The database for the developmental toxicity
of bromoxynil is robust. Developmental effects (supernumerary ribs being the most sensitive
indicator) have been observed in developmental and reproductive studies. The Agency concluded
that reliable data support using a 100-fold uncertainty factor to assess bromoxynil dietary risk for all
populations with the exception of females 13+. Upon review of the extensive developmental
toxicological database for this chemical, a concern for in utero developmental effects was noted. In
order to provide a sufficient margin of safety for the developing fetus, the 10-fold safety factor for
enhanced sensitivity to infants and children was retained for females 13+ thus requiring a 1000-fold
uncertainty factor for this population subgroup. All MOEs calculated exceeded 10,000 and,
therefore, developmental effects to any sub-population are not predicted.
Occupational Handlers and Workers
EPA has established a short- and intermediate-term dermal NOEL for bromoxynil based on
developmental effects and has also classified bromoxynil as a Group C quantifiable carcinogen. The
handler dermal risk assessment based on the Pesticide Handler's Exposure Database (PHED) data
for mixers/loaders/applicators indicates that short- and intermediate-term dermal risks and cancer
risks are acceptable (i.e., greater than 100) if such handlers wear chemical-resistant gloves in addition
to baseline attire (long-sleeve shirt, long pants, shoes, and socks) while performing mixing and
loading tasks and baseline attire while performing applicator tasks. For all tasks, other than mixing
and loading, the risks are acceptable for handlers with baseline attire. The cancer risk for the non-
commercial handlers (grower) is 2 x 10"6 or lower for all scenarios with baseline attire, except that
mixers and loaders must also wear chemical-resistant gloves. The cancer risk for commercial handlers
is 1.9 x 10"5 or lower for all scenarios with baseline attire, except that mixers and loaders must also
wear chemical-resistant gloves. The highest cancer risk estimated from these particular scenarios was
1.9 X 10"5 (commercial mixer/loaders for aerial applications and sprinkler irrigation). However, these
mixer/loader risk estimates do not account for the potential exposure reduction from the use of
"wide-mouth" containers (designed to reduce spillage) for mixer/loaders. At the present time the
PHED database does not allow the Agency to quantify this risk mitigation measure, however the use
of the "wide-mouth" containers would likely reduce the reported risk further. In addition to provide
an additional margin of safety, EPA is requiring mixers and loaders to wear a chemical-resistant
apron. Although EPA has no data to specifically assess the exposure reduction to mixers/loaders
afforded by a chemical-resistant apron, the Agency is persuaded that the exposure reduction would
be significant. Available data indicate that the preponderance of non-hand exposure to mixers/loaders
is to the front torso.
VI
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Environmental Fate
Bromoxynil octanoate was found to be chemically and physically similar to bromoxynil
heptanoate. Both esters rapidly degrade to bromoxynil per se. Bromoxynil octanoate is mobile and
non-persistent. It dissipates in the environment by abiotic hydrolysis, photolytic degradation, and
microbially-mediated metabolism in both the aerobic and anaerobic environments. Bromoxynil
octanoate readily hydrolyzes to bromoxynil phenol and then further degrades to CO2. The hydrolysis
half-life for degradation of bromoxynil octanoate ranges from 1 day up to 34 days. Degradation is
increased by exposure to sunlight and aerobic and anaerobic degradative processes. In two terrestrial
field dissipation studies, the observed half-life of bromoxynil octanoate was approximately 14 days
in California and 1 day in North Carolina.
Based on the available data, the Agency concludes that the potential for ground water
contamination from bromoxynil octanoate is low; it does not exhibit the mobility or persistence
characteristics of pesticides that are normally found in ground water. Environmental fate studies
indicate that bromoxynil (phenol and octanoate) should not persist in surface waters. The aerobic
aquatic metabolism study shows rapid degradation with a half-life of <12 hours.
Environmental Risk
The overall risk to birds (and to insects) exposed to bromoxynil octanoate is expected to be
low. For mammals the calculated risk ranges from medium to high, based on known developmental
effects. However, exposure levels high enough to cause chronic developmental effects are believed
to be unlikely to occur. The acute risk to both freshwater and estuarine fish is expected to be low;
chronic risk is expected to be minimal. The overall acute risk to freshwater invertebrates is expected
to be medium. The overall risk to both endangered and non-endangered terrestrial and semi-aquatic
plants is expected to be medium. And finally, the risk to aquatic vascular plants is uncertain at this
time due to a lack of data, while risk to nonvascular plants is expected to be minimal. Additional
testing for aquatic vascular plants is required.
The Agency is requiring additional, confirmatory data be submitted. These data include the
following: aquatic plant toxicity; and chronic estuarine/marine fish and invertebrates testing.
Additionally, this reregi strati on eligibility decision document reiterates the requirement, Federal
Register May 13, 1998, for the submission of an acceptable surface water monitoring program.
Before reregistering the products containing bromoxynil, the Agency is requiring that product
specific data, revised Confidential Statements of Formula (CSF) and revised labeling be submitted
within eight months of the issuance of this document. These data include product chemistry for each
registration and acute toxicity testing. After reviewing these data and any revised labels and finding
them acceptable in accordance with Section 3(c)(5) of FIFRA, the Agency will reregister a product.
Those products which contain other active ingredients will be eligible for reregistration only when
the other active ingredients are determined to be eligible for reregistration.
vn
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I. INTRODUCTION
In 1988, the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) was amended to
accelerate the reregi strati on of products with active ingredients registered prior to November 1,1984.
The amended Act provides a schedule for the reregi strati on process to be completed in nine years.
There are five phases to the reregi strati on process. The first four phases of the process focus on
identification of data requirements to support the reregi strati on of an active ingredient and the
generation and submission of data to fulfill the requirements. The fifth phase is a review by the U.S.
Environmental Protection Agency (referred to as "the Agency") of all data submitted to support
reregi strati on.
FIFRA Section 4(g)(2)(A) states that in Phase 5 "the Administrator shall determine whether
pesticides containing such active ingredient are eligible for reregi strati on" before calling in data on
products and either reregistering products or taking "other appropriate regulatory action." Thus,
reregi strati on involves a thorough review of the scientific data base 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 the pesticide meets the "no unreasonable adverse
effects" criterion of FIFRA.
On August 3, 1996, the Food Quality Protection Act of 1996 (FQPA) (Public Law 104-170)
was signed into law. FQPA amends both the Federal Food, Drug, and Cosmetic Act (FFDCA), 21
U.S.C. 301 et seq., and the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA), 7
U.S.C. 136 et seq. The FQPA amendments went into effect immediately. As a result, EPA is
embarking on an intensive process, including consultation with registrants, States, and other
interested stakeholders, to make decisions on the new policies and procedures that will be appropriate
as a result of enactment of FQPA. This process will include a more in depth analysis of the new
safety standard and how it should be applied to both food and non-food pesticide applications. The
FQPA did not, however, amend any of the existing reregi strati on deadlines in section 4 of FIFRA.
The Agency, will therefore, continue its ongoing reregi strati on program while it continues to
determine how best to implement FQPA.
This document presents the Agency's decision regarding the reregi strati on eligibility of the
registered uses of bromoxynil. The document consists of six sections. Section I is the introduction.
Section II describes bromoxynil, its uses, data requirements and regulatory history. Section III
discusses the human health and environmental assessment based on the data available to the Agency.
Section IV presents the reregi strati on decision for bromoxynil. Section V discusses the reregi strati on
requirements for bromoxynil. Finally, Section VI contains the Appendices which support this
Reregistration Eligibility Decision. Additional details concerning the Agency's review of applicable
data are available on request.
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II. CASE OVERVIEW
A. Chemical Overview
The following active ingredients are covered by this Reregi strati on Eligibility
Decision:
! Common Name: Bromoxynil phenol
Bromoxynil octanoate
! Chemical Name: [3,5-dibromo-4-hydroxybenzonitrile]
! Chemical Family: Benzonitrile
! CAS Registry Number: Phenol (1689-84-5)
Octanoate (1689-99-2)
! OPP Chemical Code: Phenol (035301)
Octanoate (035302)
! Empirical Formula: Phenol (C7H3Br2NO)
Octanoate (C15H17Br2NO2)
! Trade and Other Names: Buctril
! Basic Manufacturer: Rhone-Poulenc
B. Use Profile
The following is information on the currently registered uses with an overview of use
sites and application methods. A detailed table of these uses of bromoxynil is in Appendix
A.
Type of Pesticide: Postemergence herbicide
Use Sites: TERRESTRIAL FOOD CROP: Grain Crops (triticale), Root Crop
Vegetables (garlic, onion)
TERRESTRIAL FOOD+FEED CROP:
Beverage Crops (mint), Crops Grown for Oil (flax) Fiber Crops
(Flax), Flavoring and Spice Crops (peppermint, spearmint), Grain
Crops (barley, corn field, oats, rye, sorghum, triticale, wheat),
Groups of Agricultural Crops Which Cross Established Crop
Groupings (cotton), Specialized Field Crops (corn, pop; corn, sweet)
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TERRESTRIAL FEED CROP: Forage Grasses (grass,
forage/fodder/hay, millet (proso), sorghum, sudangrass), Forage
Legumes and Other Nongrass Forage Crops (alfalfa), Groups of
Agricultural Crops Which Cross Established Crop Groupings (grasses
grown for seed)
TERRESTRIAL NON-FOOD CROP: Agricultural Uncultivated
Areas (agricultural fallow/idleland), Groups of Agricultural Crops
Which Cross Established Crop Groupings (grasses grown for seed),
Nonagricultural Uncultivated Areas (industrial areas (outdoor),
nonagricultural uncultivated areas/soils), Ornamental Herbaceous
Plants, Ornamental Lawns and Turf (commercial/industrial lawns,
golf course turf, ornamental lawns and turf, ornamental sod farm
(turf))
Target Pests: Annual Sowthistle, Black Nightshade, Blue Mustard, Broadleaf
Weeds, Buffalobur, Canada Thistle, Coast Fiddleneck, Common
Cocklebur, Common Groundsel, Common Lambsquarters, Common
Ragweed, Common Tarweed, Corn Chamomile, Corn Gromwell,
Cow Cockle, Eastern Black Nightshade, FiddleneckField, Penny cress,
Giant Ragweed, Green Smartweed, Hairy Nightshade, Hemp
Sesbania, Henbit, Ivyleaf, Morningglory, Jimsonweed, Knawel,
Kochia, Ladysthumb, London Rocket, Mayweed, Pennsylvania
Smartweed, Pepperweed, Prostrate Knotweed, Prostrate Spurge,
Redroot Pigweed, Russian Thistle, Shepherdspurse, Silverleaf,
Nightshade, Spiny Pigweed, Spurweed, Sunflower, Tall
Morningglory, Tall Waterhemp, Tartary Buckwheat, Tumble Mustard,
Velvetleaf, Venice Mallow, Wild Buckwheat, Wild Mustard, Wild
Radish, Yellow Woodsorrel
Formulation Types Registered:
Technical
Crystalline/Solid 87.30 to 95.00%
Liquid 87.30%
End Use Product
Emulsifiable Concentrate 15.74 to 33.40%
Liquid 15.74 to 33.40%
Method of Application:
Equipment - Aircraft; Boom sprayer; Center pivot irrigation; Ground; Hand
move irrigation; Moving wheel irrigation; Solid set irrigation;
Spray sprinkler irrigation
-------
Method- Band treatment; Broadcast; Chemigation; Directed spray; Ground
spray; Low volume spray (concentrate); Spray
Timing - Cutting; Dormant; Established plantings; Postemergence; Prebloom;
Preemergence; Preplant; Seedling stage; When needed
C. Estimated Usage of Pesticide
This section summarizes the best usage estimates available for the pesticide uses of
bromoxynil. These estimates are derived from a variety of published and proprietary sources
available to the Agency. The data, reported on an aggregate and site (crop) basis, reflect
annual fluctuations in use patterns as well as the variability that result from using data from
various information sources.
Summary of Quantitative Usage Estimates for Bromoxynil
An estimated 2.5 to 3.0 million pounds a.i. of bromoxynil are applied annually
in the U.S., with usage appearing to be quite variable year to year. Most of this usage (91%)
is allocated to three crops: field corn (57%), wheat (26%) and barley (8%). The remaining
usage is spread among other grain crops, alfalfa, mint, onions and some minor sites. Crops
with the highest percentages of acreage treated are garlic (81%), mint (55%), onions (36%)
and flax (13%).
D. Data Requirements
Data required for the reregi strati on of bromoxynil are outlined in 40 CFR 158.150
through 158.740 for those uses supported by the registrant. There have been five (5) data
call-ins (DCI) for this chemical. The first issued on March 28, 1983, required chronic
feeding, oncogenicity and teratogenicity studies in one species. The second was issued May
3,1984 for environmental fate data, including hydroly si s, photodegredation, mobility and field
dissipation. The third DCI was issued in June of 1987 to investigate the possibility of
polyhaloginated dibenzo-p-dioxins and dibenzofurans (PCDDs and PCDFs) in technical
bromoxynil and bromoxynil octanoate. The fourth DCI was issued on August 9, 1988, and
required dermal teratology studies in the rat. Finally, in 1991, a DCI was issued for
bromoxynil requiring product chemistry data, fish and invertebrate studies and various crop
studies. Appendix B includes all data requirements identified by the Agency which are
required to support reregi strati on of currently registered uses.
E. Regulatory History
Bromoxynil was first registered in the United States in 1965 for use as a herbicide
to control grassy and broadleaf weeds on wheat and barley. In 1972, tolerances were
established for field and fodder crops, meat, and meat byproducts of cattle, goats, hogs,
horses and sheep. Throughout the 1980's, a series of additional tolerances were established
-------
for a variety of vegetable, field and fodder crops. Five DCIs were issued over the course of
the late 1980s and early 1990s (see above for further details). Regarding dioxin, it was
determined by the Agency that the data submitted in response to the 1987 dioxin DCI
indicated that PCDDs and PCDFs are not present in the bromoxynil products at levels above
the Agency-specified limits of quantitation (LOQs). The Agency has determined that analysis
for PCDDs and PCDFs is not required for bromoxynil octanoate produced by the UK
manufacturing process. The data received from the 1991 DCI are discussed in the toxicity
assessment of this report and are considered in this reregi strati on decision.
When the reregistration case for bromoxynil was opened, case 2070, bromoxynil
phenol, butyrate, heptanoate and octanoate were all incorporated. Subsequently, bromoxynil
butyrate registrations were voluntarily canceled by the registrant in 1989 due to concerns
related to developmental toxicity. Therefore, bromoxynil butyrate is not included as a part
of this reregistration decision. At that time, the Agency also had concerns for potential risks
to workers mixing, loading, and/or applying bromoxynil products. To reduce these
exposures, the registrant undertook several actions. These included label amendments,
development of a new jug (to prevent splashing) and the supply of gloves included in product
packaging.
Further changes to the reregistration case came when the registrant decided not to
support the heptanoate. However, in 1993, the registrant applied for a new heptanoate
registration, which was granted. Since only those pesticides registered prior to 1984 are
subject to reregistration, the bromoxynil heptanoate is not considered a reregistration
chemical and is not specifically incorporated for this reregistration action. However, there
are two products which include both the heptanoate and the octanoate forms of bromoxynil.
For human health, all risk values are based on exposure to the phenol (for the two labels that
contain both the octanoate and heptanoate, both esters were converted to the phenol and the
exposure calculation made). All esters of the chemical are considered to be lexicologically
similar to the phenol and, in fact, rapid conversion of the esters to the phenol occurs in the
environment. The exposure estimates, therefore, incorporate exposure to the octanoate and
the heptanoate included in the two combined labels. The percent crop treated used in the
dietary exposure considers all esters of bromoxynil.
In May 1995 (60 FR 27414), the Agency established a time-limited tolerance
under section 408 of the Federal Food, Drug and Cosmetic Act (FFDCA), for residues of
bromoxynil on cottonseed. This tolerance expired on April 1, 1997. On May 13, 1998, the
Agency issued a tolerance for cotton use. In that Notice, the maximum allowable cotton
acreage that can be treated with bromoxynil was increased from 400,000 acres (3% of cotton
acreage) to 1.3 million acres (10% of cotton acreage). This document incorporates the
information published in the May 13, 1998 Federal Register Notice.
-------
III. SCIENCE ASSESSMENT
A. Physical Chemistry Assessment
Description of Chemical
Bromoxynil [3,5-dibromo-4-hydroxybenzonitrile] is a selective herbicide which is registered
for application as the octanoic or heptanoic acid esters for postemergence control of broadleaf weeds
in various crops. There are no active products or registered uses for bromoxynil butyrate
(Shaughnessy No. 035303).
Bromoxynil Phenol
Empirical Formula: C7H3Br2NO
Molecular Weight: 276.9
CAS Registry No.: 1689-84-5
Shaughnessy No.: 035301
OH
Br
CN
15H17Br2NO2
Bromoxynil octanoate
Empirical Formula: C
Molecular Weight: 403.0
CAS Registry No.: 1689-99-2
Shaughnessy No.: 035302
o
o
* L,
CN
Bromoxynil heptanoate
Empirical Formula: C14H15Br2NO2
Molecular Weight: 389.0
CAS Registry No.: 56634-95-8
Shaughnessy No.: 128920
o
o
CN
Identification of Active Ingredient
Bromoxynil is a white to slightly yellow crystalline solid with a melting point of approximately
190 C. Bromoxynil is slightly soluble in water at 211 ppm and in hexane at 178 ppm, and is soluble
in 1-octanol (4.97 g/100 L) and methanol (8.51 g/100 mL) at 25 C.
-------
Bromoxynil octanoate and bromoxynil heptanoate are brown crystalline solids with melting
points of approximately 44 C. The esters are virtually insoluble in water. Bromoxynil octanoate is
soluble in acetone or ethanol (10 g/100 mL), benzene or xylene (70 g/100 mL), chloroform or
dichloromethane (80 g/100 mL), and cyclohexanone (55 g/100 mL). Bromoxynil heptanoate is
soluble in 1-octanol (33.8 g/100 mL), methanol (52.4 g/100 mL), hexane (77.5 g/100 mL),
dichloromethane (111.1 g/100 mL), acetone (106.4 g/100 mL), and ethyl acetate (102.7 g/100 mL).
The octanoic and heptanoic acid esters are readily hydrolyzed to bromoxynil under alkaline
conditions.
Manufacturing-Use Products
The registered bromoxynil and bromoxynil ester MPs are presented below in Table 1.
Table 1: Technical Registrations for Bromoxynil
Formulation
EPA Reg. No.
Registrant
Comments
Bromoxynil (035301)
94% T
95% T
94% T
264-229
264-473
33688-8
Rhone-Poulenc AG Company
CFPI Agro
TGAI produced by Rhone-Poulenc in the
United States.
Repackaged from a registered product.
Bromoxynil octanoate (035302)
95% T
87.3% T
87.3% FI
264-442
264-395
33688-9
Rhone-Poulenc AG Company
CFPI Agro
Produced by the UK manufacturing process.
Repackaged from a registered product.
B. Human Health Assessment
1. Toxicology Assessment
The hazard assessment addresses issues and data related to bromoxynil phenol and its
octanoic acid ester, bromoxynil octanoate, both of which are currently registered with EPA and have
been supported for reregi strati on. Technically, the term "bromoxynil phenol" is a misnomer, the
phenolic form of bromoxynil being known more properly simply as "bromoxynil". Nevertheless, the
term "bromoxynil phenol" will be used to eliminate possible confusion and to clearly distinguish the
phenolic form of the compound from all other forms of the compound. The toxicology data in
support of this reregi strati on case are complete and adequate.
a. Acute Toxicity
The acute toxicity test results and toxicity categories for bromoxynil phenol and bromoxynil
octanoate are presented in the following tables.
-------
Table 2a. Acute Toxicity Results for Bromoxynil Phenol
Study
Acute Oral LD50 (rat)1'"
Acute Dermal LD50 (rabbit)2'3
Acute Inhalation LC50 (rat)3'3
Eye Irritation (rabbit)4'"
Dermal Irritation (rabbit)5'3
Skin Sensitization (guinea pig)6'3
Result
81 mg/kg(M)
93 mg/kg (F)
>2000 mg/kg (M and F)b
0.269 mg/L (M)
0.150mg/L(F)
cornea! opacity, iritis, conjunctiva! irritation
no irritation
negative
Category
II
III
II
II
IV
N/A
M MRIDs 00124758, 00124758, 43014701, 00124758, 00124758 and 42718701, respectively; 3 Test material
was technical grade bromoxynil phenol;b Abraded skin; N/A = not applicable
Table 2b. Acute Toxicity Results for Bromoxynil Octanoate
Study
Acute Oral LD50 (rat)1'3
Acute Dermal LD50 (rabbit)2'3
Acute Inhalation LC50 (rat)3'3
Eye Irritation (rabbit)4'3
Dermal Irritation (rabbit)5'3
Skin Sensitization (guinea pig)6'3
Result
400 mg/kg (M)
238 mg/kg (F)
> 2000 mg/kg (M)b
13 10 mg/kg (F)c
0.81 mg/L (M)
0.72 mg/L (F)
cornea! opacity,
conjunctival irritation
slight erythema
positive (modified draize test)
Category
II
II
III
III
IV
N/A
>-6 MRIDs 00124112, 00124112, 42167101, 00124112, 00124112 and 41879801, respectively; 3 Test material
was technical grade bromoxynil octanoate; b Abraded skin; ° Intact skin; N/A = not applicable
b. Subchronic Toxicity
Table 3 summarizes the available subchronic toxicity information. The subchronic studies are
described in detail following the table.
-------
Table 3: Subchronic Toxicity Studies
MRID# (Species)
Doses Tested (mg/kg/day)
Systemic Toxicity (mg/kg/day)
Bromoxynil Phenol - Oral
41469101 (Rat)
42553401
(Mouse)
43 166701 (Dog)
0, 28, 58, 168 (a*)
0,35, 76, 250 (?)
0, 1.3,3.9, 13,39, 130,390
(cT, ?)
0, 1, 5, 8, 12, 16, 20, 30,
40, 50(d", ?)
NOEL (a") = 28
(?) < 35 (not established)
LOEL (a") = 58 based on I ALT, I AST, I Alkaline Phosphatase
(?) = 35 based on 1 body weight gain
NOEL (d") = 3.9
(?) =13
LOEL (o") = 13 based on t liver weights, hepatocellular
hypertrophy
(?) = 39 based on t liver weights, hepatocellular
hypertrophy, degeneration and vacuolation
NOEL (o") -< 1 (not established)
(?)=!
LOEL (o") = 1 based on 1 body weight gain
(?) = 5 based on 1 body weight gain, panting, liquid
feces
Bromoxynil Phenol - Dermal
42272301
(Rabbit)
0, 30, 300, 1000
(cT, ?)
NOEL(o", ?)= 1000
LOEL (d", ?) > 1000 (not established)
Bromoxynil Octanoate - Oral
42411901 (Rat)
42869701,
43700201 (Dog)
0006 1179 (Dog)
0, ll,45,91(cf)
0, 13,55, 111(?)
0,0.43, 1.43,7.14
(rf, ?)
0, 1, 5, 25
(cT, ?)
NOEL (o") = 45
(?) =13
LOEL (d") = 91 based on 1 body weight gain, 1 serum total
protein, 1 globulins, t degeneration/necrosis of cardiac myofibers
(?) = 55 based on 1 body weight gain, t liver weights
NOEL (a", ?) = 0.43
LOEL (a", ?) = 1.43 based on 1 body weight gain
NOEL(o", ?) < 5
LOEL (d", ?) = 5 based on occasional panting
Bromoxynil Octanoate - Dermal
42346201
(Rabbit)
0, 30, 300, 1000
(rf, ?)
NOEL (a", ?)= 1000
LOEL (a", ?) > 1000 (not established)
Bromoxynil Phenol
In a 13-week subchronic feeding study, technical grade bromoxynil phenol was administered
in the diet to groups of 15 male and 15 female Sprague Dawley rats at dose levels of 0 (control), 400,
755 or 1456 ppm (equivalent to 0, 28, 58 or 168 mg/kg/day in males and 0, 35, 76 or 250 mg/kg/day
in females). Decreased body weight gain (22%), increased alanine aminotransferase (ALT), increased
aspartate aminotransferase (AST), and increased alkaline phosphatase were observed in males at 755
ppm. At 1456 ppm, signs of severe toxicity and excessive mortality (10/15 died) were also observed
in males. Treatment-related effects were recorded in females at all dose levels. These effects were
decreased body weight gain at 400 ppm (19%) and at 755 ppm (34%), increased alkaline phosphatase
-------
at 755 and 1456 ppm, and signs of severe toxicity and excessive mortality (15/15 died) at 1456 ppm.
For male rats, the NOEL is 400 ppm (28 mg/kg/day) and the LOEL is 755 ppm (58 mg/kg/day),
based on decreased body weight gain, increased ALT, increased AST and increased alkaline
phosphatase. For female rats, no NOEL was determined in this study (<400 ppm; <35 mg/kg/day).
The LOEL is 400 ppm (3 5 mg/kg/day), based on decreased body weight gain. This study is of limited
usefulness because a NOEL was not determined for females, excessive mortality occurred in males
and females at the highest dose level tested, and an insufficient number of tissues was microscopically
examined. (MRID 41469101)
In a 12-week range-finding study, technical grade bromoxynil phenol was administered in the
diet to groups of 10 male and 10 female CD-I mice at dose levels of 0 (control), 10, 30, 100, 300,
1000 or 3 000 ppm (equivalent to 0, 1.3,3.9, 13,39, 130 or 390 mg/kg/day). Increased liver weights
and hepatocellular (HC) hypertrophy were observed in males at 100 ppm and higher. Degeneration
and vacuolization were also observed in the hepatocytes of males at 300 ppm and higher and
decreased body weight gain and additional pathological effects in the liver were observed at 1000
ppm and higher. At the highest dose level tested (3000 ppm), all male mice died during the first week
of testing. For female mice, increased liver weights, HC hypertrophy, HC degeneration and HC
vacuolization were observed at 300 ppm and higher. At dose levels of 1000 and 3000 ppm, effects
for females were the same as for males. For male mice, the NOEL is 30 ppm (3.9 mg/kg/day) and
the LOEL is 100 ppm (13 mg/kg/day), based on increased liver weights and HC hypertrophy. For
female mice, the NOEL is 100 ppm (13 mg/kg/day) and the LOEL is 3 00 ppm (39 mg/kg/day), based
on increased liver weights, HC hypertrophy, HC degeneration and HC vacuolization. This study was
a range-finding study. Ophthalmologic, hematologic, clinical chemistry and urinalyses examinations
were not conducted. In addition, a complete histopathologic examination was not performed. (MRID
42553401)
In a 13-week range-finding study, technical grade bromoxynil phenol was administered orally
in gelatin capsules to groups of 2 male and 2 female beagle dogs at dose levels of 0 (control), 1, 5,
8, 12, 16, 20, 30, 40 or 50 mg/kg/day. Treatment related decreased body weight gain was observed
in males at all dose levels tested. At 5 mg/kg/day, occasional panting and liquid feces were also noted
and at 8 and 12 mg/kg/day, frequent panting, occasional salivation, unsteady gait, decreased
erythrocyte count, decreased hemoglobin, decreased packed cell volume, and increased urea nitrogen
were observed. Dose levels of 16 mg/kg/day and higher were clearly excessive and caused mortality
and/or signs of severe toxicity. Decreased body weight gain, occasional panting and liquid feces were
observed in females at 5 mg/kg/day. At 8 mg/kg/day and higher, effects in females were the same as
in males. For males, no NOEL was determined in this study (<1 mg/kg/day). The LOEL is 1
mg/kg/day for males, based on decreased body weight gain. For females, the NOEL is 1 mg/kg/day
and the LOEL is 5 mg/kg/day, based on decreased body weight gain, panting and liquid feces. This
study was a range-finding study. Only 2 dogs/sex/dose level were used and an insufficient number
of tissues was microscopically examined in the control group and at dose levels of 12 mg/kg/day and
lower. (MRID 43166701)
10
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In a 21-day subchronic dermal study, technical grade bromoxynil phenol was applied to the
shaved dorsal skin of groups of 5 male and 5 female New Zealand white rabbits at dose levels of 0
(deionized water control), 30, 300 or 1000 mg/kg/day for 6 hours/day, 5 days/week, for 3 weeks (24-
25 days). Treatment with bromoxynil phenol did not produce any observable dermal or systemic
toxicity. The NOEL for dermal irritation and systemic toxicity is 1000 mg/kg/day, the limit dose for
a 21-day study. (MRID 42272301)
Bromoxynil Octanoate
In a 13-week subchronic feeding study, technical grade bromoxynil octanoate was
administered in the diet to groups of 20-30 male and 20-30 female Sprague Dawley rats at dose levels
of 0 (control), 150, 600 or 1100 ppm (equivalent to 0, 11, 45 or 91 mg/kg/day in males and 0, 13,
55 or 111 mg/kg/day in females). An additional group of 30 male and 30 female rats was started at
a dose level of 2100 ppm, but was sacrificed during the first week of the study due to high mortality
and signs of severe toxicity. No treatment related signs of toxicity were observed in males at 150 or
600 ppm. At 1100 ppm, the following effects were observed in males: decreased body weight gain,
decreased serum total protein, decreased globulins, possibly increased thymic lymphocyte necrosis,
and increased degeneration/necrosis of cardiac myofibers. No treatment-related effects were
observed in females at 150 ppm. At 600 ppm, decreased body weight gain and increased liver
weights were observed in females. At 1100 ppm, the following additional effects were also noted in
females: decreased serum total protein, decreased globulins, possibly increased thymic lymphocyte
necrosis, and increased degeneration/necrosis of cardiac myofibers. For male rats, the NOEL is 600
ppm (45 mg/kg/day) and the LOEL is 1100 ppm (91 mg/kg/day), based on decreased body weight
gain, decreased serum total protein, decreased globulins and increased degeneration/necrosis of
cardiac myofibers. For female rats, the NOEL is 150 ppm (13 mg/kg/day) and the LOEL is 600 ppm
(55 mg/kg/day), based on decreased body weight gain and increased liver weights. (MRID
42411901)
In a 13-week subchronic oral study, technical grade bromoxynil octanoate was administered
orally in gelatin capsules to groups of 2 male and 2 female beagle dogs at dose levels of 0 (control),
0.43, 1.43 or 7.14 mg/kg/day. The only treatment-related effect observed in males and females in this
study was decreased body weight gain. For males, mean absolute body weight gains from 0 to 13
weeks were +3.60, +2.80, +2.20 and +1.15 kg for the control, low, mid and high dose level groups
respectively. These gains corresponded to 78%, 61% and 32% of the male control group (100%)
for the low, mid and high dose level groups respectively. For females, the comparable mean absolute
body weight gains were +2.90, +2.05, +1.75 and +0.55 kg. These gains corresponded to 71%, 60%
and 19% of the female control group (100%). Although the % of body weight gain compared to
controls was 78% for low dose level males and 71% for low dose level females, the corresponding
differences in absolute body weight gains were actually less than 1 kg and since the low dose level
animals appeared healthy throughout the entire study and showed no other sign of toxicity, it was
concluded that the NOEL for both males and females in this study is 0.43 mg/kg/day and the LOEL
is 1.43 mg/kg/day, based on decreased body weight gain. This study is of limited usefulness because
only 2 dogs/sex/dose level were used and an insufficient number of tissues was microscopically
examined in the control, low and mid dose level groups. (MRID 42869701, 43700201)
11
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In a 13-week subchronic oral study, technical grade bromoxynil octanoate was administered
orally in gelatin capsules to groups of 3 male and 3 female beagle dogs at dose levels of 0 (control),
1, 5 or 25 mg/kg/day. No treatment-related effects were observed in either sex at 1 mg/kg/day. At
5 mg/kg/day, occasional panting was noted in both males and females. At 25 mg/kg/day, additional
signs of toxicity, observed in both males and females, were panting (after each dose) throughout the
study; decreased body weight gain; possibly decreased erythrocyte counts, hemoglobin, and packed
cell volume; and increased serum urea nitrogen. The NOEL for both males and females was reported
as just under 5 mg/kg/day. (MRID 00061179)
In a 21-day subchronic dermal study, technical grade bromoxynil octanoate was applied to
the shaved dorsal skin of 10 male and 10 female New Zealand white rabbits at dose levels of 0
(deionized water control), 30, 300 or 1000 mg/kg/day for 6 hours/day, 5 days/week, for 3 weeks (24-
26 days). Treatment with bromoxynil octanoate did not produce any observable systemic effects.
Significant dermal irritation, consisting of slight to moderate redness and swelling, cracking and
flaking of the skin, was observed at 300 and 1000 mg/kg/day. The NOEL for systemic toxicity is
1000 mg/kg/day, the limit dose for a 21-day study. The NOEL for dermal irritation is 30 mg/kg/day
and the LOEL is 300 mg/kg/day. (MRID 42346201)
c. Chronic Toxicity and Carcinogenicity
Table 4 summarizes the available chronic toxicity information. The chronic studies are
described in detail following Table 5.
Table 4: Chronic Toxicity Studies
MRID# (Species)
Doses Tested (mg/kg/day)
Systemic Toxicity (mg/kg/day)
Bromoxynil Phenol - Oral
00096521 (Rat)
40612501,
41374801 (Rat)
40780301*,
41304701* (Dog)
0,0.5, 1.5,5
(cf, ?)
0, 2.6, 8.2, 28 (a")
0,3.3, 11.0, 41(?)
0,0.1,0.3, 1.5,7.5
(cT, ?)
NOEL (a*, ?) = 5
LOEL (a*, ?) > 5 (not established)
NOEL (a*) = 2.6
(9) = 3.3
LOEL (a*) = 8.2 based on t incidence of spongiosis hepatis in
the liver
(?) = 11.0 based on 1 body weight gain
Threshold NOEL/LOEL (a*) = 1.5 based on significant! body
weight gain
Bromoxynil Octanoate - Oral
Bromoxynil octanoate chronic toxicity studies are satisfied by an acceptable "bridging" study(s) using bromoxynil
phenol as the test material.
* NOEL/LOEL used to determine the RfD or 0.015.
Table 5 summarizes the available carcinogenic toxicity information.
studies are described in detail following the table.
The carcinogenicity
12
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Table 5: Carcinogenicity Studies
MRID# (Species)
Doses Tested
(mg/kg/day)
Non-neoplastic lesions
Neoplastic Lesions
Bromoxynil Phenol - Oral
00096521
(Rat)
40612501,
41374801
(Rat)
00068077*
(Mouse)
43245501*,
43311701*
(Mouse)
0,0.5, 1.5,5
(cf, ?)
0, 2.6, 8.2, 28 (a*)
0,3.3, 11.0,41 (?)
0, 1.3,3.9, 13
(cf, ?)
0,3.1, 12,46(d")
0,3.7, 14, 53(?)
An increased incidence in non-
neoplastic lesions was not observed
in male and female rats
(d") I incidence in histopathological
changes in the liver; spongiosis
hepatis and foci of eosinophilic
cellular alteration.
(d") I incidence in hyperplastic
nodules in the liver.
(d", ?) I liver weights, diffusely
dark livers, t incidence in
hepatocellular centrilobular lesions;
hypertrophy, degeneration/necrosis
and pigmentation in hepatocytes
and Kupffer cells.
An increased incidence in
neoplastic lesions was not
observed in male and female rats.
An increased incidence in
neoplastic lesions was not
observed in male and female rats.
(d") t incidence in hepatocellular
combined adenomas/carcinomas
(?) Doses too low to assess
carcinogenic potential.
(d") t incidence in hepatocellular
adenomas, carcinomas and
combined adenomas/carcinomas
(?) t incidence of hepatocellular
carcinomas and combined
adenomas/carcinomas.
Bromoxynil Octanoate - Oral
Bromoxynil octanoate carcinogenicity studies are satisfied by an acceptable "bridging" study(s) using bromoxynil
phenol as the test material.
*The weight-of-evidence carcinogenicity classification and risk quantification was based primarily on these studies.
Bromoxynil Phenol
In a 12-month chronic oral toxicity study, technical grade bromoxynil phenol was
administered in gelatin capsules to groups of 6 male and 6 female beagle dogs at dose levels of 0
(control), 0.1, 0.3, 1.5 or 7.5 mg/kg/day. At the highest dose level tested (7.5 mg/kg/day), the
following treatment related effects were observed in both male and female dogs: increased incidences
of salivation, panting, liquid feces and pale gums; statistically significant decreased body weight gain
over entire duration of study, but particularly during first 8 weeks of study; statistically significant
decreased erythrocytes (RBC), hemoglobin (Hb) and packed cell volume (PCV); statistically
significant increased urea nitrogen; increased absolute liver weights and liver/body weight ratios. At
1.5 mg/kg/day, a statistically significant decreased body weight gain over the entire duration of study
was observed in the male dogs. Other "effects" at this same dose level were marginal, inconsistent
and of equivocal toxicological significance. These effects included panting; decreased RBC, Hb and
PCV; increased urea nitrogen; and increased absolute and relative liver weights in males and panting
and increased absolute and relative liver weights in females. No treatment related gross or histo-
pathological changes were observed in any organs in this study. The dose level of 1.5 mg/kg/day is
considered to be a threshold NOEL/LOEL for both male and female dogs in this study. (MRTD
#40780301, 41304701)
13
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In a 120-week combined chronic feeding/carcinogenicity study, technical grade bromoxynil
phenol was administered in the diet to groups of 60 male and 60 female Fischer 344 rats at dose levels
of 0 (control), 10, 30 or 100 ppm (equivalent to 0, 0.5, 1.5 or 5 mg/kg/day). Ten rats/sex/dose level
were sacrificed and examined at 12 months. An increase in absolute liver weights of the high dose
female rats at the 12-month interim sacrifice was considered to be of little concern since a similar
increase was not observed at the 120-week terminal sacrifice. No other effects of any kind in either
the male or female rats were observed. The NOEL for systemic effects is 100 ppm (5 mg/kg/day)
for both male and female rats. An increased incidence of neoplasms was not observed in the male
or female rats in this study; however, the dose levels were determined to be too low to assess
carcinogenic potential. (MRTD 00096521)
In a 2-year combined chronic feeding/carcinogenicity study, technical grade bromoxynil
phenol was administered in the diet to Sprague Dawley rats at dose levels of 0 (control), 60, 190 or
600 ppm (0, 2.6, 8.2 or 28 mg/kg/day in males and 0, 3.3, 11.0 or 41 mg/kg/day in females). Groups
of 105 male and 105 female rats were given the control diet and groups of 70 male and 70 female rats
were given diets containing bromoxynil phenol. Fifteen rats/sex/dose level were sacrificed and
examined at 12 months. In male rats, histopathological changes were observed in the liver at 190
ppm (spongiosis hepatis) and at 600 ppm (spongiosis hepatis and foci of eosinophilic cellular
alteration). Decreased body weight gain was also noted in male rats at 600 ppm. In female rats,
decreased body weight gain was observed at 190 ppm and 600 ppm. No neoplastic lesions were
associated with treatment. For male rats, the systemic NOEL is 60 ppm (2.6 mg/kg/day) and the
systemic LOEL is 190 ppm (8.2 mg/kg/day), based on an increased incidence of spongiosis hepatis
in the liver. For female rats, the systemic NOEL is 60 ppm (3.3 mg/kg/day) and the systemic LOEL
is 190 ppm (11.0 mg/kg/day), based on decreased body weight gain. An increased incidence of
neoplasms were not observed in the male or female rats. Dose levels used in this study were
determined to be sufficiently high to assess carcinogenic potential. (MRID 40612501, 41374801)
In an 18-month carcinogen!city study, technical grade bromoxynil phenol was administered
in the diet to groups of 60 male and 60 female Swiss albino mice at dose levels of 0 (control), 10, 30
or 100 ppm (equivalent to 0, 1.3, 3.9 or 13 mg/kg/day). A dose-related increased incidence of liver
adenomas/carcinomas combined was observed in the male mice. The increase was statistically
significant at 100 ppm. The liver tumor response in male mice was based on both benign and
malignant tumors with the carcinomas contributing to almost one-half of the total
adenomas/carcinomas at the mid- and high-dose levels. For male mice, the percentage incidences of
adenomas were 4%, 8%, 6% and 9%; the percentage incidences of carcinomas were 0%, 0%, 4% and
8%; and the percentage incidences of adenomas/carcinomas combined were 4%, 8%, 10% and 17%
for the 0, 10, 30 and 100 ppm groups, respectively. The incidences of hyperplastic nodules in male
mice, some of which may have been adenomas, were also increased at the mid- and high-dose levels.
Percentage incidences were 4%, 4%, 10% and 9% for the 0, 10, 30 and 100 ppm groups,
respectively. An increased incidence of neoplasms was not observed in female mice; however, dose
levels for the female mice in this study were determined to be too low to assess carcinogenic
potential. (MRID 00068077)
14
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In an 18-month carcinogenicity study, groups of 60 male and 60 female CD-1 mice were given
technical grade bromoxynil phenol in the diet at dose levels of 0 (control), 20, 75 or 300 ppm (0, 3.1,
12 or 46 mg/kg/day in males and 0, 3.7, 14 or 53 mg/kg/day in females). Mortality, body weights
and food consumption were not affected by treatment. The liver was the target organ. At 300 ppm,
treatment related increased liver weights, increased incidences of diffusely dark livers, and increased
incidences of non-neoplastic microscopic lesions in the livers of both male and female mice were
observed. Histopathologic lesions in the liver included hepatocellular centrilobular hypertrophy,
hepatocellular degeneration/necrosis, and pigment in hepatocytes and Kupffer cells. Similar non-
neoplastic lesions were also observed in the livers of some male and female mice at 75 ppm. The
LOEL for non-carcinogenic effects in this study for both male and female mice is 75 ppm and the
NOEL is 20 ppm. Treatment related increased incidences of hepatocellular adenomas, carcinomas,
and adenomas/carcinomas combined were observed in the male mice at all dose levels in this study.
For male mice, the percentage incidences of adenomas were 6%, 16%, 20% and 19%; the percentage
incidences of carcinomas were 4%, 16%, 4% and 21%; and the percentage incidences of
adenomas/carcinomas combined were 9%, 31%, 24% and 40% for the 0,20, 75 and 300 ppm groups,
respectively. Subsequent to the original pathology reading, liver sections from all male mice in the
study were also evaluated by a second independent pathologist. Similar results were obtained in the
second pathology evaluation. For female mice given 300 ppm, slightly increased incidences of
hepatocellular carcinomas and of adenomas/carcinomas combined also were considered to be related
to treatment with bromoxynil phenol. For female mice, the percentage incidences of carcinomas were
0%, 2%, 0% and 10%; and the percentage incidences of adenomas/carcinomas combined were 4%,
4%, 4% and 17% for the 0, 20, 75 and 300 ppm groups, respectively. Liver sections from female
mice in this study were not reevaluated by the independent pathologist. (MRID 43245501,
43311701)
Bromoxynil Octanoate
The Agency has determined that bromoxynil octanoate is lexicologically equivalent to
bromoxynil (phenol) with respect to certain oral toxicity studies (FLED RfD Peer Review Committee,
February 29, 1996). It was concluded that some of the toxicology studies using bromoxynil (phenol)
as the test material may be used for the purpose of satisfying the study requirements for bromoxynil
octanoate. Hence, there are no required chronic toxicity studies nor carcinogenicity studies in which
bromoxynil octanoate was the test material.
d. Developmental Toxicity
Table 6 summarizes the available developmental toxicity information. The developmental
studies are described in detail following the table.
15
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Table 6: Developmental Toxicity Studies
MRID
(Species)
Doses Tested
(mg/kg/day)
Maternal Toxicity
(mg/kg/day)
Developmental Toxicity
(mg/kg/day)
Bromoxynil Phenol - Oral
40466802 (Rat)
00116558*
(Rat)
Rogers et al.
1991 (Rat)
00138149
(Rabbit)
00142779
(Rabbit)
Rogers et al.
1991 (Mouse)
0, 4, 12.5, 40
(?)
0, 5, 15, 35
(?)
0, 1.7, 5, 15
(?)
0, 15, 30, 60
(?)
0, 30, 45, 60
(?)
0, 11,32,96
(?)
NOEL = 12.5
LOEL = 40 based on 1 body weight
gain, 1 food consumption
NOEL = 5
LOEL =15 based on 1 body weight
gain
NOEL = 5
LOEL =15 based on 1 body weight
gain, t liver weights
NOEL = 15
LOEL = 30 based on 1 body weight
gain, 1 food consumption
NOEL = 45
LOEL = 60 based on t mortality,
anorexia, blood discharge
NOEL =11
LOEL = 32 based on t mortality, t
liver weights
NOEL = 4
LOEL =12.5 based ont incidence of
supernumerary ribs, t post
implantation loss
NOEL < 5 (not established)
LOEL = 5 based on
t incidence of supernumerary ribs
NOEL = 5
LOEL =15 based on t incidence of
supernumerary ribs
NOEL < 15 (not established)
LOEL =15 based on t incidence of
supernumerary ribs
NOEL < 30 (not established)
LOEL = 30 based on
1 fetal weights
NOEL = 32
LOEL = 96 based on t incidence of
supernumerary ribs, 1 fetal weights, t
unossified caudal vertebrae
Bromoxynil Phenol - Dermal
40935101,
41307801
(Rabbit)
40881201,
40883601 (Rat)
0, 10, 50, 150
(?)
0, 5, 10, 50,
100 (?)
NOEL = 50
LOEL =150 based on 1 body weight
gain
NOEL = 50
LOEL = 100 based on I body weight
gain, 1 food consumption
NOEL = 10
LOEL = 50 based on t in agenesis of
intermediate lobe of the lung, t holes
in parietal bone
NOEL = 10
LOEL = 50 based on t incidence of
supernumerary ribs
Bromoxynil Octanoate - Oral
Rogers et al.
1991
(Rat)
0,2.4,7.3,21.8
(?)
NOEL = 7.3
LOEL = 21.8 based on I body weight
gain, t liver weights
NOEL = 7.3
LOEL = 21.8 based on t incidence of
supernumerary ribs, 1 fetal weights
Bromoxynil Octanoate - Dermal
41163301 (Rat)
41471901,
42183901
(Rabbit)
0, 2, 5, 10, 15,
20, 75(?)
0, 5, 10, 15, 20,
40, 80(?)
NOEL = 15
LOEL = 20 based on I body weight
gain, 1 food consumption
NOEL = 80
LOEL > 80 (not established)
NOEL = 10
LOEL =15 based on t incidence of
supernumerary ribs
NOEL = 80
LOEL > 80 (not established)
*NOEL used in the acute dietary risk assessment for the subpopulation of females 13+.
16
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Bromoxynil Phenol
In an oral developmental toxicity study, technical grade bromoxynil phenol was administered
to groups of 22 pregnant Sprague Dawley rats by gavage at doses of 0 (control), 4, 12.5 or 40
mg/kg/day on gestation days 6-15, inclusive. The developmental toxicity NOEL is 4 mg/kg/day. A
dose-related increased incidence of supernumerary (14th) ribs was observed at the developmental
toxicity LOEL of 12.5 mg/kg/day. Increased post-implantation loss was also observed at 12.5
mg/kg/day. At 40 mg/kg/day, the following additional effects were observed in the offspring:
reduced fetal weight, increased numbers of small fetuses, and increased incidences of soft tissue and
skeletal abnormalities (including anophthalmia, microphthalmia, short renal papilla, and spinal and
thoracic bone abnormalities). The maternal toxicity NOEL is 12.5 mg/kg/day and the maternal
toxicity LOEL is 40 mg/kg/day, based on decreased body weight gain throughout most of the
treatment and post-treatment period and decreased food consumption during the treatment period.
(MRID 40466802)
In an oral developmental toxicity study, groups of 28 pregnant Sprague Dawley rats received
0 (control), 5, 15 or 35 mg/kg/day of technical grade bromoxynil phenol by gavage on gestation days
5-17, inclusive. No developmental toxicity NOEL was determined in this study (below 5 mg/kg/day).
At the LOEL of 5 mg/kg/day, a dose-related increased incidence of supernumerary ribs was observed.
At the high dose of 35 mg/kg/day, additional effects included an increased incidence of late
intrauterine deaths, decreased fetal body weights and an increase in the total incidence of minor
anomalies. The maternal toxicity NOEL is 5 mg/kg/day and the maternal toxicity LOEL is 15
mg/kg/day, based on decreased body weight gain. At 35 mg/kg/day, 6/28 dams died between days
7 and 14 of gestation. (MRID 00116558)
Groups of 20-25 pregnant Sprague Dawley rats were given 0 (control), 1.7, 5 or 15
mg/kg/day of technical grade bromoxynil phenol by oral gavage on gestation days 6-15, inclusive.
In the offspring, the litter incidences of supernumerary ribs were 30%, 60%, 50% and 90% in the
control, 1.7, 5 and 15 mg/kg/day groups, respectively. The percentages of litters with supernumerary
ribs were significantly increased at the 1.7 and 15 mg/kg/day dose levels. However, the increase at
1.7 mg/kg/day was not considered to be biologically significant. The developmental toxicity NOEL
is 5 mg/kg/day and the developmental toxicity LOEL is 15 mg/kg/day, based on an increased
incidence of supernumerary ribs. The maternal toxicity NOEL is 5 mg/kg/day and the maternal
toxicity LOEL is 15 mg/kg/day, based on decreased body weight gain and increased liver weights.
No consistent effects were seen on thymus, spleen or adrenal weights suggesting there was no
generalized stress response in the dams. (Rogers, Francis, Barbee et al., 1991)
In an oral developmental toxicity study, technical grade bromoxynil phenol was administered
to groups of 18 or more pregnant New Zealand white rabbits by gavage at doses of 0 (control), 15,
30 or 60 mg/kg/day on days 5-20 of gestation. A high incidence (on a litter basis) and a dose-related
increased incidence (on a fetal basis) of fully formed bilateral 13th ribs and an increased incidence of
all forms of supernumerary ribs were observed at 15, 30 and 60 mg/kg/day. At 60 mg/kg/day, the
following additional effects were also observed: increased post-implantation loss (due primarily to
17
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5 totally resorbed litters), decreased fetal weights, and increased numbers of litters and numbers of
fetuses with major malformations (including hydrocephalus, anophthalmia, microphthalmia and
defects in skull ossification). The incidence of total minor anomalies was also increased at 60
mg/kg/day. The NOEL for developmental toxicity was not determined in this study (below 15
mg/kg/day). The developmental toxicity LOEL is 15 mg/kg/day, based on the increased incidence
of supernumerary ribs. The maternal toxicity NOEL is 15 mg/kg/day and the maternal toxicity LOEL
is 30 mg/kg/day, based on reduced body weight gain and reduced food consumption during the
treatment period. There were no deaths or clinical signs of toxicity associated with treatment.
(MRID 00138149)
In an oral developmental toxicity study, groups of 22-23 pregnant New Zealand white rabbits
were given 0 (control), 30, 45 or 60 mg/kg/day of technical grade bromoxynil phenol by gavage on
gestations days 6-18, inclusive. The number of fetuses with decreased body weights (30% below
control mean weight) was significantly increased at all dose levels, At 45 and 60 mg/kg/day, a dose-
related increase in supernumerary ribs also was observed. At 60 mg/kg/day, several vertebral and
thoracic bone abnormalities, including fused ribs, scoliosis, extra ribs, thoracic centrum misshapen
and incomplete ossification of sternebrae, were observed. A NOEL for developmental toxicity was
not determined in this study (below 30 mg/kg/day). The developmental toxicity LOEL is 30
mg/kg/day, based on decreased fetal weights. The maternal toxicity NOEL is 45 mg/kg/day and the
maternal toxicity LOEL is 60 mg/kg/day, based on increased mortality (7/23 dams died at this dose
level) and other clinical signs of toxicity, including anorexia and discharge of blood. (MRID
00142779)
Groups of 16-35 pregnant Swiss Webster (CD-I) mice were given 0 (control), 11, 32 or 96
mg/kg/day of technical grade bromoxynil phenol by oral gavage on gestation days 6-15, inclusive.
In the offspring, the litter incidences of 14th ribs were 50%, 28%, 56% and 81% in the control, 11,
32 and 96 mg/kg/day groups, respectively. The increased incidence was statistically significant at the
high dose. Also at 96 mg/kg/day, decreased fetal weights and decreased numbers of fetuses with
ossified caudal vertebrae were observed. The developmental toxicity NOEL is 32 mg/kg/day and the
developmental toxicity LOEL is 96 mg/kg/day, based on increased incidence of 14th ribs, decreased
fetal weights and decreased numbers of fetuses with ossified vertebrae. The maternal toxicity NOEL
is 11 mg/kg/day and the maternal toxicity LOEL is 32 mg/kg/day, based on increased mortality and
increased liver weights. No consistent effects were seen on thymus, spleen or adrenal weights
suggesting there was no generalized stress response in the dams. (Rogers, Francis, Barbee et al.,
1991)
In a dermal developmental toxicity study, bromoxynil phenol (solubilized in water containing
50 mg/ml sodium hydroxide and 20% triethylene glycol) was applied to groups of 20 pregnant New
Zealand white rabbits at dose levels of 0 (control), 10, 50 or 150 mg/kg/day for 6 hours/day on
gestation days 6-18, inclusive. The results in this study were compromised by 25 rabbits possibly
being improperly dosed on days 6 and/or 7 of gestation. The developmental toxicity NOEL is 10
mg/kg/day and the developmental toxicity LOEL is 50 mg/kg/day, based on an apparent increase in
agenesis of the intermediate lobe of the lung and on an increase in holes in the parietal portion of the
18
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skull. Lung agenesis has not been observed in other studies with bromoxynil and its incidence in
historical controls is highly variable. The incidence of supernumerary ribs was not affected in this
study. The maternal toxicity NOEL is 50 mg/kg/day and the maternal toxicity LOEL is 150
mg/kg/day, based on decreased body weight gain. Because of flaws in the execution of this study,
the results have been interpreted with considerable caution and the NOELs and LOELs are
considered to be tentative. (MRTD 40935101, 41307801)
In a dermal developmental toxicity study, bromoxynil phenol (solubilized in water containing
50 mg/ml sodium hydroxide and 20% triethylene glycol) was applied to groups of 23 pregnant
Sprague Dawley rats at dose levels of 0 (control), 5, 10, 50 or 100 mg/kg/day for 6 hours/day on
gestation days 6-15, inclusive. A dose-related increased incidence of supernumerary (14th) ribs was
observed in this study at 10, 50 and 100 mg/kg/day. At 10 mg/kg/day, however, the increased
incidence was not statistically significant compared to the concurrent control group and was within
the historical control range. The developmental toxicity NOEL is 10 mg/kg/day and the
developmental toxicity LOEL is 50 mg/kg/day, based on increased 14th ribs. The maternal toxicity
NOEL is 50 mg/kg/day and the maternal toxicity LOEL is 100 mg/kg/day, based on decreased body
weight gain and decreased food consumption during the treatment period. No deaths or clinical signs,
including skin irritation, were attributed to treatment with the test material in this study. (MRID
40881201,40883601)
Bromoxynil Octanoate
In an oral developmental toxicity study, technical grade bromoxynil octanoate was
administered to groups of 17-20 pregnant Sprague Dawley rats by gavage at doses of 0 (control), 2.4,
7.3 or 21.8 mg/kg/day on gestation days 6-15, inclusive. In the offspring, the litter incidences of 14th
ribs were 29%, 40%, 37% and 65% in the control, low, mid and high dose groups, respectively. The
increased incidence was statistically significant at the high dose. Reduced fetal weights were also
observed in the high dose group. The developmental toxicity NOEL is 7.3 mg/kg/day and the
developmental toxicity LOEL is 21.8 mg/kg/day, based on an increased incidence of 14th ribs and
on reduced fetal weights. The maternal toxicity NOEL is 7.3 mg/kg/day and the maternal toxicity
LOEL is 21.8 mg/kg/day, based on decreased body weight gain and increased liver weights. No
consistent effects were seen on thymus, spleen or adrenal weights suggesting there was no
generalized stress response in the dams. (Rogers, Francis, Barbee et al., 1991)
In a dermal developmental toxicity study, bromoxynil octanoate (Buctril formulation diluted
in water) was applied to groups of 25 pregnant Sprague Dawley rats at dose levels of 0 (Buctril
formulation inerts and water controls), 2, 5, 10, 15, 20 or 75 mg a.i./kg/day for 6 hours/day on
gestation days 6-15, inclusive. The developmental toxicity NOEL is 10 mg a.i./kg/day. A dose-
related increased incidence of supernumerary (14th) ribs was observed at the developmental toxicity
LOEL of 15 mg a.i./kg/day. At 20 and 75 mg a.i./kg/day, the incidences of supernumerary ribs were
increased still further. Skin irritation was observed in the Buctril formulation inerts control and 75
mg a.i./kg/day treatment groups. The maternal toxicity NOEL is 15 mg a.i./kg/day and the maternal
toxicity LOEL is 20 mg a.i./kg/day, based on decreased body weight gain and decreased food
consumption during the treatment period. (MRID 41163301)
19
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In a dermal developmental toxicity study, groups of 20 pregnant New Zealand white rabbits
were treated with bromoxynil octanoate (Buctril formulation diluted in water) at dose levels of 0
(Buctril formulation inerts and water controls), 5, 10, 15, 20, 40 or 80 mg a.i./kg/day for 6 hours/day
on gestation days 6-18, inclusive. Incidences of 13th ribs were high in control and all treatment
groups. A dose-response relationship, however, was not evident and it was concluded that no
adverse effects on offspring development were observed. The developmental toxicity NOEL is 80
mg a.i./kg/day. A developmental toxicity LOEL was not determined in this study (above 80 mg
a.i./kg/day). Significant skin irritation was observed in the Buctril formulation inerts control and all
treatment groups. At 15 mg a.i./kg/day and higher, the majority of rabbits displayed erythema,
fissuring and desquamation. The frequency and severity of skin irritation increased with increasing
concentration of Buctril. Desquamation persisted for most of the post-treatment period. Skin
irritation, however, did not appear to adversely affect maternal well-being. No systemic toxicity was
observed in the dams at any dose level. The NOEL for systemic maternal toxicity is 80 mg
a.i./kg/day. A LOEL for systemic maternal toxicity was not determined in this study (above 80 mg
a.i./kg/day). (MRID 41471901, 42183901)
e. Reproductive Toxicity
Table 7 summarizes the available reproductive toxicity information. The reproductive studies
are described in detail following the table.
Table 7: Reproductive Studies
MRID#
(Species)
Doses Tested
(mg/kg/day)
Systemic Toxicity
(mg/kg/day)
Reproductive Toxicity
(mg/kg/day)
Developmental Toxicity
(mg/kg/day)
Bromoxynil Phenol - Oral
41149301
(Rat)
00064815
(Rat)
0, 0.8, 4, 21
(rf,9)
0, 1.5,5, 15
(cT,?)
NOEL(?)=4
LOEL = 21 based on I body
weight gain in F0 and F{ ( ? )
rats, t liver weights (d", ? )
NOEL (a*,?) = 1.5
LOEL = 5 based on 1 body
weight gain in Fj and F2 (d", ? )
rats
NOEL (a",?) = 21
LOEL (a",?) >2l
(highest dose tested)
NOEL(a*,?) = 15
LOEL (a*,?) > 15
(highest dose tested)
NOEL = 4
LOEL = 21 based on I
body weight gain during
lactation, delayed eye
opening
NOEL = 5
LOEL= 15 based on I
body weight gain in F2
generation
Bromoxynil Octanoate - Dermal
41667401
(Rat)
0, 25, 50, 100
(cf,?)
NOEL (d") = 25
LOEL (a*) = 50 based on I
body weight gain
NOEL (d") = 50
LOEL (d") = 100 based
on 1 prostate weight
gland
NOEL = 100
LOEL > 100 (not
established)
Bromoxynil Phenol
In a 2-generation reproduction study, technical grade bromoxynil phenol was administered
in the diet to groups of 24 male and 24 female Sprague Dawley rats at dose levels of 0 (control), 10,
50 or 250 ppm (approximately 0, 0.8, 4 or 21 mg/kg/day) during 14 weeks prior to mating. No
20
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reproductive toxicity was observed in this study at any dose level. The NOEL for reproductive
toxicity is 250 ppm (21 mg/kg/day) and the LOEL for reproductive toxicity is greater than 250 ppm
(HDT). The NOEL for developmental toxicity in offspring is 50 ppm (4 mg/kg/day) and the LOEL
is 250 ppm (21 mg/kg/day), based on decreased body weight gain during lactation and delayed eye
opening. The NOEL for systemic toxicity in adult rats is 50 ppm (4 mg/kg/day) and the LOEL is 250
ppm (21 mg/kg/day), based on decreased body weight gain in FO and Fl females before mating,
during gestation and lactation and at study termination. In addition, possibly increased liver weights
were observed in both male and female adults. (MRTD 41149301)
In a 3-generation reproduction study, technical grade bromoxynil phenol was administered
in the diet to groups of 10 male and 20 female Wistar rats at dose levels of 0 (control), 30,100 or 300
ppm (equivalent to 0, 1.5, 5 or 15 mg/kg/day). Definitive NOELs and LOELs were not determined
in this study due to numerous deficiencies in data reporting. The following NOELs and LOELs are
therefore tentative. No reproductive toxicity was observed in this study at any dose level. The
NOEL for reproductive toxicity is 300 ppm (15 mg/kg/day) and the LOEL for reproductive toxicity
is greater than 300 ppm (HDT). The NOEL for developmental toxicity in offspring is 100 ppm (5
mg/kg/day) and the LOEL is 300 ppm (15 mg/kg/day), based on decreased body weight gain,
particularly in the F2 generation. The NOEL for systemic toxicity in adult rats is 30 ppm (1.5
mg/kg/day) and the LOEL is 100 ppm (5 mg/kg/day), based on decreased body weight gain in Fl and
F2 parents. (MRID 00064815)
Bromoxynil Octanoate
In a specially designed dermal reproduction study, groups of 20 male Crl:CRBR VAF/Plus
rats were treated for 6 hours each day for 21 days with bromoxynil octanoate (Buctril formulation
diluted in water) at dose levels of 0 (Buctril formulation inerts and water controls), 25, 50 or 100 mg
a.i./kg/day. After 21 days of treatment, the male rats were mated with untreated female rats on days
1, 7, 14, 21, 35, 56 or 113 post-exposure. No effects on mating or fertility were observed in the male
rats at any dose level. Possibly reduced prostate gland weight on day 1 post-exposure, however, was
observed at 100 mg a.i./kg/day. The NOEL for male reproductive toxicity is 50 mg a.i./kg/day
(tentative) and the LOEL is 100 mg a.i./kg/day (tentative), based on possibly decreased prostate
gland weight. No effects on offspring development were observed. The NOEL for developmental
toxicity in offspring is 100 mg a.i./kg/day (HDT) and the LOEL greater than 100 mg a.i./kg/day. The
NOEL for systemic toxicity in the adult male rats is 25 mg a.i./kg/day and the LOEL is 50 mg
a.i./kg/day, based on decreased body weight gain. At 100 mg a.i./kg/day, possibly increased liver
weights were also observed. Significant skin irritation was observed in the control group (Buctril
formulation inerts only) and Buctril treated groups, particularly at 100 mg a.i./kg/day. This study is
a specially designed study and does not satisfy the requirement for a multigeneration reproduction
study in rats (Guideline 83-4). (MRID 41667401)
f. Mutagenicity
Table 8 summarizes the available mutagenicity toxicity information. The mutagenicity studies
are described in detail following the table.
