xvEPA
United States
Environmental Protection
Agency
Prevention, Pesticides
And Toxic Substances
(7508W)
EPA 738-R-97-006
February 1998
Reregistration
Eligibility Decision (RED)
Metribuzin
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United States
Environmental Protection
Agency
Prevention, Pesticides
And Toxic Substances
(7508W)
EPA-738-F-96-006
February 1998
ฉERA R.E.D. FACTS
Metribuzin
Pesticide
Re registration
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 in 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 reregistration, EPA obtains and
reviews a complete set of studies from pesticide producers, describing the
human health and environmental effects of each pesticide. The Agency
edevelops 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 fact sheet summarizes the information in the RED document for
reregistration case 0181, metribuzin.
Metribuzin is a herbicide used to selectively control certain broadleaf
weeds and grassy weed species on a wide range of sites including vegetable
and field crops, turf grasses (recreational areas), and non-crop areas.
Formulations include wettable powder, emulsifiable concentrate, water
dispersible granules (dry flowable), and flowable concentrate. Metribuzin
is applied by various methods including aerial, chemigation, and ground
application.
Regulatory Metribuzin was first registered as a pesticide in the U.S. in 1973.
History EPA issued a Registration Standard for metribuzin in July 1985 (PB86-
174216). Data Call-Ins (DCIs) were issued in 1991 and 1995 requiring
additional product chemistry, environmental fate and groundwater, and
ecological effects data. Currently 86 metribuzin products are registered.
On August 3, 1996, the Food Quality Protection Act of 1996 (FQPA)
was signed into law. FQPA amends both the Federal Food, Drug, and
Cosmetic Act (FFDCA), and the Federal Insecticide, Fungicide, and
Rodenticide Act (FIFRA). The FQPA amendments went into effect
immediately and were considered during this reregistration decision.
Use Profile
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Human Health
Assessment
Toxicity
In studies using laboratory animals, metribuzin generally has been
shown to be of low acute toxicity. It is slightly toxic by the oral and
inhalation routes and has been placed in Toxicity Category III (the second
lowest of four categories) for this effect. It is practically non-toxic by the
dermal route of exposure and has been placed in Toxicity Category IV (the
lowest of four categories).
A 21-day dermal toxicity study and a 21-day inhalation toxicity study
were used to assess subchronic toxicity. In the dermal toxicity study,
minimal systemic changes were noted at the highest dose level and no
dermal irritation was noted at any dose level. In the inhalation study,
systemic toxicity was observed at 720 mg/m3 air (0.720 mg/L), and was
based on clinical signs of toxicity, increased liver enzyme activities, and
increased organ weights. Results of three developmental toxicity studies
and one reproduction study suggest that although metribuzin is not
considered a developmental toxicant it is associated with developmental
toxicity effects. There was a lack of evidence for carcinogenicity in the
following studies: 1) a mouse study in which there were no increases in
tumor incidences at dosing levels up to 438 mg/kg/day for males and 567
mg/kg/day for females; 2) a rat study in which the observed pituitary
adenomas and carcinomas were not statistically significant at dosing levels
up to 14.36 mg/kg/day for males and 20.38 mg/kg/day for females; and 3)
another rat study which indicated no evidence for carcinogenicity at dosing
levels up to 42.2 mg/kg/day for males and 53.6 mg/kg/day for females.
Available data also suggest that metribuzin is not mutagenic.
Dietary Exposure
People may be exposed to residues of metribuzin through the diet.
Tolerances were reassessed for metribuzin and three of its primary
metabolites. Tolerances have been established in 40 CFR 180.332 for the
following commodities: asparagus; barley, grain; barley, straw; carrots;
corn, fodder; corn, forage; grass; grass, hay; lentils (dried); lentils, forage;
peas; peas (dried), peas, forage; peas, vine hay; sainfoin, hay; soybeans;
soybeans, forage; soybeans, hay; sugarcane; tomatoes; wheat forage; wheat,
grain; and wheat straw. Additional confirmatory information are needed
before several established tolerances for animal commodities can be
reassessed. When these tolerances for animal commodities are reassessed,
a separate dietary exposure assessment will be made.
Occupational Exposure
Based on current use patterns, handlers (mixers, loaders, and
applicators) may be exposed to metribuzin during and after normal use of
liquid, wettable powder, and dry-flowable formulations. Since minimal
systemic changes were noted at the highest dose level in a 21-day dermal
toxicity study, a short-term or intermediate term dermal risk assessment was
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not required. However, an inhalation risk assessment is required based on
clinical signs of toxicity, increased liver enzyme activities, and increased
organ weights observed in a 21-day inhalation study. Based on the use
patterns and potential exposures, ten exposure scenarios for handlers were
identified and assessed for metribuzin.
Human Risk Assessment
Metribuzin generally is of low acute toxicity, and although it does
show developmental effects in animal studies, it is not considered a
developmental toxicant. It has been classified as a Group D chemical, not
classifiable as to human carcinogenicity. Many food and feed crop uses are
registered; however, dietary exposure to metribuzin residues in food and
feed are not of concern. Also, the cancer risk posed to the general
population is not of concern.
Of greater concern is the inhalation exposure risk posed to metribuzin
handlers, particularly mixers/loaders/applicators, and field workers. This
concern was identified for mixing and loading wettable powders for aerial
and chemigation applications at 6 Ibs active ingredient (ai)/acre. Exposure
and risk to workers will be mitigated by the use of PPE required by the
WPS, as well as additional risk mitigation measures described below. Post-
application reentry workers will be required to observe a 12-hour Restricted
Entry Interval.
The Agency has reassessed metribuzin food and feed related
tolerances under the standards of the FQPA and determined that, based on
available information, there is a reasonable certainty that no harm will result
to infants and children or to the general population from aggregate exposure
to metribuzin residues. The only type of exposures evaluated were dietary
and drinking water routes, since significant non-occupational exposures are
unlikely with metribuzin use.
The Agency believes that the acute and chronic total dietary (food
source and drinking water source) risks from metribuzin are minimal. The
total acute dietary (food and drinking water source) risk assessment was
performed for the sub-population females (13+ years). The MOE was 1200
(rounded to two significant digits). Metribuzin's acute dietary MOE greatly
exceeds 100; therefore, the Agency considers the MOE to be sufficiently
protective for acute total dietary risk.
EPA has also assessed the chronic dietary risk posed by metribuzin.
For the overall U.S. population and 22 subgroups, exposure from all current
metribuzin tolerances represents 36% of the Reference Dose (RfD), or
amount believed not to cause adverse effects if consumed daily over a 70-
year lifetime. 1% of the RfD is reserved for exposure to residues of
metribuzin in drinking water; therefore, the total chronic dietary risk is 37%
of the RfD for the general population. The exposure level of residues of
metribuzin in food commodities in the most highly exposed subgroup,
children (1-6 years), is 75% of the RfD. For this subgroup, 4% of the RfD
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is reserved for exposure to residues of metribuzin in drinking water;
therefore, total chronic dietary risk is 79% of the RfD. It appears that total
chronic dietary risk from food and drinking water sources is low.
EPA does not have, at this time, available data to determine whether
metribuzin has a common mechanism of toxicity with other substances or
how to include this pesticide in a cumulative risk assessment. Unlike other
pesticides for which EPA has followed a cumulative risk approach based on
a common mechanism of toxicity, metribuzin does not appear to produce a
toxic metabolite produced by other substances. For the purposes of this
tolerance action, therefore, EPA has not assumed that metribuzin has a
common mechanism of toxicity with other substances.
Environmental Assessment
An evaluation of the estimated exposure of metribuzin to the
environment and the toxicity of metribuzin to nontarget organisms is
required to assess the potential risk to the environment posed by metribuzin
use.
Exposure of metribuzin to the environment is assessed by reviewing fate
lab and field tests, and estimating terrestrial residues and aquatic
concentrations with the use of models. Toxicity of metribuzin to nontarget
organisms is extrapolated from lab studies conducted on a few species of
birds, mammals, aquatic organisms, and plants.
Environmental Fate
Based on available data, the primary routes of degradation of
metribuzin and its primary degradates are microbial metabolism and
photolytic degradation on soil. These compounds will be available for
leaching to ground water and runoff to surface water in many use
conditions because they are not volatile. Once in ground water, metribuzin
is expected to persist due to its stability to hydrolysis and the lack of light
penetration. Conversely, residues of metribuzin are not likely to persist in
clear, well-mixed, shallow surface water with good light penetration since
parent metribuzin degrades rapidly by aqueous photolysis.
Ecological Effects
Laboratory study results indicate that metribuzin is moderately toxic
to avian species on an acute oral basis, practically non-toxic to avian
species on a subacute dietary basis, slightly toxic to small mammals on an
acute oral basis, practically non-toxic to bees on an acute contact basis,
slightly toxic to practically non-toxic to freshwater fish on an acute basis,
moderately to slightly toxic to aquatic invertebrates on an acute basis,
slightly toxic to estuarine/marine fish and invertebrates on an acute basis,
and highly toxic to nontarget plants.
Ecological Effects Risk Assessment
There is potential acute and chronic risk concern for avian species,
including endangered species, for metribuzin application rates of 4 pounds
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Risk Mitigation
Additional Data
Required
(lb) active ingredient (ai) per acre or higher. Also acute and chronic risks
are likely for mammalian species, including endangered species, for rates of
1 lb ai/acre or higher. Additionally, risks are likely for nontarget terrestrial
and aquatic plant species, including endangered species, for rates of 0.5 lb
ai/acre or higher.
Although presently there are ground water advisories on metribuzin
product labels, the Agency is still concerned with potential ground water
contamination from metribuzin use. Data currently available to the Agency
indicate that metribuzin and its degradates are very mobile and highly
persistent, and thus have the potential to contaminate ground water and
surface water; however, the persistence of parent metribuzin in surface
water may be lessened by its susceptibility to photolytic degradation.
Metribuzin use could adversely affect ground-water quality, especially in
vulnerable areas. Detections have been reported in the "Pesticides in
Ground Water Database" (EPA, 1992) and other studies. These ground
water contamination concerns are enhanced by metribuzin's widespread use
patterns.
To lessen the risks to birds, mammals, and nontarget plants posed by
metribuzin, EPA is taking the following risk mitigation measures.
o prohibiting aerial application on asparagus and tomatoes;
o reducing the application rate of metribuzin being applied to sugarcane via
aerial and chemigation methods from 6.0 lb ai/acre to 2.0 lb ai/acre;
o adding specific spray drift labeling requirements.
To lessen the potential risks to humans posed by metribuzin, EPA is
taking the following risk mitigation measures.
o reducing the application rate of metribuzin being applied to sugarcane via
aerial and chemigation methods from 6.0 lb ai/acre to 2.0 lb ai/acre;
o prohibiting the use of low-pressure or high volume hand wand equipment.
To reduce the likelihood of metribuzin and its primary degradates
contaminating ground and surface water, EPA is taking the following risk
mitigation actions.
ฐ specifying on the label Best Management Practices;
o determining areas that are vulnerable to ground-water contamination by
metribuzin and recommending risk mitigation measures.
EPA is requiring the following additional generic studies for
metribuzin to confirm its regulatory assessments and conclusions:
1) magnitude of residue studies (alfalfa and field corn trials, and field
rotational crop studies, additional field trials for field corn and potatoes, and
data for wheat aspirated grain fractions; 2) processing studies for sugarcane
and wheat; 3) certified limits (GLN 62-2) and analytical methods to verify
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certified limits (GLN 62-3) for three impurities related to the active
ingredient in the 90% technical; 4) storage stability data for animal
commodity samples from the previously evaluated poultry and ruminant
feeding studies; 5) confined rotational crop and field rotational crop studies;
and 6) additional ground water information.
The Agency also is requiring product-specific data including product
chemistry and acute toxicity studies, revised Confidential Statements of
Formula (CSFs), and revised labeling for reregistration.
Product Labeling All metribuzin end-use products must comply with EPA's current
Changes pesticide product labeling requirements and with the following. For a
Red uired comprehensive list of labeling requirements, please see the metribuzin RED
document.
o For tomatoes and asparagus uses: "Aerial application is
prohibited."
o For aerial application on sugarcane: "To assure that spray will not
adversely affect adjacent sensitive nontarget plant, apply this product
by aircraft at a minimum upwind distance of 400 ft from sensitive
plants."
o For all uses: "Low-pressure and high volume hand wand
equipment is prohibited."
o For the aerial and chemigation application methods of metribuzin
on sugarcane: A "maximum application rate of 2.0 Ib ai/acre" is
specified.
o Specific spray drift label requirements are added.
o Best Management Practices to help reduce ground and surface
water contamination.
Regulatory
Conclusion
For More
Information
The use of currently registered products containing metribuzin in
accordance with approved labeling will not pose unreasonable risks or
adverse effects to humans or the environment. Therefore, all uses of these
products are eligible for reregistration under the conditions specified in this
RED.
Metribuzin products will be reregistered once the required product-
specific data, revised Confidential Statements of Formula, and revised
labeling are received and accepted by EPA.
EPA is requesting public comments on the Reregistration Eligibility
Decision (RED) document for metribuzin 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 Information and Record Integrity
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Branch, Informantion Resources and Services Division (7506C), Office of
Pesticide Programs (OPP), US EPA, Washington, DC 20460, telephone
703-305-5805.
Electronic copies of the RED and this fact sheet are available on the
Internet. See http://www.epa.gov/REDs.
Printed copies of the RED and fact sheet can be obtained from EPA's
National Center for Environmental Publications and Information
(EPA/NCEPI), PO Box 42419, Cincinnati, OH 45242-2419, telephone 1-
800-490-9198; fax 513-489-8695.
Following the comment period, the metribuzin 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 metribuzin RED, or reregistration of individual products containing
metribuzin, please contact the Special Review and Reregistration Division
(7508W), OPP, US EPA, Washington, DC 20460, telephone 703-308-8000.
For information about the health effects of pesticides, or for assistance
in recognizing and managing pesticide poisoning symptoms, please contact
the National Pesticides Telecommunications Network (NPTN). Call toll-
free 1-800-858-7378, from 6:30 am to 4:30 pm Pacific Time, or 9:30 am to
7:30 pm Eastern Standard Time, seven days a week.
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, D.C. 20460
OFFICE OF
PREVENTION, PESTICIDES
AND TOXIC SUBSTANCES
i s
CERTIFIED MATT,
Dear Registrant:
I am pleased to announce that the Environmental Protection Agency has completed its
reregistration eligibility review and decisions on the pesticide chemical case metribuzin which
includes the active ingredients 4-amino-6(l,l-dimethylethyl)-3-(methylthio)-l,2,4-triazin-5(4H)-
one. The enclosed Reregistration Eligibility Decision (RED), which was approved on
May 20,1997 contains the Agency's evaluation of the data base of these chemicals, 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
ingredients to confirm the risk assessments.
To assist you with a proper response, read the enclosed document entitled "Summary of
Instructions for Responding to the RED." This summary also refers to other enclosed documents
which include further instructions. You must follow all instructions and submit complete and
timely responses. The first set of required responses is due 90 days from the receipt of this
letter. The second set of required responses is due 8 months from the date of this letter.
Complete and timely responses will avoid the Agency taking the enforcement action of
suspension against your products.
Please note that the Food Quality Protection Act of 1996 (FQPA) became effective on
August 3,1996, amending portions of both pesticide law (FIFRA) and the food and drug law
(FFDCA). This RED takes into account, to the extent currently possible, the new safety standard
set by FQPA for establishing and reassessing tolerances. However, it should be noted that in
continuing to make reregistration determinations during the early stages of FQPA
implementation, EPA recognizes that it will be necessary to make decisions relating to FQPA
before the implementation process is complete. In making these early case-by-case decisions,
EPA does not intend to set broad precedents for the application of FQPA. Rather, these early
determinations will be made on a case-by-case basis and will not bind EPA as it proceeds with
further policy development and any rulemaking that may be required.
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If EPA determines, as a result of this later implementation process, that any of the
determinations described in this RED are no longer appropriate, the Agency will pursue whatever
action may be appropriate, including but not limited to reconsideration of any portion of this
RED.
If you have questions on the product specific data requirements or wish to meet with the Agency,
please contact the Special Review and Reregistration Division representative Jean Holmes (703)
308-8008. Address any questions on required generic data to the Special Review and
Reregistration Division representative Michael Goodis (703) 308-8157.
director
!. Review and
^registration Division
Enclosures
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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 time extensions for product specific data should
be submitted in the 90-day response. Requests for data waivers must be submitted as part of the
90-day response. All data waiver and time extension requests must be accompanied by a full
justification. All waivers and time extensions must be granted by EPA hi 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 hi 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 (attached to the DCI).
d. Two copies of the Confidential Statement of Formula (CSF) for each basic and
each alternate formulation. The labeling and CSF which you submit for each product must
comply with P.R. Notice 91-2 by declaring the active ingredient as the nominal concentration.
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You have two options for submitting a CSF: (1) accept the standard certified limits (see 40 CFR
ง158.175) 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 ง158.175(e). A copy of the CSF is enclosed;
follow the instructions on its back.
e. Certification With Respect to Data Compensation Requirements. Complete and
sign EPA form 8570-31 for each product.
4. COMMENTS IN RESPONSE TO FEDERAL REGISTER NOTICE-Comments
pertaining to the content of the RED may be submitted to the address shown in the Federal
Register Notice which announces the availability of this RED.
5. WHERE TO SEND PRODUCT SPECIFIC PCI RESPONSES (90-DAY) AND
APPLICATIONS FOR REREGISTRATION (8-MONTH RESPONSES)
BvU.S.Mail:
Document Processing Desk (RED-SRRD-PRB)
Office of Pesticide Programs (7504C)
EPA, 401 M St. S.W.
Washington, D.C. 20460-0001
Bv express:
Document Processing Desk (RED-SRRD-PRB)
Office of Pesticide Programs (7504C)
Room 266A, Crystal Mall 2
1921 Jefferson Davis Hwy.
Arlington, VA 22202
6. EPA'S REVIEWS-EPA will screen all submissions for completeness; those which are not
complete will be returned with a request for corrections. EPA will try to respond to data waiver
and time extension requests within 60 days. EPA will also try to respond to all 8-month
submissions with a final reregistration determination within 14 months after the RED has been
issued.
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REREGISTRATION ELIGIBILITY DECISION
Metribuzin
LIST A
CASE 0181
ENVIRONMENTAL PROTECTION AGENCY
OFFICE OF PESTICIDE PROGRAMS
SPECIAL REVIEW AND REREGISTRATION DIVISION
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TABLE OF CONTENTS
METRIBUZIN REREGISTRATION ELIGIBILITY DECISION TEAM i
ABSTRACT iv
I. INTRODUCTION 1
II. CASE OVERVIEW 2
A. Chemical Overview 2
B. Use Profile 3
C. Estimated Usage of Pesticide 5
D. Data Requirements 7
E. Regulatory History .7
in. SCIENCE ASSESSMENT 7
A. Physical Chemistry Assessment 7
B. Human Health Assessment 8
1. Toxicology Assessment 8
a. Acute Toxicity 8
b. Subchronic Toxicity 9
c. Chronic toxicity and Carcinogenicity. 10
d. Developmental Toxicity 12
e. Reproductive Toxicity 13
f. Mutagenicity 14
g. Metabolism 15
h. Dose-Response Assessment 15
2. Exposure Assessment 19
a. Dietary Exposure 20
b. Drinking Water Exposure 29
c. Occupational Exposure 32
3. Risk Assessment 39
a. Dietary Risk 39
b. Drinking Water Risk 40
c. Occupational Risk 41
d. Food Quality Protection Act (FQPA) Considerations 48
C. Environmental Assessment 56
1. Ecological Toxicity Data 56
a. Toxicity to Terrestrial Animals 56
b. Toxicity to Aquatic Animals 58
c. Toxicity to Plants 63
2. Environmental Fate 66
a. Environmental Fate Assessment 66
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b. Environmental Fate and Transport 67
c. Water Resources 70
3. Exposure and Risk Characterization 76
a. Ecological Exposure and Risk Characterization. 76
b. Water Resources Risk Implication for Human Health ... 93
IV. RISK MANAGEMENT AND REREGISTRATION DECISION 98
A. Determination of Eligibility 98
B. Determination of Eligibility 99
1. Eligibility Decision 99
2. Eligible and Ineligible Uses 99
C. Regulatory Position. 99
1. Food Quality Protection Act Consideration 100
2. Tolerance Reassessment 101
3. Tolerance Revocations and Import Tolerances 107
4. Summary of Risk Management Decisions 108
5. Endangered Species Statement 110
6. Occupational Labeling Rationale 110
7. Spray Drift Advisory 114
V. ACTIONS REQUIRED OF REGISTRANTS 115
A. Manufacturing-Use Products 115
1. Additional Generic Data Requirements 115
2. Labeling Requirements for Manufacturing-Use Products 115
B. End-Use Products 116
1. Additional Product-Specific Data Requirements 116
2. Labeling Requirements for End-Use Products ."... 116
a. Worker Protection Standard 116
b. .Occupational/Residential Labeling 117
c. Environmental Hazard Statements 120
d. Application Restrictions 120
e. Application Rates 121
C. Spray Drift Labeling 121
D. Existing Stocks 125
VL APPENDICES 127
APPENDIX A. Table of Use Patterns Subject to Reregistration 127
APPENDIX B. Table of the Generic Data Requirements and Studies
Used to Make the Reregistration Decision 128
APPENDIX C. Citations Considered to be Part of the Data Base
Supporting the Reregistration of Metribuzin 143
APPENDIX D. Combined Generic and Product Specific Data Call-In .. 164
Attachment 1. Chemical Status Sheets 185
Attachment 2. Combined Generic and Product Specific Data
Call-in Response Forms (Form A inserts)
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Plus Instructions 187
Attachment 3. Generic and Product Specific Requirement Status
and Registrant's Response Forms (Form B inserts)
and Instructions 191
Attachment 4. EPA Batching of End-Use Products for Meeting
Data Requirements for Reregistration 199
Attachment 5. List of AH Registrants Sent This Data Call-In
(insert) Notice 206
Attachment 6. Cost Share, Data Compensation Forms,
Confidential Statement of Formula Form
and Instructions 207
APPENDIX E. List of Available Related Documents 215
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METRIBUZIN REREGISTRATION ELIGIBILITY DECISION TEAM
Office of Pesticide Programs:
Biolosical and Economic Analysis Assessment
Jim Saulmon
Art Grube
Margaret Cogdell
Biological Analysis Branch
Economic Analysis Branch
L.U.I.S. Project
Environmental Fate and Effects Risk Assessment
Mary Powell
Kay Montague
Jim Breithaupt
Estella Waldman
Henry Nelson
Health Effects Risk Assessment
Kathryn Boyle
John Leahy
Sue Hummel
Brian Steinwand
Stephen C. Dapson
Registration Support
Vickie Walters
Mark Perry
Risk Management
Jean Holmes
Science Analysis and Coordination Staff
Ecological Effects Branch
Environmental Fate and Groundwater Branch
Environmental Fate and Groundwater Branch
Environmental Fate and Groundwater Branch
Risk Characterization and Analysis
Occupational and Residential Exposure Branch
Registration and Support Chemistry Branch
Science Analysis Branch
Toxicology Branch II
Fungicide-Herbicide Branch
Registration Support Branch
Planning and Reregistration Branch
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GLOSSARY OF TERMS AND ABBREVIATIONS
ADI Acceptable Daily Intake. A now defunct term for reference dose (RfD).
