United States Prevention, Pesticides EPA738-R-98-004
Environmental Protection And Toxic Substances March 1998
Agency (7508W)
ERA Reregistration
Eligibility Decision (RED)
Bacillus thuringiensis
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United States
Environmental Protection
Agency
Prevention, Pesticides
And Toxic Substances
(7511W)
EPA-738-F-98-001
March 1998
R.E.D. FACTS
Pesticide
Reregistration
Use Profile
* Bacillus thuringiensis *
All pesticides sold or distributed in the United States must be
registered by EPA, based on scientific studies showing that they can be used
without posing unreasonable risks to people or the environment. Because of
advances hi scientific knowledge, the law requires that pesticides which were
first registered before November 1, 1984, be reregistered to ensure that they
meet today's more stringent standards.
In evaluating pesticides for reregistxation, EPA obtains and reviews a
complete set of studies from pesticide producers, describing the human
health and environmental effects of each pesticide. The Agency develops
any mitigation measures or regulatory controls needed to effectively reduce
each pesticide's risks. EPA then reregisters pesticides that can be used
without posing unreasonable risks to human health or the environment.
When a pesticide is eligible for reregistration, EPA explains the basis
for its decision in a Reregistration Eligibility Decision (RED) document.
This feet sheet summarizes the information in the RED document for
reregistration case 0247, Bacillus thuringiensis.
' Bacillus thuringiensis is a group of similar bacteria that act as
insecticides which are used on growing agricultural crops, harvested crops in
storage, ornamentals, bodies of water, and around the home to control
various groups of insects, depending on the particular toxins, known as
delta-endotoxins, produced by the specific isolate of Bacillus thuringiensis.
Formulations include Water Dispersible Granule, Dry Flowable,
Aqueous Suspension, Granule, Technical Powder, Dust, Wettable Powder,
Emulsifiable Suspension, Aqueous Flowable, Bait, and Oil Flowable.
Bacillus thuringiensis is applied by hand sprayer, water treatment by
aerial or ground equipment, soil application by drip or overhead irrigation
systems, foliar application by aerial; conventional ground or hand-held
equipment and center-pivot irrigation systems, and sprayer or sprinkler cans.
Use practice limitations include Restricted Entry Intervals (REIs) of 4-
48 hours for agricultural uses; direct water application is not to be applied
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directly to treated, finished drinking water reservoirs or drinking water
receptacles; certain terrestrial uses are limited to terrestrial use only due to
potential aquatic hazard.
Regulatory Bacillus thuringiensis was first registered as a pesticide in the U.S. in
History 1961. EPA issued a Registration Standard for Bacillus thuringiensis in
December, 1988 (#540/RS-89-023). An associated Data Call-in (DCI)
required additional product analysis, toxicology, and nontarget organism
data.
Currently, approximately 180 Bacillus thuringiensis products are
registered under 15 EPA product code numbers. Two of the product codes
no longer have active products.
Isolates of Bacillus thuringiensis were originally grouped as
registrations under the following subspecies names, each with an EPA
product code number: Bacillus thuringiensis subspecies kurstaki, Bacillus
thuringiensis subspecies israelensis, Bacillus thuringiensis subspecies
aizawai and Bacillus thuringiensis subspecies tenebrionis, Each isolate is
now assigned its own product code number and, as part of the reregistration
process, the original registrations will be given new product numbers.
Human Health
Assessment
Toxicity/Pathogenicity
To date, no known mammalian health effects have been demonstrated
in any infectivity/pathogenicity study. Some strains of Bacillus thuringiensis
have the potential to produce various toxins that may exhibit toxic
symptoms in mammals, however the manuiacturing process includes
monitoring to prevent these toxins from appearing in products.
Dietary Exposure
An exemption from the requirements for a tolerance is currently
established for Bacillus thuringiensis in or on beeswax and honey and all
other raw agricultural commodities when it is applied either to growing
crops, or when it is applied after harvest in accordance with good
agricultural practices (40 CFR §180.1011). In addition, there is a tolerance
exemption (40 CFR 180.1001(c)) tor Bacillus thuringiensis fermentations
solids and/or solubles. The absence of any toxicological/pathogenicity
concerns for oral mammalian exposures to Bacillus thuringiensis warrants
continuation of these exemptions as long as the proper quality control
procedures are performed.
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The specific language in the tolerance .exemption does not reflect
current taxonomy designations for Bacillus thuringiensis isolates. In
addition, it includes production testing requirements which will now be
required under the product analysis data requirements in 40 CFR 158.740(a)
and will apply to all registered isolates and all uses of Bacillus thuringiensis.
To ensure that the production batch tests requirements do not lapse for any
products, the Agency will repropose the tolerance exemptions following
establishment of the new manufacturing process requirements as described in
the Reregistration Eligibility Document.
Environmental
Assessment
s Toxicity and infectivity risks due to delta-endotoxin effects to
nontarget avian, freshwater fish, freshwater aquatic invertebrates, estuarine
and marine animals, arthropod predators/parasites, honey bees, annelids and
mammalian wildlife will be minimal to nonexistent at the label use rates of
registered B. thuringiensis active ingredients. However, other toxins which
may be produced by Bacillus thuringiensis can produce adverse direct toxic
effects on nontarget species. Despite the potential for immediate toxic
effects on target, and possibly some nontarget, organisms, there is no
evidence that Bacillus thuringiensis can cause epizooatics in the field.
therefore, the Agency has concluded that there will be no potential for
adverse effects on nontarget organisms for B. thuringiensis-based products if
the the presence of soluble, heat labile exotoxins and beta-exotoxin is
minimized. However, the production process must be^cjosely controlled and
monitored or certified to assure these exotoxins are not present at levels that
can cause significant adverse ecological effects.
Risk Mitigation
Additional Data
Required
To lessen the potential for the production of various undesirable
Bacillus exotoxins, EPA is requiring the following risk mitigation measures.
o Production batch testing is required in order to detect undesirable toxins
and to detect contamination by pathogenic bacteria.
o If the organism is capable of producing beta-exotoxin, the registrant
must ensure that none is present in the TGAI and that the product is not put
in a medium, including formulated end use products that allows germination
and/or growth at any time prior to use.
o Each manufacturing process must be standardized and certified by a
Daphnia magna test using a 10 day exposure period.
EPA is requiring the submission of a new manufacturing process as an
additional generic study for Bacillus thuringiensis to confirm its regulatory
assessments and conclusions.
The Agency also is requiring product-specific data including product
chemistry and acute toxicity studies, a storage stability study, efficacy
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studies for public health uses, revised Confidential Statements of Formula
(CSFs), and revised labeling for reregistration.
Product Labeling All Bacillus thuringiensis end-use products must comply with ERVs
Changes Required current pesticide product labeling requirements and with the following. For
a comprehensive list of labeling requirements, please see the Bacillus
thuringiensis RED document.
Percent Active Ingredient: The percent active ingredient by weight for
Bacillus thuringiensis-based products is required in lieu of potency
determinations and a statement must be included "There is no direct
relationship between intended activity (potency) and the Percent Active
Ingredient by Weight."
Active Ingredients: The label must identify the active ingredient as Bacillus
thuringiensis and all toxins and/or chemical substances that are present at
levels that are known to contribute to the efficacy of the product against the
target pest(s) must be listed on the label. °
Personal Protective Equipment Requirements: A respiratory protection
statement must appear on the label for different uses as follows:
Agricultural Use'Products - The personal protective equipment (PPE)
section must include the statement: "As a general precaution when exposed
to potentially high concentrations of living microbial products such as this,
all mixer/loaders and applicators must wear a dust/mist filtering respirator
meeting NIOSH standards of at least N-95, R-95, or P-95."
Registrants may add the following engineering control statements to the PPE
section if they so choose: "When handlers use closed systems, enclosed
cabs, or aircraft in a manner that meets the requirements listed hi 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."
PPE for early entry hi the Agricultural Use Requirements box remains
unaffected.
Non-Agricultural Use Products not Used Around the Home - Either the
PPE section or the precautionary statements of the Hazards to Humans and
Domestic Animals section must include the statement: "As a general
precaution when exposed to potentially high concentrations of living
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microbial products such as this, all mixer/loaders and applicators not in
enclosed cabs or aircraft must wear a dust/mist filtering respirator meeting
NIOSH standards of at least N-95, R-95, or P-95."
Domestic (Home) Use Products - Either the PPE section or the
precautionary statements of the Hazards to Humans and Domestic Animals
- section must include the statement: "As a general precaution when exposed
to potentially high concentrations of living microbial products such as this,
wear a dust particle mask when mixing or applying this product."
Environmental Hazard Statement: All commercially applied products-with
directions for outdoor terrestrial uses must have the following statements hi
the Environmental Hazards section: "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 when cleaning equipment or
disposing of equipment washwaters." This statement should be preceded by
"For terrestrial uses," if the product has aquatic sites in addition to
terrestrial, forestry (except aerial application) and/or domestic outdoor uses.
This revised statement would then not apply to other general use patterns
aquatic (e.g., mosquito larvicides or adulticides, aquatic herbicides,
piscicides, slimicides, etc.), greenhouse and indoor uses. The "For
terrestrial uses," qualifier is not allowed on products which allow aerial
application to forests but which have no approved aquatic use sites.
For residential consumer products, the required statement is: "Do not
apply directly to water. Do not contaminate water when disposing of
equipment washwaters or rinsate."
For direct water application uses, the required statement is: "Do not
apply directly to treated, finished drinking water reservoirs or drinking
water receptacles."
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."
Regulatory The use of currently registered products containing Bacillus
Conclusion thuringiensis in accordance with approved labeling will not pose
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unreasonable risks or adverse effects to humans or the environment.
Therefore, all uses of these products are eligible for reregistration.
Bacillus thuringiensis products will be reregistered once the required
confirmatory generic data, product-specific data, revised Confidential
Statements of Formula, and revised labeling are received and accepted by
EPA.
For More EPA is requesting' public comments on the Reregistration Eligibility
Information Decision (RED) document for Bacillus thuringiensis during a 60-day time
period, as announced in a Notice of Availability published in the Federal
Register. To obtain a copy of the RED document or to submit written
comments, please contact the Pesticide Docket, Public Response and
Program Resources Branch, Field Operations Division (7506C), Office of
Pesticide Programs (OPP), US EPA, Washington, DC 20460, telephone
703-305-5805.
Electronic copies of the RED and this feet sheet can be downloaded
from the Pesticide Special Review and Reregistration Information System at
703-308-7224. They also are available on the Internet on EPA's web site at
www.epa.gov .
Printed copies of the RED and feet sheet can be obtained from EPA's
National Center for Environmental Publications and Information
(EPA/NCEPI), PO Box 42419, Cincinnati, OH 45242-0419, telephone 513-
489-8190, fex 513-489-8695.
Following the comment period, the Bacillus thuringiensis RED
document also will be available from the National Technical Information
Service (NTIS), 5285 Port Royal Road, Springfield, VA. 22161, telephone
703-487-4650.
For more information about EPA's pesticide reregistration program,
the Bacillus thuringiensis RED, or reregistration of individual products
containing Bacillus thuringiensis, please contact the Biopesticides and
Pollution Prevention Division (7511W), OPP, US EPA, Washington, DC
' 20460, telephone 703-308-8712.
For information about the health effects of pesticides, or for assistance
hi recognizing and managing pesticide poisoning symptoms, please contact
the National Pesticides Telecommunications Network (NPTN). Call toll:
free 1-800-858-7378, between 9:30 am and 7:30 pm Eastern Standard Tune,
Monday through Friday.
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SUMMARY OF INSTRUCTIONS FOR RESPONDING TO
THE REREGISTRATION ELIGIBILITY DECISION (RED)
, ;
1. DATA CALL-IN (PCD OR "90-DAY RESPONSE"-If generic data are required for
reregistration, 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 tune extensions for product specific data
should be submitted hi 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 reregistration) separately. You may, but are not
required to, delete uses which the RED says are ineligible for reregistration,. 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, if available for that study.
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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
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. WBOSRE TO SEND PRODUCT SPECIFIC PCI RESPONSES (90-DAY) AND
APPLICATIONS FOR REREGISTRATION (8-MONTH RESPONSES)
Bv U.S. Mail;
Document Processing Desk (RED-BPPD)
Office of Pesticide Programs (7504C)
EPA, 401 M St. S.W.
Washington, D.C. 20460-0001
By express:
Document Processing Desk (RED-BPPD)
Office of Pesticide Programs (7504C)
Room 266A, Crystal Mall 2
1921 Jefferson Davis Hwy.
Arlington, VA 22202
6. EPA'S REVIEWSEPA 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 tune extension requests within 60 days. EPA will also try to respond to all 8-
month submissions with a final reregistration determination within 14 months after the RED
has been issued.
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, D.C. 20460
OFFICE OF
PREVENTION, PESTICIDES
AND TOXIC SUBSTANCES
3 ! J998
CERTIFIED MAIL
Dear Registrant:
t
I am pleased to announce that the Environmental Protection Agency has completed its
reregistration eligibility review and decisions on the pesticide chemical case 0247, which
includes the active ingredient Bacillus thuringiensis. The enclosed Reregistration Eligibility
Decision (RED) contains the Agency's evaluation of the data base of this microbial pest control
agent, 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 the pesticide law (FIFRA) and the food and drug
law (FFDCA). This RED takes into account the new safety standard set by the FQPA for
establishing and reassessing tolerances. However, it should also be noted that in continuing to
make the reregistration determinations during the early stages- of FQPA implementation, EPA
recognizes that it will be necessary to make decisions relating to FQPA before the
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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 rule-making that may be required.
If EPA determines, as a result of this later implementation process, that any of the
determinations described in the 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 generic and product specific data requirements or wish to
meet with the Agency, please contact the Biopesticides and Pollution Prevention Division
representative, William R. Schneider, at (703) 308-8683, or send eMail to Schneider.william
@epamail.epa.gov
Sincerely yours,
anet L. Andersen, Ph. D., Director
Biopesticides and Pollution
Prevention Division
Enclosures
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REREGISTRATION ELIGIBILITY DECISION
Microbial Pesticides:
Bacillus thuringiensis
LISTD
CASE 0247
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TABLE OF CONTENTS
BACILLUS THURMGDENSIS REREGISTRATION ELIGIBILITY DECISION TEAM
, i
EXECUTIVE SUMMARY '. . . 1
I. INTRODUCTION 2
H. CASE OVERVIEW 3
A. Chemical Overview 3
B. Use Profile 4
C. Estimated Usage of Pesticide ~. .'. 6
D. Data Requirements 6
E. Regulatory History 7
IH. SCIENCE ASSESSMENT 8
A. Product Analysis Assessment 8
1. Identification of Active Ingredients 8
a. Product Identity 8
b. Manufacturing Process 10
c. Discussion of Formation of Unintentional Ingredients .... 11
B. Human Health Assessment 11
1. Toxicology Assessment 11
a. Acute toxicity/pathogenicity 11
b. Potential for producing Bacillus cereus enterotoxins ..... 12
c. Effects on the Immune and Endocrine Systems . 13
2. Dietary Exposure and Risk Characterization 14
3. Occupational, Residential, School and Daycare Exposure and Risk
Characterization 14
a. Occupational Exposure and Risk Characterization 14
b. Residential, School and Daycare Exposure and Risk
Characterization , 14
4. Drinking Water Exposure and Risk Characterization 14
5. Acute and Chronic Dietary Risks for Sensitive Subpopulations
Particularly Infants and Children 15
6. Aggregate Exposure from Multiple Routes Including Oral, Dermal and
Inhalation 15
C. Environmental Assessment 15
1. Ecological Toxicity Data 15
a. Toxicity to Terrestrial Animals 16
b. Toxicity to Aquatic Animals 22
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c. Toxicity to Plants 25
2. Exotoxin Effects 25
3. Environmental Fate 26
4. Exposure and Risk Characterization 26
D. Product Performance (Efficacy) Assessment 31
IV. RISK MANAGEMENT AND REREGISTRATION DECISION 32
A. Determination of Eligibility 32
1. Eligibility Decision 32
2. Eligible and Ineligible Uses 33
B. Regulatory Position 33
1. Tolerance Reassessment (40 CFR 180.1011 and 40 CFR 180.1001(c))
33
2. Risk Mitigation 34
a. Mitigation Measures for Dietary, Occupational and Residential
Risk 34
b. Mitigation Measures for Nontarget Organisms (Plants and
Wildlife), or Ground and Surface Water Contamination
.'.' . ; 34
3. Endangered Species Statement 35
4. Labeling Rationale , 35
5. Spray Drift Advisory 36
6. Product Performance (Efficacy) Reassessment 36
V. ACTIONS REQUIRED OF REGISTRANTS 37
A. Manufacturing-Use Products 37
1. Additional Generic Data Requirements 38
a. Qualitity Control Manufacturing Process Data Requirements
. . 38
b. Standarization of Manufacturing Process 39
2. Labeling Requirements for Manufacturing-Use Products 39
B. End-Use Products .42
1. Additional Product-Specific Data Requirements 42
2. Labeling Requirements for End-Use Products 43
C. Existing Stocks 50
VI. APPENDICES 51
APPENDIX A. Use Sites for the Reregistration of 0247 53
APPENDIX B Table of the Generic Data Requirements and Studies Contributing
' to the Reregistration Decision 58
APPENDIX C Data Cited as Part of the Data Base Supporting the Reregistration
of Bacillus thuringiensis 61
APPENDIX D Combined Generic and Product Specific Data Call-In 93
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BACILLUS THURINGIENSIS REREGISTRATION ELIGIBILITY DECISION TEAM
Office of Pesticide Programs:
Use Profile
Arthur H. Grube Biological & Economic Analysis Division
Sandra M. Zavolta Biological & Economic Analysis Division
Environmental Fate and Effects Risk Assessment
Zigfridas Vaituzis, Ph.D. Biopesticides & Pollution Prevention Division
Health Effects Risk Assessment
John L. Kough . Biopesticides & Pollution Prevention Division
Cindy R. Schaffer Biopesticides & Pollution Prevention Division
Registration Support
Michael L. Mendelsohn . Biopesticides & Pollution Prevention Division
Reregistration Support (
Richard W. King Biopesticides & Pollution Prevention Division
Shanaz Bacchus Biopesticides & Pollution Prevention Division
Former BPPD Scientists who contributed to preliminary reviews.
Clayton C. Beegle, Ph.D.
Mark J. Perry
Robert I. Rose, Ph.D.
'( i
Registration Eligibility Document.- team leader
William R. Schneider, Ph.D. Biopesticides & Pollution Prevention Division
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GLOSSARY OF TERMS AND ABBREVIATIONS
ADI
AE
a.i.
ARC
CAS
CI
CNS
CSF
DFR
ORES
DWEL
EEC
EP
EPA
FAO/WHO
FDA
FIFRA
FFDCA
FQPA
FOB
GLC
GM
GRAS
HA
HOT
LCSO
LD
SO
LD,0
LEL
LOG
LOD
LOEL
MATC
MCLG
jig/g
mg/L
MOE
MP
'Acceptable Daily Intake. A now defunct terin for reference dose (RfD).
Acid Equivalent
Active Ingredient
Anticipated Residue Contribution
Chemical Abstracts Service
Cation
Central Nervous System
Confidential Statement of Formula
Dislodgeable Foliar Residue
Dietary Risk Evaluation System '
Drinking Water Equivalent Level (DWEL) The DWEL represents a medium specific (i.e. drinking
water) lifetime exposure at which adverse, non carcinogenic health effects are not anticipated to
occur.
Estimated Environmental Concentration. The estimated pesticide concentration in an environment,
such as a terrestrial ecosystem.
End-Use Product
U.S. Environmental Proteclion Agency
Food and Agriculture Organization/World Health Organization
Food and Drug Administration
Federal Insecticide, Fungicide, and Rodenticide Act
Federal Food, Drug, and Cosmetic Act
Food Quality Protection Act
Functional Observation Battery
Gas Liquid Chromatography
Geometric Mean
Generally Recognized as Safe as Designated by FDA
Health Advisory (HA). The HA values are used as informal guidance to municipalities and other
organizations when emergency spills or contamination situations occur.
Highest Dose Tested
Median Lethal Concentration. A statistically derived concentration of a substance that can be
expected to cause death in 50% of test animals. It is usually expressed as the weight of substance
per weight or volume of water, air or feed, e.g., mg/1, mg/kg or ppm.
Median Lethal Dose. A statistically derived single dose that can be expected to cause death in 50 %
of the test animals when administered by the route indicated (oral, dermal, inhalation) . It is
expressed as a weight of substance per unit weight of animal, e.g., mg/kg.
Lethal Dose-low. Lowest Dose at which lethality occurs.
Lowest Effect Level
Level of Concern
Limit of Detection
Lowest Observed Effect Level
Maximum Acceptable Toxicant Concentration
Maximum Contaminant Level Goal (MCLG) The MCLG is used by the Agency to regulate
contaminants in drinking water under the Safe Drinking Water Act.
Micrograms Per Gram
Micrograms per liter
Milligrams Per Liter
Margin of Exposure ,
Manufacturing-Use Product
111
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MPCA Microbial Pest Control Agent
MPl Maximum Permissible Intake
MRID Master Record Identification (number). EPA's system of recording and tracking studies submitted.
N/A Not Applicable
NOEC No Observable 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 Data
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 (c) of FIFRA)
TC Toxic Concentration. The concentration at which a substance produces a toxic effect.
TD Toxic Dose. The dose at which a substance produces a toxic effect.
TEP Typical End-Use Product
TGAI Technical Grade Active Ingredient
TLC Thin 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.
WP Wettable Powder
WPS Worker Protection Standard
IV
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EXECUTIVE SUMMARY
The U. S. Environmental Protection Agency has completed its reregistration eligibility
decision of the group of rnicrobial pesticides registered as Bacillus thuringiensis. This decision
includes a comprehensive reassessment of the required target data and the use patterns of currently
registered products. Bacillus thuringiensis is a group of similar bacteria that act as insecticides
which are used on growing agricultural crops, harvested crops hi storage, ornamentals, bodies of
water, and around the home to control various groups of insects, depending on the particular
toxins produced by the specific isolate of Bacillus thuringiensis. The Agency has concluded that
all uses, as prescribed in this document, will not cause unreasonable risks to humans or the
environment and therefore, all uses are eligible for reregistration. In addition to the toxins that
are active against the insect pests, Bacillus thuringiensis may produce undesirable toxins. To
mitigate risks of potential toxicity to the public and/or non target species from these toxins, the
Agency is requiring continuation of the production batch quality control testing that originally
appeared in the tolerance exemption and is requiring the revaluation and standarization of the
manufacturing process for each registered technical grade of the active ingredient. In addition,
several label changes are required for all Bacillus thuringiensis rnicrobial products. The method
for determining percent active ingredient has been standardized. The revised percent active
ingredient, a statement of explanation, and the specific toxins responsible for the pesticidal
activity must now be included on the labels of all Bacillus thuringiensis products.
Before reregistering the microbial pesticide products containing Bacillus thuringiensis, the
Agency is requiring certain product specific data (product analysis and acute toxicity), a revised
Confidential Statement of Formula (CSF) and revised product labeling be submitted within eight
months of the issuance of this document. After reviewing these data and 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.
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I. INTRODUCTION
In 1988, the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) was amended
to accelerate the reregistration of products with active ingredients registered prior to November
1, 1984. The amended Act provides a schedule for the reregistration process to be completed in
nine years. There are five phases to the reregistration process. The first four phases of the process
focus on identification of data requirements to support the reregistration 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 reregistration.
FIFRA Section 4(g)(2)(A) states that in Phase 5 "the Administrator shall determine whether
pesticides containing such active ingredient are eligible for reregistration" before calling in data
on products and either reregistering products or taking "other appropriate regulatory action."
Thus, reregistration 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.
This document presents the Agency's decision regarding the reregistration eligibility of the
registered uses of the microbial pesticide, Bacillus thuringiensis. The document consists of six
sections. Section I is the introduction. Section n describes Bacillus thuringiensis, its uses, data
requirements and regulatory history. Section HI discusses the human health and environmental
assessment based on the data available to the Agency. Section IV presents the reregistration
decision for Bacillus thuringiensis. Section V discusses the reregistration requirements for Bacillus
thuringiensis. Finally, Section VI is 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
\
This Reregistration Eligibility Decision covers the group of bacterial products
(considered as pesticidal active ingredients) classified as Bacillus thuringiensis. Bacillus
. is a genus of rod-shaped bacteria that produce not more than one endospore per cell and
the sporulation is not repressed by exposure to air, have a gram-positive cell wall, and are
aerobic or facultatively anaerobic. The species thuringiensis, in the genus Bacillus, is
distinguished by the production of one or more protein parasporal crystals in parallel with
spore formation. The parasporal protein crystals are delta endotoxins that are generally
toxic to a variety of insects. Some isolates of Bacillus thuringiensis produce other toxins
that, in some cases, may contribute to the insecticidal activity.
The regulatory decisions described in this Reregistration Eligibility Decision
document, particularly those involving labeling changes, tolerance reassessment, and
manufacturing processes, will apply to all microbial products registered as a Bacillus
thuringiensis. When additional generic and/or product specific data are needed to support
1984 and earlier registrations, the data will be described in the data call-in attached to this
document. Data will be called in, when required, for post-1984 registrations by means of
notifications sent directly to registrants.
Common Names and OPP Chemical Codes*:
i
Microbial Pesticide Name: Bacillus thuringiensis (all subspecies)
OPP Chemical Code: 006400
Microbial Pesticide Name: Bacillus thunngiensis subspecies israelensis
OPP Chemical Code: 006401
Microbial Pesticide Name: Bacillus thuringiensis subspecies kurstaki
OPP Chemical Code: 006402
Microbial Pesticide Name: Bacillus thuringiensis subspecies aizawai
OPP Chemical Code: 006403
Microbial Pesticide Name: Bacillus thuringiensis subspecies tenebrionis
OPP Chemical Code: 006405
Microbial Pesticide Name: Bacillus thuringiensis subspecies kurstaki BMP123
OPP Chemical Code: 006407
Microbial Pesticide Name: Bacillus thuringiensis subspecies kurstaki EG2424 '
OPP Chemical Code: 006422
Microbial Pesticide Name: Bacillus thuringiensis subspecies kurstaki EG2371
OPP Chemical Code: 006423
Microbial Pesticide Name: Bacillus thuringiensis subspecies kurstaki EG2348
OPP Chemical Code: 006424
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Microbial Pesticide Name: Bacillus thuringiensis subspecies aizawai GC-91
OPP Chemical Code: 006426
Microbial Pesticide Name: Bacillus thuringiensis subspecies kurstaki EG7673
OPP Chemical Code: 006448
Microbial Pesticide Name: Bacillus thuringiensis subspecies kurstaki M200
OPP Chemical Code: 006452
Microbial Pesticide Name: Bacillus thuringiensis subspecies kurstaki EG7841
OPP Chemical Code: 006453
Microbial Pesticide Name: Bacillus thuringiensis subspecies kurstaki EG7826
OPP Chemical Code: 006459
* In the internal file numbering system, EPA has grouped several of the earlier
Bacillus thuringiensis registrations under the same OPP Chemical Codes. The Bacillus
thuringiensis registrations issued after the Registration Standard was published have all
been assigned separate OPP Chemical Codes. To maintain consistency, The Agency
intends to assign new Chemical Code numbers to each active ingredient that was formerly
assigned to a previously-used chemical code. This internal renumbering will not affect any
opportunity to share data from one registration to another if scientifically justified.