21
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Table 8: Mutagenicity Studies
Study
Genotoxic Effect
MRID#
Bromoxynil Phenol
Other Mutagenic Mechanisms/ In vitro unscheduled
DNA synthesis
Other Mutagenic Mechanisms/ Cell Transformation
Other Mutagenic Mechanisms/ In vitro Sister
Chromatid Exchange (CHO)
Gene Mutation/ In vitro assay in mammalian cells
(mouse lymphoma)
Other Mutagenic Mechanisms/ Bacterial DNA
Damage/Repair (E. Coli)
Cytogenetics/ In vitro assay in mammalian cells (CHO)
Cytogenetics/ In vivo mouse micronucleus assay
Gene Mutation/ In vitro assay in mammalian cells
(CHO/HGPRT)
Gene Mutation in Salmonella typhimurium
Cytogenetics/ In vivo mouse micronucleus assay
Negative
Negative
Negative (non-activated and activated)
Negative (non-activated)
Positive (activated)
Positive (non-activated and activated)
Negative (non-activated) Positive (activated)
Negative
Negative (non-activated and activated)
Negative (non-activated and activated)
Negative
00115646
00115647
00115648
00115649
00115650
00115651
00124803
41995702
41995701
42092301
Bromoxynil Octanoate
Gene Mutation in Salmonella typhimurium
Cytogenetics/ In vivo mouse micronucleus assay
Other Mutagenic Mechanisms/ In vitro unscheduled
DNA synthesis
Negative (non-activated and activated)
Negative
Negative
43022701
41930802
42078901
Bromoxynil Phenol
In an unscheduled DNA synthesis (UDS) assay, cultures of primary rat hepatocytes were
exposed to technical grade bromoxynil phenol at concentrations ranging from 0.1 to 50 ug/ml. At
50 ug/ml, all cells died. At 25 ug/ml, the next highest concentration, cell survival was 31%. Cell
survival increased with decreasing concentrations of test material. The positive control (2-
acetylaminofluorene) was adequate. Bromoxynil phenol did not cause an appreciable increase in
mean net nuclear grain counts compared to the negative solvent control at any of the evaluated
concentrations. Bromoxynil phenol did not induce a genotoxic effect in this assay system. (MRID
00115646)
In an in vitro transformation assay, cultures of mouse C3H/10T ^ CIS cells were exposed
to technical grade bromoxynil phenol at concentrations ranging from 32.5 to 390 ug/ml. Based on
results in a preliminary cytotoxicity study, cell survival at these concentrations was expected to be
between 20% and 100%. The positive control, benz(a)pyrene, was satisfactory. After incubation of
cell cultures for approximately 6 weeks, a pooled average of Type II and Type III foci/culture was
scored as frequency of transformation. The frequency of transformed foci in bromoxynil phenol
treated cultures was equal to or less than in the negative solvent control. Bromoxynil phenol did not
induce a genotoxic effect in this assay system. (MRID 00115647)
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In a sister chromatid exchange (SCE) assay, cultures of Chinese hamster ovary (CHO) cells
were exposed to technical grade bromoxynil phenol without metabolic activation at concentrations
ranging from 4.67 to 18.7 ug/ml and with metabolic activation (rat S9 mixture) at concentrations
ranging from 500 to 900 ug/ml. The solvent used was DMSO. The positive controls (mitomycin for
the non-activated system and cyclophosphamide for the activated system) were adequate. After
incubation, chromosome preparations were stained and examined. Bromoxynil phenol, without and
with metabolic activation, did not induce any significant increases in sister chromatid exchanges.
Bromoxynil phenol did not induce a genotoxic effect in this assay system. (MRTD 00115648)
In a mouse lymphoma forward mutation assay, cultures of L5178Y TK+/- cells were exposed
to technical grade bromoxynil phenol without metabolic activation at concentrations ranging from
15.6 to 250 ug/ml and with metabolic activation (rat S9 mixture) at concentrations of 3.9, 7.8, 15.6,
31.3 or 62.5 ug/ml. The solvent used was DMSO. The positive controls (ethylmethane sulfonate for
non-activated system and dimethylnitrosamine for activated system) were satisfactory. After
incubation, the mutant frequency was calculated as the ratio of mutant colonies to viable colonies.
In the non-activated system, there were no significant increases in mutant frequency at any
concentration when compared to that of the untreated and negative solvent controls—even at the
highly toxic concentration of 250 ug/ml (9.5% relative growth). Significant increases in the mutant
frequency, however, did occur in the activated system at the two highest, most toxic concentrations
of test material. At the moderately toxic concentration of 31.3 ug/ml (39.6% relative growth), there
was a 2 fold increase in mutant frequency above background levels and at the highly toxic
concentration of 62.5 ug/ml (7.9% relative growth), there was a 4.1 fold increase in mutant frequency
above background levels. Mutant frequencies in the positive control were greatly in excess of
background levels. Bromoxynil phenol did not induce a genotoxic effect in the non-activated portion
of this assay, but the dose-related increase in mutant colonies in the activated portion of this assay
was considered to be a positive genotoxic response. (MRID 00115649)
In a bacterial DNA repair test using Escherichia coli indicator strains, pol A+ (W3110) and
pol A- (p3478), cultures of both indicator strains on agar plates were exposed to technical grade
bromoxynil phenol without and with metabolic activation (rat S9 mixture) at concentrations ranging
from 1.0 to 10000 ug/plate. The test material was placed in wells of uniform diameter in the center
of each agar plate. The solvent used was DMSO. The positive controls (ethylmethane sulfonate and
methylmethane sulfonate for the non-activated system and dimethylnitrosamine for the activated
system) were adequate. The preferential inhibition of the pol A- strain, relative to the pol A+ strain,
was determined by measuring the differential zones of inhibition produced by the test material around
each well. Differential zones of inhibition, indicating a mutagenic event (involving DNA polymerase
I enzyme), were observed in both the non-activated and activated systems at concentrations from
1000 ug/plate to 10000 ug/plate. A dose-response effect was evident at concentrations from 500
ug/plate (NOEL) to 5000 ug/plate in both systems. At 10000 ug/plate, a dose-response effect may
have been obscured by the high level of background cytotoxicity. Bromoxynil phenol induced a
positive genotoxic response in both the non-activated and activated portions of this assay. (MRTD
00115650)
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In an in vitro chromosome aberration assay, cultures of Chinese hamster ovary (CHO) cells
were exposed to technical grade bromoxynil phenol without metabolic activation at concentrations
ranging from 100 to 1500 ug/ml (8 hour exposure) and from 50 to 500 ug/ml (20 hour exposure).
CHO cells were also exposed to test material with metabolic activation (rat S9 mixture) for 2 hours
at concentrations ranging from 300 to 1500 ug/ml (trial 1) and at concentration ranging from 1200
to 1600 ug/ml (trial 2). The solvent used was DMSO. The positive controls (mitomycin C for the
non-activated system and cyclophosphamide for the activated system) were adequate. After
incubation, chromosome preparations were stained and examined. In the non-activated system, there
was no significant increase in chromosome aberrations when compared to the untreated and negative
solvent controls. In the activated system, however, significant increases in chromosome aberrations
above background levels were observed. In trial 1 at 1500 ug/ml, but not at lower concentrations,
a statistically significant increase in chromosome aberrations was observed. These aberrations
included numerous simple chromosome breaks and chromatid breaks and also complex aberrations
such as chromatid interchanges. In trial 2 at all concentrations (1200 to 1600 ug/ml), significant
increases in chromosome aberrations, including simple breaks and complex chromatid aberrations,
were again observed. Bromoxynil phenol did not induce a genotoxic effect in the non-activated
portion of this assay, but the significant increase in chromosome damage in the activated portion of
this assay at concentrations equal to and above 1200 ug/ml was considered to be a positive genotoxic
response. (MRTD 00115651)
In an in vivo micronucleus assay, two doses of bromoxynil phenol were administered orally
by gavage on two consecutive days to groups of 5 male and 5 female CD-I mice at dose levels of 0
(control), 21.6, 69.0 or 215 mg/kg/day. Dose levels were based on a previously determined LD50
of 431 + 177 mg/kg/day under similar conditions. Bone marrow was taken 6 hours after the second
dose and examined for micronuclei in polychromatic erythrocytes (PCE). Normochromatic
erythrocytes (NCE) were also counted and the NCE/PCE ratio was recorded for each animal. The
positive control (cyclophosphamide) was satisfactory. At215.5 mg/kg/day, 5 mice died shortly after
dosing. At 215.5 (in survivors) and 69.0 mg/kg/day, depressed hematopoiesis, evidenced by shifts
in the NCE/PCE ratio, indicated target cell cytotoxicity. No increased frequencies of micronuclei
were observed at any dose level in the bone marrow cells of treated mice. Bromoxynil phenol did not
induce a clastogenic effect in this assay system. (MRTD 00124803)
In a forward mutation assay, cultures of Chinese hamster ovary (CHO)/HGPRT locus cells
were exposed to technical grade bromoxynil phenol without and with metabolic activation (rat S9
mixture) at concentrations ranging from 100 to 1000 ug/ml. The solvent used was DMSO. The
positive controls (5-bromo-2'-deoxyuridine for non-activated system and 3-methylcholanthrene for
activated system) were adequate. After incubation, mutation frequencies were determined and
compared to the negative solvent control. In the non-activated system, the concentration of 1000
ug/ml was severely toxic (4.5% relative growth). In the activated system, concentrations of 800
ug/ml and higher were also severely toxic (< 2.7% relative growth). Cell survival increased with
decreasing concentrations of test material. In the non-activated system, the test material did not
significantly increase the mutation frequency at the HGPRT locus. In the activated system, increases
in the mutation frequency were observed at several concentrations of test material, but were not dose-
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related, did not exceed the testing laboratory's acceptable background frequency, and therefore were
not considered to be mutagenic events. Bromoxynil phenol, without and with metabolic activation,
did not induce a genotoxic effect in this assay system. (MRID 41995702)
In a Salmonella/mammalian microsome reverse mutation assay (Ames study), strains TA98,
TA100, TA1535, TA1537 and TA1538 were exposed to technical grade bromoxynil phenol without
metabolic activation at concentrations ranging from 3.33 to 1000 ug/plate and with metabolic
activation (rat S9 mixture) at concentrations ranging from 10.0 to 3330 ug/plate. Cytotoxicity was
observed in the majority of strains exposed to 1000 ug/plate in the non-activated system and in most
strains exposed to 1000 ug/plate and higher in the activated system. The solvent used was DMSO.
The several positive controls (sodium azide, 2-nitrofluorene and ICR 191 for the non-activated
system and 2-aminoanthracene for the activated system) were satisfactory. After incubation, mean
numbers of revertant mutant colonies per plate were determined for each strain. Noncytotoxic
concentrations of bromoxynil phenol did not significantly increase the number of revertant mutant
colonies per plate over background levels in any of the 5 strains tested, without or with metabolic
activation, at any of the evaluated concentrations. Bromoxynil phenol, without and with metabolic
activation, did not induce a genotoxic effect in this assay system. (MRID 41995701)
In an in vivo micronucleus assay, single doses of technical grade bromoxynil phenol were
administered orally by gavage to groups of 5 male and 5 female CD-I mice at dose levels of 0
(control), 35, 70 or 105 mg/kg. Dose levels were based on the results in a previously conducted
toxicity study in which dose-related mortalities of up to 80% were observed between 125 and 275
mg/kg under similar conditions. Bone marrow cells, harvested at 24, 48 and 72 hours postexposure
in the high dose group and at 24 hours postexposure in the mid and low dose groups, were examined
for the frequency of micronuclei in polychromatic erythrocytes (PCE). Normochromatic erythrocytes
(NCE) were also counted and the PCE/NCE ratio was recorded for each animal. The positive control
(cyclophosphamide) was adequate. At 105 mg/kg, 1 mouse died. No evidence of a cytotoxic
response, as evidenced by an altered PCE/NCE ratio, was observed in the bone marrow cells of either
sex at any dose level or sacrifice time, but the single mortality at the high dose level was consistent
with the results in the previously conducted toxicity study and indicated that an appropriately high
dose level was evaluated in the micronucleus assay. No increased frequencies of micronuclei were
observed at any dose level or sacrifice time in the bone marrow cells of treated male or female mice.
Bromoxynil phenol did not induce a clastogenic effect in this assay system. (MRID 42092301)
Bromoxynil Octanoate
In a Salmonella/mammalian microsome reverse mutation assay (Ames study), strains TA98,
TA100, TA1535, TA1537 and TA1538 were exposed to technical grade bromoxynil octanoate
without and with metabolic activation (rat S9 mixture) at concentrations ranging from 33 to 10000
ug/plate. Compound precipitation was observed at 10000 ug/plate and minimal to moderate
cytotoxicity was observed in the majority of strains exposed to 3333 ug/plate and higher. The solvent
used was DMSO. The several positive controls (sodium azide, 2-nitrofluorene and 9-aminoacridine
for the non-activated system and 2-aminoanthracene for the activated system) were satisfactory.
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After incubation, mean numbers of revertant mutant colonies per plate were determined for each
strain. Noncytotoxic concentrations of bromoxynil phenol did not significantly increase the number
of revertant mutant colonies per plate over background levels in any of the 5 strains tested.
Bromoxynil octanoate, without and with metabolic activation, did not induce a genotoxic effect in
this assay system. (MRID 43022701)
In an in vivo micronucleus assay, single doses of technical grade bromoxynil octanoate were
administered orally by gavage to groups of 5 male CD-I mice at dose levels up to 183 mg/kg and to
groups of 5 female CD-I mice at dose levels up to 267 mg/kg. Dose levels were based on the
results in previously conducted toxicity studies in which the LD50 for males and females were
determined to be 262 and 382 mg/kg, respectively. Bone marrow cells, harvested at 24, 48 and 72
hours postexposure in the high dose group and at 24 hours postexposure in the mid and low dose
groups, were examined for the frequency of micronuclei in polychromatic erythrocytes (PCE).
Normochromatic erythrocytes (NCE) were also counted and the PCE/NCE ratio was recorded for
each animal. The positive control (cyclophosphamide) was adequate. At 183 mg/kg, no male mice
died, but at 267 mg/kg, 2 female mice died. No evidence of a cytotoxic response was observed in
the bone marrow cells of either sex at any dose level or sacrifice time, but the mortalities at the high
dose level for females were consistent with the results in the previously conducted toxicity study and
indicated that an appropriately high dose level was evaluated. In males, although no deaths occurred,
it was doubtful that the use of a higher lethal dose would have affected the outcome of the study. No
increased frequencies of micronuclei were observed at any dose level or sacrifice time in the bone
marrow cells of treated male or female mice. Bromoxynil octanoate did not induce a clastogenic
effect in this assay system. (MRID 41930802)
In an unscheduled DNA synthesis (UDS) assay, cultures of primary rat hepatocytes were
exposed to technical grade bromoxynil octanoate at concentrations ranging from 0.98 to 15.63 ug/ml.
Higher concentrations (> 31.25 ug/ml) were cytotoxic. The solvent used was DMSO. The positive
control (2-acetylamino-fluorene) was adequate. Bromoxynil octanoate did not induce an appreciable
increase in mean net nuclear grain counts compared to the negative solvent control at any of the
evaluated concentrations. Bromoxynil octanoate did not induce a genotoxic effect in this assay
system. (MRID 42078901)
g. Neurotoxicity
No potential for neurotoxicity has been observed in any of the animal studies with bromoxynil
phenol. Neither a delayed neurotoxicity study in hens (Guideline 81-7) nor a 28-day delayed
neurotoxicity in hens (Guideline 82-6) is required. The requirements for an acute neurotoxicity study
in rats (Guideline 81-8) and a 90-day neurotoxicity study in rats (Guideline 82-7) are reserved.
h. Immunotoxicity
The requirement for immunotoxicity testing (Guideline 85-7) is reserved for both the
bromoxynil phenol and octanoate. Information may be required at a later time.
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i. Metabolism
Bromoxynil Phenol
No general metabolism study (Guideline 85-1) is available in which bromoxynil phenol was
the test material. The requirement for a general metabolism study on bromoxynil phenol, however,
has been waived since sufficient information on the pharmacokinetics and metabolism of bromoxynil
phenol per se has been derived from general metabolism studies on bromoxynil octanoate and
bromoxynil heptanoate. Refer to the discussion under 1. Toxicity Equivalence below for additional
information on the bromoxynil heptanoate metabolism study.
Bromoxynil Octanoate
The absorption, distribution, excretion and metabolism of bromoxynil octanoate were studied
in male and female Sprague Dawley rats given single oral doses of 14C-bromoxynil octanoate by
gavage at dose levels of 2 or 20 mg/kg or at a dose level of 2 mg/kg following 14 days of unlabeled
bromoxynil octanoate administered by oral gavage at a dose level of 2 mg/kg/day. Results were
similar regardless of the dosing regimen. The rate of absorption was moderate in both males and
females. Peak plasma concentrations of radioactivity were not reached until 7-10 hours after dosing.
Radioactivity was widely distributed in most tissues. The highest concentrations were observed in
blood, plasma, liver, kidneys and thyroid (especially in females). Levels of radioactivity in tissues
were generally higher in females than in males. Most radioactivity was excreted in the urine (about
84-89% in males and 76-80% in females at 7 days) and considerably lesser amounts in the feces
(about 6-10% in both males and females at 7 days). Excretion was more rapid in males than in
females. Retention of radioactivity in tissues after 7 days was about 2-3% in males and 7-9% in
females. Essentially all bromoxynil octanoate was rapidly and nearly completely converted to
bromoxynil phenol via ester hydrolysis. In special studies, the only chemical species identified in
tissues was bromoxynil phenol per se; no bromoxynil octanoate was identified in tissues. In urine,
the only major species was free and conjugated bromoxynil phenol with no bromoxynil octanoate
present. In feces, however, some bromoxynil octanoate was identified. (MRID 00154756,
00154757, 42901001)
j. Dermal Penetration
The dermal absorption for the bromoxynil octanoate is 10.32% and the bromoxynil phenol
is 1.92% based on studies (40854602, 40854603) summarized below. The occupational cancer risk
was determined using the absorption factor of 10% (rounded from 10.32%).
Bromoxynil Phenol
14C-Bromoxynil phenol, solubilized in water with sodium hydroxide, was topically applied to
the skin of male Sprague Dawley rats at doses of 0.10, 1.0 or 10.0 mg/rat for durations of exposure
of 0.5, 1, 2, 4, 10 or 24 hours (4 rats/dose/duration of exposure). The quantity of radioactivity
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absorbed increased with dose and duration of exposure. Percent dermal absorption at 10 hours was
1.92%, 1.74% and 1.24% for doses of 0.10, 1.0 and 10.0 mg/rat respectively. Following a soap and
water wash (at 10 hours), 22.64%, 10.79% and 3.79% of the respective doses remained in/on the
skin. Percent dermal absorption at 24 hours was 3.12%, 3.24% and 3.02% for doses of 0.10, 1.0 and
10.0 mg/rat respectively. Following a soap and water wash (at 24 hours), 18.99%, 7.84% and 2.03%
of the respective doses remained in/on the skin. (MRID 40854602)
Bromoxynil Octanoate
14C-Bromoxynil octanoate, incorporated into the end-use product Buctril, which contained
33.4% bromoxynil octanoate as the active ingredient, was topically applied to the skin of male
Sprague Dawley rats at doses of 0.08, 0.4 or 3.4 mg/rat for durations of exposure of 0.5, 1, 2, 4, 10
or 24 hours (4 rats/dose/duration of exposure). The quantity of radioactivity absorbed increased with
dose and duration of exposure. Percent dermal absorption at 10 hours was 10.32%, 7.07% and
4.51% for doses of 0.08, 0.4 and 3.4 mg/rat respectively. Following a soap and water wash (at 10
hours), 6.46%, 8.06% and 6.13% of the respective doses remained in/on the skin. Percent dermal
absorption at 24 hours was 17.58%, 18.43% and 10.88% for doses of 0.08, 0.4 and 3.4 mg/rat
respectively. Following a soap and water wash (at 24 hours), 7.91%, 9.50% and 4.97% of the
respective doses remained in/on the skin. (MRID 40854603)
k. Other Toxic Endpoints
Bromoxynil is registered for use on transgenic cotton as a contact herbicide to control
broadleaf weeds. Non-transgenic cotton is sensitive to bromoxynil. The transgenic variety has been
engineered to resist the herbicidal effects of bromoxynil by hydrolyzing nitrile groups to a carboxylic
acid, 3, 5 - dibromo-4-hydroxybenzoic acid (DBHA).
The toxicity of DBHA must be considered as a result of the use on transgenic cotton.
Significant residues of DBHA are present on transgenic cotton. The Agency has examined the
structures of bromoxynil and DBHA. Based on this examination, there was no concern that DBHA
would exhibit significant toxicity over that of the parent bromoxynil. Bromoxynil and DBHA are
extremely similar in structure, varying only in that bromoxynil has a cyano (-CN) group that has been
converted to a carboxyl (-COOH) group in the DBHA metabolite. Conversion to a carboxyl group
is generally considered to decrease the toxicity of a molecule. The conversion to the carboxyl group
should cause the DBHA to be more polar and therefore more soluble in water and less in fats.
Additionally, the presence of the carboxyl group will allow DBHA to combine (conjugate) with
certain water soluble molecules (e.g. glucuronic acid) which should further increase DBHA's water
solubility and further decrease its solubility in fats. This increased water solubility as well as the
decreased fat solubility means that DBHA should be eliminated faster from the organism than
bromoxynil, and thus DBHA is less likely than bromoxynil to remain in the cell and engage in the
formation of additional, possibly toxic metabolites.
Additional data (four acute studies, two mutagenicity studies, and one subchronic study)
addressing the toxicity of DBHA have been submitted to the Agency. These studies are currently
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undergoing review. Based on the results of these reviews, if appropriate, the Agency will revise the
determination that DBHA has the same toxicity as the parent compound.
1. Toxicity Equivalence
The Agency has determined that bromoxynil (phenol) and bromoxynil octanoate are
lexicologically equivalent. Bromoxynil occurs in the form of the phenol (bromoxynil phenol); in the
form of the octanoate acid ester of bromoxynil (bromoxynil octanoate); and in the forms of several
other organic acid esters of bromoxynil (such as bromoxynil heptanoate, bromoxynil butyrate, etc.).
Based on the results of "bridging" studies and other relevant information, bromoxynil (phenol),
bromoxynil octanoate and bromoxynil heptanoate have been determined to be lexicologically
equivalent on a molar bases.
A critical part of the evidence supporting these conclusions was determination that ester
hydrolysis of bromoxynil octanoate to bromoxynil phenol (and octanoic acid) occurs readily and
almost completely in vivo following oral administration. Later this was shown to be the case for
bromoxynil heptanoate.
Since bromoxynil heptanoate and bromoxynil octanoate would be expected to have nearly
identical chemical/physical properties (based on their very close chemical structures), it was
hypothesized that hydrolysis of bromoxynil heptanoate to bromoxynil phenol (and heptanoic acid)
also would occur readily and completely in vivo following oral administration. Therefore, using the
phenol as the test material would yield the same, both qualitatively and quantitatively, as the results
of studies using bromoxynil heptanoate as the test material.
In addition, the Agency required that a general metabolism study and special tissue
distribution metabolite study in rats ( MRID 431914-01) using bromoxynil heptanoate as the test
material be submitted. These studies were received and reviewed. The overall conclusion of the
studies was that both bromoxynil heptanoate and bromoxynil octanoate are rapidly and nearly
completely converted to bromoxynil phenol in vivo, and the pharmacokinetic behavior, metabolism,
distribution and excretion of all three compounds are essentially identical in the animal body.
m. Dose-Response Assessment
(1) Determination of Safety for Infants and Children
Under the Food Quality Protection Act (FQPA), P.L. 104-170, which was promulgated in
1996 as an amendment to the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) and the
Federal Food, Drug and Cosmetic Act (FFDCA), the Agency was directed to "ensure that there is
a reasonable certainty that no harm will result to infants and children" from aggregate exposure to
a pesticide chemical residue. The law further states that in the case of threshold effects, for purposes
of providing this reasonable certainty of no harm, "an additional tenfold margin of safety for the
pesticide chemical residue and other sources of exposure shall be applied for infants and children to
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take into account potential pre- and post-natal toxicity and completeness of the data with respect to
exposure and toxicity to infants and children. Notwithstanding such requirement for an additional
margin of safety, the Administrator may use a different margin of safety for the pesticide residue only
if, on the basis of reliable data, such margin will be safe for infants and children."
Under this provision, the Agency will require a tenfold margin of safety if the Agency does
not have complete and reliable data to assess pre- or post-natal toxicity relating to infants and
children, or if the data indicate pre- or post-natal effects of concern. The data EPA will consider
include data submitted in compliance with EPA testing requirements, available data published in the
scientific literature, and any other data available to EPA and meeting general scientific standards.
Where reproductive and developmental data have been found acceptable by EPA, and the data do not
indicate potential pre- or post-natal effects of concern, the tenfold margin of safety can be reduced
or removed.
The bromoxynil data submitted to the Agency for review are sufficient for the assessment of
hazard to the developing organism (fifth Developmental Toxicity Peer Review Committee memo,
4/21/92). A total of 11 developmental and 3 reproductive toxicity studies were available for review.
These include oral prenatal developmental toxicity studies (three in rats, two in rabbits, and one in
mice with the phenol; one in rats with the octanoate), dermal prenatal developmental toxicity studies
(one each in rats and rabbits with both the phenol and the octanoate), and two dietary two-generation
reproduction studies in rats (one with the phenol; one with the octanoate) and one dermal
reproduction study. Developmental toxicity was observed, following in utero exposure to
bromoxynil, in multiple studies, by two routes of exposure, and in three species. The induction of
supernumerary ribs was shown to be the most sensitive indicator of developmental toxicity in fetal
rats, mice, and (in certain studies) rabbits. Upon consideration of the data base in its entirety, the
Agency determined that the developmental NOEL, for the induction of supernumerary ribs, resulting
from prenatal exposure to bromoxynil (phenol) is 4 mg/kg/day via the oral route and 10 mg/kg/day
via the dermal route. The developmental LOELs for bromoxynil phenol were 5 mg/kg/day by the oral
route and 50 mg/kg/day by the dermal route. Other forms of developmental toxicity, including
resorptions and malformations, were routinely observed in bromoxynil studies at higher dose levels.
Recently, the Agency reviewed the bromoxynil database for developmental toxicity with
particular regard to the requirements of FQPA. It was determined that the FQPA lOx factor should
be retained for the sub-population consisting of females 13+. This decision was based upon concerns
emanating from the toxicological profile, including evidence of increased susceptibility of fetuses to
bromoxynil exposure, the steep dose response curve, and the demonstrated severe developmental
effects at doses above the LOEL.
The population of concern is the developing fetus and the endpoint of concern is
supernumerary ribs. This endpoint, a developmental anomaly, results from in utero exposure;
therefore the population subgroup of concern is females 13+ years old. Although some systems in
infants and children continue developing, it is unlikely that supernumerary ribs, even though observed
across multiple species, would result from postnatal exposure. A 10-fold factor safety factor, as
required by FQPA, will provide additional protection for infants and children and ensure a reasonable
certainty of no harm to this sensitive subpopulation.
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(2) Reference Dose
The Agency has determined that the RfD for bromoxynil is 0.015 mg/kg/day, based on the
threshold NOEL/LOEL of 1.5 mg/kg/day determined in a 12-month chronic oral toxicity study in
dogs using bromoxynil phenol as the test material. (MRID 40780301, 41304701) Effects observed
at the threshold NOEL/LOEL of 1.5 mg/kg/day in the 12-month dog study were slightly decreased
body weight gains in males. At the next higher dose level (7.5 mg/kg/day), the following effects were
observed in both males and females: decreased body weight gain; increased salivation, panting, liquid
feces, and pale gums; decreased erythrocytes, hemoglobin, and packed cell volume; increased urea
nitrogen; and increased liver weights. An uncertainty factor of 100 based on interspecies
extrapolation (10X) and intraspecies variability (10X) was applied. The 10X safety factor as
required by FQPA for the protection of infants and children was removed in establishing the RfD
because the endpoint is based on systemic toxicity (decreases in body weight gains) observed in one
sex (male) of adult animals (dog) in a long-term (chronic) study (i.e., the endpoint of concern is not
a developmental endpoint).
Bromoxynil has not been reviewed by the FAO/WHO Joint Committee.
(3) Carcinogenicity Classification and Risk Quantification
Bromoxynil phenol has been classified by the Agency as a Group C, possible human
carcinogen. A low dose extrapolation model (Qj*) was applied to the experimental animal tumor
data for quantification of human risk. For the purpose of estimating carcinogenic risk to humans, the
estimated unit risk or Qx* is 1.03 x 10"1 (mg/kg/day)"1. This weight-of-the-evidence determination
was based primarily on results in two mouse carcinogenicity studies. In the first study, which used
dose levels of 10, 30 and 100 ppm in Swiss albino mice (MRID 00068077), a dose-related increased
incidence of liver adenomas/carcinomas combined was observed in the male mice. The increase was
statistically significant at 100 ppm. The liver tumor response in male mice included both benign and
malignant tumors with the carcinomas contributing to almost one-half of the total
adenomas/carcinomas at the mid- and high-dose levels. An increase in the incidence of hyperplastic
nodules, some of which may have been adenomas, was also observed in the livers of male mice at the
mid- and high-dose levels. An increased incidence of neoplasms was not observed in female mice,
but dose levels for the female mice in this study were determined to be too low to assess carcinogenic
potential. In the second study, which used dose levels of 20, 75 and 300 ppm in CD-I mice (MRID
43245501, 43311701), treatment-related increased incidences of liver adenomas, carcinomas and
adenomas/carcinomas combined were observed in male mice at all dose levels. For female mice given
300 ppm, slightly increased incidences of liver carcinomas and of adenomas/carcinomas combined
also were considered to be related to treatment with bromoxynil phenol. Dose levels in this study
were adequate. Information from genotoxicity studies, which included three positive studies, and
structure activity relationship (SAR) data provided additional support for the classification.
An increased incidence of neoplasms was not observed in carcinogenicity studies in Fischer
344 rats (MRID 00096521) or in Sprague Dawley rats (MRID 40612501, 41374801). Dose levels
in the Fischer 344 rat study, however, were determined to be too low to assess carcinogenic potential.
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n. Toxicological Endpoints for Risk Assessment
i. Acute dietary (for females 13+)
For dietary exposure, it is anticipated that the exposure will be to bromoxynil phenol, rather
than to bromoxynil octanoate, due to conversion of this ester to bromoxynil phenol in the
environment. The NOEL to be used for risk assessment is the developmental toxicity NOEL of 4
mg/kg/day from a developmental toxicity study (MRID 40466802) where bromoxynil phenol was
administered to groups of pregnant Sprague-Dawley rats orally by gavage at daily doses on gestation
days 6-15, inclusive. The developmental LOEL of 5 mg/kg/day is based on dose-related increases
in the incidence of supernumerary ribs observed in the same strain of rats (Sprague-Dawley) in
another study (MRID 00116558). The LOEL from another study was used since the LOEL (5
mg/kg/day) in this study was lower than the LOEL (12.5 mg/kg/day) established in the previous study
(MRID 40466802).
The lOx safety factor for the protection of infants and children was retained for this
population (females 13+) because the endpoint of concern is a develpmental anomaly (supernumerary
ribs) occurring following in utero exposure, and thus is relevant for the population of concern
(females 13+). Therefore, a MOE of 1000 is required for acute dietary risk assessment for females
13+. This MOE of 1000 includes lOx for inter-species extrapolation, lOx for intra-species variation
and lOx for the FQPA safety factor.
ii. Acute Dietary (All populations except females 13+)
The Agency established a NOEL of 8 mg/kg/day from the 13-week range-finding study
(MRID 43166701) in which bromoxynil phenol was administered orally in capsules to male and
female beagle dogs as the endpoint to be used for acute dietary risk assessment for all populations
except females 13+. The LOEL of 12 mg/kg/day was based on increased incidence of panting on day
1, suggestive of a compensatory reaction to the effects of the test material, which at higher doses is
expressed as elevated body temperature.
The lOx safety factor for the protection of infants and children was removed for all
populations (except females 13+) because the endpoint for acute dietary risk assessment is based on
systemic toxicity (increased incidence of panting) in adult dogs. Therefore, a MOE of 100 includes
lOx for interspecies extrapolation and lOx for intraspecies variation.
The NOEL of 8 mg/kg/day was selected solely for acute dietary risk assessment based on the
recommendations of the Toxicology Endpoint Selection Committee (document dated 5/5/97) which
differs from the study NOEL of 1 mg/kg/day (as shown in Table 4, page 11). The reason for
establishing a different NOEL is based on finding an endpoint that reflects a single exposure since this
time frame was applicable to the acute dietary exposure risk assessment. During the first day of the
study, the predominant events were mortality, elevated rectal temperatures and panting. The
Toxicology Endpoint Selection Committee considered these 3 events to be directly related to one
another. At this dose level (8 mg/kg/day), no deaths and no elevated temperatures were observed.
Although some panting was observed during the first week of treatment, it could not be established
32
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that panting occurred after a single dose of the test material on day one. Therefore, a NOEL of 8
mg/kg/day and a LOEL of 12 mg/kg/day (based on panting) were established for the first day of the
study.
iii. Short Term (1 to 7 days) and Intermediate Term (1 Week to
Several Months) Occupational Exposure
The Agency selected the NOEL of 10 mg a.i./kg/day from the developmental toxicity study
(MRID 41163301)in which bromoxynil octanoate (incorporated into Buctril formulation blank) was
applied dermally to groups of pregnant Sprague-Dawley rats. A dose-related increased litter
incidence of supernumerary ribs was observed at the developmental toxicity LOEL of 15 mg
a.i./kg/day. At 20 and 75 mg a.i./kg/day, the litter incidences of supernumerary ribs were increased
still further. The maternal toxicity NOEL is 15 mg a.i./kg/day and the maternal toxicity LOEL is 20
mg a.i./kg/day, based on decreased body weight gain and decreased food consumption. (Extracted
from "Fifth Developmental and Reproductive Toxicity Peer Review of Bromoxynil", Gary Burin and
Ann Clevenger, April 21, 1992). This endpoint is appropriate for all occupational subpopulations
because, in this case, it happens to be the most sensitive endpoint overall for estimating occupational
risks.
An uncertainty factor of 100, based on interspecies extrapolation (10X) and intraspecies
variability (10X) is recommended. An additional lOx is not required because the FQPA safety factor
is not applied for occupational exposure scenarios. Therefore, a MOE of 100 is considered
appropriate for short term and intermediate term exposure to occupational workers.
iv. Chronic (noncancer) Exposure (dermal route)
The Agency selected the developmental NOEL of 10 mg a.i./kg/day from a developmental
toxicity study (MRID 41163301) in which bromoxynil octanoate (incorporated into Buctril
formulation blank) was applied dermally to groups of pregnant Sprague-Dawley rats on gestation
days 6-15, inclusive. A dose-related increased incidence of supernumerary ribs was observed at the
developmental toxicity LOEL of 15 mg a.i./kg/day. At 20 and 75 mg a.i./kg/day, the incidences of
supernumerary ribs were increased still further. The maternal toxicity NOEL is 15 mg a.i./kg/day and
the maternal toxicity LOEL is 20 mg a.i./kg/day, based on decreased body weight gain and decreased
food consumption.
An uncertainty factor of 100, based on interspecies extrapolation (10X) and intraspecies
variability (10X) is recommended. An additional lOx is not required because the FQPA safety factor
is not applied for occupational exposure scenarios. Therefore, a MOE of 100 is considered
appropriate for chronic (non-cancer) term exposure to occupational workers.
v. Inhalation Exposure (Any time period)
Inhalation exposures are expected to be negligible compared to the dermal route. The acute
inhalation LC50 for bromoxynil octanoate is 0.81 mg/L (M) and 0.79 mg/L (F) (toxicity category III)
and the acute inhalation LC50 for Buctril formulation is 1.1 mg/liter (toxicity category III). The active
33
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ingredient for all registered end-use products is either bromoxynil octanoate or bromoxynil
heptanoate. On this basis, the Agency determined a risk assessment for exposure by the inhalation
route is not required.
phenol.
There are no repeated dose inhalation studies on either bromoxynil octanoate or bromoxynil
vi. Dermal Absorption
14C-Bromoxynil octanoate, incorporated into the end-use product Buctril, which contained
33.4% Bromoxynil octanoate as the active ingredient, was topically applied to the skin of male
Sprague-Dawley rats at doses of 0.08, 0.4 or 3.4 mg/rat for durations of exposure of 0.5, 1, 2, 4, 10
or 24 hours (4 rats/dose/duration of exposure). The quantity of radioactivity absorbed increased with
dose and duration of exposure. Percent dermal absorption at 10 hours was 10.32%, 7.07% and
4.51% for doses of 0.08, 0.4 and 3.4 mg/rat respectively. Following a soap and water wash (at 10
hours), 6.46%, 8.06% and 6.13% of the respective doses remained in/on the skin. Percent dermal
absorption at 24 hours was 17.58%, 18.43% and 10.88% for doses of 0.08, 0.4 and 3.4 mg/rat
respectively. Following a soap and water wash (at 24 hours), 7.91%, 9.50% and 4.97% of the
respective dose is assumed for this risk assessment. The occupational cancer risk was determined
using the absorption factor of 10% (rounded from 10.32%).
Table 9: Summary of Toxicological Endpoints for Bromoxynil
Exposure Duration
Acute
females 13+
Acute
general population (except females
13+)
Chronic (non-cancer)
Chronic (cancer)
Short-Term Occupational
Intermediate-Term Occupational
Inhalation (any time period)
Chronic Occupational (noncancer)
Carcinogenic Potential Occupational
Exposure Route
Dietary
Dietary
Dietary
Dietary
Dermal
Dermal
Inhalation
Dermal
Dermal
Endpoint
Developmental NOEL of 4 mg/kg/day (oral)
MRID 40466802 & 00116558
MOE = 1000
Systemic NOEL of 8 mg/kg/day (oral)
MRID 43 166701
MOE = 100
NOEL/LOEL 1.5 mg/kg/day (oral)
MRID 40780301 & 41304701
UF= 100
RfD = 0.015 mg/kg/day
Q!* = 0.103 (mg/kg/day)-1
Developmental NOEL of 10 mg/kg/day (dermal)
MRID 4 1163301
MOE =100
Developmental NOEL of 10 mg/kg/day (dermal)
MRID 4 1163301
MOE=100
Not required based on expected lack of exposure
Developmental NOEL of 10 mg/kg/day (dermal)
MRID 4 1163301
MOE =100
Q!* = 0.103 (mg/kg/day)-1
34
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2. Exposure Assessment and Risk Assessment
a. Dietary Exposure - Food Sources
i. Directions for Use
There are five bromoxynil end-use products (EPs) with food/feed uses registered to Rhone-
Poulenc Corporation. These EPs are presented below.
Table 10: EP Products With Food/Feed Uses
Active Ingredient (code)
Bromoxynil octanoate
(035302)
Bromoxynil heptanoate
(128920)
EPA Reg No.
264-437
264-438 b
264-477 c
264-53 ld
264-540 d
264-531
264-540
Label Acceptance
Date
6/95
3/95
3/95
11/95
5/95
11/95
5/95
Formulation
Class a
2 Ib/gal EC
2 Ib/gal EC
1 Ib/gal EC
4 Ib/gal WPe
4 Ib/gal EC
4 Ib/gal WPe
4 Ib/gal EC
Product Name
Buctril® Herbicide
Bronate® Herbicide
Buctril® + atrazine
Herbicide
Buctril® Gel
Buctril® 4EC Herbicide
Buctril® Gel
Buctril® 4EC Herbicide
a The active ingredients for the formulated products are expressed in terms of bromoxynil equivalents.
b EPA Reg. No. 264-438 is a MAI formulation that also contains 34.0% isooctyl ester of MCPA (2 Ib/gal
MCPA equivalents).
EPA Reg. No. 264-477 is a MAI formulation that also contains 21.6% atrazine (2 Ib/gal).
d EPA Reg. Nos. 264-531 and 264-540 are MAI formulations containing both the octanoic and heptanoic acid
esters of bromoxynil for a total of 4 Ib bromoxynil equivalent/gal.
e This is a gel formulation, designated as a WP.
Based on available data, registered labels should specify the following for rotational crops:
"After applying up to 2 pints/A/season of [Buctril® or Buctril ® 4EC], wait a minimum of
30 days from the date of the application, and then plant any rotational crop."
"After applying more than 2 pints/A/season of [Buctril® or Buctril ® 4EC], only transgenic
BXN cotton may be planted as a rotational crop."
[Acceptable studies previously submitted in support of reregistration reflect a maximum seasonal and
single application rate of 0.5 Ib ai/A, but the use on cotton constitutes a maximum seasonal
application rate of 1.5 Ib ai/A. Required limited field rotational crop studies reflecting a maximum
application rate of 1.5 Ib ai/A are on-going.]
The registrant's use directions for corn (field and pop), sorghum, onions and sudangrass are
inconsistent and should be amended:
35
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! Corn (field and pop): Use directions on labels 264-437 and 264-531 specify a maximum
seasonal rate of 0.5 Ib ai/A, while labels 264-477 and 264-540 specify a maximum seasonal
rate of 0.75 Ib ai/A. In addition, on labels 264-531 and 264-540, maximum seasonal rates
listed under "Special Use Directions" (0.75-1.25 Ib ai/A) are higher than the maximum
seasonal rates listed under "Use Restrictions" (0.5-0.75 Ib ai/A). Use directions for corn
should be amended so that all labels specify the maximum seasonal use rate of 0.5 Ib ai/A,
which is supported by available residue data.
! Sorghum: Labels 264-437 and 264-531 specify a maximum seasonal rate of 0.5 Ib ai/A,
while labels 264-477 and 264-540 specify a maximum seasonal rate of 0.75 Ib ai/A. In
addition, the maximum seasonal rate listed on label 264-540 under "Special Use Directions"
(1.25 Ib ai/A) is higher than the maximum seasonal rate listed under "Use Restrictions" (0.75
Ib ai/A). Labels 264-437 and 264-540 also list maximum single application rates of 0.5-0.75
Ib ai/A, but state "do not apply at 0.5 Ib ai/A rate to sorghum". Use directions for sorghum
should be amended so that all labels specify the maximum single and seasonal use rate of 0.5
Ib ai/A, which is supported by available residue data.
! Onions: Use directions on labels 264-437 and 264-531 restrict preemergence application to
onions grown east of the Mississippi River on muck soils with >10% organic matter. Label
264-540 should be amended to include this restriction. In addition, label 264-437 specifies
that postemergence applications should not be made using aerial equipment. This restriction
should be deleted from the label since it implies that preemergence applications using aerial
equipment are acceptable [under "Application Procedures," the only type of equipment listed
for applications on onions is ground equipment].
! Sudangrass: Labels 264-437 and 264-531 specify a pre-grazing interval (PGI) of 30 days.
The Agency does not currently permit PGIs for grasses grown only for forage. However,
since products containing bromoxynil are applied prior to the pre-boot stage, and since the
first cutting for forage would occur in approximately 30 days, the Agency will allow the PGI
to remain on registered labels.
Refer to Appendix I for a summary of the "Food/Feed Use Patterns Subject to Reregi strati on
for Bromoxynil".
ii. Plant and Livestock Metabolism
For the purpose of reregi strati on, the qualitative nature of the residue in plants is adequately
understood based on acceptable alfalfa, sweet corn, and transgenic (BXN) cotton metabolism studies
conducted using bromoxynil octanoate. The residue of concern in plants other than cotton is
bromoxynil per se. The residues of concern in transgenic BXN cotton and cotton commodities (i.e.
hulls, meal and cotton gin byproducts) are bromoxynil and its metabolite 3,5-dibromo-4-
hydroxybenzoic acid (DBHA). The DBHA metabolite is only found in transgenic cotton, and not in
other commodities.
36
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The qualitative nature of the residue in livestock is adequately understood for bromoxynil
octanoate, based on acceptable ruminant and poultry metabolism studies. Since the metabolite
DBHA is found in commodities considered to be livestock feed items, the potential for transfer of
secondary residues to livestock exists. The nature of the residue in livestock following oral dosing
with DBHA is not adequately understood. The Agency has assumed that DBHA is of potentially
equal toxicity to the parent, bromoxynil, and could transfer to livestock tissues in proportion to the
parent. Therefore, pending receipt of additional metabolism data for DBHA, EPA has concluded that
the residues of concern in livestock are bromoxynil and its metabolite DBHA. Because the registrant
has agreed with this Agency assumption and DBHA is included in the tolerance expression for cotton,
no additional studies are required.
The structures of bromoxynil, its octanoic and heptanoic acid esters, and its maj or metabolites
are presented in Figure A.
Figure A. Bromoxynil, its octanoic and heptanoic acid esters, and metabolites
Common Name/Chemical Name
Bromoxynil phenol
3,5-dibromo-4-hydroxybenzonitrile
OH
Br J\ .Br
CN
Bromoxynil octanoate
O
O
Br
.Br
CN
Bromoxynil heptanoate
O
O
Br ,A .Br
CN
37
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Common Name/Chemical Name
3,5-dibromo-4-hydroxybenzoic acid
(DBHA)
OH
Br
O OH
3,5-dibromo-4-hydroxybenzamide
OH
,-Br
O NH,
4-hydroxybenzonitrile
OH
CN
ii. Residue Analytical Method - Plants and Livestock
Adequate analytical methodology is available for data collection and tolerance enforcement
for bromoxynil per se in plants. Method I in PAM, Vol. II, is a GLC/MCD that has undergone a
successful EPA method validation on wheat grain. This method involves alkaline hydrolysis in
methanolic KOH to convert residues to bromoxynil, cleanup by liquid-liquid partitioning, methylation
using diazomethane, further cleanup on a Florisil column, and determination by GLC/MCD. Method
la is the same method, but uses GC/ECD for determination of methylated bromoxynil.
Method A is a GC/MCD or BCD method for the analysis of bromoxynil residues in livestock
tissues and is essentially the same as Method I. Method B is a GC/ECD method that is also similar
to Method I, with modifications to the cleanup procedures.
Rhone-Poulenc methods SOP 90018 and SOP 90020 and McKenizie Laboratories Method
PRM-029 were used in determining residues of bromoxynil for data collection in plants and livestock.
These are all GC/ECD methods that are similar to Method I and use modified cleanup procedures
following extraction. The limits of quantitation (LOQs) for bromoxynil using these methods are 0.02
ppm for plant commodities and 0.05 ppm for livestock commodities.
38
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The FDA PESTDATA database dated 1/94 (Pam Vol. I, Appendix I) indicates that recovery
of bromoxynil octanoate and bromoxynil butyrate using FDA Multiresidue Protocol E (PAM I
Section 211.1) is variable. Bromoxynil has recently been tested through Multiresidue Protocols B
and C; since bromoxynil was not detected through Protocol C, further testing under Protocol E was
not required. Testing under Protocols A and D was not required. This information has been
forwarded to FDA for inclusion in the PESTDATA database. No data are reported for the methyl
ether of bromoxynil.
For data collection purposes, cottonseed and gin trash samples were analyzed using the
analytical method "Bromoxynil: Method of Analysis for Bromoxynil and its Metabolite, 3,5-
Dibromo-4-hydroxybenzoic Acid in Cottonseed, Gin Trash, and Seed Processed Fractions using GC-
MSD." The method (Method RES9603) has been the subject of an Independent Laboratory
Validation (ILV) and an Agency Petition Method Validation (PMV); although there were problems
with the LOQ for DBHA in gin trash during the PMV, the Agency concludes the method is adequate
for data collection. Additional method validation data submitted to the Agency 1/7/98 address
problems encountered with the PMV, and are under review. Approval of the method for enforcement
purposes is anticipated.
There is currently no method available for data collection or tolerance enforcement for the
DBHA metabolite in livestock commodities. Although the use of measurement of parent bromoxynil
residues as a marker for the DBHA metabolite has been discussed, the Agency concluded the use of
the parent bromoxynil as a "marker" for the DBHA metabolite in meat, milk, poultry and eggs cannot
be supported, based on available residue data for bromoxynil and the DBHA metabolite in cotton gin
trash and cottonseed. The registrant has submitted an enforcement method for DBHA. It is currently
undergoing Agency review and validation.
iii. Storage Stability
No additional storage stability data are required to support currently registered uses.
Bromoxynil octanoate residues are stable in plant commodities stored at -10 C for up to 12 months.
Adequate storage stability data have been submitted on the following commodities: alfalfa (forage
and hay), barley (grain, forage, hay, and straw), field corn (grain, forage, silage, and fodder), sweet
corn (kernels, K+CWHR, cannery waste, and forage), cottonseed, flax (seed and straw), grass
(forage, hay, and seed screening), garlic, onion, sorghum (grain, forage, fodder, silage, and hay), and
wheat (grain, forage, hay, and straw). Supporting storage stability data for animal matrices are not
required since the majority of samples in both the ruminant and poultry feeding studies were analyzed
within 21 days of sacrifice.
Adequate data demonstrate stability of bromoxynil phenol in frozen storage in frozen cotton
substrates (cottonseed, meal, hulls, gin trash and cottonseed oil) for an interval of at least 9 months.
The DBHA metabolite is stable in frozen cottonseed, gin trash, meal, and oil for at least 9 months;
in cotton hulls, DBHA residues declined 50% after 1 month of storage.
39
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iv. Magnitude of the Residue/Potable Water - Not Applicable
v. Magnitude of the Residue/Fish - Not Applicable
vi. Magnitude of the Residue/Irrigated Crops - Not Applicable
vii. Magnitude of the Residue /Food Handling - Not Applicable
viii. Magnitude of the Residue/Meat, Milk, Poultry & Eggs
Tolerances are currently established for bromoxynil residues in the fat, meat, and meat by-
products of cattle, goats, hogs, horses, and sheep [40 CFR §180.324(a)(l)]. As required based on
available data, tolerances are herein established for residues in milk, eggs, and poultry. Acceptable
ruminant and poultry feeding studies have been submitted for bromoxynil. No feeding studies
conducted using the DBHA metabolite have been submitted; therefore, the results of the bromoxynil
feeding studies have been used as the basis for setting tolerances which include the DBHA metabolite.
The Agency has recommended inclusion of tolerances for secondary residues in livestock
commodities under 40 CFR §180.324(a)(2), i.e. including bromoxynil and DBHA.
Although the Agency previously concluded that residues in poultry commodities could be
classified under Category 3 of 40 CFR §180.6(a), i.e., no reasonable expectation of detectable
residues, clarification of the Agency's policy with respect to Category 3, changes this conclusion for
bromoxynil/poultry. Tolerances are now required for secondary residues of bromoxynil and DBHA
in poultry commodities. Tolerances in livestock commodities have been reassessed based on available
field trial data and label revisions for livestock feed items, including cotton commodities. The
following tolerances for bromoxynil and DBHA residues have been recommended for meat-by-
products (mbyp), fat, and meat of cattle, goats, hogs, horses and sheep and in milk, eggs and the
meat, fat, and meat by-products of poultry [refer to the "Tolerance Reassessment Summary"]:
Ruminants/Swine
meat 0.5 ppm
mbyp 3.5 ppm
fat 1.0 ppm
milk 0.1 ppm
Poultry
meat 0.05 ppm
fat 0.05 ppm
mbyp 0.3 ppm
eggs 0.05 ppm
A new poultry feeding study had been required, pending submission of additional cotton field
trial data. Based on the new field trial data and resultant theoretical maximum dietary burden for
poultry, the requirement for a new poultry feeding study is waived.
40
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ix. Magnitude of the Residue/Crop Field Trials
Processing Food and Feed
The reregistration data requirements for magnitude of the residue in plants are fulfilled for the
following crops: barley, corn (field and pop), flax, garlic, onions, sorghum, wheat, aspirated grain
fractions, alfalfa, grasses (including Sudangrass) and mint. Adequate field trial data depicting
residues of bromoxynil following applications made according to the maximum or proposed use
patterns (provided that changes stipulated under "Directions for Use" are made on registered labels)
have been submitted for these commodities. Geographic representation is adequate and a sufficient
number of trials reflecting representative formulation classes were conducted. Barley and wheat data
can be translated to oats and rye, therefore, residue data are adequate to support the currently
registered uses.
The reregistration requirements for magnitude of the residue in processed food/feed
commodities are fulfilled for barley, corn, cottonseed, flaxseed, oats, rye, sorghum, wheat and mint.
Data from the barley and wheat processing studies can be translated to oats and rye. Bromoxynil
residues do not concentrate in processed plant commodities. Residues of the metabolite DBHA
concentrate in cottonseed hulls. No additional data are required.
x. Magnitude of the Residue-Cotton Petition (PP #3F4233)
Reduced rate cotton field trials required by the Agency as a condition of extension of the time-
limited tolerances on cotton were submitted to the Agency and found to be adequate for the purpose
of tolerance assessment and for dietary risk assessment. Transgenic (BXN) cotton was treated with
two broadcast applications of bromoxynil, once at 1 Ib ai/A when cotton was 12-14 inches tall, and
again at 0.5 Ib ai/A at first bloom. The resulting (maximum) seasonal application rate was 1.5 Ib ai/A.
The Agency has accepted labels specifying: 1 or 2 applications of 0.5 Ibs ai/A/application timed prior
to planting, just prior to cotton emergence but after weed emergence, or until cotton reaches a height
of 12 inches; and a third application at 0.5 Ib ai/A after cotton is 12 inches tall during bloom but no
later than 75 days prior to harvest. Therefore, the following application instructions to transgenic
BXN cotton are required:
"Apply from just prior to planting cotton until 75 days prior to harvest. Do not exceed 2
applications before cotton is 12 inches tall and 1 application after cotton exceeds 12 inches
in height. Make the last application during bloom, but not later than 75 days before harvest."
Based on the new field trial data, revised recommended tolerances for bromoxynil and DBHA
residues in cottonseed, cotton gin by-products and cotton hulls are 1.5, 7.0 and 5.0 ppm, respectively
[refer to the Tolerance Reassessment Summary].
xi. Reduction of the Residues - Not Applicable
xii. Confined Rotational Crops
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Adequate data are available to determine the nature of the residue in rotational crops; the
residue of concern in rotational crops is bromoxynil, per se.
xiii. Field Rotational Crops
A 30-day plantback interval (FBI) is required for all crops except cotton. Required additional
limited field rotational crop studies reflecting a maximum seasonal application rate of 1.5 Ib ai/A are
ongoing. Acceptable studies previously submitted in support of reregistration reflect a maximum
seasonal and single application rate of 0.5 Ib ai/A, but the use on cotton constitutes a maximum
searsonal application rate of 1.5 Ib ai/A.
Submitted field rotational crop data indicate that registered labels should specify the
following:
"After applying up to 2 pints/A/season of [Buctril® or Buctril ® 4EC], wait a minimum of
30 days from the date of the application, and then plant any rotational crop."
"After applying more than 2 pints/A/season of [Buctril® or Buctril ® 4EC], only transgenic
BXN cotton may be planted as a rotational crop."
xiv. Anticipated Residues for Dietary Risk Assessment
In spite of a lack of monitoring data for bromoxynil, the anticipated residues summarized
below are considered to be highly refined. First, field trial residues in raw agricultural commodities
consumed by people were nondetectable; anticipated residues were based on /^ the limit of
quantitation (LOQ), and were further refined by percent crop treated data provided by the Agency.
Field trial residues from all forages (i.e. sorghum, wheat, oat, corn, alfalfa) and all hays were
averaged, and the additional refinement for percent crop treated was applied. Although forages and
hays contained detectable bromoxynil residues, the averages used were significantly lower than
tolerance-level residues.
Based on evaluation of the additional information provided by the registrant, the Agency
reduced the contribution of cotton gin products (gin trash) to the dietary burden for ruminants by
assuming it contributes 5% of the diet for beef cattle and 1% for dairy cattle. The refinement for the
proposed cotton percent crop treated was also included. The only commodities which contribute
significantly to exposure to bromoxynil and/or DBHA in the diet for the general US population (or
any subpopulation) are meat, milk, poultry and eggs, based on secondary residues resulting from
consumption of livestock feed items.
Tables 10 and 11 summarize anticipated residues (ARs) that were used in the chronic/cancer
dietary risk assessment for bromoxynil. The ARs calculated and summarized below were all
significantly lower than residues which can be reliably measured using available analytical methods.
Table 10 includes ARs for commodities other than cotton and livestock, while Table 11 includes
42
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cotton/livestock ARs for a cotton percent crop treated of 10%. The values for percent crop treated
for all commodities were incorporated into the anticipated residues, and were therefore not applied
in conducting the DRES analyses.
Table 10: Summary of Bromoxynil Anticipated Residues (Except Cotton/Livestock) for
Chronic/Cancer Dietary Risk Assessment
Commodity
Cereal Grains [wheat, corn, oats,
barley, rye, sorghum]3
Includes processed commodities
Onions
Garlic
Peppermint oil/Spearmint oil
Recommended
Tolerance (ppm)
0.05
0.1
0.1
-
Anticipated Residue
in RAC (ppm)1
0.01
0.01
0.01
0.03
% Crop
Treated2
10
62
100
71
Anticipated Residue for
DRES Run (ppm)
0.001
0.0062
0.01
0.024
Anticipated residues of 0.01 ppm represent Vithe limit of quantitation (LOQ), since there were no detectable residues.
Assuming a maximum percent crop treated of 13% for barley, 10% for corn, 13% for durum wheat, and 10% for spring and other wheats; the
likely maximum percent crop treated for remaining cereal grains (i.e. rye, oats, and sorghum) was much lower. For the current dietary risk
assessment, 10% crop treated was assumed for all cereal grains as well as for forages/hays.
Since residues do not concentrate in processed commodities of cereal grains, the anticipated residue of 0.001 ppm was used for such
commodities in the DRES analysis (i.e. corn oil, flour, etc.).
There is no established tolerance for residues in mint oil. No tolerance is required for residues in mint oil since residues are reduced during
processing of hay to produce mint oil; the tolerance for residues in the leaves (0.1 ppm) is adequate to cover residues in the oil.
Table 11: Summary of Bromoxynil Anticipated Residues in Cotton/Livestock for
Chronic/Cancer Dietary Risk Assessment
RAC
Cottonseed
Cottonseed meal
Cottonseed oil
Meat3
MBYP3
Fat3
Milk3
Swine meat
Swine MBYP
Swine fat
Poultry meat
Poultry MBYP
Poultry Skin/Fat
Eggs
Tolerance (ppm)
1.51
-
~2
0.5
3.0
1.0
0.1
0.5
3.0
1.0
n/a4
Anticipated residues with Transgenic Cotton Use
0.03
0.01
0.03
0.0030
0.0175
0.0064
0.00040
0.00016
0.00094
0.00034
0.00025
0.0014
0.00031
0.00010
Refer to the 5/13/98 FR notice for details regarding this tolerance in cotton commodities.
The residue level in cottonseed was also used for cottonseed oil in the DRES analysis.
These anticipated residues were also used for meat, fat and meat by-products of horses, goats and sheep in the DRES runs.
Tolerances are not currently established for bromoxynil residues in poultry commodities, but are required based on revised dosing levels in the
poultry feeding study (ChemS AC decision dated 10/30/97). Tolerances for poultry commodities are included in the tolerance reassessment.
43
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b. Dietary (food sources) Risk Characterization
The toxicity endpoints identified in the Dose Response Section and the Dietary Exposure
Section of this document indicate a chronic, cancer and two acute dietary risk assessments are
appropriate for bromoxynil.
i. Acute Dietary Risk (Food Sources)
Previously (9/24/97), a detailed acute dietary exposure analysis was conducted using
anticipated residues on blended commodities as applicable and tolerances. Anticipated residues were
used for grains, milk and mint oils, without the adjustment for percent crop treated. Tolerance level
residues were used for onions; garlic; fat, meat by-products and meat of cattle, goats, hogs, horses
and sheep. For bromoxynil, the acute dietary risk from food sources for the general population and
all population subgroups, exceptfemales 13+years old did not exceed the Agency's level of concern.
The MOE for females 13+ was less than 1000 and therefore exceeded the level of concern.
The registrant has since submitted an acute (probabilistic) dietary analysis including the
proposed cotton use incorporating the residue data submitted to support the lower use rates discussed
above. The assessment was performed by Novigen Sciences, Inc. for Rhone Poulenc. The
assessment used the consumption data from the 1989-1992 Continuing Survey of Food Intakes by
Individuals (CSFII). The consumption database used in this probabilistic assessment has been
provided to the Agency.
The acute dietary risk assessment was conducted as a probabilistic risk assessment, assuming
single day exposure. In the assessment, each person-day of food consumption was matched with
randomly selected residue values for this assessment from field trails submitted in support of the
chemical. Percent crop treated data were included in the assessment as zeroes to account for portions
of the crop to which bromoxynil was not applied. The assessments assumed that 10% of the cotton
crop would be treated. This process was repeated one thousand times for each person-day in the
consumption database. The assessment assumed that the treated commodities were evenly distributed
in the food supply. Secondary residues in meat and milk from consumption of treated feed items were
included in the form of a probabilistic assessment, varying residues in the diet in accordance with the
data from the field trails. The assumptions for the dietary exposure were reviewed and found to be
acceptable.
The acute assessment used a NOEL of 4 mg/kg BW/day based on developmental effects for
females 13+ years old and a NOEL of 8 mg/kg BW/day based on systemic effects for all populations
except females 13+ years old. For the acute assessment, all of the subgroups evaluated have MOEs
far in excess of the required value of 1000 for females 13+ and 100 for all populations except females
13+ years old indicating that the potential for an adverse effect from a single day dietary (food only)
exposure is unlikely. The MOE is a measure of how closely the exposure comes to the NOEL and
is calculated as a ratio of the NOEL to the exposure (NOEL/exposure). The MOEs and the exposure
values for various population subgroups are listed in Table 12 below.
44
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Table 12: Acute Dietary Assessment for Bromoxynil
Population Subgroup
US population
Non-Nursing Infants
Nursing Infants
All Infants
Children (1-6 years)
Children (7-12 years)
Females 13+
Exposure (mg/kg BW/day)
0.000137
0.000244
0.000097
0.000219
0.000288
0.000144
0.000082
MOE
>58,000
>32,000
> 82,000
> 36,000
>35,000
>55,000
>24,000
ii. Chronic Dietary Risk (Food Sources)
Previously (9/24/97), the chronic and carcinogenic dietary exposure analysis from food sources
(including cotton) were conducted using refined residue levels based on anticipated residues and
percent crop treated information. A revised chronic and carcinogenic dietary exposure analysis from
food sources (including cotton) has been conducted for bromoxynil in conjunction with Rhone-
Poulenc's 9/24/97 petition to increase the acreage for application to transgenic BXN cotton. [This
petition was granted, 5/13/98. Cotton acreage permitted for bromoxynil application increased from
400,000 acres to 1.3 million acres.] The current assessment has been prepared using new cotton
residue data submitted by Rhone-Poulenc along with other data supporting re-instatement of the time-
limited tolerances for bromoxynil and its metabolite DBHA (3,5-dibromo-4-hydroxybenzoic acid) in
cotton commodities.
Table 13 below lists the results of the chronic dietary risk analysis conducted based on the new
residue data, and on revised anticipated residues which incorporate all uses of bromoxynil (refer to
Tables 10 & 11 above).
Table 13: Chronic Dietary Risk for Bromoxynil - % of RfD
Population Subgroup
U.S. Population
Non-Nursing Infants1 (<1 Year
Old)
Registered Uses (i.e., Excluding
Cotton)
<1
<1
Cotton @ 10 %CT + Registered Uses
<1
<1
'Non-Nursing Infants is the population subgroup with the highest exposure to bromoxynil.
For chronic effects other than cancer, for all population subgroups, less than 1% of the RfD
was consumed.
Table 14 below shows the results of the carcinogenic dietary risk analyses conducted based on
the new residue data, and on revised anticipated residues which incorporate all uses of bromoxynil
(refer to Tables 10 & 11 above).