AE Acid Equivalent
a.i. Active Ingredient
ARC Anticipated Residue Contribution
CAS Chemical Abstracts Service
CI Cation
CNS Central Nervous System
CSF Confidential Statement of Formula
DFR Dislodgeable Foliar Residue
ORES Dietary Risk Evaluation System
D WEL Drinking Water Equivalent Level (DWEL) The D WEL represents a medium specific (i.e. drinking
water) lifetime exposure at which adverse, non carcinogenic health effects are not anticipated to
occur.
EEC Estimated Environmental Concentration. The estimated pesticide concentration in an environment,
such as a terrestrial ecosystem.
EP End-Use Product
EPA U.S. Environmental Protection Agency
FAO/WHO Food and Agriculture Organization/World Health Organization
FDA Food and Drug Administration
FIFRA Federal Insecticide, Fungicide, and Rodenticide Act
FFDCA Federal Food, Drug, and Cosmetic Act
FQPA Food Quality Protection Act
FOB Functional Observation Battery
GLC Gas Liquid Chromatography
GM Geometric Mean
GRAS Generally Recognized as Safe as Designated by FDA
HA Health Advisory (HA). The HA values are used as informal guidance to municipalities and other
organizations when emergency spills or contamination situations occur.
HOT Highest Dose Tested
LCi0 Median Lethal Concentration. A statistically derived concentration of a substance that can b e
expected to cause death in 50% of test animals. It is usually expressed as the weight of substance
per weight or volume of water, air or feed, e.g., mg/1, mg/kg or ppm.
LD50 Median Lethal Dose. A statistically derived single dose that can be expected to cause death in 50%
of the test animals when administered by the route indicated (oral, dermal, inhalation). It i s
expressed as a weight of substance per unit weight of animal, e.g., mg/kg.
LDlo Lethal Dose-low. Lowest Dose at which lethality occurs.
LEL Lowest Effect Level
LOG Level of Concern
LOD Limit of Detection
LOEL Lowest Observed Effect Level
MATC Maximum Acceptable Toxicant Concentration
MCLG Maximum Contaminant Level Goal (MCLG) The MCLG is used by the Agency to regulat e
contaminants in drinking water under the Safe Drinking Water Act.
Hg/g Micrograms Per Gram
yt/g/L Micrograms per liter
mg/L Milligrams Per Liter
MOE Margin of Exposure
MP Manufacturing-Use Product
MPI Maximum Permissible Intake
MRJD Master Record Identification (number). EPA's system of recording and tracking studies submitted.
11
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-------
GLOSSARY OF TERMS AND ABBREVIATIONS
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
111
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ABSTRACT
The U. S. Environmental Protection Agency has completed its reregistration eligibility
decision for the pesticide metribuzin. This decision includes a comprehensive reassessment of
the required target data and the use patterns of currently registered products. This decision
considered the requirements of the recently enacted "Food Quality Protection Act of 1996" which
amended the Federal Food, Drug, and Cosmetic Act and the Federal Insecticide, Fungicide and
Rodenticide Act, the two Federal statutes that provide the framework for pesticide regulation in
the United States. FQPA became effective immediately upon signature and all reregistration
eligibility decisions (REDs) signed subsequent to August 3,1996 are accordingly being evaluated
under the new standards imposed by FQPA.
Metribuzin is a herbicide used on a wide range of sites, including vegetable and field
crops, turf grasses (recreational areas), and non-crop areas, to selectively control certain broadleaf
weeds and grassy weed species. The Agency has concluded under FIFRA that all uses, as
prescribed in this document, will not cause unreasonable risks to humans or the environment and
therefore, all products are eligible for reregistration. To mitigate potential health risks to
mixer/loader/applicators, the Agency has accepted risk mitigation measures proposed by the
technical registrant, Bayer Corporation, requiring the removal of certain application methods
from the label and application rate reductions. Also, measures to reduce environmental risks to
birds, mammals, and non-target plants include the removal of certain application methods from
the label, application rate reductions, and spray drift label requirements. Certain product
chemistry and residue chemistry data are being required to be submitted to confirm the Agency's
risk assessment and conclusions.
In establishing or reassessing tolerances, FQPA requires the Agency to consider aggregate
exposures to pesticide residues, including all anticipated dietary exposures and other-exposures
for which there is reliable information, as well as the potential for cumulative effect from a
pesticide and other compounds with a common mechanism of toxicity. The Act further directs
EPA to consider the potential for increased susceptibility of infants and children to the toxic
effects of pesticide residue.
The Agency does not have at this time, available data to determine whether metribuzin
has a common mechanism of toxicity with other substances or how to include this pesticide in
a cumulative risk assessment. Unlike other pesticides for which EPA has followed a cumulative
risk approach based on a common mechanism of toxicity, metribuzin does not appear to produce
a toxic metabolite produced by other substances. For the purposes of this tolerance action,
therefore, EPA has not assumed that metribuzin has a common mechanism of toxicity with other
substances.
The Agency has reassessed metribuzin food and feed related tolerances under the
standards of FQPA and determined that, based on available information, there is a reasonable
certainty that no harm will result to infants and children or to the general population from
IV
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aggregate exposure to metribuzin residues. The only type of exposures evaluated were dietary
and drinking water routes, since significant non-occupational exposures are unlikely with
metribuzin use.
Before reregistering products containing metribuzin, the Agency is requiring that product
specific data, revised Confidential Statements of Formula (CSF), and revised labeling be
submitted within eight months of the issuance of this document for all products containing
metribuzin. The product specific data include product chemistry for each registration and acute
toxiciry testing. After reviewing all these data and any revised labels and finding them acceptable
in accordance with section 3(c)(5) of FIFRA, the Agency will reregister a product. However,
those products which bear uses of this or any other active ingredients which have not been
determined to be eligible for reregistration will be reregistered only when such uses and 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.
On August 3,1996, the Food Quality Protection Act of 1996 (FQPA) (Public Law 104-
170) was signed into law. FQPA amends both the Federal Food, Drug, and Cosmetic Act
(FFDCA), 21 U.S.C. 301 et seq., and the Federal Insecticide, Fungicide, and Rodenticide Act
(FIFRA), 7 U.S.C. 136 et seq. The FQPA amendments went into effect immediately. As a result,
EPA is embarking on an intensive process, including consultation with registrants, States, and
other interested stakeholders, to make decisions on the new policies and procedures that will be
appropriate as a result of enactment of FQPA. This process will include a more in depth analysis
of the new safety standard and how it should be applied to both food and non-food pesticide
applications. The FQPA did not, however, amend any of the existing reregistration deadlines in
Section 4 of FIFRA. The Agency will therefore continue its ongoing reregistration program
while it continues to determine how best to implement FQPA.
This document presents the Agency's decision regarding the reregistration eligibility of
the registered uses of metribuzin including the risk to infants and children for any potential
dietary, drinking water, dermal, inhalation or other oral exposures, and cumulative effects as
stipulated under the FQPA. The document consists of six sections. Section I is the introduction.
Section II describes metribuzin, its uses, data requirements and regulatory history. Section III
discusses the human health and environmental assessment based on the data available to the
Agency. Section IV presents the reregistration decision for metribuzin. Section V discusses the
reregistration requirements for metribuzin. 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
The following active ingredient is covered by this Reregistration Eligibility
Decision:
Common Name:
Metribuzin
Chemical Name:
4-amino-6-(l,l-dimethylethyl)-3-
(methylthio)-1,2,4-triazin-5 (4H)-one
Chemical Family:
Triazinone
CAS Registry Number:
21087-64-9
OPP Chemical Code:
101101
Empirical Formula
and Structure:
H,C
Molecular Weight:
214.28
Trade and Other Names:
Sencor, Lexone, Preview
Basic Manufacturer:
Bayer Corporation
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B. Use Profile
The following is information on the currently registered uses with an overview of
use sites and application methods. A detailed table of these uses of metribuzin is in
Appendix A.
For Metribuzin:
Type of Pesticide: Herbicide
Mode of Action: Inhibits electron transport in photosynthesis
Use Sites:
TERRESTRIAL FOOD CROP
Grain Crops: Wheat
Miscellaneous Vegetables: Asparagus
Root Crop Vegetables: Carrot (including tops)
TERRESTRIAL FOOD+FEED CROP
Agricultural Uncultivated Areas: Agricultural fallow/idleland
Fruiting Vegetables: Tomato
Grain Crops: Barley, Corn (Field), Wheat
Groups of Agricultural Crops Which Cross Established Crop Groupings: Corn,
Peas, Soybeans
Root Crop Vegetables: Potato (White/Irish)
Seed and Pod Vegetables: Garbanzos (including chick peas), Lentils, Peas (Dried-
Type, Field, Pigeon)
Sugar Crops: Sugarcane
TERRESTRIAL FEED CROP
Forage Grasses: Barley, Bermudagrass, Bluegrass, Grass Forage/Fodder/Hay,
-------
Timothy, Wheat
Forage Legumes and Other Nongrass Forage Crops: Alfalfa, Lentils, Sainfoin
TERRESTRIAL NON-FOOD CROP
Groups of Agricultural Crops Which Cross Established Crop Groupings: Grasses
grown for seed
Nonagricultural Uncultivated Areas: Nonagricultural uncultivated areas/soils,
recreational areas
TERRESTRIAL NON-FOOD
Ornamental Lawns and Turf: Ornamental Lawns and turf (No residential uses)
Target Pests:
Broadleaves: annual polemonium, ageratum, ameranth, beggarweed, bristly
starbur, buffalobur, buttercup, bedstraw, carpetweed, chickweed, clover,
cocklebur, coffeeweed, common ragweed, com cockle, Carolina geranium, cutleaf
evening primrose, dandelion, dayflower, dock, dogfennel, falseflax, field
bindweed, field pennycress, filaree, fireweed, flixweed, Florida pusley, fumitory,
galinsoga, gromwell, haloe koa, henbit, hialoa, hophornbeam copperleaf,
horsenettle, horseweed, Jacob's ladder, jimsonweed, knotweed, kochia,
ladysthumb, lambsquarters, London rocket, mallow, marestail, meadow salsify,
mexicanweed, minerslettuce, morningglory, mustard, nettleleaf goosefoot,
parsley-piert, pepperweed, pigweed, pineappleweed, prickly lettuce, purple
deadnettle, purslane, rattlebox, redweed, red tassel-flower, red sorrel, sand
catchfly, sensitiveplant, sesbania, shepherdspurse, sicklepod, spurred anoda,
smartweed, snapweed, speedwell, spurge, spurweed, sunflower, thistle, toadflax,
velvetleaf, white campion, wild buckwheat, wild poinsettia, yellow rocket;
Grasses: alexandergrass, barnyardgrass, barley, bluegrass, broadleaf panicum,
browntop millet, brome, cheat, crabgrass, crowfootgrass, fall panicum, field
sandbur, foxtail, guineagrass, Italian ryegrass, johnsongrass, junglerice, littleseed
canarygrass, quackgrass, rabbitfoot polypogon, radiate fingergrass, rescuegrass,
ricegrass, spring whitlowgrass, signalgrass, volunteer wheat, wild oat, windgrass,
wiregrass
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Formulation Types Registered:
TECHNICAL GRADE ACTIVE INGREDIENT
SOLID
MANUFACTURING PRODUCT
WETTABLE POWDER
END USE PRODUCT
EMULSIFIABLE CONCENTRATE
FLOWABLE CONCENTRATE
90.00%
50.00%
14.00 to 15.00%
41.00%
WATER DISPERSIBLE GRANULES (DRY
FLOWABLE)
WETTABLE POWDER
64.30% to 75.00%
50.00% to 70.00%
Method and Rates of Application:
(Please refer to Appendix A for site/use rate combinations.)
Equipment -
Aircraft (fixed-wing and helicopter); Center pivot irrigation; Ground; Low
pressure ground sprayer; Power sprayer; Sprayer; Sprinkler irrigation
Method and Rate -
Band treatment; Broadcast; Chemigation; Conservation tillage; Directed spray;
Low volume spray (concentrate); Soil band treatment; Soil broadcast treatment;
Soil incorporated treatment; Spot treatment; Spray
At planting; Dormant; Early postemergence; Early preplant; Early spring;
Established plantings; Fall; Fallow; Foliar; Late spring; Layby; Post-final harvest;
Postemergence; Postharvest; Postplant; Preemergence; Preplant; Preplant Spring);
Pretransplant (Spring)
C. Estimated Usage of Pesticide
This section summarizes the best estimates available for the pesticide uses of
metribuzin. These estimates are derived from a variety of published and proprietary
sources available to the Agency. The data, reported on an aggregate and site (crop) basis,
reflect annual fluctuations in use patterns as well as the variability in using data from
various information sources. The table below summarizes metrobuzin use on agricultural
crops by site.
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Table 1
Metribuzin Usage
tit*
Corn
Barley
Wheat
Sorghum
Lentils
Peas, Dry
Peas, Green
Alfalfa
Hay, Other
Potatoes
Soybeans
Sugarcane
Grasses &
Turf
Asparagus
Carrots
Tomatoes
Sainfoin
Acre*
(000)
Planted
76,200
8,200
71,500
11,600
130
170
320
24,800
36,000
1,400
59,300
900
90
100
450
NO
DATA
Acres Treated
(000)
Likely
Average
180
5
400
1
<1
60
15
200
10
830
6,540
90
30
25
5
110
Likely
Max
290
10
500
4
<1
100
30
340
30
920
11,540
140
60
50
10
130
Lb AX Applied
(000)
Likely
Average
30
3
65
1
15
4
110
4
430
1,980
90
30
25
1
60
Likely
Max
80
15
80
3
25
7
200
12
550
3,690
180
60
51
2
80
Application Rates
Ib ai/#
acre/yr
0.2
0.6
0.2
0.6
0.3
0.2
0.6
0.4
0.5
0.3
1.0
1.0
1.1
0.2
0.5
appl Ib
/year
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
ai/
A
app
1
0.2
0.6
0.2
0.6
0.3
0.2
0.6
0.4
0.5
0.3
1.0
1.0
1.1
0.2
0.5
States of Most
and % of Usage
States
IA 99%
WA UT 85%
WA OR 92%
LA 90%
ID WA 90%
WA OR 92%
WA OR UT ID
86%
NJ WA 85%
ID WA WI ME
77%
OH IL IN IA
66%
LA FL 100%
WA CA 81%
MN WI 81%
FL OH MI IN
78%
Usage
in Tnes<
MT MI
FL OR
MO MI
TN PA
NOTES
Calculations of the above numbers may not appear to agree because they are displayed as rounded.
% of each crop treated with metribuzin is 1% or less, except for soybeans. The likely average % of soybeans treated
is 11% and the likely maximum % of soybeans treated is 20%.
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NO DATA = This site is NOT covered by EPA data sources.
'Usage data primarily covers 1990 - 1994 for most sites and as early as 1987 for some sites.
Likely averages are based on weighted averages of data with most recent years and more reliable data weighted more.
Early years are weighted very low.
Likely maximums are an amount above which the actual usage is unlikely to be.
Application rates are calculated from likely averages or are based on typical rather than maximum rates.
SOURCES: EPA data, USDA, and National Center for Food and Agricultural Policy
D. Data Requirements
Data requested in the July 1985 Registration Standard for metribuzin included
studies on product chemistry, residue chemistry, toxicology, ecological effects, and
environmental fate. These data were required to support the uses listed in the Registration
Standard. Data Call-Ins were issued for metribuzin in 1991 and 1995 requiring additional
product chemistry, environmental fate and groundwater, and ecological effects data. The
ecological effects, environmental fate and groundwater data have been submitted to the
Agency and reviewed. The residue chemistry data have been initiated by the registrant
but have not been completed. Appendix B includes all data requirements identified by
the Agency for currently registered uses needed to support reregistration.
E. Regulatory History
Metribuzin was registered in the United States in 1973 for use as a herbicide. In
July, 1985, a Registration Standard (NTIS # PB86-174216) was issued for metribuzin.
The Registration Standard required submission of additional data in the areas of
toxicology, product and residue chemistry, ecological effects, and environmental fate and
groundwater. The Standard also classified metribuzin as "Restricted Use" based on
potential for groundwater contamination and possible carcinogenic effects. This
classification was deleted six months after it was instituted, following the evaluation of
additional data submitted by the registrant, Miles, now Bayer Corporation, clarifying
carcinogenicity effects. This Reregistration Eligibility Decision evaluates data submitted
in response to the Registration Standard and subsequent data call-ins.
III. SCIENCE ASSESSMENT
A. Physical Chemistry Assessment
IDENTIFICATION OF ACTIVE INGREDIENT
Metribuzin is a white crystalline solid with a melting point of about 126 ฐC. Pure
metribuzin is soluble in water at 1200 ppm, and soluble in dimethylformamide (178 g/100
g), chloroform (85 g/100 g), acetone (82 g/100 g), ethyl acetate (47 g/100 g), methanol
(35 g/100 g), ethanol (19 g/100 g), toluene (12 g/100 g), xylene (9 g/100 g), and n-hexane
(0.2 g/100 g).
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MANUFACTURING-USE PRODUCTS
As of 7/29/96 there were two metribuzin manufacturing-use products (MPs)
registered to Bayer Corporation: a 90% technical (EPA Reg. No. 3125-270) and a 50%
formulation intermediate (FI) (EPA Reg. No. 3125-305). The formulation intermediate
is a wettable powder end-use product (EP).
Physical Chemistry Assessment -
All pertinent data requirements are satisfied for the metribuzin 50% FI. (Some of
the 50% FI data requirements are fulfilled by data for the technical source product.) Data
remain outstanding for the 90% T for GLNs 62-2 and 62-3 for the three manufacturing
process impurities. The Agency has concerns that the three manufacturing impurities,
which are structurally related to metribuzin and are present at greater than 0.1% in the
product, could be of toxicological concern. The registrant must either demonstrate that
these impurities are not toxicologically significant, or provide upper certified limits. In
addition, the label claim of 90% is not in agreement with the nominal concentration of the
active ingredient Per PR Notice 91 -2, dated 5/2/91, the label claim for the product must
reflect the nominal concentration of the active ingredient.
The registrant must submit the outstanding data for the 90% T for GLNs 62-2 and
62-3 concerning the three manufacturing process impurities, and certify that the suppliers
of beginning materials and the manufacturing processes for the metribuzin MPs have not
changed since the last comprehensive product chemistry review. If changes have
occurred, then the registrant must submit complete updated product chemistry data
packages.
B. Human Health Assessment
1. Toxicology Assessment
The toxicological data base on metribuzin is adequate and will support
reregistration eligibility.
a. Acute Toxicity
Table 2 summarizes the acute toxicity and toxicity categories of metribuzin.
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Table 2: Acute Toxicity Data
GLN
No.
ง81-1
ง81-2
ง81-3
ง81-4
ง81-5
ง81-6
Study
Acute Oral - rat
Acute Dermal - rabbit
Acute Inhalation - rat
Primary Eye Irritation
- rabbit
Primary Skin
Irritation - rabbit
Dermal Sensitization -
guinea pig
% a.i.