Trade Names:
Vectobac, Dipel, BiobitWP, BiobitFC, SkeetalFC, Foray, Futura, Javelin, Bactospeine,
Bactimos, M-one, Thuricide-HPC, Larvo-BT, Trident, Ditera, Novodor, Xentari, BMP
123, Condor, Cutlass, Foil, Agree, Raven, Able, Crymax
Basic Manufacturers:
Abbott Laboratories Novartis Crop Protection
Chemical & Agricultural Products Div PO Box 18300
1401 Sheridan Rd Greensboro, NC 27419-8300
D-28R, Bldg Al (Note: All Novartis Bt products have
North Chicago, IL 60064 recently been transferred.)
Becker Microbial Products, Inc. Thermo Trilogy
9464 NW llth St 7500 Grace Drive
Plantation, FL 33222 Columbia, MD 21044-4098
Ecogen, Inc. Troy Corporation
2005 Cabot Blvd West 8 Vreeland Rd
Langhorne, PA 19047 Florham Park, NJ 07932-0955
B. Use Profile
The following is information on the currently registered uses with an overview of
4
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use sites and application methods. A detailed table summarizing the use by site for
Bacillus thuringiensis is in Appendix A.
Type of pesticide: Insecticide (microbial pest control agent)
Use sites: Terrestrial food and non-food crops, aquatic food and non-food crops,
greenhouse food and non-food crops, forestry, domestic outdoor, indoor stored
product use. Based on available pesticide survey usage information for the years
of 1987 through 1996, an average of about 1.4 million base acres of traditional
agricultural crops are likely treated with Bacillus thuringiensis (B.t.) annually. A
reasonable upper bound for possible acres treated would be about 2.1 million acres.
An additional 30,000 (50,000 likely maximum) acres of nursery and greenhouse
plants and cut flowers and greens are treated annually. B.t. is also applied for
mosquito and black fly control on an average of approximately 1 million acres (1.5
million likely maximum) and for use in forests and parks, mostly for gypsy moth
control. The forest and park average use is 750,000 acres (1.5 million likely
maximum). Base acres are those treated at least once. Some crop acreage is
treated more than once annually.
Agricultural sites with a large number of base acres treated are corn, cotton,
grapevines and leafy vegetables. Crops with a high percent of the total U.S. crop
treated include artichokes (90+ %), blackberries (50%), raspberries (30%), celery
(46%), spinach (40%), and cabbage (39%). The remaining usage is primarily on
fruits and vegetables. Areas with the largest usage are California, the Pacific
Northwest (Oregon and Washington), and Florida.
Target Pests: Lepidoptera, coleopteran and dipteran insects
Formulation Types Registered: Water Dispersible Granule, Dry Flowable,
Aqueous Suspension, Granule, Technical Powder, Dust, Wettable Powder,
Emulsifiable Suspension, Aqueous Flowable, Bait, Oil Flowable.
Methods of Application: Hand sprayer; water treatment by aerial or ground
equipment; soil application by drip or overhead irrigation systems; foliar
application by aerial, conventional ground or hand-held equipment and
center-pivot irrigation systems; sprayer or sprinkler cans.
Use Practice Limitations: Restricted Entry Intervals (REIs) of 4- 48 hours for
agricultural uses; direct water application is not to be applied directly to treated,
finished drinking water reservoirs or drinking water receptacles; certain terrestrial
uses are limited to terrestrial use only due to potential aquatic hazard.
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C. Estimated Usage of Pesticide
The table in Appendix A summarizes the best estimates available for the pesticide
uses at Bacillus thuringiensis. 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 hi use patterns as well as the variability hi using
data from various information sources.
D. Data Requirements
The December, 1988, Registration Standard for Bacillus thuringiensis required
submission of studies on characterization data. These data were required to enable EPA
to reclassify registered strains into groups of strains with similar characteristics. In
addition, data was requested which included studies on product analysis, nontarget
organisms, environmental fate, and residue analysis to support the uses listed hi the
Registration Standard. This additional data was not required to be submitted within the
time frames indicated hi the Registration Standard if the company wished to share data
between different strains or wished to utilize data already submitted to the Agency. In this
case, the timeframe for submissions would begin once the Agency has determined whether
sharing of data is warranted or whether testing performed prior to the Registration
Standard was done on strains sufficiently similar to strains currently in registered pesticide
products. Based on information from the scientific literature published subsequent to the
Registration Standard, the Agency believes that decisions on data sharing and strain
similarity should be based on the similarity of delta endotoxins and other toxic/synergistic
components contributing to the pesticidal activity of the particular strain of Bacillus
thuringiensis. Furthermore, the Agency now has sufficient information to simplify the
registration requirements for isolates of Bacillus thuringiensis. As a result, many of the
toxicity/pathogenicity and ecological effects tests are eligible for data waivers.
The submitted data plus data from the literature, which was not available at the
time of the data call-in for the registered products, has shown the Agency that testing a
laboratory-grown culture of the active ingredient as specified by 40 CFR 158.740 is not
reliable to detect the presence of certain undesirable toxins that may be produced by
Bacillus thuringiensis because their synthesis appears to depend on unpredictable aspects
of the fermentation process. Thus, one reliable method to detect these undesirable toxins
is to test each production batch. Production batch testing to detect some of the undesirable
toxins, as well as to detect contamination by pathogenic bacteria, has been required under
the tolerance exemption, 40 CFR 180.1011, and was extended to all products in the
Registration Standard, of December, 1988. Since 1988, the Agency has identified a new
concern for the heat labile exotoxins that are toxic to Daphnia, but the Agency has no
information on whether the current battery of production batch tests will detect these. The
Agency does believe that the presence of heat labile exotoxins should be minimized in
products (see section IV(B)(2)(b)). In lieu of requiring a Daphnia test on each production
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batch, this Registration Eligibility Document specifies that registrants optimize and control
their manufacturing process sufficiently to prevent production of significant amounts of
these heat labile exotoxins. Accordingly, each new manufacturing process must be tested
by a Daphnia study as an indicator of the heat labile exotoxin levels produced under those
conditions. This will assure that heat labile exotoxin levels will not exceed the levels used
by the Agency in its risk assessment. Appendix B summarizes these data requirements.
E. Regulatory History
An isolate at Bacillus thuringiensis was first registered in the United States in 1961
for use as an insecticide. At that time, the 7th edition of Bergey's Manual of Determinative
Bacteriology (1957) did not recognize any subdivisions of Bacillus thuringiensis. Later,
other isolates of Bacillus thuringiensis were discovered to contain differently shaped
protein toxin inclusion bodies (delta endotoxins) which affected different insects. Thus,
the 8th edition of Bergey's Manual of Determinative Bacteriology (1974) subclassified
Bacillus thuringiensis into 11 varieties based on the serotype of antigens found on the
flagella, and the latest edition, Bergey's Manual of Systematic Bacteriology, Vol 2 (1986)
acknowledged a larger number of these varieties but recommended they be called
subspecies. Thus the isolates of Bacillus thuringiensis registered prior to 1984 were
grouped under the following subspecies names: Bacillus thuringiensis subspecies kurstaki,
Bacillus thuringiensis subspecies israelensis and Bacillus thuringiensis subspecies aizawai.
Others, such as Bacillus thuringiensis subspecies tenebrionis, were registered later.
The Agency no longer groups new isolates under the subspecies name because it
is now known that the delta endotoxin genes, which generally reside on transferable
genetic elements (plasmids) can be readily moved from one isolate to another, regardless
to which subspecies they belong. Therefore, isolates 'registered since 1989 have been
registered as individual active ingredients. Furthermore, some of the delta endotoxins
from Bacillus thuringiensis, when produced by genetic sequences inserted into other
bacteria or plants, have also been registered separately. However, this Reregistration
Eligibility Document includes genetically manipulated delta-endotoxins only when they are
contained in Bacillus thuringiensis bacteria. The primary scientific issues addressed by
this document involve the exotoxins that may be produced by Bacillus thuringiensis; issues
which are not at all relevant to other kinds of organisms engineered to contain the delta-
endotoxin genes.
A Data Call-in was issued in conjunction with a Registration Standard in
December, 1988, (#540/RS-89"-023) for Bacillus thuringiensis requiring additional data for
Product Analysis, Toxicology, and Nontarget Organisms. This Reregistration Eligibility
Decision is based on an assessment of data which were submitted in response to the
Registration Standard.
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in. SCIENCE ASSESSMENT
A. Product Analysis Assessment
1. Identification of Active Ingredients
a. Product Identity
For a new isolate to be classified in the group of bacteria called Bacillus
thuringiensis it must be a gram positive, aerobic or facultatively anaerobic, rod
shaped bacterium containing a crystalline insecticidal protein (delta-endotoxin).
Historically, flagellar antigen serotype analysis was used to classify individual
Bacillus thuringiensis subspecies. For example, all Bacillus thuringiensis
subspecies aizawai strains have a flagella antigen of serotype H7; the serotype for
Bacillus thuringiensis subspecies israelensis is H14; Bacillus thuringiensis
subspecies kurstaki is 3a3b and Bacillus thuringiensis subspecies tenebrionis is
8a8b. However, genetic engineering techniques now allow genetic material
encoding the delta-endotoxin insecticidal protein to be moved among subspecies to
give different host spectrum ranges. Thus, the Agency will no longer use the
subspecies taxonomic unit as a primary differential characteristic of the species.
The Agency will consider each new strain (a pure culture of descendants of a single
isolation) of Bacillus thuringiensis as a new active ingredient. However, its
similarity to currently registered strains/isolates of Bacillus thuringiensis may allow
the toxicology and ecological effects data for those registered active ingredients to
support the new registration. Identification of the delta-endotoxins produced by
each strain will be useful to users of these products in pesticide resistance
management. On request by the registrant, the Agency may allow a certain amount
of genetic variation, intentional or unintentional, from the recorded characteristics
of the registered strain if documented well enough to perform an incremental risk
assessment. This type of variant might be handled through a change in the
confidential statement of formula (CSF), and, if the changes involve characteristics
of delta-endotoxins or other chemical substances that contribute to the toxicity to
the target pest, may warrant a modification to the label.
The Registration Standard for Bacillus thuringiensis, published in 1988,
required nine lands of characterization data in an attempt to provide an identity
profile for each active ingredient. The following five, out of the nine, kinds of
product identity data subsets (McClintock, J.T., C.R. Schaffer, J.L. Kough, &
R.D. Sjoblad (1995) Relevant Taxonomic Considerations for Regulation of Bacillus
thuringiensis-'Based. Pesticides by the U.S. Environmental Protection Agency. In
T-Y Feng, et al. (eds.), "Bacilus thuringiensis Biotechnology and Environmental
Benefits.", Vol. I, 313-325.) were useful hi distinguishing different isolates as
follows.
8
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(1) Biochemical and Nutritional Characteristics.
The biochemical and nutritional characteristics (as referenced in
Bergey's reference manual) are useful to differentiate Bacillus thuringiensis
from other similar Bacillus species (i.e. B. cereus, B. anthracis); and can
be useful in differentiating closely related varieties of subspecies of the
same species.
\
(2) Antibiotic Susceptibility.
Antibiotic susceptibility determinations also may be useful hi
characterizing Bacillus thuringiensis strains. Each Bacillus thuringiensis
strain was evaluated for sensitivity against and up to a total of 33 various
antibiotics. Very little difference between these strains of Bacillus
thuringiensis was observed, however these tests are inexpensive and are
likely to be useful in differentiating other strains of Bacillus thuringiensis.
This information is also useful for isolation of these strains from
environmental or clinical samples.
(3) Host Range Spectrum.
Historically, Bacillus thuringiensis subspecies have been
differentiated by their pesticidal activity against species in the following
four insect orders: Lepidoptera, Orthoptera, Diptera and Coleoptera. For
example, Bacillus thuringiensis subspecies kurstaki show strong activity
against Lepidopteran species and limited activity .on Coleopteran and
Orthopteran species; Bacillus thuringiensis subspecies israelensis strains
exhibit against Dipteran species with limited activity against Lepidopteran
and Coleopteran; Bacillus thuringiensis subspecies aizawai strains display
some activity against Coleopteran species but more activity on
Lepidopteran; and Bacillus thuringiensis subspecies tenebrionis is active on
only Coleopteran species. These generalizations were confirmed for these
particular active ingredients by these characterization data.
(4) Beta-exotoxin Activity.
Bacillus thuringiensis isolates may also produce a heat stable beta-
exotoxin called thuringiensin. The registrants must provide data"
demonstrating the lack of beta-exotoxin activity in the TGAI. The presence
of beta-exotoxin, thuringiensin, has been evaluated by HPLC and/or fly
larvae bioassay. Beta-exotoxin was observed hi one Bacillus thuringiensis
subspecies aizawai strain under laboratory conditions by demonstrating up
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to 24% mortality in the fly larvae assay. This strain may require
production batches to be discarded if beta-exotoxin is not eliminated during
production and is detected in the batch quality control testing (see section
V, Actions Required of Registrants).
(5) Intraperitoneal Assays.
The Intraperitoneal (ip) injection assay of Bacillus thuringiensis hi
mice is used as a quality control measure to demonstrate the lack of
mammalian toxicity of the TGAI, but the protocols were not fully validated
at the time of the 1988 Registration Standard. The Agency has
subsequently found that high dose levels of 10s colony forming units (CPU)
per animal in this assay often show mortality, even for bacteria generally
regarded as nonpathogenic and nontoxic, such as Bacillus subtilis. Some
of the submitted ip assays showed this mortality at high doses; however,
they supported the lack of toxicity at doses of 107 and below for these
isolates of Bacillus thuringiensis.
(6) Other Product Identity Data.
The following four kinds of product identity data subsets requested
in the 1988 Registration Standard did not prove to be sufficiently consistent,
or lacked useful information for distinguishing strains of Bacillus
thuringiensis: (1) History of the strain, (2) Insecticidal toxins produced, (3)
Plasmid profiles, and (4) Description of crystalline proteins. These data are
no longer required for registration, although identification of the
insecticidal toxins using more recent methods will be required for prdper
labeling.
b. Manufacturing Process
The technical grade active ingredient of each Bacillus thuringiensis product
is generally manufactured using a standard fermentation batch process. The
material is then concentrated, and either dried, or mixed with inerts in a liquid
form, and then packaged. Registrants have not been required to adhere to a
standardized fermentation protocol. However, the Agency is concerned about the
potential for the production of various undesirable Bacillus exotoxins because then-
synthesis appears to depend on unpredictable aspects of the fermentation process.
Accordingly, through this document the Agency is implementing measures to
mitigate these risks. Refer to Section IV, Risk Management and Reregistration
Decision, and V, Actions Required of Registrants.
10
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c. Discussion of Formation of Unintentional Ingredients
Generally, fermenter solids and solubles may be present in the final
product. An exemption from the requirements of a tolerance has been granted for
these (40 CFR 180.1001(c)) and has been reassessed in this document (see section
IV(B)(1)). It is the Agency's opinion that quality control procedures, as described
in Section V, Actions Required of Registrants, for each product which test for the
presence of contaminants such as human pathogens, or undesirable toxins in each
batch will adequately mitigate potential risks to humans. Any production batch
containing unwarranted levels of contaminants must be discarded,
B. Human Health Assessment
1. Toxicology Assessment
a. Acute toxicity/pathogenicity
The Agency has an historical toxicology data base for Bacillus thuringiensis
(See 4/23/86 Memorandum from William Woodrow to Arturo Castillo). In
addition, a summary review of mammalian toxicity studies was published by
Agency reviewers (McClintock, J.T., C.R. Schaffer, & R.D. Sjoblad (1995) A
Comparative Review of the Mammalian Toxicity of Bacillus thuringiensis- Based
Pesticides. Pestic. Sci. 45, 95-105). To date, no known mammalian health effects
have been demonstrated in any infectivity/pathogenicity study (Table 1, Acute
Mammalian Toxicity for Bacillus thuringiensis'). The sum total of all toxicology
data submitted to the Agency complete with the lack of any reports of significant
human health hazards of the various Bacillus thuringiensis strains allow the
conclusion that all infectivity/pathogenicity studies normally required under 40
Code of Federal Regulations, Part 158, for the use patterns of the registered
products be waived in the future as long as product identity and manufacturing
process testing data indicated there is no mammalian toxicity associated with the
strain. In accordance with standard practices when these studies are waived, label
language will be required assuming a Toxicity Category of IE.
11
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Table 1: Acute Mammalian Toxicity for Bacillus thuringiensis
Guideline
Numbers*
1S2A-10
(885.3050)
1S2A-12
(885.3200)
N/A
(generally
received under
151A-10,
Product
Analysis)
152A-15
(885.3400)
81-2
(870.1200)
Study
Acute Oral Toxicity/
Pathogenicity
Acute Pulmonary
Toxicity/
Pathogenicity
Acute Intraperitoneal
Toxicity/
Pathogenicity
Hypersensitivity
Incidence Reporting
Acute Dermal
Toxicity
Results
No adverse toxic effects, mfectivity,
or pathogenicity seen at doses up to
4.7x10" spores/kg.
No adverse toxic effects, mfectivity,
or pathogenicity seen at doses up to
2.6xl07 spores/kg.
Non toxic at dose levels below 108
colony forming units (CPU) per
animal. No infectivity or
pathogenicity.
Two possible incidences reported,
neither one was caused by Bacillus
thuringiensis.
No dermal toxicity observed at doses
up to 4.7x10"
Toxicity
Category
IV
IV
N/A
N/A
IV '
MRIDs
142733 96520
41046704 96527
42006502 96533
43186101 109492
40951102 246968
96529
41308603
42006503
66178 41441609
66179 41441611
90207 41441612
90208 41722507
41590302 41826608
41270301 41826609
41308607 41994303
41441504 42750401
41441505 42791301
41441506
420271
142734 419943
109493 41412705
404974
1988 Subdivision M (1995 Harmonized Guidelines)
Primary dermal irritation (81-5, 870.2500) and primary eye irritation (81-4,
870.2400) were not required under the 1988 Registration Standard because these
studies are not required for the TGAI (40 CFR 158.740). These studies are
required and will be reviewed for the manufacturing-use and the end-use products.
In general, slight to moderate skin irritation has occasionally been observed in
product tests, which may be attributed to other ingredients in the formulation, and
occasionally eye irritation has been seen in primary eye irritation tests. This is
often associated with dry, anhydrous forms of the product and may be due to
physical irritation effects as might be caused by sand or drying agents rather than
caused by traditional toxicity.
b. Potential for producing Bacillus cereus enterotoxins
The Agency is aware of research results that indicate that registered Bacillus
thuringiensis products may be able to produce the diarrhoeal enterotoxin usually
12
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associated with Bacillus cereus. A comparison of commercial Bacillus
thuringiensis strains with a clinical isolate of Bacillus cereus reported that all
commercial products tested could produce the diarrhoeal enterotoxin, but at very
low levels compared with the clinical isolate (Damgaard, D.H. (1995), Diarrhoeal
enterotoxin production by strains of Bacillus thuringiensis isolated from
commercial Bacillus thuringiensis-based insecticides. FEMS Immuno. and Med.
Microbiol. 12, 245-250). However, at this time the Agency has no valid evidence
to link actual usage of Bacillus thuringiensis insecticides with episodes of diarrhoea
following ingestion of food. Bacillus cereus, and other naturally-occurring
toxigenic microorganisms, can normally be found on many kinds of foods, but
niust multiply in the foods in order to produce the toxins responsible for the
symptoms. For this reason, standard food handling practices have been developed
to minimize the potential for microbial growth in foods. The Bacillus thuringiensis
isolates examined in the cited study, above, produce much less diarrheal toxin than
the verified toxigenic Bacillus cereus. The Centers for Disease Control and
Prevention has recently compiled morbidity data for food-borne diseases. For the
five year period from 1988 through 1992,the average number of reported outbreaks
per year attributed to Bacillus cereus is 4.2 and the proportion of the total is
0.64%. No deaths were,attributed to these outbreaks. Thus the incidence of
reported disease due to Bacillus cereus is a very small amount of the total
food-borne diseases. For these reasons, the Agency believes that the current uses
of Bacillus thuringiensis are not likely to contribute to the prevalence of diarrhoea
induced by microbial toxins hi improperly stored processed food. The Agency will
continue to survey the scientific literature, including publications from the Centers
for Disease Control on incidents of Bacillus food poisoning, and will reexamine
these conclusions if valid evidence is found that suggests a direct association
between Bacillus thuringiensis usage and illness. In addition, the Agency
emphasizes that, under section 6 (a)(2) of the Federal Insecticide Fungicide and
Rodenticide Act, registrants are required to report any information regarding
unreasonable adverse effects following registration and these effects would clearly
fall under this provision.
c. Effects on the Immune and Endocrine Systems
The Agency is not requiring information on the endocrine effects of this
microbial pesticide at this time; the Food Quality Protection Act has allowed three
years after August 3, 1996, for the Agency to implement a screening program with
respect to endocrine effects. However, the Agency has considered, among other
relevant factors, available information concerning whether Bacillus thuringiensis
may have an effect hi humans similar to an effect produced by a naturally occurring
estrogen or other endocrine effects. No known toxins or metabolites of Bacillus
thuringiensis have been identified to act as endocrine disrupters or
immunotoxicants. Therefore, adverse effects to the endocrine or immune systems
are not expected.
13
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2. Dietary Exposure and Risk Characterization
The use patterns for Bacillus thuringiensis may result in dietary exposure
with possible residues of the bacterial spores on raw agricultural commodities.
However, hi the absence of any toxicological concerns, risk from the consumption
of treated commodities is not expected for both the general population and infants"
and children.
3. Occupational, Residential, School and Daycare Exposure and Risk
Characterization
a. Occupational Exposure and Risk Characterization
The application methods suggest that the potential for eye, dermal and
inhalation exposure to mixers, loaders and applicators does exist. The label for
Bacillus thuringiensis based products may recommend wearing gloves, goggles,
and.a dust mask or equivalent pulmonary tract covering. However, because of a
lack of mammalian toxicity, the risk from occupational exposure is minimal. No
additional exposure data or changes in the proposed labels to restrict exposure are
recommended at this time.
i
b. Residential, School and Daycare Exposure and Risk
Characterization
No indoor residential, school or daycare uses currently appear on the label.
Nondietary exposure to these other use sites could occur where children are
present, but the health risk is expected to be negligible due to: (1) The lack of
toxicological concerns associated with Bacillus thuringiensis, and (2) Bacillus
thuringiensis has been used as a pesticide for approximately 50 years with no
known adverse effects.
4. Drinking Water Exposure and Risk Characterization
There is minimal potential for Bacillus thuringiensis to enter ground water
or other drinking water sources, and the bacterium does not proliferate in aquatic
habitats. Thus, the potential for drinking water exposure is negligible (section IE
(C) (3)(e), Environmental Assessment, Water Resources). In addition, the health
risk is expected to be negligible due to: (1) The lack of toxicological concerns
associated with Bacillus thuringiensis, and (2) Bacillus thuringiensis has been used
as a pesticide for approximately 50 years with no known adverse effects.
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5. Acute and Chronic Dietary Risks for Sensitive Subpopulations
Particularly Infants and Children
A battery of acute toxicity/pathogenicity studies is considered sufficient by
the Agency to perform a risk assessment for microbial pesticides. Furthermore,
the Bacillus thuringiensis delta-endotoxins affect insects via a well known
mechanism in which they bind to unique receptor sites on the cell membrane of the
insect gut, thereby forming pores and disrupting the osmotic balance. There are
no known equivalent receptor sites hi mammalian species which could be affected,
regardless of the age of the individual. Thus, there is a reasonable certainty that
-no harm will result to infants and children from dietary exposure to residues of
Bacillus thuringiensis.
6. Aggregate Exposure from Multiple Routes Including Oral, Dermal and
Inhalation
f
Bacillus thuringiensis is a naturally occurring soil bacterium. Anyone
coming in contact with the soil is likely to be exposed to this microorganism.
Because the health risk is expected to be negligible for oral, dermal, and inhalation
exposure routes, as stated above, aggregate exposure by these routes, from
naturally-occuring populations in the soil and from the use of pesticidal products,
should not pose a threat to human health.
DISCUSSION:
;
The intraperitoneal injection data and the other product characterization information
submitted for reregistration are adequate to corroborate the lack of pathogenicity/toxicity
associated with many years of use of the previously registered active ingredients and no further
toxicology data are required for previously registered technical grade of the active ingredient.
However, acute toxicity studies continue to be part of the data requirements for end-use and
manufacturing-use products. These may be new studies or registrants may cite previously
submitted studies.
15
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C. Environmental Assessment
There are no outstanding data requirements. The available data from the literature and
from the sum total of all submissions is sufficient for the Agency to make an assessment of the
environmental effects for the currently registered uses of Bacillus thuringiensis.
1. Ecological Toxicity Data
The Agency concludes that toxicity and infectivity risks due to delta-
endotoxin effects to nontarget avian, freshwater fish, freshwater aquatic
invertebrates, estuarine and marine animals, arthropod predators/parasites, honey
bees, annelids and mammalian wildlife will be minimal to nonexistent at the label
use rates of registered B. thunngiensis active ingredients. However, other toxins
which may be produced by Bacillus thuringiensis can produce adverse direct toxic
effects on nontarget species. Mitigation measures to alleviate these risks are
specified hi Section IV. Despite the potential for immediate toxic effects on target,
and possibly some nontarget, organisms, there is no evidence that Bacillus
thuringiensis can cause epizooatics hi the field. A summary of the studies reviewed
for the formal ecological assessment, by delta-endotoxin source, is provided below.