45
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Table 14: Carcinogenic Dietary Risk for Bromoxynil
Commodity
Grain/cottonseed
Bulb vegetables
Meat
Milk
Poultry
Total Dietary Risk
Registered Uses (i.e., Excluding Cotton)
2.0 x 10'7
0.7 x 10'7
3.5 x 10'7
4.0 x 10'7
O.lxlO'7
1.0 x 10 6
Cotton @ 10 %CT + Registered Uses
2.6 x 10'7
0.7 x 10'7
7.0 x 10'7
4.4 x 10'7
0.2 x 10'7
1.5 x 10 6
These risk estimates are based on anticipated residues and percent crop treated information
which represents the most refined estimate the Agency can currently conduct. The additional (0.5
in 1 million) risk resulting from the cotton use is due to high residue levels of the metabolite, DBHA.
DBHA is formed by the transgenic BXN cotton which has been engineered to hydrolyze the nitrile
group of bromoxynil to a carboxylic acid, DBHA. DBHA is currently considered lexicologically
equal to bromoxynil.
c. Dietary Exposure - Drinking Water
The Office of Pesticide Programs is in the process of developing procedures and methods for
determining the likelihood of a pesticide occurring in drinking water and, if so, the exposure levels
and associated risk. Previous exposure and risk assessments have been conducted for bromoxynil as
a possible contaminant in drinking water. The following estimation of exposure and risk from
drinking water reflects the latest information and methods for estimating drinking water exposure.
i. Ground Water
Bromoxynil octanoate does not exhibit the mobility or persistence characteristics of pesticides
that are normally found in ground water. Bromoxynil phenol (which bromoxynil octanoate readily
degrades to) has the potential to leach to ground water under certain conditions, however, it rapidly
degrades under aerobic and anaerobic conditions reducing the likelihood of ground water
contamination. Limited monitoring information for bromoxynil in ground water is available. The
"Pesticides in Ground Water Database" (EPA 1992) reports sampling for bromoxynil in 107 wells
in four counties in Oregon between 1985 and 1987. The well samples in each area (public water
supply and domestic) were selected based on suspected vulnerability, susceptibility to contamination,
and availability of information on well construction and depth. No additional information on the
details of the monitoring was available. No detections of bromoxynil were reported.
Additional monitoring data from the United States Geological Survey (USGS) National Water
Quality Program (NAQWA) represent the highest quality data and most recent data available (1993-
1994). The program was carefully designed to obtain monitoring data for surface and ground waters
from diffuse (non-point) sources. For ground water, one detection of bromoxynil (concentration not
specified) was reported from a total of 2,245 samples. Clearly, these compounds (bromoxynil phenol
and octanoate) are not considered candidates for restricted use due to ground water concerns and the
potential for ground water contamination (and exposure) from bromoxynil is extremely low.
46
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DBHA, a cotton metabolite, is not expected to be found in ground water.
ii. Surface Water
Environmental fate studies indicate that bromoxynil (phenol and octanoate) should not persist
in surface waters, although water monitoring data from the USGS NAWQA program show that
bromoxynil has been detected in 1.1% of surface water samples. Modeled estimated environmental
concentrations (EECs) were based on the cotton use and not the small grains, corn or other uses of
bromoxynil because, it has been the Agency' s experience, that using cotton as opposed to these crops
results in a higher estimated surface water exposure. Cotton represents the most conservative use
for surface water exposure (i.e. the highest possible exposure scenario).
A Tier II analysis based on the PRZM - EXAMS model (Pesticide Root Zone Model Version
2.3 plus Exposure Analysis Modeling System Version 2.94) was conducted for the cotton use.
PRZM-EXAMS uses data on the physical-chemical properties of the pesticide plus soil and
topographic characteristics, weather data, and water quality parameters for the modeled site. The
model uses this information to estimate runoff from a 10 hectare agricultural field into an immediately
adjacent 1 hectare by 2 meter deep pond. PRZM-EXAMS considers reduction in dissolved pesticide
concentrations due to adsorption of pesticide to soil or sediment, incorporation, degradation in soil
before wash off to a water body, direct deposition of spray drift into the water body, and degradation
of the pesticide within the water body.
Water monitoring data from the U.S. Geological Survey (USGS) NAWQA Program were
reported during the 1993-1995 period from 7 of 20 river basins throughout the U.S. The NAWQA
Program examined drainage basins that were primarily agricultural use. The percentage of detections
was 1.1% from a total of 1,925 surface water samples. Analysis of the 20 detections >0.03 ppb
yielded a median value of 0.105 ppb with a mean of 0.53 ppb. The maximum concentration was one
data point at 6.1 ppb (12.2 ppb when accounting for 50% recovery) measured in the South Platte
River Study Unit, CO. For urban land use, bromoxynil was not detected in surface waters. It is
important to note the laboratory recoveries were approximately 50%. Apparently the laboratory
recoveries did not vary considerably from the 50% level.
Based on model estimates (using PRZM-EXAMS), the maximum or peak estimated
concentration for bromoxynil was 12.3 parts per billion (ppb) and the maximum estimated long-term
mean was 0.24 ppb (using 36 years of weather data). These values represent what might be expected
in a small water body near a cotton field highly prone to runoff. The maximum peak estimated
concentration for bromoxynil from the model correlates with the highest value detected in the USGS
monitoring data, when this measured value is been corrected for an analytical recovery rate of 50%.
To estimate a reasonable high end exposure for the human health risk assessment, EPA focused
on the calculated time weighted annual mean concentrations of bromoxynil at each of 11 USGS
monitoring sites, which the EPA views as located in watersheds likely to have bromoxynil use.
(These values were not corrected for the analytical recovery rate of 50%.) These time weighted
annual mean concentrations ranged from 0.011 ppb to 0.18 ppb, with 10 out of the 11 sites with time
weighted annual mean concentrations below 0.05 ppb. Six of the 10 sites had time weighted annual
mean concentrations at or below 0.014 ppb. The highest annual time-weighted mean (0.18 ppb) was
47
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located in a relatively small watershed (approximately 100 square miles) in a relatively small water
body, and the calculated annual mean value at this site was significantly influenced by the presence
of a single high value (the highest value found in all of the available monitoring data). Based on this
information, EPA believes that 0.05 ppb is a reasonable high end estimate for purposes of estimating
drinking water exposure. However, because available monitoring data are variable, EPA has imposed
surface water monitoring requirements as a condition of the cotton registration. These data are
important to improve EPA's understanding of the potential human exposure to bromoxynil in
drinking water.
Table 15: Bromoxynil Exposure Values Estimated for Surface Water Sources of Drinking
Water
Subpopulation by weight, water consumption per day
Male 70kg, 2 Liters
Female 60 kg, 2 Liters
Child 10 kg, 1 Liter
Acute (mg/kg/day)1
3.5 X 10-4
3.5 X 10'4
12 X 10-4
Chronic (mg/kg/day)1
1.4 X10-6
1.6 X10'6
5 X 10-6
1 Exposure (mg/kg/day) = (concentration in water ug/L) (0.001 mg/ug) (water consumption L/day)
(body weight kg).
Where the 4-day (acute) exposure concentration is 12.2 ppb and the reasonable high end estimate for purposes of estimating drinking water exposure
(chronic) is 0.05 ppb.
iii. Dietary Risk Characterization - Drinking Water
The potential for ground water contamination (and exposure) from bromoxynil is extremely
low. Environmental fate studies indicate that bromoxynil (phenol and octanoate) should not persist
in surface waters. Estimates of exposure were based on surface water estimates for the cotton use
which, considering all of the uses of bromoxynil, represents the most conservative scenario for
drinking water exposure. The exposures and risks are summarized in Table 16 below.
Table 16: Bromoxynil Exposure and Risk from Drinking Water
Subpopulation by weight,
water consumption/ day
Male 70 kg, 2 Liters
Female 60 kg, 2 Liters
Child 10 kg, 1 Liter
Drinking water Exposure
(mg/kg/day)1
Acute
3.5 X 10'4
3.5 X 10'4
12 X 10'4
Chronic
1.4 X10'6
1.6 X lO'6
5 X lO'6
Risk from Drinking Water
Acute1 MOE
>10,000
>10,000
>10,000
Chronic2
<1%
<1%
<1%
Cancer3
0.2 x 10'6
N/A*
1 Acute Risk = MOE = NOEL (mg/kg/day) / Exposure (mg/kg/day). The NOEL for females ages 13+ is 4 mg/kg/day
and for the other Subpopulation groups is 8 mg/kg/day (for details see Dose Response Section of document). A MOE
of greater than 1000 is recommended for females 13+ and greater than 100 for all other populations except females.
To estimate acute exposure, a value of 12.2 ppb, derived from monitoring data and closely matched with modeling
estimates, was used. The drinking water chronic exposure (0.05 ppb) was estimated using a reasonable high end
estimate from monitoring data.
2 %RfD = Chronic Dietary Risk = Exposure as a percentage of the RfD (0.015 mg/kg/day). The %RfD is considered
a risk concern when it exceeds 100%.
3 The upper bound Carcinogenic Risk = risk quotient Q/ (0.103 [mg/kg/day]"1) X Chronic Exposure (1.4 x 10"6
mg/kg/day). The chronic exposure value is based on a 0.05 ppb concentration of bromoxynil in drinking water.
N/A = Not Applicable. Cancer Risk has only been estimated for the general population (in this case the average
exposure between males and females) and is based on a 70 year lifetime.
48
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There appears to be no chronic or acute risk of concern for any subpopulations from drinking
water (only) when using monitoring data or modeling data for the acute exposure and risk and when
using monitoring data for the chronic and cancer exposure and risk.
The USGS monitoring data indicate that exposure is possible on a seasonal basis, but rare
considering there was one significant concentration out of 1,925 samples (and only 20 detects total).
These data showed that approximately one percent of the samples were positive for bromoxynil.
Most importantly, the sampling was conducted predominantly in locations not representative of
drinking water intakes, and none of the samples were from "the tap".
d. Aggregate Risk
Aggregate risk is estimated by combining dietary (food and water) and residential exposures.
Bromoxynil has no residential uses, therefore, the aggregate risk estimate will be based on the dietary
exposure from food and water only, for the most highly exposed population subgroups and the
general population as appropriate. Table 23 (below) shows the aggregate risk for bromoxynil;
however, for details concerning the exposure to determine these estimated aggregate risks, see Tables
12-16. Details concerning the assumptions and risk characterizations have been previously discussed
and are in the corresponding sections of the document.
Table 17: Estimates of Aggregate Risk from Bromoxynil from Dietary Sources (Food and
Water) including the use on BXN Transgenic Cotton
Population Subgroup1
whole U.S. population
females 13+
children 1-6 years
Chronic %RfD2
%CT + Registered Uses
<1%
<1%
<1%
Acute MOE3
%CT + Registered Uses
>16,000
>1 1,000
>5,000
Cancer4
%CT + Registered Uses
l.VxlO-6**
N/A*
N/A*
For the other
1 The most highly exposed population subgroups.
2 Chronic risk is a concern when more than 100% of the RfD is consumed.
3 An MOE >1000 indicates there is no aggregate acute dietary risk concern for females 13+.
subpopulations, an MOE of >100 indicates there is no aggregate acute dietary risk concern.
MOEacute= NOEL
Aggregate exposure (food +water)
4 As discussed in Table 16 the carcinogenic risk from drinking water is 0.2 x 10"6.
N/A = Not Applicable. Cancer Risk has only been estimated for the general population (in this case the average
exposure between males and females) because it is based on a 70 year lifetime.
** The aggregate risk is based on risk from food plus the drinking water risk (0.2 X 10"6).
The chronic and acute aggregate risk estimates do not trigger a concern. The dietary (food)
exposure and risk is highly refined using anticipated residues and considering percent crop treated
information resulting in a highly refined cancer risk estimate. The estimated chronic drinking water
risk (from surface water sources) was based on a reasonable high end estimate of exposure, based
on limited monitoring data, and is potentially much lower since the level of bromoxynil may only
occasionally occur in water and fate data indicate that it degrades in approximately 7 days.
49
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Because of FQPA aggregate and cumulative risk considerations, it is important to note that
bromoxynil heptanoate (which is not part of the reregi strati on case) has some of the same uses as
bromoxynil phenol and octanoate, but not all of the same uses and no additional ones. Therefore, the
exposure and risk associated with the use of the heptanoate is not greater than that described for the
phenol and octanoate. Also, the heptanoate would not "add" to the current risk described above
since these active ingredients would be used "in place" of one another rather than in an "additive"
manner. Therefore, the exposure and risk estimates presented here for the bromoxynil phenol and
octanoate would present the same or more conservative risk estimate for the heptanoate and, it would
not be appropriate to add them together for the purposes of aggregate risk.
e. Cummulative Risk
Section 408(b)(2)(D)(V) 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 Agency believes that "available information" in this context might include not only toxicity,
chemistry, and exposure data, but also scientific policies and methodologies for understanding
common mechanisms of toxicity and conducting cumulative risk assessments. For most pesticides,
although the Agency has some information in its files that may turn out to be helpful in eventually
determining whether a pesticide shares a common mechanism of toxicity with any other substances,
EPA does not at this time have the methodology to fully resolve the scientific issues concerning
common mechanism of toxicity in a meaningful way. EPA has begun a pilot process to study this
issue further, through examination of particular classes of pesticides. The Agency hopes that the
results of this pilot process will increase the Agency's scientific understanding of this question such
that EPA will be able to develop and apply scientific principles for better determining which chemicals
have a common mechanism of toxicity and evaluating the cumulative effects of such chemicals. The
Agency anticipates, however, that even as its understanding of the science of common mechanisms
increases, decisions on specific classes of chemicals will be heavily dependent on chemical specific
data, much of which may not be presently available.
Although at present the Agency does not know how to apply the information in its files
concerning common mechanism issues to most risk assessments, there are pesticides for which the
common mechanism issues can be resolved. These pesticides include pesticides that are
lexicologically dissimilar to existing chemical substances (in which case the Agency can conclude that
it is unlikely that a pesticide shares a common mechanism of activity with other substances) and any
pesticides that produce a common toxic metabolite (in which case common mechanism of activity will
be assumed).
In the case of bromoxynil, EPA has not conducted a detailed review of common mechanism
yet to determine whether it is appropriate, or how, to include this chemical in a cumulative risk
assessment. After EPA develops a methodology to apply common mechanism of toxicity issues to
risk assessments, the Agency will develop a process (either as part of the periodic review of pesticides
or otherwise) to reexamine these tolerance decisions.
50
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3. Occupational Exposure and Risk Characterization
An occupational and/or residential exposure assessment is required for an active ingredient
if (1) certain toxicological criteria are triggered and (2) there is potential exposure to handlers
(mixers, loaders, applicators, etc.) during use or to persons entering treated sites after application is
complete.
The toxicological endpoints of concern for occupational exposure are summarized in the Dose
Response Section. It should be noted for short term and intermediate term exposure the toxicological
endpoint is from a dermal developmental study. Therefore, a separate dermal absorption factor was
not applied. The cancer risk was determined using an oral toxicity endpoint which, for occupational
risk, necessitates the use of a dermal absorption factor. The dermal absorption for the bromoxynil
octanoate is 10.32% and the bromoxynil phenol is 1.92% based on studies (MRTDs 40854602 &
40854603) summarized in the Hazard Assessment Section of this document. For the sake of
simplicity and to remain consistent, the occupational cancer risk was determined using an absorption
factor of 10% (rounded from 10.32%). Lastly, although a chronic (noncancer) endpoint was
identified for bromoxynil, a chronic-term exposure/risk assessment was not conducted. Because it
is unlikely that there will be chronic exposures to bromoxynil a chronic risk assessment is not
warranted. Inhalation exposures were considered negligible compared to the dermal route and no
inhalation endpoint was identified for use in risk assessment.
a. Handler Exposures and Risk
i. Handler Exposures and Assumptions
EPA has determined that there are potential exposures to mixers, loaders, applicators, or other
handlers during usual use patterns associated with bromoxynil. Based on the use patterns, seven
major exposure scenarios were identified for bromoxynil:
(1) mixing/loading liquids for groundboom applications;
(2) mixing/loading liquids for aerial and sprinkler irrigation applications;
(3) groundboom applications;
(4) aerial applications;
(5) flaggers;
(6) mixing/loading/applying liquid formulations by groundboom; and
(7) mixing/loading/applying liquid formulations by aircraft.
Bromoxynil is also packaged in water soluble gel packets. No exposure data are available for
the water soluble gel packets, but the exposure potential is expected to be less than for open pouring
of liquids, which is included in the risk assessment. Inhalation exposures are expected to be negligible
compared to the dermal route. The acute inhalation LC50 for bromoxynil octanoate is 0.81 mg/L (M)
and 0.79 mg/L (F) (toxicity category III) and the acute inhalation LC50 for the Buctril formulation is
1.1 mg/liter (toxicity category III). On this basis, the Agency determined a risk assessment for
exposure by the inhalation route is not required.
A chemical specific exposure study (MRTD 41730001) was reviewed and accepted by EPA
in 1991. However, EPA has concerns regarding the low field recoveries reported in the study. For
51
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example, the field recoveries fortified with the formulated product and analytical grade for the
handwash averaged 56 percent with a coefficient of variation (c.v.) of 48 percent; facial wipes
averaged 56 percent with a c.v. of 64 percent; and the whole-body dosimeters averaged 53 percent
with a c.v. of 55 percent. The Agency's concern is that the low field recoveries (especially at low
fortification levels) may have produced exposure values that are "false negatives". Therefore, and
in order to provide a criterion for comparison with the Pesticide Handlers Exposure Database
(PHED) data, the Agency characterizes the data as "low to medium grade" quality data. The PHED
based data are considered "medium to high grade" quality data. Because of the quality of the
chemical-specific study (MRTD 41730001), the risk assessment in this document is based on PHED
VI. 1 data.
PHED VI. 1 surrogate data were used to estimate exposures for handlers wearing "baseline,"
"PPE," and "engineering controls." The baseline represents: long sleeved shirts, long pants and no
gloves, and using open mixing/loading and open cab tractors. PPE is based on handlers wearing
coveralls over long sleeved shirts, long pants and chemical resistant gloves while using open
mixing/loading and open cab tractors. The engineering controls are based on long sleeved shirts, long
pants, and no gloves (except where noted) while using closed loading systems and enclosed
cockpits/tractors.
When evaluating the exposure and risk estimates presented in this document the following
should be taken into consideration:
• The PHED estimates do not account for the potential exposure reduction from the "wide-
mouth" containers designed to reduce splashing during pouring (2.5 gallon containers) used
in the chemical specific study, and therefore, potentially overestimate risks to bromoxynil.
• Data indicate that most private applicators do their own mixing and loading for groundboom
applications. The registrant indicated that approximately 95% of bromoxynil is mixed and
loaded by the same person who applies the pesticide. Therefore, these combined exposures
are included in the risk assessment.
It is reasonable to assume that for aerial and commercial groundboom applications the
mixer/loader and the applicator are separate handlers. Aerial and commercial groundboom
applications are limited. Apparently aerial applications to range land, sod and turfgrass seed
farms seldom occur, if ever.
The exposure assessments using PHED VI. 1 surrogate data are presented in Table 18. Table
19 summarizes the caveats and parameters specific to each exposure scenario and corresponding risk
assessments.
The daily dose was calculated using the following formula:
Daily Dose mg I = Daily Exposure -^L) • 1 • % dermal absorption
( Kg Day) ( Day) ( Body Weight (Kg))
52
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Table 18: Short-term and Intermediate-term Dermal Exposure to Bromoxynil
Exposure Scenario
Dermal Unit Exposure
(mg/lb ai)
Baseline"
PPEb
Engineering
Controls0
Crop Typed
Acres Treated/Day'
Maximum
Application Rate
(Ib ai/acre)f
Daily Dermal Dose (mg/kg/day)8
Baseline
PPE
Engineering
Controls
MIXER/LOADER
Mixing/Loading Liquids for Groundboom Application
Mixing Liquids for Sprinkler Irrigation and Aerial
Applications
2.9
0.023
0.0086 (gloves)
Wheat
Corn
Cotton
Garlic
Onions
Seedling Alfalfa-
East
Seedling Alfalfa-
West
Canary Grass
Oats and Rye
Barley
Mint
Sorghum
Flax
Turfgrass Seed
Farm
Sod Farm
Range Land
All
240
150
200
69
77
50
133
50
50
133
48
200
70
111
100
250
350
0.5
5.8
3.6
4.8
1.7
1.9
1.2
3.2
1.2
1.2
3.2
1.2
4.8
1.7
2.7
2.4
6.0
8.5
0.046
0.029
0.038
0.013
0.015
0.0096
0.025
0.0096
0.0096
0.025
0.0092
0.038
0.013
0.021
0.019
0.048
0.067
0.017
0.011
0.014
NA
0.0055
NA
0.0095
NA
NA
0.0095
NA
0.014
NA
0.0080
0.0072
0.018
0.025
APPLICATOR
Groundboom Applicator
0.015
0.011
0.0050
Wheat
Corn
Cotton
Garlic
Onions
Seedling Alfalfa-
East
Seedling Alfalfa-
West
Canary Grass
Oats and Rye
Barley
Mint
Sorghum
240
150
200
69
77
50
133
50
50
133
48
200
0 5
0.03
0.019
0.025
0.0086
0.0096
0.0063
0.017
0.0063
0.0063
0.017
0.006
0.025
0.022
0.014
0.018
0.0063
0.0071
0.0046
0.012
0.0046
0.0046
0.012
0.0044
0.018
0.010
0.0063
0.0083
NA
NA
NA
0.0055
NA
NA
0.0055
NA
0.0083
53
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Table 18: Short-term and Intermediate-term Dermal Exposure to Bromoxynil
Exposure Scenario
Groundboom Applicator
Aerial Application - Enclosed Cockpit
Dermal Unit Exposure
(mg/lb ai)
Baseline"
0.015
No Data
PPEb
0.011
No Data
Engineering
Controls0
0.0050
0.005
Crop Typed
Flax
Turfgrass Seed
Farm
Sod Farm
Range Land
All
Acres Treated/Day'
70
111
100
250
350
Maximum
Application Rate
(Ib ai/acre)f
Daily Dermal Dose (mg/kg/day)8
Baseline
0.0088
0.014
0.013
0.031
No Data
PPE
0.0064
0.010
0.0092
0.023
No Data
Engineering
Controls
NA
NA
NA
0.010
0.032
FLAGGERS
Flagging Liquids
0.011
0.01
0.00022
All
350
0.5
0.032
0.029
0.00064
MIXER/LOADER/APPLICATOR11
Mixing/Loading Liquids and Applying with Groundboom
Equipment
2.9
0.037
0.014
Wheat
Corn
Cotton
Garlic
Onions
Seedling Alfalfa-
East
Seedling Alfalfa-
West
Canary Grass
Oats and Rye
Barley
Mint
Sorghum
Flax
Turfgrass Seed
Farm
Sod Farm
Range Land
240
150
200
69
77
50
133
50
50
133
48
200
70
111
100
250
0.5
5.8
3.6
4.8
1.7
1.9
1.2
3.2
1.2
1.2
3.2
1.2
4.8
1.7
2.7
2.4
6.0
0.074
0.046
0.062
0.021
0.024
0.015
0.041
0.015
0.015
0.041
0.015
0.062
0.022
0.034
0.031
0.077
0.028
0.018
0.023
0.0081
0.0090
0.0058
0.016
0.0058
0.0058
0.016
0.0056
0.023
0.0082
0.013
0.012
0.029
PHED VI. 1; Baseline: handlers wearing long sleeved shirts, long pants and no gloves while using open mixing/loading and open cab tractors.
b PHED VI. 1; PPE: handlers wearing long sleeved shirts, long pants and chemical resistant gloves (no gloves for applicators) while using open mixing/loading and open cab tractors; flaggers wearing coveralls over long pants, long
sleeved shirts, and no gloves
c PHED VI. 1; Engineering Controls: long pants, long sleeved shirt, chemical resistant gloves for closed mixing/loading; long pants, long sleeved shirt, no gloves for enclosed cab tractor (groundboom) and inside truck (flagger); and
aerial applicators wearing long pants, long sleeved shirts, and no gloves while using enclosed cockpit fixed wing airplanes (open cockpit data are not available).
d,e Crop and acres. Sources: (1) Evaluation of Bromoxynil Worker Exposure Study; Memorandum from C. Lunchickto P. Parsons dated April 29, 1991. (2) Bromoxynil Heptanoate and Bromoxynil Octanoate, May 1996. Use data
for Bromoxynil Exposure Analysis; Memorandum from G.W. Keitt, PhD to S.Bachus dated 7/15/92.
f Application rates are from maximum values found in the following bromoxynil labels: 264-477, 264-438, 264-531, 264-540, and 51036-256.
g Daily Dermal Dose (mg/kg/day) = [Exposure (mg/lb ai) * Appl. Rate (Ib ai/A) * Acres Treated]/60 kg body weight. Short-term and intermediate-term toxicological endpoint is from a dermal study; therefore, adjustment for dermal
absorption is not necessary.
h Mixer/Loader estimates + Applicator estimates.
54
-------
Table 19: Exposure Scenario Descriptions for Uses of Bromoxynil
Exposure Scenario
Data Source
Standard Assumptions
Comments*
Mixer/Loader Exposure
Mixing/Loading Liquids
PHED VI. 1
Baseline: PHED VI. 1, handlers wearing long sleeved
shirts and long pants; open mixing/loading
PPE: MOE Assessment: PHED VI. 1; handlers wearing
long sleeved shirts, long pants, and chemical resistant
gloves; open mixing/loading. Cancer Assessment:
PHED VI. 1; handlers wearing long sleeved shirts, long
pants and chemical resistant gloves; open mixing/loading
Engineering Controls: PHED VI. 1; handlers wearing
long sleeved shirts and chemical resistant gloves; closed
mixing/ loading
Baseline: "Best Available" grades: Dermal and hands acceptable grades.
Dermal = 72 to 122 replicates; Hands = 53 replicates. High confidence in
dermal data. No protection factors (PFs) were necessary.
PPE: "Best Available" grades: Hands and dermal acceptable grades. Hands
= 59 replicates; Dermal = 72 to 122 replicates. High confidence in dermal
data. No PFs were necessary.
Engineering Controls: "Best Available" grades: Dermal and hands
acceptable grades. Dermal = 16 to 22 replicates; Hands = 31 replicates. High
confidence in dermal data. No PFs were necessary.
Applicator Exposures
Groundboom Tractor
Aerial Application -
Enclosed Cab
PHED VI. 1
PHED VI. 1
Baseline: PHED VI. 1; handlers wearing long sleeved
shirts and long pants
PPE: MOE Assessment: PHED V 1.1; handlers wearing
coveralls over long sleeved shirts, long pants, and
chemical resistant gloves; open mixing/loading. Cancer
Assessment: PHED VI. 1; handlers wearing long sleeved
shirts, long pants and chemical resistant gloves; open cab
tractors
Engineering Controls: PHED VI. 1; handlers wearing
long pants, long sleeved shirts, and no gloves; enclosed
tractor cab
Engineering Controls: PHED VI. 1; applicators wearing
long pants, long sleeved shirts and no gloves while using
enclosed cockpit fixed wing airplanes (open cockpit data
are not available)
Baseline: "Best Available" grades: Dermal and hands acceptable grades.
Dermal = 23 to 42 replicates; Hands = 29 replicates. High confidence in
dermal data.
PPE: "Best Available" grades: Hands grades A,B,C; dermal acceptable
grades. Hands = 21 replicates; Dermal = 23 to 42 replicates. Medium
confidence in dermal data. No PFs were necessary for the cancer assessment,
50 percent PF used to simulate coveralls for MOE assessments.
Engineering Controls: "Best Available" grades: Dermal and Hands = grades
A,B,C,. Dermal = 20 to 31 replicates; Hands = 16 replicates. Medium
confidence in data. No PFs were necessary.
Engineering Controls: "Best Available" grades: Dermal = grades A,B,C;
hands = acceptable grades. Dermal = 24 to 48 replicates; hands = 34
replicates. Medium confidence in dermal data. No PFs were necessary.
55
-------
Table 19: Exposure Scenario Descriptions for Uses of Bromoxynil
Exposure Scenario
Data Source
Standard Assumptions
Comments*
Flagger Exposure
Flagging Liquids
PHED VI. 1
Baseline: PHED VI . 1 ; flaggers wearing long pants,
long sleeved shirts, and no gloves
PPE: PHED VI. 1; flaggers wearing coveralls over long
pants, long sleeved shirts, and no gloves
Engineering Controls: PHED VI. 1; flaggers wearing
long pants, long sleeved shirts, and no gloves; inside
enclosed truck cab
Baseline: "Best Available" grades: hands and dermal = acceptable grades.
Dermal = 16 to 18 replicates; hands = 16 replicates. High confidence in
dermal data. PHED data were used for baseline, no PFs were necessary.
PPE: The PPE scenario was calculated by using a 50 percent PF for the
addition of coveralls.
Engineering Controls: Calculated by applying a 98 percent PF to the
baseline assessment.
"Best Available" grades are defined by OREB SOP for meeting Subdivision U Guidelines. Best available grades are assigned as follows: matrices with grades A and B data and a
minimum of 15 replicates; if not available, then grades A, B, and C data and a minimum of 15 replicates; if not available, then all data regardless of the quality and number of replicates.
Data confidence are assigned as follows:
High = grades A and B and 15 or more replicates per body part
Medium = grades A, B, and C and 15 or more replicates per body part
Low = grades A, B, C, D, and E or any combination of grades with less than 15 replicates
56
-------
ii. Handler Risks
The short-term and intermediate-term MOEs were calculated using the following formula:
NOEL I-OS-}
MOE = 'kg day>
Daily Dose mg }
( kg day)
For the short-term and intermediate-term risk assessment, a NOEL of 10 mg/kg/day from a dermal study was used
along with a 60 kg body weight (the standard assumption for the weight of a women) since the toxicological endpoint is
for developmental effects.
The lifetime average daily dose (LADD), used to calculate the cancer risk, was calculated using the following
formula:
LADD (mg/kg/day) =
Daily Dose (mg/kg/day) * Treatments Per Year
365 Days Per Year
40 Work Years 1
75 Lifetime Years]
The cancer risks were calculated using the following formula:
Cancer Risk = LADD (mg/kg/day) * Q.,* (mg/kg/day)"
Table 20 presents the corresponding MOE estimates for the short-term and intermediate-term exposures. Table
21 presents the cancer risk assessment for private handlers, which includes combined mixer, loader and applicator risks.
Table 22 presents the cancer risk assessments for commercial handlers, for whom the mixer/loader is assumed to be
different than the applicator.
57
-------
Table 20: Short-term and Intermediate-term Risks of Bromoxynil
Exposure Scenario
Crop Type
Dermal MOEa
Baselineb
PPEC
Engineering Controls'1
MIXER/LOADER
Mixing/Loading Liquids for Groundboom
Applicators
Mixing/Loading Liquids for Sprinkler Irrigation
and Aerial Applications
Wheat
Corn
Cotton
Garlic
Onions
Seeding Alfalfa - East
Seeding Alfalfa - West
Canary Grass
Oats and Rye
Barley
Mint
Sorghum
Flax
Turfgrass Seed Farm
Sod Farm
Range Land
All
2
o
J
2
6
5
8
o
J
8
8
o
J
8
2
6
4
4
2
1
220
350
260
760
680
1000
390
1000
1000
390
1100
260
750
470
520
210
150
590
910
710
NA
1,800
NA
1,100
NA
NA
1,100
NA
710
NA
1,300
1,400
560
400
APPLICATOR
Groundboom Applicators
Wheat
Corn
Cotton
Garlic
Onions
Seeding Alfalfa - East
Seeding Alfalfa - West
333
526
400
1,163
1,042
1,587
588
450
710
560
1,600
1,400
2,200
830
1,000
1,600
1,200
NA
NA
NA
1,800
58
-------
Table 20: Short-term and Intermediate-term Risks of Bromoxynil
Exposure Scenario
Groundboom Applicators
Aerial Application - Enclosed Cockpit
Crop Type
Canary Grass
Oats and Rye
Barley
Mint
Sorghum
Flax
Turfgrass Seed Farm
Sod Farm
Range Land
All
Dermal MOEa
Baselineb
1,587
1,587
588
1,667
400
1,136
714
769
323
No Data
PPEC
2,200
2,200
830
2,300
560
1,600
1,000
1,100
430
No Data
Engineering Controls'1
NA
NA
1,800
NA
1,200
NA
NA
NA
1,000
310
FLAGGER
Flagging Liquids
All
313
340
16,000
MIXER/LOADER/APPLICATOR6
Mixing/Loading Liquids and Applying with
Groundboom Equipment
Wheat
Corn
Cotton
Garlic
Onions
Seeding Alfalfa - East
Seeding Alfalfa - West
Canary Grass
Oats and Rye
Barley
Mint
Sorghum
Flax
2
o
J
2
6
5
8
o
J
8
8
o
J
8
2
6
140
220
160
470
420
650
240
650
650
240
680
160
460
360
560
430
1,200
1,100
1,700
630
1,700
1,700
630
1,800
430
1,200
59
-------
Table 20: Short-term and Intermediate-term Risks of Bromoxynil
Exposure Scenario
Crop Type
Turfgrass Seed Farm
Sod Farm
Range Land
Dermal MOEa
Baselineb
4
4
2
PPEC
290
320
130
Engineering Controls'1
770
830
340
a Dermal MOE = NOEL (10 mg/kg/day)/Daily Dermal Dose (mg/kg/day); refer to Table 16
b PHED VI. 1 based data. Baseline: handlers wearing long sleeved shirts, long pants and no gloves while using open mixing/loading and open cab tractors.
c PHED VI. 1; PPE: handlers wearing long sleeved shirts, long pants and chemical resistant gloves (no gloves for applicators) while using open mixing/loading and open cab tractors;
flaggers wearing coveralls over long pants, long sleeved shirts, and no gloves.
d PHED VI. 1; Engineering Controls: long pants, long sleeved shirt, chemical resistant gloves for closed mixing/loading; long pants, long sleeved shirt, no gloves for enclosed cab tractor
(groundboom) and inside truck (flagger); and aerial applicators wearing long pants, long sleeved shirts, and no gloves while using enclosed cockpit fixed wing airplanes (open cockpit
data are not available).
e Mixer/Loader estimates + Applicator estimates; refer to Table 16
Table 21: Private Handler (grower) Cancer Risks for Bromoxynil using PHED Data
Exposure Scenario
Crop Type
Typical Rate
(Ib ai/A)a
Acres
Treated/Day
Treatments per
Year3
LADD (mg/kg/day )b
Baselined
PPEd
Cancer Risk0
Baselined
PPEd
MIXER/LOADER
Mixing/Loading liquids
for Groundboom
Applications
Wheat
Corn
Cotton
Garlic
Onions
Seedling Alfalfa-
East
Seedling Alfalfa-
West
Canary Grass
Oats and Rye
Barley
0.2
0.3
0.3
0.4
0.2
0.4
0.4
0.5
0.4
0.3
240
150
200
69
77
50
133
50
50
133
1
1
2
2
2
1
1
1
1
1
3.5E-04
3.3E-04
8.7E-04
4.0E-04
2.2E-04
1.4E-04
3.9E-04
1.8E-04
1.4E-04
2.9E-04
5.1-06
4.8E-06
1.3E-05
5.9E-06
3.3E-06
2.1E-06
5.7E-06
2.7E-06
2.1E-06
4.3E-06
3.6E-05
3.4E-05
9.0E-05
4.1E-05
2.3E-05
1.4E-05
4.0E-05
1.9E-05
1.4E-05
3.0E-05
5.3E-07
4.9E-07
1.3E-06
6.1E-07
3.4E-07
2.2E-07
5.9E-07
2.8E-07
2.2E-07
4.4E-07
60
-------
Table 21: Private Handler (grower) Cancer Risks for Bromoxynil using PHED Data
Exposure Scenario
Mixing/Loading liquids
for Groundboom
Applications
Sprinkler Irrigation and
Aerial Applications
Crop Type
Mint
Sorghum
Flax
Turfgrass Seed Farm
Sod Farm
Range Land
All
Typical Rate
(Ib ai/A)a
0.3
0.3
0.3
0.5
0.5
0.5
0.5
Acres
Treated/Day
48
200
70
111
100
250
350
Treatments per
Year3
2
2
1
1
2
1
1
LADD (mg/kg/day)b
Baselined
2.1E-04
8.7E-04
1.5E-04
4.0E-04
7.2E-04
9.0E-04
1.2E-03
PPEd
3.1E-06
1.3E-05
2.2E-06
5.9E-06
1.1E-05
1.3E-05
1.8E-05
Cancer Risk0
Baselined
2.2E-05
9.0E-05
1.5E-05
4.1E-05
7.4E-05
9.3E-05
1.2E-04
PPEd
3.2E-07
1.3E-06
2.3E-07
6.1E-07
1.1E-06
1.3E-06
1.9E-06
APPLICATOR
Groundboom
Wheat
Corn
Cotton
Garlic
Onions
Seedling Alfalfa-
East
Seedling Alfalfa-
West
Canary Grass
Oats and Rye
Barley
Mint
Sorghum
Flax
Turfgrass Seed Farm
Sod Farm
Range Land
0.2
0.3
0.3
0.4
0.2
0.4
0.4
0.5
0.4
0.3
0.3
0.3
0.3
0.5
0.5
0.5
240
150
200
69
77
50
133
50
50
133
48
200
70
111
100
250
1
1
2
2
2
1
1
1
1
1
2
2
1
1
2
1
1.8E-06
1.6E-06
4.5E-06
2.1E-06
1.1E-06
7.4E-07
1.9E-06
9.3E-07
7.4E-07
1.5E-06
1.1E-06
4.5E-06
7.9E-07
2.1E-06
3.8E-06
4.7E-06
1.6E-06
1.5E-06
4.2E-06
1.9E-06
1.1E-06
6.9E-07
1.8E-06
8.7E-07
6.9E-07
1.4E-06
l.OE-06
4.2E-06
7.3E-07
1.9E-06
3.5E-06
4.4E-06
1.9E-07
1.6E-07
4.6E-07
2.2E-07
1.1E-07
7.6E-08
2.0E-07
9.6E-08
7.6E-08
1.5E-07
1.1E-07
4.6E-07
8.1E-08
2.2E-07
3.9E-07
4.8E-07
1.6E-07
1.5E-07
4.3E-07
2.0E-07
1.1E-07
7.1E-08
1.9E-07
9.0E-08
7.1E-08
1.4E-07
l.OE-07
4.3E-07
7.5E-08
2.0E-07
3.65E-07
4.5E-07
61
-------
Table 21: Private Handler (grower) Cancer Risks for Bromoxynil using PHED Data
Exposure Scenario
Aerial Application -
Enclosed Cockpit
Crop Type
All
Typical Rate
(Ib ai/A)a
0.5
Acres
Treated/Day
350
Treatments per
Year3
1
LADD (mg/kg/day)b
Baselined
6.5E-06
PPEd
6.0E-06
Cancer Risk0
Baselined
6.7E-07
PPEd
6.2E-07
FLAGGERS
Flagging liquids
All
0.5
350
1
4.3E-06
3.0E-06
4.4E-07
3.1E-07
MIXER/LOADER/APPLICATOR6
Mixing/Loading Liquids
and Applying with
Groundboom Equipment
Wheat
Com
Cotton
Garlic
Onions
Seedling Alfalfa-East
Seedling Alfalfa- West
Canary Grass
Oats and Rye
Barley
Mint
Sorghum
Flax
Turfgrass Seed Farm
Sod Farm
Range Land
0.2
0.3
0.3
0.4
0.2
0.4
0.4
0.5
0.4
0.3
0.3
0.3
0.3
0.5
0.5
0.5
240
150
200
69
77
50
133
50
50
133
48
200
70
111
100
250
1
1
2
2
2
1
1
1
1
1
2
2
1
1
2
1
3.5E-04
3.3E-04
8.7E-04
4.0E-04
2.2E-04
1.4E-04
3.9E-04
1.8E-04
1.4E-04
2.9E-04
2.0E-04
8.1E-04
1.5E-04
4.0E-04
7.2E-04
9.0E-04
6.8E-06
6.4E-06
1.7E-05
7.9E-06
4.4E-06
2.9E-06
7.5E-06
3.6E-06
2.9E-06
5.7E-06
4.1E-06
1.7E-05
3.0E-06
7.9E-06
1.4E-05
1.7E-05
3.6E-05
3.4E-05
9.0E-05
4.1E-05
2.3E-05
1.4E-05
4.0E-05
1.9E-05
1.4E-05
3.0E-05
2.1E-05
9.0E-05
1.5E-05
4.1E-05
7.4E-05
9.3E-05
7.0E-07
6.6E-07
1.8E-06
8.1E-07
4.5E-07
3.0E-07
7.7E-07
3.7E-07
3.0E-07
5.9E-07
4.2E-07
1.8E-06
3.1E-07
8.1E-07
1.4E-06
1.8E-06
a Typical Annual Usage for Bromoxynil; May 1996, Halvorson, A. BEAD/EPA.
b LADD (mg/kg/day) = [(Daily Dose (mg/kg/day) x (Treatments per year)/365 days per year)] x [40work-yrs/75 yrs-lifetime] x [0.10 dermal absorption factor]
c Cancer Risk = LADD (mg/kg/day) x Q/(mg/kg/day)-1; where Qj* = 1.03 x 10'1 (mg/kg/day)-'
d PHED V 1.1 based data. Baseline: handlers wearing long sleeved shirts, long pants and no gloves while using open mixing/loading and open cab tractors. PPE: handlers wearing long sleeved shirts, long
pants and chemical resistant gloves while using open mixing/loading and open cab tractors; flaggers wearing coveralls over long pants, long sleeved shirts, and no gloves; aerial applicators wearing long
pants, long sleeved shirts, and no gloves while using enclosed cockpit fixed wing airplanes (open cockpit data are not available).
e Mixer/Loader estimates + Applicator estimates
62
-------
Table 22: Commercial Handler Cancer Risks for Bromoxynil Using PHED Data
Exposure Scenario
Crop Type
Typical Rate
(Ib ai/A)a
Treatments per
Year1
LADD (mg/kg/day)b
Baselined
PPEd
Cancer Risk0
Baseline4
PPEd
MIXER/LOADER
Groundboom Applications
Sprinkler Irrigation and Aerial Applications
Wheat
Com
Canary Grass
Oats and Rye
Barley
Sorghum
Flax
All
0.2
0.3
0.5
0.4
0.3
0.3
0.3
0.5
21
20
21
21
21
14
7
21
7.2E-03
6.5E-03
3.8E-03
3.0E-03
5.9E-03
6.0E-03
l.OE-03
2.7E-02
1.2E-04
7.4E-05
2.6E-05
2.6E-05
6.9E-05
6.9E-05
1.2E-05
1.8E-04
7.4E-04
6.7E-04
3.9E-04
3.1E-04
6.1E-04
6.2E-04
l.OE-04
2.8E-03
1.3E-05
7.6E-06
2.7E-06
2.7E-06
7.1E-06
7.1E-06
1.3E-06
1.9E-05
APPLICATOR
Groundboom
Aerial Application - Enclosed Cockpit
Wheat
Com
Canary Grass
Oats and Rye
Barley
Sorghum
Flax
All
0.2
0.3
0.5
0.4
0.3
0.3
0.3
0.5
21
20
21
21
21
14
7
21
3.8E-05
3.3E-06
1.9E-05
1.5E-05
3.1E-05
3.1E-05
5.5E-06
No Data
3.5E-05
3.3E-05
1.9E-05
1.5E-05
2.9E-05
3.0E-05
5.2E-06
4.7E-05
3.9E-06
3.4E-07
2.0E-06
1.5E-06
3.2E-06
3.2E-06
5.7E-07
No Data
3.6E-06
3.4E-06
2.0E-06
1.5E-06
3.0E-06
3.1E-06
5.4E-07
4.8E-06
FLAGGERS
Flagging liquids
All
0.5
21
9.1E-05
6.2E-05
9.4E-06
6.4E-06
a Typical Annual Usage for Bromoxynil; May 1996, Halvorson, A. BEAD/EPA.
b LADD (mg/kg/day) = [(Daily Dose (mg/kg/day) x (Treatments per year)/365 days per year)] x [40work-yrs/75 yrs-lifetime] x [0.10 dermal absorption factor]
C Cancer Risk = LADD (mg/kg/day) x Q^mg/kg/day)'1; where Q* = 1.03 x 10'1 (mg/kg/day)'1
d PHED V 1.1 based data. Baseline: handlers wearing long sleeved shirts, long pants and no gloves while using open mixing/loading and open cab tractors. PPE: handlers wearing long
sleeved shirts, long pants and chemical resistant gloves while using open mixing/loading and open cab tractors; flaggers wearing coveralls over long pants, long sleeved shirts, and
no gloves; aerial applicators wearing long pants, long sleeved shirts, and no gloves while using enclosed cockpit fixed wing airplanes (open cockpit data are not available).
63
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Based on use of the PHED VI. 1 data the calculations of risk indicate that the MOEs for short-
term and intermediate-term exposures are greater than 100 for all scenarios either at baseline or, in the
case of mixers/loaders, when chemical-resistant gloves are worn. The cancer risk for the Private
Handler (grower) is 2 x 10"6 or lower for all the scenarios for all scenarios either at baseline or, in the
case of mixers/loaders, when chemical-resistant gloves are worn. The cancer risk for Commercial
Handlers is 1.9 x 10"5 and lower for all scenarios for all scenarios either at baseline or, in the case of
mixers/loaders, when chemical-resistant gloves are worn. These risk estimates do not account for the
potential exposure reduction from the use of "wide-mouth" containers (designed to reduce spillage) for
mixer/loaders. At the present time the PHED database does not allow the Agency to quantify this risk
mitigation measure. Therefore, the use of the "wide-mouth" containers may reduce the risk further.
Estimates of Dermal Risks from Short-Term Exposures Using PHED Data
The calculations of risk based on PHED VI. 1, which are considered medium to high grade data,
indicate that the MOEs are greater than 100 for the following scenarios:
! mixers/loaders handling liquids supporting groundboom, aerial and sprinkler irrigation
applications using open loading systems and wearing chemical-resistant gloves in addition
to long-sleeve shirts, long pants, shoes, and socks;
! applicators using open-cab groundboom equipment while wearing long-sleeve shirts and
long pants, shoes, and socks and no gloves;
! all flaggers supporting aerial applications while wearing long-sleeve shirts, long pants and
no gloves;
! mixer/loader/applicators handling liquids and performing groundboom applications using
open loading systems and open cab tractors when mixers/loaders are wearing chemical-
resistant gloves in addition to long-sleeve shirts, long pants, shoes, and socks and
applicators are wearing long-sleeve shirts, long pants, shoes, and socks;
! all aerial applicators using enclosed-cockpit aircraft while wearing long-sleeve shirts, long
pants, and no gloves.
Estimates of Cancer Risks Using PHED Data
The calculations of cancer risk based on PHED VI. 1, which are considered medium to high grade
data, indicate that the cancer risks are less than or approximately equal to 1 X 10'6 for the following
private applicator (grower) scenarios:
! all mixers/loaders supporting all applications using open loading systems and wearing
chemical-resistant gloves in addition to long-sleeve shirts and long pants;
! all applicators using open-cab groundboom equipment and wearing long-sleeve shirts and
long pants;
! all aerial applicators using enclosed-cockpit aircraft and wearing long-sleeve shirts and
long pants (note: no open-cockpit data are available);
! all flaggers supporting aerial applications and wearing long-sleeve shirts and long pants;
64
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! all mixer/loader/applicators mixing liquids and applying with groundboom equipment
using open loading systems and open-cab equipment with mixers/loaders wearing
chemical-resistant gloves in addition to long-sleeve shirts, long pants, shoes, and socks
and applicators wearing long-sleeve shirts, long pants, shoes, and socks.
The calculations of cancer risk based on PHED VI. 1 data indicate that the cancer risks are less
than or approximately equal to 1 X 10'5 for the following commercial handler scenarios:
! all mixers/loaders supporting all groundboom applications using open loading systems and
wearing chemical-resistant gloves in addition to long-sleeve shirts and long pants, shoes,
and socks;
! all applicators using open-cab groundboom equipment and wearing long-sleeve shirts and
long pants, shoes, and socks;
! all aerial applicators using enclosed-cockpit aircraft and wearing long-sleeve shirts and
long pants, shoes, and socks (note: no open-cockpit data are available);
! all flaggers supporting aerial applications and wearing long-sleeve shirts and long pants,
shoes, and socks;
! mixer/loader/applicators supporting groundboom applications to garlic, onions, seeding
alfalfa in the East, canary grass, oats and rye, mint, and flax while using closed loading
systems and enclosed cab equipment and wearing chemical-resistant gloves
(mixing/loading only) in addition to long-sleeve shirts and long pants, shoes, and socks.
For commercial handlers mixing/loading to support aerial applications and mixing/applying for
sprinkler-irrigation applications, the estimated cancer risk (calculated with PPE) based on PHED data
is 1.9 X 10"5, which is below EPA's level of concern for occupational scenarios.
b. Postapplication Exposures and Risk
EPA has determined that there is potential exposure to persons entering treated sites after
application is complete. Post application exposures may occur to /') workers following applications to
agricultural crops during routine crop production practices (e.g., cultivation, scouting, hoeing), /'/')
workers entering treated commercially grown sod, /'/'/') golf course maintenance workers following
applications to turfgrass, /v) landscape and ground maintenance workers following applications to
commercial/industrial areas and other no-crop areas.
There are no postapplication exposure data available at this time to determine potential risks from
bromoxynil uses. In lieu of chemical-specific data, a surrogate range-finder postapplication exposure
assessment was performed for occupational settings.
The range finder assessment in Table 23 is based on the application rate of 0.5 Ib ai/A for all
crops. The transfer coefficients (Tc) range from low exposure potentials such as hoeing in various field
crops (500 cm2/hr) and scouting early season cotton (1,000 cm2/hr) to high exposure potentials such
as harvesting sod (10,000 cm2/hr). Assuming an acceptable MOE of 100, the restricted entry interval
(REI) ranges from 0 days to 26 days.
65
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Table 23: Bromoxynil Short-Term and Intermediate-Term Postapplication Occupational
Surrogate Assessment (Range Finder)
DATa
DFR
(Mg/cm2)b
Dermal Dose (mg/kg/day)c
Low
High
MOEd
Low
High
All Crops Except Cotton
0
26
1.12
0.72
0.075
0.005
1.49
0.097
130
2000
7
100
Cotton (0.5 Ib ai/A)
0
4
2.2
0.78
0.30
0.10
1.2
0.42
33
100
NA
NA
a DAT = Days after treatment.
b DFR Og/cm2) = Appl. rate (Ib ai/A) x 1 1 .209 (/j.g per cmVlb ai per acre conversion) x 0.2 (fraction of ai retained
on foliage). A dissipation rate of 10 percent per day is assumed.
c Dermal Dose (mg/kg/day) = DFR (^tg/cm2) x Tc (cm2/hr) x 1 mg/1,000 ,wg conversion) x 8 (hrs/day) / 60 kg BW.
Where LOW potential exposure = 500 to 1,000 cmVhr and High potential exposure = 10,000 cm2/hr.
d MOE = NOEL (mg/kg/day) / Dermal Dose (mg/kg/day). Where NOEL = 10 mg/kg/day.
Bromoxynil is a contact herbicide and should be applied while weeds are actively growing. The
application timing for crops like corn and small grains, which comprise approximately 90% of
bromoxynil usage, is early in the season (from preemergence to prior to tassel emergence/boot stage).
Because of the use patterns and mode of action of bromoxynil, most workers entering treated fields
would likely be performing scouting tasks or low contact labor tasks such as mechanical incorporation
and cultivation. One likely exception is workers entering transgenic cotton fields. The window of
application for transgenic cotton is wider, which increases the potential for worker contact with treated
surfaces and cotton is scouted frequently. Another likely exception is post-application exposures to
workers entering commercially grown sod areas. The sod may be harvested soon after an application,
which could result in relatively high post-application exposures.
Based on the surrogate assessment, the Agency has concerns regarding low exposure activities
for cotton and high exposure activities for crops other than cotton (e.g., harvesting sod for applications
less than 26 days from harvest). The interim REI established by the WPS is 24 hours. Since the
toxicological endpoint for short-term and intermediate-term exposure is based on a NOEL for
developmental effects, EPA is concerned that the default REI of 24 hours is not protective enough,
especially for cotton workers and sod harvesters where there is significant potential for postapplication
exposures. This document reiterates the REIs of 4 days for cotton and 26 days for sod established
in the Federal Register Notice published May 13, 1998 in conjunction with the cotton use registration
action.
It is the short-term exposure driving the risk estimate for reentry concerns so EPA believes any
measures to reduce short term risks will be protective for cancer risks.
c. Epidemiological Information
Only a limited number of incidents involving the use of bromoxynil alone have been reported.
Eye or skin illnesses were the most frequently reported in the 11 cases received by the California
66
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Pesticide Illness Surveillance Program from 1982-1993, inclusively. The number of systemic incidents
per 1,000 applications for 1990 was 0 based on California use data (beginning in 1990 all agricultural
uses had to be reported, prior to that only data on restricted use applications were required). The ratio
of systemic poisonings to applications for all years is generally low when compared to organophosphate
and carbamate insecticides. No recommendations for risk mitigation are warranted based on the limited
data available on poisoning incidents.
C. Environmental Assessment
The environmental assessment consists of four sections: Ecological Toxicity, Environmental Fate
and Transport, Ecological Exposure and Risk Assessment, and Environmental Risk Characterization.
The first and third sections report the ecological toxicity data from laboratory studies, estimate
ecological exposure and assess the effects to nontarget terrestrial and aquatic organisms. The second
section depicts the environmental fate and transport data from field and laboratory studies, analyzes the
impact to water resources, and details the environmental fate assessment. The section on environmental
risk characterization integrates the exposure and effects assessments to determine the extent and
potential for risk to the environment.
1. Ecological Toxicity Data
The Agency has adequate data to assess acute and chronic hazard of bromoxynil octanoate to
nontarget species. In the risk assessment, toxicity data for bromoxynil octanoate, with the exception
of aquatic vascular plants, was used to estimate risk. This is consistent with the fate information. In
most cases, bromoxynil octanoate was more toxic to test species than bromoxynil heptanoate.
The guideline requirements for Tier 2 aquatic plant testing for bromoxynil octanoate (GLN 123-
2) are only partially fulfilled. Data must be submitted to fulfill the guideline requirement for Lemna
gibba (aquatic macrophyte). Additional data for chronic estuarine toxicity (72-4) are needed as
confirmatory data to complete the chronic assessment.
a. Toxicity to Terrestrial Animals
(1) Birds, Acute and Subacute
An oral (LD50) study (preferably mallard duck or bobwhite quail) and two subacute dietary (LC50)
studies (one species of waterfowl, preferably the mallard duck, and one species of upland game bird,
preferably bobwhite quail) are required to establish the acute and subacute toxicity of a pesticide to
birds. Results of these tests are tabulated below.
67
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Table 24: Avian Acute Oral Toxicity Findings
Species
Bobwhite Quail
Bobwhite Quail
Bobwhite Quail
Mallard Duck
% A.I. derivative
87.3 octanoate
89.3
phenol
94.8
heptanoate
87.3
octanoate
LD50 (mg ai/kg)
148
193
359
2050
MRID or Ace. No.
Author, Yr
Ace. # 248229
Fletcher, 1981
Ace. #258887
Fletcher, 1985
43030001
Campbell, 1993
Ace. #248229
Fletcher, 1981
Toxicity Category
moderately toxic
moderately toxic
moderately toxic
practically non-toxic
Fulfills Guideline
Requirement
Yes
Yes
Yes
Yes
Table 25: Avian Subacute Dietary Toxicity Findings
Species
Bobwhite Quail
Bobwhite Quail
Bobwhite Quail
Mallard Duck
Mallard Duck
Ring-necked Pheasant
Ring-necked Pheasant
% A.I.
derivative
94.8
heptanoate
87.3
octanoate
89.3
phenol
87.3
octanoate
89.3
phenol
technical
octanoate
36.6
octanoate
LC50
(ppm ai)
4530
1150
1790
1880
1230
4400
1830
MRID or Ace. No.
Author, Year
43030002
Campbell, 1993
Ace. #248229
Fletcher, 1982
Ace. #258886
Fletcher, 1985
Ace. #248229
Fletcher, 1981
Ace. #258888
Fletcher, 1985
Ace. #247924
Harper, 1965
Ace. #247924
Harper, 1965
Toxicity Category
slightly toxic
slightly toxic
slightly toxic
slightly toxic
slightly toxic
slightly toxic
slightly toxic
Fulfills Guideline
Requirment
Yes
Yes
Yes
Yes
Yes
Yes
Yes
These results indicate that bromoxynil (phenol), heptanoate, and octanoate are moderately toxic
to practically non-toxic to avian species on an acute oral basis and slightly toxic to avian species on a
subacute dietary basis. The guideline requirements (71-l(a) and 71-2(a) & (b)) are fulfilled (Accession
No. 248229, 258887, 258886, 247924, and 258888).
(2) Birds, Chronic
Avian reproduction studies are required for bromoxynil octanoate because it may be applied two
times per use season on several crops, and up to three times per season on cotton. Results of this test
are tabulated below.
Table 26: Avian Reproduction Findings
Species
Northern
Bobwhite
Mallard
Duck
% A.I.
97.2
octanoate
97.2
octanoate
NOEL
ppm
371
102
LOEL
jpm
NA
?40
Endpoints affected
NA
number of eggs laid and set, number of viable embryos, number of
ive 3-week embryos, and lesions of old yolk peritonitis or
regressing ovary
MRID No.
Author, Year
42004101,42475801
Beavers, 1991
42004102
Beavers, 1991
Fulfills Guideline
Requirement
Yes1
Yes
1 This study fulfills the guideline requirement even though it is classified as supplemental.
The results indicate that bromoxynil octanoate can impair the reproduction of birds at dietary
concentrations greater than 102 ppm. The guideline requirements (71-4(a) & (b)) are fulfilled for
bromoxynil octanoate (MRID 42004101, 42475801, and 42004102).
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b.
Mammals
Data from available mammalian studies which are used for human health risk assessment will be
used to estimate toxicity to wild mammalian species. A rat acute oral LD50 study with bromoxynil
octanoate resulted in an LD50 of 238 mg/kg for female rats and 400 mg/kg for male rats. These results
indicate that bromoxynil octanoate is moderately toxic to small mammals on an acute oral basis.
(MRID 124112)
A two-generation rat reproduction study with the technical grade of bromoxynil octanoate (97.8 -
98.1% a.i.) reported a reproductive NOEL of 250 ppm and a systemic LOEL greater than 250 ppm
based on reduced body weight gain in females. (83-4, MRID 41149301) A two-generation rat
reproductive study with the technical grade of bromoxynil phenol reported a reproductive NOEL of 50
ppm based on decreased body weight of offspring (MRID #41149301).
c.
Insects
A honeybee acute contact LD50 study was submitted for bromoxynil octanoate due to its
extensive use on cotton and other agricultural sites. A honeybee acute contact study showed that
bromoxynil octanoate (formulation not identified) is practically nontoxic to honeybees with an LD50 of
14.5 //g a^ee. There is sufficient information to characterize bromoxynil octanoate as practically non-
toxic to bees. The guideline requirement (141-1) is fulfilled. (ID No. 00018842)
d. Toxicity to Aquatic Animals
(1) Freshwater Fish
Two freshwater fish toxicity studies using the technical grade of the active ingredient are required
to establish the toxicity of a pesticide to freshwater fish. One study should use a coldwater species
(preferably the rainbow trout), and the other should use a warmwater species (preferably the bluegill
sunfish). Results of these tests are tabulated below.
Table 27: Freshwater Fish Acute Toxicity Findings
Species
Rainbow Trout
Rainbow Trout
Rainbow Trout
Rainbow Trout
Bluegill Sunfish
Bluegill Sunfish
Bluegill Sunfish
Bluegill Sunfish
Catfish (Ictalurus nebulosus)
Goldfish
% A.I. derivatives
36.6 octanoate
87.3 octanoate
2 1.5 phenol
95 phenol
94.8heptanoate
87.3 octanoate
95 phenol
2 1.5 phenol
36.6 octanoate
36.6 octanoate
LC50
(ppb a.i.)
50
100
3870
2100
29
53
4000
4945
23
170
MRID No.
Author, Year
Ace. # 247924 Harper, 1965
Ace. #264229 Sousa, 1981
Ace. # 072254 Hoberg, 1983
Ace. # 260441 Nicholson, 1985
43059601 Bettencourt, 1993
Ace. # 248229 Sousa, 1981
Ace. # 260441 Nicholson, 1985
Ace. # 072336 Sousa, 1983
Ace. # 247924 Harper and Ball, 1965
Ace. # 247924 Harper and Ball, 1965
Foxicity Category
very highly toxic
lighly toxic
moderately toxic
moderately toxic
very highly toxic
very highly toxic
moderately toxic
moderately toxic
very highly toxic
lighly toxic
Fulfills Guideline
Requirement
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Mo, supplemental
Mo, supplemental
The results of the 96-hour acute toxicity studies indicate that bromoxynil octanoate is very highly
toxic, bromoxynil heptanoate is very highly toxic, and bromoxynil phenol is moderately toxic to
69
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freshwater fish. The guideline requirements (72-l(a) & (c)) are fulfilled. (Accession 247924, 072336,
260441, 248229, 072254, 264229, 247924)
Data from fish early life-stage tests are required because bromoxynil octanoate is very highly toxic
to freshwater fish on an acute basis (acute LC50s range from 23-100 ppb). Results of this test are
tabulated below.
Table 28: Fish Early Life-Stage Toxicity Findings
Species
Fathead minnow
Fathead minnow
% A.I.
97.2 octanoate
63 octanoate
NOEL
(Ppb)
18
9
LOEL
(Ppb)
39
18
MATC
(Ppb)
26
12
MRID No.
Author/Year
41928301 Sousa, 1991
40111003 Suprenant, 1987
Endpoint Affected
decreased larval growth, survival
and embryo hatching success
decreased larval survival
Fulfills Guideline
Requirement
Yes, supplemental
No
One of the chronic fish studies is supplemental, but taken in conjunction with the previous early
life-stage fish study conducted in 1987 (MRID 40111003) they satisfy the guideline requirement (72-
4(a)). The results indicate that reproductive effects of bromoxynil octanoate to freshwater fish may
occur at levels greater than 9 ppb. The guideline requirement (72-4(a)) is fulfilled. (MRID 41928301,
40111003)
(2) Freshwater Invertebrates
A freshwater aquatic invertebrate toxicity test using the technical grade of the active ingredient
is required to assess the toxicity of a pesticide to freshwater invertebrates. The preferred test organism
is Daphnia magna, but early instar amphipods, stoneflies, mayflies, or midges may also be used.
Results of this test are tabulated below.
Table 29: Freshwater Invertebrate Toxicity Findings
Species
Daphnia magna (daphnid)
Daphnia pulex (daphnid)
Daphnia magna (daphnid)
Daphnia magna (daphnid)
Daphnia magna (daphnid)
% A.I.
87.3 octanoate
36.6 octanoate
94.8heptanoate
95 phenol
2 1.5 phenol
EC50
(ppb ai)
96
11
31
19,220
15,910
MRID NO.
Author, Year
Ace. #248229 Suprenant, 1981
Ace. # 247924 Harper, 1964
43059602 Putt, 1993
Ace. # 260441 Nicholson, 1985
00138087 Hoberg, 1983
Toxicity Category
very highly toxic
very highly toxic
very highly toxic
slightly toxic
slightly toxic
Fulfills Guideline
Requirement
Yes
Yes
Yes
Yes
Yes
The results indicate that bromoxynil octanoate and heptanoate are very highly toxic and
bromoxynil phenol is slightly toxic to aquatic invertebrates. The guideline requirement (72-2(a)) is
fulfilled. (Accession No. 247924, 260441, 248229, MRID 00138087)
Data from an aquatic invertebrate life-cycle test using Daphnia magna are required because
bromoxynil octanoate is very highly toxic to Daphnia magna (EC50 of 11 -96 ppb), is registered for uses
that involve multiple applications, and has a half-life of greater than 4 days. Results of this test are
tabulated below.