Technical
Technical
92.6%
Technical
Technical
93.5%
MRID
00106158
00106149
00157524
00106158
00106158
41555101
Results
LD50 =
m = 2.3 g/kg
f= 2.2 g/kg
LD,n>20g/kg
LC,0>0.648-mg/L
not an eye irritant
PIS = 0.33/8.0
not a dermal irritant
Not a dermal sensitizer
Category
III
IV
III '
IV
IV
NA
* Note: Data pertaining to acute eye irritation, dermal irritation, and dermal sensitization are not required to
support the reregistration of the TGAI. These data are presented only for informational purposes.
Acute toxicity studies with metribuzin indicate low toxicity. The LD50 in an acute
dermal study with rabbits was greater than 20 g/kg, no systemic toxicity and no mortality
was noted. An acute inhalation toxicity study in rats, using the maximum obtainable
concentration of technical metribuzin as dust, found the LC50 was greater than 0.648
mg/L. Metribuzin was not an eye irritant in a primary eye irritation test in rabbits. In a
primary dermal irritation study, metribuzin produced very slight irritation on rabbit skin.
Metribuzin was found not to produce a dermal sensitization reaction in guinea pigs under
conditions of the study.
b. Subchronic Toxicity
In a 21-day dermal toxicity study, New Zealand rabbits of the
HCrNZW strain from Interfauna UK Limited, Huntingdon, England were
exposed to either 0, 40, 200 or 1000 mg/kg/day of metribuzin (DIG 1468,
technical 94.0% a.L; batch 238603171). The treatment area on the backs
and flanks of the rabbits was a shaved area approximately 11 x 12 cm.
The solution of metribuzin was applied to 4-ply gauze dressings which
were held in place with adhesive strapping tape for 6 hours. At the end of
6 hours, the dressing and strapping were removed and the treatment area
washed with soap and water. The rabbits were treated only on working
days (i.e., 5 consecutive days each week) for 3 weeks. No dermal irritation
was noted. No animals died during the study. High dose males and
females had a dose-related increase in cholesterol. T3 (triiodothyronine)
was decreased in all males, but statistically significant only at the high
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dose. There was a statistically significant increase in N-demethylase and
cytochrome P450 activities in high dose males. Thus, the systemic toxicity
NOEL is 200 mg/kg/day. The systemic toxicity LOEL is 1000 mg/kg/day
based on increased plasma cholesterol and liver enzyme activities. Due to
the lack of dermal irritation, the dermal Noel is equal to or greater than
1000 mg/kg/day and the dermal toxicity LOEL is greater than 1000
mg/kg/day. (GLN 82-2; MRID 43970701).
In a 21-day inhalation toxicity study Wistar TNO/W 74 albino rats
from Winkelmann, Borchen were exposed to metribuzin (DIG 1468, 98.2
and 93.1% a.i.) in Ethanol-lutrol 1:1 (polyethylene glycol 400) at analytical
doses ranging from 32 to 720 mg metribuzin/m3 air. A control group of
males and females was exposed to the ethanol-lutrol. The animals'
conditions of exposure ensured that aerosols could only be inhaled.
Groups (10 males and 10 females) were exposed to the aerosols daily for
six hours. Systemic toxicity related to treatment with metribuzin was
noted in the high exposure level as increased clinical signs of toxicity
(disturbed behavior which was comprised of animals appearing apathetic
and with ungroomed coat), increased N-demethylase, O-demethylase, and
cytochrome P-450 activities along with increased liver weights, which
indicate increased activity in the liver. Body weight gains were decreased
in all treated groups. However, these decreases were not dose related, the
decreases were of great variability, and did not appear to be of any
toxicological significance. There were increased absolute and relative
thyroid weights. For systemic toxicity, the NOEL is 219 mg/m3 air (0.219
mg/L). The LOEL is 720 mg/m3 air (0.720 mg/L) based on clinical signs
of toxicity, increased liver enzyme activities, and increased organ weights
(GLN 82-4; MRID 00153706).
Two subchronic 90 day feeding studies in rats and one in dogs (an
unvalidated Industrial Biotest Study) were conducted. However, they were
classified as unacceptable due to multiple deficiencies. These studies were
not required to be repeated since the chronic toxicity study was acceptable.
c. Chronic toxicity and Carcinogenicity
In a two year chronic toxicity study, Beagle dogs from Appleton
Kennels, England received either 0, 25, 100, or 1500 ppm (0, 0.82, 3.44,
or 55.65 mg/kg/day for males; 0, 0.84, 3.56, or 55.3 mg/kg/day for
females) of metribuzin (BAY 94 337 technical 99.5% a.L, batch 1603/71)
in the diet. Toxicity was noted at the high dose in the form of mortality
(75% of the 1500 ppm group) along with decreased body weight, increased
relative liver weight and changes in liver and kidney function (increased
10
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SGOT and SGPT levels, increased ornithine-carbamyl transferase levels,
increased BSP retention, increased alkaline phosphatase, increased total
protein in blood and urine, increased urea, decreased creatinine, increased
blood sugar and increased cholesterol). For chronic toxicity the NOEL is
100 ppm (3.44 mg/kg/day in males, 3.56 mg/kg/day in females) and the
systemic toxicity LOEL is 1500 ppm (55.65 mg/kg/day for males, 55.3
mg/kg/day in females) based on mortality, decreased body weight,
increased liver weights and changes in clinical chemistry parameters (GLN
83-lb; MRID 00061260).
In a combined chronic toxicity and carcinogenicity study
metribuzin (BAY 94 337 technical 99.5% a.i.; batch 1603/71) was fed to
Wistar rats from Winkelmann, Kirchborchem, Kreis Paderborn for two
years at doses of 0, 25, 35, 100, or 300 ppm (0, 1.3, 1.87, 5.27, or 14.36
mg/kg/day in males; 0, 1.68, 2.28, 6.53, or 20.38 mg/kg/day in females).
Toxicity was noted at the high dose as decreased body weight gain along
with pathological changes in the liver, kidneys, uterus, and mammary
glands. Pituitary adenomas and carcinomas were observed; however, this
was not considered to be statistically significant when compared to the
historical control data. For chronic toxicity the NOEL is 100 ppm (5.27
mg/kg/day in males and 6.53 mg/kg/day in females). The LOEL is 300
ppm (14.36 mg/kg/day in males, 20.38 mg/kg/day in females) based on
decreased body weight gain and pathological changes in the liver, kidneys,
uterus, and mammary glands. There was no evidence of carcinogenicity
in either sex (MRID 00061261).
In a repeat combined chronic feeding/carcinogenicity study,
metribuzin (93.0% a.i.; Batch 77-297-50) was fed to Fischer 344 rats from
Charles River Laboratories, Raleigh, NC at doses of 0, 30, 300, or 900
ppm (0, 1.3, 13.8, or 42.2 mg/kg/day in males; 0, 1.6, 17.7, or 53.6
mg/kg/day in females) for either 52 or 104 weeks. Toxicity was noted at
300 ppm and above based on decreased body weight gain in females;
increased thyroid weight and thyroid/body weight ratio in males, increased
liver weight and liver/body weight ratio in males and females. At the
lowest dose, there were statistically significant changes in thyroxine (T4)
and triiodothyronine (T3) levels, but no other systemic effects were
observed. The OPP/HED RfD Committee determined that the 1.3
mg/kg/day dose level (males) should be considered as the NOEL since the
effects at the 1.3 mg/kg/day dose were considered to be of marginal
biological significance. This conclusion was based primarily on the
knowledge that metribuzin is a liver enzyme inducer and that the rat has
no other compensatory mechanism to re-establish normal levels of thyroid
hormones other than to increase thyroid production of these hormones, the
11
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effect observed at the lowest dose was considered a compensatory
homeostatic response and not a toxic effect. There was no evidence of
carcinogenicity and there was no increase in tumor incidence. For chronic
toxicity, the NOEL is 30 ppm (1.3 mg/kg/day in males and 1.6 mg/kg/day
in females) and the LOEL is 300 ppm (13.8 mg/kg/day in males and 17.7
mg/kg/day in females) based on decreased body weight gains in females,
increased thyroid weights in males, and increased liver weights in males
and females (GLN 83-5; MRID 42672501).
In a carcinogenicity study, dietary doses of 0, 200, 800, or 3200
ppm (0, 25, 111, or 438 mg/kg/day for males; 0, 35, 139, or 567
mg/kg/day for females) metribuzin (92.9% a.i.) were given to GDI mice
from Charles River Laboratories for two years. Systemic toxicity was
noted at the high dose as increased liver weights along with decreased
hemoglobin and hematocrit values. This study demonstrated that under
these test conditions metribuzin does not increase the incidence of tumors
in mice. For chronic toxicity, the NOEL is 800 ppm (111 mg/kg/day in
males, 139 mg/kg/day in females) and the LOEL is 3200 ppm (438
mg/kg/day for males, 567 mg/kg/day for females) based on increased liver
weights and decreased hematological parameters (GLN 83-2; MRID
00087795).
d. Developmental Toxicity
In a developmental toxicity (teratology) study, metribuzin (92.6%
a.i.; Batch No. 77-297-50) was administered in doses of 0, 25, 70, or 200
mg/kg/day by gavage on gestation days 6-18 to pregnant Charles River
CrhCD BR rats from Charles River Breeding Laboratories, Portage, MI.
Maternal toxicity was shown at all dose levels as reduced body weight
gain, reduced mean gravid uterine weights, and decreased food
consumption. The mid (70 mg/kg/day) and high (200 mg/kg/day) doses
showed an effect on the thyroid gland as demonstrated by reduced T4
levels. At the high dose there was also increased thyroid weight. The
maternal toxicity NOEL is less than 25 mg/kg/day and the maternal
toxicity LOEL is equal to or less than 25 mg/kg/day. For developmental
toxicity, the NOEL is 70 mg/kg/day and the LOEL is 200 mg/kg/day based
on decreased fetal body weight and reduced ossification or unossified skull
bones, ribs, vertebrae, sternebrae, pelvic bones, and appendages (GLN 83-
3a; MRID 00163802).
In a developmental toxicity (teratology) study, American Dutch
rabbits from Langshaw Farms, Augusta, MI were given 0, 10, 30, or 85
mg/kg/day of metribuzin (92.7% a.i.; Batch 77-297-50) by gavage on
gestation days 6-18. Maternal toxicity was noted at 30 mg/kg/day and
12
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above based on decreased maternal body weight gains on gestation days
18-28 at the mid dose level and decreased body weight gains, decreased
food consumption and decreased food efficiency on gestation days 7-19 at
the high dose level. Developmental toxicity was noted at the high dose in
the form of an increased incidence of irregular spinous processes. For
maternal toxicity, the NOEL is 10 mg/kg/day and the LOEL is 30
mg/kg/day, based on decreased weight gain on days 18-28. The
developmental toxicity NOEL is 30 mg/kg/day and the developmental
toxicity LOEL is 85 mg/kg/day based on an increase incidence of irregular
spinous processes (GLN 83-3b; MRID 41249201).
In a repeat developmental toxicity (teratology) study, New Zealand
white rabbits were given 0, 15, 45, or 135 mg/kg/day of metribuzin by
gavage on gestation days 6-18. Maternal systemic toxicity was noted at 45
mg/kg/day, as reduced body weight gain, and reduced food and water
intake. Additionally, at 135 mg/kg/day there was an increased incidence
of abortions and decreased body weights. For maternal toxicity, the NOEL
is 15 mg/kg/day and the LOEL is 45 mg/kg/day based on reduced body
weight gains and reduced food and water consumption. The
developmental toxicity NOEL is 15 mg/kg/day and the developmental
toxicity LOEL is 45 mg/kg/day based on decreased fetal body weights,
increased number of runts and increased incidence of extra and partial ribs.
(GLN 83-3b; MRID 00087796).
Based on the results of the existing studies, at this time metribuzin
is not considered to be a developmental toxin. The developmental toxicity
observed in these studies occurred at or above doses that induced maternal
toxicity.
e. Reproductive Toxicity
In a two-generation reproduction study, Crl:CD BR rats from
Charles River Breeding Laboratories, Portage, MI received in the feed 0,
30, 150, or 750 ppm (approximately 0, 1.5, 7.5, and 37.5 mg/kg/day by
standard conversion factors) metribuzin (Sencorฎ technical 92.6% a.L;
batch 77-297-50) . Systemic toxicity in both the parental animals and the
pups was noted at the mid dose as slightly decreased body weights in the
F1 high and the F2 mid and high dose pups. The Fj females had decreased
body weight gains during the gestation period for mid and high doses; F0
and F[ females had increased body weight during lactation and
hypertrophy of hepatocytes in high dose males and mid and high dose
females. The parental/offspring systemic toxicity NOEL is 1.5 mg/kg/day
and the parental/offspring systemic toxicity LOEL is 7.5 mg/kg/day based
13
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on decreased body weights and body weight gains and hypertrophy of the
hepatocytes (GLN 83-4; MRID 40838401).
f. Mutagenicity
Metribuzin was non-mutagenic in bacterial mutation assay systems
both with and without metabolic activation, using strains of SL
tvphimurium (TA1535, TA1537, TA98, and TA100), B. subtilus (NIG17
and NIG45), and E. coli (WP2 her) using concentrations of 0.2 to 2000
ug/plate of metribuzin (technical Sencorฎ 93.7% a.i.). The negative
control was DMSO. The positive controls were AAF, AF-2, 9-AA, NTG,
2-NF, and BP. (MRID# 00086770; 00109254).
No evidence of mutagenicity was seen in an in vitro CHO/HGPRT
assay when tested at doses ranging from 50-200 ug/mL with S-9 activation
and at doses ranging from 600-1000 ug/mL with out activation. The
positive control was ethyl methane sulfonate and benzo(a)pyrene. The
negative control was acetone (MRID 00157527).
In the preliminary screening cytotoxicity tests for an in vitro
Chinese hamster ovary (CHO) cell test severe cytotoxicity was observed
at doses equal to or greater than 1750 ug/ml without activation and at
doses equal to or greater than 584 ug/ml with S9 activation. For the study
the non-activated doses using a 20 hour harvest were 199, 299, 399, 499
or 598 ug/mL. The S9 activated doses using a 10 hour harvest were 37.5
or 50.0 ug/mL; and using a 20 hour harvest were 50.1, 100, 150, or 200
ug/mL. The positive control was mitomycin C and cyclophosphamide.
The negative control was ethanol. No statistically significant or dose-
related increases in aberration frequency were observed with nonactivated
metribuzin. However, in the presence of S9 activation there was an
increase in chromosome and chromatid breaks, triradials, and quadriradials
which indicates that metribuzin is possibly an in vitro clastogen. There is
no evidence of mutagenicity in the in vivo tests; therefore, the increase is
not considered to be of concern. The study was not repeated (MRID
42555102).
A series of three in vivo tests for dominant lethal mutations in
NMRI mice was performed. Males were given 300 mg of metribuzin
(Sencorฎ 99.5% a.i.) by gavage and then mated with undosed females in
two of the tests. Females were given 300 mg/kg metribuzin, and were then
mated with untreated males. On gestation day 14 females were sacrificed
and examined for the number of corporal lutea, viable implantation sites,
and dead implants. No statistically significant differences were noted
14
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(MRID 00086766).
In an in vivo cytogenetic study, metribuzin at doses of 100 mg/kg
body weight failed to induce chromosomal aberrations hi Chinese hamster
spermatogonia (MRID 00086765).
When tested at dose levels of 0.007 to 200 ug/ml, metribuzin did
not induce unscheduled DNA synthesis in rat primary hepatocytes. The
positive control was DMBA, and the negative control was ethanol or
DMSO. (MRID 00157526).
These studies taken together satisfy GLN 84.
g. Metabolism
Metabolism studies in Wistar rats from Charles River Breeding
Laboratory, Inc., (Boston, MA.) using a single low dose (5 mg/kg) of I4C-
metribuzin (98.4-99.4% a.L; SA = 20.8 mCi/nmol), a single high dose
(500mg/kg) of 14C-metribuzin, and multidoses of 5 mg/kg unlabeled
metribuzin (99.0% a.L; Lot# 51025) for 14 days followed by a single
radiolabeled dose of 5 mg/kg were performed. No significant differences
were detected in the rates and routes of I4C-elimination between male and
female rats in either the low or high dose single administration group. The
studies indicated that metribuzin was rapidly excreted in the urine and
feces, with a plateau being reached at 48 hours for all single dose groups
excepting 72 hours for the high dose female feces. From 27.3 to 43.4% of
the radiolabel was found in the urine and from 55.8 to 71.5% in feces at 96
hours. Very small amounts of metribuzin were found in the blood at 96
hours. The high dose group had higher tissue levels, as expected, with the
GI tract having higher levels. Sixteen metabolites of which 12 could be
identified were found in the urine. Very small amounts of the parent were
recovered. Many of the same metabolites were found in the feces. The
most prevalent metabolite in bom urine and feces was DA-N-Ac-Cys. The
metabolism of metribuzin in rats appears to involve deamination,
dethioalkylation, hydroxylation of the t-butyl side chain and conjugation.
(MRID 40255503).
h. Dose-Response Assessment
The OPP/HED RfD Peer Review Committee comprehensively
evaluates the toxicological database for a pesticide chemical and
establishes the RfD for the chemical. It also operates as the Agency's
quality assurance unit with respect to the acceptance or rejection of
15
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toxicological data for regulatory purposes; and determines whether a
chemical has been sufficiently tested to evaluate its carcinogenic potential
and its effects on developmental or reproductive parameters. The
OPP/HED RfD Peer Review Committee refers chemicals as necessary to
the OPP/HED Cancer Peer Review Committee and/or OPP/HED
Developmental and Reproductive Effects Peer Review Committee.
The OPP/HED Toxicity Endpoints Selection Committee (TESC)
considers the available toxicology data for a pesticide chemical and
performs the dose-response assessment by determining which of the
toxicological endpoints (if any) should be used in evaluating: 1) an acute
dietary risk assessment, 2) a short-term occupational or residential
exposure (1 to 7 days) risk assessment, 3) an intermediate-term
occupational or residential exposure (1 week to several months) risk
assessment, and 4) a chronic (non-cancer) occupational or residential
exposure risk assessment.
A NOEL is selected for use in calculating the MOE. TESC selects
the best toxicological study that most closely matches the duration of the
exposure of interest and the route of exposure. For occupational or
residential scenarios, exposure is most likely via the dermal and/or
inhalation route. Therefore, the most appropriate toxicological endpoint
is provided by a dermal or inhalation toxicity study. If adequate dermal or
inhalation studies are not available, then an oral study may be identified for
use hi risk assessment. The NOEL from the oral study would need to be
adjusted by the dermal exposure factor to reflect the dermal exposure that
occurs in an occupational scenario. If an appropriate study cannot be
identified (i.e., no effect occurs during the duration of exposure), the risk
assessment cannot be performed because the hazard that would be used in
the equation risk = hazard x exposure does not exist.
1. Reference Dose (Rfd)
The OPP/HED RfD Committee recommended that an RfD be
established on the basis of a two-year feeding study in rats (MRID
42672501). Increased absolute and relative weight of thyroid, decreased
lung weight in females, statistically significant increases in blood levels of
thyroxine (T4) and statistically significant decreases in blood levels of
triiodothyronine (T3) were observed at 30 ppm (1.3 mg/kg/day for males
and 1.6 mg/kg/day in females). However, as previously stated, the effects
observed at the lowest dose tested were considered to be of marginal
biological significance. Therefore, the RfD Committee determined that the
dose of 30 ppm (1.3 in males) should be considered as a NOEL. An
16
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uncertainty factor (UF) of 100 was applied to account for the inter-species
extrapolation and intra-species variability. On this basis, the RfD was
calculated to be 0.013 mg/kg/day. It was also recommended to use the
reproductive toxicity study (MRID 40838401) with a NOEL of 1.5
mg/kg/day as a co-critical study.
The OPP/HED RfD Peer Review Committee met on January 5,
1995, to discuss the weight of the evidence on metribuzin's carcinogenic
potential, and to determine if review to the OPP/HED Cancer Peer Review
Committee was appropriate. The Committee determined that referral was
not warranted. Metribuzin was classified as Group D, not classifiable as
to human carcinogenicity. The Committee based this classification on the
lack of evidence for carcinogenicity in the following studies: 1) a mouse
study in which there were no increases in tumor incidences at dosing levels
up to 438 mg/kg/day for males and 567 mg/kg/day for females (MRID
00087795); 2) a 1974 (MRID 00061261) rat study (SPF Wistar rats) in
which the observed pituitary adenomas and carcinomas were not
statistically significant at dosing levels up to 14.36 mg/kg/day for males
and 20.38 mg/kg/day for females; and 3) a 1993 (MRID 42672501) rat
study (Fischer [CDF(F-344)/BR] rats) which indicated no evidence for
carcinogenicity at dosing levels up to 42.2 mg/kg/day for males and 53.6
mg/kg/day for females.
2. Toxicological Endpoint Selection for Use in Human
Risk Assessment
(a) Dermal Absorption Factor
No acceptable dermal absorption data are available;
therefore, a default assumption of 100% is used in this
assessment..
(b) Acute Dietary Assessment (one day)
This risk assessment is required. The NOEL to be used for
calculating the MOE is 15 mg/kg/day from an oral
developmental toxicity study in rabbits (MRID 00087796).
(The LOEL was 45 mg/kg/day based on decreased fetal
body weight, increased number of runts, and increased
incidence of extra and partial ribs.) The NOEL from a
developmental toxicity study was selected for this
assessment since the possibility exists that the exhibited
effects could be caused by a one-day exposure. The
17.