Although the studies submitted in support of reregistration are adequate to make
an ecological assessment for the intrinsic delta-endotoxin-based properties of
Bacillus thuringiensis, the Agency's inability to assess the potential for nontarget
effects by the exotoxin(s) from the available data has resulted in the following
decisions. (1) Based on all available data, the Agency is waiving the ecological
effects data requirements for the reregistration of Bacillus thuringiensis. (2) The
Agency has concluded that there will be no potential for adverse effects on
nontarget organisms for B. tkuringiensis-based products if the the presence of
soluble, heat labile exotoxins and beta-exotoxin is minimized. (3) However, the
production process must be closely controlled and monitored or certified to assure
these exotoxins are not present at levels that can cause significant adverse
ecological effects.
a. Toxicity to Terrestrial Animals
(1) Birds, Acute and Subacute
16
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Table 1 B. thuringiensis subspecies kurstaki
GUIDELINE
NUMBER
154-16
water fowl
(mallard duck)
!
upland game
bird
(bobwhite quail)
-
MRID
NUMBER
414434-03
435830-03
416570-08
417511-08
414434-04
435830-02
416570-07
417511-09
RESULT
Practically nontoxic after 2.9 g/kg/day for 5 days
Practically nontoxic after 1.6 g/kg/day for 5 days
Practically nontoxic after 2.5 g/kg/day for 5 days
LC50 > 1.8 x 1010 spores/kg
Practically nontoxic after 2 9 g/kg/day for 5 days
Practically nontoxic after 1.6 g/kg/day for 5 days
Practically nontoxic after 2.5 g/kg/day for 5 days
LCSO > 1.8 x 1010 spores/kg
Table 2 B. thuringiensis subspecies israelensis
GUIDELINE
154-16
mallard
bobwhite
MRID
414390-05
418427-02
414390-06
418427-03
RESULT
Practically nontoxic after 3.1 g/kg/day for 5 days
Practically nontoxic after 5 ml/kg/day for 5 days
Practically nontoxic after 3.1 g/kg/day for 5 days
Practically nontoxic after 5 ml/kg/day for 5 days
Table 3 B. thuringiensis subspecies tenebrionis
\ GUIDELINE
1 154-16 mallard
| 154-17 mallard
1 MRID
1 404974-09
1 404974-10
RESULT |
No mortality following a single 10 g/kg dose 1
No mortality after 3 mg/kg injection 1
17
-------
Table 4 B. thuringiensis subspecies aizawai
GUIDELINE
154-16
mallard
bobwhite
MRID
419943-14
419748-05
419943-13
419748-04 '
RESULT
LC50 > 16.7 g/kg
LC50 > 8570 mg/kg
LC50 > 16.7 g/kg
LC50 > 8570 rag/kg
The avian study results summarized above indicate that B. thuringiensis subspecies
kurstaki, B. thuringiensis subspecies israelensis, B. thuringiensis subspecies tenebrionis and B.
thuringiensis subspecies aizawai are not toxic or pathogenic to the northern bobwhite quail or
mallard duck after acute or subacute testing. No additional avian testing is required to support the
current B. thuringiensis delta-endotoxin reregistration effort. No avian respiratory data were
submitted hi response to the Registration Standard. Although avian respiratory data had been
required by the Standard, these data are not currently needed to support reregistration.
(2) Birds, Chronic
i
Due to the lack of toxicity/pathogenicity in the acute and
subacute testing, avian chronic study requirements were not
triggered for Bacillus thuringiensis delta-endotoxins.
(3) Mammals
The acute toxicity studies performed on the laboratory rodent
with different Bacillus thuringiensis subspecies indicate that there
are not likely to be any adverse effects on wild mammals. The wild
mammal studies are required only when toxicology data are
inadequate for assessment of hazard to wild mammals.
(4) Insects
(a) Nontarget Insect Susceptibility
18
-------
Table 1 B. thuringiensis subspecies kurstaki
GUIDELINE
154-23
154-24
predaceous
neuroptera
parasitic
hymenoptera
-
predaceous
coleoptera
arthropod
predators and
parasites
honey bee
MRID
435830-10
416570-11
417511-11
414434-11
435830-08
417511-10
416570-13
435830-09
417511-12
414434-10
414434-09
419835-01
419833-01
435681-01
434917-02
RESULT
NOEL = 3000 ppm
practically nontoxic at 1 x 10s cfu/g food for 9 days; NOEL = 1 x
108 spores/g diet
practically nontoxic at 1.2 x 108 spores/g diet for 5 days; NOEL >
1 .2 x 108 spores/g diet
slightly toxic; lOx field rate resulted in 18% mortality
practically nontoxic at 3000 ppm of food for 15 days; NOEL =
3000 ppm
practically nontoxic at 2.4 x 108 spores/ml diet for 23 days; NOEL
> 2.4 x 108 spores/ml diet
practically nontoxic at 1 x 108 spores/g diet for 30 days; NOEL =
1 x 10s cfu/g
NOEL = 1500 ppm, slightly toxic
practically nontoxic at 2.4 x 108 spores/ml diet for 28 days; NOEL
> 2 4 x 108 spores/ml diet
Slightly toxic (6.2 g/L resulted in 12 to 21 % mortality)
Toxic; lOx field rate resulted in 100% mortality within '6 days
48-hour LD50 > 23.2 ug/bee; NOEL = 7.7 ug/bee
48-hour LD50 > 23.2 ug/bee; NOEL = 7.7 ug/bee
10-day LC50 118 ug/bee (consumed)
No significant effects noted at lOx field rate
19
-------
Table 2 B. thuringiensis subspecies israelensis
GUIDELINE
154-23
1 154-24
green lace-wing
larvae
parasitic
hymenoptera
predaceous
coleopteran
honey bee '
MRID
418427-08
418427-09
418427-10
418427-11
RESULT
16-day LCJO > 1.5 x 108 cfu/g diet; 16-day NOEL = 2 5 x 10"
cfu/g
30-day LC50 > 7.9 x 107 cfu/g diet
9-day LC50 > 1.8 x 108 cfu/g diet
5-day LCJO > 7.0 x 107 cfu/g diet
Table 3 B. thuringiensis subspecies tenebrionis (CrylllA)
GUIDELINE
154-24
Honey bee
larvae
Earthworm
MRID
441247-02
441247-01
RESULT
NOEL = > 100 ppm (lOOx field cone.) (18 day
test)
NOEC = > 100 ppm (120x in 1 kg soil)
(14 day test)
Table 4 B. thuringiensis subspecies aizawai
GUIDELINE
154-23
154-24
green lace-wing
larvae
parasitic
hymenoptera
predatory mite
predaceous
coleoptera
Honey bee
MRID
419943-21
422453-01
419943-19
419748-09
419943-20
429421-01
419748-08
RESULT
NOEL = 10,000 ppm
Toxic to larvae at lOx field rate
NOEL = 100 ppm
Ix field rate resulted in 24% corrected mortality
NOEL = 10,000 ppm
NOEL = 1566 ppm
Highly toxic; LEJO = 15 ppm
With the exceptions of MRIDs 414434-09 and 422453-01, the nontarget
insects, thuringiensis subspecies kurstaki, B. thuringiensis subspecies israelensis,
20
-------
B. thuringiensis subspecies tenebrionis (CrylUA) and B. thuringiensis subspecies
aizawai studies show little to no toxicity or pathogenicity in the tested neuroptera,
hymenoptera, coleoptera, arthropod and annelida group indicator species. The
above honey bee data indicate a high degree of toxicity for B. thuringiensis
subspecies aizawai and minimal toxicity for B. thuringiensis subspecies kurstaki,
B. thuringiensis subspecies israelensis and B. thuringiensis subspecies tenebrionis.
With the exception of honey bee and earthworm testing, all of the nontarget
insect studies listed above were graded as supplemental. However, since the
Agency currently waives the requirement for nontarget insect data (but .not
honeybee testing) for registration, no additional data are required. These data are
routinely waived because Bacillus thuringiensis does not cause epizooatics in the
field; it functions by a toxic mode-of-action.
(b) Target Insect Host Range Susceptibility
B. thuringiensis subspecies are differentiated by their pesticidal activity
against insects. Generally, only insect species within one order (Lepidoptera,
Coleoptera, Diptera, and Orthoptera) are susceptible to a given insecticidal delta-
endotoxin protein. Therefore, insect susceptibility results provide general
information about the delta exotoxin(s) expressed by a particular B. thuringiensis
strain.
The submitted data on insect susceptibility to the various B. thuringiensis
subspecies and varieties are summarized below.
1 As expected, B. thuringiensis subspecies aizawai strains displayed minimum
activity to Coleoptera (0% to 5%) and Orthoptera (0% to 7.5%) species, some
activity against Diptera (0% to 57%), and the greatest activity towards Lepidoptera
(100%).
Two of threeS. thuringiensis subspecies israelensis strains exhibited strong
activity against Diptera (80% and 100%) with one strain displaying minimum
efficacy (20%). Minimum activity against Lepidopter an (2.6%, 13.3%, and 28%),
Coleopteran (2.8%, 4%, 10%), -and Orthopteran (0% to 6.4%) species was
observed for all B. thuringiensis subspecies israelensis strains.
B. thuringiensis subspecies kurstaki displayed the greatest activity against
Lepidopteran (95% and 100%) species and limited activity against Coleopteran
(0%, 5%, and 17.5%) and Orthopteran (0% and 20%) species. Although three
strains displayed strong activity (100%) against Manduca sexta, a Lepidopteran
species, one strain exhibited minimum activity (7.9 %) when bioassayed against the
same insect at the same dose level. Two of the seven B. thuringiensis subspecies
21
-------
kurstafd strains exhibited a range, of activity (30% and 100%)-against Aedes
aegypti, a Dipteran species.
B. thuringiensis subspecies tenebrionis was active against Coleoptera
(100%) with only slight activity (3.1 %) observed againstM. sexta, a Lepidopteran
species.
b. Toxicity to Aquatic Animals
(1) Freshwater Fish
Table 1 B. thuringiensis subspecies kurstaki -
GUIDELINE
154-19
trout
bluegill
. MRID
414434-06
418991-01
416570-09
414434-05
RESULT
LC50 > 1.5 x 10'° cfu/1
Practically nontoxic; Aqueous LC50 > 4.9 ul/1 and oral LC50 > 2.5
nl/goffood
practically nontoxic with an aqueous LC50 > 4.6 x 10'° cfu/1 of
dilution water
practically nontoxic at 1.5 x 1010 cfu/1 of dilution water and at 1.2 x
10'° cfu/g of food for 32 days
T'a'ble 2 B. thuringiensis subspecies israelensis
GUIDELINE
154-19
trout
bluegill
MRID
414390-08
419801-05
414390-07
418427-04
RESULT
Aqueous LC50 > 8.7 x 109 cfu/1; oral LC50 > 1.7 x 10'° cfu/g food
Slightly toxic
Aqueous LC50 > 1.4 x 10'° cfu/1; oral LC50 > 5.3 x 109 cfu/g food
Aqueous LC50 > 8.9 x 109 cfli/I; oral LC50 > 1.3 x 10'° cfu/g food
Aqueous LC50 > 1.6 x 1010 cfu/1; oral LC50 > 4.3 x 109 cfu/g food
22
-------
Table 3 B. thuringiensis subspecies tenebrionis
GUIDELINE
154-19 trout
1 MRID
1 404974-11
RESULT
Aqueous NOEC = 100 mg/I
I
Table 4 B. thuringiensis subspecies aizawai
GUIDELINE
154-19
trout >
MRID
419943-15
419749-03
RESULT
Aqueous LC50 > 3.9 x 107 cfu/ml; oral LC50 > \.5\ 10'° cfu/g
food
96-hour LC50 > 100 mg/1 . ||
With aqueous LC50's ranging from 8.7 x 109 to 4.6 x 1010 cfu/1, no toxicity or pathogenicity
was evident in the bluegill or the rainbow trout with the B. thuringiensis subspecies kurstaki, B.
thuringiensis subspecies israelensis, B. thuringiensis subspecies tenebrionis and B. thuringiensis
subspecies aizawai,
(2) Freshwater Invertebf ates
Table 1 B. thuringiensis subspecies kurstaki
GUIDELINE
154-20
=====
daphnia
MRID
414434-07
418991-02
RESULT
moderately toxic; 21-day LC50 is between 5 ppm and 50 ppm
aqueous LC50 > 4.9 ul/1
Table 2 B. thuringiensis subspecies israelensis
GUIDELINE
154-20 daphnia
1 MRID
1 414390-09
RESULT - . ||
moderately toxic; 21-day LC50 is between 5 ppm and 50 ppm ||
23
-------
Table 3 B. thuringiensis subspecies tenebrionis
GUIDELINE
154-20 daphnia
1 MRID
1 404974-12
RESULT
48-hour ECSO > 100 mg/1
Table 4 B. thuringiensis subspecies aizawai
GUIDELINE
154-20
daphnia
MRID
419943-16
419748-02
RESULT
Highly toxic; 21-day NOEC = 6.4 x 108 cfu/1*
Highly toxic; 21-day estimated ECSO is 0.8-2.7 ppm
With LCSO estimates between -5 and 50 ppm, the data indicate that B. thuringiensis'
subspecies kurstaki and B. thuringiensis subspecies israelensis are moderately toxic to daphnia.
B. thuringiensis subspecies aizawai studies (MRIDs 419943-16 and 419748-02) with EC50
estimates ranging from 0.8 to 3 ppm, demonstrate a high level of toxicity to aquatic invertebrates.
In all cases examined, the toxicity was due to-factors other than the delta-endotoxin.
(3)
Estuarine and Marine Animals
Table 1 B. thuringiensis subspecies kurstaki
GUIDELINE
154-21
grass shrimp
sheepshead
minnow
copepod
MRID
435830-07
418991-03
415408-02
435830-06
418991-04
415408-01
414434-08
RESULT
Practically nontoxic; NOEL > 3.6 x 107 cfu/g food
Aqueous LCJO > 4.9 ul/1; oral LCSO > 2.5 nl/g food
NOEL > 2.9 x 109 cfu/g diet
Practically nontoxic; aqueous LCJO > 4.9 x 1010 cfu/1; oral LCSO >
3.7 x 107 cfu/g food
Aqueous LCSO > 4.9 ul/1; oral LCSO > 2.5 nl/g food
aqueous and oral NOELs are > 2.9 x 1010cfu/ml and > 2.9 x 109
cfu/g, respectively
NOEL = 500 mg/kg sediment
. 24
-------
Table 2 B. thuringiensis subspecies israelensis
GUIDELINE
54-21
grass shrimp
sheepshead
minnow
copepod
MRID
415404-02
418427-06
415404-01
418427-07
414390-10
RESULT
NOEL > 2.0 x 10'° cfu/g food
practically nontoxic; NOEL > 4.2 x 109 cfu/g food
NOEL > 2.0 x 10'° cfu/g food; oral LC50 > 2 x 1010 cfu/g food
practically nontoxic; LCSO > 7.2 x 109 cfu/g food
NOEL = 50 mg/kg sediment
Table 3 B. thuringiensis subspecies aizawai
GUIDELINE
154-21
grass shrimp
sheepshead
minnow
MRID
419943-18
419943-17
RESULT
NOEL > 1.6 x 1010 cfu/g food
aqueous LC50 > 1.6 x 10'° cfu/g food; oral LCSO > 1.6 x 1010 cfu/g
food
The estuarine and marine studies performed with B. thuringiensis subspecies kurstaki, B.
thuringiensis subspecies israelensis and B. thuringiensis subspecies aizawai do not demonstrate
toxicity or pathogenicity to the copepod, grass shrimp or sheepshead minnow.
c. Toxicity to Plants
Although 'non-target plant toxicity testing was required in the
x Registration Standard, these data are being waived to support reregistration,
because a review of the literature on B. thuringiensis and its byproducts
indicate no known detrimental effects on plant life, including Terrestrial,
Semi-aquatic and Aquatic plant life.
2.
Exotoxin Effects
Nontarget organism toxicity has not been found with delta-endotoxins when
these are separated from the bacterial growth medium. _Specifically, data
submitted to the Agency in support of registrations involving plants genetically
engineered to express delta-endotoxins show that the pure Cry delta-endotoxin does
not exhibit detectable deleterious effects upon nontarget species. A number of B.
thuringiensis fermentation-based products tested at high dose levels have shown
intrinsic toxicity to nontarget organisms. Investigations conducted to determine
25
-------
what is responsible for the nontarget activity have implicated heat-labile soluble
substances contaminating the technical material. Toxic effects have been seen in
aquatic invertebrateDaphnia magna, the honeybee, some beneficial insects and fish
(rainbow trout, bluegill) and wild mammal (mouse and rat) studies, with Daphnia
being the most sensitive indicator of toxicity. The impurities are found hi the
supernatant fluids separate from the delta-endotoxins. The toxicity does not appear
to be due to the heat stable beta-exotoxin since autoclaving of the test material
renders the supernatant fluids innocuous.
The heat-labile, soluble toxic impurities have thus far been seen in B.
thuringiensis subspecies kurstaki, aizawai, and israelensis, but may possibly be
present in other B. thuringiensis varieties. A journal article reports varying levels
of at least one soluble exotoxin in all commercial B. thuringiensis products tested
(H. Damgaard. 1995. FEMS Immunology and Medical Microbiology 12:245-250).
B. thuringiensis subspecies aizawai-based products show the greatest negative
effects on nontarget organisms. With B. thuringiensis subspecies kurstaki, the
manifestation of the toxin(s) appears to be at least partly related to production
methodology, especially the composition of the growth media used in industrial
fermentation.
3. Environmental Fate
Formal environmental fate data is not generally required for microbial
pesticides because it is not usually needed and it is difficult to evaluate due to the
potential for microbial growth under suitable environmental conditions. However,
the behavior of Bacillus thuringiensis and related bacilli has been thoroughly
studied and is well known. With regard to risk characterization it is known that B.
thuringiensis toxins degrade rapidly hi the phyllosphere as a result of exposure to
UV light. B. thuringiensis toxins may persist in soil for several months, yet a half-
life for typical B. thuringiensis products on foliage is approximately 1-4 days. As
a result, exposure to most above-ground nontargets organisms is expected to be
minimal. B. thuringiensis spores, which are nontoxic, may persist in the
environment, yet infection of insects from environmental dose levels is minimal.
4. Exposure and Risk Characterization
The available data and published literature indicate that certain B.
thuringiensis products containing fermentation by-products may cause
toxicity/pathogenicity in daphnia, the honey bee and other nontarget beneficial
insects. Since B. thuringiensis formulations used mainly for terrestrial application
are not expected to appear at significant levels hi aquatic environments, daphnia
sensitivity to these subspecies, (kurstaki, aizawai and tenebrionis) does not pose
an aquatic environmental concern, although percautionary labeling may be required
- 26
-------
for some uses to ensure that no inadvertent exposure occurs. (However, daphnia
studies are a useful screen for terrestrial species and may indicate that additional
testing is justified.) In contrast, B. thuringiensis subspecies israelensis is typically
applied to water for mosquito control. As a result, aquatic invertebrate sensitivity
is more likely to need to be addressed through label mitigation or by minimization
of soluble exotoxin production depending on the production (manufacturing
process) testing (see section V(A)(l)(b)).
a. Exposure and Risk to Nontarget Terrestrial Animals
Due to the relatively short insecticidal half-life of B. thuringiensis
spores and crystals, the exposure and subsequent risk to nontarget wildlife
is limited to the time immediately after application. B. thuringiensis delta-
endotoxin has a direct adverse effect on the target insect orders
(Lepidoptera, Coleoptera, Diptera), but susceptibility varies widely among
individual species. Any one registered product has a narrow susceptible
insect range.,In general, published literature shows a temporary reduction
in susceptible insect populations during the use period. Beneficial insects
and avian and mammalian predators are slightly impacted because of
reduced food source. Unlike with alternative chemical pesticides, however,
no significant population impact from the use of B. thuringiensis products
is noted. Furthermore, alternative chemical pesticides may have additional
direct adverse effects on birds, mammals, and nontarget insects that are not
observed with the use of B. thuringiensis products.
(1) Birds
Any effects of B. thuringiensis delta-endotoxin on
insectivorous"birds is due to a reduction of food supply. Birds that
feed on caterpillars in the spring will have a reduced number of prey
on which to feed for a short time. This forces a switch in the diet.
The number of nesting attempts per year may be reduced but not
necessarily the number of fledglings per breeding territory in the
year of application or subsequent years. ' -
No toxicity or pathogenicity to avian species was seen in the
studies submitted in support of this reregistration. Based on these
results, no unreasonable risk to avian species is expected from the
label uses of the registered B. thuringiensis products as long as the
production process is properly controlled _to prevent nontarget
effects due to exotoxins.
27
-------
(2) Mammals
Mammals, including bats, that feed on susceptible insects
might be affected indirectly by reductions in food abundance. This
may trigger a switch in diet. Unlike with many conventional
pesticides, however, they are not affected by ingestion of moribund
insects.
The submitted rodent data and the anticipated low exposure
of mammalian wildlife during use of these microbial pest control
agents indicates that risk to wild mammals from the label uses of
Bacillus thuringiensis is minimal to nonexistent as long as the
production process is properly controlled to prevent nontarget
effects due to exotoxins.
(3) Insects
The use of B. thuringiensis delta-endotoxin results in a
temporary reduction hi susceptible insect populations. In forest
uses, there is a significant decrease hi numbers of adult and larval
Lepidoptera the year of spray, with some reductions extending into
the following year hi species whose susceptible life stage occurs in
the year previous to the appearance of adults. B. thuringiensis delta-
endotoxin does not, however, affect the overall abundance of
arthropods, including beetles, sucking insects such as aphids,
leafhoppers, or cicadas and spiders. Direct toxicity to terrestrial
insect predators and parasites has not been noted hi any studies
except some low-level mortality hi a laboratory study at doses
higher than the recommended label use rates. Any effect on insect
predators and parasites appears to be indirect. Field studies on
insects other than the target pests and their parasites and predators
have found few other species of groups that are affected. Among the
susceptible nontarget insect populations that are adversely affected
during prolonged B. thuringiensis delta-endotoxin applications,
recovery takes place soon after cessation of pesticide use.
Direct toxicity to honeybees has been shown for some
strains. Exposure to honeybees could occur, but the risk is
considered minimal since the pesticide is not considered toxic to
adult honeybees at the label use rates. If excessive toxicity is seen
hi any subsequent product testing, labeling will be required to
reduce exposure to honeybees.
28
-------
Based on these results, the risk to nontarget beneficial insects
is expected to be "minimal to nonexistent from the label uses of
registered B. thuringiensis products as long as the production
process is properly controlled to prevent nontarget effects due to
exotoxins.
b. Exposure and Risk to Nontarget Aquatic Animals
(1) Freshwater Fish
Field studies on B. thuringiensis delta-endotoxin
contaminated water found no observable effects on resident fish
behavior and reproduction. Consumption of delta-endotoxin treated
insects has not affected fish to any noticeable degree. Fish that feed
on susceptible insects may be affected indirectly by reductions in
food abundance. While no toxrcity data are available on reptiles and
amphibians, B. thuringiensis delta-endotoxin is not believed to pose
a hazard to these organisms.
No toxicity' or pathogenicity was seen in studies submitted
in support of this reregistration. As a result, no unreasonable risk
to freshwater fish is expected from the label uses of registered B.
thuringiensis products as long as the production process is properly
controlled to prevent nontarget effects due to exotoxins.
(2) Freshwater Invertebrates
B. thuringiensis delta-endotoxin has no appreciable effect
on aquatic invertebrates. Field studies have concluded that there is
no adverse effect on the abundance and composition of benthic
' insects. Immature and adult stages of mayflies, caddisflies,
dragonflies, damselflies, beetles, midges, and dobsonflies are
unaffected. Studies on application of B. thuringiensis subspecies
kurstaki to a forest stream showed no measurable effects on the
microinvertebrate community composition or abundance. A brief
. reduction inpopulations of mayfly, blackfly and stonefly was noted.
Moderate to high levels of toxicity to daphnia was- seen in
studies submitted in support of this reregistration. This toxicity was
attributed to factors other than delta-endotoxin. However, the risk
to daphnids and other aquatic invertebrates is considered minimal to
nonexistent based on currently registered label use rates because the
29
-------
environmental concentration is lower than the observed laboratory
effect levels. However, some products may require labeling to
reduce exposure if the exotoxin levels can not be sufficiently
controlled during the manufacturing process. Based on these results,
no freshwater aquatic invertebrate hazard is expected from the label
uses of registered B. thuringiensis products as long as the
production process is properly controlled to prevent higher levels of
nontarget toxicity due to the exotoxins.
(3) Estuarine and Marine Animals
B. thuringiensis delta-endotoxin is not expected to have any
adverse effects on estuarine and marine animals because of lack of
toxicity and exposure. Invertebrates in marine and estuarine
ecosystems are not effected by B. thuringiensis delta-endotoxin.
Published studies report no effect to oysters, mussels, shrimp, and
periwinkles.
No toxicity or pathogenicity was seen in studies submitted
in support of this reregistration. Based on these results, no
unreasonable risk to estuarine and marine animals is expected from
the label rate uses of currently registered B. thuringiensis products
as long as the production process is properly controlled to prevent
nontarget effects due to exotoxins.
c. Exposure and Risk to Nontarget Plants
In order for B. thuringiensis delta-endotoxin to have a toxic
effect, it must be ingested by an organism and exposed to
appropriate digestive enzymes at a pH of 9.0 to 10.5. Therefore
terrestrial, semi-aquatic or aquatic plants are unaffected by Bacillus
thuringiensis delta-endotoxin because plants have no mechanism for
its ingestion. In addition, the Agency has found no reports of any
adverse plant effects caused by any other toxins that might be
produced by strains of Bacillus thuringiensis despite the extensive ,
pesticidal use of Bacillus thuringiensis on plants. An indirect
beneficial effect on plants exists as a result of reduction in plant
damaging insect populations.
d. Endangered Species
Based on the toxicity and exposure data there will not be a
"may effect" situation for endangered mammals, birds, plants and
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noninsect aquatic species: All endangered/threatened insect species
that are susceptible to the Bacillus thuringiensis delta-endotoxins
may be adversely affected if exposed.
e. Water Resources
j
_ (1) Surface Water
Bacillus thuringiensis occurs naturally in soils worldwide.
Applications of B. thuringiensis formulations do not increase levels
- of B.t. in soil, and B. thuringiensis spores and crystals persist for
a relatively short time. As all soil microbes, B. thuringiensis does
not percolate through the soil and its presence is confined to the top
10 niches of soil. Thus no ground water contamination concerns are
present.