70
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Table 30: Aquatic Invertebrate Life-Cycle Toxicity Findings
Species
Daphnia magna
(daphnid)
Daphnia magna
(daphnid)
% A.I.
97.2
octanoate
60
octanoate
NOEL
ppb ai
2.5
2.6
LOEL
ppb ai
5.9
5.3
MATC
ppb ai
3.8
3.7
MRIDNo.
Author/Year
41928302
Putt, 1991
40111001
Suprenant, 1986
Endpoint
Affected
reproduction
and growth
survival
Fulfills Guideline
Requirement
Yes
Yes
Both aquatic invertebrate studies are supplemental individually, but taken together they satisfy
the guideline requirement for a life-cycle aquatic invertebrate study. The results indicate that aquatic
invertebrate reproductive impairment may occur at bromoxynil octanoate levels greater than 2.5 ppb.
The guideline requirement (72-4(b)) is fulfilled. (MRTD 41928302, 40111001)
(3)
Estuarine and Marine Animals
Acute toxicity testing with estuarine and marine organisms (fish, shrimp and oyster embryo-larvae
or shell deposition) using the technical grade of the active ingredient is required for bromoxynil
octanoate because of aerial application and because it has use patterns associated with estuarine and
marine environments. Results of these tests are tabulated below.
Table 31: Estuarine/Marine Acute Toxicity Findings
Species
Eastern oyster
(shell deposition)
Mysid
Sheepshead minnow
% A.I.
92.4
octanoate
94.9
octanoate
97.2
octanoate
LC50 or EC50
(ppb ai)
155
65
170
MRIDNo.
Author/Year
42244501
Dionne, 1992
43487601
Machado, 1994
42250601
Machado, 1992
Toxicity
Category
highly toxic
very highly toxic
highly toxic
Fulfills Guideline
Requirement
Yes
Yes
Yes
The results indicate that bromoxynil octanoate is highly toxic to estuarine/marine fish and oysters
and very highly toxic to estuarine/marine shrimp on an acute basis. The guideline requirements (72-3
(a) & (c)) are fulfilled. (MRID 42244501, 42250601, 43487601).
Chronic testing with bromoxynil octanoate for estuarine/marine organisms (172-4 (a) & (b)) has
not been submitted and is requested at this time.
e. Toxicity to Plants
(1) Terrestrial
Terrestrial plant testing (seedling emergence and vegetative vigor) is required for all herbicides.
71
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For the seedling emergence and vegetative vigor testing, the following plant species and groups
should be tested: (1) six species of at least four dicotyledonous families, one species of which is soybean
(Glycine max), and the second of which is a root crop, and (2) four species of at least two
monocotyledonous families, one of which is corn (Zea mays). Results of these studies are tabulated
below.
Table 32: Tier 2 toxicity data on the TEP material for the most sensitive species:
Study Type
Germination
Seedling
Emergence
Vegetative
Vigor
Seedling
Emergence
Vegetative
Vigor
%AI
97.6
octanoate
94.8
heptanoate
94.8
heptanoate
33.58
octanoate
(Buctril)
33.58
octanoate
(Buctril)
Species
dicot ~ tomato
all monocots tested
dicot ~ lettuce
all monocots tested
cabbage
ryegrass
dicot --tomato
all monocots tested
dicot-tomato,
cabbage
monocot—onion
EC25
(Ib ai/A)
>0.45
>0.45
0.014
>0.45
0.011
0.19
0.12
>0.60
0.017
0.37
Most Sensitive Endpoint
germination, radicle
length
germination, radicle
length
shoot length
shoot length
shoot weight
root weight
shoot length
emergence, shoot length
plant dry weight
plant dry weight
MRID#
Author, Year
43273801
Hoberg, 1994
43059603
Hoberg, 1993
43059603
Hoberg, 1993
43633701
Hoberg, 1995
43633701
Hoberg, 1995
Fulfills Guideline
Requirements
Yes
Yes
Yes
Yes
Yes
The results indicate that non-target terrestrial plants may be affected from runoff if the soil
residues exceed an equivalent of 0.12 Ib ai/A and from drift if the drift residues exceed 0.017 Ib ai/A.
The guideline requirements (123-2) are fulfilled for seedling emergence and for vegetative vigor.
(MRID 43633701)
(2) Aquatic Plant
Currently, aquatic plant testing is required for all herbicides. The following species should be
tested: Selenastrumcapricornutum,Lemnagibba,Skeletonemacostatum, Anabaenaflos-aquae, and
a freshwater diatom. The results are tablulated in the table below.
72
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Table 33: Tier II toxicity data on the technical material
Species
Lemna gibba
Selenastrum capricornutum (green algae)
Navicula pelliculosa (Freshwater diatom)
Selenastrum capricornutum (green algae)
Skeletonema costatum (marine diatom)
Anabaenaflos-aquae (blue-green algae)
% A.I.
94.8
heptanoate
94.8
heptanoate
97.2
octanoate
97.2
octanoate
97.2
octanoate
97.2
octanoate
EC50
(ppb ai)
219
80
51
210
140
>630
MRID NO.
Author/year
43059604 Hoberg, 1993
43059605 Hoberg, 1993
41606001 Giddings,
1990
41606004 Giddings,
1990
41606002 Giddings,
1990
41606005 Giddings,
1990
Fulfills Guideline
Requirement
Yes
Yes
Yes
Yes
Yes
Yes
The results indicate that algae and diatoms are sensitive to bromoxynil octanoate and heptanoate.
The guideline requirements for Tier 2 aquatic plant testing for bromoxynil octanoate (GLN 123-2) are
only partially fulfilled. Acceptable data have not been submitted for Lemna gibba. These data must
be submitted to fulfill the guideline requirement. (MRID 4160601, 41606002, 41606004, and
41606005)
2.
Environmental Fate
a.
Environmental Fate Assessment
Bromoxynil octanoate was found to be chemically and physically similar to bromoxynil
heptanoate (one carbon difference in the ester side chain) and both esters readily hydrolyze to 3,5-
dibromo-4-hydroxybenzonitrile [referred to as bromoxynil (phenol)] which further degrades to CO2.
Bromoxynil octanoate is mobile and non-persistent. It dissipates in the environment by abiotic
hydrolysis, photolytic degradation, and microbially-mediated metabolism in both the aerobic and
anaerobic environments. The heptanoate ester was registered based on bridging data for bromoxynil
octanoate.
Laboratory studies indicate that bromoxynil octanoate is non-persistent. The hydrolysis of
bromoxynil octanoate is base-catalyzed with half-lives of 34.1, 11.5 and 1.7 days at pH 5, 7 and 9,
respectively. The major hydrolytic degradate is bromoxynil (phenol). Bromoxynil octanoate also
degrades via aqueous photolysis with a half-life of 4.6 days at pH 5. Soil photolysis is comparable to
aqueous photolysis with a reported half-life of 2.6 days. Bromoxynil octanoate is non-persistent and
degrades by microbially-mediated metabolism under both aerobic and anaerobic conditions. The
calculated half-life from the aerobic soil metabolism study is 2 days while the half-life from the
anaerobic aquatic metabolism study is 3.7 days. The aerobic aquatic metabolism study also shows rapid
degradation with a half-life of <12 hours.
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The unaged soil column leaching study indicates that bromoxynil octanoate is mobile in columns
of sand, sandy loam, and loam soils. Residues were distributed throughout the length of each soil
column and ranged from 2.7-18.2% of the applied in the leachates for the sandy loam and loam soils,
and 52.4-58.9% of the applied in the leachates for the sand soils. The aged soil column leaching study
indicates that bromoxynil octanoate residues are not mobile in four soils and aquatic sediment.
Supplemental information shows that bromoxynil octanoate has aKd of 7.0 ml/g (Koc of 1,003) in soils
with 1.2% organic matter; however, without a range of Kd (and due to the fact that this is a
supplemental study) it is difficult to assess the mobility.
The observed half-life of bromoxynil octanoate in a terrestrial field dissipation study conducted
in California was approximately 14 days while a half-life of 1 day was reported for a North Carolina
field site.
Bromoxynil octanoate bioaccumulates in bluegill sunfish with bioconcentration factors of 63X
for edible tissue, 400X for inedible tissue, and 230X for whole fish; however, depuration occurred in
14 days.
Bromoxynil octanoate does not exhibit the mobility or persistence characteristics of pesticides
that are normally found in ground water. Based on limited monitoring information, residues of
bromoxynil octanoate have not been detected in ground water. Based on information from
environmental fate studies, bromoxynil octanoate should not persist in surface waters. Limited
monitoring information is available.
b. Environmental Fate and Transport
(1) Degradation
Abiotic Hydrolysis
Hydrolysis of bromoxynil octanoate is base-catalyzed with half-lives of 34.1 days at pH 5, 11.5
days at pH 7, and 1.7 days for pH 9. The hydrolysis products were 3,5-dibromo-4-hydroxybenzonitrile
(referred to as bromoxynil (phenol)), and 3,5-dibromo-dihydroxy-cyclohexadienylnitrile. Bromoxynil
(phenol), which is stable to hydrolysis, increased throughout the study, reaching maximum
concentrations at 30 days of 35%, 77%, and 76% at pH 5, 7, and 9, respectively. The degradate 3,5-
Dibromo-dihydroxy-cyclohexadienylnitrile concentrations reached maximum concentrations of 10.4%,
10.7%, and 7.9% at pH 5, 7 and 9, respectively, but declined from those values by the end of the study,
indicating that it was not stable to hydrolysis. This data requirement is fulfilled (GLN 161-1; MRTD
41892901).
In another study bromoxynil octanoate hydrolyzed with calculated half-lives of 43 days at pH 5,
28 days at pH 7, and 1.5 days for pH 9. Hydrolysis of bromoxynil butyrate (an ester of bromoxynil
which is currently not being registered) is base-catalyzed with calculated half-lives of 44 days at pH 5,
52 days at pH 7, and 1.1 days for pH 9. Bromoxynil (phenol) was the hydrolysis product for both the
octanoate and the butyrate. It was stable to hydrolysis at pH 5, 7, and 9. The study was considered
acceptable. This data requirement is fulfilled (GLN 161-1; MRID 00130424).
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Aqueous Photolysis
Bromoxynil octanoate degraded with a calculated photolytic half-life of 4.6 days at pH 5. Each
photoperiod consisted of 12 hours of light (artificial - xenon arc lamp) and 12 hours of darkness.
Bromoxynil octanoate was stable in the dark controls with a 110.7-day half-life. In the irradiated
samples there were 3 major degradates: 4-cyano-2-bromophenyl octanoate (maximum mean
concentration of 13.9% at day 3), bromoxynil (phenol) (maximum mean concentration of 53.4% at day
30), and phenyl carbamate (maximum mean concentration of 26.6% at day 2). This data requirement
is fulfilled (GLN 161-2; MRID 42234301 and 41920401).
Soil Photolysis
Bromoxynil octanoate degraded with a calculated photolytic half-life of 2.6 days in the irradiated
samples (artificial - xenon arc lamp) and 3.6 days in the dark control. The 3.6 day half-life in the dark
controls suggests other degradation processes such as hydrolysis or microbial metabolism, were
occurring. This data guideline requirement is fulfilled (GLN 161-3; MRID 41920402).
Aerobic Soil Metabolism
[Cyano labeled 14C]-bromoxynil octanoate degraded in a sandy loam soil with a calculated half-life
of 2 days. The major degradate was CO2 which accounted for 64.28% of the applied radioactivity at
90 days. (GLN 162-1; MRID 42234302 and MRID 41897701). Bromoxynil (phenol) exhibited half-
lives of 51 hr in sandy loam and 31 hr in loam soils (GLN 162-1; MRID 00142958). This data
requirement is fulfilled (GLN 162-1; MRID 42234302, 41897701 and 00142958).
Anaerobic Aquatic Metabolism
Bromoxynil octanoate degraded in a sandy loam sediment with a calculated half-life of 3.7 days
based on the results obtained over the first 14 days of the experiment. The degradate 4-
hydroxybenzonitrile reached a maximum concentration of 45.52% by Day 14 before decreasing to
0.14% at 26 weeks. Bromoxynil (phenol) was also formed, reaching a maximum concentration of
48.5% by day 7, then decreasing to 3.5% at 8 weeks. This data requirement is fulfilled (GLN 162-3;
MRID 42234303 and 41892902).
Aerobic Aquatic Metabolism
Bromoxynil octanoate degraded with a half-life of <12 hours when treated sandy loam soil was
flooded with pond water which was aerobically incubated in the dark at approximately 25 °C.
Bromoxynil octanoate was 87.64% of the applied at time 0 and declined to undetectable levels by 48
hours posttreatment. The major nonvolatile degradates were bromoxynil (phenol), p-
hydroxybenzonitrile, 3-bromo-4-hydroxybenzonitrile, and 3,5-dibromo-4-hydroxybenzoic acid. The
degradate bromoxynil (phenol) was 6.59% of the applied immediately posttreatment, 66.47% at 12
hours, 78.77% at 48 hours posttreatment, 39.68% at 168 hours, and 2.39-4.56% at 336 through 720
hours. This data requirement is fulfilled (GLN 162-4; MRTD 42364901).
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(2) Mobility
Unaged Soil Column Leaching [14C]Bromoxynil Octanoate
Bromoxynil octanoate was mobile in columns of sand, sandy loam, and loam soils that were
treated at 228.9 //g/column with phenyl ring-labeled [14C] bromoxynil octanoate and leached with 50.8
cm of a 0.005 M calcium chloride solution. Residues were distributed throughout the length of each
soil column and ranged from 2.7-18.2% of the applied in the leachates from the sandy loam-1, sandy
loam-2, and loam soil columns; and from 52.4-58.9% in the leachates from the sand soil columns. In
the 0-7 cm segment of the columns for sandy loam-1, sandy loam-2 and sand soil, the recoveries were
approximately 31-43%, 31-35%, and 13%, respectively. This data requirement is fulfilled
(MRID 42271101).
Aged Bromoxynil Octanoate Residues
Aged bromoxynil octanoate (2,6-dibromo-4-cyanophenyl octanoate) residues were not mobile
in columns of four soils and an aquatic sediment that were treated with bromoxynil octanoate that had
been aerobically aged (aerobic half-lives of 28-100 hours) and then leached with 50.8 cm of a 0.01 M
calcium chloride solution. Residues in the sandy loam, loam, clay loam, and aquatic sediment columns
were concentrated in the segment composed of the aged soil and the segment immediately beneath it:
14C in the leachates was < 0.27% of the applied. Residues in the sand soil columns moved slightly more
than in the other soils, but remained concentrated in the upper two segments of the columns (top 10
cm); any 14C-residues in the leachates were [14C]-carbonates and were 3.50-3.58% of the applied. This
data requirement is fulfilled (GLN 163-1; MRID 42271101 and 43775001).
Adsorption/Desorption Batch Equilibrium
Bromoxynil octanoate was found to be mobile in sandy loam soil with pH 7.2 and 1.1% organic
matter. The Kd was 7.0 (Koc=l,003). The study was considered supplemental and did not satisfy data
requirements because the study authors failed to show that the aerobic soil metabolism half-life of the
sandy loam soil was much greater than the equilibration time of 24 hours in the batch equilibrium study
(163-1; MRID #00116557 and 00114338). However, this data requirement is fulfilled using the aged
and unaged column leaching studies (GLN 163-1; MRID 42271101 and 43775001).
Laboratory Volatility and Field Volatility
This data requirement was waived based on the low vapor pressure (1.39 x 10 "6 mm Hg) and
estimated Henry's Law Constant (9.76 x 10 '8 atm-m3/mol). (GLN 163-2, 163-3; EFGWB # 91-0200-
0199, 1/17/91).
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(3) Accumulation
Fish Accumulation
[14C]Bromoxynil octanoate residues accumulated in bluegill sunfish continuously exposed to
[14C]bromoxynil octanoate at 1.3-4.7 //g/L. The maximum bioconcentration factors were 63x for edible
tissue, 400x for inedible tissue, and 230x for whole fish. Depuration occurred with 85-97% of the
accumulated residues eliminated by Day 14. This data requirement is fulfilled (GLN 165-4; MRTD
42277301-a and 42277301-b).
(4) Field Dissipation
Terrestrial Field Dissipation
Bromoxynil, spray applied at 0.56 kg ai/ha to plots planted in wheat, dissipated with observed
half-lives (DT50) of approximately 14 days from a Sorrento silt loam soil in California and 1 day from
a Norfolk sandy loam soil in North Carolina. At both sites, bromoxynil octanoate residues were not
detected below the 0-15 cm soil depth indicating leaching was not an important route of dissipation.
In San Juan Bautista, California, air temperatures ranged from 39° to 96° F and the soil temperatures
(10-cm depth) ranged from 55° to 77°F . The field plots in California were irrigated with 30.5 mm of
water to supplement the limited rainfall before day 20. In Clayton, North Carolina, air temperatures
ranged from 19° to 35° C and soil temperatures (10-cm depth) ranged from 23° to 30° C. Total rainfall
during the study was 245 mm; therefore, irrigation was not applied to field plots. Results of a freezer
storage stability study indicate there was no significant degradation of either bromoxynil octanoate or
bromoxynil (phenol) in the California or North Carolina soils used in the field studies. This data
requirement is fulfilled (GLN 164-1; MRID 41653701 and 43071001).
Nitrification Inhibition
Bromoxynil has been shown to inhibit nitrification in soils (Frear, 1976). Nitrification is defined
as the oxidation of reduced nitrogen (e.g., ammonium) by bacteria (Nitrosomonas, Nitrobacter species)
to nitrate through the intermediate product, nitrite (Brady and Weil, 1996). Various environmental
factors such as soil reaction (acidity and alkalinity), aeration, moisture, carbon sources, temperature and
nutrient availability influence the nitrification process. For certain environmental conditions,
commercially-available nitrification inhibitors (Dwell®, N-Serve®) are used in production agriculture
to temporarily slow conversion of ammonium fertilizers to nitrate because nitrate can be lost through
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leaching or denitrification. In the environment, adaptation to nitrification inhibitors, such as bromoxynil,
is demonstrated by the increasing bromoxynil concentrations that are needed to cause 50% inhibition
(Frear, 1976). In addition, these adaptation studies support the observation that microbial-mediated
metabolism (aerobic soil metabolism half-lives of 31-51 hours; field dissipation half-life of 1-14 days)
is an important process for degradation of bromoxynil in soils; therefore, nitrification inhibition would
generally occur only on a temporary basis. Thus, nitrification inhibition by bromoxynil does not appear
to be a concern.
(5) Spray Drift
No specific spray drift studies for bromoxynil were reviewed. Droplet size spectrum (201-1) and
drift field evaluation (202-1) studies were required since the different products may be applied by
aircraft and because of a concern for potential risk to nontarget aquatic organisms. However, to satisfy
these requirements the registrant in conjunction with other registrants of other pesticide active
ingredients formed the Spray Drift Task Force (SDTF). The SDTF has completed and submitted to
the Agency its series of studies which are intended to characterize spray droplet drift potential due to
various factors, including application methods, application equipment, meteorological conditions, crop
geometry, and droplet characteristics. In the near future, EPA plans completion of its evaluation of
these studies. In the interim and for this assessment of bromoxynil, the Agency is relying on previously
submitted spray drift data and the open literature for off-target drift rates. The rates are 1% of the
applied spray volume from ground applications and 5% from aerial applications at 100 feet downwind.
After its review of the new studies the Agency will determine whether a reassessment of the potential
risks to nontarget organisms is warranted.
c. Water Resources
(1) Ground Water
The Office of Pesticide Programs (OPP) evaluates the persistence and mobility of each pesticide
for ground water concerns. If the data indicate that the parent and/or degradates are persistent and
mobile, then a small-scale prospective ground water study may be requested. The basic triggering
criteria include: 1) weight of the evidence from laboratory and field dissipation studies indicating that
the pesticide has properties and characteristics similar to pesticides that are known to leach or have been
detected in ground water; 2) movement of the parent or degradates 75-90 centimeters through the soil
profile or plow layer in a field dissipation study; 3) reports of detections in ground water from other
monitoring studies; and 4) information about toxicity. In addition, use patterns, application rates,
timing of application, potential acreage treated, depth to ground water, soil types, hydraulic gradient,
and climate are also evaluated as part of the triggering criteria.
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Persistence, mobility and detections in ground water are used also to evaluate a chemical to
determine whether its use should be restricted. A pesticide may be recommended as a candidate for
restriction if it exceeds one or more criteria for each of the three factors (persistence, mobility, and
detections).
Persistence and Mobility
Bromoxynil octanoate was evaluated for persistence and mobility in relation to its potential to
leach to ground water. Bromoxynil octanoate is not considered a candidate for restricted use due to
ground water concerns. Below is a summary of that evaluation. This table does not include degradate
data.
Table 34: Mobility and Persistence of Bromoxynil Octanoate Relative to Restricted Use Criteria
Factor
Persistence
Mobility
Characteristic
Field dissipation half-life
Lab-derived aerobic soil metabolism half-life
Hydrolysis half-life
Photolysis half-life (soil)
Soil adsorption: Kd
Soil adsorption: Koc
Depth of leaching in field dissipation study
Restricted Use Criteria
> 3 weeks or
> 3 weeks or
< 10% in 30 days or
< 10% in 30 days and
< 5 ml/g or
< 500 ml/g or
75 - 90 cm
Reported Value(s)
14 days
2 days
calculated 44%,130%,882%
pH 5,7,9, respectively
calculated 326%
7.0 ml/g
1,003 ml/g
not below 15 cm
Ground Water Detections
Limited monitoring information for bromoxynil octanoate in ground water is available. The
"Pesticides in Ground Water Database" (EPA, 1992) reports sampling for bromoxynil (no distinction
made between esters and the phenolic compound) in 107 wells in four counties in Oregon between 1985
and 1987. The wells sampled in each area (public water supply and domestic) were selected based on
suspected vulnerability, susceptibility to contamination, and availability of information on well
construction and depth. No information on the details of the monitoring was available. No detections
of bromoxynil octanoate were reported. Below is a summary of that evaluation.
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Table 35: Detections of Bromoxynil Octanoate Relative to Restricted Use Criteria
Criterion
Detections
Characteristic
Number of wells per state with
detections
Number of counties with detections >
10% of reference point
Restricted Use Criteria
25 wells in 4 or more states
or
3 counties at >10% of MCL
or HAL
Reported Detections
No Detections
No MCL or HA Established;
Calculated HA from Reference
Dose 1 1 /-ig/L
Ground-Water Concerns
Based on the available data, the Agency concludes that the potential for ground water
contamination from bromoxynil octanoate is low; it does not exhibit the mobility or persistence
characteristics of pesticides that are normally found in ground water. Although bromoxynil octanoate
has been found to be mobile under certain conditions (sand, sandy loam, and loam soils as reported in
the acceptable unaged column leaching study), it dissipates in the environment by abiotic hydrolysis,
photodegradation and microbially-mediated metabolism.
Since bromoxynil octanoate readily degrades to bromoxynil (phenol) via hydrolysis (half-life 2-34
days), the mobility and persistence of the phenol were examined also. Bromoxynil (phenol) is an anion
in environmentally significant pH ranges, has a water solubility of 130 ppm, and is stable to hydrolysis
at pH 5, 7 and 9. Batch equilibrium and soil column leaching studies indicate that bromoxynil (phenol)
is mobile in sandy soils with low organic matter content (Kd 1.4; 1.3% OM). If heavy rainfall occurred
to a sandy soil with low organic matter content, bromoxynil (phenol) could potentially leach to ground
water. However, based on the aerobic soil metabolism study, bromoxynil (phenol) degrades very
rapidly to CO2 (33.6% of the applied), and to the non-volatile degradates 3,5-dibromo-4-
hydroxybenzamide (which decreased from 21.6% to 0.3% by day 28), and 3,5-dibromo-4-
hydroxybenzoic acid (which decreased from 34.8% to 0.4% by day 28). Also, based on the anaerobic
aquatic metabolism study, bromoxynil (phenol) degrades under anaerobic conditions (levels were 3.6%
after 8 weeks). Therefore, although bromoxynil (phenol) has the potential to leach to ground water
under certain conditions, its rapid aerobic and anaerobic degradation reduces the likelihood of ground
water contamination. The Agency does not consider bromoxynil (phenol) to be a candidate for
restricted use due to ground water concerns. The potential for ground water contamination from
bromoxynil (phenol) is low.
Status of Ground Water Monitoring Requirements
The small-scale prospective (GLN 166-1) and the small-scale retrospective (GLN 166-2) ground
water monitoring studies were reserved pending preliminary assessment of potential for leaching to
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ground water based upon the results of laboratory and terrestrial field dissipation studies. The (166-3)
large-scale retrospective ground water monitoring study was reserved pending the review of the results
from the small-scale retrospective ground water monitoring study. Based on the results from the
laboratory and terrestrial field dissipation studies, bromoxynil octanoate does not have the mobility or
persistence characteristics of pesticides that are normally found in ground water. Therefore, no ground
water monitoring studies are required for bromoxynil octanoate at this time.
(2) Surface Water
Information from environmental fate studies indicates that bromoxynil octanoate should not
persist in surface waters. Based on the aerobic aquatic and anaerobic aquatic metabolism studies,
bromoxynil octanoate degrades quickly to the phenolic compound (which further degrades to
approximately 2% of the applied) with a half-life of <12 hours and 3.7 days, respectively. Laboratory
studies indicate that photolytic degradation occurs rapidly with a half-life of 4.6 days. In aquatic
systems abiotic hydrolysis of bromoxynil octanoate is base-catalyzed with the major degradate being
bromoxynil (phenol). Reported hydrolysis half-lives were 34.1, 11.5 and 1.7 days at pH 5, 7 and 9.
The reported vapor pressure (1.39 x 10"6 mm Hg) and the Henry's constant (9.76 x 10"8 atm
nrVmol) indicate that bromoxynil octanoate should not readily volatilize from surface water
environments. Based on the Freundlich adsorption coefficient (Kd =7.0 ml/g) from a supplemental
study, bromoxynil octanoate might be transported in surface runoff waters. However, bromoxynil
octanoate is not predicted to persist in surface waters.
Estimated Aquatic Concentrations Tier 1: Tier 1 Estimated Environmental Concentrations (EECs)
were calculated for bromoxynil octanoate application to a variety of crops at several different rates and
using several application patterns. These EECs, calculated using the GENeric Estimated
Environmental Concentration Program (GENEEC), represent a screen and depend on basic chemical
parameters and pesticide label application information. GENEEC uses a chemical's soil/water partition
coefficient and degradation half-life values to estimate runoff from a ten hectare field into a one hectare
by two meter deep pond. It was designed to specifically model runoff from agricultural fields.
GENEEC uses application information for each crop, but uses the same site for all applications. The
site is in Yazoo, Mississippi and has a Loring silt loam soil.
GENEEC calculates both acute and chronic generic EEC values. It considers reduction in
dissolved pesticide concentration due to adsorption of pesticide to soil or sediment, incorporation,
degradation in soil before washoff to a water body, direct deposition of spray drift into the water body,
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and degradation of the pesticide within the water body. Because the review of the Spray Drift Task
Force data has not been completed, spray drift is assumed to be 1% of the application rate for ground
applications and 5% of the application rate for aerial applications.
The following values were used for input into the GENEEC program:
Soil organic carbon partitioning coefficient: 1003
Soil aerobic metabolic half-life 2 days
Aqueous photolysis half-life: 4.6 days
Aerobic aquatic metabolism half-life: 1 day
Water solubility: 0.08 ppm
Table 36 : Generic EECs for bromoxynil octanoate
Crop
Corn, Small
Grains
Corn
Small Grains
Cotton
Cotton
Cotton
Cotton
Application
Method
Broadcast -
ground & aerial
Broadcast- ground
& aerial
Broadcast -
ground & aerial
Broadcast-
ground
Broadcast -
ground
Aerial
Aerial
Application Rate in Ibs a.i./A
(number of apps.)
0.5 (1) maximum rate
0.28 (1) typical rate
0.31 (1) typical rate
0.5 (3) maximum rate - 10 day
application interval
0.4 (2) typical rate - 10 day
application interval
0.5 (3) maximum rate - 10 day
application interval
0.4 (2) typical rate - 10 day
application interval
Peak EEC
(ppb)
4.5
2.6
3.0
9.4
8.0
10.0
8.4
4-day EEC
(ppb)
2.2
1.2
1.3
4.5
3.8
5.0
4.1
21 -day EEC
(ppb)
0.4
0.3
0.3
0.9
0.7
1.0
0.9
56-day EEC
(ppb)
0.15
0.15
0.15
0.3
0.3
0.4
0.3
Peak exposure levels range from 2.6 to 10.0 ppb (wg/L), with 21-day average values ranging from
0.3 to 1.0 ppb (//g/L), and, 56-day average values ranging from 0.15 to 0.4 ppb (ug/L). For a single
ground application applied at 0.5 Ib ai/A, the peak EEC was 4.5 ppb for both corn and small grains.
The peak EEC for corn and small grains decreased with the typical use rates of 0.31 and 0.28 Ib ai/A,
respectively. The EEC for cotton was estimated using three applications with a ten day interval at a
maximum application rate of 0.5 Ib ai/A. The peak EEC was 9.4 and 10.0 ppb for ground and aerial
applications, respectively. Using a typical application rate of 0.4 Ib ai/A, the peak EEC decreased for
both the ground and aerial applications.
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The preceding EECs were used to assess the risk of bromoxynil octanoate to nontarget aquatic
organisms. They were compared to ecotoxicity information for bromoxynil octanoate in the risk
assessment portion of this document (Section 3(2)).
Estimated Aquatic Concentrations (Tier 2) for Drinking Water Exposure and Human Health
Assessment: Bromoxynil octanoate rapidly degrades to bromoxynil, therefore all calculations have been
performed for bromoxynil, rather than for bromoxynil octanoate. The purpose of this analysis was to
generate aquatic exposure estimates for use in the human health risk assessment for bromoxynil. These
Tier 2 EECs were also used to further refine the ecological risk of bromoxynil octanoate application
to cotton.
A Tier 2 EEC uses a single site which represents a high exposure scenario for the use of the
pesticide on a particular crop or non-crop use site. The weather and agricultural practice are simulated
at the site over multiple (in this case, 20) years so that the probability of an EEC occurring at that site
can be estimated. EEC's were calculated for the Buctril 2EC (Registration Number 264-540)
formulation because this was the formulation being registered for use on cotton.
The Tier 2 EEC's generated in this analysis were calculated using PRZM 2.3 for simulating the
agricultural field and EXAMS 2 for fate and transport in surface water. Spray drift was simulated using
an assumption that 5% of applied bromoxynil reached surface water at the time of application and that
75% of the chemical was deposited on site. The other 20% is assumed to either remained airborne or
be deposited on the ground beyond the pond.
The scenario chosen was a cotton field in Yazoo, Mississippi. The scenario was chosen to
represent a site that was expected to produce more runoff than 90% of the sites used for cotton. The
simulation was made with the maximum application rate of 0.5 Ib-acre"1 with the maximum number of
yearly applications, three. The interval between applications was 14 days. The Tier 2 upper tenth
percentile EEC's for cotton are listed in Table 37. The EEC's have been calculated so that in any given
year, there is a 10% probability that the maximum average concentration of that duration in that year
will equal or exceed the EEC at the site.
Table 37: Tier 2 Upper Tenth Percentile EEC's for Bromoxynil Octanoate (as Bromoxynil) on
Cotton
Maximum
12.3 Mg -I/1
4 Day
10.0 iig -I/1
21 Day
5.3 Mg -I/1
60 Day
2.5 Mg -I/1
90 Day
i.eng-L-1
Long-term Mean*
0.24 iig -I/1
*Upper 90% confidence bound on the 20 year mean with the variance calculated from the annual means.
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Limitations of this analysis for drinking water exposure estimates: There are certain limitations
imposed when Tier 2 EEC's are used for drinking water exposure estimates. A single 10 hectare field
with a 1 hectare pond does not accurately reflect the dynamics in a watershed large enough to support
a drinking water facility. A basin of this size would certainly not be planted completely to a single crop
nor be completely treated with a pesticide. Additionally, treatment with the pesticide would likely occur
over several days or weeks, rather than all on a single day. This would reduce the magnitude of the
concentration peaks, but also make them broader, reducing the acute exposure but perhaps increasing
the chronic exposure. The fact that the simulated pond has no outlet is also a limitation as water bodies
in this size range would have at least some flow through (rivers) or turnover (reservoirs). In spite of
these limitations, a Tier 2 EEC can provide a reasonable upper bound on the concentration found in
surface water if not an accurate assessment of the real concentration. Risk assessment using Tier 2
values can capably be used as refined screens to demonstrate that the risk is below the level of concern.
Characterization of Surface Water Monitoring Data for Bromoxynil
This section summarizes the water resource monitoring data for bromoxynil collected by the
USGS National Water Quality Assessment (NAWQA) Program from 1993-1995. Comparisons
between the surface water modeling results (Tiers 1 and 2) and the USGS monitoring data suggest
reasonable agreement for estimating surface water environmental concentrations using either data
source. However, the agreement between modeling results and monitoring data would not be expected
based on the variation in hydrologic settings. Table 38 shows the maximum and long-term mean values
from Tier 1 and 2 modeling compared to the USGS NAWQA maximum, mean and median values.
Table 38: Modeling and Monitoring Data for Bromoxynil in Surface Waters
Data Source
Tier 1 Modeling
Tier 2 Modeling
USGS Monitoring
Maximum Concentration ( ug/L )
6.9
12.3
6.1
Annual Mean ( ug/L )
Not estimated
0.24
0.105 (median; all data)
0.53 (mean; all data)
0.60 (median; data > 0.2 ug/L)
Note: "all data" indicates results (n = 20) reported as "detects" by the USGS; "non-detects" were not included.
Bromoxynil water resource monitoring data from the USGS NAWQA Program were reported
during the 1993-1995 period from 7 of the 20 river basins (termed "Study Units" by the USGS)
throughout the U. S. The NAWQA Program examined drainage basins that were primarily agricultural
land use. The percentage of detections was 1.1% from a total of 1,925 surface water samples
(minimum reporting limit = 0.035 |ig/L). Analysis of the 20 detections >0.03 |ig/L yielded a median
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value of 0.105 |ig/L with a mean of 0.53 |ig/L (Table 38). The maximum concentration of 6.1 |ig/L
was measured at the Lonetree Creek location in the South Platte River Study Unit, CO. For reported
concentrations above 0.2 jig/L (range of 0.45-6.1 |ig/L), the median value was 0.60 jig/L.
Geographically, the highest concentrations were reported for samples collected in Colorado, Indiana,
Nebraska and Washington. For urban land use, bromoxynil was not detected in surface waters, and
one detection in groundwater (0.07 |ig/L) was reported from a total of 2,245 samples. Specific
information on application of bromoxynil in each of the Study Units was not available for this
evaluation.
The following table provides detected concentrations of bromoxynil in surface water - USGS
NAWQA data (1993-1995):
Table 39: Bromoxynil Detections in Surface Waters - USGS NAWQA (1993-1995)
Study Unit
South Platte, CO
White River, IN
Red River - North
(ND/MN)
Central Nebraska
Columbia Plateau, WA
Willamette Valley, OR
Trinity River
Location
Lonetree Creek
Kessinger Ditch
Cliffy Creek
Red River
Snake River
Prairie Creek
Shell Creek
EL 68D Wasteway
Palouse River
Zollner Creek
Pudding River
not listed
Date
06/29/94
05/11/94
06/30/93
07/12/94
05/25/94
06/29/93
06/16/94
07/06/95
06/16/94
06/20/94
07/28/94
06/29/93
05/16/94
05/04/94
05/25/93
04/27/93
05/05/93
10/28/94
04/14/95
06/07/95
Concentration (ug/L)
6.1
0.93
0.45
0.10
0.09
0.77
0.06
0.25
0.12
0.10
0.08
0.55
0.09
0.02
0.02
0.60
0.13
0.11
0.03
0.05
NOTE: The minimum reporting limit (0.035 ug/L) equals the method detection limit calculated with the U.S.EPA
method (1992). For bromoxynil in surface waters, the instrument detection limit (single operator) was 0.011 ug/L with
a mean accuracy (percent of the true concentration) of 52% and a relative standard deviation (RSD) of 7%.
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Surface water monitoring of the South Platte River Study Unit at the Lonetree Creek Basin
displayed the highest and most frequent detectable levels of bromoxynil. Land use information for this
basin indicates irrigated agriculture is predominant in the lower portion of the basin near the sampling
station (Kimbrough and Litke, 1996). The contributing drainage area for the study was estimated to
be 202 square kilometers. Precipitation in the basin is approximately 40 cm/year (about 16 inches/year)
and occurs primarily as infrequent, high-intensity storm events such as summer thunderstorms.
Information describing the representativeness of the Lonetree Creek Basin to other surface water basins
where bromoxynil was applied is not currently known.
Monitoring results from the NAWQA Program represent high quality data. All aspects of the
program were carefully designed to obtain monitoring data for surface and ground waters from diffuse
(non-point) sources. However, several limitations and uncertainties should be considered before using
the USGS monitoring data to estimate surface water concentrations for human health risk assessment.
The NAWQA data were not specifically collected to assess water quality at drinking-water supply
intakes; however, some sampling locations may be representative of source waters in certain areas. It
is important to note the laboratory recoveries were approximately 50%; therefore, the measured values
may be roughly one-half of the actual water concentrations. For bromoxynil in surface waters, the low
laboratory recoveries did not vary considerably from the 50% recovery level as shown by the relative
standard deviation (RSD) of 7% (USGS Open-File Report 96-216). The samples for the NAWQA
monitoring program were collected from single locations at varying sampling dates and analyzed by a
multi-analyte method. Differences in stream flow levels among the various sampling locations could
significantly influence environmental concentrations, therefore, it might be more appropriate to evaluate
monitoring results reported as "flow-weighted concentrations". Monitoring data were not available for
surface water reservoirs, lakes and estuaries.
Comparison of the Tier 1 (GENEEC) and Tier 2 (PRZM-EXAMS) estimated environmental
concentrations (EECs) with the USGS NAWQA monitoring data suggests reasonable agreement among
the various data sources. If the maximum USGS value is multiplied by 2 (approximate "correction" for
50% laboratory recovery), the result of «12 |ig/L shows good agreement with the maximum Tier 2
EEC. It is unclear why surface water modeling results using a "static pond" hydrologic scenario are
relatively close to the stream and river hydrologic systems monitored by the USGS.
The bromoxynil surface water protocol drafted in response to the cotton registration decision
outlines the monitoring procedure to track the potential movement of bromoxynil from field application
sites through surface water resources for evaluating potential impact to surface water drinking water
utilities. This monitoring program is discussed in three phases: 1) survey of surface water drinking
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water utilities, 2) potential impact to surface drinking water utilities at the watershed scale, and 3)
intensive, field-scale surface runoff and watershed studies with edge-of-field monitoring. These three
phases should be conducted concurrently in an attempt to gain a more complete picture of the
monitored compound in surface waters. The pesticide levels at drinking water utilities will be
considered in the water exposure assessment component of dietary risk assessments as required in
FQPA. The field runoff studies are required to document the source(s), extent and magnitude of
pesticide residues which may be transported via surface runoff and spray drift.
For the bromoxynil surface water monitoring study, the study locations must cover the range for
the major agricultural uses (principally corn, cotton and small grains). Since bromoxynil degrades
relatively rapidly (DT50 <14 days), both the field scale and basin scale monitoring will require intensive
sampling during the period of time from application through several half-lives of the compound. There
are no degradates of concern with this compound, therefore, only parent compound will be monitored.
Also, since bromoxynil does not bioaccumulate in tissues or bind to sediments, biota or sediment
samples are not required at this time.
To estimate a reasonable high end exposure, EPA focused on the calculated time weighted annual
mean concentrations of bromoxynil at each of 11 USGS monitoring sites, which the EPA views as
located in watersheds likely to have bromoxynil use. (These values were not corrected for the analytical
recovery rate of 50%.) These time weighted annual mean concentrations ranged from 0.011 ppb to
0.18 ppb, with 10 out of the 11 sites with time weighted annual mean concentrations below 0.05 ppb.
Six of the 10 sites had time weighted annual mean concentrations at or below 0.014 ppb. The highest
annual time-weighted mean (0.18 ppb) was located in a relatively small watershed (approximately 100
square miles) and a relatively small water body, and the calculated annual mean value at this site was
significantly influenced by the presence of a single high value (the highest value found in all of the
available monitoring data). Based on this information, EPA believes that 0.05 ppb is a reasonable high
end estimate for purposes of estimating drinking water exposure.
3. Exposure and Risk Characterization
a. Ecological Exposure and Risk Characterization
Explanation of the Risk Quotient (RQ) and the Level of Concern (LOC): The Levels of
Concern are criteria used to indicate potential risk to nontarget organisms. The criteria indicate that
a chemical, when used as directed, has the potential to cause undesirable effects on nontarget
organisms. There are two general categories of LOC (acute and chronic) for each of the four nontarget
faunal groups and one category (acute) for each of two nontarget floral groups. In order to determine
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if an LOG has been exceeded, a risk quotient must be derived and compared to the LOC's. A risk
quotient (RQ) is calculated by dividing an appropriate exposure estimate (e.g., the estimated
environmental concentration (EEC)), by an appropriate toxicity test effect level (e.g., the LC50). The
acute effect levels are:
-EC25 (terrestrial plants),
-EC50 (aquatic plants and invertebrates),
-LC50 (fish and birds), and
-LD50 (birds and mammals)
The chronic test results are the:
-NOEL (sometimes referred to as the NOEC) for avian and mammal reproduction studies, and
either the NOEL for chronic aquatic studies, or the Maximum Allowable Toxicant Concentration
(MATC) which is the geometric mean of the NOEL and the LOEL (sometimes referred to as the
LOEC) for chronic aquatic studies.
When the risk quotient exceeds the LOG for a particular category, risk to that particular category
is presumed to exist. Risk presumptions are presented along with the corresponding LOC's.
Levels of Concern (LOC) and Associated Risk Presumption
Mammals, Birds
IF THE LOC
acute RQ> 0.5
acute RQ> 0.2
acute RQ> 0.1
chronic RQ> 1
Fish, Aquatic invertebrates
IF THE LOC
acute RQ> 0.5
acute RQ> 0.1
PRESUMPTION
Potentially high acute risk
Risk that may be mitigated through
restricted use
Endangered species may be affected
acutely
Chronic risk, endangered species may be
affected chronically
PRESUMPTION
Potentially high acute risk
Risk that may be mitigated through
restricted use
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acute RQ> 0.05 Endangered species may be affected
acutely
chronic RQ> 1 Chronic risk, endangered species may be
affected chronically
Plants
IF THE LOG PRESUMPTION
RQ> 1 Potentially high risk
RQ (using the NOEC or EC05) > 1 Endangered plants may be
affected
Currently, there are no separate criteria for restricted use or chronic effects for plants.
Bromoxynil octanoate use patterns addressed in risk assessment: Bromoxynil octanoate is
used on a wide variety of agricultural crops such as corn and small grains (oats, wheat, barley).
Terrestrial Animals and Terrestrial and Semi-aquatic Plants: The majority of use sites have
a maximum use rate of 0.5 Ibs ai/A or less (there are no uses with a higher application rate). This
includes such sites as corn, cotton, and small grains. These use sites make up over 90% of bromoxynil
octanoate usage based on pounds applied annually. Bromoxynil octanoate is registered on a variety of
other sites, all of which are less than 3% of the annual pounds applied (garlic/onions 1%, sorghum 2%,
and alfalfa 1%). The typical use rates of 0.4 Ibs ai/A for cotton, 0.28 Ibs ai/A for corn, and 0.31 Ibs ai/A
for small grains were also used to calculate EECs.
Aquatic Animals and Plants: Aquatic EECs were calculated using GENEEC for the several
use rates and patterns [see EEC section].
The application rates for the minor uses of bromoxynil octanoate (including alfalfa, flax, mint, and
turf) were not used to estimate EECs because they are lower than those for the major crops. As a
result, exposure from these use patterns would not be higher than exposure from other uses where
GENEEC was used to estimate exposure.
(1) Exposure and Risk to Nontarget Terrestrial Animals
(a) Birds
Residues expected on dietary food items following application are compared to LC50 values to
predict hazard to birds. Day 0 residues on vegetation were estimated based on the work of Hoerger
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and Kenaga (1972) as modified by Fletcher et al. (1994) for a maximum application rate of 0.5 Ibs and
the typical application rate of 0.4 Ib ai/A.
For cotton (0.5 Ib ai/A), the highest (peak) residues after the third application were estimated
using a computerized dissipation program that uses first-order dissipation kinetics at an assumed rate
to calculate daily estimated residues after repeated applications. The use rate per application is 0.5 Ib
ai/A with a between application interval of 10 days, during which time the residues from the previous
applications would partially degrade. A half-life of 7 days was used to estimate the degradation of
bromoxynil octanoate on vegetation. This half-life was chosen based on the hydrolysis, aerobic soil
metabolism, and terrestrial field dissipation half-lives. This value is consistent with the estimated half-
lives for other pesticides (Willis and McDowell, 1987).
Risk from bromoxynil octanoate at typical use rates is not greater than the risk at the higher
application rates; therefore, RQs were not calculated for these rates. The predicted 0 day maximum
residues of bromoxynil octanoate that are expected to occur on different avian food items following the
two highest applications, and their corresponding acute risk quotients, are presented in the table below:
Table 40: Maximum Estimated Environmental Concentrations and Acute Dietary Risk
Quotients for Birds*
Food items
Short Grasses
Long Grasses
Broadleaf Plants and
insects
Fruits and pods
Appl. Rate (Ibs ai/A)
0.4
0.5
0.4
0.5
0.4
0.5
0.4
0.5
0.4
0.5
0.4
0.5
0.4
0.5
0.4
0.5
No. of Aplications
\
2
3
\
2
3
\
2
3
\
2
3
EEC ( ppm)
139
174
209
261
64
80
96
120
78
99
117
148
9
12
13
17
RQ
0.12
0.15
0.15
0.3
0.06
0.07
0.09
0.01
0.07
0.08
0.1
0.12
0.007
0.01
0.01
0.01
* Based on an LC50 = 1,150 ppm
The LOG for endangered species (0.1) has been slightly exceeded for all modeled use rates on
short grasses; both single and multiple applications; and on broadleaf plants and insects. Therefore, a
may effect for endangered birds has been identified. The risk quotients at the maximum use rate for
cotton assuming three applications, exceed the restricted use LOG (0.2) by a small margin on short
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grasses. However, the use of bromoxynil octanoate is expected to pose minimal overall acute risk to
avian species, as further described in Section b., Environmental Risk Characterization. Maximum
residues and their corresponding chronic risk quotients are presented in the table below.
Table 41: Maximum Estimated Environmental Concentrations and Chronic Dietary Risk
Quotients for Birds*
Food items
Short Grasses
Long Grasses
Broadleaf Plants and insects
Fruits and pods
Appl. Rate ( Ibs ai/A)
0.4
0.5
0.4
0.5
0.4
0.5
0.4
0.5
0.4
0.5
0.4
0.5
0.4
0.5
0.4
0.5
No. Of Applications
\
2
3
\
2
3
\
2
3
\
2
3
EEC ( ppm)
139
174
209
261
64
80
96
120
78
99
117
148
9
12
13
17
RQ
1.5
1.5
1.5
3
0.6
0.7
0.9
1.2
0.7
1
1.16
1.5
0.09
0.12
0.13
0.15
* Based on an NOEL = 102 ppm
For both single and multiple applications, the chronic LOC (1) for endangered and nonendangered
species has been exceeded by a small margin for the two highest use rates on short grasses and on
broadleaf plants and insects. Therefore, a chronic may effect for endangered birds has been identified.
However, the use of bromoxynil octanoate is expected to pose minimal overall chronic risk to avian
species, as further described in Section b., Environmental Risk Characterization.
(b) Mammals
Mammals are assumed to be exposed to dietary residues similar to birds. The EEC's calculated
for avian species will be used to estimate exposure to mammals.
Acute Risk
Acute hazard to small mammals was addressed using the acute oral LD50 value for the rat
converted to an estimated LC50 value for dietary exposure. The estimated LC50 was derived using the
following formula:
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LC50 = LD50 x body weight (g) / food consumed per day (g)
Acute risk to mammals was assessed by calculating RQs for three representative species: the
meadow vole, the field mouse, and the least shrew. Estimated mammalian LC50 values for these three
species of small mammals are presented below:
Table 42: Estimated Small Mammal Dietary Exposure (Based on an LD50 = 238 mg/kg)
Small Mammal
Meadow vole
Adult field mouse
Least shrew
Body Weight (g)
46
13
5
Percent of Weight
Eaten Per Day
61%
16%
110%
Food Consumed
Per Day (g)
28.1
2.1
5.5
Estimated LC50
(ppm)
390
1473
216
The above table is based on information contained in Principles of Mammalogy by D. E. Davis and F. Golly, published
by Reinhold Corporation, 1963.
The risk quotients are calculated by dividing the EECs (i.e. residues) by the estimated LC50's. The
table below shows the risk quotients for peak exposures of bromoxynil.
Table 43: Mammalian Acute Risk Quotients
Species and Diet
Meadow vole consuming
short grasses
Adult field mouse
consuming seeds
Least shrew consuming
insects
Application Rate (Ib ai/A)
0.5 (single app)
0.4
0.4 (two apps)
0.5 (three apps)
0.5 (single app)
0.4 (single app)
0.4 (two apps)
0.5 (three apps)
0.5 (single app)
0.4 (single app)
0.4 (two apps)
0.5 (three apps)
Maximum EEC1 in Food Item
(ppm)
174
139
209
261
12
9
13
17
99
78
117
148
Acute Risk Quotient
0.16
0.13
0.19
0.24
0.01
0.01
0.02
0.02
0.09
0.07
0.11
0.13
'Based on Hoeger and Kenaga (1972) with modifications by Fletcher et al. (1994).
For the modeled use rates (0.4 and 0.5, with two and three applications, respectively), the LOG
for presumption of risk (0.5) has been exceeded for the meadow vole and the least shrew. The LOG for
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risk that may be mitigated through restricted use (0.2) classification has also been exceeded for these
use rates for the vole and the least shrew. The LOG for presumption of risk to endangered species
(0.1) has been exceeded for these use rates for the vole, the field mouse, and the least shrew. This
indicates that the use of bromoxynil at these rates poses an acute risk to mammals, both endangered and
non-endangered. However, the acute risk to mammals, including threatened and endangered species
is expected to be low, as further described in Section b., Environmental Risk Characterization.
Chronic Risk
Risk quotients were calculated for chronic effects of bromoxynil to mammals. Although rat
reproductive studies revealed little reproductive effects, bromoxynil has been shown to be a
developmental toxicant. Therefore, in order to assess chronic affects to mammals, results from a
developmental toxicity study will be used (NOEC = 50 ppm). The maximum EEC's and chronic risk
quotients are shown in the table below.
Table 44: Mammalian Chronic Risk Quotients (Based on a Rat NOEL=50 ppm2)
Application rate
0.5 (single appl.)
0.4 (single appl.)
0.4 (two appl.)
0.5 (three appl.)
Food item
Short grasses
Long grasses
Broadleaf plants and insects
Fruits and pods
Short grasses
Long grasses
Broadleaf plants and insects
Fruits and pods
Short grasses
Long grasses
Broadleaf plants and insects
Fruits and pods
Short grasses
Long grasses
Broadleaf plants and insects
Fruits and pods
Maximum EEC (ppm)
174
80
99
12
140
64
78
9
209
96
117
13
261
120
148
17
Chronic Risk Quotient
3.5
1.6
2.0
0.2
2.8
1.3
1.6
0.2
4.2
1.9
2.3
0.3
5.2
2.4
3.0
0.3
'Based on Hoeger and Kenaga (1972) with modifications by Fletcher et al. (1994).
2 MRID 41149301, rat reproduction study for phenol. NOEL of 4 mg/kg/day (50 ppm) is based on decreased body weight gain of offspring.
All of the chronic RQs on all food items except fruits and pods exceed the LOG of 1 for all use
rates. These results indicate that all use rates of bromoxynil pose a risk of causing chronic effects to
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mammals and may cause chronic adverse effects to threatened and endangered species of mammals. The
chronic risk to mammals is developmental and reproductive. It is, however, uncertain whether or not
they would be exposed to high enough residues to cause chronic effects, as further described in Section
b. of the Environmental Risk Characterization.
(c) Insects
Bromoxynil (technical grade) is practically non-toxic to honeybees. Therefore, minimal risk to
honeybees is presumed.
(2) Exposure and Risk to Nontarget Aquatic Animals
(a) Freshwater Fish
Acute
The table below shows the EEC's, from GENEEC, and acute risk quotients for
freshwater fish.
Table 45: Acute risk quotients for freshwater fish (Species LC50 for bluegill sunfish = 53 ppb
and channel catfish = 23 ppb)
Crop
Corn, Small Grains
Corn
Small Grains
Cotton
Cotton
Cotton
Cotton
Application
Method
Broadcast - ground & aerial
Broadcast- ground & aerial
Broadcast - ground & aerial
Broadcast- ground
Broadcast - ground
Aerial
Aerial
Application Rate in Ibs a.i./A (number of apps.)
0.5 (1) maximum rate
0.28(1) typical rate
0.31 (1) typical rate
0.5 (3) maximum rate - 10 day application interval
0.4 (2) typical rate - 10 day application interval
0.5 (3) maximum rate - 10 day application interval
0.4 (2) typical rate - 10 day application interval
Peak EEC (ppb)
4.5
2.6
3.0
9.4
8.0
10.0
8.4
Acute RQ
Sunfish
0.08
0.05
0.02
0.18
0.15
0.19
0.16
Catfish
0.20
0.11
0.13
0.4
0.3
0.4
0.4
Risk quotients for both the rainbow trout and the channel catfish were calculated to estimate risk
to freshwater species. In this case, the catfish was more sensitive to bromoxynil octanoate. The catfish
is also considered representative of species that would inhabit waters near cotton fields.
Bromoxynil octanoate, when applied to cotton, corn, and small grains, at both the maximum and
typical application rates, slightly exceeds the LOG (0.05) for endangered species and the LOG (0.1) for
risk that may be mitigated through restricted use. Therefore, applications of bromoxynil octanoate at
these rates may affect endangered freshwater fish species.
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Chronic
The table below shows the EEC's, from GENEEC, and risk quotients for freshwater fish.
Table 46: Chronic risk quotients for freshwater fish (Species MATC = 12 ppb for fathead
minnow)
Crop
Corn, Small Grains
Corn
Small Grains
Cotton
Cotton
Cotton
Cotton
Application Method
Broadcast - ground & aerial
Broadcast- ground
Broadcast - ground
Broadcast- ground
Broadcast - ground
Aerial
Aerial
Application Rate in Ibs a.i./A (number of apps.)
0.5 (1) maximum rate
0.28(1) typical rate
0.31 (1) typical rate
0.5 (3) maximum rate - 10 day application interval
0.4 (2) typical rate - 10 day application interval
0.5 (3) maximum rate - 10 day application interval
0.4 (2) typical rate - 10 day application interval
56 day EEC ppb
0.15
0.15
0.15
0.3
0.3
0.4
0.3
Chronic RQ
0.01
0.01
0.01
0.03
0.03
0.04
0.03
Based on the MATC from the fathead minnow early life stage study (12 ppb) and the 56-day
average GEECs, no LOCs are exceeded. Therefore, all use sites represent minimal chronic risk to fish.
(b)
Freshwater Invertebrates
Acute
The table below shows the EEC's, from GENEEC, and acute risk quotients for freshwater
invertebrates.
Table 47: Acute risk quotients for freshwater invertebrates (Species EC50 = 11 ppb for the
Daphnia pulex)
Crop
Corn, Small Grains
Corn
Small Grains
Cotton
Cotton
Cotton
Cotton
Application Method
Broadcast - ground
Broadcast- ground
Broadcast - ground
Broadcast- ground
Broadcast - ground
Aerial
Aerial
ApplicationRate in Ibs a.i./A (number of apps.)
0.5 (1) maximum rate
0.28(1) typical rate
0.31 (1) typical rate
0.5 (3) maximum rate - 10 day application interval
0.4 (2) typical rate - 10 day application interval
0.5 (3) maximum rate - 10 day application interval
0.4 (2) typical rate - 10 day application interval
Peak EEC (ppb)
4.5
2.6
3.0
9.4
8.0
10.0
8.4
Acute RQ
0.4
0.3
0.3
0.9
0.7
0.9
0.7
Treating corn and small grains with bromoxynil octanoate using either aerial or ground equipment
at either the maximum single application rate (0.5 Ibs ai/A) or the typical application rate (0.3 Ibs ai/A)
result in acute risk quotients for freshwater invertebrates that exceed the restricted use LOG (0.1).
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Bromoxynil octanoate, when applied to cotton using either aerial or ground equipment at the
maximum application rate of 0.5 Ibs ai/A (applied three times), results in acute risk quotients for
freshwater invertebrates that exceed the high acute risk LOG (0.5) by a small margin.
All use sites when treated using either ground or aerial equipment, exceed the endangered species
LOG (0.05). Therefore, bromoxynil octanoate use may effect endangered invertebrate species.
Chronic
The table below shows the chronic EEC's, from GENEEC, and chronic risk quotients for
freshwater invertebrates.
Table 48: Chronic risk quotients for freshwater invertebrates (Species MATC = 3.7 ppb for
the Daphnia magna)
Crop
Corn, Small Grains
Corn
Small Grains
Cotton
Cotton
Cotton
Cotton
Application Method
Broadcast - ground and aerial
Broadcast- ground and aerial
Broadcast - ground and aerial
Broadcast- ground
Broadcast - ground
Aerial
Aerial
Application Rate in Ibs a.i./A (number of apps.)
0.5 (1) maximum rate
0.28(1) typical rate
0.31 (1) typical rate
0.5 (3) maximum rate - 10 day application interval
0.4 (2) typical rate - 10 day application interval
0.5 (3) maximum rate - 10 day application interval
0.4 (2) typical rate - 10 day application interval
21 -day EEC (ppb)
0.4
0.3
0.3
0.9
0.7
1.0
0.9
Chronic RQ
0.12
0.07
0.07
0.3
0.15
0.3
0.3
Based on the aquatic invertebrate MATC from the Daphnia magna life-cycle study (3.7 ppb) and
21-day average GENEEC EECs, the use of bromoxynil octanoate represents minimal chronic risk to
aquatic invertebrates. Also, based on the GENEEC simulation, concentrations of bromoxynil octanoate
are below the MATC by day 4.
(c) Estuarine and Marine Animals
Acute
The table below shows the EEC's, from GENEEC, and acute risk quotients for estuarine/marine
organisms.
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Table 49: Acute risk quotients for estuarine/marine organisms (Species EC50= 65 ppb for the
Mysid)
Crop
Corn, Small Grains
Corn
Small Grains
Cotton
Cotton
Cotton
Cotton
Application
Method
Broadcast - ground and aerial
Broadcast- ground and aerial
Broadcast - ground and aerial
Broadcast- ground
Broadcast - ground
Aerial
Aerial
Application Rate in Ibs a.i./A
(number of apps.)
0.5 (1) maximum rate
0.28 (1) typical rate
0.31 (1) typical rate
0.5 (3) maximum rate - 10 day
application interval
0.4 (2) typical rate - 10 day
application interval
0.5 (3) maximum rate - 10 day
application interval
0.4 (2) typical rate - 10 day
application interval
Peak EEC
(ppb)
4.5
2.6
3.0
9.4
8.0
10.0
8.4
Acute RQ
0.07
0.04
0.04
0.15
0.12
0.15
0.13
Risk quotients shown are only for the mysid shrimp, which had the lowest EC50 of the three
estuarine species tested. Risk quotients using the acute toxicity for oysters and fish would not have
exceeded any LOCs. Minimal acute risk to oysters and estuarine fish is expected from all bromoxynil
octanoate uses.
Bromoxynil octanoate, when applied to cotton using either aerial or ground equipment at both
the maximum application rate of 0.5 Ibs ai/A (applied three times) or the typical application rate of 0.4
Ibs ai/A (applied twice), results in acute risk quotients for estuarine shrimp that exceed the endangered
species LOG of 0.05 by a small margin, and slightly exceed the LOG of 0.1 for risk that may be
mitigated through restricted use. Therefore, endangered species of estuarine shrimp, may be effected
from these uses of bromoxynil octanoate.
Chronic
No chronic data with estuarine species were submitted. Because the freshwater species for both
invertebrates and fish are more sensitive than the estuarine species in the acute studies, it is assumed
that the conclusion of minimal chronic risk for freshwater species is applicable to estuarine species.
Testing on estuarine fish and invertebrates is needed in order to confirm this assumption. Therefore,
additional testing (GDLN 72-4) on bromoxynil octanoate is required as confirmatory data.
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(3) Exposure and Risk to Nontarget Plants
(a) Terrestrial and Semi-aquatic
Separate risk assessments are done for nontarget terrestrial and semi-aquatic plants. Nontarget
terrestrial plants inhabit non-aquatic areas which are generally well drained. Nontarget semi-aquatic
plants inhabit low-lying areas that are usually wet, although they may be dry during certain times of the
year. Semi-aquatic plants are not obligatory aquatic plants in that they do not live in a continuously
aquatic environment. Both the terrestrial and semi-aquatic plants are exposed to pesticides from runoff
and drift. They differ, however, in that terrestrial plants are assumed to be exposed via sheet runoff,
whereas semi-aquatic plants are assumed to be exposed via channelized runoff. Calculating runoff
exposure is done using a simple model which assumes that a certain percent of that which is applied is
transported with runoff. The percent is based on solubility. Since the solubility of bromoxynil is 0.08
ppm, it is assumed that no more than 1% of the applied bromoxynil octanoate would run off. Drift from
aerial applications is assumed to be 5%, while drift from ground applications would not be expected
to exceed 1% of the applied.
Nonendangered Terrestrial and Semi-aquatic Plants
Risk quotients for terrestrial and semi-aquatic plants are derived by dividing an exposure estimate,
in Ib ai/A, by an EC25, also expressed in Ib ai/A. The total loading rate (runoff plus spray drift) is used
with the EC25 of the most sensitive species in the seedling emergence study to determine the risk
quotient for exposure to emerging seedlings. The loading from spray drift alone is used with the EC25
value of the most sensitive species in the vegetative vigor study to determine the risk to adult plants
from foliar exposure. The following table outlines the acute risk quotients for terrestrial and semi-
aquatic plants using results from toxicity testing with bromoxynil octanoate.
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Table 50: Exposure and Risk Quotients for Terrestrial and Semi-aquatic Plants
Application
method & rate
Ground, 0.5 Ibs
ai/A
(corn, cotton*,
small grains)
Aerial, 0.5 Ibs
ai/A
(corn, cotton*,
small grains)
Plant type
Terrestrial
Semi-aquatic
Terrestrial & semi-
aquatic
Terrestrial
Semi-aquatic
Terrestrial & semi-
aquatic
Exposure scenario
Sheet runoff + spray
drift (1%)
Channelized runoff +
spray drift (1 %)
Spray drift (1%)
Sheet runoff + spray
drift (5%)
Channelized runoff +
spray drift (5 %)
Spray drift (5%)
Exposure
(Ib ai/A)
0.015
0.09
0.007
0.04
0.11
0.04
EC25 (Ib ai/A)
0.12 (seedling emergence)
0.12 (seedling emergence)
0.017 (veg. vigor)
0.12 (seedling emergence)
0.12 (seedling emergence)
0.017 (veg. vigor)
Risk
Quotient
0.12
0.7
0.4
0.4
0.9
2.0
*Cotton use involves multiple applications, however, the model used to estimate exposure does not handle multiple
applications well. It is expected that the risk numbers could be higher with multiple applications at 0.5 Ibs ai/A.