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Agency considers an MOE of 100 to be acceptable when
the NOEL is taken from an animal study.
(c) Chronic Dietary
The RfD is the traditionally accepted endpoint for
calculating a chronic dietary assessment.
(d) Short Term (1 to 7 days) Occupational Dermal
Assessment
and
Intermediate Term (1 week to several months) Occupational
Dermal Assessment
These risk assessments are not required. In the 21-day
dermal toxicity study in rabbits (MRID 43970701) minimal
systemic changes were noted at the 1000 mg/kg/day. However, no
dermal irritation was noted at any dose level. Since the dermal
NOEL is equal to or greater than 1000 mg/kg/day (highest dose
tested), the 21-day dermal study does not support performing a
short term or intermediate term DERMAL risk assessment.
(e) Short Term (1 to 7 days) Occupational Inhalation
Assessment
and
Intermediate Term (1 week to several months) Occupational
Inhalation Assessment
These risk assessments are required. The NOEL to be used
for calculating the MOE is 219 mg/m3 from a 21-day inhalation
toxicity study (MRID 00153706). (The LOEL is 720 mg/m3 (0.720
mg/L) based on clinical signs of toxicity, increased liver enzyme
activities and increased organ weights).
Route-to-route extrapolation was used to convert the animal
inhalation concentration into a mg/kg dose by the following
equation:
(mg/L/dav)CAVRWDฅAF) = mg/kg/day
BW
where:
mg/L/day = 0.219 mg/L/day from the 21-day inhalation toxicity
18
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study
A = absorption of inhaled material = l(i.e., 100%, which is a
default assumption used by the Agency)
RV = 8.46 L/hr = mean liters of air respired per hour by the rat
D = 6 hr = daily duration of exposure during the 21-day study
AF = 1 = default animal activity factor
BW = 0.190 kg = mean rat weight
f0.219ฅlฅ8.46ฅ6)m = 58.5 mg/kg/day
(0.190)
The Agency considers a MOE equal to or greater than 100 to be
sufficiently protective when the NOEL is taken from an animal
study.
3.
WHO
2.
The Joint FAO/WHO Meeting on Pesticide Residues has not
evaluated metribuzin.
Exposure Assessment
The residue chemistry data base for metribuzin is now substantially
complete for reregistration purposes. A reasonable dietary risk assessment of
metribuzin can be performed using the available residue data. The need for
additional/revised tolerances or revisions to exposure assessments will be made
upon review of any new data.
The Residue Chemistry Chapter of the Reregistration Standard was issued
12/20/84. As previously stated, the Metribuzin Reregistration Standard Guidance
Document was issued 6/85 and the Reregistration Standard Update was issued
4/10/90. These documents summarized the regulatory conclusions based on the
available residue chemistry data and specified the additional data required for
reregistration purposes. Several data submissions have been received and
evaluated since the Update; a few submissions are still under review.
The Agency has recently updated the Livestock Feeds Table (Table II of
the Pesticide Assessment Guidelines, Subdivision O, Residue Chemistry, issued
19
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September 1995). Any new data requirements as a result of Table II changes are
being imposed at the issuance of the RED. The need for additional tolerances
and/or revisions to exposure/risk assessments will be made upon receipt of the
required data.
New alfalfa and field corn trials, and field rotational crop studies need to
be submitted as confirmatory data. These studies have been initiated by the
registrant. Tolerances for these commodities will be reassessed once the data have
been submitted and reviewed.
The available data for alfalfa forage and hay are insufficient to completely
support the established tolerances on these commodities because of inadequate
geographic representation of data. The western growing region is not represented,
and the states for which residue data are adequate (e.g., states where tests were
conducted according to the parameters of registered metribuzin uses on alfalfa)
represent less than one-fourth of the 1988 U.S. alfalfa hay production. The
tolerances may be revised once confirmatory data, which is in progress, is
submitted and reviewed.
a. Dietary Exposure
GLN 171-4 (a): Plant Metabolism
The qualitative nature of the residue in plants is adequately
understood based on upgraded soybean and wheat metabolism studies
which are supported by supplemental alfalfa, potato, sugarcane, and
tomato metabolism data. The residues of concern in plants are metribuzin
and its triazinone metabolites.
The metabolism of metribuzin in plants occurs via deamination
and/or dethiomethylation to yield triazinone moieties and their conjugates.
The requirements for radiovalidation of the current or any proposed
enforcement analytical method using samples from soybean and wheat
metabolism studies have been waived. The waiver was granted after
comparing the methodologies employed in these metabolism studies with
the current enforcement method, and because samples from these studies
have been depleted.
Soybean Metabolism Study: The total radioactive residues (TRR,
expressed as metribuzin equivalents) found following a preemergence soil
application of [14C]metribuzin at 0.3 Ib ai/A (active ingredient/acre) were
12.1 ppm in soybean plants and 0.48 ppm in mature soybean seeds. The
major organosoluble residue identified in soybean plant tissue was 6-(l,l-
20
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dimethylethyl)-3,5-(diketo)-1,2,4-triazin-5-(2H,4H)-dione (DADK), which
is 19.2% of the TRR. The minor organosoluble residues include
metribuzin, 4-ammo-6-(l,l-dimethylethyl)-3,5-(diketo)-l,2,4-triazin-5-
(2H,4H)-dione (DK), hydroxy-t-buryl DADK, hydroxy-t-butyl metribuzin,
and 3-amino-DA which collectively accounted for ~3.6% of the TRR. In
soybean seeds, the major organosoluble residue identified was free or
conjugated DADK which is 44.5% of the TRR. There was a supplemental
study designed to determine the nature of the residue in the aqueous
fraction. The glucose conjugates of DADK (17% of the TRR) were found
in soybean plant tissues. The glucose conjugates of DK (10.7% of the
TRR) were found in seeds.
Wheat Metabolism Study: Wheat grown to the 3-tiller stage was treated
postemergence with [5-14C]metribuzin at 0.15 Ib ai/A; the resulting TRRs
at the following pre-harvest intervals (PHI) are listed below:
Table 3: Total Radioactive Residues in Wheat
Commodity
Forage
Forage
Straw
Grain
PHI (days)
0
7
33
33
TRR (ppm, expressed as metribuzin equivalents)
5.4
1.2
5.5
0.2
The organosoluble residues identified in wheat forage were
metribuzin (42.8% of TRR), DADK (6.8% of TRR), and DK (7.5% of
TRR). The organosoluble residues identified in wheat straw were
metribuzin (3.9% of TRR), DADK (11.2% of TRR), DK (3.5% of TRR),
6-(l,l-dimethylethyl)-3-(methylthio)-l,2,4-triazin-5-(4H)-one(DA)(0.7%
of TRR), 3-amino DA (4.3% of TRR), and hydroxy-*-butyl-DADK (0.6%
of TRR). A large percentage of the metribuzin residues in wheat straw
were bound and shown to be associated with lignin (~25% of TRR) or
other biopolymers (10-15% of TRR) such as starch or protein. In grain,
residues were found to consist of metribuzin, DADK, DK, DA, hydroxy-?-
butyl-DADK, and hydroxy-f-butyl-DA which collectively accounted for
9.3% of the TRR. In a separate study designed to elucidate the nature of
the residue in the aqueous fraction, the only residue identified was tert-
leucine (10.7% TRR).
GLN 171-4 CbV. Animal Metabolism
The qualitative nature of the residue in animals is adequately
21
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understood based on acceptable poultry and ruminant metabolism studies
reflecting oral exposure. The residues of concern in animal commodities
are metribuzin and its triazinone metabolites. The requirements for
radiovalidation of the enforcement method using samples from the animal
metabolism studies have been waived.
Ruminant Metabolism Study: Two goats were orally dosed with
[5-14C]metribuzin at approximately 410 ppm (approximately 59x the
calculated dietary burden of metribuzin for ruminants) in the diet for three
consecutive days. The TRR were 12.66 ppm in liver, 4.27 ppm in kidney,
0.97 ppm in fat, 0.44 ppm in muscle, and 0.25-2.09 ppm in milk. The
major residues identified in muscle, fat, kidney, and liver tissue of goats
were metribuzin, its major metabolites (butylthion, DA, the sulfamate
conjugate of metribuzin, and the glucuronide conjugate of 2-methyl-DK),
and its minor metabolites (DADK, DK, and 2-methyl-DADK).
The OPP/HED Metabolism Committee met on October 21, 1993,
and concluded that the three metabolites (butylthion, 2-methyl-DADK and
the glucuronide conjugate of 2-methyl-DK) which are found only in
ruminant tissues need not be specifically included in the tolerance
expression (Le., methodology for the separate determination of these three
compounds is not needed).
Poultry Metabolism Study: Laying hens were orally dosed with
[5-14C]metribuzin at approximately 400 ppm (approximately 500x the
calculated dietary burden of metribuzin for poultry) in the diet for three
consecutive days. The TRR were 33.6 ppm in liver, 36.3 ppm in kidney,
1.6 ppm in muscle, 5.3 ppm in gizzard, 4.0 ppm in fat, 4.5 ppm in skin, 5.3
ppm in heart, and 0.2-1.0 ppm in eggs. The study adequately characterized
and identified the majority of the total radioactivity including 64.4% of the
TRR in liver, 55.9% in kidney, 84.2% in muscle, 92.8% in fat, 75.9% in
skin, and 63.2% in eggs. The terminal residues in poultry liver, muscle,
and fat tissues; and in eggs were metribuzin and its metabolites DA,
DADK, and DK; and their conjugates.
GLN 171-4 (c) and (d): Residue Analytical Methods - Plants and
Animals
Adequate methods are available for tolerance enforcement and data
collection for residues of metribuzin and three of its triazinone metabolites
(DK, DA, and DADK) in/on plant and animal commodities. The chemical
structures of these four chemicals are presented in Figure A.
22
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Figure A. The Chemical Structures of Metribuzin and Three of its Triazinone
Metabolites.
CH, O
H,C^ ^y ^N
N
-tf ^S
metribuzin: 4-amino-6-(l,l-
dimethylethyl)-3-(methylthio)-l,2,4-triazin-
5-(4H)-one
CH,
H3C
H,C
NH
,CH3
DA: 6-(l, 1 -dimethylethyl)-3-(methylthio)-
1,2,4-triazin-5-(4H)-one
,NH2
DK: 4-amino-6-(l,l-dimethylethyl)-3,5-
(diketo)-1,2,4-triazin-5-(2H,4H)-dione
DADK: 6-(l, l-dimethylethyl)-3,5-(diketo>
1,2,4-triazin-5-(2H,4H)-dione
Tolerance enforcement methods (plant commodities): The Pesticide
Analytical Manual (PAM, Vol. II, Section 180.332) lists two gas
chromatography (GC) methods, designated as Methods I and II, with
electron capture detection (BCD) and a detection limit of 0.01 ppm for
determination of metribuzin, DK, DA, and DADK in/on plant
commodities. Method I is suitable for determination of residues of
metribuzin and DADK only. Method II, the preferred enforcement
method, is suitable for determination of residues of metribuzin, DK, DA,
and DADK. Method II can detect all four compounds even if they are
present as water-soluble conjugates.
Tolerance enforcement methods ranitnal commodities'): Although there are
no methods listed in PAM Vol. II for the enforcement of animal
commodity tolerances, an adequate method is available. A GC/ECD
method, designated as Mobay Method Report No. 42257, is suitable for
determination of residues of metribuzin, DK, DA, and DADK in animal
tissues, milk, and eggs. In this method, metribuzin per se is converted to
DK, and DA is converted to DADK. Mobay Method Report No. 42257
23
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had been subjected to successful Agency method tryouts and should be
forwarded to FDA for inclusion in PAM Vol. II.
Data collection methods: Field and processing data submitted for
tolerance reassessment were collected using the current enforcement
methods or modifications thereof. The registrant provided adequate
method validation data to verify the suitability of these methods for data
collection.
Multiresidue methods: The FDA PESTDATA database dated 1/94 (PAM
Vol. I, Appendix I) indicates that metribuzin, DK, DA, and DADK are not
recovered using multiresidue method PAM Vol. I Sections 303 (Mills,
Onley, Gaither method) and 304 (Mills fatty food method). The database
also indicates that when Section 302 (Luke method) is used, DA is
completely (>80%) recovered, and metribuzin is variably recovered;
however, DK and DADK are not recovered.
GLN 171-4 (el: Storage Stability
Residues of metribuzin per se are stable under frozen storage
conditions (20 ฐC) for up to 24 months in/on field corn grain, forage, and
fodder; sweet corn; soybeans and soybean hay; tomatoes; and in corn oil.
Residues of metribuzin are stable for up to 17 months in tomato catsup and
tomato juice; and wheat bran, flour, and shorts. Residues of metribuzin are
stable for up to 12 months in/on asparagus, declining approximately 30%
after 18 months and approximately 50% after 24 months of storage.
Metribuzin residues are stable in/on soybean forage for up to 18 months,
declining approximately 50% after 24 months. Residues of metribuzin are
stable for up to 18 months in corn meal declining approximately 35% after
24 months. In tomato pomace residues of metribuzin degrade
immediately, declining approximately 35% after 1 month of frozen storage
and approximately 40% after 3 months of storage. The level then remains
constant through 17 months of storage. Since residues of metribuzin per
se were not consistently stable, all future residue studies must be
supported by concurrent storage stability data.
Residues of DADK and DA (metribuzin's metabolites) are stable
under frozen storage conditions for up to 24 months in/on asparagus; field
corn grain, forage, and fodder; sweet corn; soybeans, forage, and hay;
tomatoes; and in corn oil and meal. Residues are also stable for up to 17
months in tomato catsup, juice, and pomace; and wheat bran, flour, and
shorts. Residues of DK are relatively stable under frozen storage
conditions for up to 24 months in/on sweet corn, soybeans, tomatoes, and
24
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corn meal; and for up to 17 months in wheat flour. However, for
asparagus; field corn grain, forage, and fodder; soybean forage and hay;
corn oil; tomato catsup, juice, and pomace; and wheat bran and shorts,
recoveries of DK from storage stability samples were consistently less than
concurrent method recoveries, indicating declines during storage of up to
-60%.
There are additional storage stability data indicating that residues
of metribuzin per se are stable during frozen storage in/on alfalfa forage
and potatoes for up to 1 year, green peas for 2 years, soybeans for 1.5
months, and tomatoes for 3 years, but that residues of metribuzin and
DADK are not stable in/on carrots during frozen storage.
Information concerning the storage conditions and intervals of
animal commodity samples from the previously evaluated poultry (MRID
00045284, 00045286) and ruminant (MRID 00045283,00036772) feeding
studies are required to confirm that animal commodity samples from these
studies were stored at the storage intervals for which residues of
metribuzin and its metabolites of concern had been found to be stable in
muscle (3 months), milk (17 months), and eggs (3 months). If animal
commodity samples were stored, for longer intervals, then new animal
feeding studies may be required.
GLN 171-4 (k): Magnitude oftheResidue in Plants
The reregistration requirements for magnitude of the residue in
plants are fulfilled for the following commodities: asparagus; barley grain,
forage, hay, and straw; carrots; corn (field) forage and fodder; grass forage
and hay; lentils; lentil forage; peas (succulent and dry); pea vines and hay;
sainfoin forage and hay; soybeans, forage and hay; sugarcane; tomatoes;
and wheat grain, forage, hay, and straw. Adequate residue data, from field
trials conducted according to maximum registered use patterns are
available for these commodities (or representative commodities).
The registrant has indicated that additional trials on field corn and
potatoes have been initiated in lieu of providing storage stability data for
the length of time these commodities were stored. Once completed, the
results must be submitted to EPA for evaluation.
. Aspirated Grain Fractions:. The Agency has recently revised its policy on
aspirated grain fractions (previously referred to as "grain dust"), and
determined that it should be considered a raw agricultural commodity. The
Agency has also determined that aspirated grain fraction tolerances should
25
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be established based on the use of the pesticide on corn, wheat, sorghum,
and soybeans. Presently, there are registered uses of metribuzin on com,
wheat, and soybeans. The available field corn aspirated grain fraction data
indicate that residues of metribuzin and its metabolites DA and DADK
were nondetectable ( < the level of detection (LOD) of 0.01 ppm) and
residues of DK were nondetectable ( < LOD of 0.03 ppm) following
treatment at 5x. The tolerance for metribuzin residues of concern in/on
aspirated grain fractions will be evaluated after the outstanding data for
wheat aspirated grain fractions are submitted.
Carrots: The labels for Miles' 75% DF (EPA Reg. Nos. 3125-325 and
3125-402) were amended 9/14/94 to include metribuzin uses on carrots.
The presently registered uses of metribuzin on carrots are supported by
adequate residue data. The available field residue data, reviewed in
conjunction with the establishment of the tolerance petition PP#4E3112,
indicate that the combined residues of metribuzin and its triazinone
metabolites were below the established tolerance of 0.3 ppm following
multiple postemergence applications of the 75% DF at up to 4x the
maximum rate in trials conducted in CA, DE, IL, MI, NJ, TX, and WA.
Grass Forage and Hay: There are no registered FIFRA Section 3
metribuzin uses on grassier se. The established tolerances of 2 ppm and
7 ppm for grass forage and hay, respectively, were established to cover
metribuzin residues on grasses which may be treated incidentally in mixed
alfalfa pastures. Adequate data are available to support the established
tolerances for these commodities. These data are also sufficient to cover
any residues that may arise from metribuzin uses under several recent
Section 24(c) registrations on grasses grown for seed (SLNs OR900025,
OR900028 and WA930003, MT950007, WY950003).
GLN 171-4 (Ti: Magnitude of the Residue in Processed Food/Feed
Adequate processing studies have been conducted, to determine the
potential for concentration or reduction of the residues of metribuzin and
its triazinone metabolites, in processed products of the following raw
agricultural commodities: field corn, potatoes and soybeans. Additional
processing studies on sugarcane, tomatoes, and wheat have been initiated
and the results, once completed, must be submitted to EPA for evaluation.
The wheat processing data will be translated to fulfill the reregistration
requirements for a barley processing study.
26
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GLN 171-4 (T): Magnitude of the Residue in Meat. Milk. Poultry.
and Eggs
The reregistration requirements for magnitude of the residue in
animals are tentatively fulfilled pending submission of acceptable
confirmatory data on storage stability of animal commodity samples.
There are no registered direct animal treatments for metribuzin on cattle,
goats, hogs, horses, sheep, or poultry.
The maximum dietary burdens for beef and dairy cattle were
previously calculated in the Metribuzin Registration Standard to be 7 ppm.
(See Table 4)
Table 4: Ruminant Dietary Burden
Commodity
Barley or wheat grain
Alfalfa or sainfoin forage
Soybean forage
Dehydrated tomato pomace
Tolerance
(ppm)
0.75
2 '
4
2
%Dry
Matter
21
24
Total
Beef Cattle
% of Diet
40
35
20
5
100
Burden
(ppm)
0.3
3.3
3.3
0.1
7.0
Dairy Cattle
%of
Diet
40
35
20
5
100
Burden
(ppm)
0.3
3.3
3.3
0.1
7.0
It will be necessary to recalculate the dietary burden for ruminants
after the outstanding field and processing data for ruminant feed
commodities have been submitted and evaluated.
Beef Cattle Feeding Study: An unspecified breed of cattle was fed
unlabeled metribuzin at 3 or 10 ppm in the diet (approximately 0.4x and
1.4x the calculated dietary burden, respectively) for approximately 30
days. The detected residues are given in Table 5. As previously stated in
the discussion on Residue Analytical Methods, in animal tissues,
metribuzin per se is converted to DK, thus being detected as a single peak,
(level of detection (LOD) meat = 0.01 ppm). Similarly, DA is converted
to DADK and is also detected as a single peak, (LOD meat = 0.02 ppm).
Dairy Cattle Feeding Study: An unspecified breed of dairy cattle was fed
unlabeled metribuzin at 3 or 10 ppm in the diet (approximately 0.4x and
1.4x the calculated dietary burden, respectively) for approximately 30
days. The residues detected in milk are also given in Table 5. This
procedure also converts metribuzin per se to DK (LOD milk = 0.002 ppm),
and DA to DADK (LOD milk = 0.002 ppm).
27
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Table 5: Results of Beef and Dairy Cattle Feeding Studies
TISSUE
Total Residues
(Metribuzin, DK, DA, and
(ppm)
DADK)
Diet of 10 ppm Metribuzin
muscle
liver
kidney
fat
milk
Non-Detectable (<0
03)
0.55-1.01
0.08-0.17
0.06-1.13
O.004 - 0.007
Diet of 3 ppm Metribuzin
muscle
liver
kidney
fat
milk
Non-Detectable (< 0.
03)
0.27 - 0.40
O.03-0.10
<0.05 - 0.07
O.004 - 0.006
The maximum expected dietary intake of metribuzin residues by
poultry was previously calculated to be approximately 0.8 ppm from a diet
consisting of 50% barley or wheat grain, 30% soybeans, 10% wheat milled
by-products, 7% potato waste, and 3% sugarcane molasses. It will be
necessary to recalculate the dietary burden for poultry after the outstanding
field and processing data for poultry feed commodities have been
submitted and evaluated.
Poultry Feeding Study: Laying hens were fed unlabeled metribuzin at 5
ppm, 15 ppm, or 50 ppm in the diet (approximately 6.3x, 19x, and 63x the
calculated dietary burden, respectively) for 28 consecutive days. The
resulting combined residues of metribuzin per se, DK, DA, and DADK,
expressed as metribuzin equivalents, in eggs and poultry tissues are given
in Table 6.