- (2) Degradation
The microorganism Bacillus thuringiensis (B. thuringiensis)
is ubiquitous in many soils throughout the world. B. thuringiensis
is not known as an aquatic bacterium, and therefore is not expected
to proliferate in aquatic habitats. Although the potential exists for
a minimal amount of the B. thuringiensis which is applied to enter
ground water or other drinking water sources, the amount would in
all probability be undetectable or more than several orders of
magnitude lower than those levels which are tested and are
considered necessary for safety. Moreover, Bacillus thuringiensis
is not considered to be a risk to drinking water. Drinking water is
accordingly not being screened for B. thuringiensis as a potential
indicator of microbial contamination or as a direct pathogenic
contaminant. Low percolation through soil and municipal treatment
of drinking water would reduce the possibility of exposure to B.
thuringiensis through drinking water. The protein delta-endotoxin
is quickly degraded by soil microorganisms. Therefore, the potential
of significant transfer to drinking water is minimal to nonexistent.
D. Product Performance (Efficacy) Assessment
The Agency has waived all requirements to submit efficacy data for review unless the
pesticide product bears a claim -to control pests that pose a threat to human health. Bacillus
thuringiensis is used to control one class of public health pests, i.e. mosquitoes. Product
performance data for these uses have not been reviewed for this Reregistration Eligibility
Document because they are conducted on the end-use products. These assessments will be done
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during product reregistration using the data submitted in response to the Data Call-in associated
with this Reregistration Eligibility Document.
IV. RISK MANAGEMENT AND REREGISTRATION DECISION
A. Determination of Eligibility
i
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 reregistration. The Agency has previously identified and
required the submission of the generic (i.e. active ingredient specific) data required to
support reregistration of products containing Bacillus thuringiensis active ingredients. 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 Bacillus thuringiensis.
Appendix B identifies the generic data requirements that the Agency reviewed as part of
its determination of reregistration eligibility of Bacillus thuringiensis, 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 Bacillus thuringiensis and to determine that Bacillus thuringiensis can
be used without resulting in unreasonable adverse effects to humans and the environment,
providing that an approved manufacturing process be used hi order to minimize or
eliminate the production of certain toxic unintentional ingredients. The Agency therefore
finds that all products containing Bacillus thuringiensis as the active ingredients are eligible
for reregistration. 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 found that all uses of Bacillus thuringiensis are
eligible for reregistration, 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 Bacillus thuringiensis, 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 ingredients Bacillus
thuringiensis, the Agency has sufficient information on the health effects of
Bacillus thuringiensis and on its potential for causing adverse effects in fish and
«
32
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wildlife and the environment. The Agency has determined" that Bacillus
thuringiensis products, manufactured, labeled and used as specified in this
Reregistration Eligibility Decision, will not pose unreasonable risks or adverse
effects to humans or the environment. Therefore, the Agency concludes that
products containing Bacillus thuringiensis for all uses are eligible for
reregistration.
2. Eligible and Ineligible Uses
The Agency has determined that all uses of Bacillus thuringiensis are
eligible for reregistration.
B. Regulatory Position
The following is a summary of the regulatory positions and rationales for Bacillus
thuringiensis. Where labeling revisions are imposed, specific language is in Section V.
1. Tolerance Reassessment (40 CFR 180.1011 and 40 CFR 180.1001(c))
An exemption from the requirements for a tolerance is currently established
for Bacillus thuringiensis in or on beeswax and honey and all other raw agricultural
commodities when it is applied either to growing crops, or when it is applied after
harvest in accordance with good agricultural practices (40 CFR §180.1011). In
addition, there is a tolerance exemption (40 CFR I80.1001(c)) for Bacillus
thuringiensis fermentations solids and/or solubles. The absence of any
toxicological/pathogenicity concerns for oral mammalian exposures to Bacillus
thuringiensis warrants continuation of these exemptions as long as. the proper
quality control procedures are performed as described hi Section V(A)(l)(a) of this
Reregistration Eligibility Document.
The specific language in the tolerance exemption, 40 CFR 180.1011, dates
from 1971 and does not reflect current taxonomy designations for Bacillus
thuringiensis- isolates. This exemption also includes the quality control
specifications for production of Bacillus thuringiensis designed to prevent changes
in characteristics of the active ingredient, contamination with other
microorganisms, and/or presence of detectable levels of beta-exotoxin or other
mammalian toxins. These batch testing requirements for production of food use
Bacillus thuringiensis should also apply to nonfood uses that are not subject to the
40 CFR 1011 tolerance exemption. Therefore, these production testing
requirements will now be required under the product analysis data requirements ha
40 CFR 158.740(a) and will apply to all registered isolates and all uses of Bacillus
thuringiensis. An additional benefit of this appearing hi only one place is that if
the Agency needs to modify these production batch tests it will only have to change
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the product analysis requirements for Bacillus thuringiensis. To ensure that the
production batch tests requirements do not lapse for any products, the Agency will
repropose the tolerance exemptions following publication of this Reregistration
Eligibility Document.
2. Risk Mitigation
a. Mitigation Measures for Dietary, Occupational and Residential Risk
The potential risk to humans from dietary, non-dietary and occupational
exposures of the delta-endotoxins and most of the cellular components of Bacillus
thuringiensis are considered negligible. However, direct exposure to dry,
anhydrous preparations have caused eye irritation effects and those products must
require protective eye equipment on the lable to reduce eye exposure.
The Agency is concerned about the potential for the production of various
undesirable Bacillus exotoxins for environmental effects because their synthesis
appears to depend on unpredictable aspects of the composition of the fermentation
media or growth conditions. These toxins may be inducible toxins, dependent on
the presence of certain chemicals being present to turn on the biochemical pathway
to synthesize them, they may be toxic metabolites, requiring the presence of certain
chemicals for their synthesis, or their synthesis may depend on physical growth
parameters such as temperature. Production batch testing is required in order to
detect some of these toxins and to detect contamination by pathogenic bacteria.
These quality control testing requirements are described in section V, Actions
Required by Registrants. In addition, as described in the Registration Standard,
there may be a potential for strains of Bacillus thuringiensis to produce beta-
exotoxin during subsequent growth in formulated products, despite none being
detected in production batches. If the organism is capable of producing beta-
exotoxin, the registrant should ensure that none is present in the TGAI and that the
product is not put in a medium, including formulated end use products that allows
germination and/or growth at any time prior to use. End use product testing
options for beta-exotoxin are discussed in section V, Actions Required by
Registrants.
b. Mitigation Measures for Nontarget Organisms (Plants and Wildlife),
or Ground and Surface Water Contamination
As described in the environmental assessment, section ni(C), there should
be no unreasonable adverse effects on nontarget organisms, or ground or surface
water contamination concerns, from the delta-endotoxins and most of the cellular
components of Bacillus thuringiensis when used according to currently approved
34
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label rates. The assessment assumed that the Bacillus thuringiensis was produced
in accordance with the quality control testing required for each batch produced.
However, the Agency has no information on whether the current battery of tests
will detect the heat labile exotoxins that have been detected in various non target
species tests, but would like to minimize their presence in the product. A Daphnia
magna test using a 10 day exposure period appears to be the most sensitive assay
of those we have reviewed. This test will be required to certify each manufacturing
process as described in section V, Actions Required of Registrants.
3. Endangered Species Statement
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 that will eliminate the adverse impacts. The program would 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.
4. Labeling Rationale
In accordance with the Federal Insecticide, Fungicide, and Rodenticide Act,
section 2(n)(l), the label of each pesticide product must bear a statement which
contains the "name and percentage of each active ingredient, the total percentage
by weight of all inert ingredients; ...". Bacillus thuringiensis manufacturers have
attempted to meet this requirement by using arbitrary conversions from potency
units or by various chemical assay methods as previously specified by the Agency.
(Tompkins, et al. 1990). However, because there is no longer any public
organization to standardize bioassays and the chemical assays do not adequately
reflect potency (see section 6, below), EPA will no longer require these methods
to be used to satisfy the legally mandated label statement. Instead, a conversion
factor will be used to determine the actual weight per spore-crystal or cell-toxin
complex to use in calculating a percent active ingredient for the concentration of
the spore-crystals or cell-toxin complexes in the products. In order to avoid
misleading the consumer, the label must state that the percent active ingredient
35
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value is not necessarily related to the pesticidal activity of Bacillus thuringiensis-
based products.
In addition to the percent active ingredient value, above, the label must
identify the active ingredient as Bacillus thuringiensis. Furthermore, all toxins
and/or chemical substances that are present at levels that are known to contribute
to the efficacy of the product against the target pest(s) must be listed on the label.
This is particularly important in order to allow consumers to select the most
appropriate product for use in conjunction with the plants that express
delta-endotoxins derived from Bacillus thuringiensis or with other Bacillus
thuringiensis-based microbial pesticides. In addition, the strain identity and a
nationally-recognized culture collection accession number must appear in the
Confidential Statement of Formula and may be placed on the label.
5. 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.
6. Product Performance (Efficacy) Reassessment
The Agency has an established policy that the submission of efficacy data
may be waived, unless the pesticide bears a claim to control pests that pose a threat
to human health. However, even if the submission of the efficacy data is waived,
each registrant must ensure through testing that his products are efficacious when
used in accordance with the label directions and commonly accepted pest control
practices. The Agency reserves the right to require, on a case-by-case basis,
submission of efficacy data for any pesticide registered or proposed for
registration/reregistration.
Public Health Uses: In this case, the registrants of all Bacillus thuringiensis
products with label claims to control mosquitoes, blackflies, or other public health
pests, are required to either submit/cite product performance (efficacy) data, or
delete the label claims for controlling these pests as part of product reregistration. _
Public Health and Non-public Health Uses: Because the efficacy of Bacillus
thuringiensis products may vary greatly from one production batch to another, each
36
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production batch must be analysed for potency. The results of these studies should
not be routinely submitted to the Agency for review, but must be available if the
Agency requests the the data on a case-by-case basis. The potency (killing power)
must be assessed using a bioassay procedure for the following reasons:
Industry has also used chemical analysis methods to quantify the amount of
the delta-endotoxins present in their products. However chemical analysis methods
do not measure the quality of the toxins which may vary widely in their potency
between different production batches. In addition, there are factors other than the
delta-endotoxins that contribute to the efficacy of some Bacillus thuringiensis
products. The spores may germinate and establish an infection secondary to the
direct toxic damage. Other toxins, such as the recently-described VipSA (Estruch,
et al., 1996. VipSA, a novel Bacillus thuringiensis vegetative insecticidal protein
with a wide spectrum of activities against lepidopteran insects, Proc. Natl. Acad.
Sci. USA 93:5389-5394), may have activity similar to, or may be synergistic to,
the delta-endotoxins. The genetic control of toxin synthesis may also affect the
activity of the toxins, e.g. in some cases the delta-endotoxin is synthesized
throughout the growth cycle of the cell rather than during spore formation. None
of these factors can be accounted for by the chemical analysis methods.
Industry originally used a bioassay, using a standarized culture of Bacillus
thuringiensis subspecies kurstaki (HD-1) and a standard susceptible insect,
Trichoplusia ni, to establish the potency which was expressed hi International
Units. However, the use of the term "international units" may, hi some cases, not
be appropriate because there is no longer a publicly-available standardized bioassay
or standarized cultures. In addition, the proliferation of Bacillus thuringiensis
isolates that express new types of delta-endotoxins have expanded the range of
target organisms so that different insect species may have to be used. In the
absence of a public organization to oversee standarization of these assays, industry
must be responsible for maintaining appropriate internal standards for these assays.
It should be noted that these assays can no longer be relied on to compare one
company's products with products from another company.
V.. ACTIONS REQUIRED OF REGISTRANTS
This section specifies the data requirements and responses necessary for the reregistration
of both manufacturing-use and end-use products.
A. Manufacturing-Use Products
This section specifies the data requirements and responses necessary for the
reregistration of manufacturing-use products which, for Bacillus thuringiensis, include
37
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additional confirmatory generic data for reregistration of the TGAI." These data
requirements apply also to end use products for which there is no manufacturing-use
product.
1. Additional Generic Data Requirements
The generic data base supporting the reregistration of Bacillus thuringiensis
for all uses has been reviewed and determined to be substantially complete.
Because of potential variation in production batches, confirmatory data are needed
to ensure that no unintentional ingredients, e.g. toxins, are present at significant
levels. These additional data are specified in Appendix D, the Generic Data Call-in
Notice.
a. Qualitity Control Manufacturing Process Data Requirements
Each production batch must be tested by at least the following tests as
originally listed in the tolerance exemption, 40 CFR 180.1011. The Agency
recognizes that better tests may be developed to detect undesirable toxic
contaminants and encourages submission of such tests for evaluation by Agency
scientists. If more appropriate tests are found acceptable, the Agency will allow
registrants to substitute them for currently required tests or may modify these
quality control test requirements for all registrants.
A new manufacturing process must be submitted that includes a description
of the qualitity control procedures as follows.
Quality Control Testing Required for each Production Batch: (1) Bacillus
thuringiensis shall be produced by pure culture fermentation procedures with
adequate control measures during production to detect any changes from the
characteristics of the parent strain or contamination by other microorganisms. (2)
Each production batch, prior to the addition of other materials, shall be tested by
subcutaneous injection of at least 1 million spores, or equivalent for asporogenic
strains, into each of five laboratory test mice weighing 17 grams to 23 grams.
Such test shall show no evidence of infection or injury in the test animals when
observed for 7 days following injection. ("Evidence of infection or injury" is any
indication of either systemic or localized infectivity or toxicity) (3) Production
batches shall be free of the Bacillus thuringiensis beta-exotoxin when tested with
the fly larvae toxicity test ("Microbial Control of Insects and Mites." R.P.M.
Bond, et al., p.280ff., 1971). This specification can be satisfied either by
determining that each master seed lot brought into production is a Bacillus
thuringiensis strain which does not produce beta-exotoxin under standard
manufacturing conditions or by periodically determining that beta-exotoxin
synthesized during the manufacturing process is eliminated by the subsequent
38
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manufacturing process procedure(s). (If the organism is capable of producing beta-
exotoxin, the registrant should ensure that none is present in the TGAI and that the
product is not put in a medium, including formulated end use products that allows
germination and/or growth at any time prior to use.) Some registrants have been
authorized to use an HPLC method instead of the fly larvae test. In order to
reconfirm the accuracy of Agency records, those registrants must resubmit, or cite,
their request to use HPLC and the supporting data to show that the method is at
least as sensitive as the fly larvae test.
In addition to the above testing for undesirable components of each
production batch, each production batch must be analyzed for potency by bioassay
because the efficacy at Bacillus thuringiensis products may vary greatly from one
production batch to another. The results of these studies should not be routinely
submitted to the Agency for review, but must be available if the Agency requests
the data on a case-by-case basis.
b. Standardization of Manufacturing Process
Registrants must optimize and control their manufacturing process
sufficiently to prevent production of significant amounts of the heat labile
exotoxins. The manufacturing process must include the fermentation medium
composition and the growth conditions. In lieu of requiring SL Daphnia test on each
production batch, as an indicator of the heat labile exotoxin levels, a representative
sample of the active ingredient from each manufacturing process is to be tested by
a Daphnia study incorporating a 10 day exposure period using a maximum hazard
dose. If the test shows significant lethality, a dose response Daphnia test must be
performed to derive an LC50.
A specific, detailed description of the manufacturing process and the
Daphnia testing must be submitted for approval by the Agency. Further testing or
mitigation measures may be required following Agency review (Figure 1).
2. Labeling Requirements for Manufacturing-Use Products
To remain hi 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: -
"Only for formulation into an Insecticide 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
39
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to an MP label under "Directions for Use" to permit the refonhulation 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 requirements regarding
support of such, use(s)."
In Addition, for Bacillus thuringiensis manufacturing use products, a "point
source discharge" is a possibility - where effluent from the manufacturing plant
may contain Bacillus thuringiensis or toxic fermentation byproducts. The
following National Pollutant Discharge Elimination System (NPDES) statement (as
outlined in Pesticide Regulation (PR) Notice 93-10 (Reference: PR-93-10)) is
required on such products:
"Do not discharge effluent containing this product into lakes, streams, ponds,
estuaries, oceans, or other waters unless in accordance with the requirements of a
National Pollutant Discharge Elimination System (NDPES) permit and the
permitting authority has been notified in writing prior to discharge. Do not
discharge effluent containing this product to sewer systems without previously
notifying the local sewage treatment plant authority. For guidance contact your
State Water Board or Regional Office of the EPA."
Further, P.R. Notice 95-1 (Reference: PR-95-01) exempts certain products
(i.e., products in containers of less than 5 gallons (liquid), less than 50 pound?
(solid, dry weight) and in aerosol containers of any size) from bearing effluent
discharge statements specified by P.R. Notice 93-10. P.R. Notice 93-10 still
applies to the following kinds of pesticide products that may result in discharges
to the waters of the United States or to municipal sewer systems, including but not
limited to: (A) all technical grade and manufacturing use products; and (B) end-use
products packaged hi containers equal to or greater than 5 gallons (liquid) or 50
pounds (solid, dry weight), and registered for industrial preservative, water
treatment, other industrial processing uses (such as cooling tower water systems,
pulp and paper mill water systems, secondary oil recovery injection water systems,
food processing operations, leather tanning, wood protection and textile treatment)
and commercial and institutional uses (including, but not limited to, hospitals,
hotels/motels, office buildings and prisons).
40
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The exemption of certain containers from the labeling requirements of P.R.
Notice 93-10 does not relieve a producer or user of such products from the
requirements of the Clean Water Act or state or local requirements.
Figure 1. Testing standardized manufacturing process.
Test representative manufacturing process with
Daphnia study
Negative
No more data needed
No additional labeling
Positive 1
Eco effects: Risk issue - may affect nori target organisms from toxin present in product
Determine LC50 in a Daphnia study to allow a quantative risk assessment
i
If LC50/risk is high
Test other non-target species
to determine proper labeling
and/or mitigate (below)
If LCsn/risk is low
"50'
No further testing or
labeling is needed
I
Reevaluate uses in
order to reduce
exposure
Inactivate toxin
genes
Optimize manufacturing
process to minimize toxin
production
41
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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. The product specific data requirements are listed hi Appendix D, the
Product Specific Data Call-in Notice and are summarized below.
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. In
addition to the conventional data requirements, a storage stability study is required
for certain end-use products, and, in cases where claims are made for controlling
public health pests, product performance studies are required to be submitted.
a. Conventional Data Requirements }
Product Analysis data and Acute Toxicology data must be
submitted, or cited, to support all manufacturing-use and end-use products.
The Acute Toxicology data consists of an acute oral toxicity study in the
rat, an acute dermal toxicity study, and acute inhalation toxicity study in the
rat, a primary eye irritation study in the rabbit, and a primary dermal
irritation study. On a case-by-case basis, the Agency may accept waivers
for some of these data requirements based on the known toxicity of the
ingredients or other arguments provided by the registrant. For example,
the Agency may accept a proposal to require goggles when the product may
be predicted to cause adverse eye effects as for a dry hydroscopic powder
or silica containing formulations. In other cases, a particular study may not
be needed because the formulations contain well characterized ingredients
that are not likely to present an unreasonable risk.
b. Storage Stability Study
. The Registration Standard of 1989 asked for a storage stability study
for end use products to determine concentrations of beta-exotoxin because
the Agency suspected that beta-exotoxin may be formed in certain end use
products subsequent to formulation. Many registrants requested waivers
because they did not believe their product would support microbial growth.
42
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The Agency considered these requests and we have now established
standards for requiring the storage stability studies as follows. A storage
stability study will -be required for all aqueous products that can support
gram positive bacterial growth. If the storage stability studies were already
submitted in response to the Registration Standard, they may be cited.
c. Product Performance (Efficacy)
The Agency has waived all requirements to submit efficacy data for
review unless the pesticide product bears a claim to control pests that pose
a threat to human health. Thus, product performance data must be
submitted or cited for ^Bacillus thuringiensis products that have mosquito,
blackfly, or other public health pest control uses. This product
performance data requirement may be satisfied by submission of a properly
controlled potency test as discussed in section IV(B)(6) of this
Reregistration Eligibility Document.
2. Labeling Requirements for End-Use Products
a. Percent Active Ingredient
Because there currently is no accountable way to factor potency into
the required label statement, EPA will no longer require potency as part of
the legally mandated label statement. The following method will be used
to provide a conversion'factor for the weight of an "active" unit for use in
converting the product concentration to satisfy the FIFRA requirements: A
laboratory culture of the bacterium is grown in a soluble medium, such as
trypticase soy broth, and when the culture sporulates and lyses, the number
of spores per mililiter (ml) is determined by standard bacteriological
counting methods. In the case where the Bacillus thuringiensis toxins are
being produced in a non-spore forming bacterium, the number of vegetative
cells per ml would be determined. Then concentrate the spore-crystal or
cell-toxin complex by centrifugation or filtration, dry the concentrate, and
determine the weight hi grams of the dry spore-crystal or cell-toxin
complex. The percent active ingredient by weight for Bacillus
thuringiensis-based products must then be calculated for label purposes by
determining the number of spores or cells per gram of product, multiplying
that value by the weight of an individual spore-crystal or cell-toxin
complex, and multiplying that value by 100.
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c. Potency Determination
The label for both public health and non-public health uses may
include potency statements; however, in accordance with 40 CFR
156.10(a)(5)(ii), the statement must not be false or misleading. See section
IV(B)(6) of this Reregistration Eligibility Document for guidance in
conducting appropriate tests.
d. Worker Protection Standard
Any product whose labeling reasonably permits use in the
production of an agricultural plant on any farm, forest, nursery, or
greenhouse must comply with the labeling requirements of PR Notice 93-7,
"Labeling Revisions Required by the Worker Protection Standard (WPS)",
and PR Notice 93-11, "Supplemental Guidance for PR Notice 93-7", which
reflect the requirements of EPA' s labeling regulations for worker
protection statements (40 CFR part 156, subpart K). These labeling
revisions are necessary to implement the Worker Protection Standard for
Agricultural Pesticides (40 CFR part 170) and must be completed in
accordance with, and within the deadlines specified in, PR Notices 93-7 and
93-11. Unless otherwise specifically directed in this RED, all statements
required by PR Notices 93-7 and 93-11 are to be on the product label
exactly as instructed in those notices.
After April 21, 1994, except as otherwise provided in PR Notices
93-7 and 93-11, all products within the scope of those notices must bear
WPS PR Notice complying labeling when they are distributed or sold by the
primary registrant or any supplementally registered distributor.
After October 23,1995, except as otherwise provided in PR Notices
93-7 and 93-11, all products within the scope of those notices must bear
WPS PR Notice complying labeling when they are distributed or sold by
any person.
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.
e. Other
(1) A respiratory protection statement must appear on the label
for different uses as follows:
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100 x conversion factor x Number of units/gram in the product = % active ingredient by weight
The conversion factor is "Weight (grams)/unit" and a unit is either one spore-crystal complex or one
cell-toxin complex.
In order to avoid misleading the consumer, a statement must appear
on the label below the percent active ingredient value: "There is no direct
relationship between intended activity (potency) and the Percent Active
Ingredient by Weight."
b. Active Ingredients
In addition to the percent active ingredient value, above, the label
must identify the active ingredient as Bacillus thuringiensis. Furthermore,
all toxins and/or chemical substances that are present at levels that are
known to contribute to the efficacy of the product against the target pest(s)
must be listed on the label. This is particularly important hi order to allow
consumers to select the most appropriate product for use hi conjunction
with the plants that express delta-endotoxins derived from Bacillus
thuringiensis or with other Bacillus Ihuringiehsis-based microbial pesticides.
In addition, the strain identity and a nationally-recognized culture collection
accession number must appear hi the Confidential Statement of Formula and
may be placed on the label. At this time, the Agency recommends that the
delta-endotoxins be classified hi accordance with the standards being
developed by the Bacillus thuringiensis delta-endotoxin nomenclature
committee which was set up hi 1993 hi order to update the nomenclature
originally devised hi 1989 by Hofte and Whiteley (Microbiological Reviews
53:242-255). This new nomenclature is based on the similarities between
the full length toxin sequences rather than on the assessment of biological
properties. References to this new nomenclature may be found at (1)
Revision of the Nomenclature for the Bacillus thurhigiensis Pesticidal cry
Genes. N. Crickmore, D. R. Zeigler, J.Feitelson, E. Schnepf, B. Lambert,
D. Lereclus, J. Baum and D.H. Dean (1995) In: Program and Abstracts
of the 28th Annual Meeting of the Society for Invertebrate Pathology. p!4.
Society for Invertebrate Pathology, Bethesda, MD, and (2) Bacillus
thurhigiensis delta-endotoxin nomenclature N. Crickmore, D.R. Zeigler,
J.Feitelson, E. Schnepf, D. Lereclus, J. Baum, J. Van Rie and D.H. Dean
(1997) WWW site: http://epunix.biols.susx.ac.uk/ Home/Neil_Crickmore/
Bt/ index.html. At such time the new nomenclature is validly published and
accepted, the Agency may require it to be used for delta-endotoxin
classification.
44
-------
(a) Agricultural Use Products
The personal protective equipment (PPE) section must
include the statement:
"As a general precaution when exposed to potentially high
concentrations of living microbial products such as this, all
mixer/loaders and applicators must wear a dust/mist filtering
respirator meeting NIOSH standards of at least N-95, R-95,
or P-95."
Registrants may add the following engineering control
statements to the PPE section if they so choose:
"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."
PPE for early entry in the Agricultural Use Requirements box
remains unaffected.
(b) Non-Agricultural Use Products not Used Around the
Home
Either the PPE section or the precautionary statements of the
Hazards to Humans and Domestic Animals section must
include the statement:
"As a general precaution when exposed to potentially high
concentrations of living microbial products such as this, all
mixer/loaders and applicators not in enclosed cabs or aircraft
must wear a dust/mist filtering respirator meeting NIOSH
standards of at least N-95, R-95, or P-95."
(c) Domestic (Home) Use Products
Either the PPE section or the precautionary statements of the
Hazards to Humans and Domestic Animals section must
include the statement:
"As a general precaution when exposed to potentially high
46
-------
concentrations of living microbial products such as this, wear
a dust particle mask when mixing or applying this product."
(2) All commercially applied products with directions for
outdoor terrestrial uses must have the following statements hi the
Environmental Hazards section:
\ _
1 i
"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 when cleaning equipment or "disposing of
equipment washwaters." -
This statement should be preceded by "For terrestrial uses,"
if the product has aquatic sites hi addition to terrestrial, forestry
(except aerial application) and/or domestic outdoor uses.' This
revised statement would then not apply to other general use patterns
aquatic (e.g., mosquito larvicides or adulticides, aquatic
herbicides, piscicides, slimicides, etc.), greenhouse and indoor uses.
The "For terrestrial uses," qualifier is not allowed on products
which allow aerial application to forests but which have' no
approved aquatic use sites.