The LOG (=1) for risk to terrestrial and semi-aquatic plant species has not been exceeded for the
highest application rate for either ground or aerial application, with the exception of the spray drift
aerial application (RQ = 2.0) which exceeds the LOG by a small margin. This indicates that risk to the
vegetative vigor of nontarget terrestrial and semi-aquatic plants may result from exposure to bromoxynil
octanoate through drift.
The Agency assumes that risk from bromoxynil octanoate at typical use rates is not greater than
the risk from use at the highest application rates, therefore, RQs were not calculated for these rates.
Endangered Terrestrial and Semi-aquatic Plants
Risk quotients for endangered terrestrial and semi-aquatic plants are derived by dividing an
exposure estimate, in Ib ai/A, by an NOEC, also expressed in Ib ai/A. The lowest NOEC for terrestrial
plants is 0.015 Ib ai/A (MRID 43633701). The risk quotients for endangered plants based on this
NOEC compared to the range of exposures predicted would be from 0.3 to 5. This indicates that risk
to threatened and endangered terrestrial and semi-aquatic plants may result from exposure to
bromoxynil octanoate through runoff and drift.
(b) Aquatic
The same aquatic exposure values used to estimate risk to fish and invertebrates will be used to
estimate risk to aquatic plants.
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Nonendangered and Endangered Aquatic Vascular Plants
Risk quotients for nonendangered plants are calculated by dividing the GEEC by the aquatic plant
EC50 values. Risk quotients for endangered plants are calculated by dividing the GEEC by the NOEC.
Data requirements for the aquatic macrophyte (Lemna gibba) for bromoxynil octanoate have not
been satisfied, however, there are data for bromoxynil heptanoate. Therefore, the risk quotients for
aquatic vascular plants used the EC50 of 219 ppb (//g/L) (NOEC 77) for duckweed (Lemna gibba)
based on testing with bromoxynil heptanoate. A study using bromoxynil octanoate is required for
confirmatory purposes.
A risk quotient for nonvascular aquatic plants is based on the most sensitive algal or diatom
species tested. For bromoxynil octanoate, the most sensitive nonvascular plant tested was the
freshwater diatom Naviculapelliculosa with an EC50 of 51 ppb (ag/L) (NOEC 9.3).
The following table outlines the risk quotients for aquatic vascular plants using results from
toxicity testing with bromoxynil heptanoate.
Table 51: Risk quotients for aquatic vascular plants using data from bromoxynil heptanoate
(Species EC50 = 219 ppb; NOEC = 77 ppb)
Crop
Corn, Small Grains
Corn
Small Grains
Cotton
Cotton
Cotton
Cotton
Application
Method
Broadcast - ground and aerial
Broadcast- ground and aerial
Broadcast - ground and aerial
Broadcast- ground
Broadcast - ground
Aerial
Aerial
Application Rate in Ibs a.i./A
(number of apps.)
0.5 (1) maximum rate
0.28 (1) typical rate
0.31 (1) typical rate
0.5 (3) maximum rate - 10 day
application interval
0.4 (2) typical rate - 10 day
application interval
0.5 (3) maximum rate - 10 day
application interval
0.4 (2) typical rate - 10 day
application interval
Peak EEC
(ppb)
4.5
2.6
3.0
9.4
8.0
10.0
8.4
Acute
RQ
0.015
0.01
0.01
0.04
0.04
0.04
0.04
End. sp
RQ
0.06
0.03
0.04
0.12
0.10
0.13
0.1
Typical and maximum applications of bromoxynil heptanoate do not represent a risk to aquatic
vascular plants, however, overall risk to aquatic vascular plants cannot be dismissed at this time due to
the lack of data. In order to fully assess the risk to aquatic vascular plants from bromoxynil octanoate,
testing with Lemna gibba is required.
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The following table outlines the risk quotients for aquatic nonvascular plants using results from
toxicity testing with bromoxynil octanoate:
Table 52: Risk quotients for aquatic nonvascular plants (representing algae and diatoms)
(Species EC50 = 51 ppb; NOEC = 9.3 ppb)
Crop
Corn, Small Grains
Corn
Small Grains
Cotton
Cotton
Cotton
Cotton
Application
Method
Broadcast - ground and aerial
Broadcast- ground and aerial
Broadcast - ground and aerial
Broadcast- ground
Broadcast - ground
Aerial
Aerial
Application Rate in Ibs a.i./A
(number of apps.)
0.5 (1) maximum rate
0.28 (1) typical rate
0.31 (1) typical rate
0.5 (3) maximum rate -10 day
application interval
0.4 (2) typical rate - 10 day
application interval
0.5 (3) maximum rate - 10 day
application interval
0.4 (2) typical rate - 10 day
application interval
Peak EEC
(ppb)
4.5
2.6
3.0
9.4
8.0
10.0
8.4
Acute
RQ
0.09
0.04
0.06
0.2
0.16
0.2
0.16
End. sp
RQ
0.4
0.3
0.3
1.0
0.9
1.0
0.9
Use of typical and maximum applications to many of the large acreage crops for which
bromoxynil octanoate is registered do not represent a risk to nonendangered aquatic nonvascular plants.
The risk quotients for endangered aquatic plants range from 0.03 to 1.0. The LOG (1) for endangered
plants has been met for the maximum application rate to cotton. Therefore, use of the maximum
application rate on cotton may represent a risk to endangered aquatic nonvascular plants.
(4) Endangered Species
The use of bromoxynil octanoate may adversely effect endangered species of birds and mammals,
both acutely and chronically; fish and invertebrates (both freshwater and estuarine/marine species)
acutely; and terrestrial, semi-aquatic, and aquatic nonvascular plants.
When the Endangered Species Protection Program becomes final, limitations in the use of
bromoxynil octanoate may be required to protect endangered and threatened species, but these
limitations have not been defined and may be formulation specific. EPA anticipates that a consultation
with the Fish and Wildlife Service may be conducted in accordance with the species-based priority
approach described in the Program. After completion of consultation, registrants will be informed if
any required label modifications are necessary. Such modifications would most likely consist of the
generic label statement referring pesticide users to use limitations contained in county Bulletins.
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b. Environmental Risk Characterization
(1) Background Information
The Agency concentrated on data for bromoxynil octanoate because it was found to be chemically
and physically similar to bromoxynil heptanoate (one carbon difference in the ester chain) and both
esters hydrolyze, photolyze and can microbially metabolize to bromoxynil (phenol) which further
degrades to CO2. The heptanoate ester was registered based on bridging data for bromoxynil
octanoate. Also, bromoxynil octanoate and bromoxynil (phenol) were determined to be lexicologically
equivalent on a molar basis. In the risk assessment, toxicity data for bromoxynil octanoate, with the
exception of aquatic vascular plants, was used to estimate risk. This is consistent with the fate
information in that fate parameters were derived from testing with the octanoate. In most cases, the
octanoate was more toxic to test species than bromoxynil heptanoate.
(2) Environmental Fate and Transport Assessment
Based on available information from environmental fate studies, the fate and transport of
bromoxynil octanoate under laboratory and field conditions is adequately known. Results from the
laboratory studies done on the TGAI (e.g., octanoate or heptanoate) are consistent with the field study
results where the end use product (mixtures of the different technicals) is used.
Bromoxynil octanoate is mobile and is non-persistent. It dissipates in the environment by
hydrolysis, photolysis, and microbially-mediated metabolism. Residues are more likely to be found in
surface runoff waters, but it is not expected to persist in surface waters. Bromoxynil octanoate
accumulates in bluegill sunfish, however, depuration occurs by Day 14. Bromoxynil octanoate was not
persistent in the field.
Based on environmental fate information the potential for ground water contamination from
bromoxynil octanoate is low. Limited monitoring information for ground water is available. Surface
water monitoring is described in section 2(c)2.
(3) Risk to Nontarget Animals
Endocrine Effects: Bromoxynil octanoate has been shown to impair reproduction in birds, fish, and
aquatic invertebrates. The nature of the impairment observed, lesions of old yolk peritonitis, regressing
ovaries, and reduced number of viable embryos in birds, and decreased growth and embryo hatching
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success in fish, suggests an endocrine disruption etiology. Although the available information indicates
that the risk of exposures sufficient enough to elicit endocrine disruption is minimal, bromoxynil
octanoate should still be considered a potential endocrine disputer and candidate for future screening
and testing of this mode of action.
Birds: The acute risk to birds from bromoxynil octanoate is expected to be low. The avian LOG for
endangered species (0.1) has been slightly exceeded for all modeled use rates on short grasses; using
both single and multiple applications; and on broadleaf plants and insects. Therefore, a may effect for
endangered birds has been identified. The risk quotients at the maximum use rate for cotton, with three
applications, exceed the restricted use LOG (0.2) by a small margin on short grasses.
The overall chronic risk to birds from bromoxynil octanoate is expected to be low. A chronic
"may affect" for endangered birds has been identified for the two highest use rates on short grasses and
on broadleaf plants and insects. The RQs, based on day 0 concentrations, which rapidly decrease due
to degradation (hydrolysis/photolysis) and metabolism, ranged from 0.12 to 3. EECs are predicted to
exceed the mallard NOEL (102 ppm) for up to 7 days on short grasses.
Currently, no chronic avian data for bromoxynil phenol are available. The phenol is substantially
less acutely toxic to birds than the octanoate. Likewise, it can be presumed that the phenol would be
less toxic on a chronic basis than the octanoate. The octanoate readily hydrolyzes to the phenol, which
is the compound birds would be exposed to in the long term. Therefore, it is likely that chronic risk to
birds from bromoxynil would be low.
Mammals: The acute risk to mammals, including threatened and endangered species, from exposure
to bromoxynil octanoate is expected to be low. LOCs for acute risk and restricted use were marginally
exceeded at the higher application rates for the meadow vole and the least shrew. The LOG for
presumption of risk to endangered species was exceeded for the higher application rates for the vole,
the field mouse, and the least shrew. In addition, a 2-generation reproductive toxicity study with rats
reported no mortality at levels greater than 250 ppm (NOEL for acute and subacute effects). The
maximum estimated concentration on mammalian food items is 180 ppm. Because the maximum EEC
is less than the NOEL, where no effects, either sublethal or lethal occurred, it is unlikely that mammals
(including endangered species) would be exposed to enough bromoxynil octanaote to cause adverse
acute effects.
The chronic risk to mammals, including threatened and endangered species, would be expected
to be high if mammals were exposed to high enough residues of bromoxynil octanoate. Although the
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RQs were not excessively high (0.2-5.2), bromoxynil has been shown to be a developmental toxicant
in several toxicology studies. The data suggest a high risk of reproductive impairment. If mammals
were exposed to bromoxynil at high enough levels, chronic developmental effects may occur. Small
mammals do use corn and cotton fields for cover, brood rearing, and foraging. It is also likely that they
would be present during time of application as well as before and after. It appears that use of
bromoxynil may have adverse impacts to mammals on a chronic basis.
Fish: The overall acute risk to freshwater fish from exposure to bromoxynil octanoate is expected to
be low. The endangered species LOG has been exceeded based on results from all modeled use sites,
therefore, applications of bromoxynil octanoate may affect endangered freshwater fish species. The
environmental fate characteristics of bromoxynil octanoate indicate that once it is in the aqueous
environment, it hydrolyzes readily to the phenol, which is practically nontoxic, and then further
degrades to CO2. Therefore, endangered species are likely to be acutely affected only during the short
time before the octanoate degrades (half-lives of 1-11 days). Likewise, the acute risk to estuarine fish
is expected to be low.
The chronic risk to freshwater fish and estuarine fish from exposure to bromoxynil octanoate is
expected to be minimal. No LOCs were exceeded. Again, bromoxynil octanoate is not likely to remain
in water long enough to cause chronic adverse effects. However, because the catfish appears to be
more sensitive on an acute level, it may be more sensitive on a chronic level. The MATC for the catfish
may be lower than that for the fathead minnow, but it is still unlikely that any LOCs would be exceeded
based on the low EECs. It was assumed that the chronic assessment for freshwater species is applicable
to estuarine species.
In order to further address the risk to aquatic organisms from bromoxynil octanoate application
to transgenic cotton, Tier 2 PRZM-EXAMS modeling was performed using environmental fate
information for bromoxynil (Section 2.c.(2)). The EECs ranged from 12.3 ppb (peak) to 2.5 ppb (60
day). Although the bromoxynil phenol EECs were higher than the bromoxynil octanoate EECs,
bromoxynil phenol is substantially less toxic to aquatic organisms than the octanoate, therefore, the risk
is minimal. The overall acute risk to freshwater fish from exposure to bromoxynil due to application
of bromoxynil octanoate to transgenic cotton is expected to be low. No LOCs were exceeded.
Invertebrates: The overall acute risk to freshwater invertebrates is expected to be medium. All
use sites exceed the endangered species LOG, therefore, the use of bromoxynil octanoate may affect
endangered invertebrates. The high risk LOG has also been exceeded slightly for the cotton use and
the restricted use LOG has been exceeded for cotton, corn, and small grains uses. When a restricted
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use LOG has been exceeded, this suggests that risk to the nontarget species may be mitigated through
restricted use labeling. This increases the possibilities that the pesticide will be handled properly, and
label directions followed, in order to minimize exposure and thus reduce risk. Although bromoxynil
octanoate degrades rapidly in the aqueous environment, it is likely to remain for a duration long enough
to cause acute effects.
The overall acute risk to estuarine organisms is expected to be low. The endangered species LOG
(0.05) for estuarine shrimp has been exceeded by a small margin for bromoxynil octanoate when applied
to cotton (both typical and maximum application rates), therefore, applications of bromoxynil octanoate
may affect endangered estuarine shrimp species. However, there are no endangered estuarine shrimp
species at this time. The endangered species are likely to be acutely affected during the short time
before the octanoate degrades (half-lives of 1-11 days).
The chronic risk to freshwater and estuarine invertebrates is expected to be minimal. No LOCs
were exceeded. Bromoxynil octanoate is unlikely to remain in water long enough to cause chronic
effects. It was assumed that the chronic assessment for freshwater species is applicable to estuarine
species. Chronic testing with estuarine fish and invertebrates are needed in order to confirm this
assumption (GLN 72-4).
The overall acute risk to freshwater invertebrates from exposure to bromoxynil due to application
of bromoxynil octanoate to transgenic cotton is expected to be low. No LOCs were exceeded.
(4) Risk to Nontarget Plants
Terrestrial and Semi-aquatic: The overall risk to both endangered and non-endangered terrestrial
and semi-aquatic plants is expected to be medium. The LOCs were exceeded for spray drift from the
aerial application of bromoxynil octanoate at the maximum label rate. This indicates that risk to the
vegetative vigor of nontarget terrestrial and semi-aquatic plants may result from exposure to bromoxynil
octanoate through drift. Although the LOCs were only exceeded by a small margin, the risk to these
plants is likely underestimated because the model does not take into account multiple applications. An
incident reported from the State of Oregon also supports the assumption of risk to nontarget terrestrial
and semi-aquatic plants (I# 001664). In 1994, the Oregon Department of Agriculture received a report
of an aerial application of several pesticides inconsistent with their labeling. As a result of this, pea
fields, approximately 1A mile from the wheat fields being treated, exhibited adverse symptoms consistent
with those attributed to the herbicides used on the wheat. Analyses of samples taken from the pea field
determined the presence of bromoxynil octanoate residues consistent with that applied to the wheat
fields.
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Aquatic: Risk to aquatic vascular plants (endangered and non-endangered) from the use of bromoxynil
octanoate is uncertain at this time. An estimate of risk (based on data from bromoxynil heptanoate)
indicated that aquatic vascular plants are not likely to be affected by bromoxynil octanoate application.
However, in order to confirm risk to aquatic vascular plants, bromoxynil octanoate testing with Lemna
gibba is required.
Risk to aquatic nonvascular plants (endangered and nonendangered) is expected to be minimal.
The LOG for endangered species was met, but not exceeded for the maximum application rate to cotton
using EEC's derived from GENEEC. Using Tier II EECs and taking into account all of the available
toxicity information, overall risk to aquatic plants due to bromoxynil from application of bromoxynil
octanoate to transgenic cotton is expected to be low. Since this is the highest exposure scenario,
overall risks are expected to be low.
IV. RISK MANAGEMENT AND REREGISTRATION DECISION
A. Determination of Eligibility
Section 4(g)(2)(A) of FIFRA calls for the Agency to determine, after submission of relevant data
concerning an active ingredient, whether products containing the active ingredients are eligible for
reregi strati on. The Agency has previously identified and required the submission of the generic (i.e.
active ingredient specific) data required to support reregi strati on of products containing bromoxynil 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 bromoxynil. Appendix
B identifies the generic data requirements that the Agency reviewed as part of its determination of the
reregistration eligibility of bromoxynil, and lists the submitted studies that the Agency found acceptable.
The data identified in Appendix B were sufficient to allow the Agency to assess the registered
uses of bromoxynil and to determine that bromoxynil can be used without resulting in unreasonable
adverse effects to humans and the environment. The Agency therefore finds that all products containing
bromoxynil as an active ingredient are eligible for reregistration provided the registrant follows all
requirements as set forth in this document. The reregistration of particular products is addressed in
Section V of this document.
The Agency made its reregistration eligibility determination based upon the target data base
required for reregistration, the current guidelines for conducting acceptable studies to generate such
data, published scientific literature, and the data identified in Appendix B. Although the Agency has
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found that all uses of bromoxynil are eligible for reregi strati on, it should be understood that the Agency
may take appropriate regulatory action, and/or require the submission of additional data to support the
registration of products containing bromoxynil, if new information comes to the Agency's attention or
if the data requirements for registration (or the guidelines for generating such data) change.
1. Eligibility Decision
Based on the reviews of the generic data for the active ingredient bromoxynil, the Agency has
sufficient information on the health effects of bromoxynil and on its potential for causing adverse effects
in fish and wildlife and the environment. The Agency has determined that bromoxynil products, labeled
and used as specified in this Reregi strati on Eligibility Decision, will not pose unreasonable risks to
humans or the environment. Therefore, the Agency concludes that products containing bromoxynil for
all uses are eligible for reregi strati on, provided the registrant follows all requirements as set forth in this
document.
2. Eligible and Ineligible Uses
The Agency has determined that all uses of bromoxynil are eligible for reregi strati on, provided
the registrant follows all requirements as set forth in this document.
B. Regulatory Position
The following is a summary of the regulatory positions and rationales for bromoxynil. Where
labeling revisions are imposed, specific language is set forth in Section V. of this document.
1. Tolerance Reassessment
Based on the tolerances published in the FR Notice dated 6/18/97 and the FR Notice dated
5/13/98, and on additional data, proposed label amendments, and clarification of the Agency's policy
on 40 CFR §180.6(a)(3), a revised tolerance reassessment summary was required and is provided
below.
Separate tolerance expressions listed under 40 CFR §180.324(a), (b), and (c) were redundant,
and, therefore, the tolerance expression is revised to delete tolerances listed under § 180.324(b) and (c),
and to place reassessed and new tolerances under §180.324(a). The 6/18/97 FR Notice provided a
revised §180.324(a), with the previously recommended tolerances under §180.324(a)(l), and tolerances
for residues in cotton and livestock commodities under §180.324(a)(2). In addition, it is noted that
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§180.324(b), (c), and (d) are reserved for Section 18 emergency exemptions, tolerances with regional
registrations, and indirect or inadvertent residues, respectively. The revised tolerance reassessment
table reflects the changes associated with the establishment of tolerances for residues in cotton
commodities. Note that tolerances for residues in livestock commodities have been moved from
180.324(a)(l) to 180.324(a)(2) based on a determination that secondary residues of the metabolite
DBHA transfer to livestock.
The tolerance expression for §180.324(a)(l)is as follows:
"Tolerances are established for residues of the herbicide bromoxynil (3,5-dibromo-4-
hydroxybenzonitrile) resulting from application of its octanoic and/or heptanoic acid ester in or
on the following commodities:"
The tolerance expression for §180.324(a)(2) is as follows:
"Tolerances are established for residues of the herbicide bromoxynil (3,5-dibromo-4-
hydroxybenzonitrile) and its metabolite 3,5-dibromo-4-hydroxybenzoic acid resulting from
application of its octanoic and/or heptanoic acid ester in or on the following commodities:"
Table 53: Revised Tolerance Reassessment Summary
Commodity
Current Tolerance
(ppm)
Tolerance
Reassessment (ppm)
Comment/Correct Commodity Definition
Tolerances listed under 40 CFR §180.324 (a)(l):
Alfalfa, seedling
Barley, forage, green
Barley, grain
Barley, straw
Corn, fodder, (dry)
Corn, forage, (green)
Corn, grain
Corn, fodder, field
(dry)
Corn, forage, field
(green)
Corn, grain, field
Flaxseed
Flax straw
Garlic
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.1
Revoke
Revoke
0.05
4.0
Revoke
0.2
0.3
0.05
0.1
Revoke
0.1
Tolerances should be proposed for alfalfa forage and hay (see
below).
Barley forage is no longer a regulated feed item.
Based upon available residue data, tolerances for residues in
all cereal grains should be lowered to 0.05 ppm.
The proposed tolerance is supported by the available data.
Tolerances are already established for residues in field corn
commodities and separate tolerances should be established
for residues in pop corn commodities.
The proposed tolerance is supported by available data;
Corn, field, stover.
Based upon available data, the tolerance should be increased;
Corn, field, forage.
See comment under barley grain; Corn, field, grain.
Flax, seed.
Flax straw is no longer a regulated feed item.
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Table 53: Revised Tolerance Reassessment Summary
Commodity
Grass, canary, annual,
seed
Grass, canary, annual,
straw
Mint hay
Oats, forage, green
Oats, grain
Oats, straw
Onions (dry bulb)
Rye, forage, green
Rye, grain
Rye, straw
Sorghum, fodder
Sorghum, forage
Sorghum, grain
Wheat, forage, green
Wheat, grain
Wheat, straw
Current Tolerance
(ppm)
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.1
Tolerance
Reassessment (ppm)
Revoke
0.1
0.3
0.05
4.0
0.1
1.0
0.05
2.0
0.2
0.5
0.05
1.0
0.05
2.0
Comment/Correct Commodity Definition
Concomitant with establishing tolerances in grass
commodities, tolerances for residues in canary grass seed and
straw should be revoked.
Peppermint, tops and Spearmint, tops.
Based on residue data translated from barley forage, the
tolerance should be increased; Oats, forage.
See comment under barley grain.
Based on residue data translated from barley straw, the
tolerance should be increased.
Onion, bulb
Based on residue data translated from wheat forage, the
tolerance should be increased; Rye, forage.
See comment under barley grain.
See comment under wheat, straw.
Based on available residue data, the tolerance should be
increased.
See comment under barley grain.
Based on available data, the tolerance should be increased;
Wheat, forage.
See comment under barley grain.
Based on available data, the tolerance should be increased.
Tolerances to be Listed under 40 CFR §180.324(a)(2):
Cotton gin by-products
Cotton hulls
Cotton, undelinted
seed
Cattle, fat
Cattle, mbyp
Cattle, meat
Milk
Hogs, fat
Hogs, mbyp
Hogs, meat
Horses, fat
Horses, mbyp
Horses, meat
Poultry, meat
Poultry, fat
Poultry, eggs
50
21
7
0.1
0.1
0.1
None
0.1
0.1
0.1
0.1
0.1
0.1
None
None
None
7.0
5.0
1.5
1.0
3.5
0.5
0.1
1.0
3.5
0.5
1.0
3.5
0.5
0.05
0.05
0.05
Originally established as stated in the FR Notice dated
6/18/97
Based upon the available feeding study data, tolerances
should be increased.
The registrant should propose the tolerance for residues in
milk, based on data from the ruminant feeding study.
Based upon the available feeding study data, tolerances
should be increased [tolerances translated from cattle].
Based upon the available feeding study data, tolerances
should be increased [tolerances translated from cattle].
Residues in poultry can no longer be classified under
Category 3 of 40 CFR §180.6(a).
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Table 53: Revised Tolerance Reassessment Summary
Commodity
Poultry, mbyp
Goats, fat
Goats, mbyp
Goats, meat
Sheep, fat
Sheep, mbyp
Sheep, meat
Current Tolerance
(ppm)
None
0.1
0.1
0.1
0.1
0.1
0.1
Tolerance
Reassessment (ppm)
0.3
1.0
3.5
0.5
1.0
3.5
0.5
Comment/Correct Commodity Definition
Based upon the available feeding study data, tolerances
should be increased.
Based upon the available feeding study data, tolerances
should be increased [tolerances translated from cattle].
New Tolerances Required under 40 CFR §180.324(a)(l):
Alfalfa, hay
Alfalfa, forage
Aspirated grain
fractions
Barley, hay
Corn, pop, fodder
Corn, pop, grain
Grass, forage
Grass, hay
Oats, hay
Wheat, hay
None
None
None
None
None
None
None
None
None
None
0.5
0.1
0.3
9.0
0.2
0.05
3.0
3.0
9.0
4.0
The registrant should propose the tolerance, based on
available data.
The registrant should propose the tolerance, based on
available data.
The registrant should propose the tolerance, based on
available data.
The registrant should propose the tolerance, based on
available data.
The registrant should propose the tolerance, based on
available data;
Corn, pop, stover.
See comment under barley grain;
Corn, pop, grain
A crop group tolerance should be proposed for residues in
forage and hay of grasses. Note that grass forages/hay have
not been included in ruminant diets, since bromoxynil is only
used on grass grown for seed and on grass grown under the
CRP. Changes in the use on grass may require revision of
livestock tolerances.
The registrant should propose the tolerance, based on
available barley hay data.
The registrant should propose the tolerance, based on
available wheat hay data.
§180.324(b) Section 18 emergency exemptions [Reserved]
§180.324(c) Tolerances with regional registrations [Reserved]
§180.324(d) Indirect or inadvertent [Reserved]
CODEX HARMONIZATION
Since there are no established or proposed Codex MRLs for bromoxynil residues, no
compatibility questions exist with respect to U.S. tolerances and Codex.
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2. Summary of Risk Management Decisions
a. Human Health
(1) Dietary
EPA has determined that the established tolerances forbromoxynil, with amendments and changes
as specified in this document, meet the safety standards under the FQPA amendments to section
408(b)(2)(D) requiring a reasonable certainty of no harm for the general population. In reaching this
determination, EPA has considered the available information on the aggregate exposures (both acute
and chronic) from food and drinking water. There are no residential exposures from bromoxynil. For
cumulative effects, in the case of bromoxynil, EPA has not yet conducted a detailed review of common
mechanism to determine whether it is appropriate, or how to include this chemical in a cumulative risk
assessment. After EPA develops a methodology to incorporate common mechanism of toxicity
evaluations in risk assessments, the Agency will develop a process (either as part of the periodic review
of pesticides or otherwise) to reexamine these tolerance decisions. For the purpose of the tolerance
reassessment in this RED, EPA has assumed that bromoxynil does not have a common mechanism of
toxicity with other non-bromoxynil substances.
Children
EPA has determined that the establi shed tolerances for bromoxynil, with amendments and changes
as specified in this document, meet the safety standards under the FQPA amendments to section
408(b)(2)(D) for infants and children. The safety determination for infants and children considers the
factors noted above for the 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 bromoxynil residues in this population
subgroup.
Based on the current data requirements, bromoxynil has a complete database for developmental
and reproductive toxicity. Studies cited earlier in this document indicate a well-established
developmental endpoint (supernumerary ribs) which occurs at dose levels lower than those that show
evidence of maternal toxicity. The Agency has concluded that the FQPA safety factor is necessary to
protect the developing fetus due to evidence of increased susceptability for that sensitive subpopulation.
EPA based its decision upon concerns emanating from the toxicological profile, including evidence of
increased susceptibility of fetuses to bromoxynil exposure, although it is recognized that there are
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extensive and reliable data available and there are no outstanding uncertainties regarding the effects on
developing animals following pre- and/or postnatal exposure to bromoxynil. Therefore the Agency
retained the FQPA safety factor only for the population consisting of females 13+ to protect the
developing fetus from effects resulting from in utero exposure.
In deciding to continue to make reregi strati on determinations during the early stages of FQPA
implementations, EPA recognizes that it will be necessary to make decisions relating to FQPA before
the implementation process is complete. In making these early, case-by case decisions, EPA does not
intend to set broad precedents for the application of FQPA to its regulatory determinations. Rather,
these early decisions will be made on a case-by-case basis and will not bind EPA as it proceeds with
further policy development and rulemaking that may be required.
If EPA determines, as a result of this later implementation process, that any of the determinations
described in this RED are no longer appropriate, the Agency will consider itself free to pursue whatever
action may be appropriate, including but not limited to, reconsiderations of any portion of this RED.
The dietary findings are summarized below.
Acute Dietary
The acute dietary risks (calculated as MOEs) from food sources (including cotton) for the general
population and subgroups are all greater than 10,000, indicating that there is no acute risk concern
resulting from exposure to bromoxynil. There appears to be no acute risk to the general population or
any subgroup from drinking water. The acute MOEs calculated for drinking water are > 10,000. The
aggregate acute risks from food, including cotton, and water for the general population and all
subgroups are all greater than 10,000, indicating there is no aggregate acute risk concern.
Chronic Dietary (including cancer)
There is no chronic risk from food sources or drinking water, both of which have a risk of < 1%
of the RfD. The aggregate chronic risks from food and water is also <1% of the RfD for the general
population and all subgroups. The Agency considers percentages approaching 100% to be of concern.
Therefore, there is no chronic risk concern.
The cancer risk from food sources is above 1.5 x 10"6. This risk estimate is based on anticipated
residues and percent crop treated data which represent the most refined estimate the Agency can
currently conduct. One of the assumptions made in the risk assessment is that 10% (1.3 million acres)
of the cotton crop is treated with bromoxynil. Treatment of >10% cotton acreage is not permitted
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under the current registration. Changes in the percent crop treated will necessarily change the risk
estimate. There appears to be no cancer risk from drinking water alone with risk calculated to be 0.2
x 10"6. The aggregate dietary cancer risk from food and water consumption was calculated to be 1.7
x 10"6. This risk represents a worst case scenario.
The Agency has determined the aggregate cancer risk from bromoxynil meets the reasonable
certainty of no harm standard. EPA believes that, given the weight-of-the-evidence, the bromoxynil
risk is "negligible". The Agency does not apply the negligible risk standard as a bright line test because
of the lack of precision in quantitative cancer risk assessment. There are a significant number of
uncertainties in both the toxicological data used to derive the cancer potency of a substance and in the
data used to measure and calculate exposure.
Endocrine Disrupter Effects
EPA is required to develop a screening program to determine whether certain substances
(including all pesticides and inerts) "may have an effect in humans that is similar to an effect produced
by a naturally occurring estrogen, or such other endocrine effect...." The Agency is currently working
with interested stakeholders, including other government agencies, public interest groups, industry and
research scientists in developing a screening and testing program and a priority setting scheme to
implement this program. Congress has allowed 3 years from the passage of FQPA (August 3, 1999)
to implement this program. At that time, EPA may require further testing of this active ingredient and
end use products for endocrine disrupter effects.
b. Environmental
No risk mitigation is required at this time as the result of ecological effects concerns. While there
were some small exceedances of levels of concern (LOCs), generally the risks from the use of
bromoxynil are relatively low. These risks are summarized below. Outstanding data requirements
include: 123-2 with Lemna gibba; and 172-4 (a & b) for chronic estuarine toxicity testing.
(1) Avian
Acute
The acute risk to birds is considered to be low. A may effect for endangered avian species has
been identified. No risk quotient exceeded 0.3.
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Chronic
The chronic risk to birds is considered to be low. A chronic may effect for endangered birds has
been identified for the two highest use rates for cotton on short grasses. No risk qotient exceeded 3.0.
Bromoxynil phenol is substantially less acutely toxic to birds than the octanoate. It can be presumed
that it would also be less toxic on a chronic basis. Since the octanoate readily degrades to the phenol,
the compound to which birds would be exposed to on a chronic basis is the phenol.
(2) Mammals
Acute
The acute risk to mammals, including threatened and endangered species, from exposure to
bromoxynil octanoate is expected to be low. LOCs for high acute risk, restricted use and endangered
species were slightly exceeded at the higher application rates for the meadow vole and the least shrew.
No risk quotient exceeded 0.24.
Chronic
The chronic risk to mammals, including threatened and endangered species, from exposure to
bromoxynil octanoate would be expected to be high if mammals were exposed to high enough residues.
Although the risk quotients (RQs) were not excessively high (0.2 - 5.2), bromoxynil octanoate has been
shown to be a developmental toxicant in several studies. If mammals were exposed to bromoxynil at
high enough levels, chronic developmental effects may occur. However, such levels are believed to be
unlikely to occur.
(3) Insects
Bromoxynil octanoate is practically non-toxic to bees; therefore minimal risk is presumed.
(4) Freshwater Fish
The acute risk to freshwater fish is expected to be low. Using EECs derived from GENEEC, no
risk quotient exceeds 0.4. The endangered species LOG has been slightly exceeded based on results
from all modeled use sites, therefore, applications of bromoxynil octanoate may affect endangered
freshwater fish species. However, the environmental fate characteristics of the chemical indicate that
once it is in the aqueous environment, it metabolizes readily to the phenol, which is practically nontoxic
to freshwater fish, and then further degrades to CO2. Therefore, endangered species are likely to be
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exposed only a short time before the octanoate degrades (half life of 1-14 days). The overall chronic
risk to freshwater fish is anticipated to be minimal.
(5) Estuarine and Marine Organisms
Acute risk quotients derived from GENEEC using the lowest EC50 value of three estuarine
species tested (mysid shrimp), ranged from 0.04 - 0.15. Acute toxicity of bromoxynil to oysters and
estuarine fish is less than that for the shrimp, therefore, minimal acute risk to oysters and estuarine fish
is expected from all bromoxynil octanoate uses.
No chronic data with estuarine species were submitted. Because the freshwater species for both
invertebrates and fish are more sensitive than the estuarine species in the acute studies, it is assumed
that the conclusion of minimal chronic risk for freshwater species is applicable to the estuarine species.
Additional data on bromoxynil octanoate are required as confirmatory data.
(6) Aquatic invertebrates (Freshwater and Estuarine/Marine)
The overall acute risk to freshwater invertebrates is expected to be low. Risk quotients, using
EECs derived from GENEEC range from 0.3 to 0.9. For the cotton scenario, which represents the
worst case, EECs from the Tier II model (PRZM-EXAMS) were used. In this case no LOCs were
exceeded. The acute risk to estuarine organisms is expected to be low. The acute endangered species
LOG for estuarine shrimp has been exceeded by a small margin for the cotton use. However, there are
currently no endangered estuarine shrimp species. Based on the Daphnia magna life-cycle study and
the EECs calculated from GENEEC, the chronic risk to aquatic invertebrates is expected to be minimal.
Risk quotients ranged from 0.07 - 0.15. The environmental fate characteristics of bromoxynil indicate
that once it is in the aqueous environment, it metabolizes readily to the phenol, which is practically
nontoxic, and then further degrades to CO2. Therefore, endangered species are likely to be exposed
only a short time before the octanoate degrades (half life of 1-14 days).
(7) Nontarget Plants (Terrestrial, Semi-Aquatic, and Aquatic)
The overall risk to both endangered and non-endangered terrestrial and semi-aquatic plants is
expected to be medium. However, compared to other herbicides, it is relatively low. The only LOG
exceeded is for spray drift from the aerial application of bromoxynil octanoate at the maximum label
rate. This LOG indicates that risk to the vegetative vigor of nontarget terrestrial and semi-aquatic
plants may result from exposure to bromoxynil octanoate through drift. The LOCs were exceeded by
only a small margin (RQ=2.0). However, this risk may be underestimated for the cotton use, which
allows multiple applications, because the exposure model used does not account for multiple
applications. Label language addressing spray drift concerns is required.
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Risk to aquatic vascular plants (endangered and non-endangered) from the use of bromoxynil
octanoate appears to be low. An estimate of risk (based on data from bromoxynil heptanoate) indicated
that aquatic vascular plants are not likely to be affected by bromoxynil octanoate application. However,
in order to confirm this assessment, bromoxynil octanoate testing with Lemna gibba is required.
Risk to aquatic nonvascular plants (endangered and nonendangered) is expected to be minimal.
The LOG for endangered species was met, but not exceeded for the maximum application rate to
cotton. Taking into account all of the available toxicity information, overall risk to aquatic plants due
to bromoxynil from application of bromoxynil octanoate to transgenic cotton is expected to be low.
(8) Endangered Species
See applicable sections under each category above.
(9) Surface Water
Information from environmental fate studies indicates that bromoxynil octanoate should not
persist in surface waters. Risks to aquatic organisms are expected to be low.
(10) Ground Water
The potential for ground water contamination from bromoxynil is low. Bromoxynil octanoate
readily degrades to bromoxynil phenol via hydrolysis. Although bromoxynil phenol has the potential
to leach to ground water under certain conditions, its rapid aerobic and anaerobic degradation reduces
the likelihood of ground water contamination. Based on the results from the laboratory and terrestrial
field dissipation studies, bromoxynil octanoate does not have the mobility or persistence characteristics
of pesticides that are normally found in ground water.
c. Restricted Use Classification
None of the products containing bromoxynil as the active ingredient are classified as restricted
use. No action to classify any use as restricted is required.
d. Reference Dose Exceedance
Only < 1% of the RfD is occupied by the current uses of bromoxynil. There is no exceedence
concern.
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e. Endangered Species Statement
Levels of concern for endangered avian, terrestrial and aquatic plant and mammal species were
exceeded for bromoxynil, as discussed above in the science section.
Currently, the Agency is developing a program ("The Endangered Species Protection Program")
to identify all pesticides whose use may cause adverse impacts on endangered and threatened species
and to implement mitigation measures where necessary. The program may require use restrictions to
protect endangered and threatened species at the county level. Consultations with the Fish and Wildlife
Service may be necessary to assess risks to newly listed species or from proposed new uses. In the
future, the Agency plans to publish a description of the Endangered Species Program in the Federal
Register and have available voluntary county-specific bulletins. Because the Agency is taking this
approach for protecting endangered and threatened species, it is not imposing label modifications at this
time through the RED. Rather, any requirements for product use modifications will occur in the future
under the Endangered Species Protection Program.
f. Labeling Rationale
In order to remain in compliance with FIFRA, it is the Agency's position that the labeling of all
registered pesticide products containing bromoxynil must comply with the Agency's current pesticide
labeling requirements. The Agency has determined that the current manufacturing and end-use label
precautions are still appropriate and required for product reregi strati on. In addition, it is the Agency's
position that the label statements/precautions listed in Section V of this RED must be included on all
affected products in order to remain in compliance with FIFRA.
g. Spray Drift Advisory
The Agency has been working with the Spray Drift Task Force, EPA Regional Offices and State
Lead Agencies for pesticide regulation to develop the best spray drift management practices. The
Agency is now requiring interim measures that must be placed on product labels/labeling as specified
in Section V. Once the Agency completes its evaluation of the new data base submitted by the Spray
Drift Task Force, a membership of U.S. pesticide registrants, the Agency may impose further
refinements in spray drift management practices to further reduce off-target drift and risks associated
with this drift.
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h. Occupational and Residential Labeling Rationale/Risk Mitigation
At this time, all products containing bromoxynil are intended primarily for occupational use (i.e.
mixed, loaded, and applied by commercial applicators only and generally not available to homeowners).
No registered use is allowed at residential sites.
(1) The Worker Protection Standard (WPS)
EPA's Worker Protection Standard for Agricultural Pesticides (WPS) affects all pesticide
products whose labeling reasonably permits use in the commercial or research production of agricultural
plants on any farm, forest, nursery, or greenhouse. In general, WPS products had to bear WPS-
complying labeling when sold or distributed after April 21, 1994. The WPS labeling requirements
pertaining to personal protective equipment (PPE), restricted-entry intervals (REI), and notification are
interim. These requirements are to be reviewed and revised, as appropriate, during reregi strati on and
other Agency review processes. At this time some of the registered uses of bromoxynil are within the
scope of the WPS and some uses are outside the WPS scope.
(2) Determination of Requirements for Handlers
For each end-use product, personal protective equipment and engineering control requirements
for pesticide handlers are set during reregi strati on as follows:
! Based on risks posed to handlers by the active ingredient, EPA may establish
active-ingredient specific (a.i. specific) handler requirements for end-use products
containing that active ingredient. If such risks are minimal, EPA may choose not
to establish a.i. specific handler requirements.
! EPA establishes handler PPE requirements for most end-use products based on
each product's acute toxicity characteristics.
! If a.i. specific requirements have been established, they must be compared to the
PPE specified for the end-use product. The more stringent choice for
each type of PPE (i.e., bodywear, hand protection, footwear, eyewear, etc.) must
be placed on the label of the end-use product. Engineering controls are considered
more stringent than PPE requirements.
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3. Occupational-Use Products (WPS Uses and Non-WPS Uses)
EPA is establishing a.i. specific requirements for occupational handlers for bromoxynil. Since
potential handler exposure is similar for WPS and nonWPS uses, the a.i. specific handler requirements
are the same for WPS and nonWPS occupational uses of bromoxynil end-use products.
EPA has established a short- and intermediate-term dermal NOEL for bromoxynil based on
developmental effects and has also classified bromoxynil as a Group C quantifiable carcinogen. The
handler dermal risk assessment based on the Pesticide Handler's Exposure Database (PHED) data for
mixers/loaders/applicators indicates that short- and intermediate-term dermal risks and cancer risks are
acceptable (i.e., greater than 100) if such handlers wear chemical-resistant gloves in addition to baseline
attire (long-sleeve shirt, long pants, shoes, and socks) while performing mixing and loading tasks and
baseline attire while performing applicator tasks. For all tasks, other than mixing and loading, the risks
are acceptable for handlers with baseline attire. The cancer risk for the non-commercial handlers
(grower) is 2 x 10"6 or lower for all scenarios with baseline attire, except that mixers and loaders must
also wear chemical-resistant gloves. The cancer risk for commercial handlers is 1.9 x 10"5 or lower for
all scenarios with baseline attire, except that mixers and loaders must also wear chemical-resistant
gloves. The highest cancer risk estimate from these particular scenarios was 1.9 X 10"5 (commercial
mixer/loaders for aerial applications and sprinkler irrigation). However, these mixer/loader risk
estimates do not account for the potential exposure reduction from the use of "wide-mouth" containers
(designed to reduce spillage) for mixer/loaders. At the present time the PHED database does not allow
the Agency to quantify this risk mitigation measure, however the use of the "wide-mouth" containers
would likely reduce the reported risk further. In addition to provide an additional margin of safety,
EPA is requiring mixers and loaders to wear a chemical-resistant apron. Although EPA has no data to
specifically assess the exposure reduction to mixers/loaders afforded by a chemical-resistant apron, the
Agency is persuaded that the exposure reduction would be significant. Available data indicate that the
preponderance of non-hand exposure to mixers/loaders is to the front torso.
EPA has determined that occupational exposures to bromoxynil would be adequately mitigated
with the following PPE: mixers/loaders wearing long sleeved shirts, long pants, shoes, and socks plus
chemical resistant gloves while using open mixing/loading. All other handlers (i.e., applicators, flaggers,
etc.) must wear baseline attire (i.e., long-sleeve shirt, long pants, shoes, and socks). For applicators
using fixed- and rotary-wing aircraft to apply bromoxynil, the risks are acceptable (i.e., 310) when
enclosed cockpits are assumed. Since the Pesticide Handlers Exposure Database does not contain
sufficient data to estimate exposure to applicators using aircraft with open cockpits, only exposure for
aerial applicators using engineering controls, (i.e., enclosed cockpits) was estimated. However, the
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MOEs are acceptable at baseline attire for applicators using groundboom equipment and for flaggers,
and the MOEs are high for applicators using enclosed cockpits, therefore, EPA does not have concerns
for handlers who may apply bromoxynil using aircraft with open cockpits. Since risks are acceptable
for human flaggers without engineering controls, the existing labeling requirements that "human flaggers
are prohibited unless in enclosed vehicles" is not being retained.
Engineering-control requirements would also contribute to exposure reduction for mixers and
loaders. Some bromoxynil end-use products are already formulated to provide a type of engineering
control exposure-reduction for mixers and loaders. These include products formulated in water-soluble
gel packets and those formulated in wide-mouth jugs designed to reduce splashing. These offer
additional protection for mixers and loaders.
The Agency is retaining the present labeling restrictions regarding chemigation, including that (1)
hand-moved pipe must not be handled in any way until 24 hours after chemigation has been completed
and residues have been flushed from the system, and (2) no person may enter the application site during
the chemigation, except in an enclosed vehicle.
The Agency is also retaining the present labeling restrictions regarding prohibiting aerial
application within 300 feet of residential areas, including homes, schools, playgrounds, shopping areas,
and hospitals. Also being retained are the present labeling restrictions regarding application to non-
residential turf only. The labeling will specifically prohibit applications to residential, playground, or
schoolyard turf.
The Agency is retaining and expanding the present labeling restrictions regarding application with
backpack or hand-held application equipment. Presently the label prohibits application to non-
residential turf with such equipment. The new label statement will prohibit application to any crop with
backpack or hand-held application equipment.
Finally, since the Agency has determined that the heptanoate ester is lexicologically equivalent
to the octanoate ester, the handler requirements established here also apply to end-use products
containing the heptanoate ester.
4. Post-Application/Entry Restrictions
a. Occupational-Use Products (WPS Uses)
Restricted-entry intervals, early-entry PPE. and "double" notification:
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The interim Worker Protection Standard (WPS) restricted-entry intervals (REI's) for agricultural
workers are based solely on the acute dermal toxicity and skin and eye irritation potential of the active
ingredient. In addition, the WPS retains two types of REI's established by the Agency before the
promulgation of the WPS: (1) product-specific REI's established on the basis of adequate data, and (2)
interim REI's that are longer than those that would be established under the WPS.
The WPS prohibits routine entry to perform hand labor tasks during the REI and requires PPE
to be worn for other early-entry tasks that require contact with treated surfaces.
"Double" notification is the statement on the labels of some WPS pesticide products requiring
employers to notify workers about pesticide-treated areas orally as well as by posting of the treated
areas. The interim WPS "double" notification requirement was imposed if the active ingredient is
classified as toxicity category I for acute dermal toxicity or skin irritation potential.
During the reregi strati on process, EPA establishes REI's, early-entry PPE, and double
notification requirements based on consideration of all available relevant information about the active
ingredient, including acute toxicity, other adverse effects, epidemiological information, and post-
application data. Since the Agency has determined that the heptanoate ester is lexicologically
equivalent to the octanoate ester, the WPS entry restrictions established here also apply to end-use
products containing the heptanoate ester.
Restricted-entry intervals: EPA is establishing a 24-hour REI for all uses of bromoxynil other
than cotton and turf grown for transplanting (e.g., on sod farms). The basis for this decision is the
classification of bromoxynil as toxicity category II for eye irritation potential and concerns about risks
due to developmental effects and cancer effects resulting from post-application activities in crops such
as corn and small grains. The application timing for such crops, which comprise approximately 90%
of bromoxynil usage, is early in the season (from preemergence to prior to tassel emergence/boot
stage). Because of the use patterns and mode of action of bromoxynil, most workers entering treated
fields would likely be performing scouting tasks or low contact labor tasks such as mechanical
incorporation and cultivation. In these situations, the risks to post-application workers should be
acceptable at 24 hours following application.
Since the toxicological endpoint for short-term and intermediate-term exposure is based on a
NOEL for developmental effects, EPA is concerned that the default REI of 24 hours is not protective
for cotton workers and sod harvesters where there is significant potential for postapplication exposures.
The window of application for transgenic cotton is wider, which increases the potential for worker
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contact with treated surfaces. In addition, cotton crops are scouted frequently leading to more
opportunities for exposure than for the corn and small grain crops. Commercially grown sod may be
harvested soon after an application, which could result in relatively high post-application exposures to
workers and to exposures to persons at residential sites. Based on these concerns and a surrogate post-
application exposure and risk assessment, EPA is establishing a 4-day REI for uses of bromoxynil on
cotton and a 26-day REI for uses of bromoxynil on turf grown for transplanting (e.g., on sod farms).
EPA believes that measures to reduce short- and intermediate-term risks also will reduce cancer risks.
These REIs reconfirm the REIs of 4 days for cotton and 26 days for sod established in the Federal
Register Notice published May 13, 1998, in conjunction with the cotton use registration action.
Early-Entry PPE: The WPS prohibits routine entry to perform hand labor tasks during the REI
and requires PPE to be worn for other early-entry tasks that require contact with treated surfaces. As
the result of Agency concerns about risks due to developmental effects and cancer effects resulting from
post-application activities, EPA is requiring the following early-entry PPE for all in-scope WPS uses
of products containing bromoxynil: coveralls, shoes plus socks, and chemical-resistant gloves. In
addition, protective eyewear is required, because bromoxynil is classified as category II for eye irritation
potential
"Double" Notification: "Double" notification is the statement on the labels of some WPS
pesticide products requiring employers to notify workers about pesticide-treated areas orally as well
as by posting of the treated areas. The interim WPS "double" notification requirement was imposed
if the active ingredient is classified as toxicity category I for acute dermal toxicity or skin irritation
potential. EPA has determined that double notification is required for uses of bromoxynil on cotton and
on turf grown for transplanting because of Agency concerns about developmental effects and the
possibility of inadvertent entry following uses at these sites.
b. Occupational-Use Products (NonWPS Uses)
Since EPA has concerns about post-application exposures to persons after nonWPS occupational
uses of bromoxynil, it is establishing entry restrictions for all nonWPS occupational uses. However,
since the anticipated frequency, duration, and degree of exposure following nonWPS occupational
applications do not warrant a 24-hour entry restriction, the Agency is restricting entry into treated areas
after such applications only until sprays have dried.
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C. Other Labeling Requirements
The Agency is also requiring other use and safety information to be placed on the labeling of all
end-use products containing bromoxynil. For the specific labeling statements, refer to Section V of this
document.
V. ACTIONS REQUIRED OF REGISTRANTS
This section specifies the data requirements and responses necessary for the reregi strati on of both
manufacturing-use and end-use products.
A. Manufacturing-Use Products
1. Additional Generic Data Requirements
The generic data base supporting the reregi strati on of bromoxynil for the above eligible uses has
been reviewed and determined to be substantially complete. However, additional confirmatory data are
needed to fulfill requirements for the guidelines listed below:
• Aquatic Plant Toxicity (Anabaena flos-aquae and Lemna gibba)
• Chronic Estuarine/Marine Fish and Invertebrates
The Agency also does not have acute toxicity information for a bromoxynil technical product and
is requesting that that information be supplied to the Agency. Specific data requirements are listed in
Appendix G.
Additionally, in order to allow more precise estimates of exposure to bromoxynil in drinking
water, the Agency herein reiterates the requirement of the submission of an acceptable surface water
monitoring program as specified in the FR Notice, 63FR26473.
2. Labeling Requirements for Manufacturing-Use Products
a. Formulation Statements
To remain in compliance with FIFRA, manufacturing use product (MP) labeling must be revised
to comply with all current EPA regulations, PR Notices and applicable policies. The MP labeling must
bear the following statement under Directions for Use:
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"Only for formulation into an herbicide for the following use(s) [fill blank only
with those uses that are being supported by MP registrant]."
An MP registrant may, at his/her discretion, add one of the following statements to an MP label
under "Directions for Use" to permit the reformulation of the product for a specific use or all
additional uses supported by a formulator or user group:
(a) "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)."
(b) "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)."
b. Plantback Intervals
A 30-day plantback interval (FBI) is required for all crops except cotton. For cotton required
additional limited field rotational crop studies have not been submitted to the Agency; acceptable
studies previously submitted in support of reregi strati on reflect a maximum seasonal and single
application rate of 0.5 Ib ai/A, but the use on cotton constitutes a maximum seasonal application rate
of 1.5 Ib ai/A. Pending receipt of these studies registered labels must restrict rotation of treated cotton
fields treated with more than 0.5 a.i./A/season to BXN cotton.
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 study MRID numbers should be cited according to the instructions in the Requirement
Status and Registrants Response Form provided for each product.
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2. Labeling Requirements for End-Use Products
Worker Protection Standard: The labels and labeling of all products must comply with EPA's
current regulations and requirements as specified in 40 CFR §156.10 and other applicable notices.
a. PPE/Engineering Control Requirements for Pesticide Handlers
For sole-active-ingredient end-use products that contain bromoxynil (including end-use products that
contain the octanoic acid ester, the heptanoic acid ester, or a combination of the two esters):
! Revise the product labeling to adopt the handler personal protective equipment/
engineering control requirements set forth in this section.
! Remove any conflicting PPE requirements on the current labeling.
For multiple-active-ingredient end-use products that contain bromoxynil:
! Compare the handler personal protective equipment/engineering control requirements set
forth in this section to the requirements on the current labeling.
! Retain the more protective requirements. (For guidance on which requirements are
considered more protective, see PR Notice 93-7.)
b. Products Intended Primarily for Occupational Use (WPS and
nonWPS)
(Note that this reregi strati on action is not intended to serve as the reregistraton action required
for the heptanoic ester. However, because the heptanoic form is included in two labels with the
octanoic ester form, the Agency is acting to correct the combined labels).
Active-Ingredient Specific Engineering Control Requirements
EPA is not establishing active-ingredient specific controls for occupational uses of bromoxynil
end-use products, because all MOEs and cancer risk estimates for handlers were acceptable at baseline
or with additional PPE, .
Active-Ingredient Specific Personal Protective Equipment Requirements
EPA is establishing the following active-ingredient-specific PPE for occupational uses of
bromoxynil end-use products.
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"Applicators and other handlers must wear:
— long-sleeved shirt and long pants,
— shoes plus socks,
—chemical-resistant gloves* for cleaning, equipment, mixing and loading,
-chemical-resistant apron for cleaning equipment, mixing, and loading."
*For the glove statement, use the statement established for bromoxynil through the instructions
in Supplement Three of PR Notice 93-7.
Determining PPE Labeling Requirements for End-use Products Containing This Active
Ingredient
The PPE that would be established on the basis of the acute toxicity category of the end-use
product must be compared to the active-ingredient specific personal protective equipment specified
above. The more protective PPE must be placed on the product labeling. For guidance on which PPE
is considered more protective, see PR Notice 93-7. If the acute inhalation toxicity of the bromoxynil
end-use product is in category I or II, making a respirator necessary for pesticide handlers, the
following type of respirator is appropriate: A dust/mist filtering respirator (MSHA/NIOSH approval
number prefix TC-21C).
Placement in Labeling
The personal protective equipment requirements must be placed on the end-use product labeling
in the location specified in PR Notice 93-7, and the format and language of the PPE requirements must
be the same as is specified in PR Notice 93-7.
c. Entry Restrictions
For sole-active-ingredient end-use products that contain bromoxynil, including end-use products
that contain the octanoic acid ester, the heptanoic acid ester, or a combination of the two esters: revise
the product labeling to adopt the entry restrictions set forth in this section; and remove any conflicting
entry restrictions on the current labeling.
For multiple-active-ingredient end-use products that contain bromoxynil:
compare the entry restrictions set forth in this section to the entry restrictions on the current labeling;
and retain the more protective restrictions. (A specific time period in hours or days is considered more
protective than "sprays have dried" or "dusts have settled.")
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3. Products Intended Primarily for Occupational Use
a. WPS Uses
(1) Restricted-entry interval:
With the exception of cotton and turf grown for transplanting (e.g., on sod farms), a 24-hour
restricted-entry interval (REI) is required for uses, within the scope of the WPS on all bromoxynil end-
use products. The REI for cotton is 4 days and the REI for turf grown for transplanting (e.g., on sod
farms) is 26 days. The exact wording of the restricted-entry interval for cotton must be as follows:
"The restricted-entry interval (REI) for cotton is 4 days and includes scouts and crop advisors. The
exemption in the Worker Protection Standard for certified crop advisors does not apply to bromoxynil.
Scouts and crop advisors are prohibited from entering the treated area during the entire 4-day REI for
bromoxynil. Applicators and other users must inform crop advisors and scouts of this requirement."
(2) Early-entry personal protective equipment (PPE):
The PPE required for early entry is:
- coveralls,
— chemical-resistant gloves,
— shoes plus socks, and
— protective eyewear.
(3) WPS notification statement:
The following statement must be added to all end-use product labeling that contains directions
for cotton or turf grown for transplanting (e.g., on sod farms):
"For uses on cotton or on turf grown for transplanting (e.g., on sod farms): notify
workers of the application by warning them orally and by posting warning signs at
entrances to treated areas."
(4) Placement in labeling:
The REI must be inserted into the standardized REI statement required by Supplement Three of
PR Notice 93-7.
127
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The PPE required for early entry must be inserted into the standardized early-entry PPE statement
required by Supplement Three of PR Notice 93-7.
b. Non-WPS Uses
(1) Entry restrictions: the Agency is establishing the following entry
restrictions for nonWPS occupational uses of bromoxynil end-use products: "Do
not enter or allow others to enter the treated area until sprays have dried."
(2) Placement in labeling: If WPS uses are also on label — Follow the
instructions in PR Notice 93-7 for establishing a Non-Agricultural Use
Requirements box, and place the appropriate nonWPS entry restrictions in that
box. If no WPS uses are on the label - Place the appropriate nonWPS entry
restrictions in the Directions for Use, under the heading "Entry Restrictions."
4. Labeling for Products Intended Primarily for Occupational Use
The Agency is requiring the following labeling statements to be located on all end-use products
containing bromoxynil that are intended primarily for occupational use:
a. 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."
"Aerial application is prohibited within 300 feet of residential areas (e.g., homes,
schools, playgrounds, shopping areas, hospitals, etc.)."
"Apply to non-residential turf only. Do not apply to residential, playground, or
schoolyard turf."
"Do not apply with backpack or hand-held application equipment."
"Application by chemigation must be done by fixed pipe, overhead sprinkler
systems or hand-moved pipe. If hand-moved pipe is used, for chemigation, the pipe must
not be handled in any way until 24 hours after chemigation has been completed and
128
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residues have been flushed from the system. When applying by chemigation, no person
may enter the application site during the chemigation unless in an enclosed vehicle."
b. Engineering Controls
Place the following user safety requirements immediately following the personal protective
equipment and engineering control requirements:
"When handlers use closed systems, enclosed cabs, or aircraft in a manner that
meets the requirements listed in the Worker Protection Standard (WPS) for agricultural
pesticides (40 CFR 170.240(d)(4-6), the handler PPE requirements may be reduced or
modified as specified in the WPS."
c. User Safety Requirements
Place the following user safety requirements immediately following the engineering control
statement above. The heading "user safety requirements" is not required — just the following
statements:
"Discard clothing or other absorbent materials that have been drenched or heavily
contaminated with this product's concentrate. Do not reuse them."
"Follow manufacturer's instructions for cleaning/maintaining PPE. If no
such instructions for washables, use detergent and hot water. Keep and wash PPE
separately from other laundry."
"To reduce exposure to residues, wash the spray rig, tractor, and all other
equipment used to handle or apply this product with water daily or before using the
equipment for any other purpose."
5. User Safety Recommendations
Place the following user safety recommendations inside a box with the heading "User Safety
Recommendations." The box must be located on the labeling immediately following the user safely
requirements listed above.
129
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"Users should wash hands before eating, drinking, chewing gum,
using tobacco, or using the toilet."
"Users should remove clothing 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."
The labels and labeling of all products must comply with EPA's current regulations and
requirements as specified in 40 CFR §156.10 and other applicable notices.
a. Spray Drift Labeling
The following language must be placed on each product label that can be applied aerially:
Avoiding spray drift at the application site is the responsibility of the applicator. The interaction
of many equipment-and-weather-related factors determine the potential for spray drift. The applicator
and the grower are responsible for considering all these factors when making decisions.
The following drift management requirements must be followed to avoid off-target drift
movement from aerial applications to agricultural field crops. These requirements do not
apply to forestry applications, public health uses or to applications using dry formulations.
1. The distance of the outer most nozzles on the boom must not exceed 3/4
the length of the wingspan or rotor.
2. Nozzles must always pointbackward parallel with the air stream and never
be pointed downwards more than 45 degrees.
Where states have more stringent regulations, they should be observed.
The applicator should be familiar with and take into account the
information covered in the Aerial Drift Reduction Advisory Information.
130
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The following aerial drift reduction advisory information must be
contained in the product labeling:
[The section is advisory in nature and does not supersede the mandatory label
requirements.]
INFORMATION ON DROPLET SIZE
The most effective way to reduce drift potential is to apply large droplets. The
best drift management strategy is to apply the largest droplets that provide
sufficient coverage and control. Applying larger droplets reduces drift potential,
but will not prevent drift if applications are made improperly, or under
unfavorable environmental conditions (see Wind, Temperature and Humidity, and
Temperature Inversions).
CONTROLLING DROPLET SIZE
! Volume - Use high flow rate nozzles to apply the highest practical spray
volume. Nozzles with higher rated flows produce larger droplets.
! Pressure - Do not exceed the nozzle manufacturer's recommended
pressures. For many nozzle types lower pressure produces larger droplets. When
higher flow rates are needed, use higher flow rate nozzles instead of increasing
pressure.
! Number of nozzles - Use the minimum number of nozzles that provide
uniform coverage.
! Nozzle Orientation - Orienting nozzles so that the spray is released parallel
to the airstream produces larger droplets than other orientations and is the
recommended practice. Significant deflection from horizontal will reduce droplet
size and increase drift potential.
! Nozzle Type - Use a nozzle type that is designed for the intended
application. With most nozzle types, narrower spray angles produce larger
droplets. Consider using low-drift nozzles. Solid stream nozzles oriented straight
back produce the largest droplets and the lowest drift.
131
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BOOM LENGTH
For some use patterns, reducing the effective boom length to less than 3/4 of the
wingspan or rotor length may further reduce drift without reducing swath width.
APPLICATION HEIGHT
Applications should not be made at a height greater than 10 feet above the top of
the largest plants unless a greater height is required for aircraft safety. Making
applications at the lowest height that is safe reduces exposure of droplets to
evaporation and wind.
SWATH ADJUSTMENT
When applications are made with a crosswind, the swath will be displaced
downward. Therefore, on the up and downwind edges of the field, the applicator
must compensate for this displacement by adjusting the path of the aircraft
upwind. Swath adjustment distance should increase with increasing drift
potential (higher wind, smaller drops, etc.)
WIND
Drift potential is lowest between wind speeds of 2-10 mph. However, many
factors, including droplet size and equipment type determine drift potential at any
given speed. Application should be avoided at wind speeds below 2 mph due to
variable wind direction and high inversion potential. NOTE: Local terrain can
influence wind patterns. Every applicator should be familiar with local wind
patterns and how they affect spray drift.
TEMPERATURE AND HUMIDITY
When making applications in low relative humidity, set up equipment to produce
larger droplets to compensate for evaporation. Droplet evaporation is most
severe when conditions are both hot and dry.
TEMPERATURE INVERSIONS
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Applications should not occur during a temperature inversion because drift
potential is high. Temperature inversions restrict vertical air mixing, which causes
small suspended droplets to remain in a concentrated cloud. This cloud can move
in unpredictable directions due to the light variable winds common during
inversions. Temperature inversions are characterized by increasing temperatures
with altitude and are common on nights with limited cloud cover and light to no
wind. They begin to form as the sun sets and often continue into the morning.
Their presence can be indicated by ground fog; however, if fog is not present,
inversions can also be identified by observing the movement of smoke from a
ground source or an aircraft smoke generator. Smoke that layers and moves
laterally in a concentrated cloud (under low wind conditions) indicates an
inversion, while smoke that moves upward and rapidly dissipates indicates good
vertical air mixing.