28
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Table 6: Combined Residues of Metribuzin (ppm) in Eggs and Poultry Tissues
Tissues
28-Day Eggs
Giblet
Muscle
Fat
Skin
Feeding level
5 ppm
0.011-0.020
0.12-0.17
<0.02-0.02
0.04-0.05
0.04-0.07
15 ppm
0.032-0.053
0.23-0.27
0.06-0.07
0.04-0.08
0.03-0.08
50 ppm
Not reported
1.13-1.80
Not reported
Not reported
Not reported
GLNs 165-1 and 165-2: Confined/Field Rotational Crops
A confined rotational study (MRID 40838402) had been submitted,
evaluated, and classified as supplemental, not upgradable since (1) the test
substance was applied at 0.5x the maximum rate for crops which can be
rotated and (2) no storage stability data were provided. (A new confined
rotational study is required.)
Although the above study was classified as supplemental, it
indicates that metribuzin residues accumulated in confined rotational crops
(kale, red beets, and wheat) planted in sandy loam soil 32, 122, or 270
days following treatment of the soil with [14C]metribuzin at 0.19 Ib ai/A.
The major residue identified in the crops and soil was DADK; minor
residues that were identified were DA, DK, OH-t-butyl-DADK, and 3-
amino-DA.
b. Drinking Water Exposure
Acute (1 dav~) Exposure
A metribuzin concentration appropriate for use in an acute drinking
water assessment is 21 ppb. This concentration was the highest value
detected in drinking water wells in the Central Sands area of Wisconsin.
Exposure was calculated using the equation:
,-3 '
Exposure (mg/kg/day) = (ppb (ug/L) metribuzin in the water consumed) (10
ug/mg) (2L/day) divided by 60kg.
in which 60 kg is the default assumption for female body weight and 2L is the
default assumption for the amount of water consumed by an adult in a day.
29
-------
Exposure = 0.0007 mg/kg/day
Chronic Drinking Water Exposure
Water consumption is defined as all water obtained from the
household tap that is consumed either directly as a beverage or is used to
prepare foods (mixing water with a can of soup) and beverages (diluting
frozen juice concentrate). Two generally accepted default values for water
consumption are 2 liters (28.6 g/kg-body wt/day) or 1.5 liters (21.4 g/kg-
body wt/day). The 22.6 g/kg-body wt/day used in this calculation was
derived using water consumption values and self reported body weights
obtained from USDA's 1977-1978 Nationwide Food Consumption Survey.
The other assumption used is assuming that water from the same
source containing the same contaminant level is consumed throughout a
70 year lifetime. Most of the US population moves at some time during
their life and does not live in the same area, drinking from the same water
source for a 70 year lifetime. It could be 'considered as either an over-
estimation or an under-estimation of risk depending on the contaminant
levels in the other sources of drinking water.
The chronic drinking water exposure assessment is based on a small
scale retrospective study conducted in Portage County, Wisconsin, in
which metribuzin and its DK, and DADK metabolites were detected in
groundwater (six wells). All analyses of the DA metabolites were reported
as BQL (Below Quantitation Limit). The information supplied indicated
that sampling occurred from June 1988 through September 1989 with no
samples taken January through April 1989, (i.e. 12 samples for each well).
Analysis was by GC/MS (gas chromatography with a mass-selective
detector) with a specified LOQ (Limit of Quantitation) of 1 ppb. A
monthly concentration for each well was calculated by adding the
detections of metribuzin, DK, and DADK. Concentrations reported as
BQL were averaged in as 0.5 ppb, which is one-half of the LOQ. Then,
the concentrations from the 12 samples for each well were averaged to
obtain a yearly concentration.
The yearly average values calculated for the six wells are:
AW1
AW2
AW3
AW4
4.275 ppb
5.3667 ppb
3.7 ppb
5.25 ppb
30
-------
AW5 3.925 ppb
AW6 5.2 ppb
Exposure was calculated using the equation:
Exposure (mg/kg/day) = (ppb metribuzin + DA + DK + DADK)(10'6)(22.6)
For the general population, the exposure values in mg/kg/day calculated for the
6 wells are:
AW1
AW2
AW3
AW4
AW5
AW6
0.0000966
0.0001212
0.0000836
0.0001186
0.0000887
0.0001175
For children (1-6), the exposure values in mg/kg/day calculated for the 6 wells are:
AW1
AW2
AW3
AW4
AW5
AW6
0.0004275
0.0005366
0.00037
0.000525
0.0003925
0.00052
Metribuzin and its degradates are persistent and mobile. Thus, it
is expected that metribuzin and its degradates would be available for
runoff. Metribuzin has been detected in surface water samples with
concentrations ranging from below the detection limit of 0.05 ppb to 7.6
ppb. No information on detections of metribuzin degradates in surface
water are available. A USGS stream reconnaissance survey of numerous
midwestern streams in 1989, 1994, and 1995 collected samples during the
first major runoff event after application. Thus, these samples could be
considered to represent peak concentrations, not time-weighted averages.
The 90th percentile concentrations for 1989, 1994, and 1995 respectively
were 1.4, 1.2, and 0.5 ppb.
These concentrations are less than the estimated yearly averages for
groundwater, although of the same order of magnitude. Thus, the
exposures would be comparable. Annual means in surface water, unlike
sometimes for groundwater, are typically substantially less than peak
concentrations.
31
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c. Occupational Exposure
An occupational and/or residential exposure assessment is required
for an active ingredient if (1) certain toxicological criteria are triggered and
(2) there is potential exposure to handlers (such as mixers, loaders,
applicators) during use or to persons entering treated sites after application
is complete.
All products containing metribuzin are intended primarily for
occupational use; no products containing metribuzin are intended
primarily for homeowner use. Therefore, a handler assessment for a
residential scenario will not be conducted.
Handler (Mixer/Loader/Applicator) Exposure Scenarios
The Agency has determined that there is a potential for exposures
to mixers, loaders, applicators, or other handlers during usual use-patterns
associated with metribuzin. There are potential exposures to:
mixer/loaders supporting ground, aerial, and chemigation applications of
liquid, wettable powder, and dry-fiowable formulations; mixers/loaders
impregnating fertilizer with metribuzin and supporting impregnated
fertilizer applications; applicators using ground and aerial equipment to
apply as a spray; applicators using granular equipment to apply the
impregnated dry-bulk fertilizer; applicators using high-volume hand
equipment to apply liquid formulations (commercial turfgrass); fiaggers
participating in aerial application of sprays; and persons mixing, loading,
and applying using low-pressure handwand equipment.
Based on the use patterns and potential exposures described above,
ten exposure scenarios for handlers were identified for metribuzin: (1)
mixing/loading the liquid formulation, (2) mixing/loading the dry-flowable
formulation, (3) mixing/loading the wettable powder formulation, (4)
mixing/loading the impregnated dry-bulk fertilizer (5) applying as a spray
with aerial equipment, (6) applying as a spray with groundboom sprayer,
(7) applying the impregnated dry-bulk fertilizer, (8) applying liquid
formulation with high-volume hand equipment, (9) flagging during aerial
spray application, and (10) mixing/loading/applying liquid formulations
with low-pressure handwand equipment. The mixing/loading to support
ground-boom applications scenario is considered worse-case (i.e. highest
exposure) for mixers/loaders supporting ground applications (other than
chemigation) using other types of equipment. Therefore, a separate
assessment for mixer/loaders supporting high volume turfgrass sprayer
applications is not necessary. The assumptions used in defining the
32
-------
exposure scenarios are described in Table 7.
As previously explained, a NOEL for calculating a MOE for dermal
exposure was not identified. Therefore, a dermal exposure occupational
assessment will not be performed. Only a NOEL for calculating an
inhalation exposure was identified. Therefore, only inhalation exposures
for agricultural workers have been assessed. Baseline inhalation exposure
values for uses of metribuzin are presented in Table 8. Note that the
description of the calculations is in the footnotes.
33
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Post-Application Exposures
The Agency has determined that there is potential inhalation exposure to persons entering
treated sites after application is complete. These post-application .exposures may occur (1) to
agricultural workers following applications to vegetables and agronomic crops and to turfgrass
being grown for sod, and (2) to employees and the public following applications to turfgrass in
recreational areas.
No active-ingredient-specific data are available for post-application inhalation exposures
to metribuzin. Although these exposures cannot be estimated, the Agency is not requiring this
data at this time.
3. Risk Assessment
a. Dietary Risk
Acute (1 day) Dietary Risk
As previously stated, the endpoint for acute dietary risk
characterization is the NOEL from the rabbit developmental toxicity study,
15 mg/kg/day (MRID 00087796). Since this endpoint is from a
developmental toxicity study, the population subgroup females (13+ years)
was used to represent women of child-bearing age. It was assumed that
one hundred percent of each commodity was treated with metribuzin
(100% CT), that all residues were at the current or reassessed tolerance
level as specified in Table 46, and that metribuzin is uniformly distributed
in the commodity supply.
The Margin of Exposure (MOE) is a measure of how closely the
estimated high end exposure comes to the NOEL. The MOE for acute
dietary exposure for metribuzin was calculated using the following
formula:
MOE = 15 mg/kg/day
Exposure
The calculated exposure of those individuals most highly exposed is 0.012
mg/kg/day. Thus:
MOE=15jng/kg/day_ =1,250
0.012 mg/kg/day
The MOE is not less than 100; therefore, the Agency considers the MOE
39
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to be sufficiently protective.
Chronic Dietary Risk
The RfD (0.013 mg/kg bwt/day) is used for assessing chronic
dietary risk. It was assumed that one hundred percent of each commodity
was treated with metribuzin (100% CT), that all residues were at the
current or reassessed tolerance level as specified in Table 11, and that
metribuzin is uniformly distributed hi the commodity supply.
The Theoretical Maximum Residue Contribution (TMRC) was
calculated for the U.S. population and 22 subgroups. The TMRC for the
U.S. population is 0.0046 which is 36% of the RfD. The commodity with
the largest contribution to the %RfD is wheat flour which is 7% of the
RfD. The two subgroups with the highest %RfDs are non-nursing infants
(less than 1 year) with the TMRC equal to 0.0081 and %RfD equal to 62%,
and children (1 - 6 years) with the TMRC equal to 0.0097 and %RfD equal
to 75%. For children (1-6 years) the commodity with the largest
contribution to the %RfD is wheat flour which is 16% of the RfD. The
second largest is boneless beef (lean without removable fat) which is 11%
of the RfD.
These calculations represent a "worst case" estimate of dietary
exposure for metribuzin since tolerance level residues and 100 %CT were
assumed. The RfD was not exceeded; therefore, the Agency's chronic
dietary risk concerns are not exceeded.
b. Drinking Water Risk
Acute Drinking Water Risk
The acute MOE for drinking water is calculated in the same manner
as the acute dietary (food source).
MOE=15fmg/kg/dav)
exposure (mg/kg/day)
Chronic Drinking Water Risk
Metribuzin chronic dietary risk from drinking water is calculated
using the RfD, which is 0.013 mg/kg/day, and exposure is based on a
groundwater study. Thus, risk can be estimated using the equation
40
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% RfD = [exposure/RfD](100)
The % RfD for the general population from drinking water are as
follows:
AW1 0.7%
AW2 0.9%
AW3 0.6%
AW4 0.9%
AW5 0.7%
AW6 0.9%
The % RfD for children (1-6) are:
AW1 3%
AW2 4%
AW3 3%
AW4 4%
AW5 3%
AW6 4%
All values are less than 1% of the RfD for the general population
and no more than 4% for the children (1-6). Metribuzin has been detected
in surface water at concentrations less than the estimated yearly averages
for groundwater, although of the same order of magnitude. Thus, the %
RfDs would be comparable. The RfD was not exceeded; therefore, the
Agency's chronic dietary consumption of metribuzin in drinking water
(groundwater and surface water) is not exceeded.
c. Occupational Risk
A NOEL of 58.5 mg/kg/day, based on a 21-day inhaltion toxicity
study, is used for calculating MOEs for the short-term and intermediate
term inhalation scenarios.
MOE =NOEL (58.5 mg/kg/dav)
inhalation exposure
The inhalation MOEs are in Table 9.
41
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Table 9. Baseline Short-Term and Intermediate-Term Inhalation Risk
Exposure Scenario (Seen. #)
Crop
Baseline Daily
Inhalation Dosef
(mg/kg/day)
Baseline Inhalation
MOEb
Mixer/Loader Risk
Mixing AH Liquids For Aerial\Chemigation Application (la)
Mixing All Liquids for Groundboom Application (Ib)
Mixing Dry Flowables for Aerial\Chemigation Application
(2a)
Mixing Dry Flowables for Groundboom Application (2b)
Mixing Wettable Powder for AerialXChemigation Application
(3a)
Mixing Wettable Powder for Groundboom Application (3b)
Sugar Cane/Noncrop
Asparagus
Other Crops
Carrots
Sugar Cane/Noncrop
Asparagus
Other Crops
Carrots
__ Sugar CaneWoncrop_
Asparagus
Other Crops
Carrots
Sugar Cane/Noncrop^
Asparagus
Other Crops
Carrots
__ Sugar Cane/Noncrop___
Asparagus
Other Crops
Carrots
Sugar Cane/Noncrop _
__ ...Asparagus
Other Crops
Carrots
0.03
0.01
0.006
0.002
0.007
0.003
0.001
0.0003
0.02
0.008
0.004
0.001
0,005
0.002
0.0009
* 0.0003
1,30
0.43
0.22
0.05
0,30
0,10
0,05
0.01
1,950
5,850
9,750
29,250
8,357
19,500
58,500
195,000
2,925
7,313
14,625
58,500
11,700
29,250
65,000
195,000
45
136
266
1170
195
585
5.850
42
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Exposure Scenario (Seen. #)
Mixing/Loading Dry Bulk Fertilizer (4)
Crop
Soybeans
Alfalfa
Baseline Daily
Inhalation Dose*
(mg/kg/day)
0.45ฐ
Baseline Inhalation
MOE*
130'
Applicator Risk
Aerial (Liquid Application)-Enclosed Cockpit (5)
Groundboom Tractor (6)
Granular Drop-Type Spreader (Fertilizer Application) (7)
Spreader Truck (Metribuzin Impregnated Fertilizer
Application) (7)
High Volume Hand Sprayer Turf Grass Applications (8)
Flagging (liquid applications) (9)
Sugar Cane/Noncrop
Asparagus
Other Crops
Carrots
Sugar Cane/Noncrop
Asparagus
Other Crops
Carrots
Soybeans
Alfalfa
Soybeans'
Alfalfa
Turf
Flagger Risk
Su|ar Cane/Noncrqp
Asparagus
Other Crops
Carrots
0.002
0.0007 .
0.0003
0.00009
0.005
0.002
0.0009
0.0001
0.001
0.021=
0.00009
0.008
0.003
0.001
0.0003
29,250
83,571
195,000
650,000
11,700
29,250
65,000
585,000
58,500
2,786'
650,000
7,313
19,500
58,500
195,000
Mixer/Loader/Applicator Risk
Low Pressure Hand Wand (10)
Sugar Cfme/Noncrop^
Asparagus
Other Crops
Carrots
0.002
M9.0.?.
0.0004
0.0001
.29,250
65,000
146,250
585,000
The baseline inhalation unit exposure assumes no respirator. Daily Inhalation Dose
(mg/kg/day;) = Daily Inhalation Exposure (mg/day; see Table 8)/70 kg. Note that 70kg
is the Agency's default male body weight
MOE = NOEL (mg/kg/day)/Daily Inhalation Dose (mg/kg/day). The inhalation NOEL
(rat) = 58.5 mg/kg/day.
Registrant supplied data was used because no data was in PHED. Discussion to follow.
43
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All of the MOEs were calculated using the 70 kg default male body
weight. If these MOEs were to be re-calculated using the 60 kg default
female body weight, the MOEs would be slightly smaller. The calculated
MOEs were greater than 100 except for scenario 3a, mixing loading
wettable powders for aerial and chemigation applications, although only
at the highest label rate of 6 Ibs ai/acre. A dust/mist filtering respirator
(MSHA/NIOSH approval number prefix TC-21C) would provide an 80%
protection factor. Thus, exposure would be considered to be 20% of the
baseline inhalation exposure. (See Tables 8 and 9 for an explanation of the
calculations.)
Daily Inhalation Exposure = (43.4)(.2)(0.001) (6) (350) = 18.228
Where: 43.4 is the unit inhalation exposure value for open
mixing/loading of wettable powders (mg/lb/ai) protection
factor.
.2 is the 20% from the protection factor of 80%.
0.001 is the conversion factor from ug to mg.
6 is the application rate (Ibs ai/acre).
350 is the area treated (acres).
Daily Inhalation Dose = 18.228/70 = 0.26
MOE = 58.5/0.26 = 225
A possible alternative to the use of a respirator would be the use of
water soluble packets. Another possible alternative to the use of a
respirator would be to lower the label rate of 6 Ibs ai/acre since label rates
of 2, 1, and 0.25 Ibs ai/acre had MOEs greater than 100.
The Agency has determined that no additional risk mitigation
measures are required at this time for mixers/loaders impregnating dry bulk
fertilizer, or for applicators applying fertilizer impregnated with
metribuzin. This determination is based on information provided to the
Agency by Bayer Corporation in a letter dated August 21, 1996, in which
the processes involved in treating fertilizer with metribuzin and applying
the treated fertilizer were described. The Agency has used surrogate data
from the Pesticide Handlers Exposure Database (PHED, Version 1.1) to
estimate risks to these workers. A more detailed explanation follows.
Mixers/Loaders Impregnating Dry Bulk Fertilizer
At the Agency's request information was provided by Bayer describing the
process for impregnating dry bulk fertilizer with metribuzin and for applying
44
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metribuzin impregnated fertilizer. Bayer stated in their letter, dated August 21,
1996, that the inhalation exposure to the mixer at the dealer site (where the
impregnation takes place) is very similar to that of a worker who performs open
system mixing under typical field use conditions. Therefore, open mixing/loading
of wettable powders was used as the most appropriate scenario for surrogate data.
The unit inhalation exposure value for open mixing/loading wettable powders is
43.4 //g/lb ai (PHED Vl.l, inhalation grades A, B, and C, 44 replicates; medium
confidence).
The amount of fertilizer and metribuzin handled (at the dealer location)
depends on the number of acres to be treated. According to metribuzin labels,
impregnated fertilizer is applied to alfalfa and soybeans at a maximum rate of 1
Ib active ingredient metribuzin per acre. From 200 to 450 Ibs of treated fertilizer
may be applied per acre.
Bayer stated that mixers/loaders can treat 2-3 tons of fertilizer per batch,
and that it takes 15 to 20 minutes to treat one batch. At 1 Ib active ingredient per
200 Ibs fertilizer, each ton of fertilizer would require 10 Ibs of metribuzin active
ingredient.
If mixers/loaders prepare 3 batches per hour (an average of 20 minutes
per batch), 24 batches could be prepared during an 8-hour work period. At 3 tons
per batch and 10 Ibs ai per ton, mixers/loaders would prepare 72 tons in a day and
would handle 720 Ibs of metribuzin. This would equal 144,000 Ibs treated
fertilizer (72 x 2,000 = 144,000) which would be sufficient to treat 720 acres at the
rate of 200 Ibs fertilizer per acre (144,000/200 = 720). This appears to be a
reasonable estimate since Bayer estimates that dealers apply fertilizer to an
average of 700 to 800 acres per day. Bayer indicates that in most cases dealers
make the application because in February and March, when most applications are
made, growers often do not have the appropriate equipment up and running.
Additionally, dealers use spreader trucks which, according to Bayer, provides a
more uniform application. Bayer indicates that dealers can treat from 400 - 1,200
acres per day using spreader trucks, with 700 - 800 being the average.
Risk for mixers/loaders impregnating dry bulk fertilizer was estimated as
follows:
Daily inhalation exposure (mg/day) is calculated using the following equation:
unit exposure (uฃ/lb ai) x Ibs ai handled per day x 1/1,000 (ug to mg conversion)
Given, inhalation unit exposure value = 43.4 ng/lb ai, and
720 Ib ai handled per day.
45
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Therefore,
43.4 ng x 720 Ibs handled/day x 1/1,000 (conversion to mg) = 31.3 mg/day.
Daily inhalation dose (mg/kg/day) is calculated by dividing the daily exposure (mg/day)
by the body weight (bw) of the worker:
Given,
Daily exposure = 31.3 mg/day, and
bw = 70 kg.
Therefore,
31.3 mg/day - 70 kg = 0.45 mg/kg/day.
Risk, in terms of margins of exposure, is calculated by using the following equation:
NOEL (mg/kg/day) / daily dose (mg/kg/day) = MOE.
Given,
NOEL = 58.5 mg/kg/day, and
Daily inhalation dose = 0.45 mg/kg/day.
Therefore, the MOE for handlers mixing/loading to impregnate fertilizer with metribuzin
is
58.5 mg/kg/day / 0.45 mg/kg/day = 130.
Because the MOE for mixers/loaders impregnating fertilizer exceeds 100, the
Agency does not recommend that any additional measures to mitigate risk to these
workers be required.