(3) For residential consumer products, the required statement is:
"Do not apply directly to water. Do not contaminate water when
disposing of equipment washwaters or rinsate."
(4) For direct water application uses, the required statement is:
"Do not apply directly to treated, finished drinking water reservoirs
or drinking water receptacles."
f. 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."
47
-------
Page Intentionally Blank
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Page Intentionally Blank
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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 point backward 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.
The following aerial drift reduction advisory information must be
contained hi the product labeling:
[This section is advisory hi 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. Apply ing 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.
48 .
-------
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.
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
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 hi low relative humidity, set up
s
49
-------
equipment to produce larger droplets to compensate for evaporation.
Droplet evaporation is most severe when conditions are both hot and dry.
TEMPERATURE INVERSIONS
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 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 Reregistration 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 Bacillus
thuringiensis 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.
50
-------
VI. APPENDICES
51
-------
Page Intentionally Blank
52
-------
APPENDIX A. Use Sites for the Reregistration of 0247
i
Bacillus thuringiensis Case #0247 Quantitative Usage Analysis
Site
Blackberries
Blueberries
Cranberries
Raspberries
Strawberries
Citrus, Other
Grapefruit
Lemons
Oranges
Apples
Pears
Pome-Like Fruit, Other
Avocados
Nectarines
Apricots
Cherries
Peaches
Plums & Prunes
Grapes
Almonds
Pecans
Walnut
Acres
(000)
Grown
5
59
29
11
51
51
194
63
867
572
78
-58
82
29
19
128
212
140
825
429
488
205
Acres Treated (000) %
Weighted
Average Max
1
4
4
3
8
1
0
0
21
19
1
3
1
10
4
4
11
8
43
38
11
2
2
11
9
11
15
2
1
0
39"
50
5
14
3
22
8
8
23
25
86
64
30
5
of Crop Treated
Est Weighted Est
Average Max
19%
1%
13%
30%
16%
1%
0%
0%
2%
3%
1%
5%
1%
34%
20%
3%
',5%
6%
, 5%
9%
2%
1% "
45%
18%
32%
100%
31%
3%
0%
0%
4%
9%
6%
24%
3%
74%
39%
6%
11%
18%
10%
15%
6%
2%
1.0
5.4
1.0
1.7
1.0
1.0
1.3
1.0
1.0
1.9
1.0
1.2
1.0
1.0
1.0
1.5
1.7
1.2
1.6
1.8
1.2
1.1
States of Most Usage
(% of total Ibai
# appl used on this site)
/year
CA 100%
CA 100%
CA 100%
CA 100%
WA MI OH
CA CO WA
CA 100%
CAFL
CA
WACANY
CA91%
AZ81%
100%
86%
CA OR 100%
CA 82%
CA 100%
' TXOKAL81%
CA 100%
Vegetables, Bulb
Eggplant
Peppers
Celery
Greens
Kale
Lettuce -
Spinach
Parsley
Broccoli
Cabbage
396
16
44
11%
2.0
CA EL 86%
4
235
37
2
6
268
19
2
114
85
1
27
17
1
0
56
8
0
22
33
3
45
24
0
0
100
16
1
29
43
28%
11%
46%
46%
0%
21%
40%
15%
19%
39%
79%
19%
65%
0%
0%
37%
87%
66%
26%
51%
4.2
5.4
1.0
4.4
1.0
2.0
. 1.0
1.0
1.1
1.4
FLTXCA
-
AZMI
CAAZFL
CA
84%
,
85%
Acres
Acres Treated (000) % of Crop Treated ,
States of Most Usage
53
-------
Site
Cauliflower
Collards
Cucumbers
Squash
Cantaloupes
Melons, Honeydew
Watermelons
Artichokes
Asparagus
Beets
Potatoes
Roots/Tubers
Sweet Corn
Tomatoes
Beans/Peas, Dry
Beans/Peas, Green
Com
Barley
Oats/Rye
Rice
Sorghum
Wheat, Spring
Wheat, Winter
Hay, Other
Pasture
Alfalfa
Peanuts
Soybeans
Sunflower
Cotton
Sugar Beets
Sugarcane
Other crops
Tobacco
(000)
Grown
58
11
146
53
113
27
258
9
88
12
1,421
244
784
500
2,181
723
72,284
7,505
6,133
2,921
11,280
20,799
45,854
33,427
86,960
23,949
1,610
62,879
2,745
12,689
1,415
852
2,515
695
Weighted
Average
13
4
11
1
16
2
11
9
3
0
20
9
3
91
6
13
151
1 "
0
1
0
2
1
0
29
54
2
88
3
377
4
0
16
32
Max
22
8
28
4
32
6
21
9
9
-1
45
17
6
171
33
23
381
6
1
2
0
9
1
0
100
89
6 .
275
9
787
14
0
27
47
Est
Average
23%
31%
8%
1%
14%
6%
4%
93%
3%
2%
1%
4%
0%
18%
0%
2%
0%
0%
0%
0%
0%
0%
0%
0%
0%
0%
0%
0%
0%
3%
0%
0%
1%
,5%
Weighted Est
Max
38%
67%
19%
7%
28%
22%
8%
100%
10%
7%
3%
7%
1%
34%
2%
3%
1%
0%
0%
0%
0%
0%
0%
0%
0%
0%
0%
0%
0%_
6%
1%
0%
1%
7%
1.9
1.0
1.0
1.0
1.0
1.7
1.0
1.0 -
1.0
1.0
3.6
3.6
1.3
3.9
1.1
2.6
1.1
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
2.3
1.0
1.0
3.2
1.4
(% of. total Ib ai
# appl used on this site)
/year
CANYOHORTXWI.%
RIMACTVA85%
FLTN91%
MA FL MI NC CA MD 76%
FLCAAL83%
CA FL 100%
FLGAAZKY83%
NECOOHFLIL81%
ND 100%
LA, 100%
ND 100%
WV 100%
FL 100%
OK 100%
CAAZ93%
MS LA 89%
ND CA 100%
ALMSLATXAR81%
ND88%
FL100%
CAND88%
NC GA FL 89%
54
-------
Site
Agricultural total
Nursery & Greenhouse
Woodland
Water
Crp Acres-long term
Idle Cropland
Acres
(000) ,
Grown
1,350
3,717
62,825
68,617
7,461
Acres Treated (000) % of Crop Treated States of Most Usage
fOf «£ +~*«l lu .
Weighted
Average Max
2,138
30 50
0 0
unknown, probably
1 1
0 2
Est Weighted
Average
1% 1%
0% 0%
not significant
0% 0%
0% 0%
Est # appl used on this site)
Max /year
1.0
1.8
1.0
1.4 LA 100%
Landscape maintainance
Lots/Farmsteads 49,630
Public health (mosquito control) '
Rights of way
Structural pest control
Non agricultural total
Total
2,632
unknown, probably not significant
2 4 0% 0%
1,250 1,500
spot treatments, amount unknown
unknown, probably not significant
1,283 1,420
3,558
3.6
NHCACOLAMN85%
COLUMN HEADINGS
Weighted averagethe most recent years and more reliable data are weighted more heavily.
Est Max = Estimated maximum, which is estimated from available data.
Average application rates are calculated from the weighted averages.
NOTES ON TABLE DATA
Usage data primarily covers 1987 - 1996.
Calculations of the above numbers may not appear to agree because they are displayed as rounded:
to the nearest 1000 for acres treated or Ib. a.i. (Therefore 0 = < 500)
to the nearest whole percentage point for % of crop treated. (Therefore 0% = < 0.5%)
0* = Available EPA sources indicate that no usage is observed in the reported data for this site, which implies that there is
little or no usage.
A dash (-) indicates that information on this site is NOT available in EPA sources or is insufficient.
* Other/Crop Groups
Bulb Crops include garlic, leeks, and onions.
Citrus, Other includes kumquats, limes, tangelos, and tangerines.
Cucurbits includes cucumber, squash, and pumpkin.
Nut Trees, Other includes chestnuts, filberts, hazelnuts, hickory nuts, macadamia nuts, pistachios, lychie nuts, and palm.
Pome-Like Fruit, Other includes figs, kiwifruit, persimmons, pomegranates, carambolas, and papaya.
Root and Tuber Crops include red beets, carrots, horseradish, parsnips, radish, rutabagas, sweet potatoes, turnips, and yams.
Other crops include popcorn and rapeseed/canola
SOURCES: EPA data, USDA, and National Center for Food and Agricultural Policy
55
-------
Page Intentionally Blank
56
-------
GUIDE TO APPENDIX B
Appendix B contains listings of data requirements which support the reregistration for active ingredients
within the case 0247 covered by this Reregistration Eligibility Decision Document. It contains generic
data requirements that apply to 0247 in all products, including data requirements for which a "typical
formulation" is the test substance.
The data table is organized in the following format:
v
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.
'57
-------
APPENDIX B
Data Supporting Guideline Requirements for the Reregistration of Baciltis thuringiensis
REQUIREMENT USE PATTERN CITATION(S)
PRODUCT CHEMISTRY
885.1100 Product Identity
All
885.1200
Manufacturing Process
All
885.1300
Formation of Unintentional Ingredients All
885.1400
Analysis of Samples
All
. 41439001, 41459403, 41429701,
41435401, 41751101, 42015901,
41441501-31, 41444601-41, 41459401,
41459402, 41459404, 41429601
41439001, 41459403, 41429702,
41435401, 42080101, 42015901,
41490801-03, 41459401, 41459402,
41459404, 41429602
41439001, 41459403, 41429703,
41435401, 41751102, 42015901,
41490801-03, 41459401, 41459402,
41459404, 41429603
41439002, 41880001, 41980101,
41429703, 41939901, 41435402,
41883801, 41751103, 42015901,
41789701, 41653901, 41657002,
' 41646702, 41429603, 41939901
58
-------
Data Supporting Guideline Requirements for the Reregistration of Bacittis thuringiensis
REQUIREMENT
USE PATTERN
CITATION(S)
885.1500
885.1600
' Certification of Limits/Analytical
Methods
Physical & Chemical Limits
TIER I TOXICOLOGY
885.3050 Acute Oral Toxicity/Pathogenicity
885.3150 , Acute Pulmonary
885.3200
885.3400
Toxicity/Pathogenicity
Acute Intravenous -
Toxicity/Pathogenicity
Hypersensitivity Incidents
All
All
All
All
All
All
41439002, 41980101, 41429703,
41435402, 41751104, 42015901,
41789701, 41653901, 41657002,
41646702, 41429603
41439002, 41503903, 41429704,
41435402, 42080102, 42015901,
41429704, 41653901, 41503902,
41503904, 41429604
waived1
waived1
waived1
42027101
59
-------
Data Supporting Guideline Requirements for the Reregistration of BacilHs thuringiensis
REQUIREMENT USE PATTERN CITATION(S)
NON-TARGET ORGANISMS
885.4050 Avian oral pathogenicity/toxicity - ABD Conditionally waived2
885.4200 Freshwater Fish toxicity/pathogenicity - ABD Conditionally waived2
trout
885.4240 Freshwater Invertebrate ABD Conditionally waived2
toxicity/pathogenicity
885.4280 Estuarine and Marine animal - ABD Conditionally waived2
toxicity/pathogenicity
885.4300 Nontarget plant studies ABD Waived2
885.4340 Nontarget insect testing ABD Conditionally waived2
885.4380 Honey bee testing ABD Conditionally waived2
1. Toxicology studies have been waived based on the sura total of all toxicology studies submitted to the Agency, the scientific literature, and the lack
of any reports of significant human health hazards despite considerable exposure from years of use of Bacillus thuringiensis products.
2. Nontarget Organism studies have been either waived, or conditionally waived, based on the sum total of all nontarget organism studies submitted to
the Agency, the scientific literature, and the lack of any reports of significant adverse effects on nontarget organisms despite considerable exposure from
years of use of Bacillus thuringiensis products. Because Agency data shows a potential for Bacillus thuringiensis to produce exotoxins that can adversely
affect nontarget organisms, and the manifestation of these appears to be at least partly related to production methodology, a representative product sample
for each specific manufacturing process will be tested by a Daphnia test as a screen to rule out excessive exotoxin systhesis. Additional nontarget studies
may be required to certify any manufacturing process that results in significant levels of toxicity to Daphnia.
60
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APPENDIX C. Citations Considered to be Part of the Data Base Supporting the
Reregistration of 0181
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 hi the
Reregistration Eligibility Document. Primary sources for studies hi this bibliography have been
the body of data submitted to EPA and its predecessor agencies hi support of past regulatory
decisions. Selections from other sources including the published literature, hi 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 hi,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 hi 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 to4dentify volumes of submitted studies (see paragraph 4(d)(4)
below for further explanation). In a few cases, entries added to the bibliography late hi 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, hi 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.
b. Document date. The date of the study is taken directly from the
61
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document. When the date is followed by a question mark, the
bibliographer has deduced the date from the evidence contained hi the
document. When the date appears as (19??), the Agency was unable to
determine or estimate the date of the document.
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.
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.
62
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MRID
BIBLIOGRAPHY
CITATION
00066178
00066179
00090207
00090208
00096527
00096529
Williams, W.L.; Esposito, R.G.; Hernandez, H.G. (19??) To
Determine the Effect of Intra-peritoneal Injection of Biotrol 10W on
Weight Gain and Mortality of Mice: Experiment Nutrilite Products,
Inc. #1 (504-1). (Unpublished study received Jan 4, 1977 under
6296-13; submitted by Nutrilite Products, Inc., Buena Park, Calif.;
CDL:230811-A)
Williams, W.L.; Esposito, R.G.; Hernandez, H.G. (19??) To
Determine the Effect of Intra-peritoneal Injection of Biotrol
10W-fi"Bacillus thuringiensis~Berliner~followed by Serial Passage of
Blood Intra-peritoneally through Four Consecutive Passages hi Mice:
Experiment Nutrilite Products, Inc. #2 (504-5). (Unpublished study
received Jan 4, 1977 under 6296-13; submitted by Nutrilite Products,
Inc., Buena Park, Calif.; CDL:230811-C) >
Williams, W.L.; Esposito, H.G.; Hernandez, H.G. (19??) To
Determine the Effect of Intra-peritoneal Injection of Lavatrol on
Weight Gain and Mortality of Mice. (Unpublished study received Jun
30, 1959 under PPOSlO; submitted by Nutrilite Products, Inc., Buena
Park, Calif.; CDL:090329-B)
Williams, W.L.; Esposito, R.G.; Hernandez, H.G. (19??) To
Determine the Effect of Intra-peritoneal Injection of Larvatrol-Bacillus
thuringiensis'BerlinerFollowed by Serial Passage of Blood
Intra-peritoneally through Four Consecutive Passages hi Mice.
(Unpublished study received Jun 30, 1959 under PP0310; submitted by
Nutrilite Products, Inc., Buena Park, Calif.; CDL:090329-C)
Lankas, G.R.; Hogan, G.K.; Fasanella, J.; et al. (1981) A Single Oral
. Dose Toxicity/Infectivity Study of Thuricide 32 B hi Rats: Project No.
80-2523; Export No. T-l-2/23/81. (Unpublished study received Mar
8, 1982 under 11273-2; d by Bio/dynamics, Inc., submitted by Sandoz,
Inc.-Crop Protection, San Diego,Calif.; CDL:246967-A)
Ben-Dyke, R.; Hogan, G.K.; Hoffman, C.A.; et al. (1981) An Acute
Inhalation Toxicity and Infectivity Study of Thuricide 32-B hi the Rat:
Project No. 80-7472; rt No. T-3-3/16/81. (Unpubblished study
received Mar 8, 1982 under 11273-2; prepared by Bio/dyanamics, Inc.,
submitted by Sandoz, Inc.Crop Protection, San Diego, Calif.;
CDL:246967-C)
63
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MRID
BIBLIOGRAPHY
CITATION
00096533
00109492
00109493
00142733
00142734
40497400
40497409
40497410
World Health Organization (1980) Data Sheet on the Biological Control
Agent'Bacillus thuringiensis" Serotype H-14 (de Barjac 1978):
WHO/VBC/79.750. (Unpublished study; CDL:246969-B)
Lankas, G.; McCormack, R.; Hogan, G.; et al. (1981) Single Oral
Dose Toxicity/Infectivity Study of Thuricide 32B in the Rat: Project
No. 80-2523; Report No. T-l-2/23/81. Final rept. (Unpublished study
received Aug 9, 1982 under 11273-2; prepared in cooperation with
Bio/dynamics, Inc., submitted by Sandoz, Inc., Crop Protection, San
Diego, CA; CDL:248007-E)
Lankas, G.; McCormack, R.; Hogan, G.; et al. (1981) Acute Dermal
Toxicity/Infectivity Study of Thuricide 32B in the Rat: Project No.
80-2531; Report No. T-l-3/11/81. Final rept. (Unpublished study
received Aug 4, 1982 under 11273-2; prepared in cooperation with
Bio/dynamics, Inc., submitted by Sandoz, Inc., Crop Protection, San
Diego, CA; CDL:248007-F)
StoU, R. (1984) Acute Oral LD50 Toxicity/Infectivity Study of Teknar
in the Rat: Project No. T-1866. Unpublished study prepared by
Sandoz, Inc. 25 p.
Stoll, R. (1984) Acute Dermal LD50 Toxicity/Infectivity Study in the
Rat on Teknar: Project No. T-1867. Unpublished study prepared by
Sandoz, Inc. 18 p.
Sandoz Crop Protection Corporation (1988) Submission of Chemistry,
Toxicity and Residue Data on SAN 418-SC-62 in Support of Trident
Biological Insecticide Registration. Transmittal of 13 studies.
Beavers, J.; Jaber, M. (1987) SAN 418 SC 62 Bacillus Thuringiensis
Tenebrionis: An Avian Acute Oral LD50 Pathogenicity Study in the
Mallard": Study No. 131-132. Unpublished study performed by
Wildlife International Ltd. 19 p.
Beavers, J.; Jaber, M. (1987) SAN 418 SC 62 Bacillus Thuringiensis
Tenebrionis: An Avian Intraperitoneal Injection Pathogenicity Study in
the Mallard: Study No. 131-133. Unpublished study performed by
Wildlife International Ltd. 19 p.
64
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MRID
BIBLIOGRAPHY
CITATION
40497411
40497412
40951100
41270301
41308600
41308603
41308607
41412705
Surprenant, D. (1987) Static Acute Toxicity of SAN 418 SC62 (B. t. .
tenebrionis) to Rainbow Trout (Salmo gairdneri): Report No.
87-10-2520. Unpublished study performed by Springborn Life
Sciences, Inc. 18 p.
Surprenant, D. (1987) Static Acute Toxicity of SAN 418 SC62 (B. t.
tenebrionis) to Daphnids (Daphnia magna): Report No.87-10-2519.
Unpublished study performed by Springborn Life Sciences, Lie. 17 p.
Ecogen, Inc. (1988) Submission of Chemistry and Toxicity Data in
Support of Foil Oil Flowable Insecticide. Transmittal of 10 studies.
Robbins, G. (1989) Intraperitoneal Safety Test in Mice: BMP 144(2X)
(3X): Study No. S2032. Unpublished study prepared by Cosmopolitan
Safety Evaluation, Inc. 18 p.
Ecogen, Inc. (1989) Submission of data in support of registration of
Foil Oil Flowable Bioinsecticide: Toxicity studies. Transmittal of 8
studies.
Sherwood, R. (1989) EPA Subdivision M Tier I Acute Pulmonary
Toxicity/Pathogenicity Testing of Foil Oil Flowable and Technical
Biopesticides: Final Report: IIT Project Number L08245, Study No. 1.
Unpublished study prepared by IIT Institute, Life Sciences Research.
44 p.
Sherwood, R. (1989) Acute Intraperitoneal Toxicity/Pathogenicity
Testing of Foil Technical Powder, a Microbial Pesticide: Final Report:
HTRI Project Number L08239: Study No. 7. Unpublished study
prepared by IIT Research Institute, Life Sciences Research. 19 p.
Berg, N. (1989) Acute Dermal Toxicity Study in Rabbits with SP 408,
PPQ 2585 in Support of Registration of Novodor Technical: Lab
Project I.D.: 13188. Unpublished study prepared by Novo-Nordisk
A/S, Enzyme Toxicology Laboratory. 16 p.
65
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MRID
BIBLIOGRAPHY
CITATION
41429701
41429702
41429703
41429704
41435401
41435402
41439001
41439002
Peter, S.; Boon, B.; Charmoille, L. (1990) Registration Standard No.
0247: Bacillus thuringiensis var. israelensis: Bactomos Primary
Powder: Product Identity and Disclosure of Ingredients ...: Lab Project
Number: 56637/10/90: BT:RS. Unpublished study prepared by Solvay
&Cie. 59 p.
Peter, J.- Boon, B.; Malcorps, C. (1990) Registration Standard No.
0247: Bacillus thuringiensis var. israelensis: Bactomos Primary
Powder: Description of Manufacturing Process ...: Lab Project
Number: BT:RS: 56637/16/90. Unpublished study prepared by Solvay
&Cie. 89 p.
Peter, S.; Boon, B. (1990) Registration Standard No. 0247: Bacillus
thuringiensis var. israelensis: Bactomos Primary Powder: Product
Analysis Data ...: Lab Project Number: BT:RS: 56637/17/90.
Unpublished study prepared by Solvay & Cie. 16 p.
Peter, S.; Boon, B. (1990) Registration Standard No. 0247: Bacillus
thuringiensis var. israelensis: Bactomos Primary Powder: Physical and
Chemical Properties ...: Lab Project Number: BT:RS: 566/37/18/90.
Unpublished study prepared by Solvay & Cie. 5 p.
Coddens, M.; Cooper, R. (1990) Product Analysis: Product Chemistry
Based on Bacillus Thuringiensis, Subspecies Kurstaki (ATCC-SD-1275
as the Active Ingredient: Lab Project Number: Abbott Lab-FMU-02.
Unpublished study prepared by Abbott Laboratories. 23 p.
Coddens, M. (1990) Dipel FMU: Product Chemistry Based on Bacillus
thuringiensis, subspecies Kurstakis (ATCC-SD-1275) as an Active
Ingredient: Lab Project Number: ABBOTT/LAB-FMU-02.
Unpublished study prepared by Abbott Laboratories. 92 p.
Smith, R.; Cooper, R. (1990) Vectobac Technical Powder... Product
Chemistry Based on Bacillus thuringiensis, Subspecies Israelensis
Strain AM65-52 (ATCC-SD-1276) as the Active Ingredient: Lab
Project Nos. Abbott Lab-VTp-02: 910-8906. Unpublished study
prepared by Abbott Laboratories. 174 p.
Coddens, M. (1990) Vectobac Technical Powder...Product Chemistry
Based on Bacillus thuringiensis, Subspecies Israelensis, Strain
66
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MRID
41439003
41439005
41439006
41439007
41439008
41439009
41439010
BIBLIOGRAPHY
CITATION
AM65-52 (ATCC-SD-1276) as the Active Ingredient: Lab Project Nos.
Abbott Lab-VTP-03; 910-8902. Unpublished study prepared by Abbott
Laboratories. 186 p.
David, R. (1990) Acute Oral Toxicity/Pathogenicity Study of Vectobac
Technical Material (Bacillus thuringiensis var. Israelensis) in Rats:
Final Report: Lab Study No. G-7264.222. Unpublished study prepared
by Microbiological Associates, Inc. 61 p.
Lattin, A.; Grimes, J.; Hoxter, K.;.et al. (1990) Vectobac Technical
Material (Bacillus thuringiensis var Israelensis): An Avian Oral
Toxicity and Pathogenicity Study in the Mallard: Project No. 161-115.
Unpublished study prepared by Wildlife International Ltd. 24 p.
Lattin, A.; Hoxter, K.; Smith, G. (1990) Vectobac Technical Material
(Bacillus thuringiensis var Israelensis): An Avian Oral Toxicity and
Pathogenicity Study hi the Bobwhite: Project No. 161-114.
Unpublished study prepared by Wildlife International Ltd. 29 p.
Christenserr, K. (1990) Vectobac Technical Material (Bacillus
thuringiensis var. Israelensis)Infectivity and Pathogenicity to Bluegill
Sunfish (Lepomis macrochirus) during a 30-day Static Renewal Test:
Final Report: SLI Report 90-2-3228; SLI Study 2439.0889.6104.158.
Unpublished study prepared by Springborn Laboratories, Inc. 55 p.
Christensen, K. (1990) Vectobac Technical Material (Bacillus
thuringiensis var. Israelensis)~Infectivity and Pathogenicity to Rainbow
Trout (Oncorhynchus mykiss) during a 32-day Static Renewal Test:
Final 'Report: SLI Report 90-2-3242; SLI Study 2439.0889.103.157.
Unpublished study prepared by Springborn Laboratories, Inc. 55 p
Ward, T.; Boeri, R. (1990) Chronic Toxicity of Vectobac Technical
Material (Bacillus thuringiensis var. Israelensis) to the Daphnid,
Daphnia magna: Lab Study No. 9022-A; Method No. IPM-2.
Unpublished study prepared by EnviroSystems Div., Resource
Analysts, Inc. 46 p.
Chandler, G. (1990) Chronic Toxicity of Bacillus thuringiensis var.
Israelensis Technical Material to the Benthic Harpacticoid Copepod,
Amphiascus minutus under Static Conditions: Report No.
67
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MRID
41441501
41441502
41441503
41441504
41441505
41441506
41441507
BIBLIOGRAPHY
CITATION
USC-SPH-2-90: Abbott Lab-VTP-12. Unpublished study prepared by
Univ. of South Carolina, School of Public Health and the Belle W.
Baruch Insitute for Marine Biology and Coastal Research. 43 p.
Smith, R.; Regan, K. (1990) Biochemical and Morphological
Characteristics of Bacillus thuringiensis subsp. Aizawai Strain SA2
with a Discussion of Strain History Included: Final Report: Final
Report No.: 90/02/02B. Unpublished study prepared by Sandoz Crop
Protection Corp. 63 p.
Smith, R.; Regan, K. (1990) Biochemical and Morphological
Characteristics of Bacillus thuringiensis subsp. Israelensis Strain SA3
with a Discussion of Strain History Included: Final Report: Final
Report No.: 90/02/02D. Unpublished study prepared by Sandoz Crop
Protection Corp. 38 p.
Smith, R.; Regan, K. (1990) Biochemical and Morphological
Characteristics of Bacillus thuringiensis subsp. Israelensis Strain SA3A
with a Discussion of Strain History Included: Final Report: Final
Report No.: 90/02/02A. Unpublished study prepared by Sandoz Crop
Protection Corp. 63 p.