SENSITIVE AREAS
The pesticide should only be applied when the potential for drift to adjacent
sensitive areas (e.g. residential areas, bodies of water, known habitat for
threatened or endangered species, non-target crops) is minimal (e.g. when wind
is blowing away from the sensitive areas).
C. Existing Stocks
Registrants may generally distribute and sell products bearing old labels/labeling for 26
months from the date of the issuance of this Reregi strati on Eligibility Decision (RED). Persons
other than the registrant may generally distribute or sell such products for 50 months from the
date of the 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"; Federal
Register. Volume 56, No. 123, June 26, 1991.
The Agency has determined that registrants may distribute and sell bromoxynil products
bearing old labels/labeling for 26 months from the date of issuance of this RED. Persons other than
the registrant may distribute or sell such products for 50 months from the date of the issuance of this
RED. Registrants and persons other than registrants remain obligated to meet pre-existing Agency
imposed label changes and existing stocks requirements applicable to products they sell or distribute.
133
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134
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VI. APPENDICES
135
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LUIS 5.2 - Page: 1
APPENDIX A REPORT
Case 2070 [Bromoxynil, and esters] Chemical 035302 [Bromoxynil octanoate]
4444444444444444444444444444444444444444444444444444444444444444444444444^
SITE Application Type, Application Form(s) Min. Appl. Max. Appl. Soil Max. # Apps Max. Dose [(AI Min. Re- Geographic Limitations Use
Timing, Application Equipment ) Rate (AI un- Rate (AI Tex. @ Max. Rate unless noted Interv Entry Allowed Disallowed Limitations
Surface Type (Antimicrobial only) & Effica- less noted unless noted Max. /crop /year otherwise)/AI (days) Intv. Codes
cy Influencing Factor (Antimicrobial only) otherwise) otherwise) Dose cycle /crop /year
cycle
FOOD/FEED USES
ALFALFA
Broadcast, Seedling stage, Ground
EC NA
Use Group: TERRESTRIAL FEED CROP
EC NA
Chemigation, Seedling stage, Moving wheel EC
irrigation
EC NA
136
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APPENDIX A REPORT
Case 2070 [Bromoxynil, and esters] Chemical 035302 [Bromoxynil octanoate]
SITE Application Type, Application
Timing, Application Equipment )
Form(s) Mln. Appl.
Rate (AI un-
Surface Type (Antimicrobial only) & Effica-
cy Influencing Factor (Antimicrobial only)
Geographic Limitations
USES ELIGIBLE FOR REREGISTRATION
FOOD/FEED USES (con't)
BARLEY (con't)
Use Group: TERRESTRIAL FOOD+FEED CROP (con't)
1 Ib (AE) A * NS NS NS NS NS 0. 5 d
UC * NS NS NS NS NS 0. 5 d
UC * NS NS
UC * NS NS
UC * NS NS
NS NS NS 0. 5 d
NS NS NS NS
UC NS NS 0. 5 d
137
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PRD Report Date: 09/13/95
LUIS 5.2 - Page:
APPENDIX A REPORT
Case 2070 [Bromoxynil, and esters] Chemical 035302 [Bromoxynil octanoate]
44444444444444444444444444444444444
SITE Application Type, Application Form(s) Mln. Appl. Max. Appl. Soil Max. # Apps Max. Dose [(AI Mln. Re-
Timing, Application Equipment ) Rate (AI un- Rate (AI Tex. @ Max. Rate unless noted Interv Entry
Surface Type (Antimicrobial only) & Effica- less noted unless noted Max. /crop /year otherwise)/AI (days) Intv.
cy Influencing Factor (Antimicrobial only) otherwise) otherwise) Dose cycle /crop /year
cycle
Geographic Limitations Use
USES ELIGIBLE FOR REREGISTRATION
FOOD/FEED USES (con't)
BARLEY (con't)
FM/L NA
SC/L NA
SC/L NA
CORN, FIELD
Broadcast, Postemergence, Boom sprayer EC NA
EC NA
EC NA
EC NA
EC NA
EC NA
EC NA
NS NS NS
NS NS 0. 5 d
NS NS 0. 5 d
Use Group: TERRESTRIAL FOOD+FEED CROP
138
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Report Run Date: 11/24/98 ) Time 11:47
PRD Report Date: 09/13/95
APPENDIX A REPORT
Case 2070 [Bromoxynil, and esters] Chemical 035302 [Bromoxynil octanoate]
SITE Application Type, Application
Timing, Application Equipment )
Form(s) Min. Appl.
Rate (AI un-
Geoqraphic Limitations
USES ELIGIBLE FOR REREGISTRATION
FOOD/FEED USES (con't)
FM/L
.375 Ib (AE)
A
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PRO Report Date: 09/13/95
APPENDIX A REPORT
Case 2070 [Bromoxynil, and esters] Chemical 035302 [Bromoxynil octanoate]
SITE Application Type, Application
Timing, Application Equipment )
Form(s) Min. Appl.
Rate (AI un-
Geoqraphic Limitations
USES ELIGIBLE FOR REREGISTRATION
FOOD/FEED USES (con't)
Use Group: TERRESTRIAL FOOD+FEED CROP (con't)
FM/L
.375 Ib (AE)
A
140
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PRD Report Date: 09/13/95
LUIS 5.2 - Page:
APPENDIX A REPORT
Case 2070 [Bromoxynil, and esters] Chemical 035302 [Bromoxynil octanoate]
SITE Application Type, Application
Timing, Application Equipment )
Form(s) Min. Appl.
Rate (AI un-
Geographic Limitations
USES ELIGIBLE FOR REREGISTRATION
FOOD/FEED USES (con't)
CORN, FIELD (con't)
Spray, Postemergence, Aircraft
FM/L
EC NA
WP NA
Use Group: TERRESTRIAL FOOD+FEED CROP (con't)
UC * 2 NS UC NS 7 0. 5 d
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LUIS 5.2 - Page:
APPENDIX A REPORT
Case 2070 [Bromoxynil, and esters] Chemical 035302 [Bromoxynil octanoate]
44444444444444444444444444444444444
SITE Application Type, Application Form(s) Mln. Appl. Max. Appl. Soil Max. # Apps Max. Dose [(AI Mln. Re-
Timing, Application Equipment ) Rate (AI un- Rate (AI Tex. @ Max. Rate unless noted Interv Entry
Surface Type (Antimicrobial only) & Effica- less noted unless noted Max. /crop /year otherwise)/AI (days) Intv.
cy Influencing Factor (Antimicrobial only) otherwise) otherwise) Dose cycle /crop /year
cycle
Geographic Limitations Use
USES ELIGIBLE FOR REREGISTRATION
FOOD/FEED USES (con't)
CORN, FIELD (con't)
Spray, Preplant, Boom sprayer
Use Group: TERRESTRIAL FOOD+FEED CROP (con't)
Use Group: TERRESTRIAL FOOD+FEED CROP
EC NA
EC NA
.375 Ib (AE)
A
EC NA
EC NA
EC NA
EC NA
EC NA
142
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Report Run Date: 11/24/98 ) Time 11:47
PRD Report Date: 09/13/95
APPENDIX A REPORT
Case 2070 [Bromoxynil, and esters] Chemical 035302 [Bromoxynil octanoate]
SITE Application Type, Application
Timing, Application Equipment )
Form(s) Min. Appl.
Rate (AI un-
Geoqraphic Limitations
USES ELIGIBLE FOR REREGISTRATION
FOOD/FEED USES (con't)
.5 Ib
(AE)
143
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PRD Report Date: 09/13/95
Time 11:47
APPENDIX A REPORT
Case 2070 [Bromoxynil, and esters] Chemical 035302 [Bromoxynil octanoate]
SITE Application Type, Application
Timing, Application Equipment )
Form(s) Min. Appl.
Rate (AI un-
Max. Appl. Soil Max. # Apps Max. Dose [(AI Min. Re-
Rate (AI Tex. @ Max. Rate unless noted Interv Entry
unless noted Max. /crop /year otherwise)/AI (days) Intv.
otherwise) Dose cycle /crop /year
cycle
Geoqraphic Limitations
USES ELIGIBLE FOR REREGISTRATION
FOOD/FEED USES (con't)
Use Group: TERRESTRIAL FOOD+FEED CROP (con't)
FM/L NA
144
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Report Run Date: 11/24/98 ) Time 11:47
PRD Report Date: 09/13/95
APPENDIX A REPORT
Case 2070 [Bromoxynil, and esters] Chemical 035302 [Bromoxynil octanoate]
SITE Application Type, Application
Timing, Application Equipment )
Form(s) Min. Appl.
Rate (AI un-
Geoqraphic Limitations
USES ELIGIBLE FOR REREGISTRATION
FOOD/FEED USES (con't)
WP NA
EC NA
SC/L NA
FM/L NA
Use Group: TERRESTRIAL FOOD+FEED CROP (con't)
145
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Report Run Date: 11/24/98 ) Time 11:47
PRO Report Date: 09/13/95
11
APPENDIX A REPORT
Case 2070 [Bromoxynil, and esters] Chemical 035302 [Bromoxynil octanoate]
SITE Application Type, Application
Timing, Application Equipment )
Form(s) Mln. Appl.
Rate (AI un-
Surface Type (Antimicrobial only) & Effica-
cy Influencing Factor (Antimicrobial only)
Geographic Limitations
USES ELIGIBLE FOR REREGISTRATION
FOOD/FEED USES (con't)
CORN, SWEET
Spray, Postemergence, Aircraft
Spray, Preemergence, Ground
COTTON (UNSPECIFIED)
Band treatment, Postemergence, Ground EC NA
EC NA
Band treatment, Preemergence, Ground EC NA
EC NA
Band treatment, Preplant, Ground EC NA
Use Group: TERRESTRIAL FOOD+FEED CROP
UC * NS NS UC NS NS 0. 5 d
UC * NS NS UC NS NS 0. 5 d
Use Group: TERRESTRIAL FOOD+FEED CROP
NS NS 0. 5 d
.5 Ib (AE) A
3 NS
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APPENDIX A REPORT
Case 2070 [Bromoxynil, and esters] Chemical 035302 [Bromoxynil octanoate]
44444444444444444444444444444444444
SITE Application Type, Application Form(s) Mln. Appl. Max. Appl. Soil Max. # Apps Max. Dose [(AI Mln. Re-
Timing, Application Equipment ) Rate (AI un- Rate (AI Tex. @ Max. Rate unless noted Interv Entry
Surface Type (Antimicrobial only) & Effica- less noted unless noted Max. /crop /year otherwise)/AI (days) Intv.
cy Influencing Factor (Antimicrobial only) otherwise) otherwise) Dose cycle /crop /year
cycle
USES ELIGIBLE FOR REREGISTRATION
FOOD/FEED USES (con't)
Use Group: TERRESTRIAL FOOD+FEED CROP (con't)
EC NA
Use Group: TERRESTRIAL FOOD+FEED CROP
Spray, Postemergence, Aircraft
Spray, Postemergence, Ground
GARLIC
Broadcast, Postemergence, Ground
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13
APPENDIX A REPORT
Case 2070 [Bromoxynil, and esters] Chemical 035302 [Bromoxynil octanoate]
SITE Application Type, Application
Timing, Application Equipment )
Form(s) Min. Appl.
Rate (AI un-
Geographic Limitations
USES ELIGIBLE FOR REREGISTRATION
FOOD/FEED USES (con't)
Spray, Postemergence, Aircraft
Spray, Postemergence, Ground
MILLET (PROSO)
Broadcast, Postemergence, Ground
EC
EC
EC
Use Group: TERRESTRIAL FEED CROP
NS NS NS NS WI
Use Group: TERRESTRIAL FOOD+FEED CROP
.5 Ib (AE) A * NS NS NS NS NS 0. 5 d
1 Ib (AE) A * NS NS NS NS NS 0. 5 d
UC * NS NS NS
C92, CAL, 601(30)
C92, CAL, GN5
C92, CAL, 601(30)
148
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LUIS 5.2 - Page: 14
APPENDIX A REPORT
Case 2070 [Bromoxynil, and esters] Chemical 035302 [Bromoxynil octanoate]
44444444444444444444444444444444444
SITE Application Type, Application Form(s) Mln. Appl. Max. Appl. Soil Max. # Apps Max. Dose [(AI Mln. Re-
Timing, Application Equipment ) Rate (AI un- Rate (AI Tex. @ Max. Rate unless noted Interv Entry
Surface Type (Antimicrobial only) & Effica- less noted unless noted Max. /crop /year otherwise)/AI (days) Intv.
cy Influencing Factor (Antimicrobial only) otherwise) otherwise) Dose cycle /crop /year
cycle
USES ELIGIBLE FOR REREGISTRATION
FOOD/FEED USES (con't)
Use Group: TERRESTRIAL FOOD+FEED CROP (con't)
1 Ib (AE) A * NS NS
UC * NS NS
.5 Ib (AE) A * NS NS
NS NS NS 0. 5 d
NS NS NS 0. 5 d
NS NS NS 0. 5 d
149
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Time 11:48
APPENDIX A REPORT
Case 2070 [Bromoxynil, and esters] Chemical 035302 [Bromoxynil octanoate]
SITE Application Type, Application
Timing, Application Equipment )
Form(s) Min. Appl.
Rate (AI un-
Geoqraphic Limitations
USES ELIGIBLE FOR REREGISTRATION
FOOD/FEED USES (con't)
EC
EC
Use Group: TERRESTRIAL FOOD+FEED CROP (con't)
UC * NS NS NS NS NS 0. 5 d
Use Group: TERRESTRIAL FOOD CROP
NS NS NS 0. 5 d
150
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Time 11:48
LUIS 5.2 - Page:
APPENDIX A REPORT
Case 2070 [Bromoxynil, and esters] Chemical 035302 [Bromoxynil octanoate]
SITE Application Type, Application
Timing, Application Equipment )
Form(s) Min. Appl.
Rate (AI un-
Geographic Limitations
USES ELIGIBLE FOR REREGISTRATION
FOOD/FEED USES (con't)
ONION (con't)
Spray, Preemergence, Ground
PEPPERMINT
Broadcast, Dormant, Ground EC NA
EC NA
Broadcast, Established plantings, Ground EC NA
EC
Chemigation, Dormant, Sprinkler EC
irrigation
Chemigation, Established plantings, EC
Sprinkler irrigation
Spray, Dormant, Ground
Spray, Established plantings, Ground
RYE
Broadcast, Postemergence, Ground
Use Group: TERRESTRIAL FOOD CROP (con't)
UC * NS NS NS NS
Use Group: TERRESTRIAL FOOD+FEED CROP
NS NS 0. 5 d
NS NS 0. 5 d
Use Group: TERRESTRIAL FOOD+FEED CROP
* NS NS NS NS
151
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APPENDIX A REPORT
Case 2070 [Bromoxynil, and esters] Chemical 035302 [Bromoxynil octanoate]
SITE Application Type, Application
Timing, Application Equipment )
Form(s) Min. Appl.
Rate (AI un-
Geographic Limitations
USES ELIGIBLE FOR REREGISTRATION
FOOD/FEED USES (con't)
Spray, Postemergence, Aircraft
Use Group: TERRESTRIAL FOOD+FEED CROP (con't)
UC * NS NS NS NS NS 0. 5 d
UC * NS NS NS NS NS 0. 5 d
1 Ib (AE) A * NS NS
UC * NS NS
.5 Ib (AE) A * NS NS
NS NS 0. 5 d
NS NS 0. 5 d
NS NS 0. 5 d
Use Group: TERRESTRIAL FEED CROP
152
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APPENDIX A REPORT
Case 2070 [Bromoxynil, and esters] Chemical 035302 [Bromoxynil octanoate]
44444444444444444444444444444444444
SITE Application Type, Application Form(s) Mln. Appl. Max. Appl. Soil Max. # Apps Max. Dose [(AI Mln. Re-
Timing, Application Equipment ) Rate (AI un- Rate (AI Tex. @ Max. Rate unless noted Interv Entry
Surface Type (Antimicrobial only) & Effica- less noted unless noted Max. /crop /year otherwise)/AI (days) Intv.
cy Influencing Factor (Antimicrobial only) otherwise) otherwise) Dose cycle /crop /year
cycle
USES ELIGIBLE FOR REREGISTRATION
FOOD/FEED USES (con't)
Use Group: TERRESTRIAL FEED CROP (con't)
EC NA
EC NA
EC NA
EC NA
EC NA
EC NA
153
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Time 11:48
APPENDIX A REPORT
Case 2070 [Bromoxynil, and esters] Chemical 035302 [Bromoxynil octanoate]
SITE Application Type, Application
Timing, Application Equipment )
Form(s) Min. Appl.
Rate (AI un-
Geoqraphic Limitations
USES ELIGIBLE FOR REREGISTRATION
FOOD/FEED USES (con't)
FM/L
Use Group: TERRESTRIAL FEED CROP (con't)
UC * NS NS UC NS NS 0. 5 d
154
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APPENDIX A REPORT
Case 2070 [Bromoxynil, and esters] Chemical 035302 [Bromoxynil octanoate]
SITE Application Type, Application
Timing, Application Equipment )
Form(s) Min. Appl.
Rate (AI un-
Geoqraphic Limitations
USES ELIGIBLE FOR REREGISTRATION
FOOD/FEED USES (con't)
Use Group: TERRESTRIAL FEED CROP (con't)
EC NA
FM/L NA
NS NS 12 h
FM/L
WP NA
.375 Ib (AE) * 2 NS
A
155
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Time 11:48
APPENDIX A REPORT
Case 2070 [Bromoxynil, and esters] Chemical 035302 [Bromoxynil octanoate]
SITE Application Type, Application
Timing, Application Equipment )
Form(s) Min. Appl.
Rate (AI un-
Geoqraphic Limitations
USES ELIGIBLE FOR REREGISTRATION
FOOD/FEED USES (con't)
Spray, Preplant, Boom sprayer
WP NA
EC NA
EC NA
Use Group: TERRESTRIAL FEED CROP (con't)
UC NS NS 12 h
Use Group: TERRESTRIAL FOOD+FEED CROP
156
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APPENDIX A REPORT
Case 2070 [Bromoxynil, and esters] Chemical 035302 [Bromoxynil octanoate]
44444444444444444444444444444444444
SITE Application Type, Application Form(s) Mln. Appl. Max. Appl. Soil Max. # Apps Max. Dose [(AI Mln. Re-
Timing, Application Equipment ) Rate (AI un- Rate (AI Tex. @ Max. Rate unless noted Interv Entry
Surface Type (Antimicrobial only) & Effica- less noted unless noted Max. /crop /year otherwise)/AI (days) Intv.
cy Influencing Factor (Antimicrobial only) otherwise) otherwise) Dose cycle /crop /year
cycle
USES ELIGIBLE FOR REREGISTRATION
FOOD/FEED USES (con't)
Use Group: TERRESTRIAL FOOD+FEED CROP (con't)
EC NA
EC NA
EC NA
157
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Time 11:48
APPENDIX A REPORT
Case 2070 [Bromoxynil, and esters] Chemical 035302 [Bromoxynil octanoate]
SITE Application Type, Application
Timing, Application Equipment )
Form(s) Min. Appl.
Rate (AI un-
Max. Appl. Soil Max. # Apps Max. Dose [(AI Min. Re-
Rate (AI Tex. @ Max. Rate unless noted Interv Entry
unless noted Max. /crop /year otherwise)/AI (days) Intv.
otherwise) Dose cycle /crop /year
cycle
Geoqraphic Limitations
USES ELIGIBLE FOR REREGISTRATION
FOOD/FEED USES (con't)
EC NA
EC NA
FM/L
Use Group: TERRESTRIAL FOOD+FEED CROP (con't)
UC * 2 NS UC NS 7 0. 5 d
FM/L NA
Low volume spray (concentrate), Preplant, EC NA
Aircraft
158
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APPENDIX A REPORT
Case 2070 [Bromoxynil, and esters] Chemical 035302 [Bromoxynil octanoate]
SITE Application Type, Application
Timing, Application Equipment )
Form(s) Min. Appl.
Rate (AI un-
Geoqraphic Limitations
USES ELIGIBLE FOR REREGISTRATION
FOOD/FEED USES (con't)
Use Group: TERRESTRIAL FOOD+FEED CROP (con't)
FM/L NA
SC/L NA
NS NS 0. 5 d
159
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APPENDIX A REPORT
Case 2070 [Bromoxynil, and esters] Chemical 035302 [Bromoxynil octanoate]
SITE Application Type, Application
Timing, Application Equipment )
Form(s) Min. Appl.
Rate (AI un-
Geographic Limitations
USES ELIGIBLE FOR REREGISTRATION
FOOD/FEED USES (con't)
Use Group: TERRESTRIAL FOOD+FEED CROP (con't)
FM/L NA
SPEARMINT
Broadcast, Dormant, Ground EC NA
EC NA
Broadcast, Established plantings, Ground EC NA
EC
Chemigation, Dormant, Sprinkler EC
irrigation
Chemigation, Established plantings, EC
Sprinkler irrigation
Use Group: TERRESTRIAL FOOD+FEED CROP
160
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LUIS 5.2 - Page: 26
APPENDIX A REPORT
Case 2070 [Bromoxynil, and esters] Chemical 035302 [Bromoxynil octanoate]
SITE Application Type, Application
Timing, Application Equipment )
Form(s) Min. Appl.
Rate (AI un-
Geographic Limitations
USES ELIGIBLE FOR REREGISTRATION
FOOD/FEED USES (con't)
SPEARMINT (con't)
Spray, Established plantings, Ground SC/L NA
SUDANGRASS
Broadcast, Postemergence, Aircraft EC NA
EC NA
Spray, Postemergence, Aircraft
Spray, Postemergence, Ground
TRITICALE
Broadcast, Postemergence, Ground
EC
EC
Use Group: TERRESTRIAL FOOD+FEED CROP (con't)
UC * NS NS UC NS NS 0. 5 d
Use Group: TERRESTRIAL FEED CROP
* 2 NS .5 Ib NS NS 0.5 d
.5 Ib
(AE)
Use Group: TERRESTRIAL FOOD CROP
.5 Ib (AE) A * NS NS NS NS NS 0. 5 d
.5 Ib (AE) A * NS NS NS NS NS 0. 5 d
Use Group: TERRESTRIAL FOOD+FEED CROP
UC * NS NS NS NS NS 0. 5 d
UC * NS NS NS NS NS 0. 5 d
161
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LUIS 5.2 - Page:
APPENDIX A REPORT
Case 2070 [Bromoxynil, and esters] Chemical 035302 [Bromoxynil octanoate]
44444444444444444444444444444444444
SITE Application Type, Application Form(s) Mln. Appl. Max. Appl. Soil Max. # Apps Max. Dose [(AI Mln. Re-
Timing, Application Equipment ) Rate (AI un- Rate (AI Tex. @ Max. Rate unless noted Interv Entry
Surface Type (Antimicrobial only) & Effica- less noted unless noted Max. /crop /year otherwise)/AI (days) Intv.
cy Influencing Factor (Antimicrobial only) otherwise) otherwise) Dose cycle /crop /year
cycle
USES ELIGIBLE FOR REREGISTRATION
FOOD/FEED USES (con't)
TRITICALE (con't)
Spray, Postemergence, Aircraft
Spray, Postemergence, Ground
WHEAT
Broadcast, Postemergence, Ground
EC
EC
UC * NS NS UC NS NS 0. 5 d
Use Group: TERRESTRIAL FOOD+FEED CROP
NS NS NS 0. 5 d
162
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APPENDIX A REPORT
Case 2070 [Bromoxynil, and esters] Chemical 035302 [Bromoxynil octanoate]
SITE Application Type, Application
Timing, Application Equipment )
Form(s) Min. Appl.
Rate (AI un-
Geoqraphic Limitations
USES ELIGIBLE FOR REREGISTRATION
FOOD/FEED USES (con't)
)))))))))))))
WHEAT (con't)
EC
FM/L
SC/L
Use Group: TERRESTRIAL FOOD+FEED CROP (con't)
1 Ib (AE) A * NS NS NS NS NS 0. 5 d
UC * NS NS NS NS NS 0. 5 d
.5 Ib (AE) A * NS NS NS NS NS 0. 5 d
NS NS NS 0. 5 d
NS NS NS NS
UC NS NS 0. 5 d
NS NS NS NS
UC NS NS 0. 5 d
NS NS NS 0. 5 d
CAC
C92, CAL, 601(30)
C92, CAL, 601(30)
A6RICULTURAL FALLOW/IDLELAND
Broadcast, Postemergence, 6round
EC
EC
Use 6roup: TERRESTRIAL NON-FOOD CROP
1 Ib (AE) A * NS NS NS NS NS 0. 5 d
UC * NS NS NS NS NS 0. 5 d
.5 Ib (AE) A * NS NS NS NS NS 0. 5 d
C48, C92, CAL, 696
C92, CAL, 6K3
C92, CAL, 6K3
163
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APPENDIX A REPORT
Case 2070 [Bromoxynil, and esters] Chemical 035302 [Bromoxynil octanoate]
SITE Application Type, Application
Timing, Application Equipment )
Form(s) Min. Appl.
Rate (AI un-
Geographic Limitations
USES ELIGIBLE FOR REREGISTRATION
NON-FOOD/NON-FEED (con't)
AGRICULTURAL FALLOW/IDLELAND (con't)
Spray, When needed, Aircraft
SC/L NA
SC/L
SC/L
COMMERCIAL/INDUSTRIAL LAWNS
Broadcast, Established plantings, Ground EC
EC
Broadcast, Preemergence, Ground EC
EC
EC
UC * NS NS
.5 Ib (AE) A * NS NS
UC * NS NS
NS NS 0. 5 d
NS NS 0. 5 d
NS NS 0. 5 d
Use Group: TERRESTRIAL NON-FOOD CROP
UC * NS NS NS NS NS 0. 5 d
.5 Ib (AE) A * NS NS NS NS NS 0. 5 d
UC * NS NS NS NS NS 0. 5 d
.5 Ib (AE) A * NS NS NS NS NS 0. 5 d
UC * NS NS NS NS NS 0. 5 d
C92, CAL
C92, CAL, GK3
C92, CAL
C92, CAL, GK3
C92, CAL, CSA(IO)
164
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APPENDIX A REPORT
Case 2070 [Bromoxynil, and esters] Chemical 035302 [Bromoxynil octanoate]
SITE Application Type, Application
Timing, Application Equipment )
Form(s) Min. Appl.
Rate (AI un-
Geographic Limitations
USES ELIGIBLE FOR REREGISTRATION
NON-FOOD/NON-FEED (con't)
EC
Spray, Seedling stage, Aircraft
Spray, Seedling stage, Ground
GOLF COURSE TURF
Broadcast, Established plantings, Ground EC
EC
Broadcast, Preemergence, Ground EC
EC
EC
GRASSES GROWN FOR SEED
Broadcast, Established plantings, Ground EC NA
EC NA
Broadcast, Postemergence, Ground EC NA
Use Group: TERRESTRIAL NON-FOOD CROP
UC * NS NS NS NS NS 0. 5 d
.5 Ib (AE) A * NS NS NS NS NS 0. 5 d
UC * NS NS NS NS NS 0. 5 d
.5 Ib (AE) A * NS NS NS NS NS 0. 5 d
UC * NS NS NS NS NS 0. 5 d
Use Group: TERRESTRIAL NON-FOOD CROP
UC * NS NS NS NS NS 0. 5 d
.5 Ib (AE) A * NS NS NS NS NS 0. 5 d
1 Ib (AE) A * NS NS NS NS NS 0. 5 d
C92, CAL
C92, CAL, GK3
C92, CAL
C92, CAL, GK3
C92, CAL, CSA(IO)
165
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Time 11:49
31
APPENDIX A REPORT
Case 2070 [Bromoxynil, and esters] Chemical 035302 [Bromoxynil octanoate]
SITE Application Type, Application
Timing, Application Equipment )
Form(s) Min. Appl.
Rate (AI un-
Geographic Limitations
USES ELIGIBLE FOR REREGISTRATION
NON-FOOD/NON-FEED (con't)
EC
EC
EC
EC NA
EC NA
EC NA
Spray, Established plantings, Aircraft SC/L NA
Spray, Seedling stage, Ground
INDUSTRIAL AREAS (OUTDOOR)
Broadcast, When needed, Ground
Low volume spray (concentrate), When EC NA
needed, Aircraft
Use Group: TERRESTRIAL NON-FOOD CROP (con't)
UC * NS NS NS NS NS 0. 5 d
.5 Ib (AE) A * NS NS NS NS NS 0. 5 d
UC * NS NS NS NS NS 0. 5 d
UC * NS NS NS NS NS 0. 5 d
Use Group: TERRESTRIAL NON-FOOD CROP
NS NS NS 0. 5 d
166
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APPENDIX A REPORT
Case 2070 [Bromoxynil, and esters] Chemical 035302 [Bromoxynil octanoate]
44444444444444444444444444444444444
SITE Application Type, Application Form(s) Mln. Appl. Max. Appl. Soil Max. # Apps Max. Dose [(AI Mln. Re-
Timing, Application Equipment ) Rate (AI un- Rate (AI Tex. @ Max. Rate unless noted Interv Entry
Surface Type (Antimicrobial only) & Effica- less noted unless noted Max. /crop /year otherwise)/AI (days) Intv.
cy Influencing Factor (Antimicrobial only) otherwise) otherwise) Dose cycle /crop /year
cycle
USES ELIGIBLE FOR REREGISTRATION
NON-FOOD/NON-FEED (con't)
EC
NONAGRICULTURAL UNCULTIVATED AREAS/SOILS
Broadcast, When needed, Ground EC
Spray, Seedling stage, Aircraft
Spray, Seedling stage, Ground
ORNAMENTAL HERBACEOUS PLANTS
Broadcast, Dormant, Ground
EC NA
ORNAMENTAL LAWNS AND TURF
Broadcast, Established plantings, Ground EC NA
Use Group: TERRESTRIAL NON-FOOD CROP (con't)
UC * NS NS NS NS NS 0. 5 d
Use Group: TERRESTRIAL NON-FOOD CROP
NS NS NS 0. 5 d
.375 Ib (AE) *
A
167
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APPENDIX A REPORT
Case 2070 [Bromoxynil, and esters] Chemical 035302 [Bromoxynil octanoate]
SITE Application Type, Application
Timing, Application Equipment )
Form(s) Min. Appl.
Rate (AI un-
Geographic Limitations
USES ELIGIBLE FOR REREGISTRATION
NON-FOOD/NON-FEED (con't)
EC
EC
EC
EC
Spray, Established plantings, Aircraft SC/L NA
Spray, Established plantings, Ground SC/L NA
Spray, Seedling stage, Aircraft SC/L NA
NA
Spray, Seedling stage, Ground
ORNAMENTAL SOD FARM (TURF)
Broadcast, Established plantings, Ground EC
EC
Broadcast, Preemergence, Ground EC
EC
Use Group: TERRESTRIAL NON-FOOD CROP (con't)
.5 Ib (AE) A * NS NS NS NS NS 0. 5 d
UC * NS NS NS NS NS 0. 5 d
.5 Ib (AE) A * NS NS NS NS NS 0. 5 d
UC * NS NS NS NS NS 0. 5 d
UC * NS NS NS NS NS 0. 5 d
Use Group: TERRESTRIAL NON-FOOD CROP
UC * NS NS NS NS NS 0. 5 d
.5 Ib (AE) A * NS NS NS NS NS 0. 5 d
UC * NS NS NS NS NS 0. 5 d
.5 Ib (AE) A * NS NS NS NS NS 0. 5 d
C92, CAL, GK3
C92, CAL
C92, CAL, GK3
C92, CAL, CSA(IO)
C92, CAL, 695
C92, CAL, GK3
C92, CAL, G95
C92, CAL, GK3
168
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Time 11:49
APPENDIX A REPORT
Case 2070 [Bromoxynil, and esters] Chemical 035302 [Bromoxynil octanoate]
SITE Application Type, Application
Timing, Application Equipment )
Form(s) Min. Appl.
Rate (AI un-
Geographic Limitations
USES ELIGIBLE FOR REREGISTRATION
NON-FOOD/NON-FEED (con't)
Spray, Established plantings, Aircraft SC/L NA
Spray, Established plantings, Ground SC/L NA
Spray, Seedling stage, Aircraft SC/L NA
169
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APPENDIX A REPORT
Case 2070 [Bromoxynil, and esters] Chemical 035302 [Bromoxynil octanoate]
4444444
LEGEND
444444
Sort: Uses Eligible or Ineligible for Re-registration, Food/Feed or Non-Food/Non-Feed Uses, Alpha Site Name, Use Group Name, Alpha Application Type/Timing/Equipment
Description, Formulation, Maximum Application Rate Unit/Area Quantity, Minimum Application Rate
HEADER ABBREVIATIONS
Min. Appl. Rate (AI unless : Minimum dose for a single application to a single site. System calculated. Antimicrobial claims only.
noted otherwise)
Max. Appl. Rate (AI unless : Maximum dose for a single application to a single site. System calculated.
noted otherwise)
: Maximum dose for a single application to a single site as related to soil texture (Herbicide claims only).
: Maximum number of Applications at Maximum Dosage Rate. Example: "4 applications per year" is expressed as "4/1 yr"; "4 applications per 3
years" is expressed as "4/3 yr"
: Maximum dose applied to a site over a single crop cycle or year. System calculated.
Soil Tex. Max. Dose
Max. # Apps @ Max. Rate
Max. Dose [(AI unless
noted otherwise)/A]
Min. Interv (days)
Re-Entry Intv.
PRD Report Date
Minimum Interval between Applications (days)
Reentry Intervals
LUIS contains all products that were active or suspended (and that were available from OPP Document Center) as of this date. Some products
registered after this date may have data included in this report, but LUIS does not guarantee that all products registered after this date have
data that has been captured.
SOIL TEXTURE FOR MAX APP. RATE
* : Non-specific
C : Coarse
M : Medium
F : Fine
O : Others
EC : EMULSIFIABLE CONCENTRATE
FM/L : FORM NOT IDENTIFIED/LIQUID
SC/L : SOLUBLE CONCENTRATE/LIQUID
WP : WETTABLE POWDER
ABBREVIATIONS
AN : As Needed
NA : Not Applicable
NS : Not Specified (on label)
UC : Unconverted due to lack of data (on label), or with one of following units: bag, bait, bait block, bait pack, bait station, bait station(s), block, briquet,
briquets, bursts, cake, can, canister, capsule, cartridges, coil, collar, container, dispenser, drop, eartag, grains, lure, pack, packet, packets, pad, part,
parts, pellets, piece, pieces, pill, pumps, sec, sec burst, sheet, spike, stake, stick, strip, tab, tablet, tablets, tag, tape, towelette, tray, unit, --
APPLICATION RATE
DCNC : Dosage Can Not be Calculated
No Calc : No Calculation can be made
W : PPM calculated by weight
V : PPM Calculated by volume
U : Unknown whether PPM is given by weight or by volume
170
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LUIS 5.2 - Page:
APPENDIX A REPORT
Case 2070 [Bromoxynil, and esters] Chemical 035302 [Bromoxynil octanoate]
USE LIMITATIONS CODES
C13
C46
C48
C92
CAC
CAL
CCB
CSA
CWE
CWH
CWL
G01
G83
G95
G96
GC1
GK3
GN5
GN6
GO 3
GP1
HOI
Groundwater restriction.
Do not apply through any type of irrigation system.
Conservation Reserve Acres.
For terrestrial uses, do not apply directly to water or to areas where surface water is present or to intertidal areas below the mean high water mark.
Keep out of lakes, streams, and ponds.
Do not contaminate water, food or feed.
Rotational/plant back crop restriction.
Do not apply when wind velocity is mph or greater.
This product
highly toxic to birds, fish, and other wildlife. Birds, especially waterfowl, feeding or drinking on treated areas may be killed.
Do not contaminate water by cleaning of equipment or disposal of equipment wash waters.
Do not contaminate water, food, or feed by storage or disposal.
day(s) pregrazing interval.
day(s) prefeeding interval.
Do not feed to livestock.
Do not graze livestock in treated areas or cut treated crops for feed.
Do not graze treated areas.
Do not feed forage to livestock or allow livestock to graze in treated areas.
Do not graze treated fields for 30 days following treatment.
Do not cut crop for feed or graze within 30 days after application.
Do not cut green crop for feed or forage purposes.
Do not graze or feed treated crop to livestock.
day(s) preharvest interval.
NUMBER IN PARENTHESES REPRESENTS THE NUMBER OF TIME UNITS (HOURS,DAYS, ETC.) DESCRIBED IN THE LIMITATION.
GEOGRAPHIC CODES
West of the Mississippi River
East of the Mississippi River
California
Colorado
Michigan
Montana
Oregon
Washington
Wisconsin
Wyoming
REENTRY INTERVAL ABBREVIATIONS
d : day(s)
h : hour(s)
UNIT DESCRIPTIONS
171
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APPENDIX A REPORT
Case 2070 [Bromoxynil, and esters] Chemical 128920 [3,5-Dibromo-4-hydroxyphenyl cyanide heptanoate]
44444444444444444444444444444444444
SITE Application Type, Application Form(s) Mln. Appl. Max. Appl. Soil Max. # Apps Max. Dose [(AI Mln. Re-
Timing, Application Equipment ) Rate (AI un- Rate (AI Tex. @ Max. Rate unless noted Interv Entry
Surface Type (Antimicrobial only) & Effica- less noted unless noted Max. /crop /year otherwise)/AI (days) Intv.
cy Influencing Factor (Antimicrobial only) otherwise) otherwise) Dose cycle /crop /year
cycle
USES ELIGIBLE FOR REREGISTRATION
FOOD/FEED USES
EC NA
Use Group: TERRESTRIAL FEED CROP
Chemigation, Seedling stage, Moving wheel EC
irrigation
Spray, Seedling stage, Aircraft
Use Group: TERRESTRIAL FOOD+FEED CROP
.3701 Ib A * NS NS NS NS NS 0. 5 d
.3701 Ib A * NS NS NS NS NS 0. 5 d
172
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APPENDIX A REPORT
Case 2070 [Bromoxynil, and esters] Chemical 128920 [3,5-Dibromo-4-hydroxyphenyl cyanide heptanoate]
44444444444444444444444444444444444
SITE Application Type, Application Form(s) Mln. Appl. Max. Appl. Soil Max. # Apps Max. Dose [(AI Mln. Re-
Timing, Application Equipment ) Rate (AI un- Rate (AI Tex. @ Max. Rate unless noted Interv Entry
Surface Type (Antimicrobial only) & Effica- less noted unless noted Max. /crop /year otherwise)/AI (days) Intv.
cy Influencing Factor (Antimicrobial only) otherwise) otherwise) Dose cycle /crop /year
cycle
USES ELIGIBLE FOR REREGISTRATION
FOOD/FEED USES (con't)
BARLEY (con't)
UC * NS NS UC NS NS 0. 5 d
.3523 Ib A * NS NS NS NS NS 0.5 d
Use Group: TERRESTRIAL FOOD+FEED CROP
.5552 Ib A * 2 NS .5552 NS 7 0.5 d
Ib
173
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APPENDIX A REPORT
Case 2070 [Bromoxynil, and esters] Chemical 128920 [3,5-Dibromo-4-hydroxyphenyl cyanide heptanoate]
SITE Application Type, Application
Timing, Application Equipment )
Form(s) Min. Appl.
Rate (AI un-
Geographic Limitations
USES ELIGIBLE FOR REREGISTRATION
FOOD/FEED USES (con't)
Spray, Preemergence, Aircraft
Use Group: TERRESTRIAL FOOD+FEED CROP (con't)
Use Group: TERRESTRIAL FOOD+FEED CROP
174
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APPENDIX A REPORT
Case 2070 [Bromoxynil, and esters] Chemical 128920 [3,5-Dibromo-4-hydroxyphenyl cyanide heptanoate]
44444444444444444444444444444444444
SITE Application Type, Application Form(s) Mln. Appl. Max. Appl. Soil Max. # Apps Max. Dose [(AI Mln. Re-
Timing, Application Equipment ) Rate (AI un- Rate (AI Tex. @ Max. Rate unless noted Interv Entry
Surface Type (Antimicrobial only) & Effica- less noted unless noted Max. /crop /year otherwise)/AI (days) Intv.
cy Influencing Factor (Antimicrobial only) otherwise) otherwise) Dose cycle /crop /year
cycle
USES ELIGIBLE FOR REREGISTRATION
FOOD/FEED USES (con't)
EC NA
Use Group: TERRESTRIAL FOOD+FEED CROP (con't)
.5552 Ib A
.5552
Ib
EC NA
EC NA
.5552 NS NS 0.5 d
Ib
.5552 Ib A
.5552
Ib
C92, CAL, GN6
CCB, CWE,
175
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APPENDIX A REPORT
Case 2070 [Bromoxynil, and esters] Chemical 128920 [3,5-Dibromo-4-hydroxyphenyl cyanide heptanoate]
44444444444444444444444444444444444
SITE Application Type, Application Form(s) Mln. Appl. Max. Appl. Soil Max. # Apps Max. Dose [(AI Mln. Re-
Timing, Application Equipment ) Rate (AI un- Rate (AI Tex. @ Max. Rate unless noted Interv Entry
Surface Type (Antimicrobial only) & Effica- less noted unless noted Max. /crop /year otherwise)/AI (days) Intv.
cy Influencing Factor (Antimicrobial only) otherwise) otherwise) Dose cycle /crop /year
cycle
USES ELIGIBLE FOR REREGISTRATION
FOOD/FEED USES (con't)
CORN, SWEET
Spray, Postemergence, Aircraft
SC/L NA
Spray, Preemergence, Ground SC/L NA
COTTON (UNSPECIFIED)
Band treatment, Postemergence, Ground EC NA
Band treatment, Preemergence, Ground EC NA
EC NA
EC NA
EC NA
Use Group: TERRESTRIAL FOOD+FEED CROP
UC * NS NS UC NS NS 0. 5 d
UC * NS NS UC NS NS 0. 5 d
Use Group: TERRESTRIAL FOOD+FEED CROP
.3701 Ib A * 3 NS 1.11 Ib NS NS 0.5 d
176
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LUIS 5.2 - Page:
APPENDIX A REPORT
Case 2070 [Bromoxynil, and esters] Chemical 128920 [3,5-Dibromo-4-hydroxyphenyl cyanide heptanoate]
SITE Application Type, Application
Timing, Application Equipment )
Form(s) Min. Appl.
Rate (AI un-
Geographic Limitations
USES ELIGIBLE FOR REREGISTRATION
FOOD/FEED USES (con't)
COTTON (UNSPECIFIED) (con't)
Broadcast, Preplant, Ground
Spray, Postemergence, Aircraft
Spray, Postemergence, Ground
GARLIC
Broadcast, Postemergence, Ground
EC
EC
EC
EC
Use Group: TERRESTRIAL FOOD+FEED CROP
.1851 Ib A * NS NS NS NS NS 0. 5 d
.1851 Ib A * NS NS NS NS NS 0. 5 d
Use Group: TERRESTRIAL FOOD CROP
.3701 Ib A * NS NS NS NS NS 0. 5 d
.3701 Ib A * NS NS NS NS NS 0. 5 d
177
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LUIS 5.2 - Page:
APPENDIX A REPORT
Case 2070 [Bromoxynil, and esters] Chemical 128920 [3,5-Dibromo-4-hydroxyphenyl cyanide heptanoate]
44444444444444444444444444444444444
SITE Application Type, Application Form(s) Mln. Appl. Max. Appl. Soil Max. # Apps Max. Dose [(AI Mln. Re-
Timing, Application Equipment ) Rate (AI un- Rate (AI Tex. @ Max. Rate unless noted Interv Entry
Surface Type (Antimicrobial only) & Effica- less noted unless noted Max. /crop /year otherwise)/AI (days) Intv.
cy Influencing Factor (Antimicrobial only) otherwise) otherwise) Dose cycle /crop /year
cycle
USES ELIGIBLE FOR REREGISTRATION
FOOD/FEED USES (con't)
EC NA
Use Group: TERRESTRIAL FOOD+FEED CROP
Spray, Postemergence, Aircraft
.3701 Ib A * NS NS
SC/L NA
Use Group: TERRESTRIAL FOOD CROP
.2776 Ib A * NS NS NS NS NS 0.5 d
178
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LUIS 5.2 - Page:
APPENDIX A REPORT
Case 2070 [Bromoxynil, and esters] Chemical 128920 [3,5-Dibromo-4-hydroxyphenyl cyanide heptanoate]
SITE Application Type, Application
Timing, Application Equipment )
Form(s) Min. Appl.
Rate (AI un-
Geographic Limitations
USES ELIGIBLE FOR REREGISTRATION
FOOD/FEED USES (con't)
ONION (con't)
Broadcast, Preemergence, Ground
Broadcast, Preplant, Ground
EC
EC
EC
Spray, Postemergence, Ground
Spray, Preemergence, Aircraft
Spray, Preemergence, Ground
PEPPERMINT
Broadcast, Dormant, Ground
NA
Spray, Dormant, Ground SC/L NA
Spray, Established plantings, Ground SC/L NA
RYE
Broadcast, Postemergence, Ground EC NA
Use Group: TERRESTRIAL FOOD CROP (con't)
.2776 Ib A * NS NS NS NS NS 0.5 d
.2776 Ib A * NS NS NS NS NS 0.5 d
.2776 Ib A * NS NS NS NS NS 0.5 d
UC * NS NS
UC * NS NS
UC * NS NS
NS NS NS 0. 5 d
NS NS NS 0. 5 d
NS NS NS 0. 5 d
Use Group: TERRESTRIAL FOOD+FEED CROP
Use Group: TERRESTRIAL FOOD+FEED CROP
.3701 Ib A * NS NS NS NS NS 0. 5 d
179
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APPENDIX A REPORT
Case 2070 [Bromoxynil, and esters] Chemical 128920 [3,5-Dibromo-4-hydroxyphenyl cyanide heptanoate]
44444444444444444444444444444444444
SITE Application Type, Application Form(s) Mln. Appl. Max. Appl. Soil Max. # Apps Max. Dose [(AI Mln. Re-
Timing, Application Equipment ) Rate (AI un- Rate (AI Tex. @ Max. Rate unless noted Interv Entry
Surface Type (Antimicrobial only) & Effica- less noted unless noted Max. /crop /year otherwise)/AI (days) Intv.
cy Influencing Factor (Antimicrobial only) otherwise) otherwise) Dose cycle /crop /year
cycle
USES ELIGIBLE FOR REREGISTRATION
FOOD/FEED USES (con't)
Use Group: TERRESTRIAL FEED CROP
.5552 Ib A * 2 NS .5552 NS 7 0.5 d
Ib
180
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APPENDIX A REPORT
Case 2070 [Bromoxynil, and esters] Chemical 128920 [3,5-Dibromo-4-hydroxyphenyl cyanide heptanoate]
44444444444444444444444444444444444
SITE Application Type, Application Form(s) Mln. Appl. Max. Appl. Soil Max. # Apps Max. Dose [(AI Mln. Re-
Timing, Application Equipment ) Rate (AI un- Rate (AI Tex. @ Max. Rate unless noted Interv Entry
Surface Type (Antimicrobial only) & Effica- less noted unless noted Max. /crop /year otherwise)/AI (days) Intv.
cy Influencing Factor (Antimicrobial only) otherwise) otherwise) Dose cycle /crop /year
cycle
USES ELIGIBLE FOR REREGISTRATION
FOOD/FEED USES (con't)
Use Group: TERRESTRIAL FEED CROP (con't)
Low volume spray (concentrate), Preplant, EC
Aircraft
Spray, Postemergence, Aircraft
C92, CAL, GN6
CCB, CWE,
181
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LUIS 5.2 - Page: 11
APPENDIX A REPORT
Case 2070 [Bromoxynil, and esters] Chemical 128920 [3,5-Dibromo-4-hydroxyphenyl cyanide heptanoate]
44444444444444444444444444444444444
SITE Application Type, Application Form(s) Mln. Appl. Max. Appl. Soil Max. # Apps Max. Dose [(AI Mln. Re-
Timing, Application Equipment ) Rate (AI un- Rate (AI Tex. @ Max. Rate unless noted Interv Entry
Surface Type (Antimicrobial only) & Effica- less noted unless noted Max. /crop /year otherwise)/AI (days) Intv.
cy Influencing Factor (Antimicrobial only) otherwise) otherwise) Dose cycle /crop /year
cycle
USES ELIGIBLE FOR REREGISTRATION
FOOD/FEED USES (con't)
EC NA
EC NA
Use Group: TERRESTRIAL FEED CROP (con't)
.02644 gal A * NS NS NS NS NS 12 h
Use Group: TERRESTRIAL FOOD+FEED CROP
.5552 Ib A
2 NS .5552 NS 7 0.5 d
EC NA
.2776 Ib A * NS NS .5552
Ib
.3701 Ib A * NS NS .5552 NS NS 0.5 d
.3701 Ib A * NS NS .5552 NS NS 0.5 d
.2776 Ib A * NS NS .5552 NS NS 0.5 d
NS NS 0. 5 d
182
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12
APPENDIX A REPORT
Case 2070 [Bromoxynil, and esters] Chemical 128920 [3,5-Dibromo-4-hydroxyphenyl cyanide heptanoate]
SITE Application Type, Application
Timing, Application Equipment )
Form(s) Min. Appl.
Rate (AI un-
Geographic Limitations
USES ELIGIBLE FOR REREGISTRATION
FOOD/FEED USES (con't)
SORGHUM (con't)
Spray, Postemergence, Ground
Spray, Postemergence, Sprayer
SPEARMINT
Broadcast, Dormant, Ground
SC/L
WP
SC/L
WP
Spray, Dormant, Ground
Spray, Established plantings, Ground
SUDANGRASS
Spray, Postemergence, Aircraft
Spray, Postemergence, Ground
TRITICALE
Broadcast, Postemergence, Ground
Use Group: TERRESTRIAL FOOD+FEED CROP (con't)
UC * 2 NS UC NS 7 0. 5 d
.01763 gal A * NS NS NS NS NS 12 h
Use Group: TERRESTRIAL FOOD+FEED
Ib A * NS NS
.2776 Ib A
NS NS 0. 5 d
Use Group: TERRESTRIAL FEED CROP
UC * NS NS NS
UC * NS NS NS
Use Group: TERRESTRIAL FOOD+FEED
Ib A * NS NS NS
Ib A * NS NS NS
183
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APPENDIX A REPORT
Case 2070 [Bromoxynil, and esters] Chemical 128920 [3,5-Dibromo-4-hydroxyphenyl cyanide heptanoate]
44444444444444444444444444444444444
SITE Application Type, Application Form(s) Mln. Appl. Max. Appl. Soil Max. # Apps Max. Dose [(AI Mln. Re-
Timing, Application Equipment ) Rate (AI un- Rate (AI Tex. @ Max. Rate unless noted Interv Entry
Surface Type (Antimicrobial only) & Effica- less noted unless noted Max. /crop /year otherwise)/AI (days) Intv.
cy Influencing Factor (Antimicrobial only) otherwise) otherwise) Dose cycle /crop /year
cycle
USES ELIGIBLE FOR REREGISTRATION
FOOD/FEED USES (con't)
TRITICALE (con't)
Spray, Postemergence, Ground
WHEAT
Broadcast, Postemergence, Ground
EC
EC
UC * NS NS UC NS NS 0. 5 d
Use Group: TERRESTRIAL FOOD+FEED CROP
.3701 Ib A * NS NS NS NS NS 0. 5 d
.3701 Ib A * NS NS NS NS NS 0. 5 d
184
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14
APPENDIX A REPORT
Case 2070 [Bromoxynil, and esters] Chemical 128920 [3,5-Dibromo-4-hydroxyphenyl cyanide heptanoate]
SITE Application Type, Application
Timing, Application Equipment )
Form(s) Min. Appl.
Rate (AI un-
Geographic Limitations
USES ELIGIBLE FOR REREGISTRATION
FOOD/FEED USES (con't)
)))))))))))))
WHEAT (con't)
EC NA
AGRICULTURAL FALLOW/IDLELAND
Broadcast, Postemergence, Ground
Spray, When needed, Aircraft
EC
EC
SC/L NA
SC/L NA
COMMERCIAL/INDUSTRIAL LAWNS
Broadcast, Established plantings, Ground EC NA
Use Group: TERRESTRIAL NON-FOOD CROP
.3701 Ib A * NS NS NS NS NS 0. 5 d
.3701 Ib A * NS NS NS NS NS 0. 5 d
185
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APPENDIX A REPORT
Case 2070 [Bromoxynil, and esters] Chemical 128920 [3,5-Dibromo-4-hydroxyphenyl cyanide heptanoate]
SITE Application Type, Application
Timing, Application Equipment )
Form(s) Min. Appl.
Rate (AI un-
Geographic Limitations
USES ELIGIBLE FOR REREGISTRATION
NON-FOOD/NON-FEED (con't)
COMMERCIAL/INDUSTRIAL LAWNS (con't)
Broadcast, Preemergence, Ground
EC
EC
Spray, Seedling stage, Aircraft
Spray, Seedling stage, Ground
GOLF COURSE TURF
Broadcast, Established plantings, Ground
Broadcast, Preemergence, Ground
EC
EC
EC
GRASSES GROWN FOR SEED
Broadcast, Established plantings, Ground
Broadcast, Preemergence, Ground
EC
EC
EC
Use Group: TERRESTRIAL NON-FOOD CROP (con't)
.3701 Ib A * NS NS NS NS NS 0. 5 d
.3701 Ib A * NS NS NS NS NS 0. 5 d
Use Group: TERRESTRIAL NON-FOOD CROP
.3701 Ib A * NS NS NS NS NS 0. 5 d
.3701 Ib A * NS NS NS NS NS 0. 5 d
.3701 Ib A * NS NS NS NS NS 0. 5 d
Use Group: TERRESTRIAL NON-FOOD CROP
.3701 Ib A * NS NS NS NS NS 0. 5 d
.3701 Ib A * NS NS NS NS NS 0. 5 d
.3701 Ib A * NS NS NS NS NS 0. 5 d
186
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LUIS 5.2 - Page:
APPENDIX A REPORT
Case 2070 [Bromoxynil, and esters] Chemical 128920 [3,5-Dibromo-4-hydroxyphenyl cyanide heptanoate]
SITE Application Type, Application
Timing, Application Equipment )
Form(s) Min. Appl.
Rate (AI un-
Geographic Limitations
Spray, Seedling stage, Ground
ORNAMENTAL LAWNS AND TURF
Broadcast, Established plantings, Ground EC
Broadcast, Preemergence, Ground EC
EC
USES ELIGIBLE FOR REREGISTRATION
NON-FOOD/NON-FEED (con't)
)))))))))))))))))))))))));
GRASSES GROWN FOR SEED (con't)
Spray, Established plantings, Aircraft SC/L NA
Spray, Established plantings, Ground
Spray, Seedling stage, Aircraft
Spray, Seedling stage, Ground
INDUSTRIAL AREAS (OUTDOOR)
Broadcast, When needed, Ground EC
EC
NONAGRICULTURAL UNCULTIVATED AREAS/SOILS
Broadcast, When needed, Ground EC
EC
UC * NS NS NS NS NS 0. 5 d
Use Group: TERRESTRIAL NON-FOOD CROP
.3701 Ib A * NS NS NS NS NS 0. 5 d
.3701 Ib A * NS NS NS NS NS 0. 5 d
Use Group: TERRESTRIAL NON-FOOD CROP
.3701 Ib A * NS NS NS NS NS 0. 5 d
.3701 Ib A * NS NS NS NS NS 0. 5 d
UC * NS NS NS NS NS 0. 5 d
Use Group: TERRESTRIAL NON-FOOD CROP
.3701 Ib A * NS NS NS NS NS 0. 5 d
.3701 Ib A * NS NS NS NS NS 0. 5 d
.3701 Ib A * NS NS NS NS NS 0. 5 d
187
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APPENDIX A REPORT
Case 2070 [Bromoxynil, and esters] Chemical 128920 [3,5-Dibromo-4-hydroxyphenyl cyanide heptanoate]
SITE Application Type, Application
Timing, Application Equipment )
Form(s) Min. Appl.
Rate (AI un-
Geographic Limitations
USES ELIGIBLE FOR REREGISTRATION
NON-FOOD/NON-FEED (con't)
Spray, Established plantings, Aircraft SC/L
Spray, Established plantings, Ground
Spray, Seedling stage, Aircraft
Spray, Seedling stage, Ground
ORNAMENTAL SOD FARM (TURF)
Broadcast, Established plantings, Ground EC
EC
EC
Spray, Established plantings, Aircraft SC/L
NA
Spray, Established plantings, Ground SC/L NA
Spray, Seedling stage, Aircraft SC/L NA
SC/L NA
UC * NS NS NS NS NS 0. 5 d
Use Group: TERRESTRIAL NON-FOOD CROP
.3701 Ib A * NS NS NS NS NS 0. 5 d
.3701 Ib A * NS NS NS NS NS 0. 5 d
.3701 Ib A * NS NS NS NS NS 0. 5 d
188
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18
APPENDIX A REPORT
Case 2070 [Bromoxynil, and esters] Chemical 128920 [3,5-Dibromo-4-hydroxyphenyl cyanide heptanoate]
LEGEND
444444
HEADER ABBREVIATIONS
Min. Appl. Rate (AI unless : Minimum dose for a single application to a single site. System calculated. Antimicrobial claims only.
noted otherwise)
Max. Appl. Rate (AI unless : Maximum dose for a single application to a single site. System calculated.
noted otherwise)
: Maximum dose for a single application to a single site as related to soil texture (Herbicide claims only).
: Maximum number of Applications at Maximum Dosage Rate. Example: "4 applications per year" is expressed as "4/1 yr"; "4 applications per 3
years" is expressed as "4/3 yr"
: Maximum dose applied to a site over a single crop cycle or year. System calculated.
Max. Dose [(AI unless
noted otherwise)/A]
Min. Interv (days)
Re-Entry Intv.
PRD Report Date
Minimum Interval between Applications (days)
Reentry Intervals
LUIS contains all products that were active or suspended (and that were available from OPP Document Center) as of this date. Some products
registered after this date may have data included in this report, but LUIS does not guarantee that all products registered after this date have
data that has been captured.
SOIL TEXTURE FOR MAX APP. RATE
* : Non-specific
C : Coarse
M : Medium
F : Fine
O : Others
EC : EMULSIFIABLE CONCENTRATE
SC/L : SOLUBLE CONCENTRATE/LIQUID
WP : WETTABLE POWDER
ABBREVIATIONS
AN : As Needed
NA : Not Applicable
NS : Not Specified (on label)
UC : Unconverted due to lack of data (on label), or with one of following units: bag, bait, bait block, bait pack, bait station, bait station(s), block, briquet,
briquets, bursts, cake, can, canister, capsule, cartridges, coil, collar, container, dispenser, drop, eartag, grains, lure, pack, packet, packets, pad, part,
parts, pellets, piece, pieces, pill, pumps, sec, sec burst, sheet, spike, stake, stick, strip, tab, tablet, tablets, tag, tape, towelette, tray, unit, --
APPLICATION RATE
DCNC : Dosage Can Not be Calculated
No Calc : No Calculation can be made
W : PPM calculated by weight
V : PPM Calculated by volume
U : Unknown whether PPM is given by weight or by volume
189
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Time 11:57
APPENDIX A REPORT
Case 2070 [Bromoxynil, and esters] Chemical 128920 [3,5-Dibromo-4-hydroxyphenyl cyanide heptanoate]
USE LIMITATIONS CODES
Do not apply through any type of irrigation system.
For terrestrial uses, do not apply directly to water or to areas where surface water is present or to intertidal areas below the mean high water mark.
Do not contaminate water, food or feed.
Rotational/plant back crop restriction.
Do not apply when wind velocity is mph or greater.
This product is highly toxic to birds, fish, and other wildlife. Birds, especially waterfowl, feeding or drinking on treated areas may be killed.
Do not contaminate water by cleaning of equipment or disposal of equipment wash waters.
Do not contaminate water, food, or feed by storage or disposal.
day(s) pregrazing interval.
day(s) prefeeding interval.
Do not feed to livestock.
Do not graze treated areas.
Do not feed forage to livestock or allow livestock to graze in treated areas.
Do not cut crop for feed or graze within 30 days after application.
Do not cut green crop for feed or forage purposes.
Do not graze or feed treated crop to livestock.
day(s) preharvest interval.
NUMBER IN PARENTHESES REPRESENTS THE NUMBER OF TIME UNITS (HOURS,DAYS, ETC.) DESCRIBED IN THE LIMITATION.
GEOGRAPHIC CODES
West of the Mississippi River
California
Colorado
Montana
REENTRY INTERVAL ABBREVIATIONS
d : day(s)
h : hour(s)
UNIT DESCRIPTIONS
A :
gal :
Ib :
190
-------
GUIDE TO APPENDIX B
Appendix B contains listings of data requirements which support the reregi strati on for active
ingredients within the case BROMOXYNIL covered by this Reregi strati on Eligibility Decision
Document. It contains generic data requirements that apply to BROMOXYNIL in all products,
including data requirements for which a "typical formulation" is the test substance.
The data table is organized in the following format:
1. Data Requirement (Column 1). The data requirements are listed in the order in which they
appear in 40 CFR Part 158. the reference numbers accompanying each test refer to the test protocols
set in the Pesticide Assessment Guidelines, which are available from the National Technical
Information Service, 5285 Port Royal Road, Springfield, VA 22161 (703) 487-4650.
2. Use Pattern (Column 2). 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 non-food
D Aquatic food
E Aquatic non-food outdoor
F Aquatic non-food industrial
G Aquatic non-food residential
H Greenhouse food
I Greenhouse non-food
J Forestry
K Residential
L Indoor food
M Indoor non-food
N Indoor medical
O Indoor residential
3. Bibliographic citation (Column 3). If the Agency has acceptable data in its files, this column lists
the identifying number of each study. This normally 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 for a complete citation of the study.