Applicators Applying Dry Bulk Fertilizer Impregnated with Metribuzin
Bayer also stated, in the August 21,1996 letter, that a grower using conventional
fertilizer-spreading equipment can treat from 100 to 300 acres per day; however, a dealer
using a spreader truck can treat 400 to 1,200 acres per day. It was noted that spreader
trucks are equipped with an activated charcoal filtering system.
Because the Agency has no data for spreader trucks applying treated fertilizer,
"applying using a granular drop-type spreader" was determined to be the most appropriate
46
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surrogate data scenario from PHED for use estimating impregnated dry bulk fertilizer
applicator exposure to metribuzin. The unit exposure value for granular drop-type
spreader applicator is 1.24 ng/lb ai (PHED Vl.l, inhalation acceptable grades, 5
replicates; low confidence). Since spreader trucks may have functioning air filtering
devices, this should be considered a worst case scenario for fertilizer application.
Daily inhalation exposure (mg/day) is calculated using the following equation:
unit exposure (ug/lb ai) x application rate (Ibs ai/acre) x number of acres treated x 1/1,000
(ug to mg conversion)
Given,
inhalation unit exposure value = 1.24 ug/lb ai,
maximum application rate is 1 Ib ai per acre, and
maximum number of acres treated is 1,200
Therefore,
1.24 ug x 1 Ibs ai/acre x 1,200 acres x 1/1,000 (conversion to mg) = 1.49 mg/day.
Daily inhalation dose (mg/kg/day) is calculated by dividing the daily exposure (mg/day)
by the body weight (bw) of the worker:
Given,
Daily exposure = 1.49 mg/day, and
bw = 70 kg.
Therefore,
1.49 mg/day * 70 kg = 0.021 mg/kg/day.
Risk is calculated by using the following equation:
NOEL (mg/kg/day) / daily dose (mg/kg/day) = MOE.
Given,
NOEL = 58.5 mg/kg/day, and
Daily inhalation dose = 0.021 mg/kg/day.
Therefore, the MOE for applicators applying fertilizer impregnated with metribuzin is
47
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58.5 mg/kg/day / 0.021 mg/kg/day = 2,786.
Because the MOB for applicators applying fertilizer impregnated with metribuzin
exceeds 100, the Agency does not recommend that any additional measures to mitigate
risk to these workers be required.
Risk From Post-Application Exposures
There are no data available to address post-application exposure for
persons reentering areas treated with metribuzin. However, because no
dermal endpoints of concern have been identified for metribuzin, the
Agency has no special occupational post-application dermal exposure
concerns. Also, because metribuzin has a low vapor pressure and because
the potential level of inhalation exposure following applications is low, the
Agency has no special inhalation exposure concerns for workers or others
reentering areas following metribuzin applications as long as the entry is
delayed at least until sprays and dusts have settled out of the ah".
Additional Occupational Exposure Studies
No additional occupational exposure studies are required for
reregistration at this time.
d. Food Quality Protection Act (FQPA) Considerations
The FQPA of 1996 amended the FFDCA by setting a new
safety standard for the establishment of tolerances. In determining
whether a tolerance meets the new safety standard, section
408(b)(2)(C) directs EPA to consider information concerning the
susceptibility of infants and children to pesticide residues in food,
and available information concerning aggregate exposure to infants
and children of such residues, as well as the potential for
cumulative effects from pesticide residues and other substances that
have a common mechanism of toxicity.
The FQPA amendments to section 408(b)(2)(C) require
EPA to apply an additional 10-fold uncertainty (safety) unless
reliable data demonstrate that the additional factor is unnecessary
to protect infants and children.
Section 408(b)(2)(D) establishes factors that the Agency
must consider in determining whether the safety standard is met in
deciding to issue or reassess tolerances. These factors include the
48
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consideration of available information on the aggregate exposures
to the pesticide from dietary sources including drinking water as
well as non-occupational exposures such as those derived from
pesticides used in and around the home. The Agency must also
consider the potential cumulative effects of the pesticide for which
a tolerance is being sought as well as other substances that have a
common mechanism of toxicity.
Because metribuzin has food uses, specific consideration of
the risks to infants and children, as well as aggregate exposures and
potential cumulative effects is warranted.
1)
Potential Risks to Infants and Children
In determining whether a safety factor different than the
additional 10-fold factor is or is not appropriate for assessing risks
to infants and children, EPA considers all reliable data and makes
a decision using a weight of evidence approach taking into account
the completeness and adequacy of the toxicity database, the nature
and severity of the effects observed in pre- and post-natal studies,
and other information such as epidemiological data.
For the purpose of assessing pre-and post-natal toxicity of
metribuzin, the Agency has evaluated three developmental studies
and one reproductive study. Based on the current data
requirements, these studies, when considered with other required
guideline toxicity studies, constitute a complete database for
evaluating pre- and post-natal effects for food-use chemicals.
However, as the Agency fully implements the requirements of
FQPA, additional data related to the special sensitivity of infants
and children may be required.
Developmental and Reproductive Effects
The effects observed in the metribuzin developmental and
reproductive studies can be summarized as follows:
In a developmental toxicity study, metribuzin was
administered by gavage on gestation days 6-18 to pregnant Charles
River Crl:CD BR rats. Maternal toxicity was shown at all dose
levels as reduced body weight gain, reduced mean gravid uterine
weights, and decreased food consumption. The maternal toxicity
NOEL is less than 25 mg/kg/day and the maternal toxicity LOEL
49
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is equal to or less than 25 mg/kg/day. For developmental toxicity,
the NOEL is 70 mg/kg/day and the LOEL is 200 mg/kg/day based
on decreased fetal body weight and reduced ossification or
unossified skull bones, ribs, vertebrae, steraebrae, pelvic bones,
and appendages.
In a developmental toxicity study, American Dutch rabbits
were given metribuzin by gavage on gestation days 6-18. Maternal
toxicity was noted at 30 mg/kg/day and above based on decreased
maternal body weight gains on gestation days 18-28 at the mid
dose level and decreased body weight gains, decreased food
consumption and decreased food efficiency on gestation days 7-19
at the high dose level. Developmental toxicity was noted at the
high dose in the form of an increased incidence of irregular spinous
processes. The maternal toxicity NOEL is 10 mg/kg/day and the
maternal toxicity LOEL is 30 mg/kg/day, based on decreased
weight gain on days 18-28. For developmental toxicity, the NOEL
is 30 mg/kg/day and the LOEL is 85 mg/kg/day based on an
increase incidence of irregular spinous processes.
In a repeat developmental toxicity study, New Zealand
white rabbits were given metribuzin by gavage on gestation days
6-18. Maternal systemic toxicity was noted at 45 mg/kg/day, as
reduced body weight gain, and reduced food and water intake.
Additionally, at the highest dose tested (135 mg/kg/day) there was
an increased incidence of abortions and decreased body weights.
The maternal toxicity NOEL is 15 mg/kg/day and the maternal
toxicity LOEL is 45 mg/kg/day based on reduced body weight
gains and reduced food and water consumption. For
developmental toxicity, the NOEL is 15 mg/kg/day and the LOEL
is 45 mg/kg/day based on decreased fetal body weights, increased
number of runts and increased incidence of extra and partial ribs.
In a two-generation reproduction study, Crl:CD BR rats
received feed containing metribuzin. Systemic toxicity in both the
parental animals and the pups was noted at the mid dose as slightly
decreased body weights in the FH high and the F2 mid and high dose
pups. The Fj females had decreased body weight gains during the
gestation period for mid and high doses; F0 and Fj females had
increased body weight during lactation and hypertrophy of
hepatocytes in high dose males and mid and high dose females.
The parental/offspring systemic toxicity NOEL is 1.5 mg/kg/day
and the parental/offspring systemic toxicity LOEL is 7.5 mg/kg/day
50
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based on decreased body weights and body weight gains and
hypertrophy of the hepatocytes.
Uncertainty Factor
In the three metribuzin developmental studies discussed
above, the NOELs for developmental effects are equal to or greater
than the NOELs for maternal effects. Generally, the Agency would
be concerned when developmental effects are seen at doses lower
than those which would cause maternal effects. Thus, for
metribuzin there is no unique sensitivity from pre-natal exposure
based on the current toxicological data requirements. The Agency
concludes that an additional uncertainty factor to account for any
special sensitivity to infants and children is not warranted for the
metribuzin risk assessment.
2) Aggregate (Multipathway) Exposure and Resultant
Risk
In examining aggregate exposure, FQPA directs EPA to
take into account available information concerning exposures from
pesticide residues in food and all other non-occupational exposures.
The primary non-food sources of exposure the Agency looks at
include drinking water (whether from groundwater or surface
water), and exposure through pesticide use in gardens, lawns, or
buildings (residential and other indoor uses). Risk assessments for
aggregate exposure consider both short-term and long-term
(chronic) exposure scenarios, considering the toxic effects which
would likely be seen for each exposure duration.
Short-term aggregate exposure considers high-end spikes in
exposure that could occur during a short time period (typically 1 -
7 days) for a variety of reasons; ex. a lawn/indoor pesticide
application is made on a particular day on which a person would
also consume residues of this same pesticide in the diet (food and
water). To estimate risk, this short-term exposure spike is
compared to pesticide levels at which toxic effects were seen in
short-term toxicity studies.
Similarly, long-term aggregate exposure considers average
exposure to a population over a lifetime. This average exposure is
then compared to pesticide levels at which toxic effects were seen
in long-term (usually chronic) toxicity studies to estimate risk.
51
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Acute Risk:
Acute (1 day) Dietary ffood source): The endpoint for acute
dietary risk characterization is the NOEL from the previously
described rabbit developmental toxicity study, 15 mg/kg/day.
Since this endpoint is from a developmental toxicity study, the
population subgroup females (13+ years) was used to represent
women of child-bearing age. It was assumed that one hundred
percent of each commodity was treated with metribuzin (100%
CT), that all residues were at the current or reassessed tolerance
level and that metribuzin is uniformly distributed in the commodity
supply.
The Margin of Exposure (MOE) is a measure of how
closely the estimated high end acute dietary exposure (0.012
mg/kg/day) comes to the NOEL (15 mg/kg/day). Thus, the MOE
for acute dietary exposure for the population subgroup females
(13+ years) for metribuzin is 1,250 (15 mg/kg/day/ 0.012
mg/kg/day). The MOE is not less than 100; therefore, the Agency
considers the MOE to be sufficiently protective for acute dietary
(food source) risk.
Acute Drinking Water: For the population sub-group females 13+,
the estimated exposure for acute drinking water is 0.0007
mg/kg/day. The MOE is a measure of how closely the estimated
high end acute drinking water exposure (0.0007 mg/kg/day) comes
to the NOEL (15 mg/kg/day). Thus, the MOE for acute .drinking
water exposure for the population subgroup females (13+ years) for
metribuzin is 21,000 (rounded to two significant figures) (15
mg/kg/day/0.0007 mg/kg/day). The MOE is not less than 100;
therefore, the Agency considers the MOE to be sufficiently
protective for acute dietary (drinking water source) risk.
For the population sub-group females 13+, the estimated
exposure for acute dietary (food source) is 0.012 mg/kg/day. The
estimated exposure for acute drinking water is 0.0007 mg/kg/day.
Thus, the total acute dietary exposure (food source + drinking
water) is 0.0127 mg/kg/day. Using this total exposure, the
aggregate MOE for acute exposure for the population sub-group
females 13+ is 1200 (rounded to two significant digits). The MOE
is not less than 100; therefore, the Agency considers the MOE to be
sufficiently protective for total acute dietary exposure.
52
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Chronic Risk:
Chronic Dietary (food source): The RfD (0.013 mg/kg bwt/day) is
used for assessing chronic dietary risk. The Reference Dose for
metribuzin was established at 0.013 mg/kg/day based upon a two-
year feeding study in rats with a NOEL of 1.3 mg/kg/day and an
uncertainty factor of 100. The effect observed at the LOEL (13.8
mg/kg/day) was decreased body weight gains, increased thyroid
and liver weights. The reproductive study with a NOEL of 1.5
mg/kg/day was considered to be a co-critical study.
It was assumed that one hundred percent of each
commodity was treated with metribuzin (100% CT), that all
residues were at the current or reassessed tolerance level, and that
metribuzin is uniformly distributed in the commodity supply.
The Theoretical Maximum Residue Contribution (TMRC)
was calculated for the U.S. population and 22 subgroups. The
TMRC is 36% of the RfD for the U.S. population; 62% of the RfD
for non-nursing infants (less than 1 year); and 75% of the RfD for
children (1-6 years). These later groups represent the two
subgroups with the highest %RfDs. These calculations represent
an over-estimate of chronic dietary exposure for metribuzin since
tolerance level residues and 100 %CT were assumed. Actual risks
will be much lower. The RfD was not exceeded; therefore, the
Agency's chronic dietary (food source) risk is not exceeded.
Chronic Drinking Water: As stated previously, the drinking water
exposure assessment is based on a small scale retrospective study
conducted in Portage County, Wisconsin, in which metribuzin and
its DK, and DADK metabolites were detected in groundwater (six
wells). (For more details see the drinking water exposure and risk
assessments sections.)
For the general population the yearly average
concentrations in well water ranged from 3.7 ppb to 5.3667 ppb,
calculated exposures based on consumption ranged from
0.0000887 mg/kg/day to 0.0001212 mg/kg/day. All values were
less than 1 % of the RfD.
For the chronic dietary risk (food source), the highest %
RfD for a population sub-group was 75% for children (1-6). For
this population sub-group the yearly average concentrations in well
53
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water ranged from 3.7 ppb to 5.3667 ppb, calculated exposures
based on consumption ranged from 0.00037 mg/kg/day to
0.0005366 mg/kg/day. All values were less than 4% of the RfD.
Metribuzin has been detected in surface water at
approximate peak concentrations less than the estimated yearly
averages for groundwater, although of the same order of
magnitude. Peaks in surface water generally are much greater than
means. Thus, the %RfDs would be comparable. Therefore, the
Agency has no concerns for chronic dietary consumption of
metribuzin in groundwater or surface water, but believes that
reserving 1% of the RfD for the general population and 4% of the
RfD for children (1-6) for drinking water to be appropriate
assumptions.
When total chronic dietary risk is assessed for the
population sub-group with the highest %RfDs (children 1-6), the
Agency has concluded that 4 % of the RfD will be reserved for
exposure to residues of metribuzin in drinking water and 75 % of
the RfD will be utilized by exposure to residues of metribuzin in
food commodities. The total chronic dietary risk is 79 % of the
RfD, thus, not exceeding the Agency's risk concern level.
Non-occupational risk
Metribuzin is not labeled for use by homeowners or
certified applicators in the residential setting. However, metribuzin
can be used on turf in public areas such as parks, athletic fields, or
golf courses. Therefore, non-occupational exposure would be
limited to postapplication exposure to persons such as employees
and the public following applications to turfgrass in treated
recreational areas. No active-ingredient-specific data are available
to estimate post-application exposures for persons exposed to
metribuzin-treated turf in recreational areas. However, because no
dermal endpoints of concern have been identified for metribuzin,
the Agency has no special post-application dermal exposure
concerns. The Agency has no inhalation concerns for persons
exposed to metribuzin-treated turf as long as entry is delayed at
least until sprays and dusts have settled out of the air.
Additionally, given the nature of activities and therefore the
exposure in an outdoor public setting, the Agency believes that
such a short-time exposure is very unlikely to contribute any
54
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significant amount to an aggregate risk.
3)
Cumulative Effects
Section 408(b)(2)(D)(v) requires that, when considering
whether to establish, modify, or revoke a tolerance, the Agency
consider "available information" concerning the cumulative effects
of a particular pesticide's residues and "other substances that have
a common mechanism of toxicity." The Agency believes that
"available information" in this context might include not only
toxicity, chemistry, and exposure data, but also scientific policies
and methodologies for understanding common mechanisms of
toxicity and conducting cumulative risk assessments. For most
pesticides, although the Agency has some information in its files
that may turn out to be helpful in eventually determining whether
a pesticide shares a common mechanism of toxicity with any other
substances, EPA does not at this time have the methodologies to
resolve the complex scientific issues concerning common
mechanism of toxicity in a meaningful way. EPA has begun a pilot
process to study this issue further through the examination of
particular classes of pesticides. The Agency hopes that the results
of this pilot process will increase the Agency's scientific
understanding of this question such that EPA will be able to
develop and apply scientific principles for better determining which
chemicals have a common mechanism of toxicity and evaluating
the cumulative effects of such chemicals. The Agency anticipates,
however, that even as its understanding of the science of common
mechanisms increases, decisions on specific classes of chemicals
will be heavily dependent on chemical specific data, much of
which may not be presently available.
Although at present the Agency does not know how to
apply the information in its files concerning common mechanism
issues to most risk assessments, there are pesticides as to which the
common mechanism issues can be resolved. For example,
pesticides that are toxicologically dissimilar to existing chemical
substances (in which case the Agency can conclude that it is
unlikely that a pesticide shares a common mechanism of activity
with other substances) and pesticides that produce a common toxic
metabolite (in which case common mechanism of activity will be
assumed).
In the case of metribuzin, EPA does not have at this time,
55
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available data to determine whether metribuzin has a common
mechanism of toxicity with other substances or how to include this
pesticide in a cumulative risk assessment. Unlike other pesticides
for which EPA has followed a cumulative risk approach based on
a common mechanism of toxicity, metribuzin does not appear to
produce atoxic metabolite produced by other substances. For the
purposes of this tolerance action, therefore, EPA has not assumed
that metribuzin has a common mechanism of toxicity with other
substances.
C. Environmental Assessment
1. Ecological Toxicity Data
a. Toxicity to Terrestrial Animals
(1) Birds, Acute and Subacute
An acute oral toxicity study using the technical grade of the
active ingredient is required to establish the toxicity of a pesticide
to birds. The preferred test species is either mallard duck (a
waterfowl) or bobwhite quail (an upland gamebird). Results of this
test are tabulated below.
Table 10. Avian Acute Oral Toxicity
Species
Northern bobwhite quail 97
(Colima virginlamu)
LD50 (mg/kg)
169.2
Toxicity Category
moderately toxic
MRIDNo.
Author/Year
255025
Lamb/1992
Study
Classification
core
These results indicate that metribuzin is moderately toxic to
avian species on an acute oral basis. The guideline requirement
(71-1) is fulfilled (ACC # 255025).
Two subacute dietary studies using the technical grade of
the active ingredient are required to establish the toxicity of a
pesticide to birds. The preferred test species are mallard duck and
bobwhite quail. Results of these tests are tabulated below.
56
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Table 11. Avian Subacute Dietary Toxicity
Species
Northern bobwhite quail
(Colinus virginianus)
Mallard duck
(Anas platyrhynchos)
% ai LC50 (ppm)
92.6 >4000
99 >5000
Toxicity Category
practically non-toxic
practically non-toxic
MRIDNo.
Author/Year
262228
1986
065507
Burke & Lamb/1977
Study
Classification
core
core
These results indicate that metribuzin is practically non-
toxic to avian species on a subacute dietary basis. The guideline
requirement (71-2) is fulfilled (ACC # 262228, and 065507).
(2) Birds, Chronic
Avian reproduction studies using the technical grade of the
active ingredient are required for metribuzin because the following
conditions are met: (1) birds may be subject to repeated or
continuous exposure to the pesticide, especially preceding or
during the breeding season, (2) the pesticide is stable in the
environment to the extent that potentially toxic amounts may
persist in animal feed, (3) the pesticide is stored or accumulated in
plant or animal tissues, and/or, (4) information derived from
mammalian reproduction studies indicates reproduction in
terrestrial vertebrates may be adversely affected by the anticipated
use of the product. The preferred test species are mallard duck and
bobwhite quail. Results of these tests are tabulated below.
Table 12. Avian Reproduction
Species % ai
Northern bobwhite quail 93.5
(Colinus virginiamts)
Mallard duck 93.5
(Anas platyrhynchos)
NOEC/LOEC
(ppm)
growth: < 62/62
other: 385/>385
368/>368
Endpoints Affected
14-day hatchling body
weight
No other effects reported
None
MRIDNo.
Author/Year
43926601
Hancock/1996
43860501
Hancock/1996
Study Classification
Core
Core
There was a statistically significant reduction in body
weight at 14-days post-hatch at all levels tested in the bobwhite
quail study. No other effects were observed in this study. No
effects were observed at any level tested in the mallard study.
Since there was some doubt as to whether the 14-day body weight
effect was treatment-related in the bobwhite study, and since no
reproductive parameters were affected in either study, the mallard
NOEC of 368 ppm will be used in the risk quotients. The guideline
requirement (71-4) is fulfilled (MRTD # 43926601, and 43860501).
57
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(3) Mammals
Wild mammal testing is required on a case-by-case basis,
depending on the results of lower tier laboratory mammalian
studies, intended use pattern and pertinent environmental fate
characteristics. In most cases, rat or mouse toxicity values obtained
from the Agency's Health Effects Division substitute for wild
mammal testing. These toxicity values are reported in the table
below.
Table 13. Mammalian Toxicity
Species % ai
Test Type
Toxicity Values
MRIDNo.
laboratory rat
(Rattus norvegicus)
Laboratory mouse (Mas
miaculiu)
acute oral
acute oral
2200 mg/kg (female)
2300 mg/kg (male)
711 mg/kg (female)
698 mg/kg (male)
00106158
00106158
The results indicate that metribuzin is slightly toxic
(Category III) to small mammals on an acute oral basis.