Shindler, J. (1990) Single Intraperitoneal Administration of Bacillus
thuringiensis Strain SA-2 in Mice: SRI Project Number LSC-8491: SRI
Study No. 8491-MO2-89. Unpublished study prepared by SRI
International. 38 p.
Schindler, J. (1990) Single Intraperitoneal Administration of Bacillus
Thuringiensis Strain SA-3 in Mice: SRI Project Number LSC-8491:
SRI Study No. 8491-M03-89. Unpublished study prepared SRI
International. 15 p.
Schindler, J. (1990) Single Intraperitoneal Administration of Bacillus
thuringiensis Strain SA-3A in Mice: SRI Project Number LSC-8491:
SRI Study No. 8491-M04-89. Unpublished study prepared by SRI
International. 16 p.
'
Chen, C.; Macuga, R. (1990) Plasmid Profile of Bacillus thuringiensis
subsp. Aizawai, Strain SA2: Final Report: Final Report No.
90/02/03E. Unpublished study prepared by Sandoz Crop Protection
68
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MRID
BIBLIOGRAPHY
CITATION
Corp. 40 p.
41441508 Chen, C.; Macuga, R. (1990) Plasmid Profile of Bacillus thuringiensis
subsp. Israelensis, Strain SA3: Final Report: Final Report No.
90/02/03C. Unpublished study prepared by Sandoz Crop Protection
Corp. 40 p.
41441509 Chen, C.; Macuga, R. (1990) Plasmid Profile of Bacillus thuringiensis,
subsp. Israelensis, Strain SA3A: Final Report: Final Report
No.90/02/03D. Unpublished study prepared by Sandoz Crop
Protection Corp. 40 p.
41441510 Chen, 'C.; Macuga, R. (1990) Flagella Antigen Serotyping of Bacillus
thuringiensis subsp. Aizawai, Strain SA2: Final Report: Final Report
No. 90/02/12E. Unpublished study prepared by Sandoz Crop
Protection Corp. 23 p.
41441511 Chen, C.; Macuga, R. (1990) Flagella Antigen Serotyping of Bacillus
thuringiensis subsp. Israelensis, Strain SA3: Final Report: Final Report
No. 90/02/12C. Unpublished study prepared by Sandoz Crop
Protection Corp. 23 p.
41441512 Chen, C.; Macuga, R. (1990) Flagella Antigen Serotyping of Bacillus
thuringiensis subsp. Israelensis, Strain SA3A: Final Report: Final '
Report No. 90/02/12D. Unpublished study prepared by Sandoz Crop
Protection Corp. 23 p.
41441513 " Smith, R.; Regan, K. (1990) Antibiotic Sensitivity Patterns for
Bacillus thuringiensis subsp. Aizawai, Strain SA2: Final Report:
Final Report No. 89/12/12C. Unpublished study prepared by Sandoz
Crop Protection Corp. 28 p.
41441514 Smith, R.; Regan, K. (1989) Antibiotic Sensitivity Patterns for
Bacillus thuringiensis subsp-. Israelensis Strain SA3: Final Report:
Final Report No. 89/12/12D. Unpublished study prepared by Sandoz
Crop Protection Corp. 38 p.
41441515 Smith, R.; Regan, K. (1989) Antibiotic Sensitivity Patterns for
Bacillus thuringiensis subsp. Israelensis Strain SA3A: Final Report:
Final Report No. 89/12/12E. Unpublished study prepared by Sandoz
69
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MRID
BIBLIOGRAPHY
CITATION
Crop Protection Corp. 38 p.
41441516 Cerf, D. (1990) Susceptibility of Four Orders of Insects
(Lepidoptera, Diptera, Coleoptera, and Orthoptera) to Technical
Grade Active Ingredients (TGAI's), Manufacturing. . . and
tenebrionis in SA10): Final Report: Final Report No. 90/03/12.
Unpublished study prepared by Sandoz Crop Protection Corp. 40 p.
41441517 Chen, C.; Macuga, R. (1990) Description of Endotoxin Proteins
Produced by Bacillus thuringiensis subsp. Aizawai, Strain SA2: Final
Report: Final Report No. 90/02/21C. Unpublished study prepared
by Sandoz Crop Protection Corp. 30 p.
41441518 Chen, C.; Macuga, R. (1990) Description of Endotoxin Proteins
Produced by Bacillus thuringiensis subsp. Israelensis, Strain SA3:
Final Report: Final Report No. 90/02/21E. Unpublished study
prepared by Sandoz Crop Protection Corp. 27 p.
41441519 Chen, C.; Macuga, R. (1990) Description of Endotoxin Proteins
Produced by Bacillus thuringiensis subsp. Israelensis, Strain SA3A:
Final Report: Final Report No. 90/02/21F. Unpublished study
prepared by Sandoz Crop Protection Corp. 27 p.
41441520 Chen, C.; Macuga, R.; Cerf, D. (1990) Insecticidal Toxins Produced
by Bacillus thuringiensis subsp. Aizawai, Strain SA2. I. Effect of
Autoclaving: Final Report: Final Report No. 90/01/3IE.
Unpublished study prepared by Sandoz Crop Protection Corp. 19 p.
{
41441521 Chen, C.; Macuga, R.; Cerf, D. (1990) Insecticidal Toxins Produced
by Bacillus thuringiensis subsp. Israelensis, Strain SA3.1. Effect of
Autoclaving: Final Report: Final Report No. 90/01/31. Unpublished
study prepared by Sandoz Crop Protection Corp. 19 p.
41441522 Chen, C.; Macuga, R.; Cerf, D. (1990) Insecticidal Toxins Produced
by Bacillus thuringiensis subsp. Israelensis, Strain SA3A. I. Effect of
Autoclaving: Final Report: Final Report No. 90/01/31D.
Unpublished study prepared by Sandoz Crop Protection Corp. 19 p.
41441523 Chen, C.; Cerf, D.; Sjolander, A.; et al. (1990) Insecticidal Toxins
Produced by Bacillus thuringiensis subsp. Aizawai, Strain. II.
70
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MRID
BIBLIOGRAPHY
CITATION
Concentration of beta-Exotoxin: Final Report: Final Report No.
90/02/07E. Unpublished study prepared by Crop Protection Corp.
36 p.
41441524
41441525
41441526
41441527
41441528
41441529
41441530
41441531
Chen, C.; Cerf, D.; Sjolander, A.; et al. (1990) Insecticidal Toxins
Produced by Bacillus thuringiensis subsp. Israelensis, Strain SA3. II.
Concentration of beta-Exotoxin: Final Report: Final Report No.
90/02/07C. Unpublished study prepared by Sandoz Crop Protection
Corp. 36 p.
Chen, C.; Cerf, D.; Sjolander, A.; et al. (1990) Insecticidal Toxins
Produced by Bacillus thuringiensis subsp. Israelensis, Strain SA3A.
II. Concentration of beta-Exotoxin: Final Report: Final Report No.
90/02/07D. Unpublished study prepared by Sandoz Crop Protection
Corp. 36 p.
Fowler, J. (1989) Physical Properties of SA-2 Technical Grade -
Active Ingredient: Final Report: Final Report No. 89/11/30E.
Unpublished study prepared by Sandoz Crop Protection Corp. 32 p.
Fowler, J. (1989) Physical Properties of SA-3 Technical Grade
Active Ingredient (TGAI): Final Report: Final Report No.
89/11/30A. Unpublished study prepared by Sandoz Crop Protection
Corp. 32 p.
Fowler, D. (1989) Physical Properties of Certan: Final Report: Final
Report No. 89/11/30D. Unpublished study prepared by Sandoz Crop
Protection Corp. 32 p.
Fowler, J. (1989) Physical Properties of Teknar: Final Report: Final
Report No. 89/11/30. Unpublished study prepared by Sandoz Crop
Protection Corp. 32 p.
Fowler, J. (1989) Physical Properties of Teknar HPD: Final Report:
Final Reppi* No. 89/11/30B. Unpublished study prepared by Sandoz
Crop-Protection Ccrp. 32 p.
Fowler, J. (1989) Physical Properties of SA-3A Technical Grade
Active Ingredient (TGAI): Fi^al Report: Final Report No. '
89/11/30C. Unpublished study prepared by Sandoz Crop Protection
71
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MRID
BIBLIOGRAPHY
CITATION
Corp. 32 p.
41441601 Smith, R.; Regan, K. (1990) Biochemical and Morphological
Characteristics of Bacillus thuringiensis subsp. kurstaki Strain SA12
with a Discussion of Strain History Included: Lab Project Number
90/02/02F. Unpublished study prepared by Sandoz Crop Protection
Corp. 63 p.
41441602 ' Smith, R.; Regan, K. (1990) Biochemical and Morphological
Characteristics of Bacillus thuringiensis subsp. tenebrionis Strain SA
10 with a Discussion of Strain History Included: Final Report: Lab
Project Number: 90/02/02. Unpublished study prepared by Sandoz
Crop Protection Corp. 63 p.
41441603 Smith, R. ; Regan, K. (1990) Biochemical and Morphological
Characteristics of Bacillus thuringiensis subsp. kurstaki Strain
INT-15-313 with a Discussion of Strain History Included: Final
Report: Project Number: 90/02/02C. Unpublished study prepared by
Sandoz Crop Protection Corp. 63 p.
41441604 Smith, R.; Regan, K. (1990) Biochemical and Morphological
Characteristics of Bacillus Thuringiensis Subsp. kurstaki Strain
SA11001C98-1-1 with a Discussion of Strain History Included: Final
Report: Project Number: 90/02/02E. Unpublished study prepared by
Sandoz Crop Protection Corp. 63 p.
41441605 Chen, C.; Macuga, R.; Cerf, D. (1990) Insecticidal Toxins Produced
by Bacillus Thuringiensis Subsp. Tenebrionis Strain SA10.1. Effect
of Autoclaving: Final Report: Lab Project Number: 90/01/3 IF.
Unpublished study prepared by Sandoz Crop Protection Corp. 19 p.
41441606 Chen, C.; Macuga, R.; Cerf, D. (1990) Insecticidal Toxins Produced
by Bacillus thuringiensis subsp. kurstaki Strain SA11001C98-1-1.1.
Effect of Autoclaving: Final Report: Lab Project Number:
90/01/31 A. Unpublished study prepared by Sandoz Crop Protection
Corp. 19 p.
41441607 Chen, C.; Macuga, R.; Cerf, D. (1990) Insecticidal Toxins Produced
by Bacillus thuringiensis subsp. kurastaki Strain INT-15-313. I.
Effect of Autoclaving: Final Report: Lab Project Number: 90/01/31.
72
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MRID
41441608
41441609
BIBLIOGRAPHY
CITATION
Unpublished study prepared by Sandoz Crop Protection Corp. 19 p.
Chen, C.; Macuga, R.; Cerf, D. (1990) Insecticidal Toxins Produced
by Bacillus thuringiensis subsp. kurstaki Strain SA12. I. Effect of
Autoclaving: Lab Project Number: 90/01/31B. Unpublished study
prepared by Sandoz Crop Protection Crop. 19 p.
Schindler, J. (1990) Single Intraperitoneal Administration of Bacillus
thuringiensis Strain SA-10 hi Mice: Lab Project Number:
8491-M05-89: LSC-8491. Unpublished study prepared by SRI
International, 15 p.
41441610
41441611
41441612
41441613
41441614
41441615
Schindler, J. (1990) Single Intraperitoneal Administration of Bacillus
thuringiensis Strain SA-12 in Mice: Lab Project Number:
8491-M07-89: LSC-8491. Unpublished study prepared by SRI
International. 17 p.
Schindler, J. (1990) Single Intraperitoneal Administration of Bacillus
thuringiensis Strain 313 hi Mice: Lab Project Number: 891-M01-89:
LSC-8491. Unpublished study prepared by SRI International. 15 p.
Schindler, J. (1990) Single Intraperitoneal Administration of Bacillus
thuringiensis Strain SA-11 in Mice: Lab Project Number:
8491-M06-89: LSC-8491. Unpublished study prepared by SRI
International. 15 p.
Chen, C.; Macuga, R. (1990) Plasmid Profile of Bacillus
thuringiensis subsp. tenebrionis Strain SA10: Lab Project No:
90/02/03F. Unpublished study prepared by Sandoz Crop Protection
Corp. 40 p.
Chen, C.; Macuga, R. (1990) Plasmid Profile of Bacillus
thuringiensis subsp. kurstaki Strain SA11001C98-1-1: Lab Project
Number: 90/0203A. Unpublished study prepared by Sandoz Crop
Protection Corp. 40 p.
Chen, C.; Macuga, R. (1990) Plasmid Profile of Bacillus
thuringiensis subsp. kurstaki Strain INT-15-313: Lab Project
Number: 90/02/03. Unpublished study prepared by Sandoz Crop
73
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MRID
BIBLIOGRAPHY
CITATION
Protection Corp. 40 p.
41441616 Chen, C.; Macuga, R. (1990) Plasmid Profile of Bacillus
thuringiensis subsp. kurstaki Strain SA12: Lab Project Number:
90/02/03B. Unpublished study prepared by Sandoz Crop Protection
Corp. 40 p.
41441617 Chen, C.; Macuga, R. (1990) Flagella Antigen Serotyping of Bacillus
thuringiensis subsp. tenebrionis Strain SA10: Lab Project Number:
90/02/12F. Unpublished study prepared by Sandoz Crop Protection
Corp. 23 p.
41441618 Chen, C.; Macuga, R. (1990) Flagella Antigen Serotyping of Bacillus
thuringiensis subsp. kurstaki Strain SA11001C98-1-1: Lab Project
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41441619 Chen, C.; Macuga, R. (1990) Flagella Antigen Serotyping of Bacillus
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,1 .
41441620 Chen, C.; Macuga, R. (1990) Flagella Antigen Serotyping of Bacillus
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41441621 Smith, R.; Regan, K. (1989) Antibiotic Sensitivity Patterns for
Bacillus thurrngiensis subsp. tenebrionis Strain SA10: Lab Project
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41441622 Smith, R.; Regan, K. (1989) Antibiotic Sensitivity Patterns for
Bacillus thuringiensis subsp. kurstaki Strain SA11001C98-l-l:Lab
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41441623 Smith, R.; Regan, K. (1989) Antibiotic Sensitivity Patterns for
Bacillus thuringiensis subsp. kurstaki Strain INT-15-313: Lab Project
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74
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/
41441624 Smith, R.; Regan, K. (1989) Antibiotic Sensitivity Patterns for
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41441625 Cerf, D. (1990) Susceptibility of Four Orders of Insects
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41441626 Chen, C.; Macuga, R. (1990) Description of Endotoxin Proteins
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41441627 Chen, C.; Macuga, R. (1990) Description of Endotoxin Proteins
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41441628 Chen, C.; Macuga, R, (1990) Description of Endotoxin Proteins
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41441629 ^' Chen, C.; Macuga, R. (1990) Description of Endotoxin Proteins
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41441630 Chen, C.; Cerf, D.; Sjolander, A.; et al. (1990) Insecticidal Toxins
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75
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41441632
41441633
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Chen, C.; Cerf, D.; Sjolander, A.; et al. (1990) Insecticidal Toxins
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Jensen, B.; Sorensen, E.; Rugh, S.; et al. (1991) Product Analysis
Data: Sample Analysis and Analytical Methods: Skeetal Flowable
Concentrate: Lab Project Number: NOVO/SFCRERE/VOL3.
Unpublished study prepared by Novo Nordisk A/S & Novo Nordisk
Bioindustrials Inc. 41 p.
Harde, T. (1991) Bacillus thuringiensis var. Israelensis: Acute Oral
Toxicity/Pathogenicity Study hi Rats given Bti Tox Batch PPQ 3044
(NB 31): Lab Project Number: 90055: NOVO/SFCRERE/VOL5.
Unpublished study prepared by Novo Nordisk A/S. 47 p.
86
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Oshodi, R.; Robb, D. (1990) BTi Preparation: Acute Inhalation
Toxicity Study in Rats: Skeetal Flowable Concentrate: Lab Project
Number: 650314. Unpublished study prepared by Inveresk Research
International. 49 p.
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Christensen, K. (1990) Bacillus thuringiensis var. Israelenisis:
Infectivity and Pathogencity to Rainbow Trout (Oncorhynchus
mykiss) During a 32-Day Static Renewal Test: Lab Project Number:
90-8-3459: 12262.1289.6102.157. Unpublished study prepared by
Springborn Laboratoreis, Inc. 50 p.
Atkins, E. (1991) Bee Adult Toxicity Dusting Test Evaluating the
Comparative Acute Contact and Stomach Poison Toxicity of BTIQ
Dry Flowable (Bacillus ihuringiensis var. Kurstaki) to Honey Bee
Worker Adults: Lab Project Number: 91/838. Unpublished study
. prepared by Univ. of California, Riverside. 13 p.
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Atkins, E. (1991) Bee Adult Toxicity Dusting Test Evaluating the
Comparative Acute Contact and Stomach Poison Toxicity of BT I
Dry Flowable (Baccillus thuringiensis var. kurstaki) To Honey
Worker Adults: Lab Project Number: 91/836. Unpublished study
prepared by Univ. of California. 13 p.
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Ciba-Geigy Corp. (1991) Submission of toxicity and product
chemistry data in support of registration of Agree insecticide and
Ciba-Geigy Technical 237218. Transmittal of 22 studies.
Vlachos, D. (1991) Acute Intraperitoneal Toxicity/Pathogenicity
Screening Studies of Technical CGA-237218 in Mice: Lab Project
Number: 7961-91: 7963-91: 7965-91. Unpublished study prepared by
Stillmeadow, Inc. 103 p.
Lattin, A. (1990) CGA-237218 Technical (GC-91): An Avian Oral
Pathogenicity and Toxicity Study hi the Bdbwhite: Lab Project
Number 108-308. Unpublished study prepared by Wildlife
International Ltd. 21 p.
Lattin, A. (1990) CGA-237218 Technical (GC-91): An Avian Oral
Pathogenicity and Toxicity Study in the Mallard: Lab Project
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Number 108-309. Unpublished study prepared by Wildlife
International Ltd. 22 p.
41994315 Christensen, K. (1991) CGA-237218 Technical Material: Infectivity
and Pathogenicity to Rainbow Trout (Oncorhyncus mykiss) During a
32-Day Static Renewal Test: Lab Project Number: 90-6-3363.
Unpublished study prepared by Springborn Labs, Inc. 52 p.
41994316 Christensen, K. (1991) CGA-237218: Chronic Toxicity to Daphnids
(Daphnia magna) Under Static Renewal Conditions: Lab Project
Number: 90-7-3385. Unpublished study prepared by Springborn
Labs, Inc. 90 p.
41994317 Christensen, K. (1991) CGA-237218: Infectivity and Pathogenicity to
Sheepshead Minnow (Cyprinodon variegatus) During a 30-Day Static
Renewal Test: Lab Project Number: 90-8-3439. Unpublished study
prepared by Springborn Labs, Inc. 50 p.
41994318 Christensen, K. (1991) CGA-237218 Technical Material: Infectivity
and Pathogenicity to Grass Shrimp (Palaemonetes vulgaris) During a
30-Day Static Renewal Test: Lab Project Number: 90-6-3445.
Unpublished study prepared by Springborn Labs, Inc. 48 p.
41994319 Whiter, P. (1991) CGA-237218: A Dietary Pathogenicity and
Toxicity Study with the Parasitic Hymenopteran Uga menoni: Lab
Project Number: 108-311 A. Unpublished study prepared by Wildlife
International Ltd. 21 p.
41994320 Thompson, M. (1991) CGA-237218: A Dietary and Toxicity Study
with Ladybird Beetles: Lab Project Number: 108-313. Unpublished
study prepared by Wildlife International Ltd. 18 p.
41994321 Thompson, M. (1991) CGA-237218: A Dietary and Toxicity Study
with the Green Lacewing Larvae: Lab Project Number: 108-312.
Unpublished study prepared by Wildlife International Ltd. 18 p.
42006502 Hossack, D. (1990) Acute Oral Toxicity and Infectivity/Pathogenicity
Study of CGA-237218 (Bacillus thuringiensis var. Aizawai) in Rats:
Lab Project Number: CBG 517-1. Unpublished study prepared by
Huntingdon Research Centre, Ltd. 35 p.
88
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42016001
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42245301
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Hossack, D. (1990) Acute Pulmonary Toxicity and
Infectivity/Pathogenicity Study of CGA-237218 (Bacillus
thuringiensis var. Aizawai in Rats: Lab Project Number: CBG 517-2.
Unpublished study prepared by Huntingdon Research Centre, Ltd.
40 p.
Knoll, H. (1990) Bacillus Thuringiensis kurstaki: Generic and
Manufacturing Use Product Data. Unpublished study prepared by
Knoll Bioproducts Company, Inc. 14 p.
Knoll, H. (1990) Generic Acute Oral and Acute Pulmonary Toxicity
and Pathogenicity Data 152A-10 and 152A-12, and Intravenous
Toxicity/Pathogenicity Data 152A-13. Unpublished study prepared
Knoll Bioproducts Co., Inc. 19 p.
Novo Nordisk Bioindustrials, Inc. (1991) Submission of Additional
Data Regarding Unreasonable Adverse Effects of Foray 48B on
Humans for Section 6(a)(2) Requirements. Transmittal of 1 study.
Barridge, B. (1990) Delta BT--Manufactunng Process: Lab Project
Number: DBP 1989-101. Unpublished study prepared by Delta
Biological Products, Inc. 8 p.
Barridge, B. (1990) Delta BT-Physical and Chemical Properties: Lab
Project Number: DPB 1989-105. Unpublished study prepared by
Delta Biological Products, Inc. 6 p.
Nelson, R. (1991) The Effects of Bacillus thuringiensis, ABG-6305
Technical Powder, on the Common Green Lacewing, Chrysoperla
Carna (Stephens): Lab Project Number: 91.043. Unpublished study
prepared by Plant Sciences, Inc. 30 p.
Cozzi, E. (1993) Intraperitoneal and Subcutaneous Injection Tests
with ABG-6345 Technical Powder: Final Report: Lab Project
Number: 6345-85K-1. Unpublished study prepared by Abbott Labs.
29 p.
Cozzi, E. (1993) Intraperitoneal and Subcutaneous Injection Tests
with ABG-6346 Technical Powder (Bacillus thuringiensis subsp.
aizawai): Final Report: Lab Project-Number: 6346-85K-1.
89
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Unpublished study prepared by Abbott Labs. 28 p.
42942101 Palmer, S.; Beavers, J. (1993) Xentari Technical Powder
(ABG-6305): A Dietary Pathogenicity and Toxicity Study with the
Ladybird Beetle (Hippodamia convergens): Final Report: Lab Project
Number: 161-126A. Unpublished study prepared by Wildlife
International Ltd. 36 p.
PUBLICATIONS
Crickmore N., D. R. Zeigler, J.Feitelson, E. Schnepf, B. Lambert, D. Lereclus, J. Baum & D.H.
Dean (1995) Revision of the Nomenclature for the Bacillus thuringiensis Pesticidal cry Genes. In:
Program and Abstracts of the 28th Annual Meeting of the Society for Invertebrate Pathology. p!4.
Society for Invertebrate Pathology, Bethesda, MD,
Crickmore N., D.R. Zeigler J.Feitelson, E. Schnep, D. Lereclus, J. Baum, J. Van Rie and D.H.
Dean (1997) Bacillus thuringiensis delta-endotoxin nomenclature WWW site:
http://epurdx.biols.susx.ac.uk/ Home/Neil_Crickmore/ Bt/ index.html
Damgaard, D.H. (1995), Diarrhoeal enterotoxin production by strains of Bacillus thuringiensis
isolated from commercial Bacillus thuringiensis-based insecticides. FEMS Immuno. andMed.
Microbiol 12, 245-250.
Estmch.J.J., G.W. Warren, MA Mullins, G.J. Nye, J.A. Craig, & M.G. Koziel (1996) VipSA, a
novel Bacillus thuringiensis vegetative insecticidal protein with a wide spectrum of activities
against lepidopteran insects. Proc. Natl. Acad. Sci. USA 93 5389-5394.
Hofte H. & H.R. Whiteley (1989) Insecticidal Crystal Proteins of Bacillus thuringiensis. Microbiol
Revs 53 242-255.
Jackson, S.G., R.B. Goodbrand, R. Ahmed, & S. Kasatiya (1995) Bacillus cereus and Bacillus
thuringiensis isolated in a gastroenteritis outbreak investigation. Letters in Applied Microbiology 21,
103-105.
McClintock, J.T., C.R. Schaffer, J.L. Kough, & R.D. Sjoblad (1995) Relevant Taxonomic
Considerations for Regulation of Bacillus thuringiensis-Based Pesticides by the U.S. Environmental
Protection Agency. In T-Y Feng, et al. (eds.), "Bacilus thuringiensis Biotechnology and
Environmental Benefits.", Vol. I, 313-325.
McClintock, J.T., C.R. Schaffer, & R.D. Sjoblad (1994) Mammalian Toxicity of Bacillus
thuringiensis-Based Pesticides. In "Proceedings of the Pacific Rim Conference on Biotechnology of
Bacilus thuringiensis and Its Impact to the Environment."
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McClintock, J.T., C.R. Schaffer, & R.D. Sjoblad (1995) A Comparative Review of the Mammalian
Toxicity of Bacillus thuringiensis- Based Pesticides. Pestic. Sci. 45, 95-105.
Tompkins, G., R. Engler, M. Mendelsohn, & P. Hutton (1990) Historical Aspects of the
Quantification of the Active Ingredient Percentage for Bacillus thuringiensis Products. In L.A.
Hickle & W.L. Fitch (Eds) ACS Symposium Series No. 432 Analytical Chemistry of Bacillus
thuringiensis. 9-13.
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, D.C. 20460
OFFICE OF
PREVENTION, PESTICIDES
AND TOXIC SUBSTANCES
1'iAR 3 ! 1998
GENERIC AND PRODUCT SPECIFIC
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 A 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. Within 90 days after you receive this Notice you must
respond as set forth in Section El below. Your response must state:
1. How you will comply with the requirements set forth in this
Notice and its Attachments 1 through 7; or
2. Why you believe you are exempt from the requirements listed hi
this Notice and hi Attachment 3 (for both generic and product
specific data), the Requirements Status and Registrant's Response
Form, (see section ffl-B); or
3. Why you believe EPA should not require your submission of data
in the manner specified by this Notice (see section DI-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 hi Attachment 2. All products are listed on both the
generic and product specific Data Call-in Response Forms. Also included is 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
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Rodenticide Act as amended (FIFRA), 7 U.S.C. section 136a(c)(2)(B). Collection of this _
infonnation is authorized under the PaperworkNReduction Act by OMB Approval No.