191
-------
192
-------
APPENDIX B
Data Supporting Guideline Requirements
for the Reregistration of Bromoxynil
REQUIREMENT
USE PATTERN CITATION(S)(MRID#)
PRODUCT CHEMISTRY
61-1 Chemical Identity
61-2A Start. Mat. & Mnfg. Process
61-2B Formation of Impurities
62-1 Preliminary Analysis
62-2 Certification of Limits
62-3 Analytical Method
63-2 Color
63-3 Physical State
63-4 Odor
63-5 Melting Point
63-7 Density
63-8 Solubility
63-9 Vapor Pressure
63-10 Dissociation Constant
63-11 Octanol/Water Partition
63-12 pH
63-13 Stability
63-14 Oxidizing/Reducing Action
63-17 Storage Stability
63-18 Viscosity
ALL
ALL
ALL
ALL
ALL
ALL
ALL
ALL
ALL
ALL
ALL
ALL
ALL
ALL
ALL
ALL
ALL
ALL
ALL
All
41943901
41943901
41943901
41943901
41943901
41943901
41943901
41943901
41943901
41943901
42333601, 41943901
41943901, 42087401
41943901,42130101
42066401
41943901, 42333601
41943901, 42333601
41943901
42333601
42333601
41943901
TOXICOLOGY
81-1 Acute Oral Toxicity - Rat
81-2
Acute Dermal Toxicity - Rabbit/Rat
A,B,C,K,
L,M
A,B,C,K,
L,M
00124758,00124112
00124758,00124112
193
-------
Data Supporting Guideline Requirements
for the Reregistration of Bromoxynil
REQUIREMENT
81-3
81-4
81-5
81-6
81-8
82-1A
82-1A
Acute Inhalation Toxicity - Rat
Primary Eye Irritation - Rabbit
Primary Dermal Irritation - Rabbit
Dermal Sensitization - Guinea Pig
Acute Neurotoxicity - Rat
90-Day Feeding - Rat
90-Day Feeding - Mouse
USE PATTERN
A,B,C,K,
L,M
A,B,C,K,
L,M
A,B,C,K,
L,M
A,B,C,K,
L,M
A,B,C,K,
L,M
A,B,C,K,
L,M
A,B,C,K,
L,M
CITATION(S)(MRID#)
43014701,42167101
00124758,00124112
00124758,00124112
42718701,41879801
Reserved
41469101,42411901
42553401
82-IB 90-Day Feeding - Non-rodent
82-3 90-day Dermal - Rabbit
82-7 90-Day Neurotoxicity - Rat
83-1A Chronic Feeding Toxicity- Rat
83-1B Chronic Feeding Toxicity - Non-rodent
8 3 -2 A Oncogeni city - Rat
83-2B Oncogeni city - Mouse
83-3A Developmental Toxicity - Rat
83-3B Developmental Toxicity - Rabbit
A,B,C,K, L,M
A,B,C,K, L,M
A,B,C,K,
L,M
A,B,C,K, L,M
A,B,C,K, L,M
A,B,D,H,L
A,B,D,H,L
A,B,C,K,
L,M
ABDHL
43166701,42869701,
43700201,00061179
42272301, 42346201
Reserved
00096521, 40612501,
41374801
40780301, 41304701
00096521, 40612501,
41374801
00068077, 43245501,
43311701
40466802,00116558,
40881201,40883601,
41163301
00138149, 00142779,
40935101,41307801,
41471901,42183901
194
-------
Data Supporting Guideline Requirements
for the Reregistration of Bromoxynil
REQUIREMENT
USE PATTERN CITATION(S)(MRID#)
83-4 2-Generation Reproduction - Rat
84-2A Gene Mutation (Ames Test)
84-2B Structural Chromosomal Aberration
84-4 Other Genotoxic Effects
85-1 General Metab oli sm
A,B,C,K,
L,M
A,B,C,K,
L,M
A,B,C,K,
L,M
A,B,C,K,
L,M
A,B,D,H,L
41149301,00064815,
41667401
41995701, 43022701,
00115649,41995702
00115651,00124803,
42092301, 41930802
00115646,001156547,
00115648,00115650,
42078901
43191401,00154756,
00154757, 42901001,
85-2 Dermal Penetration
85-7 Immunotoxicity
ENVIRONMENTAL FATE
161-1 Hydrolysis
161-2
161-3
162-1
162-3
162-4
163-1
164-1
166-1
166-2
Photodegredation - Water
Photoegradation - Soil
Aerobic Soil Metabolism
Anaerobic Aquatic Metabolism
Aerobic Aquatic Metabolism
Leach/adsorp/desorp
Terrestrial Field Dissipation
Small Scale Prospective - Groundwater
Small Scale Retrospective - Groundwater
ALL
A,B,C,K, L,M
A,B,C,K,
L,M
A,B,C,D
E,F,G,J
A,B,C,J
A,B,C,H I,J,K
A,B,C,D
E,F,G,J
D,E,F,G J
A,B,C,D
E,F,G,H I,J,K
A,B,C,K
A,B,C,K
A,B,C,K
40854602, 40854603
Reserved
41892901, 00130424
42234301, 41920401
41920402
42234302, 41897701,
00142958
42234303, 41892902
42364901
42271101,43775001
41653701,43071001
Reserved
Reserved
195
-------
Data Supporting Guideline Requirements
for the Reregistration of Bromoxynil
REQUIREMENT
USE PATTERN
CITATION(S)(MRID#)
ENVIRONMENTAL TOXICOLOGY
71-1A
71-2A/B
71-4A/B
72-1 A
72- 1C
72-2A
72-3A
72-3C
72-4A
72-4B
123-2
141-1
172-4
Acute Avian - Oral
Acute Avian - Dietary, Quail/Duck
Avain Repro - Quail/Duck
Fish Toxicity - Bluegill
Fish Toxicity - Rainbow Trout
Invertebrate Toxicity
Estuarine/Marine Toxicity - Fish
Estuarine/Marine Toxicity - Shrimp
Early Life Stage - Fish
Early Life Stage - Invertebrate
Seed Germ/Emergence - Vegatative
Vigor
Honey Bee Acute Contact
Estuarine/Marine Organisms - Chronic
A,B,C,D,
E,F,J,K
A,B,C,D,
E,F,J,K
A,B,C,D,
E,F,J,K
A,B,C,D,
E,F,J,K
A,B,C,D,
E,F,J,K
A,B,C,D,
E,F,J,K
A,B,C,D,
E,F,J,K
A,B,C,D,
E,F,J,K
A,B,C,D,
E,F,J,K
A,B,C,D,
E,F,J,K
A,B,C,D,
E,F,J,K
A,B,C,D,
E,F,J,K
A,B,C,D,
E,F,J,K
248229, 258887,
43030001
4303002, 248229,
258886, 258888, 247924
42004101, 42475801,
42004102
248229, 43059601,
247924, 264229, 072254,
260441
247924, 260441, 248229,
00138087
42250601
42244501, 43487601
41928301,4011103
41928302,40111001
43633701,4160601,
41606002, 41606004,
4 1606005; Data Gap
00018842
Data Gap
196
-------
Data Supporting Guideline Requirements
for the Reregistration of Bromoxynil
REQUIREMENT
USE PATTERN CITATION(S)(MRID#)
RESIDUE CHEMISTRY
860.1200 Directions for Use
860.1300 Plant Metabolism
860.1300 Livestock Metabolism
860.1340 Residue Analytical Methods
860.1360 Multiresidue Methods - Plants and
Livestock
860.1380 Storage Stability
860.1480 Meat, Milk, Poultry and Eggs
860.1500 Crop Field Trials
All
A,B,C,K,
L,M
A,B,C,K,
L,M
A,B,C,K,
L,M
A,B,C,K,
L,M
A,B,C,K,
L,M
A,B,C,K,
L,M
A,B,C,K,
L,M
860.1900 Processed Food/Feed
A,B,C,K,
L,M
00115594,00165547
42346401, 42346402
00075671, 00084589
00139591
43108801
43389001, 43307001
42950101, 42540601,
42757601, 42540602,
43648102, 42950102,
43648101,43506901,
43108801
42460502, 42571401,
42571401,43648101,
42465401, 42950103
197
-------
GUIDE TO APPENDIX C
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 Reregi strati on 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.
198
-------
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 (19??), 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.
199
-------
MRID
BIBLIOGRAPHY
CITATION
00061186 Harper, K.H.; Ball, I.R. (1965) The Acute Toxicity of NPH 1320 Formulation of
M & B 10731 to (b) the Rainbow Trout (Salmogairdnerii Richardson):
1234/65/151. (Unpublished study received Jun 24, 1965 under unknown admin.
no.; prepared by Huntingdon Research Centre, England, submitted by ?;
CDL: 107617-1)
00061188 Harper, K.H.; Ball, I.R. (1965) The Acute Toxicity of Herbicide M & B 10731 to
(d) the Catfish (Ictalurus nebulosus): 1237/65/154. (Unpublished study received
Jun 24, 1965 under unknown admin, no.; prepared by Huntingdon Rsearch
Centre, England, submitted by ?; CDL:107617-K)
00061179 Noel, P.R.; Thomson, M.; Street, A.E. (1965) Chronic Toxicity of M & B 10731
(Technical Grade) in the Dog: 1177/65/94:3. (Unpublished study received Jun
24, 1965 under unknown admin, no.; prepared by Huntingdon Research Centre,
England, submitted by ?; CDL:107617-B)
00064815 Stevens, K.R.; Babish, J.G. (1978) Evaluation of the Effects of Bromoxynil on
the Reproductive Performance of FDRL Wistar Rats through Three Successive
Generations: Laboratory No. 5096. (Unpublished study received Mar 24, 1980
under 264-204; prepared by Food and Drug Research Laboratories, Inc.,
submitted by Union Carbide Agricultural Products Co., Inc., Ambler, Pa.; CDL:
242060-D)
00068077 Johnson, W.D.; Becci, P.J.; Parent, R.A. (1980) The Evaluation of the Oncogenic
Potential of Bromoxynil Administered in the Diet to Swiss Albino Mice for 18
Consecutive Months: Laboratory No. 5798. (Unpublished study received Jan 23,
1981 under 264-204; prepared by Food and Drug Research Laboratories, Inc.,
submitted by Union Carbide Agricultural Products Co., Inc., Ambler, Pa.;
CDL:244203-A; 244204)
00096521 Re, T.A.; Rucci, G.; Becci, P.J.; et al. (1982) Evaluation of the Oncogenic
Potential and Chronic Toxicity Effects of Technical Bromoxynil in Fischer 344
Rats: FDRL Study No. 5815. (Unpublished study received Mar 9, 1982 under
264-204; prepared by Food and Drug Research Laboratories, Inc., submitted by
Union Carbide Agricultural Products Co., Inc., Ambler, Pa.; CDL: 246957-A;
246958; 246959)
200
-------
Bibliography
00109415 Harper, K.; Ginn, H. (1965) The Acute Toxicity to Pheasant Chicks
of Technical Grade M & B 10731 and NPH 1320 Formulation of M &
B 10731: 1339/65/257. (Unpublished study received Jul 28, 1982
under 359-564; prepared by Huntingdon Research Centre, Eng.,
submitted by Rhone-Poulenc, Inc., Monmouth Junction, NJ; CDL:
247924-C)
00109417 Harper, K.; Ball, I. (1964) The Acute Toxicity of NPH 1320 Formulation of M &
B 10731 to (a) Daphnia (Crustacea cladocera): 1093/65/9. (Unpublished study
received Jul 28, 1982 under 359-564; prepared by Huntingdon Research Centre,
Eng., submitted by Rhone-Poulenc, Inc., Monmouth Junction, NJ;
CDL:247924-E)
00109418 Harper, K.; Ball, I. (1965) The Acute Toxicity of Herbicide M & B 10731 to (c)
the Goldfish (Carassius auratus): 1125/65/42. (Unpublished study received Jul
28, 1982 under 359-564; prepared by Huntingdon Research Centre, Eng.,
submitted by Rhone-Poulenc, Inc., Monmouth Junction, NJ; CDL:247924-G)
00114101 Fletcher, D. (1981) Report to Union Carbide Agricultural Products Company:
Acute Oral Toxicity Study with Bromoxynil Octanoate, Technical, in Bobwhite
Quail: BLAL No. 81 QD 6. (Unpublished study received Aug 31, 1982 under
264-204; prepared by Bio-Life Assoc., Ltd., submitted by Union Carbide
Agricultural Products Co., Inc., Research Triangle Park, NC; CDL:248229-B)
00114102 Fletcher, D. (1981) Report to Union Carbide Agricultural Products Company:
Acute Oral Toxicity Study with Bromoxynil Octanoate, Technical, in Mallard
Ducks: BLAL No. 81 DD 4. (Unpublished study received Aug 31, 1982 under
264-204; prepared by Bio-Life Assoc., Ltd., submitted by Union Carbide
Agricultural Products Co., Inc., Research Triangle Park, NC; CDL:248229-C)
00114105 Fletcher, D. (1981) Report to Union Carbide Agricultural Products Company:
8-day Dietary LC50 Study with Bromoxynil Octanoate in Bobwhite Quail: BLAL
No. 81 QC 9. (Unpublished study received Aug 31, 1982 under 264-204;
prepared by Bio-Life Assoc., Ltd., submitted by Union Carbide Agricultural
Products Co., Inc., Research Triangle Park, NC; CDL:248229-F)
201
-------
Bibliography
00114106 Fletcher, D. (1981) Report to Union Carbide Agricultural Products Company:
8-day Dietary LC50 Study with Bromoxynil Octanoate in Mallard Ducklings:
BLAL No. 81 DC 9. (Unpublished study received Aug 31, 1982 under 264-204;
prepared by Bio-Life Assoc., Ltd., submitted by Union Carbide Agricultural
Products Co., Inc., Research Triangle Park, NC; CDL:248229-G)
00114107 LeBlanc, G.; Sousa, J. (1981) Acute Toxicity of Bromoxynil Octanoate to
Bluegill ...: Report #BW-81-12-1063. (Unpublished study received Aug 31, 1982
under 264-204; prepared by EG & G, Bionomics, submitted by Union Carbide
Agricultural Products Co.,Inc., Research Triangle Park, NC; CDL:248229-H)
00114109 LeBlanc, G.; Surprenant, D. (1981) Acute Toxicity of Bromoxynil Octanoate to
the Water Flea ...: Report #BW-81-12-1071. (Unpublished study received Aug
31, 1982 under 264-204; prepared by EG & G, Bionomics, submitted by Union
Carbide Agricultural Products Co., Inc., Research Triangle Park, NC;
CDL:248229-J)
00114338 Parkins, M.; Heintzelman, R. (1981) A Comparison of the Adsorption Coefficient
of Bromoxynil Octanoate and Bromoxynil Butyrate: File No. 30647.
(Unpublished study received Sep 10, 1982 under 264-204; submitted by Union
carbide Agricultural Products Co., Inc., Research Triangle Park, NC;
CDL:248308-C)
00115646 Myhr, B.; McKeon, M. (1982) Evaluation of Bromoxynil, Marks in the Primary
Rat Hepatocyte Unscheduled DNA Synthesis Assay: LBI Project No. 20991.
Final rept. (Unpublished study received Oct 5, 1982 under 264-204; prepared by
Litton Bionetics, Inc., submitted by Union Carbide Agricultural Products Co.,
Inc., Research Triangle Park, NC; CDL:248546-A)
00115647 Rundell, J.; Matthews, E. (1982) Evaluation of Bromoxynil Phenol in the in vitro
Transformation of C3H/10T1/2C1 8 Cells Assay: LBI Project No. 20992. Final
rept. (Unpublished study received Oct 5, 1982 under 264-204; prepared by
Litton Bionetics, Inc., submitted by Union Carbide Agricultural Products Co.,
Inc., Research Triangle Park, NC; CDL:248546-B)
00115648 Galloway, S.; Lebowitz, H. (1982) Mutagenicity Evaluation of Bromoxynil
Phenol, Marks in the Sister Chromatid Exchange Assay with Chinese Hamster
202
-------
Bibliography
(CHO) Cells: LBI Project No. 20990. Final rept. (Unpublished study received
Oct 5, 1982 under 264-204; prepared by Litton Bionetics, Inc., submitted by
Union Carbide Agricultural Products Co., Inc., Research Triangle Park, NC;
CDL:248546-C)
00115649 Cifone, M.; Balinas, V. (1982) Mutagenicity Evaluation of Bromoxynil Phenol
(Marks) in the Mouse Lymphoma Forward Mutation Assay: LBI Project No.
20989. Rev. final rept. (Unpublished study received Oct 5, 1982 under
264-204; prepared by Litton Bionetics, Inc., submitted by Union Carbide
Agricultural Products Co., Inc., Research Triangle Park, NC; CDL:248546-D)
00115650 Jagannath, D.; Brusick, D.; Rabenold, C. (1982) Evaluation of the Test Article
Bromoxynil Phenol (Marks) in the Bacterial DNA Repair Test: LBI Project No.
20988. Rev. final rept. (Unpublished study received Oct 5, 1982 under 264-204;
prepared by Litton Bionetics, Inc., submitted by Union Carbide Agricultural
Products Co., Inc., Research Triangle Park, NC; CDL:248546-E)
00115651 Galloway, S.; Lebowitz, H. (1982) Mutagenicity Evaluation of Bromoxynil
Phenol (Marks) in an in vitro Cytogenetic Assay Measuring Chromosome
Aberration Frequencies in Chinese Hamster Ovary (CHO) Cells: LBI Project No.
20990. Rev. final rept. (Unpublished study received Oct 5, 1982 under 264-204;
prepared by Litton Bionetics, Inc., submitted by Union Carbide Agricultural
Products Co., Inc., Research Triangle Park, NC; CDL:248546-F)
00116557 Parkins, M.; Heintzelman, R. (1982) The Adsorption Coefficient of Bromoxynil
Octanoate on Sandy Loam Soil: File No. 29831. (Unpublished study received
Aug 31, 1982 under 264-204; submitted by Union Carbide Agricultural Products
Co., Inc., Researchm Triangle Park, NC; CDL:248228-B)
00116558 Copping, G. (1981) Bromoxynil Technical: Teratogenicity Study by the Oral
Route in the Rat: Report Ref R. Tox. 66. (Unpublished study received Sep 10,
1982 under 264-340; prepared by May & Baker, Ltd., Eng., submitted by Union
Carbide Agricultural Products Co., Inc., Research Triangle Park, NC;
CDL:071084-A)
00124112 Myers, R.; Coleman, J.; Condra, N; et al. (1982) Bromoxynil Octanoate: Acute
Toxicity and Irritancy Study: Project Report 45-56. (Unpublished study received
Dec 28, 1982 under 264-395; submitted by Union Carbide Agricultural Products
Co., Inc., Research Triangle Park, NC; CDL:249136-B)
203
-------
Bibliography
00124758 Myers, R.; Coleman, 1; Fowler, E.; et al. (1982) Bromoxynil Phenol: Acute
Toxicity and Irritancy Studies: Project Report 44-135. (Unpublished study
received Dec 28, 1982 under 264-229; submitted by Union Carbide Agricultural
Products Co., Inc., Research Triangle Park, NC; CDL:249155-A)
00124803 Holmstrom, M.; McGregor, D. (1982) Bromoxynil: Micronucleus Test in CD-I
Mice: IRI Project No. 705635. (Unpublished study received Jan 11, 1983 under
264-204; prepared by Inveresk Research International, submitted by Union
Carbide Agricultural Products Co., Inc., Research Triangle, NC; CDL:249219-A)
00130424 Huhtanen, K.; Storm, 1; Hientzelman, R. (1983) Hydrolysis of Bromoxynil
Octanoate and Butyrate in Aqueous Buffered Solutions: Project No. 854R10.
(Unpublished study received Jul 1, 1983 under 264-339; submitted by Union
Carbide Agricultural Products Co., Inc., Research Triangle Park, NC;
CDL:251058-A)
00138086 Surprenant, D.; Sousa, J. (1983) Acute Toxicity of AXF-1240 to Rainbow Trout
(Salmo gairdneri): Bionomics Study #070-1183-H87-103; Bionomics Report
#BW-83-l 1-1497. (Unpublished study received Jan 10, 1984 under 264-408;
prepared by EG&G Bionomics, submitted by Union Carbide Agricultural
Products Co., Inc., Research Triangle Park, NC; CDL:072254-A)
00138087 Surprenant, D.; Hoberg, J. (1983) Acute Toxicity of AXF-1240 to Daphnia
magna: Bionomics Study #070-1183-H87-110; Bionomics Report
#BW-83-l 1-1498. (Unpublished study received Jan 10, 1984 under 264-408;
prepared by EG&G Bionomics, submitted by Union Carbide Agricultural
Products Co., Inc., Research Triangle Park, NC; CDL:072254-B)
00138149 Copping, G.; Brown, P. (1983) Bromoxynil Technical: Teratogenicity Study by
the Oral Route in the Rabbit: Report Ref. R.TOX.219. (Unpublished study
received Nov 17, 1983 under 359-564; prepared by May & Baker, Ltd., Eng.,
and Univ. of Bristol, Eng., submitted by Rhone-Poulenc, Inc., Monmouth
Junction, NJ; CDL:252166-A; 252165)
00139538 Myers, R.; Christopher, S.; Monteleone, T.; et al. (1983) AXF-1240: Acute
Toxicity and Irritancy Study: Project Report 46-134. (Unpublished study
received Jan 10, 1984 under 264-408; submitted by Union Carbide Agricultural
Products Co., Inc., Research Triangle Park, NC; CDL:072255-A)
204
-------
Bibliography
00142779 Holson, J. (1984) Teratology Potential of Bromoxynil Phenol in New Zealand
White Rabbits: UNC/SAI1282017. Unpublished study prepared by Science
Applications, Inc. 199 p.
00142958 Williams, C. (1984) Bromoxynil: Metabolism in Sandy-loam and Loam Soils
under Aerobic Conditions: Report Ref. AG.TECH.421 Unpublished study
prepared by May & Baker Ltd. 221 p.
00147094 Fletcher, D. (1985) 8-Day Dietary LC50 Study with Bromoxymil Phenol in
Bobwhite Quail: BLAL No. 85 QC 50. Unpublished study prepared by Bio-Life
Assoc., Ltd. 17 p.
00147095 Fletcher, D. (1985) Acute Oral Toxicity Study with Bromoxymil Phenol in
Bobwhite Quail: BLAL No. 85 QD 51. Unpublished study prepared by Bio-Life
Assoc., Ltd. 21 p.
00147096 Fletcher, D. (1985) 8-Day Dietary LC50 Study with Bromoxymil Phenol
in Mallard Ducklings: BLAL No. 85 DC 51. Unpublished study pre-
pared by Bio-Life Assoc., Ltd. 16 p.
00155070 Surprenant, D. (1985) Acute Toxicity of Bromoxynil Phenol to Daphnids
(Daphnia magna): Study #565-0285-6110-110: Report #BW-85-9-1840.
Unpublished study prepared by Springborn Bionomics, Inc. 15 p.
00155071 Surprenant, D. (1985) Acute Toxicity of Bromoxynil Phenol to Blue-
gill (Leopomis macrochirus): Study #565.0285.6110.100: Report
#BW-85-10-1854. Unpublished study prepared by Springborn Bio-
nomics, Inc. 15 p.
00155072 Surprenant, D. (1985) Acute Toxicity of Bromoxynil Phenol to Rainbow Trout
(Salmo gairdneri): Study #565.0285.6110.103: Report #BW-85-10-1855.
Unpublished study prepared by Springborn Bionomics, Inc. 15 p.
00159171 Surprenant, D. (1983) Acute Toxicity of AXF-1240 to Bluegill (Lepomis
macrochirus): Bionomic Report #BW-83-12-1507. Unpublished study prepared
by EG&G Bionomics, lip.
205
-------
Bibliography
40111001 Surprenant, D.; Bentley, R.; Hoberg, J. et al. (1986) The Chronic Toxicity of
Bromoxynil Octanoate to Daphnia magna under Flow-through Conditions:
Report No. BW 86-9-2159: Study No. 565-1084- 6106-130. Unpublished
study prepared by Springborn Bionomics, Inc. 38 p.
40111003 Surprenant, D. (1987) The Toxicity of Bromoxynil Octanoate to Fathead
Minnow (Pimephales promelas) Embryos and Larvae: Report #BW-87-2-2016:
Study #565-1084-6106-120. Unpublished study prepared by Springborn
Bionomics, Inc. 40 p.
40466802 Rubin, Y.; Nyska, A. (1987) Bromoxynil Tech: Teratology Study in the Rat:
Laboratory Project ID AGN/161/BRO. Unpublished study performed by Life
Science Research Israel Ltd. 242 p.
40612501 Hamada, N. (1988) Combined Chronic Toxicity and Oncogenicity Study with
Bromoxynil Phenol in Rats: HLA Study No. 400-712. Unpublished study
prepared by Hazleton Laboratories, Inc. 3213 p.
40780301 Harling, R.; Burford, P.; Horner, S.; et al. (1988) Bromoxynil- Oral Toxicity in
Beagle Dogs Repeated Daily Dosage for 52 Weeks: Study No. M&B/248.
Unpublished study prepared by Huntingdon Research Centre Ltd. 350 p.
40854602 Bosch, A. (1988) Dermal Absorption of [carbon 14]-Bromoxynil Phenol in Male
Rats: Final Report: Project ID: HLA 6224-111 A. Unpublished study prepared by
Hazleton Laboratories America, Inc. 78 p.
40881201 Hoberman, A. (1988) Developmental Toxicity (Embryo-fetal Toxicity and
Teratogenicity) Study of Bromoxynil Phenol Administered Percutaneously to
Crl:CD (SD)BR Presumed Pregnant Rats: Argus Project No. 310-003.
Unpublished study prepared by Argus Research Laboratories, Inc. 345 p.
40883601 Hoberman, A. (1988) Argus Research Laboratories Historical Control Data:
Supplement to Study submitted Sept. 28, 1988 entitled Developmental Toxicity
(Embryo-fetal Toxicity and Teratogenicity) Study of Bromoxynil Phenol
administered Percutaneously to CR1 :CD (SD)BR Presumed Pregnant Rats.
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41149301 Higgins, C. (1989) Bromoxynil: Effects Upon Reproductive Performance of Rats
Treated Continuously Throughout Two Successive Generations: LSR Report No.
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with Bromoxynil Phenol in Rats: Addendum: Lab Project Number: HLA
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41471901 Hoberman, A. (1990) Developmental Toxicity (Embryo-Fetal Toxicity and
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41606001 Giddings, J. (1990) Bromoxynil Octanoate—Toxicity to the Freshwater Diatom
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41606002 Giddings, J. (1990) Bromoxynil Octanoate—Toxicity to the Marine Diatom
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41606004 Giddings, J. (1990) Bromoxynil Octanoate—Toxicity to the Freshwater Green
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41653701 Norris, F. (1989) A Small Scale Field Soil Dissipation Study with Bromoxynil
(Buctril Herbicide): Lab Project Number: EC/P-89-0011 RPT R072-023,027;
R150-028,029; R150-30,031. Unpublished study prepared by McKenzie Labs,
Inc. in cooperation with A & L Eastern Ag Labs, Inc. and Rhone-Poulenc Ag,
NC. 105 p.
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Dermal Administration: Lab Project Number: 210-010. Unpublished study
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41730001 Jones, P.; Rotondaro, A. (1990) Worker Mixer, Loader, Applicator Exposure to
Bromoxynil: Lab Project Number: EF-89-32: HLA 6224-163. Unpublished study
prepared by Pan-Agricultural Laboratories, Inc. in Association with Hazleton
Laboratories America, Inc. 493 p.
41879801 Myers, R. (1989) Bromoxynil Octanoate: Dermal Sensitization Study in the
Guinea Pig: Revised: Lab Project Number: 45/154. Unpublished study prepared
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208
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41928301 Sousa, J. (1991) Bromoxynil Octanoate: Toxicity to Fathead Minnow
(Pimephales promelas) Embryos and Larvae: Final Report: Lab Project Number:
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(Daphnia magna) Under Flow-Through Conditions: Lab Project Numb-
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41995701 Lawlor, T. (1991) Mutagenicity Test on Bromoxynil Phenol in the
Salmonella/Mammalian-Microsome Reverse Mutation Assay (Ames Test): Final
Report: Lab Project Number: 12550-0-401. Unpublished study prepared by
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Forward Mutation Assay: Final Report: Lab Project Number: 12550-0-435.
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42004101 Beavers, I; Sipler, O.; Smith, G.; et al (1991) Bromoxynil Octanoate:
One-Generation Reproduction Study with the Bobwhite (Colinus virginianus):
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42092301 Holmstrom, M.; Innes, D.; Craig, W. (1991) Bromoxynil Phenol: Micronucleus
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42167101 Holbert, M. (1991) Bromoxynil Octanoate Tech.: Acute Inhalation Toxicity
Study in Rats: Lab Project Number: 8239-91. Unpublished study prepared by
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42183901 Hoberman, A. (1992) Developmental Toxicity (Embryo-Fetal Toxicity and
Teratogenic Potential) Study of Bromoxynil Octanoate Administered
Percutaneously to New Zealand White Rabbits: Lab Project Number: 218-006.
Unpublished study prepared by Argus Research Labs., Inc. 16 p.
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Aqueous Solution Buffered at pH 5 Under Artificial Sunlight:
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Addendum to: Lab Project Number: SPY-92-36. Unpublished study prepared by
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under Flow-Thru Conditions: Lab Project Number: 92-2-4106:
10566.0191.6179.504. Unpublished study prepared by Springborn Labs, Inc.
55p.
42250601 Machado, M. (1992) Bromoxynil Octanoate Technical-Acute Toxicity to
Sheepshead Minnow (Cyprinodon variegatus) under Flow-through Conditions:
Lab Project Number: 91-7-3853. Unpublished study prepared by Springborn
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42271101 Grau, J.; Fitzmaurice, M. (1992) Ring-carbon 14Bromoxynil Octanoate: Leaching
Study with Four Soils: Lab Project No. P91/046. Unpublished study prepared by
Rhone-Poulenc Ag. Ltd. 62 p.
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Rabbits: Lab Project Number: HWI 6224-169. Unpublished study prepared by
Hazleton Wisconsin, Inc. 271 p.
42277301 Yenne, S.; Macy, L.; Andrawes, N.; et al. (1992) Uptake, Depuration and
Bioconcentration of [carbon 14]-Bromoxynil Octanoate by Bluegill Sunfish
(Lepomis macrochirus): Lab Project Number: EC91-144. Unpublished study
prepared by ABC Labs., Inc. and Rhone-Poulenc Ag Co. 624 p.
42346201 Kenwood, S. (1992) 3-Week Dermal Toxicity Study with Bromoxynil Octanoate
in Rabbits: Lab Project Number: 6224-168. Unpublished study prepared by
Hazleton Wisconsin, Inc. 364 p.
42364901 Gorman, M. (1990) Aerobic Aquatic Metabolism of [carbonl4]-Bromoxynil
Octanoate in Flooded Sandy Loam Soil:ABC Revised Final Report: Lab Project
Number: 38288. Unpublished study prepared by Analytical Bio-Chemistry Labs.,
Inc. 55 p.
42411901 Kenwood, S. (1992) 13-Week Dietary Toxicity Study with Bromoxynil
Octanoate in Rats: [Final Report]: Lab Project Number: HWI 6224-170.
Unpublished study prepared by Hazleton Wisconsin, Inc. 1022 p.
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42475801 Beavers, J. (992) Bromoxynil Octanoate: A One-Generation Reproduction Study
with the Bobwhite (Colinus viriginianus) An Addendum: Lab Project Number:
JBB/ch/CHW5/MfflAICH. Unpublished study prepared by Wildlife International
Ltd. 8 p.
42553401 Williams, K. (1992) Subchronic Toxicity Study with Bromoxynil Phenol in Mice:
Final Report: Lab Project Number: HWI 6224-167. Unpublished study prepared
by Hazleton Wisconsin, Inc. 294 p.
42718701 Rush, R. (1992) Dermal Sensitization Study in Guinea Pigs with Bromoxynil
Phenol—Modified Buehler Design: Lab Project Number: 3147.154. Unpublished
study prepared by Springborn Lab., Inc. 35 p.
42869701 Makin, A. (1993) Bromoxynil Octanoate: Toxicity to Dogs by Repeated Oral
Administration for 13 Weeks: Final Report: Lab Project Number: RNP
416/930670: RNP 416. Unpublished study prepared by Huntingdon Research
Centre, Ltd. 124 p.
43014701 Holbert, M. (1993) Bromoxynil Phenol: Acute Inhalation Toxicity Study in Rats:
Lab Project Number: 0454-93. Unpublished study prepared by Stillmeadow, Inc.
41 p.
43022701 Dillon, D. (1993) Bromoxynil Octanoate, Batch No. HN 81536: Testing for
Mutagenic Activity with Salmonella typhimurium TA1535, TA 1537, TA 1538,
TA 98, and TA 100: Lab Project Number: 754148: 9904: IRI 754148.
Unpublished study prepared by Inveresk Research International. 52 p.
43030001 Campbell, S.; Beavers, J. (1993) Bromoxynil Heptanoate: An Acute Oral Toxicity
Study with the Northern Bobwhite: Lab Project Number: 171-134. Unpublished
study prepared by Wildlife International Ltd. 21 p.
43030002 Campbell, S.; Beavers, J. (1993) Bromoxynil Heptanoate: A Dietary LC50 Study
with the Northern Bobwhite: Lab Project Number: 171-133. Unpublished study
prepared by Wildlife International Ltd. 43 p.
212
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43059601 Bettencourt, M. (1993) Bromoxynil Heptanoate-Acute Toxicity toBluegill
Sunfish (Lepomis macrochirus) Under Flow-Through Conditions: Lab Project
Number: 93-10-5006: 10566.0693. 6303.105. Unpublished study prepared by
Springborn Labs., Inc., Environmental Sciences Div. 72 p.
43059602 Putt, A. (1993) Bromoxynil Heptanoate-Acute Toxicity to Daphnids (Daphnia
magna) Under Flow-Through Conditions: Lab Project Number: 93-11-5050:
10566.0693.6304.115. Unpublished study prepared by Springborn Labs., Inc.,
Environmental Sciences Div. 74 p.
43059603 Hoberg, J. (1993) Bromoxynil Heptanoate-Determination of Effects on Seed
Germination, Seedling Emergence and Vegetative Vigor of Ten Plant Species:
Lab Project Number: 93-10-5003: 10566.0493. 6287.610. Unpublished study
prepared by Springborn Labs., Inc., Environmental Sciences Div. 217 p.
43059604 Hoberg, J. (1993) Bromoxynil Heptanoate-Toxicity to Duckweed, Lemna gibba:
Lab Project Number: 93-11-5040: 10566.0693.6301.410. Unpublished study
prepared by Springborn Labs., Inc., Environmental Sciences Div. 68 p.
43059605 Hoberg, J. (1993) Bromoxynil Heptanoate-Toxicity to the Freshwater Alga,
Selenastrum capricornutum: Lab Project Number: 93-11-5035:
10566.0693.6302.430. Unpublished study prepared by Springborn Labs., Inc.,
Environmental Sciences Div. 66 p.
43071001 Norris, F. (1993) Storage Stability of Bromoxynil and Bromoxynil Octanoate in
Frozen Soil: Addendum to MRID 41653701: Lab Project Number: EC-92-205:
41383. Unpublished study prepared by McKenzie Laboratories, Inc. 118 p.
43166701 Harling, R.; Burford, P.; Fryer, S. et al. (1988) Bromoxynil: Preliminary Oral
Toxicity Study in Beagle Dogs: Final Report-Repeated Daily Dosage for 13
Weeks: Lab Project Number: M&B/245: M&B 245/861692. Unpublished study
prepared by Huntingdon Research Center Ltd. 180 p.
43245501 Williams, K. (1994) Oncogenicity Study with Bromoxynil Phenol in Mice: Final
Report: Lab Project Number: HWI 6224-174. Unpublished study prepared by
Hazleton Wisconsin, Inc. 1929 p
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Hoberg, J. (1994) Bromoxynil Octanoate—Determination of Effects on Seed
Germination of Ten Plant Species: Final Report: Lab Project Number: 94-4-5225:
10566.0394.6339.610. Unpublished study prepared by Springborn Lab., Inc. 72
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Machado, M. (1994) Bromoxynil Octanoate Technical—Acute Toxicity to Mysids
(Mysidopsis bahia) Under Flow-through Conditions: Final Report: Lab Project
Number: 94-10-5502:10566.0894.6344.515. Unpublished study prepared by
Springborn Labs, Inc. 70 p.
Hoberg, J. (1995) Buctril-Determination of Effects on Seedling Emergence and
Vegetative Vigor of Ten Plant Species: Final Report: Lab Project Number:
95-4-5778: 10566.0395.6354.610. Unpublished study prepared by Springborn
Labs, Inc. 271 p.
Makin, A. (1993) Bromoxynil Octanoate: Toxicity to Dogs by Repeated Oral
Administration for 13 Weeks: (Final Report): Addendum: Lab Project Number:
RNP 416: RNP 416/930670. Unpublished study prepared by Huntingdon
Research Centre Ltd. 122 p.
Cooper, J.; Jones, M.; Lowden, P. et al. (1995) Herbicides: Bromoxynil
Octanoate: Aged Leaching in Four Soils and a Sediment: Addendum to MRID
42271101: Lab Project Number: P95/089: DOCMAP 200996: ONG 688.
Unpublished study prepared by Rhone-Poulenc Ag. Co. 303 p.
Fisher, P. (1993) Bromoxynil Heptanoate: Biokinetics & Metabolism Study in the
Rat: Lab Project Number: SA 93027. Unpublished study prepared by
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Experimental Pathology Laboratories, Inc. (1994) Oncogenicity Study with
Bromoxynil Phenol in Mice: Review of Liver Sections from Male Mice Pathology
Report: Addendum to MRID 43245501: Lab Project Number: HWI 6224-174:
259-009:6224-174. Unpublished study. 31 p.
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York. p.81.
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EPA food-chain (Kenaga) nomogram, an instrument for estimating pesticide residues on plants.
Environ. Toxicol. Chem. 13:1383-1391.
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Herbicides: Chemistry, Degradation and Mode of Action. 2nd ed. Marcel Dekker, Inc., NY. pp.
582-587.
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Representative Data as a Basis for Estimation of Their Magnitude in the Environment. Environ.
Quality I: 9-28. Academic Press, New York.
Kimbrough, R.A. and D.W. Litke. 1996. Pesticides in Streams Draining Agricultural and Urban
Areas in Colorado. Environ. Sci. Technol. 30(3):908-916.
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1971-1991, EPA 734-12-92-001, September, 1992.
Werner, S.L., M.L. Burkhardt, and S.N. DeRusseau. 1996. Methods of Analysis by the U.S.
Geological Survey National Water Quality Laboratory - Determination of Pesticides in Water by
Carbopak-B Solid-Phase Extraction and High-Performance Liquid Chromatography. U.S.
Geological Survey Open-File Report 96-216, Denver, CO.
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215
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216
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
\^|^r/ WASHINGTON, D.C. 20460
OFFICE OF
PREVENTION, PESTICIDES
AND TOXIC SUBSTANCES
GENERIC DATA CALL-IN NOTICE
CERTIFIED MAIL
Dear Sir or Madam:
This Notice requires you and other registrants of pesticide products containing the active ingredient(s)
identified in Attachment 1 of this Notice, the Data Call-In Chemical Status Sheet, to submit certain
data as noted herein to the U. S. Environmental Protection Agency (EPA, the Agency). These data are
necessary to maintain the continued registration of your product(s) containing this active ingredient(s).
Within 90 days after you receive this Notice you must respond as set forth in Section III below. Your
response must state:
1. how you will comply with the requirements set forth in this Notice and its Attachments 1
through 4; or,
2. why you believe you are exempt from the requirements listed in this Notice and in
Attachment 3. Requirements Status and Registrant's Response Form, (see section III-B); or,
3. why you believe EPA should not require your submission of data in the manner specified by
this Notice (see section III-D).
If you do not respond to this Notice, or if you do not satisfy EPA that you will comply with its
requirements or should be exempt or excused from doing so, then the registration of your product(s)
subject to this Notice will be subject to suspension. We have provided a list of all of your products
subject to this Notice in Attachment 2, Data Call-In Response Form, as well as a list of all registrants
who were sent this Notice (Attachment 4).
The authority for this Notice is section 3(c)(2)(B) of the Federal Insecticide, Fungicide and
Rodenticide Act as amended (FIFRA), 7 U.S.C. section 136a(c)(2)(B). Collection of this information
is authorized under the Paperwork Reduction Act by OMB Approval No. 2070-0107 and 2070-0057
(expiration date 3-31-99).
217
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This Notice is divided into six sections and five Attachments. The Notice itself contains
information and instructions applicable to all Data Call-In Notices. The Attachments contain specific
chemical information and instructions. The six sections of the Notice are:
Section I - Why You Are Receiving This Notice
Section II - Data Required By This Notice
Section III - Compliance With Requirements Of This Notice
Section IV - Consequences Of Failure To Comply With This Notice
Section V - Registrants' Obligation To Report Possible Unreasonable Adverse Effects
Section VI - Inquiries And Responses To This Notice
The Attachments to this Notice are:
Attachment 1 - Data Call-In Chemical Status Sheet
Attachment 2 - Data Call-In Response Form (Insert A)
Attachment 3 - Requirements Status And Registrant's Response Form (Insert B)
Attachment 4 - List Of All Registrants Sent This Data Call-In Notice
SECTION I. WHY YOU ARE RECEIVING THIS NOTICE
The Agency has reviewed existing data for this active ingredient(s) and reevaluated the data needed
to support continued registration of the subject active ingredient(s). This reevaluation identified
additional data necessary to assess the health and safety of the continued use of products containing
this active ingredient(s). You have been sent this Notice because you have product(s) containing the
subject active ingredient(s).
SECTION II. DATA REQUIRED BY THIS NOTICE
A. DATA REQUIRED
The data required by this Notice are specified in the Requirements Status and Registrant's
Response Form (Insert B). Depending on the results of the studies required in this Notice, additional
testing may be required.
B. SCHEDULE FOR SUBMISSION OF DATA
You are required to submit the data or otherwise satisfy the data requirements specified in
Attachment 3, Requirements Status and Registrant's Response Form (Insert B), within the time
frames provided.
C. TESTING PROTOCOL
All studies required under this Notice must be conducted in accordance with test standards
outlined in the Pesticide Assessment Guidelines for those studies for which guidelines have been
established.
218
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These EPA Guidelines are available from the National Technical Information Service (NTIS),
Attn: Order Desk, 5285 Port Royal Road, Springfield, Va 22161 (tel: 703-487-4650).
Protocols approved by the Organization for Economic Cooperation and Development
(OECD) are also acceptable if the OECD-recommended test standards conform to those specified in
the Pesticide Data Requirements regulation (40 CFR § 158.70). When using the OECD protocols,
they should be modified as appropriate so that the data generated by the study will satisfy the
requirements of 40 CFR § 158. Normally, the Agency will not extend deadlines for complying with
data requirements when the studies were not conducted in accordance with acceptable standards.
The OECD protocols are available from 2001 L Street, N.W., Washington, D.C. 20036 (Telephone
number 202-785-6323; Fax telephone number 202-785-0350).
All new studies and proposed protocols submitted in response to this Data Call-In Notice
must be in accordance with Good Laboratory Practices [40 CFR Part 160.3(a)(6)].
D. REGISTRANTS RECEIVING PREVIOUS SECTION 3(c)(2)(B) NOTICES ISSUED BY
THE AGENCY
Unless otherwise noted herein, this Data Call-In does not in any way supersede or change the
requirements of any previous Data Call-In(sX or any other agreements entered into with the Agency
pertaining to such prior Notice. Registrants must comply with the requirements of all Notices to
avoid issuance of a Notice of Intent to Suspend their affected products.
SECTION HI. COMPLIANCE WITH REQUIREMENTS OF THIS NOTICE
A. SCHEDULE FOR RESPONDING TO THE AGENCY
The appropriate responses initially required by this Notice must be submitted to the Agency
within 90 days after your receipt of this Notice. Failure to adequately respond to this Notice within
90 days of your receipt will be a basis for issuing a Notice of Intent to Suspend (NOIS) affecting your
products. This and other bases for issuance of NOIS due to failure to comply with this Notice are
presented in Section IV-A and IV-B.
B. OPTIONS FOR RESPONDING TO THE AGENCY
The options for responding to this Notice are: 1) voluntary cancellation, 2) delete use(s), (3)
claim generic data exemption, (4) agree to satisfy the data requirements imposed by this Notice or
(5) request a data waiver(s).
A discussion of how to respond if you chose the Voluntary Cancellation option, the Delete
Use(s) option or the Generic Data Exemption option is presented below. A discussion of the various
options available for satisfying the data requirements of this Notice is contained in Section III-C. A
discussion of options relating to requests for data waivers is contained in Section III-D.
219
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There are two forms that accompany this Notice of which, depending upon your response,
one or both must be used in your response to the Agency. These forms are the Data-Call-in Response
Form (Insert A) and the Requirements Status and Registrant's Response Form (Insert B). The Data
Call-In Response Form (Insert A) must be submitted as part of every response to this Notice. Please
note that the company's authorized representative is required to sign the first page of the Data Call-In
Response Form (Insert A) and Requirements Status and Registrant's Response Form (Insert B) and
initial any subsequent pages. The forms contain separate detailed instructions on the response
options. Do not alter the printed material. If you have questions or need assistance in preparing your
response, call or write the contact person identified in Attachment 1.
1. Voluntary Cancellation - You may avoid the requirements of this Notice by
requesting voluntary cancellation of your product(s) containing the active ingredient(s) that
is the subject of this Notice. If you wish to voluntarily cancel your product, you must submit
a completed Data Call-In Response Form (Insert A), indicating your election of this option.
Voluntary cancellation is item number 5 on the Data Call-In Response Form (Insert A). If you
choose this option, this is the only form that you are required to complete.
If you choose to voluntarily cancel your product, further sale and distribution of your
product after the effective date of cancellation must be in accordance with the Existing Stocks
provisions of this Notice which are contained in Section IV-C.
2. Use Deletion - You may avoid the requirements of this Notice by eliminating the uses
of your product to which the requirements apply. If you wish to amend your registration to
delete uses, you must submit the Requirements Status and Registrant's Response Form (Insert
B), a completed application for amendment, a copy of your proposed amended labeling, and
all other information required for processing the application. Use deletion is option number
7 on the Requirements Status and Registrant's Response Form (Insert B). You must also
complete a Data Call-In Response Form (Insert A) by signing the certification, item number
8. Application forms for amending registrations may be obtained from the Registration
Support and Emergency Response Branch, Registration Division, (703) 308-8358.
If you choose to delete the use(s) subject to this Notice or uses subj ect to specific data
requirements, further sale, distribution, or use of your product after one year from the due
date of your 90 day response, must bear an amended label.
3. Generic Data Exemption - Under section 3(c)(2)(D) of FIFRA, an applicant for
registration of a product is exempt from the requirement to submit or cite generic data
concerning an active ingredient(s) if the active ingredient(s) in the product is derived
exclusively from purchased, registered pesticide products containing the active ingredient(s).
EPA has concluded, as an exercise of its discretion, that it normally will not suspend the
registration of a product which would qualify and continue to qualify for the generic data
exemption in section 3 (c)(2)(D) of FIFRA. To qualify, all of the following requirements must
be met:
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a. The active ingredient(s) in your registered product must be present solely
because of incorporation of another registered product which contains the subject
active ingredient(s) and is purchased from a source not connected with you; and,
b. every registrant who is the ultimate source of the active ingredient(s) in your
product subject to this DCI must be in compliance with the requirements of this
Notice and must remain in compliance; and
c. you must have provided to EPA an accurate and current "Confidential
Statement of Formula" for each of your products to which this Notice applies.
To apply for the Generic Data Exemption you must submit a completed Data Call-In
Response Form (Insert A), and all supporting documentation. The Generic Data Exemption
is item number 6a on the Data Call-In Response Form (Insert A). If you claim a generic data
exemption you are not required to complete the Requirements Status and Registrant's
Response Form (Insert B). Generic Data Exemption cannot be selected as an option for
product specific data.
If you are granted a Generic Data Exemption, you rely on the efforts of other persons
to provide the Agency with the required data. If the registrant(s) who have committed to
generate and submit the required data fail to take appropriate steps to meet the requirements
or are no longer in compliance with this Data Call-In Notice, the Agency will consider that
both they and you are not in compliance and will normally initiate proceedings to suspend
the registrations of both your and their product(s), unless you commit to submit and do
submit the required data within the specified time. In such cases the Agency generally will
not grant a time extension for submitting the data.
4. Satisfying the Data Requirements of this Notice - There are various options available
to satisfy the data requirements of this Notice. These options are discussed in Section III-C
of this Notice and comprise options 1 through 6 on the Requirements Status and Registrant's
Response Form (Insert B) and option 6b and 7 on the Data Call-In Response FormQnsert A).
If you choose option 6b or 7, you must submit both forms as well as any other
information/data pertaining to the option chosen to address the data requirement.
5. Request for Data Waivers. Data waivers are discussed in Section III-D of this Notice
and are covered by options 8 and 9 on the Requirements Status and Registrant's Response
Form (Insert B). If you choose one of these options, you must submit both forms as well as
any other information/data pertaining to the option chosen to address the data requirement.
C. SATISFYING THE DATA REQUIREMENTS OF THIS NOTICE
If you acknowledge on the Data Call-In Response Form (Insert A) that you agree to satisfy
the data requirements (i.e. you select option 6b and/or 7), then you must select one of the six options
on the Requirements Status and Registrant's Response Form (Insert A) related to data production for
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each data requirement. Your option selection should be entered under item number 9, "Registrant
Response." The six options related to data production are the first six options discussed under item
9 in the instructions for completing the Requirements Status and Registrant's Response Form (Insert
B). These six options are listed immediately below with information in parentheses to guide
registrants to additional instructions provided in this Section. The options are:
1. I will generate and submit data within the specified time frame (Developing Data),
2. I have entered into an agreement with one or more registrants to develop data jointly
(Cost Sharing),
3. I have made offers to cost-share (Offers to Cost Share),
4. I am submitting an existing study that has not been submitted previously to the
Agency by anyone (Submitting an Existing Study),
5. I am submitting or citing data to upgrade a study classified by EPA as partially
acceptable and upgradeable (Upgrading a Study),
6. I am citing an existing study that EPA has classified as acceptable or an existing study
that has been submitted but not reviewed by the Agency (Citing an Existing Study).
Option 1. Developing Data
If you choose to develop the required data it must be in conformance with Agency
deadlines and with other Agency requirements as referenced herein and in the attachments.
All data generated and submitted must comply with the Good Laboratory Practice (GLP) rule
(40 CFRPart 160), be conducted according to the Pesticide Assessment Guidelines (PAG),
and be in conformance with the requirements of PR Notice 86-5. In addition, certain studies
require Agency approval of test protocols in advance of study initiation. Those studies for
which a protocol must be submitted have been identified in the Requirements Status and
Registrant's Response Form (Insert B) and/or footnotes to the form. If you wish to use a
protocol which differs from the options discussed in Section II-C of this Notice, you must
submit a detailed description of the proposed protocol and your reason for wishing to use it.
The Agency may choose to reject a protocol not specified in Section II-C. If the Agency
rejects your protocol you will be notified in writing, however, you should be aware that
rejection of a proposed protocol will not be a basis for extending the deadline for submission
of data.
A progress report must be submitted for each study within 90 days from the date you
are required to commit to generate or undertake some other means to address that study
requirement, such as making an offer to cost-share or agreeing to share in the cost of
developing that study. A 90-day progress report must be submitted for all studies. This 90-
day progress report must include the date the study was or will be initiated and, for studies
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to be started within 12 months of commitment, the name and address of the laboratory(ies)
or individuals who are or will be conducting the study.
In addition, if the time frame for submission of a final report is more than 1 year,
interim reports must be submitted at 12 month intervals from the date you are required to
commit to generate or otherwise address the requirement for the study. In addition to the
other information specified in the preceding paragraph, at a minimum, a brief description of
current activity on and the status of the study must be included as well as a full description
of any problems encountered since the last progress report.
The time frames in the Requirements Status and Registrant's Response Form (Insert
B) are the time frames that the Agency is allowing for the submission of completed study
reports or protocols. The noted deadlines run from the date of the receipt of this Notice by
the registrant. If the data are not submitted by the deadline, each registrant is subject to
receipt of a Notice of Intent to Suspend the affected registration(s).
If you cannot submit the data/reports to the Agency in the time required by this Notice
and intend to seek additional time to meet the requirement(s), you must submit a request to
the Agency which includes: (1) a detailed description of the expected difficulty and (2) a
proposed schedule including alternative dates for meeting such requirements on a step-by-
step basis. You must explain any technical or laboratory difficulties and provide
documentation from the laboratory performing the testing. While EPA is considering your
request, the original deadline remains. The Agency will respond to your request in writing.
If EPA does not grant your request, the original deadline remains. Normally, extensions can
be requested only in cases of extraordinary testing problems beyond the expectation or
control of the registrant. Extensions will not be given in submitting the 90-day responses.
Extensions will not be considered if the request for extension is not made in a timely fashion;
in no event shall an extension request be considered if it is submitted at or after the lapse of
the subject deadline.
Option 2. Agreement to Share in Cost to Develop Data ~
If you choose to enter into an agreement to share in the cost of producing the required
data but will not be submitting the data yourself, you must provide the name of the registrant
who will be submitting the data. You must also provide EPA with documentary evidence
that an agreement has been formed. Such evidence may be your letter offering to join in an
agreement and the other registrant's acceptance of your offer, or a written statement by the
parties that an agreement exists. The agreement to produce the data need not specify all of
the terms of the final arrangement between the parties or the mechanism to resolve the terms.
Section 3(c)(2)(B) provides that if the parties cannot resolve the terms of the agreement they
may resolve their differences through binding arbitration.
Option 3. Offer to Share in the Cost of Data Development —
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If you have made an offer to pay in an attempt to enter into an agreement or amend
an existing agreement to meet the requirements of this Notice and have been unsuccessful,
you may request EPA (by selecting this option) to exercise its discretion not to suspend your
registration(s), although you do not comply with the data submission requirements of this
Notice. EPA has determined that as a general policy, absent other relevant considerations,
it will not suspend the registration of a product of a registrant who has in good faith sought
and continues to seek to enter into a joint data development/cost sharing program, but the
other registrant(s) developing the data has refused to accept your offer. To qualify for this
option, you must submit documentation to the Agency proving that you have made an offer
to another registrant (who has an obligation to submit data) to share in the burden of
developing that data. You must also submit to the Agency a completed EPA Form 8570-32,
Certification of Offer to Cost Share in the Development of Data. In addition, you must
demonstrate that the other registrant to whom the offer was made has not accepted your offer
to enter into a cost sharing agreement by including a copy of your offer and proof of the other
registrant's receipt of that offer (such as a certified mail receipt). Your offer must, in addition
to anything else, offer to share in the burden of producing the data upon terms to be agreed
or failing agreement to be bound by binding arbitration as provided by FIFRA section
3 (c)(2)(B)(iii) and must not qualify this offer. The other registrant must also inform EPA of
its election of an option to develop and submit the data required by this Notice by submitting
a Data Call-In Response Form (Insert A) and a Requirements Status and Registrant's
Response Form (Insert B) committing to develop and submit the data required by this Notice.
In order for you to avoid suspension under this option, you may not withdraw your
offer to share in the burdens of developing the data. In addition, the other registrant must
fulfill its commitment to develop and submit the data as required by this Notice. If the other
registrant fails to develop the data or for some other reason is subject to suspension, your
registration as well as that of the other registrant will normally be subject to initiation of
suspension proceedings, unless you commit to submit, and do submit the required data in the
specified time frame. In such cases, the Agency generally will not grant a time extension for
submitting the data.
Option 4. Submitting an Existing Study —
If you choose to submit an existing study in response to this Notice, you must
determine that the study satisfies the requirements imposed by this Notice. You may only
submit a study that has not been previously submitted to the Agency or previously cited by
anyone. Existing studies are studies which predate issuance of this Notice. Do not use this
option if you are submitting data to upgrade a study. (See Option 5).
You should be aware that if the Agency determines that the study is not acceptable,
the Agency will require you to comply with this Notice, normally without an extension of the
required date of submission. The Agency may determine at any time that a study is not valid
and needs to be repeated.
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To meet the requirements of the DCI Notice for submitting an existing study, all of
the following three criteria must be clearly met:
a. You must certify at the time that the existing study is submitted that the raw
data and specimens from the study are available for audit and review and you must
identify where they are available. This must be done in accordance with the
requirements of the Good Laboratory Practice (GLP) regulation, 40 CFRPart 160.
As stated in 40 CFR 160.3(7)" raw data means any laboratory worksheets, records,
memoranda, notes, or exact copies thereof, that are the result of original observations
and activities of a study and are necessary for the reconstruction and evaluation of the
report of that study. In the event that exact transcripts of raw data have been prepared
(e.g., tapes which have been transcribed verbatim, dated, and verified accurate by
signature), the exact copy or exact transcript may be substituted for the original
source as raw data. Raw data may include photographs, microfilm or microfiche
copies, computer printouts, magnetic media, including dictated observations, and
recorded data from automated instruments." The term "specimens", according to 40
CFR 160.3(7), means "any material derived from a test system for examination or
analysis."
b. Health and safety studies completed after May 1984 must also contain all
GLP-required quality assurance and quality control information, pursuant to the
requirements of 40 CFR Part 160. Registrants must also certify at the time of
submitting the existing study that such GLP information is available for post-May
1984 studies by including an appropriate statement on or attached to the study signed
by an authorized official or representative of the registrant.
c. You must certify that each study fulfills the acceptance criteria for the
Guideline relevant to the study provided in the FIFRA Accelerated Reregistration
Phase 3 Technical Guidance and that the study has been conducted according to the
Pesticide Assessment Guidelines (PAG) or meets the purpose of the PAG (both
available from NTIS). A study not conducted according to the PAG may be
submitted to the Agency for consideration if the registrant believes that the study
clearly meets the purpose of the PAG. The registrant is referred to 40 CFR 158.70
which states the Agency's policy regarding acceptable protocols. If you wish to
submit the study, you must, in addition to certifying that the purposes of the PAG are
met by the study, clearly articulate the rationale why you believe the study meets the
purpose of the PAG, including copies of any supporting information or data. It has
been the Agency's experience that studies completed prior to January 1970 rarely
satisfied the purpose of the PAG and that necessary raw data are usually not available
for such studies.
If you submit an existing study, you must certify that the study meets all
requirements of the criteria outlined above.
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If EPA has previously reviewed a protocol for a study you are submitting, you
must identify any action taken by the Agency on the protocol and must indicate, as
part of your certification, the manner in which all Agency comments, concerns, or
issues were addressed in the final protocol and study.
If you know of a study pertaining to any requirement in this Notice which
does not meet the criteria outlined above but does contain factual information
regarding unreasonable adverse effects, you must notify the Agency of such a study.
If such a study is in the Agency's files, you need only cite it along with the
notification. If not in the Agency's files, you must submit a summary and copies as
required by PR Notice 86-5.
Option 5. Upgrading a Study —
If a study has been classified as partially acceptable and upgradeable, you may submit
data to upgrade that study. The Agency will review the data submitted and determine if the
requirement is satisfied. If the Agency decides the requirement is not satisfied, you may still
be required to submit new data normally without any time extension. Deficient, but
upgradeable studies will normally be classified as supplemental. However, it is important to
note that not all studies classified as supplemental are upgradeable. If you have questions
regarding the classification of a study or whether a study may be upgraded, call or write the
contact person listed in Attachment 1. If you submit data to upgrade an existing study you
must satisfy or supply information to correct all deficiencies in the study identified by EPA.
You must provide a clearly articulated rationale of how the deficiencies have been remedied
or corrected and why the study should be rated as acceptable to EPA. Your submission must
also specify the MRID number(s) of the study which you are attempting to upgrade and must
be in conformance with PR Notice 86-5.
Do not submit additional data for the purpose of upgrading a study classified as
unacceptable and determined by the Agency as not capable of being upgraded.
This option should also be used to cite data that has been previously submitted to
upgrade a study, but has not yet been reviewed by the Agency. You must provide the MRID
number of the data submission as well as the MRID number of the study being upgraded.
The criteria for submitting an existing study, as specified in Option 4 above, apply
to all data submissions intended to upgrade studies. Additionally your submission of data
intended to upgrade studies must be accompanied by a certification that you comply with
each of those criteria as well as a certification regarding protocol compliance with Agency
requirements.
Option 6. Citing Existing Studies —
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If you choose to cite a study that has been previously submitted to EPA, that study
must have been previously classified by EPA as acceptable or it must be a study which has
not yet been reviewed by the Agency. Acceptable toxicology studies generally will have
been classified as "core-guideline" or "core minimum." For ecological effects studies, the
classification generally would be a rating of "core." For all other disciplines the classification
would be "acceptable." With respect to any studies for which you wish to select this option
you must provide the MRID number of the study you are citing and, if the study has been
reviewed by the Agency, you must provide the Agency's classification of the study.
If you are citing a study of which you are not the original data submitter, you must
submit a completed copy of Certification with Respect to Citations of Data (in PR Notice
98-5) EPA Form 8570-34 .
D. REQUESTS FOR DATA WAIVERS
There are two types of data waiver responses to this Notice. The first is a request for a low
volume/minor use waiver and the second is a waiver request based on your belief that the data
requirement(s) are inapplicable and do not apply to your product.
1. Low Volume/Minor Use Waiver — Option 8 on the Requirements Status and
Registrant's Response Form (Insert B). Section 3(c)(2)(A) of FIFRA requires EPA to
consider the appropriateness of requiring data for low volume, minor use pesticides. In
implementing this provision EPA considers as low volume pesticides only those active
ingredient(s) whose total production volume for all pesticide registrants is small. In
determining whether to grant a low volume, minor use waiver the Agency will consider the
extent, pattern and volume of use, the economic incentive to conduct the testing, the
importance of the pesticide, and the exposure and risk from use of the pesticide. If an active
ingredient(s) is used for both high volume and low volume uses, a low volume exemption
will not be approved. If all uses of an active ingredient(s) are low volume and the combined
volumes for all uses are also low, then an exemption may be granted, depending on review
of other information outlined below. An exemption will not be granted if any registrant of
the active ingredient(s) elects to conduct the testing. Any registrant receiving a low volume
minor use waiver must remain within the sales figures in their forecast supporting the waiver
request in order to remain qualified for such waiver. If granted a waiver, a registrant will be
required, as a condition of the waiver, to submit annual sales reports. The Agency will
respond to requests for waivers in writing.
To apply for a low volume, minor use waiver, you must submit the following
information, as applicable to your product(s), as part of your 90-day response to this Notice:
a. Total company sales (pounds and dollars) of all registered product(s)
containing the active ingredient(s). If applicable to the active ingredient(s), include
foreign sales for those products that are not registered in this country but are applied
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to sugar (cane or beet), coffee, bananas, cocoa, and other such crops. Present the
above information by year for each of the past five years.
b. Provide an estimate of the sales (pounds and dollars) of the active
ingredient(s) for each major use site. Present the above information by year for each
of the past five years.
c. Total direct production cost of product(s) containing the active ingredient(s)
by year for the past five years. Include information on raw material cost, direct labor
cost, advertising, sales and marketing, and any other significant costs listed
separately.
d. Total indirect production cost (e.g. plant overhead, amortized plant and
equipment) charged to product(s) containing the active ingredient(s) by year for the
past five years. Exclude all non-recurring costs that were directly related to the active
ingredient(s), such as costs of initial registration and any data development.
e. A list of each data requirement for which you seek a waiver. Indicate
the type of waiver sought and the estimated cost to you (listed separately for
each data requirement and associated test) of conducting the testing needed
to fulfill each of these data requirements.
f A list of each data requirement for which you are not seeking any waiver and
the estimated cost to you (listed separately for each data requirement and associated
test) of conducting the testing needed to fulfill each of these data requirements.
g. For each of the next ten years, a year-by-year forecast of company sales
(pounds and dollars) of the active ingredient(s), direct production costs of product(s)
containing the active ingredient(s) (following the parameters in item c above),
indirect production costs of product(s) containing the active ingredient(s) (following
the parameters in item d above), and costs of data development pertaining to the
active ingredient(s).
h. A description of the importance and unique benefits of the active
ingredient(s) to users. Discuss the use patterns and the effectiveness of the active
ingredient(s) relative to registered alternative chemicals and non-chemical control
strategies. Focus on benefits unique to the active ingredient(s), providing
information that is as quantitative as possible. If you do not have quantitative data
upon which to base your estimates, then present the reasoning used to derive your
estimates. To assistthe Agency in determining the degree of importance of the active
ingredient(s) in terms of its benefits, you should provide information on any of the
following factors, as applicable to your product(s):
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(1) documentation of the usefulness of the active ingredient(s) in
Integrated Pest Management, (b) description of the beneficial impacts on the
environment of use of the active ingredient(s), as opposed to its registered
alternatives, (c) information on the breakdown of the active ingredient(s) after use and
on its persistence in the environment, and (d) description of its usefulness against a
pest(s) of public health significance.
Failure to submit sufficient information for the Agency to make a determination regarding
a request for a low volume minor use waiver will result in denial of the request for a waiver.
2. Request for Waiver of Data —Option 9 on the Requirements Status and Registrant's
Response Form (Insert B). This option may be used if you believe that a particular data
requirement should not apply because the corresponding use is no longer registered or the
requirement is inappropriate. You must submit a rationale explaining why you believe the
data requirements should not apply. You must also submit the current label(s) of your
product(s) and, if a current copy of your Confidential Statement of Formula is not already on
file you must submit a current copy.