(4) Insects
A honey bee acute contact study using the technical grade
of the active ingredient is required for metribuzin because its use
(foliar, postemergent, and on established plants for several
terrestrial food crops) may result in honey bee exposure. Results of
this test are tabulated below.
Table 14. Nontarget Insect Acute Contact Toxicity
Species
LD50
(us/bee)
Toxicity Category
MRIDNo.
Author/Year
Study
Classification
Honeybee
(Apis mcllifera)
tech
60.4
practically non-toxic
028772
1973
The results indicate that metribuzin is practically non-toxic
to bees on an acute contact basis. The guideline requirement (141-
1) is fulfilled (MRID 028772).
b. Toxicity to Aquatic Animals
(1) Freshwater Fish
a. Freshwater Fish, Acute
Two freshwater fish toxicity studies using the
58
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technical grade of the active ingredient are required to
establish the toxicity of a pesticide to fish. The preferred
test species are rainbow trout (a coldwater fish) and bluegill
sunfish (a warmwater fish). Results of these tests are
tabulated below.
Table 15. Freshwater Fish Acute Toxicity
Species %ai LCSO(ppm) Toxicity Category
Rainbow trout
(Oncorhynchus mykiss)
Bluegill sunfish
(Lepomis macrochirus)
90
70
97
50
90
97
50
42
99
76.77
147
92
75.96
131.1
slightly toxic
slightly toxic
slightly toxic
practically non-toxic
slightly toxic
slightly toxic
practically non-toxic
MRIDNo.
Author/Year
40098001
F.L. Mayer/1986
090427
McCann/1984
255025
Lamb/1972
255025
Lamb/1972
40098001
F.L. Mayer/1986
255025
Lamb/1972
255025
Lamb/1972
Study
Classification
core
core
core
core
core
core
core
These results indicate that metribuzin is slightly
toxic to practically non-toxic to freshwater fish on an acute
basis. The guideline requirement (72-1) is fulfilled (ACC
# 255025, 40098001, and 090427).
b. Freshwater Fish, Chronic
A freshwater fish early life-stage test using the
technical grade of the active ingredient is required for
metribuzin because the end-use product may be applied
directly to water or is expected to be transported to water
from the intended use site, and the following conditions are
met: (1) the pesticide is intended for use such that its
presence in water is likely to be continuous or recurrent
regardless of toxicity, (2) any aquatic acute LC50 or EC50
is less than 1 mg/1, (3) the EEC in water is equal to or
greater than 0.01 of any acute LC50 or EC50 value, or, (4)
the actual or estimated environmental concentration in
water resulting from use is less than 0.01 of any acute LC50
or EC50 value and any one of the following conditions
exist: studies of other organisms indicate the reproductive
physiology of fish may be affected, physicochemical
properties indicate cumulative effects, or the pesticide is
persistent in water (e.g., half-life greater than 4 days). The
59
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preferred test species is rainbow trout. Results of this test
are tabulated below.
Table 16. Freshwater Fish Early Life-Stage Toxicity
Species
Rainbow trout
(Oncorhynchus
myklss)
NOEC/LOEC
% ai (ppm)
94 noNOEC
LOEC=3.0
MATC
(ppm)
not
determined
Endpoints
Affected
growth
MRIDNo.
Author/Year
42447801
Gagliano &
Roney/1992
Study
Classification
core
No NOEC was achieved in this study due to effects on
growth at all levels tested. However, since the LOEC was above
exposure estimates calculated at the time of the study, it was
classified as core. The guideline requirement (72-4a) is fulfilled
(MRID 42447801).
A freshwater fish life-cycle test using the technical grade of
the active ingredient is not required for metribuzin.
(2) Freshwater Invertebrates
a. Freshwater Invertebrates, Acute
A freshwater aquatic invertebrate toxicity test using
the technical grade of the active ingredient is required to
establish the toxicity of a pesticide to invertebrates. The
preferred test species is Daphnia magna. Results of this
test are tabulated below.
Table 17. Freshwater Invertebrate Toxicity
Species
Waterflea
(Daplwia magna)
%ai
93
84
LC50/
ECSO (ppm)
4.2
98.5
Toxicity Category
moderately toxic
slightly toxic
MRIDNo.
Author/Year
72083
Roney/1979
34016
1978
Study
Classification
core
supplemental
The results indicate that metribuzin is moderately to
slightly toxic to aquatic invertebrates on an acute basis.
The guideline requirement (72-2) is fulfilled (ACC #
72083).
b. Freshwater Invertebrate, Chronic
A freshwater aquatic invertebrate life-cycle test
60
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using the technical grade of the active ingredient is required
for metribuzin since the end-use product may be applied
directly to water or expected to be transported to water from
the intended use site, and the following conditions are met:
(1) the pesticide is intended for use such that its presence in
water is likely to be continuous or recurrent regardless of
toxicity, (2) any aquatic acute LC50 or EC50 is less than 1
mg/1, or, (3) the EEC in water is equal to or greater than
0.01 of any acute EC50 or LC50 value, or, (4) the actual or
estimated environmental concentration in water resulting
from use is less than 0.01 of any aquatic acute EC50 or
LC50 value and any of the following conditions exist:
studies of other organisms indicate the reproductive
physiology of invertebrates may be affected,
physicochemical properties indicate cumulative effects, or
the pesticide is persistent in water (e.g., half-life greater
than 4 days). The preferred test species is Daphnia magna.
Results of this test are tabulated below.
Table 18. Freshwater Aquatic Invertebrate Life-Cycle Toxicity
Species " % ai
Waterflea 93
(Daphnia magna)
NOEC/LOEC
(ppin)
NOEC=1.29
LOEC = 2.62
MATC
(ppm)
1.84
Endpoints
Affected
# offspring
length
MRIDNo.
Author/Year
42447802
Gagliano &
Bowers/1992
Study
Classification
core
A NOEC was achieved for number of offspring and
length; however, there were effects on weight at all levels
tested, so a NOEC for weight was not achieved. The
guideline requirement (72-4) is fulfilled (MRID #
42447802).
(3) Toxicity to Estuarine and Marine Animals
a. Estuarine and Marine Fish, Acute
Acute toxicity testing with estuarine/marine fish
using the technical grade of the active ingredient is required
for metribuzin because the end-use product is intended for
direct application to the marine/estuarine environment or
the active ingredient is expected to reach this environment
because of its use in coastal counties. The preferred test
species is sheepshead minnow. Results of these tests are
tabulated below.
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Table 19. Estuarine/Marine Fish Acute Toxicity
Species %ai LCSO (ppm)
Toxicity Category
MRIDNo.
Author/Year
Study
Classification
Sheepshead minnow
(Cyprinodon variegatus)
92.6
85
slightly toxic
42094502
Nicholson &
Suprenanat/1986
The results indicate that metribuzin is slightly toxic
to estuarine/marine fish on an acute basis. The guideline
requirement (72-3a) is fulfilled (MRID # 42094502).
b. Estuarine and Marine Fish, Chronic
An estuarine/marine fish early life-stage toxicity test
using the technical grade of the active ingredient is not
required for metribuzin.
c. Estuarine and Marine Invertebrates, Acute
Acute toxicity testing with estuarine/marine
invertebrates using the technical grade of the active
ingredient is required for metribuzin because the end-use
product is intended for direct application to the
marine/estuarine environment or the active ingredient is
expected to reach this environment because of its use in
coastal counties. The preferred test species are mysid
shrimp and eastern oyster. Results of these tests are
tabulated below.
Table 20. Estuarine/Marine Invertebrate Acute Toxicity
Species %ai. LC50/EC50 (ppm)
Eastern oyster
(shell deposition or embryo-
larvae)
(Crasiostrea virginica)
Pink shrimp
(Penaeia duorarum)
92
92
92.6
92.6
92
42
40.7
49.8
52 (shell dep.)
48.3
Toxicity Category
slightly toxic
slightly toxic
slightly toxic
slightly toxic
slightly toxic
MRIDNo.
Author/Year
43851
1975
106197
Heitmuller/1975
42094501
1986
47023411
Dionne &
Suprenant/1986
106197
Heitmuller/1975
Study
Classification
supplemental
core
core
supplemental
core
The results indicate that metribuzin is slightly toxic
to estuarine/marine invertebrates on an acute basis. The
guideline requirements (72-3b and 72-3c) are fulfilled
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(MRID # 106197 and 42094501).
c. Toxicity to Plants
(1) Terrestrial
Terrestrial plant testing (seedling emergence and vegetative
vigor) is required for herbicides that have terrestrial non-residential
outdoor use patterns and that may move off the application site
through volatilization (vapor pressure >1.0 x 10"5mm Hg at 25ฐC)
or drift (aerial, ground, or chemigation) and/or that may have
endangered or threatened plant species associated with the
application site.
Currently, terrestrial plant testing is not required for
pesticides other than herbicides except on a case-by-case basis
(e.g., labeling bears phytotoxicity warnings, incident data, or
literature that demonstrate phytotoxicity).
For seedling emergence and vegetative vigor testing the
following plant species and groups should be tested: (1) six species
of at least four dicotyledonous families, one species of which is
soybean (Glycine max), and the second of which is a root crop, and
(2) four species of at least two monocotyledonous families, one of
which is corn (Zea mays).
Terrestrial Tier II studies are required for all low dose
herbicides (those with the maximum use rate of 0.5 Ibs ai/A or
less). Terrestrial plant testing is required for metribuzin because it
is an herbicide with the majority of use rates at 0.5 Ibs ai/A or less.
Tier II tests measure the response of plants, relative to a
control, at five or more test concentrations. Results of Tier II
toxicity testing on the technical material are tabulated below.
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Table 21. Nontarget Terrestrial Plant Seedling Emergence Toxicity (Tier II)
Species
Monocot- corn
Monocot- onion
Monocot- wheat
Monocot- pea
Dicot- turnip
Dicot- soybean
Dicot- cotton
Dicot- cucumber
Dicot- tomato
Dicot- sorghum
%ai
91.3
91.3
91.3
91.3
91.3
91.3
94.1
91.3
91.3
91.3
EC25
(Ibsai/A)
Endpoint
Affected
0.059 weight
0.020 survival
0.024 % emer. &
weight
not determined
0.008 % emer.
not determined
0.0423 weight
0.029 height
not determined
0.043 weight
NOECorEC05
(Ibs ai/A)
Endpoint
Affected
0.056 weight
0.014 survival
0.014 weight
0.113 weight
0.007 %emer.
0.225 all
0.0281 weight
0.014 height
0.1 13 survival
0.028 weight
MRIDNo.
Author/Year
42447803
Burge/1992
42447803
Burge/1992
42447803
Burge/1992
42447803
Burge/1992
42447803
Burge/1992
42447803
Burge/1992
43208301
Johns/1994
42447803
Burge/1992
42447803
Burge/1992
42447803
Burge/1992
Study Classification
core
core
core
core
core
core
core
core
core
core
For Tier II seedling emergence, turnip is the most sensitive
dicot, and onion and wheat are the most sensitive monocots. The
guideline requirement (123-1) is fulfilled (MRID#43208301 and
42447803).
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Table 22. Nontarget Terrestrial Plant Vegetative Vigor Toxicity (Tier II)
Species
Monocot- corn
Monocot- onion
Monocot- wheat
Monocot- pea
Dicot- turnip
Dicot- soybean
Dicot- cotton
Dicot- cucumber
Dicot- tomato
Dicot- sorghum
%ai
91.3
91.3
91.3
91.3
91.3
91.3
91.3
91.3
91.3
91.3
EC251
(Ibsai/A)
Endpoint
Affected
not determined
0,017 weight
0.041 weight
not determined
0.005 weight
not determined
0.016 weight
0.024 weight
not determined
not determined
NOECorECOS
(Ibs ai/A)
Endpoint
Affected
0.090 none
0.0112
height/weight
0.0225 weight
0.0900 none
0.0028 weight
0.0450 weight
0.0028 weight
0.01 12 weight
0.0900 none
0.0450 weight
MRIDNo.
Author/Year
42447803
Burge/1992
42447803
Burge/1992
42447803
Burge/1992
42447803
Burge/1992
42447803
Burge/1992
42447803
Burge/1992
42447803
Burge/1992
42447803
Burge/1992
424478703
Burge/1992
42447803
Burge/1992
Study Classification
core
core
core
core
core
core
core
core
core
core
1 EC is the effective concentration. EC25 is 25% detrimental effect on plant growth (mass or
rate).
For Tier II vegetative vigor, turnip is the most sensitive
dicot and onion is the most sensitive monocot. The guideline
requirement (123-1) is fulfilled (MRID#42447803).
(2) Aquatic
Aquatic plant testing is required for any herbicide that has
outdoor non-residential terrestrial uses that may move off-site by
runoff (solubility >10 ppm in water), by drift (aerial, ground, or
chemigation), or that is applied directly to aquatic use sites (except
residential). Terrestrial Tier II studies are required for all low dose
herbicides (those with the maximum use rate of 0.5 Ibs ai/A or
less). The following species should be tested at Tier I: Kirchneria
subcapitata and Lemna gibba. The following species should be
tested at Tier II: Kirchneria subcapitata, Lemna gibba,
Skeletonema costatum, Anabaena flos-aquae, and a freshwater
diatom. Aquatic plant testing is required for metribuzin because
it is an herbicide which is relatively mobile (Koc=41), and many of
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the uses are 0.5 Ib ai/A or less.
Results of Tier n toxicity testing on the technical/TEP material are
tabulated below.
Table 23. Nontarget Aquatic Plant Toxicity (Tier II)
Species
Vascular Plants
Duckweed
Lemnagibba
Nonvascular Plants
Green algae
Kirchncria svbcapilata
Marine diatom
Skeletonema costanan
Freshwater diatom
Naviculapelliculosa
Blue-green algae
Anctbaennflos-aquae
% ai EC50 (ppm)
94.2 0.13
94.1 0.021
93.5 0.0087
99.0 0.0119
94.2 0.017
NOECorECOS
(ppm)
0.018
0.004
0.0058
0.0089
0.0097
MRIDNo.
Author/Year
43893501
Boerietal./1995
43133601
Gagliano &
Orr/1994
43867701
Bowers/1995
43826101
Bowers/1995
43893502
Boerietal/1995
Study
Classification
supplemental
core
core
core
supplemental
2.
The Tier n results indicate that Skeletonema costatum is the
most sensitive non-vascular aquatic plant. The guideline
requirement (123-2) is fulfilled for green algae, marine diatom and
freshwater diatom (MRID43867701, 43133601, and 43826101).
The guideline requirement (123-2) is not fulfilled for vascular
plants and blue-green algae; however, enough information on
aquatic plants is available to conduct a risk assessment.
Environmental Fate
a.
Environmental Fate Assessment
Based on available data, the primary routes of degradation of
metribuzin and its main degradates diketo metribuzin (DK) and
deaminated diketo metribuzin (DADK) are microbial metabolism and
photolytic degradation on soil. These compounds will be available for
leaching to ground water and runoff to surface water in many use
conditions. This is because metribuzin and its degradates are not volatile.
In addition, while the rate of photodegradation is rapid for exposed
chemicals, only approximately the top 1mm of soil is actually exposed to
sunlight. Once in ground water, metribuzin is expected to persist due to
its stability to hydrolysis and the lack of light penetration. Conversely,
residues of metribuzin in surface water are not likely to persist in clear,
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well-mixed, shallow surface water with good light penetration since parent
metribuzin degrades rapidly by aqueous photolysis with a calculated half-
life of 4.3 hours. However, if the surface water that receives metribuzin
runoff contains significant sediments, metribuzin is expected to persist
since it is stable to hydrolysis and since light penetration would be limited.
Parent metribuzin is very stable to abiotic hydrolysis and relatively
stable to both aerobic and anaerobic soil metabolism (T1/2's of 106 and 112
days, respectively). Even though direct photolysis in water and on soil
appear to degrade metribuzin rapidly in the laboratory (T1/2's of 4.3 hours
and 2.5 days), only metribuzin that is on the surface of the soil is affected
by photolysis. For that reason, persistence in field soil appears to be more
affected by soil metabolism (aerobic and anaerobic) than by photolysis,
with field half-lives of 40-128 days. Because of the potential for runoff,
photolysis in H2O results are critical. The major photolytic products were
deaminated metribuzin in H2O and pentylidene and hexylidene metribuzin
on soil.
Metribuzin and its degradates diketo metribuzin (DK) and
deaminated diketo metribuzin (DADK) are persistent and mobile in soil.
They have also been found in ground water in 12 states as a result of
normal agricultural applications done under a wide range of
hydrogeological and climatic conditions. According to state monitoring
data from Wisconsin, documented concentrations in ground water are as
high as 54 ppb compared to the Health Advisory of 100 ppb. In a
retrospective ground water monitoring study submitted to the Agency,
metribuzin was detected in ground water at levels ranging up to 2.3 ppb
metribuzin parent and up to 7.6 ppb total metribuzin residues. In surface
waters, metribuzin and its degradates have been found in the Midwestern
U.S. at several ppb.
b. Environmental Fate and Transport
(1) Degradation
Hvdrolvsis (161-1)
Metribuzin was stable in sterile aqueous buffer solutions (pH 5, 7,
and 9) that were incubated in darkness at 25ฐ C. The guideline requirement
was fulfilled (TRID 47017-008).
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Aqueous Photolysis (161-2)
Metribuzin had a half-life of 4.3 hours in pH 6.6 water irradiated
with natural sunlight in Kansas City, MO at 25 ฐC. The identified
degradate was deaminated metribuzin (DA; major degradate), and 3
unknown degradates each comprised <5.2%. Metribuzin was stable in the
dark controls. The guideline requirement was fulfilled (TRID 470173-
007).
Soil Photolysis (161-3)
Metribuzin had a half-life of 2.5 days on sandy loam soil irradiated
outdoors in Kansas City, Missouri at temperatures up to 31 ฐC. The major
degradates were deaminated metribuzin (DA), and the distinct
photoproducts pentylidene metribuzin and hexylidene metribuzin.
Metribuzin was stable in the dark controls. The guideline requirement was
fulfilled (MRID 470173-009).
Aerobic Soil Metabolism (162-1)
Metribuzin degraded with a half-life of 106 days in sandy loam soil.
The identified major degradates were deaminated, diketo metribuzin
(DADK) and diketo metribuzin (DK). The identified minor degradates
were deaminated metribuzin (DA), 2-methyl-DADK, 4-methyl-DADK,
and 3-amino-DA. The guideline requirement was fulfilled (MRID
40367602).
Anaerobic Soil Metabolism (162-2)
Metribuzin had a half-life of 112 days following 30 days of
anaerobic incubation. During the anaerobic portion of the study, the
degradates identified were DADK, DA, DK, and 2-methyl-DADK.
Seventy-eight to 88 % of all radioactivity was in the organic phase from
the methanol extractions of soil and <5 % was in the aqueous phase. The
guideline requirement is fulfilled (MRID 40367603).
(2) Mobility
Leaching-adsorption-desorption (163-1)
Unaged leaching-adsorption-desorption. Parent metribuzin was very
mobile in sandy (0.58 % OC), sandy loam (0.64 % OC), silt loam (1.68 %
OC), and clay loam (1.28 % OC) soils with Freundlich Kads values of 0.25,
68
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0.02,0.22, and 0.20, respectively. Freundlich Kdes values were 0.56, 0.14,
0.51, and 0.41, respectively. K^^ were 47, 3, 15, and 17 and Kocdes values
were 106, 24, 33, and 36, respectively. The N values were 0.92, 0.66,
0.86, and 0.94 for adsorption and 0.76, 0.60, 0.77, and 0.84 for desorption,
respectively. The guideline requirement is fulfilled (MRID 42283001).
Agedleaching-adsorption-desorption. DADK was very mobile in Astatula
sand (0.35 % OC), Arkport sandy loam (1.57 % OC), Drummer silt loam
(1.92 % OC), and Trix clay (0.52 % OC) soils with Freundlich Kads values
of 0.13, 0.47, 0.51, and 0.19, respectively. Kdes values were 0.21, 1.1, 1.2,
and 0.61, respectively, Kocads values were 37, 30, 27, and 36 and ^.des
values were 60, 70, 63, and 117, respectively. N values were 0.86, 0.94,
0.93, and 0.96 for adsorption and 0.80, 0.99,0.95, and 1.09 for desorption,
respectively. The guideline requirement is fulfilled (MRID 43058501).
DK was very mobile in Astatula sand (0.35 % OC), Arkport sandy
loam (1.57 % OCM), Drummer silt loam (1.92 % OC), and Trix clay (0.52
% OC) soils with Freundlich Kads values of 0.15, 0.70, 0.95, and 0.29,
respectively. Kdes values were 0.82, 3.3, 1.13, and 0.56, respectively.
Kocads values were 43, 45, 50, and 56 and Kocdes values were 236, 211, 59,
and 107, respectively. N values were 0.94, 1.0, 0.91, and 0.96 for
adsorption and 0.94, 0.1.07, 0.85, and 0.87 for desorption, respectively.
Aged soil column leaching. Metribuzin and its oxidative degradates were
very mobile in an aged soil column leaching study. Kansas sandy loam
soil spiked with 7.4 ppm of metribuzin was added to sandy loam, silt loam,
and silty clay soils packed in 30-cm columns and leached with 50.8 cm of
water. The amount of applied radioactivity in the leachate was 23, 42, 28,
and 55 % in the silt loam, silty clay, Kansas sandy loam, and California
sandy loam. Most of the radioactivity in the leachate was parent
metribuzin, and the degradates DA, DADK, and DK ranged from 1-3.1 %
of the applied radioactivity. The guideline requirement is fulfilled
(Accession # 263702).