2070-0107 and 2070-0057 (expiration date 3-31-99).
This Notice is divided into six sections and seven 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 ffl - 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 - Generic Data Call-In and Product Specific Data Call-In Response
Forms with Instructions (Form A)
3 - Generic Data Call-in and Product Specific Data Call-In
Requirements Status and Registrant's Response Forms with
Instructions (Form B)
4 - List of Registrants Receiving This Notice
5 - Cost Share and Data Compensation Forms
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 mgredient(s). You have been sent this Notice because you have
product(s) containing the subject active ingredients.
SECTION H. DATA REQUIRED BY THIS NOTICE
H-A. DATA REQUIRED
The data required by this Notice are specified in the Requirements Status and Registrant's
Response Forms: Attachment 3 (for both generic and product specific data requirements).
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Depending on the results of the studies required in this Notice, additional studies/testing may
be required.
n-B. SCHEDULE FOR SUBMISSION OF DATA
You are required to submit the data or otherwise satisfy the data requirements specified in
the Requirements Status and Registrant's Response Forms (Attachment 3) within the"
timeframes provided.
n-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 (Telephone number:
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 202-785-0350).
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].
E-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(s). 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.
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SECTION HI. COMPLIANCE WITH REQUIREMENTS OF THIS NOTICE
You must use the correct forms and instructions when completing your response to this
Notice. The type of Data Call-In you must comply with (Generic or Product Specific) is
specified hi item number 3 on the four Data Call-In forms (Attachments 2 and 3).
HI-A. SCHEDULE FOR RESPONDING TO THE AGENCY
The appropriate responses initially required by this Notice for generic and 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.
m-B. OPTIONS FOR RESPONDING TO THE AGENCY
1. Generic Data Requirements
The options for responding to this Notice for generic data requirements are: (a) voluntary
cancellation, (b) delete use(s), (c) claim generic data exemption, (d) agree to satisfy the generic
data requirements imposed by this Notice or (e) request a data waiver(s).
A discussion of how to respond if you choose 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 generic data requirements of this Notice is
contained in Section ffl-C. A discussion of options relating to requests for data waivers is
contained hi Section m-D.
Two forms apply to generic data requirements, one or both of which must be used hi
responding to the Agency, depending upon your response. These two forms are the
Data-Call-in Response Form, and the Requirements Status and Registrant's Response Form.
(contained in Attachments 2 and 3, respectively).
The Data Call-In Response Forms must be submitted as part of every response to this
Notice. The Requirements Status and Registrant's Response Forms also must be submitted if
you do not qualify for a Generic Data Exemption or are not requesting voluntary cancellation
of your registration(s). Please note that the company's authorized representative is required to
sign the first page of both Data Call-in Response Forms and the Requirements Status and
Registrant's Response Forms (if this form is required) 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 hi preparing your response, call or write the
contact person(s) identified in Attachment 1.
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a. Voluntary Cancellation -
i
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 completed Generic and Product Specific Data
Call-In Response Forms (Attachment 2), indicating your election of this option. Voluntary
cancellation is item number 5 on both Data Call-In Response Fonn(s'). If you choose this
option, these are the only forms 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.
I
"b. . 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 (Attachment 3), 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 under
item 9 in the instructions for the Requirements Status and Registrant's Response Forms. You
must also complete a Data Call-in Response Form by signing the certification, item number 8.
Application forms for amending registrations may be obtained from the Registration Support
Branch, Registration Division, Office of Pesticide Programs, EPA, by calling (703) 308-8358.
If you choose to delete the use(s) subject to this Notice or uses subject to specific data
requirements, further sale, distribution, or use of your product after one year from the due date
of your 90 day response, is allowed only if the product bears an amended label.
c. 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 if the active
ingredient hi the product is derived exclusively from purchased, registered pesticide products
containing the active ingredient. 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:
i
(i). The active ingredient in your registered product must be present solely because of
incorporation of another registered product which contains the subject active ingredient and
is purchased from a source not connected with you;
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(ii). Every registrant who is the ultimate source of the active ingredient in your product
subject to this DCI must be in compliance with the requirements of this Notice and must
remain in compliance; and
«
(iii). 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. Attachment 2 and all supporting documentation. The Generic Data Exemption
is item, number 6a on the Data Call-in Response Form. If you claim a generic data exemption
you are not required to complete the Requirements Status and Registrant's Response Form.
Generic Data Exemption cannot be selected as an option for responding to product specific data
requirements.
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 requirements or are no
longer in compliance with this Data Call-In Notice, the Agency will consider that both they
and you are not 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.
d. Satisfying the Generic Data Requirements of this Notice
There are various options available to satisfy the generic data requirements of this Notice.
These options are discussed in Section IQ-C.l. of this Notice and comprise options 1 through 6
of item 9 in the instructions for the Requirements Status and Registrant's Response Form and
item 6b on the Data Call-In Response Form. If you choose item 6b (agree to satisfy the
generic data requirements), you must submit the Data Call-In Response Form and the
Requirements Status and Registrant's Response Form as well as any other information/data
pertaining to the option chosen to address the data requirement. Your response must be on the
forms marked "GENERIC" in item number 3.
e. Request for Generic Data Waivers.
Waivers for generic data are discussed in Section IH-D.l. of this Notice and are covered by
options 8 and 9 of item 9 in the instructions for the Requirements Status and Registrant's
Response Form. 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.
2. Product Specific Data Requirements
The options for responding to this Notice for product specific data are: (a) voluntary
98
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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 choose 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 hi Section ni-C.2. A discussion of
options relating to requests for data waivers is contained hi Section ID-D.2.
Two forms apply to the product specific data requirements one or both of which must be
used in responding to the Agency, depending upon your response. These forms are the
Data-Call-in Response Form, and the Requirements Status and Registrant's Response Form.
for product specific data (contained hi Attachments 2 and 3, respectively). 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 also must be submitted for
each product listed on the Data Call-In Response Form unless the voluntary cancellation option
is selected. Please note that the company's authorized representative is required to sign the
first page of the Data Call-In Response Form and Requirements Status and Registrant's
Response Form (if this form is required) 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 hi preparing your response, call or write the contact
person(s) identified in Attachment 1.
a. 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.
indicating your election of this option. Voluntary cancellation is item number 5 on both the
Generic and Product Specific Data Call-in Response Forms. If you choose this
option, you must complete both Data Call-in response forms. These are the only forms that
you are required to complete.
v
If you choose to voluntarily cancel your product, further sale and distribution of your
product after the effective date of cancellation must be hi accordance with the Existing Stocks
provisions of this Notice which are contained hi Section IV-C.
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b. 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 m-C.2. of this Notice and comprise options 1
through 6 of item 9 in the instructions for the product specific Requirements Status and
Registrant's Response Form and item numbers 7a and 7b (agree to satisfy the product specific
data requirements for an MUP or EUP as applicable) on the product specific Data Call-in
Response Form. Note that the options available for addressing product specific data
requirements differ slightly from those options for fulfilling generic data requirements.
Deletion of a use(s) and the low volume/minor use option are not valid options for fulfilling
product specific data requirements. It is important to ensure that you are using the correct
forms and instructions when completing your response to the Reregistration Eligibility
Decision document.
c. Request for Product Specific Data Waivers.
Waivers for product specific data are discussed in Section ffi-D.2. of this Notice and are
covered by option 7 of item 9 in the instructions for the Requirements Status and Registrant's
Response Form. If you choose this option, you must submit the Data Call-in Response Form
and the Requirements Status and Registrant's Response Form as well as any other
information/data pertaining to the option chosen to address the data requirement. Your
response must be on the forms marked "PRODUCT SPECIFIC" hi item number 3.
m-C SATISFYING THE DATA REQUIREMENTS OF THIS NOTICE
1. Generic Data
If you acknowledge on the Generic Data Call-in Response Form that you agree to satisfy
the generic data requirements (i.e. you select item number 6b), then you must select one of the
six options on the Generic Requirements Status and Registrant's Response Form 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 Form. These six options are listed
immediately below with information in parentheses to guide you to additional instructions
provided in this Section. The options are:
(1) I will generate and submit data within the specified timeframe
(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)
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(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 confonnance with Agency
deadlines and with other Agency requirements as referenced herein and hi the attachments. All
data generated and submitted must comply with the Good Laboratory Practice (GLP) rule (40
CFR Part 160), be conducted according to the Pesticide Assessment Guidelines (PAG) and be
hi confonnance with the requirements of PR Notice 86-5. In addition, certain studies require
Agency approval of test protocols hi advance of study initiation. Those studies for which a
protocol must be submitted have been identified hi the Requirements Status and Registrant's
Response Form and/or footnotes to the form. If you wish to use a protocol which differs from
the options discussed hi Section n-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 hi Section n-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 hi the cost of
developing that study. This 90-day progress report must include the date the study was or will
be initiated and, for studies 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 tune 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 tune frames hi the Requirements Status and Registrant's Response Form are the tune
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).
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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 not grant
your request, the original deadline remains. Normally, extensions can be requested only in
cases of extra-ordinary 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 wUl 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
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 mis 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
registrants) developing the data has refused to accept the offer. To qualify for this option, you
must submit documentation to the Agency proving mat 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 to 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
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Response Form and a Requirements Status and Registrant's Response Form 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 burden 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 normally will be subject to initiation of suspension
proceedings, unless you commit to submit, and do submit, the required data in the specified
tune 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 hi 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 '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
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instruments." The term "specimens", according to 40 CFR 160.3,
means "any material derived from a test system for examination
or analysis."
b. Health and safety studies completed after May 1984 also must
also contain all GLP-required quality assurance and quality
control information, pursuant to the requirements of 40 CFR Part
160. Registrants also must 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 (if
there are any applicable 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 usually are 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 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 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.
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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 hi Attachment 1. If you submit data to upgrade an existing study you must satisfy or
supply information to correct all deficiencies hi 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 MRDD
number(s) of the study which you are attempting to upgrade and must be hi 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 also should 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 ha 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
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 EPA Form 8570-31, Certification with Respect to Data Compensation
Requirements.
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2. Product Specific Data
If you acknowledge on the product specific Data Call-In Response Form that you agree to
satisfy the product specific data requirements (i.e. you select option 7a or 7b), then you must
select one of the six options on the Requirements Status and Registrant's Response Form
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 Form. 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 The requirements for developing product specific data are the
same as those described for generic data (see Section ULC.l, Option 1) except that normally
no protocols or progress reports are required.
Option 2. Agree to Share in Cost to Develop Data If you enter into an agreement to cost
share, the same requirements apply to product specific data as to generic data (see Section
m.C.l, Option 2). However, 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.
Option 3. Offer to Share in the Cost of Data Development The same requirements for generic
data (Section m.C.l., Option 3) apply to this option. This option only applies to acute toxicity
and certain efficacy data as described in option 2 above.
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Option 4. Submitting an Existing Study - The same requirements described for generic data
(see Section DI.C.l., Option 4) apply to this option for product specific data.
Option 5. Upgrading a Study The same requirements described for generic data (see Section
HI.C.l., Option 5) apply to this option for product specific data.
Option 6. Citing Existing Studies The same requirements described for generic data (see
Section HI.C.l., Option 6) apply to this option for product specific data..
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 and the
Requirements Status and Registrant's Response Form, and hi the generic data requirements
section (ffl. C. 1.), as. appropriate.
HI-D REQUESTS FOR DATA WAIVERS
1. Generic Data
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 not appropriate for your product.
a.Low Volume/Minor Use Waiver
Option 8 under item 9 on the Requirements Status and Registrant's Response Form. 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 low volume
pesticides to be only those active ingredients 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 peslicide, and the exposure and risk from use of the
pesticide. If an active ingredient 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 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 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 hi 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 hi 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:
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(i). Total company sales (pounds and dollars) of all registered product(s) containing the
active ingredient. If applicable to the active ingredient, include foreign sales for those products
that are not registered in this country but are applied 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.
(ii) Provide an estimate of the sales (pounds and dollars) of the active ingredient for each
major use site. Present the above information by year for each of the past five years.
(iii) Total direct production cost of product(s) containing the active ingredient 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. ^
(iv) Total indirect production cost (e.g. plant overhead, amortized plant and equipment)
charged to product(s) containing the active ingredient by year for the past five years. Exclude
all non-recurring costs that were directly related to the active ingredient, such as costs of initial
registration and any data development.
(v) 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.
i.
(vi) 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.
(vii) For each of the next ten years, a year-by-year forecast of company sales (pounds and
dollars) of the active ingredient, direct production costs of product(s) containing the active
ingredient (following the parameters in item 2 above), indirect production costs of product(s)
containing the active ingredient (following the parameters in item 3 above), and costs of data
development pertaining to the active ingredient.
(viii) A description of the importance and unique benefits of the active ingredient to users.
Discuss the use patterns and the effectiveness of the active ingredient relative to registered
alternative chemicals and non-chemical control strategies. Focus on benefits unique to the
active ingredient, 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 assist the Agency in determining the degree of importance of the active
ingredient in terms of its benefits, you should provide information on any of the following
factors, as applicable to your product(s): (a) documentation of the usefulness of the active
ingredient in Integrated Pest Management, (b) description of the beneficial impacts on the
environment of use of the active ingredient, as opposed to its registered alternatives, (c)
information on the breakdown of the active ingredient after use and on its persistence in the
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environment, and (d) description of its usefulness against a pest(s) of public health
significance. r
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.
b. Request for Waiver of Data
Option 9, under Item 9, on the Requirements Status and Registrant's Response Form. This
option may be used if you believe that a particular data requirement should not apply because
the requirement is inappropriate. You must submit a rationale explaining why you believe the
data requirements should not apply. You also must 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 are not appropriate 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 vour productfs). 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 indicating the option chosen. - ,
2. Product Specific Data
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 product specific 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 hi force.
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SECTION IV. CONSEQUENCES OF FAILURE TO COMPLY WITH THIS
NOTICE
t
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, 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 1H-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 hi 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:
i. Inform EPA of intent to develop and submit the data required
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by this Notice on a Data Call-in Response Form and a
Requirements Status and Registrant's Response Form.
ii. Fulfill the commitment to develop and submit the data as
required by this Notice; or
iii. Otherwise take appropriate steps to meet the requirements
stated in this Notice,
v
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 tune following the issuance of this Notice.
IV-B. BASIS FOR DETERMINATION THAT SUBMITTED STUDY
IS UNACCEPTABLE
t
The Agency may determine that a study (even if submitted within the required tune) 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 of contained in PR 86-5.
All studies must be submitted hi 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 CANCELLED
PRODUCTS
EPA has statutory authority to permit continued sale, distribution and use of existing stocks
of a pesticide product which has been suspended or cancelled if doing so would be consistent
with the purposes of the Act.
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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 generally would
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 also must 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 mil 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 cancelled products containing an active ingredient for which the Agency has
particular risk concerns will be determined on a-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 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.
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SECTION VL 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.
i - ""'~~ ~ T
" All responses to this Notice must include completed Data Call-In Response Forms (Attachment
2)and completed Requirements Status and Registrant's Response Forms (Attachment 3), for both
(generic and product specific data) and any other documents required by this Notice, and should be
submitted textile contact person(s) identified'in Attachment 1. If the voluntary cancellation or
generic data exemption option is chosen, only the Generic and Product Specific Data Call-In
Response Forms 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 .ypurs, .. -'-.. -
st L. Andersen, Director
'Biopesticides and Pollution Prevention Division
Attachments
The Attachments to this Notice are:
1 - ' Data Call-fa Chemical Status Sheet
2 - Generic Data Call-in and Product Specific Data Call-in Response
Forms with Instructions ~ -
3- , Generic Data Call-In and Product Specific Data Call-in
Requirements Status and Registrant's Response Forms with
Instructions
4 - ' List of Registrants Receiving This Notice
5 - Confidential Statement of Formula. Cost Share and Data
Compensation Forms
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Page Intentionally Blank
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Attachment 1 Data Call-in Chemical Status Sheet
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Page Intentionally Blank
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0247 DATA CALL-IN CHEMICAL STATUS SHEET . . -
INTRODUCTION
You have been sent this Data Call-In Notice because you have product(s) containing 0247
This Data Call-In Chemical Status Sheet contains an overview of dalla required by this notice, and point
of contact for inquiries pertaining to the reregistration of 0247. For the Genetic Data Call-In, this
attachment is to be used in conjunction with (1) the Generic Data Call-In Notice,, (2) the Generic Data Call-
in Response Form, (3) the Requirements Status and Registrant's Form, (4) a list of registrants receiving this
DCI, and (5) the Cost Share and Data Compensation Forms in replying to this 0247 Generic Data Call-in.
For the Product Specific Data Call-In, 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, (4) a list of registrants receiving this DCI, and (5) the Cost
Share and Data Compensation Forms in replying to this 0247 Product Specific Data Call-In. Instructions
and guidance accompany each form.
DATA 'REQUIRED BY THIS NOTICE
>,
The additional data requirements needed to complete the database for 0247 are contained in the
Requirements Status and Registrant's Response. The Agency has concluded that additional data on 0247
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 0247 products.
INQUIRIES AND RESPONSES TO THIS NOTICE
If you have any questions regarding the generic or product specific data requirements and procedures
established by this Notice, please contact William R. Schneider at (703) 308-8683.
All responses to this Notice for the Generic or the Product Specific data requirements should be submitted
to:
William R. Schneider, Ph.D.
Microbial and Plant Pesticide Branch
Biopesticides and Pollution Prevention Division (7511W)
Office of Pesticide Programs
U.S. Environmental Protection Agency
401 M St S.W.
Washington, D.C. 20460 ,
RE: 0247
117
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Page Intentionally Blank
118
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Attachment 2.
Combined Generic and Product Specific Data Call-In
Response Forms (Form A inserts) Plus Instructions
119
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Page Intentionally Blank
120
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DRAFT COPY
Page 1 of 1
United States. Environmental Protection Agency
Washington, D. C. 20460
DATA CALL-IN RESPONSE
INSTRUCTIONS- Please type or print in ink. Please read carefully the attached instructions and supply the information requested
Use additional sheet (s) if necessary. , \
1. Company name and Address 2. Case (f and Name
SAMPLE COMPANY ,. 0247 BT
NO STREET ADDRESS
NO CITY, XX 00000
4. EPA Product'
Registration
5. I wish to
cancel this
product regis-
tration volun-
tarily.
8. Certification
I certify that the statements made on ti
I acknowledge that any knowingly false c
or both under applicable law.
Signature and Title of Company's Authors
6. Generic Data r
6a. I am claimlmg a Generic
Data Exemption because I
obtain the active ingredient
from the source EPA regis-
tration number listed below.
-
6b. I agree to satisfy Generic
Data requirements as indicated
on the atcachea torm entitled ,
"Requirements Status and
Regis trant ' s Response . "
i
~, *
lis form and all attachments are true, accurate, and complete.
r misleading statement may be punishable by fine, imprisonment
zed Representative
7. Product Specific
Form Approved
OMB No. 2070-0107 '
2070-0057
Approval Expires 03-3X-96
on this form.
3; Date and Type of DCI
{GENERIC
i
Data ,
7a. My product is a MUP and
I agree to satisfy' the MUP
, requirements on the attached
form entitled "Requirements
Status and Registrant's
Response."
-
10. Name of Company Contact
/
7b My product is an EUP and
I agree to satisfy the EUP
requirements on the attached
form entitled "Requirements
Status and Registrant's
Response."
-
9. Date
11.
Phone Number
<
>
-------
Page Intentionally Blank
122
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DRAFT COPY
Page 1 of 1
1 »
K)
UJ
-United States Environmental Protection Agency
Washington, D. C. 20460
DATA CALL-IN RESPONSE
INSTRUCTIONS Please type or print in ink Please read carefully the attached instructions and supply the information requested
Use additional sheet (s) if necessary.
1 Company name and Address 2 Case ff and Name
SAMPLE COMPANY ' 0247 BT
NO STREET ADDRESS
NO CITY, XX 00000
4. EPA Product
Registration
NNNNNN-NNNNN
5 I wish to
cancel this
product regis-
tration volun-
tarily
-
8 Certification
I certify that the statements made on th
I acknowledge that any knowingly false c
or both under applicable law
Signature and Title of Company's Authori
6 Generic Data
6a I am claj.mimg a Generic
Data Exemption because I
obtain the active ingredient
from the source EPA regis-
tration number listed below
N.A.
6b I agree to satisfy Generic
Data requirements as indicated
on the attached form entitled
"Requirements Status and
Registrant ' s Response . "
N.A.
is form and all attachments are true, accurate, and complete.
r misleading statement may be punishable by fine, imprisonment
zed Representative
7 Product Specific
Form Approved
OMB No 2070-0107
2070-0057
Approval Expires 03'31-96
on this form
3 Date and Type of DCI
PRODUCT SPECIFIC
Data
7a My product is a MUP and
I agree to satisfy the MUP
requirements on the ^attached
form entitled "Requirements
Status and Registrant's
Response "
10 Name of Company Contact
-
7b. My product is an EUP and
I agree to satisfy the EUP
requirements on the attached
form entitled "Requirements
Status and Registrant's
Response "
9 Date
11
Phone Number
t ^
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Page Intentionally Blank
124
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INSTRUCTIONS FOR COMPLETING THE "D.ATA CALL-IN RESPONSE FORMS" FOR THE
GENERIC AND PRODUCT SPECIFIC DATA CALL-IN
INTRODUCTION ,
These instructions apply to the Generic and Product Specific "Data Call-In Response Forms" and are to be
used by registrants to respond to generic and product specific Data Call-Ins as part of EPA's Reregistration
Program under the Federal Insecticide, Fungicide, and Rodenticide Act. If you are an end-use product
registrant only and have been sent this DCI letter as part of a RED document you have been sent just the
product specific "Data Call-In Response Forms." Only registrants responsible for generic data have been sent
the generic data response form. The type of Data Call-In (generic or product specific) is indicated in item
number 3 ("Date and Type of DCI") on each form.
Although the form is the same for both generic and product specific data, instructions for completing these
forms are different. Please read these instructions carefully before filling out the forms.
EPA has developed these forms individually for each registrant, and has preprinted these forms with a
number of items. DO NOT use these forms for any other active ingredient.
Items 1 through 3 have been preprinted on the form. Item 4 has been preprinted on the product specific
form but must be filled in by the registrant on the generic 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.
The 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 reyiewing the collection of information. Send comments regarding the
burden estimate or any other aspect of this collection-of information, including suggestions for reducing this
burden, to Chief, Information Policy Branch, Mail Code 2136, 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 FOR COMPLETING THE DATA CALL-IN RESPONSE FORMS
Generic and Product Specific Data Call-In
Item 1. ON BOTH FORMS: This item identifies your company name, number and
address.
Item 2. ON BOTH FORMS: This item identifies the case number, case name, EPA
chemical number and chemical name.
Item 3. ON BOTH FORMS: This item identifies the type of Data Call-In. The date
of issuance is date stamped. '
Item 4. ON BOTH FORMS: 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 .
125
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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. The number will be preprinted on the product specific form. On the
generic form, you must list all technical grade active ingredient and
manufacturing use registrations.
Item 5. ON BOTH FORMS: Check 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. Since this Data Call-In requires both generic and product
specific data, you must complete item 5 on both Data Call-In response forms.
You do not need to complete any item on the Requirements Status and
Registrant's Response Forms.
Item 6a. ON THE GENERIC DATA FORM: Check this Item if the Data Call-in is
for generic data as indicated in Item 3 and 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.
Item6b. ON THE GENERIC DATA FORM: Check this Item if the Data Call-In is
for generic data 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 that indicates how you will satisfy
those requirements.
NOTE: Item 6a and 6b are not applicable for Product Specific Data.
Item 7a. ON THE PRODUCT SPECIFIC DATA FORM: 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 rtyes."
126
-------
FOR BOTH MUP and EUP products
You should also respond "yes" to this item (7a for MUP's and 7b for EUP's) if
your product is identical to another product and you qualify for a data
exemption. You must provide the EPA registration numbers of your
source(s); do 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.
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.
NOTE: Item 7a and 7b are not applicable for Generic Data.
Item 8. ON BOTH FORMS: 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
initialled and dated in the space provided for the certification.
Item 9. ON BOTH FORMS: Enter the date of signature.
Item 10. ON BOTH FORMS: Enter the name of the person EPA should contact with
questions regarding your response.
Item 11. ON BOTH FORMS: Enter the phone number of your company contact.
Note You may provide additional information that does not fit on tins foim in a signed letter that accompanies your response For example, you may wish to
report that your product has already been transferred to another company or that you have already voluntarily cancelled this product For these cases,
please supply all relevant details so that EPA can ensure that its records are correct.
127
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Page Intentionally Blank
128
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Attachments.
Generic and Product Specific Requirement Status and
Registrant's Response Forms (Form B inserts) and
Instructions
129
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Page Intentionally Blank
130
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t-age x
United States Environmental Protection Agency
Washington, D.C. 20460
REQUIREMENTS STATUS AND REGISTRANT'S RESPONSE '
Form Approved
OMB No; 2070-0107
2070-0057
Approval Expires 03-31-99
INSTRUCTIONS: Please type or print in ink. Please read carefully the attached instructions and supply, the information requested on this form.
Use additional sheet (s) if necessary ' ,
1. Company name and Address
SAMPLE COMPANY
NO STREET ADDRESS
NO CITY, XX 00000
4. Guideline
Requirement
Number -
151A-11 *
5. Study Title
Manufacturing process
P
R
0
T
0
C
0
L
2. Case # and Name
0247 BT
i
, i
Progress
Reports
1
2
3 ,
6. Use
Pattern
A
'
7. Test
Substance
, i
10. Certification
I certify that the stat
I acknowledge that any
or both under applicabl
Signature and Title of
ements made on this form arid all attachments are true, accurate, and complete.
uiowingly false or misleading statement may be punishable by fine, imprisonment
e law.
Company's Authorized Representative
12. Name of Company Contact
3. Date and Type of DCI
GENERIC
8 .; Time
Frame
12
mos.
s
9. Registrant
Response
',
11. Date
-
13. Phone Number
-------
Page Intentionally Blank
132
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Page 1 of 2
United States Environmental Protection Agency
Washington, B.C. 20460
!
* COMMENTS FOR GUIDELINE REQUIREMENTS
Case # and Name
0247 BT
Chemical ft and Name
GUIDELINE COMMENT
151A-11 The Manufacturing process must include both quality control testing for each production
batch and a standarized, specific, detailed description of the process as tested to
minimize or eliminate the heat labile exotoxins.