You will be informed of the Agency's decision in writing. If the Agency determines
that the data requirements of this Notice do not apply to your product(s), you will not be
required to supply the data pursuant to section 3(c)(2)(B). If EPA determines that the data
are required for your productfsX you must choose a method of meeting the requirements of
this Notice within the time frame provided by this Notice. Within 30 days of your receipt of
the Agency's written decision, you must submit a revised Requirements Status and
Registrant's Response Form (Insert B) indicating the option chosen.
IV. CONSEQUENCES OF FAILURE TO COMPLY WITH THIS NOTICE
A. NOTICE OF INTENT TO SUSPEND
The Agency may issue a Notice of Intent to Suspend products subject to this Notice due to
failure by a registrant to comply with the requirements of this Data Call-In Notice, pursuant to FIFRA
section 3(c)(2)(B). Events which may be the basis for issuance of a Notice of Intent to Suspend
include, but are not limited to, the following:
1. Failure to respond as required by this Notice within 90 days of your receipt of this
Notice.
2. Failure to submit on the required schedule an acceptable proposed or final protocol
when such is required to be submitted to the Agency for review.
3. Failure to submit on the required schedule an adequate progress report on a study as
required by this Notice.
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4. Failure to submit on the required schedule acceptable data as required by this Notice.
5. Failure to take a required action or submit adequate information pertaining to any
option chosen to address the data requirements (e.g., any required action or
information pertaining to submission or citation of existing studies or offers,
arrangements, or arbitration on the sharing of costs or the formation of Task Forces,
failure to comply with the terms of an agreement or arbitration concerning joint data
development or failure to comply with any terms of a data waiver).
6. Failure to submit supportable certifications as to the conditions of submitted studies,
as required by Section III-C of this Notice.
7. Withdrawal of an offer to share in the cost of developing required data.
8. Failure of the registrant to whom you have tendered an offer to share in the cost of
developing data and provided proof of the registrant's receipt of such offer, or failure
of a registrant on whom you rely for a generic data exemption either to:
a. inform EPA of intent to develop and submit the data required by this Notice
on a Data Call-In Response Form (Insert A) and a Requirements Status and
Registrant's Response Form (Insert B); or,
b. fulfill the commitment to develop and submit the data as required by this
Notice; or,
c. otherwise take appropriate steps to meet the requirements stated in this
Notice, unless you commit to submit and do submit the required data in the specified
time frame.
9. Failure to take any required or appropriate steps, not mentioned above, at any time
following the issuance of this Notice.
B. BASIS FOR DETERMINATION THAT SUBMITTED STUDY IS UNACCEPTABLE
The Agency may determine that a study (even if submitted within the required time) is
unacceptable and constitutes a basis for issuance of a Notice of Intent to Suspend. The grounds for
suspension include, but are not limited to, failure to meet any of the following:
1. EPA requirements specified in the Data Call-In Notice or other documents
incorporated by reference (including, as applicable, EPA Pesticide Assessment Guidelines,
Data Reporting Guidelines, and GeneTox Health Effects Test Guidelines) regarding the
design, conduct, and reporting of required studies. Such requirements include, but are not
limited to, those relating to test material, test procedures, selection of species, number of
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animals, sex and distribution of animals, dose and effect levels to be tested or attained,
duration of test, and, as applicable, Good Laboratory Practices.
2. EPA requirements regarding the submission of protocols, including the incorporation
of any changes required by the Agency following review.
3. EPA requirements regarding the reporting of data, including the manner of reporting,
the completeness of results, and the adequacy of any required supporting (or raw) data,
including, but not limited to, requirements referenced or included in this Notice or contained
in PR 86-5. All studies must be submitted in the form of a final report; a preliminary report
will not be considered to fulfill the submission requirement.
C. EXISTING STOCKS OF SUSPENDED OR CANCELED PRODUCTS
EPA has statutory authority to permit continued sale, distribution and use of existing stocks
of a pesticide product which has been suspended or canceled if doing so would be consistent with
the purposes of the Federal Insecticide, Fungicide, and Rodenticide Act.
The Agency has determined that such disposition by registrants of existing stocks for a
suspended registration when a section 3(c)(2)(B) data request is outstanding would generally not be
consistent with the Act's purposes. Accordingly, the Agency anticipates granting registrants
permission to sell, distribute, or use existing stocks of suspended product(s) only in exceptional
circumstances. If you believe such disposition of existing stocks of your product(s) which may be
suspended for failure to comply with this Notice should be permitted, you have the burden of clearly
demonstrating to EPA that granting such permission would be consistent with the Act. You must also
explain why an "existing stocks" provision is necessary, including a statement of the quantity of
existing stocks and your estimate of the time required for their sale, distribution, and use. Unless you
meet this burden the Agency will not consider any request pertaining to the continued sale,
distribution, or use of your existing stocks after suspension.
If you request a voluntary cancellation of your product(s) as a response to this Notice and your
product is in full compliance with all Agency requirements, you will have, under most circumstances,
one year from the date your 90 day response to this Notice is due, to sell, distribute, or use existing
stocks. Normally, the Agency will allow persons other than the registrant such as independent
distributors, retailers and end users to sell, distribute or use such existing stocks until the stocks are
exhausted. Any sale, distribution or use of stocks of voluntarily canceled products containing an
active ingredient(s) for which the Agency has particular risk concerns will be determined on case-by-
case basis.
Requests for voluntary cancellation received after the 90 day response period required by this
Notice will not result in the Agency granting any additional time to sell, distribute, or use existing
stocks beyond a year from the date the 90 day response was due unless you demonstrate to the
Agency that you are in full compliance with all Agency requirements, including the requirements of
this Notice. For example, if you decide to voluntarily cancel your registration six months before a
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3 year study is scheduled to be submitted, all progress reports and other information necessary to
establish that you have been conducting the study in an acceptable and good faith manner must have
been submitted to the Agency, before EPA will consider granting an existing stocks provision.
SECTION V. REGISTRANTS' OBLIGATION TO REPORT POSSIBLE UNREASONABLE
ADVERSE EFFECTS
Registrants are reminded that FIFRA section 6(a)(2) states that if at any time after a pesticide is
registered a registrant has additional factual information regarding unreasonable adverse effects on the
environment by the pesticide, the registrant shall submit the information to the Agency. Registrants
must notify the Agency of any factual information they have, from whatever source, including but not
limited to interim or preliminary results of studies, regarding unreasonable adverse effects on man or
the environment. This requirement continues as long as the products are registered by the Agency.
SECTION VI. INQUIRIES AND RESPONSES TO THIS NOTICE
If you have any questions regarding the requirements and procedures established by this Notice, call
the contact person listed in Attachment 1, the Data Call-In Chemical Status Sheet.
All responses to this Notice (other than voluntary cancellation requests and generic data exemption
claims) must include a completed Data Call-In Response Form (Insert A) and a completed
Requirements Status and Registrant's Response Form (Insert B) and any other documents required by
this Notice, and should be submitted to the contact person identified in Attachment 1. If the voluntary
cancellation or generic data exemption option is chosen, only the Data Call-In Response Form (Insert
A) need be submitted.
The Office of Compliance (OC) of the Office of Enforcement and Compliance Assurance (OECA),
EPA, will be monitoring the data being generated in response to this Notice.
Sincerely yours,
Lois A. Rossi, Director
Special Review and
Reregistration Division
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Bromoxynil DATA CALL-IN CHEMICAL STATUS SHEET
INTRODUCTION
You have been sent this Generic Data Call-In Notice because you have product(s) containing
bromoxynil.
This Generic Data Call-In Chemical Status Sheet, contains an overview of data required by this
notice, and point of contact for inquiries pertaining to the reregi strati on of bromoxynil. This
attachment is to be used in conjunction with (1) the Generic Data Call-In Notice, (2) the Generic Data
Call-In Response Form (Attachment 2), (3) the Requirements Status and Registrant's Form
(Attachment 2), (4) a list of registrants receiving this DCI (Attachment 4), (5) the EPA Acceptance
Criteria (Attachment 5), and (6) the Cost Share and Data Compensation Forms in replying to this
DEET Generic Data Call In (Attachment F). Instructions and guidance accompany each form.
DATA REQUIRED BY THIS NOTICE
The additional data requirements needed to complete the generic database for bromoxynil are
contained in the Requirements Status and Registrant's Response. Attachment C. The Agency has
concluded that additional product chemistry data on bromoxynil are needed. These data are needed
to fully complete the reregi strati on of all eligible bromoxynil products.
INQUIRIES AND RESPONSES TO THIS NOTICE
If you have any questions regarding the generic data requirements and procedures established by this
Notice, please contact Linda Werrell at (703) 308-8033.
All responsades to this Notice for the generic data requirements should be submitted to:
Linda Werrill, Chemical Review Manager
Reregi strati on Branch
Special Review and Registration Division (H7508W)
Office of Pesticiafde Programs
U.S. Environmental Protection Agency
Washington, D.C. 20460
RE: Bromoxynil
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SPECIFIC INSTRUCTIONS FOR THE GENERIC DATA CALL-IN RESPONSE FORM
(INSERT A)
This Form is designed to be used to respond to call-ins for generic and product specific data for the
purpose of reregistering pesticides under the Federal Insecticide Fungicide and Rodenticide Act. Fill
out this form each time you are responding to a data call-in for which EPA has sent you the form
entitled "Requirements Status and Registrant's Response."
Items 1-4 will have been preprinted on the form Items 5 through 7 must be completed by the
registrant as appropriate Items 8 through 11 must be completed by the registrant before submitting
a response to the Agency.
Public reporting burden for this collection of information is estimated to average 15 minutes per
response, including time for reviewing instructions, searching existing data sources, gathering and
maintaining the data needed, and completing and reviewing the collection of information. Send
comments regarding the burden estimate or any other aspect of this collection of information,
including suggesting for reducing this burden, to Chief, Information Policy Branch, PM-223, U S
Environmental Protection Agency, 401 M St, S W , Washington, D C 20460; and to the Office of
Management and Budget, Paperwork Reduction Project 2070-0107, Washington, D C 20503.
INSTRUCTIONS
Item 1. This item identifies your company name, number and address.
Item 2. This item identifies the ease number, ease name, EPA chemical number and chemical
name.
Item 3. This item identifies the date and type of data call-in.
Item 4. This item identifies the EPA product registrations relevant to the data call-in. Please
note that you are also responsible for informing the Agency of your response
regarding any product that you believe may be covered by this data call-in but that
is not listed by the Agency in Item 4. You must bring any such apparent omission
to the Agency's attention within the period required for submission of this response
form.
Item 5. Cheek this item for each product registration you wish to cancel voluntarily. If a
registration number is listed for a product for which you previously requested
voluntary cancellation, indicate in Item 5 the date of that request. You do not need
to complete any item on the Requirements Status and Registrant's Response Form
for any product that is voluntarily canceled.
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Item 6a. Check this item if this data call-in is for generic data as indicated in Item 3 and if you
are eligible for a Generic Data Exemption for the chemical listed in Item 2 and used
in the subject product. By electing this exemption, you agree to the terms and
conditions of a Generic Data Exemption as explained in the Data Call-In Notice.
If you are eligible for or claim a Generic Data Exemption, enter the EPA registration
Number of each registered source of that active ingredient that you use in your
product.
Typically, if you purchase an EPA-registered product from one or more other
producers (who, with respect to the incorporated product, are in compliance with
this and-any other outstanding Data Call-In Notice), and incorporate that product
into all your products, you may complete this item for all products listed on this form
If, however, you produce the active ingredient yourself, or use any unregistered
product (regardless of the fact that some of your sources are registered), you may
not claim a Generic Data Exemption and you may not select this item.
Item 6b. Check this Item if the data call-in is a generic data call-in as indicated in Item 3 and
if you are agreeing to satisfy the generic data requirements of this data call-in.
Attach the Requirements Status and Registrant's Response Form (Insert A) that
indicates how you will satisfy those requirements.
Item 7a. Check this item if this call-in if a data call-in as indicated in Item 3 for a
manufacturing use product (MUP), and if your product is a manufacturing use
product for which you agree to supply product-specific data. Attach the
Requirements Status and Registrants' Response Form (Insert A) that indicates how
you will satisfy those requirements.
Item 7b. Check this item if this call-in is a data call-in for an end use product (EUP) as
indicated in Item 3 and if your product is an end use product for which you agree to
supply product-specific data. Attach the Requirements Status and Registrant's
Response Form (Insert A) that indicates how you will satisfy those requirements.
Item 8. This certification statement must be signed by an authorized representative of your
company and the person signing must include his/her title. Additional pages used in
your response must be initialed and dated in the space provided for the certification.
Item 9. Enter the date of signature.
Item 10. Enter the name of the person EPA should contact with questions regarding your
response.
Item 11. Enter the phone number of your company contact.
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SPECIFIC INSTRUCTIONS FOR COMPLETING THE REQUIREMENTS STATUS AND
REGISTRANTS RESPONSE FORM (INSERTS)
Generic Data
This form is designed to be used for registrants to respond to call-in- for generic and product-specific
data as part of EPA's reregi strati on program under the Federal Insecticide Fungicide and Rodenticide
Act. Although the form is the same for both product specific and generic data, instructions for
completing the forms differ slightly. Specifically, options for satisfying product specific data
requirements do not include (1) deletion of uses or (2) request for a low volume/minor use waiver.
These instructions are for completion of generic data requirements.
EPA has developed this form individually for each data call-in addressed to each registrant, and has
preprinted this form with a number of items. DO NOT use this form for any other active ingredient.
Items 1 through 8 (inclusive) will have been preprinted on the form. You must complete all other
items on this form by typing or printing legibly.
Public reporting burden for this collection of information is estimated to average 30 minutes per
response, including time for reviewing instructions, searching existing data sources, gathering and
maintaining the data needed, and completing and reviewing the collection of information. Send
comments regarding the burden estimate or any other aspect of this collection of information,
including suggesting for reducing this burden, to Chief, Information Policy Branch, PM-223, U.S.
Environmental Protection Agency, 401 M St., SW., Washington, D.C. 20460; and to the Office of
Management and Budget, Paperwork Reduction Project 2070-0107, Washington, D.C. 20503.
INSTRUCTIONS
Item 1. This item identifies your company name, number, and address.
Item 2. This item identifies the case number, case name, EPA chemical number and chemical name.
Item 3. This item identifies the date and type of data call-in.
Item 4. This item identifies the guideline reference numbers of studies required to support the
product(s) being reregistered. These guidelines, in addition to requirements specified in the
Data Call-In Notice, govern the conduct of the required studies.
Item 5. This item identifies the study title associated with the guideline reference number and
whether protocols and 1, 2, or 3-year progress reports are required to be submitted in
connection with the study. As noted in Section III of the Data Call-In Notice, 90-day
progress reports are required for all studies.
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If an asterisk appears in Item 5, EPA has attached information relevant to this
guideline reference number to the Requirements Status and Registrant's Response
Form (Insert B).
Item 6. This item identifies the code associated with the use pattern of the pesticide. A brief
description of each code follows:
A. Terrestrial food
B. Terrestrial feed
C. Terrestrial non-food
D. Aquatic food
E. Aquatic non-food outdoor
F. Aquatic non-food industrial
G. Aquatic non-food residential
H. Greenhouse food
I. Greenhouse non-food crop
J. Forestry
K. Residential
L. Indoor food
M. Indoor non-food
N. Indoor medical
O. Indoor residential
Item 7. This item identifies the code assigned to the substance that must be used for testing. A brief
description of each code follows.
EP End-Use Product
MP Manufacturing-Use Product
MP/TGAI Manufacturing-Use Product and Technical Grade Active
Ingredient
PAI Pure Active Ingredient
PAI/M Pure Active Ingredient and Metabolites
PAI/PAIRA Pure Active Ingredient or Pure Active Ingredient
Radiolabelled
PAIRA Pure Active Ingredient Radiolabelled
PAIRA/M Pure Active Ingredient Radiolabelled and Metabolites
PAIRA/PM Pure Active Ingredient Radiolabelled and Plant Metabolites
TEP Typical End-Use Product
TEP _ * Typical End-Use Product, Percent Active Ingredient
Specified
TEP/MET Typical End-Use Product and Metabolites
TEP/PAI/M Typical End-Use Product or Pure Active Ingredient and
Metabolites
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TGAI/PAIRA Technical Grade Active Ingredient or Pure Active Ingredient
Radiolabelled
TGAI Technical Grade Active Ingredient
TGAI/TEP Technical Grade Active Ingredient or Typical End-Use
Product
TGAI/PAI Technical Grade Active Ingredient or Pure Active Ingredient
MET Metabolites
IMP Impurities
DEGR Degradates
*See: guideline comment
Item 8. This item identifies the time frame allowed for submission of the study or protocol identified
in item 2. The time frame runs from the date of your receipt of the Data Call-In Notice.
Item 9. Enter the appropriate Response Code or Codes to show how you intend to comply with each
data requirement. Brief descriptions of each code follow. The Data Call-In Notice contains
a fuller description of each of these options.
1. (Developing Data) I will conduct a new study and submit it within the time frames
specified in item 8 above. By indicating that I have chosen this option, I certify that
I will comply with all the requirements pertaining to the conditions for submittal of
this study as outlined in the Data Call-In Notice and that I will provide the protocol
and progress reports required in item 5 above.
2. (Agreement to Cost Share) I have entered into an agreement with one or more
registrants to develop data jointly. By indicating that I have chosen this option, I
certify that I will comply with all the requirements pertaining to sharing in the cost
of developing data as outlined in the Data Call-In Notice.
3. (Offer to Cost Share) I have made an offer to enter into an agreement with one or
more registrants to develop data jointly. I am submitting a copy of the form
"Certification of Offer to Cost Share in the Development of Data" that describes this
offer/agreement. By indicating that I have chosen this option, I certify that I will
comply with all the requirements pertaining to making an offer to share in the cost
of developing data as outlined in the Data Call-In Notice.
4. (Submitting Existing Data) I am submitting an existing study that has never before
been submitted to EPA. By indicating that I have chosen this option, I certify that
this study meets all the requirements pertaining to the conditions for submittal of
existing data outlined in the Data Call-In Notice and I have attached the needed
supporting information along with this response.
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5. (Upgrading a Study) I am submitting or citing data to upgrade a study that EPA has
classified as partially acceptable and potentially upgradeable. By indicating that I
have chosen this option, I certify that I have met all the requirements pertaining to
the conditions for submitting or citing existing data to upgrade a study described in
the Data Call-In Notice. I am indicating on attached correspondence the Master
Record Identification Number (MRID) that EPA has assigned to the data that I am
citing as well as the MRID of the study I am attempting to upgrade.
6. (Citing a Study) I am citing an existing study that has been previously classified by
EPA as acceptable, core, core minimum, or a study that has not yet been reviewed
by the Agency. I am providing the Agency's classification of the study.
7. (Deleting Uses) I am attaching an application for amendment to my registration
deleting the uses for which the data are required.
8. (Low Volume/Minor Use Waiver Request) I have read the statements concerning
low volume-minor use data waivers in the Data Call-In Notice and I request a
low-volume minor use waiver of the data requirement. I am attaching a detailed
justification to support this waiver request including, among other things, all
information required to support the request. I understand that, unless modified by the
Agency in writing, the data requirement as stated in the Notice governs.
9. (Request for Waiver of Data) I have read the statements concerning data waivers
other than low volume minor-use data waivers in the Data Call-In Notice and I
request a waiver of the data requirement. I am attaching an identification of the basis
for this waiver and a detailed justification to support this waiver request. The
justification includes, among other things, all information required to support the
request. I understand that, unless modified by the Agency in writing, the data
requirement as stated in the Notice governs.
Item 10. This item must be signed by an authorized representative of your company. The
person signing must include his/her title, and must initial and date all other pages of
this form.
Item 11. Enter the date of signature.
Item 12. Enter the name of the person EPA should contact with questions regarding your
response.
Item 13. Enter the phone number of your company contact.
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, D.C. 20460
OFFICE OF
PREVENTION, PESTICIDES
AND TOXIC SUBSTANCES
DATA CALL-IN NOTICE
CERTIFIED MAIL
Dear Sir or Madam:
This Notice requires you and other registrants of pesticide products containing the active
ingredient identified in Attachment 1 of this Notice, the Data Call-In Chemical Status Sheet, to
submit certain product specific data as noted herein to the U.S. Environmental Protection Agency
(EPA, the Agency). These data are necessary to maintain the continued registration of your
product(s) containing this active ingredient. Within 90 days after you receive this Notice you must
respond as set forth in Section III below. Your response must state:
1. How you will comply with the requirements set forth in this Notice and its
Attachments 1 through 5; or
2. Why you believe you are exempt from the requirements listed in this Notice and in
Attachment 3, Requirements Status and Registrant's Response Form, (see section
III-B); or
3. Why you believe EPA should not require your submission of product specific data
in the manner specified by this Notice (see section III-D).
If you do not respond to this Notice, or if you do not satisfy EPA that you will comply with
its requirements or should be exempt or excused from doing so, then the registration of your
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product(s) subject to this Notice will be subject to suspension. We have provided a list of all of
your products subject to this Notice in Attachment 2, Data Call-In Response Form, as well as a list
of all registrants who were sent this Notice (Attachment 5).
The authority for this Notice is section 3(c)(2)(B) of the Federal Insecticide, Fungicide and
Rodenticide Act as amended (FIFRA), 7 U.S.C. section 136a(c)(2)(B). Collection of this
information is authorized under the Paperwork Reduction Act by OMB Approval No. 2070-0107
and 2070-0057 (expiration date 03-31-99).
This Notice is divided into six sections and six Attachments. The Notice itself contains
information and instructions applicable to all Data Call-In Notices. The Attachments contain
specific chemical information and instructions. The six sections of the Notice are:
Section I - Why You Are Receiving This Notice
Section II - Data Required By This Notice
Section III - Compliance With Requirements Of This Notice
Section IV - Consequences Of Failure To Comply With This Notice
Section V - Registrants' Obligation To Report Possible Unreasonable Adverse
Effects
Section VT - Inquiries And Responses To This Notice
The Attachments to this Notice are:
1 - Data Call-In Chemical Status Sheet
2 - Product-Specific Data Call-In Response Form (Insert A)
3 - Requirements Status and Registrant's Response Form (Insert B)
4 - EPA Batching of End-Use Products for Meeting Acute Toxicology Data
Requirements for Reregistration
5 - List of Registrants Receiving This Notice
SECTIONI. WHY YOU ARE RECEIVING THIS NOTICE
The Agency has reviewed existing data for this active ingredient and reevaluated the data
needed to support continued registration of the subject active ingredient. The Agency has
concluded that the only additional data necessary are product specific data. No additional generic
data requirements are being imposed. You have been sent this Notice because you have product(s)
containing the subject active ingredient.
SECTION II. DATA REQUIRED BY THIS NOTICE
II-A. DATA REQUIRED
The product specific data required by this Notice are specified in Attachment 3, Requirements
Status and Registrant's Response Form (Insert B). Depending on the results of the studies required in
this Notice, additional testing may be required.
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II-B. SCHEDULE FOR SUBMISSION OF DATA
You are required to submit the data or otherwise satisfy the data requirements specified in Insert B,
Requirements Status and Registrant's Response Form (Insert BX within the time frames provided.
II-C. TESTING PROTOCOL
All studies required under this Notice must be conducted in accordance with test standards
outlined in the Pesticide Assessment Guidelines for those studies for which guidelines have
been established.
These EPA Guidelines are available from the National Technical Information Service
(NTIS), Attn: Order Desk, 5285 Port Royal Road, Springfield, Va 22161 (tel: 703-487-4650).
Protocols approved by the Organization for Economic Cooperation and Development
(OECD) are also acceptable if the OECD-recommended test standards conform to those
specified in the Pesticide Data Requirements regulation (40 CFR § 158.70). When using the
OECD protocols, they should be modified as appropriate so that the data generated by the
study will satisfy the requirements of 40 CFR § 158. Normally, the Agency will not extend
deadlines for complying with data requirements when the studies were not conducted in
accordance with acceptable standards. The OECD protocols are available from OECD, 2001
L Street, N.W., Washington, D.C. 20036 (Telephone number 202-785-6323; Fax telephone
number 202-785-03 50).
All new studies and proposed protocols submitted in response to this Data Call-In
Notice must be in accordance with Good Laboratory Practices [40 CFR Part 160.3(a)(6)].
II-D. REGISTRANTS RECEIVING PREVIOUS SECTION 3(c)(2)(B) NOTICES
ISSUED BY THE AGENCY
Unless otherwise noted herein, this Data Call-In does not in any way supersede or change
the requirements of any previous Data Call-In(sX or any other agreements entered into with
the Agency pertaining to such prior Notice. Registrants must comply with the requirements of
all Notices to avoid issuance of a Notice of Intent to Suspend their affected products.
SECTION III. COMPLIANCE WITH REQUIREMENTS OF THIS NOTICE
III-A. SCHEDULE FOR RESPONDING TO THE AGENCY
The appropriate responses initially required by this Notice for product specific data
must be submitted to the Agency within 90 days after your receipt of this Notice. Failure to
adequately respond to this Notice within 90 days of your receipt will be a basis for issuing a
Notice of Intent to Suspend (NOIS) affecting your products. This and other bases for issuance
of NOIS due to failure to comply with this Notice are presented in Section IV-A and IV-B.
III-B. OPTIONS FOR RESPONDING TO THE AGENCY
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The options for responding to this Notice for product specific data are: (a) voluntary
cancellation, (b) agree to satisfy the product specific data requirements imposed by this notice
or (c) request a data waiver(s).
A discussion of how to respond if you chose the Voluntary Cancellation option is
presented below. A discussion of the various options available for satisfying the product
specific data requirements of this Notice is contained in Section III-C. A discussion of
options relating to requests for data waivers is contained in Section III-D.
There are two forms that accompany this Notice of which, depending upon your
response, one or both must be used in your response to the Agency. These forms are the Data-
Call-in Response Form (Insert A), and the Requirements Status and Registrant's Response
Form (Insert B). The Data Call-In Response Form must be submitted as part of every response
to this Notice. In addition, one copy of the Requirements Status and Registrant's Response
Form (Insert B) must be submitted for each product listed on the Data Call-In Response Form
(Insert A) unless the voluntary cancellation option is selected or unless the product is
identical to another (refer to the instructions for completing the Data Call-In Response
Form(Insert A). Please note that the company's authorized representative is required to sign
the first page of the Data Call-In Response Form (Insert A) and Requirements Status and
Registrant's Response Form (Insert B), initial any subsequent pages. The forms contain
separate detailed instructions on the response options. Do not alter the printed material. If
you have questions or need assistance in preparing your response, call or write the contact
person(s) identified in Attachment 1.
1. Voluntary Cancellation - You may avoid the requirements of this Notice by
requesting voluntary cancellation of your product(s) containing the active ingredient that is
the subject of this Notice. If you wish to voluntarily cancel your product, you must submit a
completed Data Call-In Response Form (Insert AX indicating your election of this option.
Voluntary cancellation is item number 5 on the Data Call-In Response Form (Insert B). If you
choose this option, this is the only form that you are required to complete.
If you chose to voluntarily cancel your product, further sale and distribution of your
product after the effective date of cancellation must be in accordance with the Existing Stocks
provisions of this Notice which are contained in Section IV-C.
2. Satisfying the Product Specific Data Requirements of this Notice There are various
options available to satisfy the product specific data requirements of this Notice. These
options are discussed in Section III-C of this Notice and comprise options 1 through 5 on the
Requirements Status and Registrant's Response Formdnsert A) and item numbers 7a and 7b
on the Data Call-In Response Formdnsert B). Deletion of a use(s) and the low volume/minor
use option are not valid options for fulfilling product specific data requirements.
3. Request for Product Specific Data Waivers. Waivers for product specific data are
discussed in Section III-D of this Notice and are covered by option 7 on the Requirements
Status and Registrant's Response Form (Insert B). If you choose one of these options, you
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must submit both forms as well as any other information/data pertaining to the option chosen
to address the data requirement.
III-C SATISFYING THE DATA REQUIREMENTS OF THIS NOTICE
If you acknowledge on the Data Call-In Response Form (Insert A) that you agree to
satisfy the product specific data requirements (i.e. you select item number 7a or 7b), then you
must select one of the six options on the Requirements Status and Registrant's Response Form
(Insert A) related to data production for each data requirement. Your option selection should
be entered under item number 9, "Registrant Response." The six options related to data
production are the first six options discussed under item 9 in the instructions for completing
the Requirements Status and Registrant's Response Formdnsert A). These six options are
listed immediately below with information in parentheses to guide registrants to additional
instructions provided in this Section. The options are:
(1) I will generate and submit data within the specified time frame (Developing Data)
(2) I have entered into an agreement with one or more registrants to develop data jointly
(Cost Sharing)
(3) I have made offers to cost-share (Offers to Cost Share)
(4) I am submitting an existing study that has not been submitted previously to the
Agency by anyone (Submitting an Existing Study)
(5) I am submitting or citing data to upgrade a study classified by EPA as partially
acceptable and upgradeable (Upgrading a Study)
(6) I am citing an existing study that EPA has classified as acceptable or an existing study
that has been submitted but not reviewed by the Agency (Citing an Existing Study)
Option 1, Developing Data ~ If you choose to develop the required data it must be in
conformance with Agency deadlines and with other Agency requirements as referenced here
in and in the attachments. All data generated and submitted must comply with the Good
Laboratory Practice (GLP) rule (40 CFRPart 160), be conducted according to the Pesticide
Assessment Guidelines(PAG), and be in conformance with the requirements of PR Notice 86-
5.
The time frames in the Requirements Status and Registrant's Response Form (Insert A)
are the time frames that the Agency is allowing for the submission of completed study reports.
The noted deadlines run from the date of the receipt of this Notice by the registrant. If the
data are not submitted by the deadline, each registrant is subject to receipt of a Notice of
Intent to Suspend the affected registration(s).
If you cannot submit the data/reports to the Agency in the time required by this Notice
and intend to seek additional time to meet the requirements(s), you must submit a request to
the Agency which includes: (1) a detailed description of the expected difficulty and (2) a
proposed schedule including alternative dates for meeting such requirements on a step-by-step
basis. You must explain any technical or laboratory difficulties and provide documentation
from the laboratory performing the testing. While EPA is considering your request, the
original deadline remains. The Agency will respond to your request in writing. If EPA does
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not grant your request, the original deadline remains. Normally, extensions can be requested
only in cases of extraordinary testing problems beyond the expectation or control of the
registrant. Extensions will not be given in submitting the 90-day responses. Extensions will
not be considered if the request for extension is not made in a timely fashion; in no event shall
an extension request be considered if it is submitted at or after the lapse of the subject
deadline.
Option 2, Agreement to Share in Cost to Develop Data ~ Registrants may only choose this
option for acute toxicity data and certain efficacy data and only if EPA has indicated in the
attached data tables that your product and at least one other product are similar for purposes of
depending on the same data. If this is the case, data may be generated for just one of the
products in the group. The registration number of the product for which data will be
submitted must be noted in the agreement to cost share by the registrant selecting this option.
If you choose to enter into an agreement to share in the cost of producing the required data but
will not be submitting the data yourself, you must provide the name of the registrant who will
be submitting the data. You must also provide EPA with documentary evidence that an
agreement has been formed. Such evidence may be your letter offering to join in an
agreement and the other registrant's acceptance of your offer, or a written statement by the
parties that an agreement exists. The agreement to produce the data need not specify all of the
terms of the final arrangement between the parties or the mechanism to resolve the terms.
Section 3(c)(2)(B) provides that if the parties cannot resolve the terms of the agreement they
may resolve their differences through binding arbitration.
Option 3, Offer to Share in the Cost of Data Development — This option only applies to
acute toxicity and certain efficacy data as described in option 2 above. If you have made an
offer to pay in an attempt to enter into an agreement or amend an existing agreement to meet
the requirements of this Notice and have been unsuccessful, you may request EPA (by
selecting this option) to exercise its discretion not to suspend your registration(s), although
you do not comply with the data submission requirements of this Notice. EPA has determined
that as a general policy, absent other relevant considerations, it will not suspend the
registration of a product of a registrant who has in good faith sought and continues to seek to
enter into a joint data development/cost sharing program, but the other registrant(s)
developing the data has refused to accept your offer. To qualify for this option, you must
submit documentation to the Agency proving that you have made an offer to another registrant
(who has an obligation to submit data) to share in the burden of developing that data. You
must also submit to the Agency a completed EPA Form 8570-32, Certification of Offer to
Cost Share in the Development of Data, Attachment 7. In addition, you must demonstrate that
the other registrant to whom the offer was made has not accepted your offer to enter into a
cost sharing agreement by including a copy of your offer and proof of the other registrant's
receipt of that offer (such as a certified mail receipt). Your offer must, in addition to anything
else, offer to share in the burden of producing the data upon terms to be agreed or failing
agreement to be bound by binding arbitration as provided by FIFRA section 3(c)(2)(B)(iii)
and must not qualify this offer. The other registrant must also inform EPA of its election of
an option to develop and submit the data required by this Notice by submitting a Data Call-In
Response Form (Insert A) and a Requirements Status and Registrant's Response Form (Insert
B) committing to develop and submit the data required by this Notice.
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In order for you to avoid suspension under this option, you may not withdraw your
offer to share in the burdens of developing the data. In addition, the other registrant must
fulfill its commitment to develop and submit the data as required by this Notice. If the other
registrant fails to develop the data or for some other reason is subject to suspension, your
registration as well as that of the other registrant will normally be subject to initiation of
suspension proceedings, unless you commit to submit, and do submit the required data in the
specified time frame. In such cases, the Agency generally will not grant a time extension for
submitting the data.
Option 4, Submitting an Existing Study ~ If you choose to submit an existing study in
response to this Notice, you must determine that the study satisfies the requirements imposed
by this Notice. You may only submit a study that has not been previously submitted to the
Agency or previously cited by anyone. Existing studies are studies which predate issuance of
this Notice. Do not use this option if you are submitting data to upgrade a study. (See Option
5).
You should be aware that if the Agency determines that the study is not acceptable, the
Agency will require you to comply with this Notice, normally without an extension of the
required date of submission. The Agency may determine at any time that a study is not valid
and needs to be repeated.
To meet the requirements of the DCI Notice for submitting an existing study, all of
the following three criteria must be clearly met:
a. You must certify at the time that the existing study is submitted that the raw data and
specimens from the study are available for audit and review and you must identify
where they are available. This must be done in accordance with the requirements of
the Good Laboratory Practice (GLP) regulation, 40 CFR Part 160. As stated in 40 CFR
160.3(j)" 'raw data' means any laboratory worksheets, records, memoranda, notes, or
exact copies thereof, that are the result of original observations and activities of a
study and are necessary for the reconstruction and evaluation of the report of that
study. In the event that exact transcripts of raw data have been prepared (e.g., tapes
which have been transcribed verbatim, dated, and verified accurate by signature), the
exact copy or exact transcript may be substituted for the original source as raw data.
'Raw data' may include photographs, microfilm or microfiche copies, computer
printouts, magnetic media, including dictated observations, and recorded data from
automated instruments." The term "specimens", according to 40 CFR 160.3(k), means
"any material derived from a test system for examination or analysis."
b. Health and safety studies completed after May 1984 must also contain all GLP-
required quality assurance and quality control information, pursuant to the
requirements of 40 CFR Part 160. Registrants must also certify at the time of
submitting the existing study that such GLP information is available for post-May
1984 studies by including an appropriate statement on or attached to the study signed
by an authorized official or representative of the registrant.
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c. You must certify that each study fulfills the acceptance criteria for the Guideline
relevant to the study provided in the FIFRA Accelerated Reregistration Phase 3
Technical Guidance and that the study has been conducted according to the Pesticide
Assessment Guidelines (PAG) or meets the purpose of the PAG (both available from
NTIS). A study not conducted according to the PAG may be submitted to the Agency
for consideration if the registrant believes that the study clearly meets the purpose of
the PAG. The registrant is referred to 40 CFR 158.70 which states the Agency's policy
regarding acceptable protocols. If you wish to submit the study, you must, in addition
to certifying that the purposes of the PAG are met by the study, clearly articulate the
rationale why you believe the study meets the purpose of the PAG, including copies of
any supporting information or data. It has been the Agency's experience that studies
completed prior to January 1970 rarely satisfied the purpose of the PAG and that
necessary raw data are usually not available for such studies.
If you submit an existing study, you must certify that the study meets all requirements
of the criteria outlined above.
If you know of a study pertaining to any requirement in this Notice which does not
meet the criteria outlined above but does contain factual information regarding unreasonable
adverse effects, you must notify the Agency of such a study. If such study is in the Agency's
files, you need only cite it along with the notification. If not in the Agency's files, you must
submit a summary and copies as required by PR Notice 86-5.
Option 5, Upgrading a Study ~ If a study has been classified as partially acceptable and
upgradeable, you may submit data to upgrade that study. The Agency will review the data
submitted and determine if the requirement is satisfied. If the Agency decides the requirement
is not satisfied, you may still be required to submit new data normally without any time
extension. Deficient, but upgradeable studies will normally be classified as supplemental.
However, it is important to note that not all studies classified as supplemental are
upgradeable. If you have questions regarding the classification of a study or whether a study
may be upgraded, call or write the contact person listed in Attachment 1. If you submit data to
upgrade an existing study you must satisfy or supply information to correct all deficiencies in
the study identified by EPA. You must provide a clearly articulated rationale of how the
deficiencies have been remedied or corrected and why the study should be rated as acceptable
to EPA. Your submission must also specify the MRID number(s) of the study which you are
attempting to upgrade and must be in conformance with PR Notice 86-5.
Do not submit additional data for the purpose of upgrading a study classified as
unacceptable and determined by the Agency as not capable of being upgraded.
This option should also be used to cite data that has been previously submitted to
upgrade a study, but has not yet been reviewed by the Agency. You must provide the MRID
number of the data submission as well as the MRID number of the study being upgraded.
The criteria for submitting an existing study, as specified in Option 4 above, apply to
all data submissions intended to upgrade studies. Additionally your submission of data
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intended to upgrade studies must be accompanied by a certification that you comply with each
of those criteria as well as a certification regarding protocol compliance with Agency
requirements.
Option 6, Citing Existing Studies ~ If you choose to cite a study that has been previously
submitted to EPA, that study must have been previously classified by EPA as acceptable or it
must be a study which has not yet been reviewed by the Agency. Acceptable toxicology
studies generally will have been classified as "core-guideline" or "core minimum." For all
other disciplines the classification would be "acceptable." With respect to any studies for
which you wish to select this option you must provide the MRID number of the study you are
citing and, if the study has been reviewed by the Agency, you must provide the Agency's
classification of the study.
If you are citing a study of which you are not the original data submitter, you must
submit a completed copy of EPA Form 8570-34, Certification with Respect to Citations of
Data (in PR Notice 98-51.
Registrants who select one of the above 6 options must meet all of the requirements
described in the instructions for completing the Data Call-In Response Form (Insert A) and
the Requirements Status and Registrant's Response Form (Insert B), as appropriate.
III-D. REQUESTS FOR DATA WAIVERS
If you request a waiver for product specific data because you believe it is
inappropriate, you must attach a complete justification for the request, including technical
reasons, data and references to relevant EPA regulations, guidelines or policies. (Note: any
supplemental data must be submitted in the format required by PR Notice 86-5). This will be
the only opportunity to state the reasons or provide information in support of your request. If
the Agency approves your waiver request, you will not be required to supply the data pursuant
to section 3(c)(2)(B) of FIFRA. If the Agency denies your waiver request, you must choose an
option for meeting the data requirements of this Notice within 30 days of the receipt of the
Agency's decision. You must indicate and submit the option chosen on the Requirements
Status and Registrant's Response Form. Product specific data requirements for product
chemistry, acute toxicity and efficacy (where appropriate) are required for all products and the
Agency would grant a waiver only under extraordinary circumstances. You should also be
aware that submitting a waiver request will not automatically extend the due date for the study
in question. Waiver requests submitted without adequate supporting rationale will be denied
and the original due date will remain in force.
IV. CONSEQUENCES OF FAILURE TO COMPLY WITH THIS NOTICE
IV-A NOTICE OF INTENT TO SUSPEND
The Agency may issue a Notice of Intent to Suspend products subject to this Notice
due to failure by a registrant to comply with the requirements of this Data Call-In Notice,
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pursuant to FIFRA section 3(c)(2)(B). Events which may be the basis for issuance of a Notice
of Intent to Suspend include, but are not limited to, the following:
1. Failure to respond as required by this Notice within 90 days of your receipt of this
Notice.
2. Failure to submit on the required schedule an acceptable proposed or final protocol
when such is required to be submitted to the Agency for review.
3. Failure to submit on the required schedule an adequate progress report on a study as
required by this Notice.
4. Failure to submit on the required schedule acceptable data as required by this Notice.
5. Failure to take a required action or submit adequate information pertaining to any
option chosen to address the data requirements (e.g., any required action or
information pertaining to submission or citation of existing studies or offers,
arrangements, or arbitration on the sharing of costs or the formation of Task Forces,
failure to comply with the terms of an agreement or arbitration concerning joint data
development or failure to comply with any terms of a data waiver).
6. Failure to submit supportable certifications as to the conditions of submitted studies,
as required by Section III-C of this Notice.
7. Withdrawal of an offer to share in the cost of developing required data.
8. Failure of the registrant to whom you have tendered an offer to share in the cost of
developing data and provided proof of the registrant's receipt of such offer or failure of
a registrant on whom you rely for a generic data exemption either to:
a. inform EPA of intent to develop and submit the data required by this Notice on
a Data Call-In Response Formdnsert A) and a Requirements Status and
Registrant's Response Formdnsert B):
b. fulfill the commitment to develop and submit the data as required by this
Notice; or
c. otherwise take appropriate steps to meet the requirements stated in this Notice,
unless you commit to submit and do submit the required data in the specified
time frame.
9. Failure to take any required or appropriate steps, not mentioned above, at any time
following the issuance of this Notice.
IV-B. BASIS FOR DETERMINATION THAT SUBMITTED STUDY IS
UNACCEPTABLE
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The Agency may determine that a study (even if submitted within the required time) is
unacceptable and constitutes a basis for issuance of a Notice of Intent to Suspend. The
grounds for suspension include, but are not limited to, failure to meet any of the following:
1. EPA requirements specified in the Data Call-In Notice or other documents incorporated by
reference (including, as applicable, EPA Pesticide Assessment Guidelines, Data Reporting
Guidelines, and GeneTox Health Effects Test Guidelines) regarding the design, conduct, and
reporting of required studies. Such requirements include, but are not limited to, those relating
to test material, test procedures, selection of species, number of animals, sex and distribution
of animals, dose and effect levels to be tested or attained, duration of test, and, as applicable,
Good Laboratory Practices.
2. EPA requirements regarding the submission of protocols, including the incorporation of
any changes required by the Agency following review.
3. EPA requirements regarding the reporting of data, including the manner of reporting, the
completeness of results, and the adequacy of any required supporting (or raw) data, including,
but not limited to, requirements referenced or included in this Notice or contained in PR 86-5.
All studies must be submitted in the form of a final report; a preliminary report will not be
considered to fulfill the submission requirement.
IV-C EXISTING STOCKS OF SUSPENDED OR CANCELED PRODUCTS
EPA has statutory authority to permit continued sale, distribution and use of existing
stocks of a pesticide product which has been suspended or canceled if doing so would be
consistent with the purposes of the Act.
The Agency has determined that such disposition by registrants of existing stocks for a
suspended registration when a section 3(c)(2)(B) data request is outstanding would generally
not be consistent with the Act's purposes. Accordingly, the Agency anticipates granting
registrants permission to sell, distribute, or use existing stocks of suspended product(s) only in
exceptional circumstances. If you believe such disposition of existing stocks of your
product(s) which may be suspended for failure to comply with this Notice should be
permitted, you have the burden of clearly demonstrating to EPA that granting such permission
would be consistent with the Act. You must also explain why an "existing stocks" provision is
necessary, including a statement of the quantity of existing stocks and your estimate of the
time required for their sale, distribution, and use. Unless you meet this burden the Agency
will not consider any request pertaining to the continued sale, distribution, or use of your
existing stocks after suspension.
If you request a voluntary cancellation of your product(s) as a response to this Notice
and your product is in full compliance with all Agency requirements, you will have, under
most circumstances, one year from the date your 90 day response to this Notice is due, to sell,
distribute, or use existing stocks. Normally, the Agency will allow persons other than the
registrant such as independent distributors, retailers and end users to sell, distribute or use
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such existing stocks until the stocks are exhausted. Any sale, distribution or use of stocks of
voluntarily canceled products containing an active ingredient for which the Agency has
particular risk concerns will be determined on case-by-case basis.
Requests for voluntary cancellation received after the 90 day response period required
by this Notice will not result in the Agency granting any additional time to sell, distribute, or
use existing stocks beyond a year from the date the 90 day response was due unless you
demonstrate to the Agency that you are in full compliance with all Agency requirements,
including the requirements of this Notice. For example, if you decide to voluntarily cancel
your registration six months before a 3 year study is scheduled to be submitted, all progress
reports and other information necessary to establish that you have been conducting the study
in an acceptable and good faith manner must have been submitted to the Agency, before EPA
will consider granting an existing stocks provision.
SECTION V. REGISTRANTS' OBLIGATION TO REPORT POSSIBLEUNREASONABLE
ADVERSE EFFECTS
Registrants are reminded that FIFRA section 6(a)(2) states that if at any time after a pesticide
is registered a registrant has additional factual information regarding unreasonable adverse effects on
the environment by the pesticide, the registrant shall submit the information to the Agency.
Registrants must notify the Agency of any factual information they have, from whatever source,
including but not limited to interim or preliminary results of studies, regarding unreasonable adverse
effects on man or the environment. This requirement continues as long as the products are registered
by the Agency.
SECTION VI. INQUIRIES AND RESPONSES TO THIS NOTICE
If you have any questions regarding the requirements and procedures established by
this Notice, call the contact person(s) listed in Attachment 1, the Data Call-In Chemical Status
Sheet.
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All responses to this Notice (other than voluntary cancellation requests and generic
data exemption claims) must include a completed Data Call-In Response Form (Insert A) and
a completed Requirements Status and Registrant's Response Form (Insert B) for product
specific data) and any other documents required by this Notice, and should be submitted to
the contact person(s) identified in Attachment 1. If the voluntary cancellation or generic data
exemption option is chosen, only the Data Call-In Response Form (Insert A) need be
submitted.
The Office of Compliance Monitoring (OCM) of the Office of Pesticides and Toxic
Substances (OPTS), EPA, will be monitoring the data being generated in response to this
Notice.
Sincerely yours,
Lois A. Rossi, Director
Special Review and
Reregistration Division
Attachments
1 - Data Call-In Chemical Status Sheet
2 - Product-Specific Data Call-In Response Form (Insert A)
3 - Requirements Status and Registrant's Response Form (Insert B)
4 - EPA Batching of End-Use Products for Meeting Acute Toxicology Data Requirements
for Reregistration
5 - List of Registrants Receiving This Notice
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BROMOXYNIL DATA CALL-IN CHEMICAL STATUS SHEET
INTRODUCTION
You have been sent this Product Specific Data Call-In Notice because you have product(s)
containing bromoxynil.
This Product Specific Data Call-In Chemical Status Sheet contains an overview of data required
by this notice, and point of contact for inquiries pertaining to the reregi strati on of bromoxynil. This
attachment is to be used in conjunction with (1) the Product Specific Data Call-In Notice, (2) the
Product Specific Data Call-In Response Form (Attachment 2), (3) the Requirements Status and
Registrant's Form (Attachment 3), (4) EPA's Grouping of End-Use Products for Meeting Acute
Toxicology Data Requirement (Attachment 4), (5) the EPA Acceptance Criteria (Attachment 5), (6) a
list of registrants receiving this DCI (Attachment 6) and (7) the Cost Share and Data Compensation
Forms in replying to this bromoxynil Product Specific Data Call-In (Attachment 7). Instructions and
guidance accompany each form.
DATA REQUIRED BY THIS NOTICE
The additional data requirements needed to complete the database for bromoxynil are contained
in the Requirements Status and Registrant's Response. Attachment 3. The Agency has concluded that
additional data on bromoxynil are needed for specific products. These data are required to be submitted
to the Agency within the time frame listed. These data are needed to fully complete the reregistration
of all eligible bromoxynil products.
INQUIRIES AND RESPONSES TO THIS NOTICE
If you have any questions regarding this product specific data requirements and procedures
established by this Notice, please contact Karen Jones at (703) 308-8047.
All responses to this Notice for the Product Specific data requirements should be submitted to:
Chemical Review Manager Team 81
Product Reregistration Branch
Special Review and Reregistration Branch 7508W
Office of Pesticide Programs
U.S. Environmental Protection Agency
Washington, D.C. 20460
RE: BROMOXYNIL
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INSTRUCTIONS FOR COMPLETING THE DATA CALL-IN RESPONSE FORM FOR
PRODUCT SPECIFIC DATA
Item 1-4. Already completed by EPA.
Item 5. If you wish to voluntarily cancel your product, answer "yes." If you choose this option,
you will not have to provide the data required by the Data Call-In Notice and you will
not have to complete any other forms. Further sale and distribution of your product after
the effective date of cancellation must be in accordance with the Existing Stocks
provision of the Data Call-In Notice (Section IV-C).
Item 6. Not applicable since this form calls in product specific data only. However, if your
product is identical to another product and you qualify for a data exemption, you must
respond with "yes" to Item 7a (MUP) or 7B (EUP) on this form, provide the EPA
registration numbers of your source(s); you would not complete the "Requirements
Status and Registrant's Response" form. Examples of such products include repackaged
products and Special Local Needs (Section 24c) products which are identical to
federally registered products.
Item 7a. For each manufacturing use product (MUP) for which you wish to maintain
registration, you must agree to satisfy the data requirements by responding "yes."
Item 7b. For each end use product (EUP) for which you wish to maintain registration, you must
agree to satisfy the data requirements by responding "yes." If you are requesting a data
waiver, answer "yes" here; in addition, on the "Requirements Status and Registrant's
Response" form under Item 9, you must respond with Option 7 (Waiver Request) for
each study for which you are requesting a waiver. See Item 6 with regard to identical
products and data exemptions.
Items 8-11. Self-explanatory.
NOTE: You may provide additional information that does not fit on this form in a signed letter
that accompanies this form. For example, you may wish to report that your product has
already been transferred to another company or that you have already voluntarily
canceled this product. For these cases, please supply all relevant details so that EPA can
ensure that its records are correct.
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INSTRUCTIONS FOR COMPLETING THE REQUIREMENTS STATUS AND
REGISTRANT'S RESPONSE FORM FOR PRODUCT SPECIFIC DATA
Item 1-3 Completed by EPA. Note the unique identifier number assigned by EPA in Item 3.
This number must be used in the transmittal document for any data submissions in
response to this Data Call-In Notice.
Item 4. The guideline reference numbers of studies required to support the product's continued
registration are identified. These guidelines, in addition to the requirements specified in
the Notice, govern the conduct of the required studies. Note that series 61 and 62 in
product chemistry are now listed under 40 CFR 158.155 through 158.180, Subpart C.
Item 5. The study title associated with the guideline reference number is identified.
Item 6. The use pattern(s) of the pesticide associated with the product specific requirements is
(are) identified. For most product specific data requirements, all use patterns are covered
by the data requirements. In the case of efficacy data, the required studies only pertain
to products which have the use sites and/or pests indicated.
Item 7. The substance to be tested is identified by EPA. For product specific data, the product
as formulated for sale and distribution is the test substance, except in rare cases.
Item 8. The due date for submission of each study is identified. It is normally based on 8 months
after issuance of the Reregistration Eligibility Document unless EPA determines that
a longer time period is necessary.
Item 9 Enter only one of the following response codes for each data requirement to show
how you intend to comply with the data requirements listed in this table. Fuller
descriptions of each option are contained in the Data Call-In Notice.
1. I will generate and submit data by the specified due date (Developing Data). By
indicating that I have chosen this option, I certify that I will comply with all the
requirements pertaining to the conditions for submittal of this study as outlined in the
Data Call-In Notice. By the specified due date, I will also submit: (1) a completed
"Certification with Respect to Citations of Data (in PR Notice 98-5)" form (EPA
Form 8570-34) and (2) two completed and signed copies of the Confidential
Statement of Formula (EPA Form 8570-4)
2. I have entered into an agreement with one or more registrants to develop data jointly
(Cost Sharing). I am submitting a copy of this agreement. I understand that this
option is available only for acute toxicity or certain efficacy data and only if EPA
indicates in an attachment to this Notice that my product is similar enough to another
product to qualify for this option. I certify that another party in the agreement is
committing to submit or provide the required data; if the required study is not submitted
on time, my product may be subject to suspension. By the specified due date, I will also
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submit: (1) a completed "Certification with Respect to Citations of Data (in PR
Notice 98-5)" form (EPA Form 8570-34) and (2) two completed and signed copies of
the Confidential Statement of Formula (EPA Form 8570-4)
3. I have made offers to share in the cost to develop data (Offers to Cost Share). I
understand that this option is available only for acute toxicity or certain efficacy data and
only if EPA indicates in an attachment to this Data Call-In Notice that my product is
similar enough to another product to qualify for this option. I am submitting evidence
that I have made an offer to another registrant (who has an obligation to submit data)
to share in the cost of that data. I am also submitting a completed "Certification of
Attempt to Enter into an Agreement with other Restraints for Development of
Data " (EPA Form 8570-32). I am including a copy of my offer and proof of the other
registrant's receipt of that offer. I am identifying the party which is committing to submit
or provide the required data; if the required study is not submitted on time, my product
may be subject to suspension. I understand that other terms under Option 3 in the Data
Call-In Notice (Section III-C.l.) apply as well. By the specified due date, I will also
submit: (1) a completed "Certification With Respect To Data Compensation
Requirements" form (EPA Form 8570-34) and (2) two completed and signed copies
of the Confidential Statement of Formula (EPA Form 8570-4)
4. By the specified due date, I will submit an existing study that has not been submitted
previously to the Agency by anyone (Submitting an Existing Study). I certify that this
study will meet all the requirements for submittal of existing data outlined in Option 4
in the Data Call-In Notice (Section III-C.l.) and will meet the attached acceptance
criteria (for acute toxicity and product chemistry data). I will attach the needed
supporting information along with this response. I also certify that I have determined
that this study will fill the data requirement for which I have indicated this choice. By
the specified due date, I will also submit a completed "Certification With Respect To
Data Compensation Requirements" form (EPA Form 8570-34) to show what data
compensation option I have chosen. By the specified due date, I will also submit: (1) a
completed "Certification With Respect To Data Compensation Requirements"
form (EPA Form 8570-34) and (2) two completed and signed copies of the
Confidential Statement of Formula (EPA Form 8570-4)
5. By the specified due date, I will submit or cite data to upgrade a study classified by the
Agency as partially acceptable and upgradable (Upgrading a Study). I will submit
evidence of the Agency's review indicating that the study may be upgraded and what
information is required to do so. I will provide the MRID or Accession number of the
study at the due date. I understand that the conditions for this option outlined Option
5 in the Data Call-In Notice (Section III-C.l.) apply. By the specified due date, I will
also submit: (1) a completed "Certification With Respect To Data Compensation
Requirements" form (EPA Form 8570-34) and (2) two completed and signed copies
of the Confidential Statement of Formula (EPA Form 8570-4)
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6. By the specified due date, I will cite an existing study that the Agency has classified as
acceptable or an existing study that has been submitted but not reviewed by the Agency
(Citing an Existing Study). If I am citing another registrant's study, I understand that
this option is available only for acute toxicity or certain efficacy data and only if the cited
study was conducted on my product, an identical product or a product which EPA has
"grouped" with one or more other products for purposes of depending on the same data.
I may also choose this option if I am citing my own data. In either case, I will provide
the MRID or Accession number(s) for the cited data on a "Product Specific Data
Report" form or in a similar format. By the specified due date, I will also submit: (1) a
completed "Certification With Respect To Data Compensation Requirements"
form (EPA Form 8570-34) and (2) two completed and signed copies of the
Confidential Statement of Formula (EPA Form 8570-4)
7. I request a waiver for this study because it is inappropriate for my product (Waiver
Request). I am attaching a complete justification for this request, including technical
reasons, data and references to relevant EPA regulations, guidelines or policies. [Note:
any supplemental data must be submitted in the format required by P.R. Notice 86-5].
I understand that this is my only opportunity to state the reasons or provide information
in support of my request. If the Agency approves my waiver request, I will not be
required to supply the data pursuant to Section 3(c)(2)(B) of FIFRA. If the Agency
denies my waiver request, I must choose a method of meeting the data requirements of
this Notice by the due date stated by this Notice. In this case, I must, within 30 days of
my receipt of the Agency's written decision, submit a revised "Requirements Status and
Registrant's Response" Form indicating the option chosen. I also understand that the
deadline for submission of data as specified by the original data call-in notice will not
change. By the specified due date, I will also submit: (1) a completed "Certification
With Respect To Data Compensation Requirements" form (EPA Form 8570-34)
and (2) two completed and signed copies of the Confidential Statement of Formula
(EPA Form 8570-4)
Items 10-13. Self-explanatory.
NOTE: You may provide additional information that does not fit on this form in a signed letter
that accompanies this form. For example, you may wish to report that your product has
already been transferred to another company or that you have already voluntarily
canceled this product. For these cases, please supply all relevant details so that EPA can
ensure that its records are correct.
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EPA'S BATCHING OF BROMOXYNIL PPRODUCTS FOR MEETING ACUTE
MAMMALIAN 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 reregi strati on of products containing Bromoxynil as the 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 that 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. Notwith-standing the batching process, the Agency reserves the right to require,
at any time, acute toxicity data for an individual product should the 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, or only their own products within a batch, or to generate all the required acute toxicological
studies for each of their own products. If a 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 a 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, 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 a registrant supplies the data to support a batch of products, he/she
must select 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.
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Nineteen active products were found which contain Bromoxynil as the active ingredient. These
products have been placed into five batches and a "no batch" group in accordance with the active and
inert ingredients, type of formulation and current labeling.
Batch
1
EPA Reg. No.
264-229
264-473
33688-8
% Active Ingredient
94.0*
95.0*
94.0*
Formulation Type
Solid
Solid
Solid
Batch
2
EPA Reg. No.
264-395
33688-9
% Active Ingredient
87.3
87.3
Formulation Type
Solid
Solid
Batch
3
EPA Reg. No.
264-437
51036-256
% Active Ingredient
33.4
33.4
Formulation Type
Liquid
Liquid
Batch
4
EPA Reg. No.
264-477
9779-348
51036-255
% Active Ingredient
Bromoxynil 15.74
Atrazine21.62
Bromoxynil 15.74
Atrazine21.62
Bromoxynil 15.74
Atrazine21.62
Formulation Type
Liquid
Liquid
Liquid
Batch
5
EPA Reg. No.
264-438
51036-254
% Active Ingredient
Bromoxynil 31.7
Isooctyl ester of 2-methyl-chlorophen-
oxyacetic acid 34.0
Bromoxynil 31.7
Isooctyl ester of 2-methyl-chlorophen-
oxyacetic acid 34.0
Formulation Type
Liquid
Liquid
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No Batch
EPA Reg. No.
264-442
264-531
264-533
264-540
264-544
264-551
9779-346
% Active Ingredient
95.0
Bromoxynil [oct] 28.7
Bromoxynil [hep] 27.6
Bromoxynil [oct] 48.8
Bromoxynil [hep] 47.2
Bromoxynil [oct] 28.0
Bromoxynil [hep] 27.0
Bromoxynil [oct] 18.6
Bromoxynil [hep] 17.9
Isooctyl ester of 2-methyl-chlorophen-
oxyacetic acid 39.7
Bromoxynil [oct] 14.6
Bromoxynil [hep] 14.1
Artazine 39.8
33.4*
Formulation Type
Solid
Gel
Solid
Liquid
Gel
Gel
Liquid
(*) Contains the phenolic form of Bromoxynil.
273
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This page has been inserted as a place marker and is replaced by an electronically generated PDCI
List of Registrants page number 1 in the actual Printed version of the Red document
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Pesticide Registration Forms are available at the following EPA internet site:
http ://www. epa. gov/opprdOO I/forms/.
Pesticide Registration 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 hardcopy 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 atwilliams.nicole@epamail.epa.gov.
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
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 Restraints for
Development of Data
Certification with Respect to Citations of Data
(in PR Notice 98-5)
Data Matrix (in PR Notice 98-5)
http://www.epa.gov/opprd001/forms/8570-l.pdf.
http://www.epa.gov/opprd001/forms/8570-4.pdf.
http://www.epa.gov/opprd001/forms/8570-5.pdf.
http://www.epa. gov/opprdOO l/forms/8570- 1 7.pdf.
http://www.epa.gov/opprd001/forms/8570-25.pdf.
http://www.epa.gov/opprd001/forms/8570-27.pdf.
http://www.epa.gov/opprd001/forms/8570-28.pdf.
http://www.epa.gov/opprd001/forms/8570-30.pdf.
http://www.epa.gov/opprd001/forms/8570-32.pdf.
http://www.epa.gov/opppmsdl/PR Notices/pr98-5.pdf.
http://www.epa.gov/opppmsdl/PR Notices/pr98-5.pdf.
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8570-36
8570-37
Summary of the Physical/Chemical Properties
(in PR Notice 98-1)
Self-Certification Statement for the
Physical/Chemical Properties (in PR Notice
98-1)
http://www.epa.gov/opppmsdl/PR Notices/pr98-l .pdf.
http://www.epa.gov/opppmsdl/PR Notices/pr98-l .pdf.
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Pesticide Registration Kit www.epa.gov/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 83-3 Label Improvement Program—Storage and Disposal Statements
b. 84-1 Clarification of Label Improvement Program
c. 86-5 Standard Format for Data Submitted under FIFRA
d. 87-1 Label Improvement Program for Pesticides Applied through Irrigation Systems
(Chemigation)
e. 87-6 Inert Ingredients in Pesticide Products Policy Statement
f 90-1 Inert Ingredients in Pesticide Products; Revised Policy Statement
g. 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, Formulator's Exemption Statement
d. EPA Form No. 8570-34, Certification with Respect to Citations of Data
e. EPA Form No. 8570-35, Data Matrix
4. General Pesticide Information (Some of these forms are in PDF format and will require the
Acrobat reader.)
a. Registration Division Personnel Contact List
Biopesticides and Pollution Prevention Division (BPPD) Contacts
Antimicrobials Division Organizational Structure/Contact List
c. 53 F.R. 15952, Pesticide Registration Procedures; Pesticide Data Requirements (PDF
format)
d. 40 CFR Part 156, Labeling Requirements for Pesticides and Devices (PDF format)
e. 40 CFR Part 158, Data Requirements for Registration (PDF format)
f. 50 F.R. 48833, Disclosure of Reviews of Pesticide Data (November 27, 1985)
Before submitting your application for registration, you may wish to consult some additional sources
of information.
These include:
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1. The Office of Pesticide Programs' Web Site
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)
the following address:
National Technical Information Service (NTIS)
5285 Port Royal Road
Springfield, VA 22161
The telephone number for NTIS is (703) 605-6000 and (800) 553- 6847. Please note that EPA
is currently in the process of updating this booklet to reflect the changes in the registration program
resulting from the passage of the FQPA and the reorganization of the Office of Pesticide Programs. We
anticipate that this publication will become available during the Fall of 1998.
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 Web site.
4. The National Pesticide Telecommunications Network (NPTN) can provide information on active
ingredients, uses, toxicology, and chemistry of pesticides. You can contact NPTN by telephone
at 1-800-858-7378 or through their Web site.
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
the 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 CAS number
if one has been assigned.
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Documents Associated with this RED
The following documents are part of the Administrative Record for this RED document and may
included in the EPA's Office of Pesticide Programs Public Docket. Copies of these documents are not
available electronically, but may be obtained by contacting the person listed on the respective Chemical
Status Sheet.
1. Health and Environmental Effects Science Chapters.
2. Detailed Label Usage Information System (LUIS) Report.
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