(1) Quality Control Procedures: A new manufacturing process must be submitted that
includes a description of the qualitity control procedures as follows: QUALITY CONTROL
TESTING REQUIRED FOR EACH PRODUCTION BATCH: (a) Bacillus thuringiensis shall be produced
by pure culture, fermentation procedures with .adequate control measures during production
w to detect any changes from the characteristics of' t;he parent- strain or contamination by
w other microorganisms, (b) Each production batch, prior to the addition of other
materials, shall be tested by subcutaneous injection'of at least .1 million spores, or
equivalent for asporogenic strains, into each of five laboratory test mice weighing 17
grams to 23 grams. Such test shall show no evidence'of infection or injury in the test
animals when observed for 7 days following injection. ("Evidence of infection or injury-"
is 'any indication of either'systemic or .localized infection or'toxicity) (c.) Production
' batches shall be.free of the Bacillus thuringiensis beta-exotoxin when tested*with the*
fly larvae toxicity test ("Microbial Control of Insects and Mites." R>P>M> Bond, et al.,
p.280ff., 1971). This specification can be satisfied either by determining that each
master seed lot brought Into production is a .Bacillus thuringiensis strain which does
not produce beta-exotoxin under standard manufacturing conditions or by periodically
determining that beta-exotoxin syhnthesized during the manufacturing process is
eliminated by the subsequent manufacturing process procedures(s). (If the organism is
capable of producing beta-exotoxin, the registrant should ensure that none is prese.nt in
the TGAI and that the product is not put in a medium,- including formulated .end use'
products that allow germination' and/or growth at any time prior to use.) Some
registrants have been authorized to use an HPLC method instead of the fly larvae test.
In order to reconfirm the accuracy of Agency records, those registrants must resubmit,
or cite, their request to use HPLC and the supporting data to show that the method is at
least as sensitive as the fly larvae test.
-------
Page 2 of 2
United States Environmental Protection Agency
Washington, B.C. 20460
* COMMENTS FOR GUIDELINE REQUIREMENTS .
Case ff and Name
0247 BT
Chemical (f and Name
GUIDELINE COMMENT
(2) Standarization of the Manufacturing Process, The description of the manufacturing
process must also include the fermentation medium composition'and the growth condition's.
The process must be designed to prevent production of significant amounts of the heat
labile exotoxins. A sample from a production batch, using this exact process must be
tested by a Daphnia study incorporating a 10 day exposure period using a maximum hazard
dose. If the Daphnia test shows significant lethality, a dose response Daphnia test
must be performed to derive an LC50. If different media are to be used, a separate
manufacturing process (and testing) must be submitted for each.
-------
DRAFT COPY
Page 1 of
United States Environmental Protection Agency
Washington, D. C. 20460
REQUIREMENTS STATUS AND REGISTRANT'S RESPONSE
Form Approved
OMB No 2070-0107
2070-0057
Approval Expires 03 31 96
INSTRUCTIONS Please type or print in ink Please read carefully the attached instructions and supply the information requested on this form
Dse additional sheet (s) if necessary
1. Company name and Address 2 Case (f and Name
SAMPLE COMPANY 0247 BT
NO STREET ADDRESS
NO CITY, XX 000 00 > EPA Reg. No. NNNNNN-NNNNN
4. Guideline
Requirement
Number
151A-16(g)
81-1
81-2 .
81-3
81-4
81-5
t
B Study Title
^
Prod Chem - Microbxal
Storage stability (50)
Acute Toxic - Reqular Chemical
Acute oral toxicity-rat (1,37)
AOUte dermal (1,2,37)
toxicity-rabbit/rat
Acute inhalation toxictty-rat (3}
Primary eye irritation-rabbit (2)
Primary dermal xmtation. (1)2)
Efficacy -, Invertebrate. Control. Agents
Mosouito, Blackfly. Bitj.nqr.Hj.acre
Treatments
y
R
0
T
0
C
0
L
Progress
Reports
1
-
2
3
-
6. Use
Pattern
ABCDEFGHIJKLMNO
ABCDEFGHIJKLMNO
ABCDEFGHIJKLMNO
ABCDEFGHIJKLMNO
ABCDEFGHIJKLMNO
ABCDEFGHIJKLMNO
-
3 Date and Type of DCI
PRODUCT SPECIFIC
ID# NNNNNN-RD-NNNN
7 Test
Substance
MP/EP
MP/EP
MP/EP.
MP/EP -
MP/EP
MP/EP '
10. Certification
I certify that the statements made on this form and all attachments are true, accurate, and complete.
I acknowledge that any knowingly false or misleading statement may be punishable by fine, imprisonment
or both under applicable law
Signature and Title of Company's Authorized Representative
12 Name of Company Contact ,
i
'
8. Time
Frame
,
'
15 mos .
8 mos.
8 mos.
8 mos.
8 mos,.
8 mos.
' »
9 Registrant
Response
.
11 Date
1
-
13. Phone Number
-------
DRAFT COPY
Page 2 of 2
United States Environmental Protection Agency
Washington, D. C. 20460
REQUIREMENTS STATUS AND REGISTRANT'S RESPONSE
Form Approved
OMB No. 2070-0107
2070-0057
Approval Expires 03-31-96
INSTRUCTIONS: Please type or print in ink. Please read carefully the attached instructions and supply the information requested on this form.
Use additional sheet(s) i£ necessary.
1. Company name and Address
SAMPLE COMPANY
NO STREET ADDRESS
NO CITY, XX 00000
2. Case If and Name
0247 BT
EPA Reg. No. NNNNNN-NNNNN
3 Date and Type of DCI
PRODUCT SPECIFIC
ID# NNNNNN-RD-NNNN
4 Guideline
Requirement
Number
5. Study Title
Progress
Reports
6. Use
Pattern
7. Test
Substance
8. Time
Frame
9. Registrant
Response
95-10
Laboratory efficacy
evaluation
(1,3,4)
A CDE
JK
EP
8 mos.
Initial to indicate certification as to information on this page
(full text of certification is on page one)
Date
-------
DRAFTCOPY , Page 1 o£\ 1
United States Environmental Protection Agency
Washington, D. C. 20460
FOOTNOTES AND KEY DEFINITIONS FOR GUIDELINE REQUIREMENTS
Case # and Name: 0247 BT
Key MP = manufacturing-use product, EP = end-use product; provided formulators purchase their active ingredient(s) from a registered source, they need not submit or cite
data pertaining to the purchased product.[NOTE. If a product is a 100 percent repackage of another registered product, registrants are not subject to any data requirement;
identified in the tables ]; TEP = typical end-use product;TGAI = technical grade of the active ingredient, PAI = "pure" active ingredient; PAIRA = "pure" active
ingredient, radiolabeled
Dse Categories Key
A - Terrestrial food crop B - Terrestrial food feed crop C - Terrestrial nonfood crop D - Aquatic food crop E - Aquatic nonfood outdoor
F - Aquatic nonfood Industrial G - Aquatic nonfood residential H Greenhouse food crop I - Greenhouse nonfood crop J - Forestry
K Residential outdoor" L - Indoor food M - Indoor nonfood N Indoor Medical 0 - Indoor residential,
FOOtnOteS: (The following notes are referenced in column two (5 Study Title) of the REQUIREMENTS STATUS AND REGISTRANT'S RESPONSE form ]
Prod Chera - Microbial
50 A storage stability study determining concentrations of beta-exotoxin must be determined in each EP immediately prior to packaging and 6 months later (unless a
sooner or later interval can be demonstrated to be a more typical storage period) The fly larva bioassay as well as a specific confirmatory method, such as HPLC,
must both be used for analysis This study is required only for all aqueous products that can support gram positive bacterial growth
Acute Toxic - Regular Chemical
1 Not required if test material is a gas or highly volatile ' '
2 Not required if test material is corrosive to skin or has pH less than 2 or greater than 11 5, such a product will be classified as Toxicity Category I on the basis
of potential eye and dermal irritation effects.
3 Required if the product consists of, or under conditions of use will result in, an inhalable material (e g., gas, volatile substances, or aerosol/particulate),
37 Testing of the EP dilution in addition to the EP or MP is required if it can be reasonably anticipated that the results' of such testing may meet the criteria for
restriction to use by certified applicators specified in 40 CFR 152.170 (b) or the criteria for initiation of special review specified in 40 CFR 154.7 (a)(1).
!
Efficacy - Invertebrate Control Agents
1 The agency has waived all requirements to submit efficacy data for invertebrate control agents for nonpublic health uses However, each registrant must ensure
through testing that his products are efficacious when used in accordance with label directions and commenly accepted pest control practices The registrant must
develop and maintain the relevant data upon which the determination of efficacy is based The Agency reserves the right to require, on a case by-case ba^is (e g.,
significant'new uses or benefits data in cases of special reviews) submission of efficacy data for any pesticide product, registered or proposed for registration
when necessary
3 Efficacy evaluations can be conducted'under laboratory, greenhouse, or field conditions >
4 Required to be developed and maintained in the Registrant's file for all pests claimed on the label when resistance to the pestcide has been demonstrated
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Page Intentionally Blank
138
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3. INSTRUCTIONS FOR COMPLETING THE "REQUIREMENTS STATUS AND REGISTRANT'S
RESPONSE FORMS" FOR THE GENERIC AND PRODUCT SPECIFIC DATA CALL-IN
INTRODUCTION
These instructions apply to the Generic and Product Specific "Requirements Status and Registrant's
Response Forms" and are to be used by registrants to respond to generic and product specific Data Call-in's
as part of EPA's reregistration program under the Federal Insecticide, Fungicide, and Rodenticide Act. If
you are an end-use product registrant only and have been sent this DCI letter as part of a RED document
you have been sent just the product specific "Requirements Status and Registrant's Response Forms." Only
registrants responsible for generic data have been sent the generic data response forms. The type of Data
Call-in (generic or product specific) is indicated in item number 3 ("Date and Type of DCI") on each
form.
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 incltfde
(1) deletion of uses or (2) request for a low volume/minor use waiver. Please read these instructions
carefully before filling out the forms.
EPA has developed these forms individually for each registrant, and has preprinted these forms to
include certain information unique to this chemical, DO NOT use these forms for any other active
ingredient.
Items 1 through 8 have been preprinted on the form. Item 9 must be completed by the registrant as
appropriate. Items 10 through 13 must be completed by the registrant before submitting a response to the
Agency.
The 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 suggestions for
reducing this burden, to Chief, Information Policy Branch, Mail Code 2136, 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 FOR COMPLETING THE "REQUIREMENTS STATUS AND REGISTRANT'S
RESPONSE FORMS"
Generic and Product Specific Data Call-In
Item 1. ON BOTH FORMS: This item identifies your company name, number and
address.
Item 2. ON THE GENERIC DATA FORM: This item identifies the case number,
case name, EPA chemical number and chemical name.
139
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ON THE PRODUCT SPECIFIC DATA FORM: This item identifies the
case number, case name, and the EPA Registration Number of the product
for which the Agency is requesting product specific data.
Item 3. ON THE GENERIC DATA FORM: This item identifies the type of Data
Call-In. The date of issuance is date stamped.
ON THE PRODUCT SPECIFIC DATA FORM: This item identifies the
type of Data Call-in. The date of issuance is also date stamped. Note the
unique identifier number (ID#) assigned by the Agency. This ID number
must be used in the transmittal document for any data submissions in
response to this Data Call-in Notice.
Item 4. ON BOTH FORMS: This item identifies the guideline reference number of
studies required. These guidelines, in addition to the requirements specified
in the Data Call-In 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. ON BOTH FORMS: 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.
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.
Item 6. ON BOTH FORMS: This item identifies the code associated with the use
pattern of the pesticide. In the case of efficacy data (product specific
requirement), the required study only pertains to products which have the
use sites and/or pests indicated. 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
140
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Item 7.
Item 8.
N Indoor medical
O Indoor residential
ON BOTH FORMS: This item identifies the code assigned to the
substance that must be used for testing. A brief description of each code
follows:
v
EUP 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 Indredient or Pute Active Ingredient
Radiolabelled
PAIRA Pure Active Ingredient Radiolabelled
PAIRA/M Pure Active Ingredient Radiolabelled and Metabolites
PAERA/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
TGAI Technical Grade Active Ingredient
TGAI/PAI Technical Grade Active Ingredient or Pure Active Ingredient
TGAI/PAIRA Technical Grade Active Ingredient or Pure Active Ingredient
Radiolabelled
TGAI/TEP Technical Grade Active Ingredient or Typical End-Use
Product
MET Metabolites
IMP Impurities
DEGR Degradates
* See: guideline comment
This item completed by the Agency identifies the time frame allowed for
submission of the study or protocol identified in item 5.
ON THE GENERIC DATA FORM: The time frame runs from the date of
your receipt of the Data Call-In notice.
ON THE PRODUCT SPECIFIC DATA FORM: The due date for
submission of product specific studies begins from the date stamped on the
letter transmitting the Reregistration Eligibility Decision document, and not
from the date of'receipt. However, your response to the Data Call-In itself
is due 90 days from the date of receipt.
141
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Item 9. ON BOTH FORMS: 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.
Option 1. ON BOTH FORMS: (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 protocols and
progress reports required in item 5 above.
Option 2. ON BOTH FORMS: (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.
However, for Product Specific Data, I understand that this
option is available for acute toxicity or certain efficacy data ONLY
if the Agency 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.
OptionS. ON BOTH FORMS: (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
also submitting a completed "Certification of offer to Cost Share in the
Development of Data" form. 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 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 apply
as well.
However, for Product Specific Data, I understand that
this option is available only for acute toxicity or certain efficacy data
and only if the Agency indicates in an attachment to this Data
Call-in Notice that my product is similar enough to another product
to qualify for this option.
Option 4. ON BOTH FORMS: (Submitting Existing Data) I will submit an existing
study by the specified due date 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
, , , 142
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outlined in the Data Call-In Notice and I have attached the needed
supporting information along with this response.
Option 5. ON BOTH FORMS: (Upgrading a Study) I will submit by the specified
due date, or will cite 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
ani attempting to upgrade.
Option 6. ON BOTH FORMS: (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. If reviewed, I am
providing the Agency's classification of the study.
However, for Product Specific Data, 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 the Agency 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). If I cite
another registrant's data, I will submit a completed "Certification With
Respect To Data Compensation Requirements" form.
FOR THE GENERIC DATA FORM ONLY; The following three options (Numbers 7, 8, and 9)
are responses that apply only to the "Requirements Status and Registrant's Response Form" for
generic data.
Option 7. (Deleting Uses) I am attaching an application for amendment to my
registration deleting the uses for which the data are required.
Option 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.
"" (
Option 9. (Request for Waiver of Data) I have read the statements concerning data
waivers other than lowvolume minor-use data waivers in the Data Call-In
Notice and I request a waiver of the data requirement. I ani attaching a
rationale explaining why I believe the data requirements do not apply. I am
also submitting a copy of my current labels. (You must also submit a copy
143
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of your Confidential Statement of Formula if not already on tile with EPA).
I understand that, unless modified by the Agency in writing, the data
requirement as stated in the Notice governs.
FOR PRODUCT SPECIFIC DATA; The following option (number 7) is a response that applies to
the "Requirements Status and Registrant's Response Form" for product specific data.
Option 7. Waiver Request) I request a waiver for this study because it is
inappropriate for my product. 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" form specifying 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.
Item 10. ON BOTH FORMS: 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. ON BOTH FORMS: Enter the date of signature.
Item 12. ON BOTH FORMS: Enter the name of the person EPA should contact with
questions regarding your response.
Item 13. ON BOTH FORMS: Enter the phone number of your company contact.
NOTE You may provide additional information that does not fit on this form in a signed letter that accompanies this your response For example you
may wish to report that your product has already been transferred to another company or that you have already voluntarily cancelled this
144
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Attachment 4.
List of Registrants Sent this Data Call-In Notice
145
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Page Intentionally Blank
146
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LIST OF REGISTRANTS SENT THIS DATA CALL-IN NOTICE
Case # 0247 Name: Bacillus thuringiensis
Company Company Name ' Additional Name
Number
000004 Bomde Products, Inc
000016 Dragon Corp.
000070 Sureco, Inc.
000100 NovarQs Crop Protection, Inc
000192 Dexol Industries
000270 Famam Companies, Inc.
000275 Abbott Laboratories Chemical & Agricultural Products Div
000299 C. J. Martin Co
000524 Monsanto Co Agent for- Monsanto Agricultural Co
000829 Southern Agricultural insecticides, Inc
000869 Green Light Company
001386 Universal Cooperatives, Inc
002935 Wilbur Ellis Co.
003342 Cape Fear Chemicals, Inc
003772 -Bomde Products, Inc Agent for: Earl May Seed & Nursery L.P.
005481 Amvac Chemical Corp Attn: W.F. Millar
005887 Sureco, Inc.
006218 Summit Chemical Co
007401 Voluntary Purchasing Group, Inc
008329 Clarke Mosquito Control Products Inc
008660 H.R. Mclane, Inc. Agent For: Pursell Industries Inc
010107 Corn Belt Chemical Company
010951 Bntz Fertilizers, Inc Attn: David Britz
034704 Cherie' Garner Agent For: Platte Chemical Co Inc
036208 Loveland Industries, Inc Scott Baker
036488 Ringer Corp.
042697 Safer, Inc
049585 Alljack, Division of United Industries Corp.
Address
2 Wurz Ave
Box 73 11
10012 N. Dale Mabry, Ste. 221
Box 18300
1450 w. 228* St
301 W. Osborn Rd
1401 Sheridan Rd, D-28R, Bldg Al
Box 630009
700 14m St, N.W. Suite 1100
Box 218
P.O. Box 17985
P.O. Box 460 7801 Metro Parkway
191 W Shaw Ave
Box 695
2 Wurz Ave
21 10 Da vie Avenue
10012 N. Dale Mabry, Ste. 221
7657 Canton Center Dr
Box 460
159 N Garden Ave
7210 Red Road Suite 206
Box 410
Box 60011
Box 667
Box 1289
9555 James Avenue S., Suite 200
9555 James Avenue S., Suite 200 ,
Box 15842
City & State
Yorkvffle, NY
Roanoke, VA
Tampa, FL
Greensboro, NC
Torrance, CA
Phoenix, AZ
North Chicago, IL
Nacogdoches, TX
Washington, DC
Palmetto, FL
San Antonio, TX
Minneapolis, MN
Fresno, CA
Elizabeth Town, NC
Yorkville, NY
Commerce, CA
Tampa, FL
Baltimore, MD
Bonham, TX
Roselle, IL
Miami, FL
McCook, NE
Fresno, CA
Greeley, CO
Greeley, CO
Bloomington, MN
Bloomington, MN
St Louis, MO
Zip
13495
24019
3361S
27419
90501
85013
60064
75963
20005
34220
78217
55440
93704
28337
13495
90040
33618
21224
75418
60172
33143
69001
93794
80632
80632
55431
55431
63114
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LIST OF REGISTRANTS SENT THIS DATA CALL-IN NOTICE
Case # 0247 Name: Bacillus thuringiensis
Company Company Name
Number
Additional Name
Address
City & State
Zip
053S71 Troy Biosciences, Incorporated 2620 North 37" Drive
055638 Ecogen, Inc. 2005 Cabot Blvd West
059623 California Dept of Food & Agriculture Pesticide Consultation & Analysis 1220 N Street
060372 Ciiy of Stockton Municipal Utilities Dept 2500 Navy Drive
062637 Becker Microbial Products 9464 NW 11* St
065247 Calgene, Inc 1920 Fifth St
067572 Contract Packaging, Inc. Bldg 1, 4132 U.S. Hwy 278
068467 Mycogen Plant Sciences 4980 Carroll Canyon Rd
069504 Merdian, LLC 5137 14"1 Ave South
070051 Thermo Trilogy Corp. 7500 Grace Dr
Phoenix, AZ
Langhorne, PA
Sacramento, CA
Stockton, CA
Plantation, FL
Davis, CA
Covington, GA
San Diego, CA
Minneapolis, MN
Columbia, MD
85009
19047
95814
95206
33322
95616
30209
92121
55417
21044
148
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Attachment 5.
Cost Share, Data Compensation Forms, Confidential
Statement of Formula Form and Instructions
149
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Page Intentionally Blank
150
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Instructions for Completing the Confidential Statement of Formula
The Confidential Statement of Formula (CSF) Form 8570-4 must be used. Two legible, signed copies of the
form are required. Following are basic instructions:
a. All the blocks on the form must be filled in and answered completely.
b. If any block is not applicable, mark it N/A.
c. The CSF rmftt be signed, dated and the telephone number of the responsible party must be,provided.
d. All applicable information which is on the product specific data submission must also be reported on the
CSF.
e.All weights reported under item 7 must be in pounds per gallon for liquids and pounds per cubic feet for
solids.
f. Flashpoint must be in degrees Fahrenheit and flame extension in inches. Y
g.For all active ingredients, the EPA Registration Numbers for the ^currently registered source products must'
be reported under column 12.
h. The Chemical Abstracts Service (CAS) Numbers for all actives and inerts and all common names for the
trade names must be reported.
i. For the active ingredients, the percent purity of the source ^products must be reported under column 10
and must be exactly the same as on the source product's label.
j. All the weights in columns 13.a. and 13.b. must be in pounds, kilograms, or grams. In no case will
volumes be accepted. Do not mix English and metric system units (i.e., pounds and kilograms).
k. All the items under column 13.b. must total 100 percent.
1. All items under columns 14.a and 14.b. for the active ingredients must represent pure active form.
m The upper and lower certified limits for all active and inert ingredients must follow the 40 CFR 158.175
instructions. An explanation must be provided if the proposed limits are different than standard certified ,
- limits.
n. When new CSFs are submitted and approved, all previously submitted CSFs become obsolete for that
specific formulation.
151
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Page Intentionally Blank
152
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_ Office of Pesticida Prognms (TS 7671
O CD A Washington. DC 20460
\/ EZ r M Confidential Statement of Formula
1 . Name and Address of Applicant/Registrant (Include ZIP Code)
3. Product Name
EPA USE ONLY
10 Component; in Formulation (List as actually introduced
into the formulation G/ve commonly accepted chemical
name, trade name, and CAS numbtr 1
1 J Basic Formulation
LJ Alternate Formulation
Page
ol
Sea Instructions on Back
2. Name and Address of Producer (Include ZIP Code)
4 Registration No /File Symbol
7. Pounds/Gal or Bulk Density
1 1. Supplier Name & Address
-
5 EPA Product Mgr/Team No
8 pH
12 EPA Reg No
1 6. Typed Name of Approving Official
18. Signature of Approving Official
13 Each Component
in Formulation
a. Amount b %t>yW«ijh
17 Total Weight
19. Title
100%
6 Country Where Formulated
9 Flash Point/Flame Extension
14 Certified Limits
% by Weight
I Upper Limn b lowtr limit
1 5 Purpose in
Formulation
20 Phone No {Include Area Code!
21 Date
EPA Form 8570-4 (Rev. 12-90) Previous editions are obsolete. If you can photocopy this, please submit an additional copy White- EPA File Copy (original) Yellow- Applicant copy
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Page Intentionally Blank
154
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P/EPA
United States Environmental Protection Agency
Washington, DC 20460
CERTIFICATION OF OFFER TO COST
SHARE IN THE DEVELOPMENT OF DATA
Form Approved
OMB No. 2070-0106
2070-0057
Approval Expires 3-31-96
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 suggestions for reducing this burden, to Chief, Information Policy
Branch, PM-223, U.S. Environmental Protection Agency, 401 M St., S.W., Washington, DC 20460; and to the Office
of Management and Budget, Paperwork Reduction Project (2070-0106), Washington, DC 20503.
Please fill In blanks below.
Company Name
Product Name
Company Number
EPA Reg. No.
I Certify that:
My company is willing to develop and submit the data required by EPA under the authority of the Federal
Insecticide, Fungicide and Rodenticide Act (FIFRA), if necessary. However, my company would prefer to
enter into an agreement with one or more registrants to develop jointly or share in the cost of developing
data.
My firm has offered in writing to enter into such an agreement. That offer was irrevocable and included an
offer to be bound by arbitration decision under section 3{c)(2)(B)(iii} of FIFRA if final agreement on all
terms could not be reached otherwise. This offer was made to the following firm(s) on the following
date(s):
Name of Flrm(s)
Oats of Offer
Certification:
I certify that I am duly authorized to represent the company named above, and that the statements that I have made on
this form and all attachments therein are true, accurate, and complete. I acknowledge that any knowingly false or
misleading statement may be punishable by fine or imprisonment or both under applicable law.
Signature of Company's Authorized Representative
Date .
Name and Title (Please Type or Print)
EPA Form 8570-32 (5/91) Replaces EPA Form 8580, which is obsolete
155
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156
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United States Environmental Protection Agency
Washington, DC 20460
CERTIFICATION WITH RESPECT TO
DATA COMPENSATION REQUIREMENTS
Form Approved
OMB No. 2070-0107,
2070-0057
Approval Expires
3-31-96
bhc reporting burden for this collection of information is estimated to average 15 minutes per response including time for
iewing instructions, searching existing data sources gathering and maintaining the data needed, and completing and reviewing the
lection of information. Send comments regarding the burden estimate or any other aspect of this collection of information,
luding suggestions for reducing this.burden to, Chief Information Policy Branch PM-233, U.S. Environmental Protection
ancy, 401 M St., S.W,, Washmgton/DC 20460, and to the Office of Management and Budget, Paperwork Reduction Project
70-0106), Washington, DC 20503.
sase fill in blanks below.
npany Name
duct Name
Company Number
EPA Reg No
2rtify that:
For each study cited in support of registration or reregistratiion under the Federal Insecticide, Fungicide and Rodenticide Act
rRA) that is an exclusive use study, I am the original data submitter, or I have obtained the written permission of the original
a submitter to cite that study.
That for each study cited in support of registration or reregistration under FIFRA that is NOT an exclusive use study, I am the
jinal data submitter, or I have obtained the written permission of the original data submitter, or I have notified in writing the
npany(ies) that submitted data I have cited and have offered to: (a) Pay compensation for those data in accordance with sections
)(1)(F) and 3(c)(2)(D) of FIFRA- and (b) Commence negotiation to determine which data are subject to the compensation
uirement of FIFRA and the amount of compensation due, if any. The companies I have notified are. (check one)
] The companies who have submitted the studies listed on the back of this form or attached sheets or indicated on the attached "R
gistrants1 Response Form"
That I have previously complied with section 3(c)(1)(F) of FIFRA for the studies I have cited in support of registration or reregistrs
lature
Date
ie and Title (Please Type or Print)
NERAL OFFER TO PAY: I hereby offer and agree to pay compensation to other persons, with regard to the registration or r
products, to the extent required by FIFRA section 3(c){1)(F) and 3(c)(2)(D)
lature
Date
le and Title (Please type or Print)
>rm 8570-31 (4-96)
157
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