(3) Field Dissipation
Terrestrial (164-1)
The calculated half-lives of metribuzin (Sencor 75 DF) in
sandy loam soils in California were 128 and 40 days at Watsonville
and Fresno, respectively. No leaching of metribuzin or its
oxidative degradate DADK were observed below 12 inches of
depth at either site except for some detections that were probable
69
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c.
contamination or sampling error in the Fresno site. The other
degradates of interest, DA and DK, were not found below 6 inches
of depth (MRID 42236101).
The calculated half-lives of metribuzin (Sencor 75 DF) in
silty clay loam, muck sandy loam, muck clay loam, and sandy loam
soils in Maine, Michigan, and California were 58 to 107 days
(MRID 40380901).
The guideline requirement for the terrestrial field dissipation
study (164-1) is fulfilled.
Retrospective Ground-Water Monitoring (166-2)
Metribuzin and two of its degradates (DK and DADK) were
detected in ground water in a small scale retrospective study
conducted in Portage County, Wisconsin on a minor use crop
(potatoes). Concentrations ranged up to 2.3 ppb parent metribuzin
and 7.6 ppb total residues. Results indicated that metribuzin and its
metabolites were extremely persistent under the conditions
illustrated by this study, and residues were still detected in ground
water over two years after an application (DP Barcode S261873).
New monitoring information in Wisconsin indicates that metribuzin
can leach to ground water at concentration up to 54 ppb or 54
percent of the lifetime Health Advisory. Residues up to 21 ppb
have been detected in Wisconsin drinking water wells. For this
reason, the registrant is required to determine those areas that are
vulnerable to ground-water contamination by metribuzin and
recommend restrictions for its use to prevent continued
contamination at these levels
(4) Spray Drift
The registrant is required to submit data to support the
Spray Drift data requirements because aerial application of
metribuzin may cause damage to nontarget plants due to spray
drift. Bayer Corporation is a member of the Spray Drift Task Force
(SDTF), and therefore, may elect to satisfy these data requirements
through the SDTF. If the registrant wishes to satisfy these data
requirements in this manner, the procedures outlined in PR Notice
90-3 should be followed.
Water Resources
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(1) Ground Water
Background
The requirement for a large-scale ground-water monitoring
study for metribuzin was issued in the June 1985 Registration
Standard. In an amendment to the Standard, the Agency requested
two studies: one to be conducted on a minor use crop and the other
to be conducted on a major use crop. In 1987, Bayer (then Mobay)
had not yet initiated the studies, and the requirement was changed
to a small-scale retrospective study. This monitoring study was
designed to evaluate the impact of continued metribuzin use on
ground water in a vulnerable area. One small-scale retrospective
study was conducted from 1988 to 1989 in Portage County,
Wisconsin on potatoes. Results indicated that metribuzin and its
metabolites were extremely persistent under the conditions
illustrated by this study. Over one year after the final metribuzin
application, up to 2.3 ppb metribuzin parent and up to 7.6 ppb total
metribuzin residues were detected in ground water on the site. Up
to 1.4 ppb metribuzin and 6.7 ppb total residues were still present
over two years after the metribuzin application.
Although the small-scale retrospective study on a major use
crop has not been conducted, the Agency believes that the
determination of those areas that are vulnerable to ground-water
contamination by metribuzin will provide more useful information.
Occurrence of Metribuzin in Ground Water
The Pesticides and Ground Water Database (PGWDB)
indicates that metribuzin has been detected in ground water in 12
states including Connecticut, Iowa, Illinois, Kansas, Maine,
Minnesota, Missouri, New Jersey, Ohio, South Dakota, Virginia,
and Wisconsin because of probable nonpoint source use.
Concentrations in ground water range up to 25.1 ppb (EPA, 1992).
Monitoring for metribuzin in 11 other states did not yield any
detections (EPA, 1992).
Recent evidence suggests that metribuzin is likely to be
detected in ground waters that are vulnerable to contamination in
areas where it is used. According to some of the initial results from
the National Water Quality Assessment (NAWQA) Program of the
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U.S. Geological Survey (Kolpin and others, in preparation),
metribuzin was detected in shallow ground water in both urban and
agricultural areas, but the concentrations were low. The herbicide
was detected at or above 0.004 ppb in five of the nine agricultural
settings examined. The maximum concentration measured in these
studies was 0.30 ppb.
In the Central Sands area of Wisconsin, metribuzin is used
primarily on potatoes. In this area, metribuzin has been detected in
21 out of 27 monitoring wells and in 91 private drinking water
wells. Metribuzin concentrations in ground water are also higher
here; up to 54 ppb has been found in the monitoring wells and up
to 21 ppb found in the drinking water wells. However, most
detections range from about 1 to 5 ppb and the chemical appears to
dissipate quickly in the Central Sands area.
Ground-Water Exposure Assessment
Risk Concerns:
Quality of Ground-water resources:
Metribuzin has been detected in a variety of environments
in 12 states because of nonpoint source use, although generally
below toxicity thresholds for humans and animals. Considering the
widespread use of metribuzin and its detection in many states, the
Agency is concerned about the degradation of water quality that
occurs in metribuzin use areas.
Non-target terrestrial plants:
Concentrations of metribuzin in ground water have not
exceeded the LOG for terrestrial plants. However, levels detected
in ground water have approached approximately 40 percent of the
concentration that could present a risk. Therefore, although there
is not a concern at the present time, in areas where irrigation water
is contaminated with metribuzin, residues could pose a threat to
plants.
Recommendations
1. Metribuzin meets the triggers for classification as a
Restricted Use compound for ground-water concerns, as it
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(2)
is stated in the proposed Restricted Use rule. When the rule
becomes final, metribuzin may be considered a candidate
for restricted use for ground-water concerns.
2. Metribuzin is clearly a compound that will leach to
ground water in vulnerable areas. At the present time, most
of the concentrations found in ground water are low
compared to the levels of concern for human and ecosystem
health. However, in some areas, metribuzin residues have
been found in ground water at relatively high levels and the
Agency is concerned that these concentrations are 54
percent of the HAL. In addition, concentrations up to 21
percent of the HAL have been found in drinking water
wells. For these reasons, the registrant must examine the
metribuzin use area, determine those areas that are
vulnerable to ground-water contamination by metribuzin
and recommend restrictions for its use to prevent continued
contamination at these levels.
3. The Agency is requiring that the registrant develop
educational materials to inform applicators about the
potential problems that metribuzin poses to ground-water
quality.
Surface Water
Metribuzin can contaminate surface water at application via
spray drift. Substantial fractions of applied metribuzin could be
available for runoff to surface waters for several weeks to months
post-application (aerobic soil metabolism half-life of 40 and 106
days, terrestrial field dissipation half-lives of 15 to 149 days).
Although metribuzin is susceptible to photodegradation on soil
(half-life = 2.5 days), its much longer half-lives in terrestrial field
dissipation studies reflect that only the metribuzin in approximately
the top 1 mm of soil is probably exposed to sunlight. The low
soil/water partitioning of metribuzin (SCS/ARS database Koc = 60,
Freundlich binding constants < 1) indicates that most of metribuzin
runoff will occur via dissolution in runoff water (as opposed to
adsorption to eroding soil particulates).
Metribuzin is susceptible to direct aqueous photolysis (half-
life 4.3 hours) which should limit its persistence in the water
column of well mixed, shallow surface water with low light
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attenuation. However, its resistance to abiotic hydrolysis, low
volatilization potential (Henry's Law constant = 3.5 X 10"11
atm*m3/mol), only moderate susceptibility to aerobic and anaerobic
metabolism and only slightly greater susceptibility to anaerobic
metabolism (anaerobic soil metabolism half-life of 25-59 days)
should make it more persistent in other types of surface water,
particularly those with rather long hydrological residence times.
Freundlich soil/water binding constants < 1 and Freundlich
exponents close to one indicate that dissolved concentrations of
metribuzin in sediment pore water will be greater than
concentrations adsorbed to suspended and bottom sediment.
Although dissolved metribuzin concentrations in the water column
will be lower than dissolved concentrations in the sediment pore
water they may be at least somewhat comparable to the
concentrations adsorbed to suspended and bottom sediment.
The major degradates of metribuzin in soil include diketo
metribuzin (DK) and deaminated diketo metribuzin (DADK). Both
are reported to exhibit similar mobility and persistence to that of
the parent. Consequently, like metribuzin, both DK and DADK are
expected to:
(1) be available for runoff for extended periods due to their
persistence in soil,
(2) run off primarily via dissolution in runoff water as opposed
to adsorption to eroding soil,
(3) have dissolved concentrations in the water column
comparable to concentrations adsorbed to suspended and
bottom sediment.
The USGS (Goolsby/Thurman 1991; Goolsby 1995;
Goolsby 1996) conducted reconnaissance surveys of numerous
midwestern streams in 1989, 1990, 1994, and 1995 to determine
pre-application, post-application, and Fall concentrations of various
herbicides including metribuzin. Pre-application and Fall
metribuzin concentrations were much less than 1 ug/L and
generally below the detection limit of 0.05 ug/L. Since post-
application samples were generally collected during the first major
runoff event after application, the concentrations in those samples
may often approximately represent peak concentrations. The 90th
percentile (upper 10th percentile) post-application metribuzin
concentrations for 1989, 1994, and 1995 were 1.4, 1.2 and 0.5
ug/L, respectively. The 90th percentile concentrations for 1989 and
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1994 were comparable, but the 1989 data for 129 streams included
nine concentrations (from 2.2 to 7.6 ug/L) greater than the 1994
and 1995 maximums (1.9 and 1.4, respectively) for 50 of those
streams.
Based upon data on other major use herbicides, peak
metribuzin concentrations in streams may generally be higher than
in rivers and reservoirs but elevated levels of metribuzin may be
present longer in rivers and reservoirs. Concentrations in edge of
the field farm ponds may be substantially greater than in streams.
The USGS (Coupe et al 1995) sampled 8 locations on rivers
within the Mississippi Basin from April 1991 through September
1992 and analyzed the samples for numerous insecticides and
herbicides including metribuzin. Samples were collected twice per
week from May 6 to July 15 1991, once per every two weeks from
November 1991 to February 1992, and once per week at other
times. Filtered (0.7 u) (dissolved) metribuzin was detected above
a detection limit of 0.05 ug/L at all of the locations, but in less than
3% to 28% of the samples at each location. The maximum
concentration detected was 0.38 ug/L. Only 5 additional samples
had metribuzin concentrations > 0.2 ug/L.
The USGS (Goolsby et al 1993) sampled each of 76
midwestem reservoirs at least eight times from April 1992 through
September 93 and analyzed them for various herbicide degradates
and herbicides including metribuzin. Metribuzin was detected
above a detection limit of 0.05 ug/L in 36/732 = 4.9% of the 732
samples collected from 15/76 = 20% of the 77 reservoirs samples.
The only concentrations > 0.5 ug/L were 0.67 ug/L (Huntington
Lake IN), 0.67 ug/L (Mississinewa Lake IN), and 0.91 ug/L, and
1.3 ug/L (Salamonie Lake IN).
The State of Illinois (Taylor 1994) recently summarized
pesticide data for surface water samples collected from 34 stations
from 10/1/85 through 2/15/94. A total of 1278 samples were
analyzed for metribuzin at a detection limit of 0.05 ug/L.
Apparently assuming non-detects were equal to the detection limit,
Illinois reported maximum, 95th percentile and mean unfiltered
sample (total) metribuzin concentrations of 3.7 ug/L, 0.11 ug/L,
and 0.065 ug/L, respectively.
3. Exposure and Risk Characterization
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a. Ecological Exposure and Risk Characterization
Risk characterization integrates the results of the exposure and
ecotoxicity data to evaluate the likelihood of adverse ecological effects.
The means of integrating the results of exposure and ecotoxicity data is
called the quotient method. For this method, risk quotients (RQs) are
calculated by dividing exposure estimates by ecotoxicity values, both acute
and chronic.
RQ = EXPOSURE^TOXICITY
RQs are then compared to OPP's levels of concern (LOCs). These
LOCs are criteria used by OPP to indicate potential risk to nontarget
organisms and the need to consider regulatory action. The criteria indicate
that a pesticide used as directed has the potential to cause adverse effects
on nontarget organisms. LOCs currently address the following risk
presumption categories: (1) acute high - potential for acute risk is high and
regulatory action may be warranted in addition to restricted use
classification (2) acute restricted use - the potential for acute risk is high,
but this may be mitigated through restricted use classification (3) acute
endangered species- the potential for acute risk to endangered species is
high, and regulatory action may be warranted, and (4) chronic risk- the
potential for chronic risk is high, and regulatory action may be warranted.
Currently, the Agency has no procedures for assessing chronic risk to
plants, acute or chronic risks to nontarget insects, or chronic risk from
granular/bait formulations to mammalian or avian species.
The ecotoxicity test values (i.e., measurement endpoints) used in
the acute and chronic risk quotients are derived from the results of required
studies. Examples of ecotoxicity values derived from the results of short-
term laboratory studies that assess acute effects are: (1) LC50 (fish and
birds) (2) LD50 (birds and mammals (3) EC50 (aquatic plants and aquatic
invertebrates) (4) EC25 (terrestrial plants) and (5) EC05 or NOEC
(endangered plants). Examples'of toxicity test effect levels derived from
the results of long-term laboratory studies that assess chronic effects are:
(1) LOEC (birds, fish, and aquatic invertebrates) (2) NOEC (birds, fish and
aquatic invertebrates) and (3) MATC (fish and aquatic invertebrates). For
birds and mammals, the NOEC value is generally used as the ecotoxicity
test value in assessing chronic effects. Other values may be used when
justified. Generally, the MATC (defined as the geometric mean of the
NOEC and LOEC) is used as the ecotoxicity test value in assessing chronic
effects to fish and aquatic invertebrates. However, the NOEC is used if the
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measurement end point is production of offspring or survival.
Risk presumptions, along with the corresponding RQs and LOCs
are tabulated below.
Table 24. Risk Presumptions for Terrestrial Animals
Risk Presumption RQ
LOG
Birds
Acute High Risk
Acute Restricted Use
Acute Endangered Species
Chronic Risk
Wild Mammals
Acute High Risk
Acute Restricted Use
Acute Endangered Species
Chronic Risk
EECVLC50 or LDSO/sqft or LOSO/day1 0.5
EEC/LC50 or LD50/sqft or LD50/day (or LD50 < 50 mg/kg) 0.2
EEC/LC50orLD50/sqftorLD50/day 0.1
EEC/NOEC 1
EEC/LC50orLD50/sqftorLD50/day 0.5
EEC/LC50 or LDSO/sqft or LD50/day (or LD50 < 50 mg/kg) 0.2
EEC/LC50 or LDSO/sqft or LD50/day 0.1
EEC/NOEC 1
1 abbreviation for Estimated Environmental Concentration (ppm) on avian/mammalian food items
1 me/ff 3 mg of toxicant consumed/day
LD50 * wt. of bird LD50 * wt. of bird
Table 25. Risk Presumptions for Aquatic Animals
Risk Presumption
Acute High Risk
Acute Restricted Use
Acute Endangered Species
Chronic Risk
RQ
EECYLCSOorECSO
EEC/LC50orEC50
EEC/LC50orEC50
EEC/MATCorNOEC
LOG
0.5
0.1
0.05
1
1 EEC = (ppm or ppb) in water
Table 26. Risk Presumptions for Plants
Risk Presumption
RQ
LOG
Acute High Risk
Acute Endangered Species
Acute High Risk
Acute Endangered Species
Terrestrial and Semi-Aquatic Plants
EECVEC25
EEC/ECOSorNOEC
Aquatic Plants
EEC2/EC50
EEC/EC05 or NOEC
1 EEC = lbsai/A
2 EEC = (ppb/ppm) in water
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(1) Exposure and Risk to Nontarget Terrestrial Animals
For pesticides applied as a nongranular product (e.g., liquid, dust), the
estimated environmental concentrations (EECs) on food items following product
application are compared to LC50 values to assess risk. The predicted 0-day
maximum and mean residues of a pesticide that may be expected to occur on
selected avian or mammalian food items immediately following a direct single
application at 1 Ib ai/A are tabulated below.
Table 27. Estimated Environmental Concentrations on Avian and Mammalian Food Items (ppm) Following a Single
Application at 1 Ib ai/A)
EEC (ppm)
EEC (ppm)
Food Items Predicted Maximum Residue1 Predicted Mean Residue!
Short grass
Tall grass
Broadleaf/forage plants, and small insects
240
110
135
15
85
36
45
7
1 Predicted maximum and mean residues are for a 1 Ibs ai/a application rate and are based on Hoerger and Kenaga (1972) as modified by Fletcher
Predicted residues (EECs) resulting from multiple
applications are calculated in various ways. For the purpose of
metribuzin the following procedure was used:
(a) Birds
The acute risk quotients for broadcast applications of
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nongranular products are tabulated below.
Table 28. Avian Acute Risk Quotients for a Single Application of Nongranular Products (Broadcast) Based on a quail LC50 of 4000.
Site/Application
Method
Application
Rate
(Ibs ai/A)
Food Items
Maximum EEC
(ppm)
LC50 (ppm)
Acute RQ
(EEC/LCSO)
sugarcane 6.0
aerial
Short
grass
Tall
grass
Broadleaf
1,440
660
810
4000
4000
4000
0.36
0.17
0.20
potato
ground
0.9975
sugarcane
ground
4.025
plants/Insects
Seeds 90
short grass 239
Tall grass 110
Broadleaf plants/Insects 135
Seeds 15
Short 966
grass
Tall 443
grass
Broadleaf 543
plants/Insects
Seeds 60
4000
4000
4000
4000
4000
4000
4000
4000
4000
0.02
0.06
0.03
0.03
0.00
0.24
0.11
0.14
0.02
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Table 29. Avian Acute Risk Quotients for Multiple Applications o f Nongranular Products (Broadcast) Based on a quail LC50 of 4000 ppm.
EECs were calculated with the FATE program using the soil metabolic half-life of 106 days.
Site/Application
Method
turf
ground
sugarcane
ground
Application
Rate in Ibs ai/A
(No. of
Applications)
0.5(2)
4(2)
Food Items
Short
grass
Tall
grass
Broadleaf
plants/Insects
Seeds
Short
grass
Tall
grass
Broadleaf
plants/Insects
Seeds
Maximum EEC
(ppm)
235
108
132
15
1836
842
1033
115
LC50 (ppm)
4000
4000
4000
4000
4000
4000
4000
4000
Acute RQ
(EEC/LC50)
0.06
0.03
0.03
0.00
0.46
0.21
0.26
0.03
The results indicate that for broadcast applications of
nongranular products, avian acute restricted use and endangered
species levels of concern are exceeded at registered maximum
application rates equal to or above 4.0 Ibs ai/A.
The chronic risk quotients for broadcast applications of
nongranular products are tabulated below.
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Table 30. Avian Chronic Risk Quotients for Nongranular Products (Broadcast) Based on a mallard reproduction NOEC of
368 ppm.
Site/Application
Method
Sugarcane
aerial
Turf
ground
Application
Rate in Ibs ai/A
(No. of
Applications)
4(2)
0.5(2)
Food Items
Short
grass
'Tall
grass
Broadleaf
plants/Insects
Seeds
Short
grass
Tall
grass
Broadleaf
plants/Insects
Seeds
Maximum EEC
(ppm)
1836
842
1033
115
235
107
132
15
NOEC (ppm)
368
368
368
368
368
368
. 368
368
Chronic RQ
(EEC/NOEC)
4.99
2.29
2.81
0.31
0.64
0.29
0.36
0.04
The above results indicate that for broadcast applications of
nongranular products, the avian chronic level of concern is
exceeded at registered maximum application rates equal to or
above 4.0 Ibs ai/A. If the bobwhite growth NOEC of 62 ppm is
used, all rates equal to or greater than 0.5 would exceed the chronic
level of concern; however, since there was some doubt whether the
effects seen on hatchling growth in the bobwhite study were truly
treatment-related, and no effects of this nature were observed in the
mallard study, the mallard reproductive NOEC of 368 ppm was
used.
(b)
Mammals
Birds and mammals have similar responses to xenobiotics,
their differences being more quantitative rather than qualitative.
Since metribuzin does not present an acute risk to endangered
birds, mammals are also presumed to be protected.
Estimating the potential for adverse effects to wild
mammals is based upon EEB's draft 1995 SOP of mammalian risk
assessments and methods used by Hoerger and Kenaga (1972) as
modified by Fletcher et dl. (1994). The concentration of
metribuzin in the diet that is expected to be acutely lethal to 50%
of the test population (LC50) is determined by dividing the LD50
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value (usually rat LD50) by the percent of body weight consumed.
A risk quotient is then determined by dividing the EEC by the
derived LC50 value. Risk quotients are calculated for three
separate weight classes of mammals (15, 35, and 1000 g), each
presumed to consume four different kinds of food (grass, forage,
insects, and seeds). The acute risk quotients for broadcast
applications of nongranular products are tabulated below.
Table 31. Mammalian (Herbivore/Insectivore) Acute Risk Quotients for Single Application of Nongranular Products
(Broadcast) Based on a rat LD50 of 2200 mg/kg.
Site/
Application
Method/
Rate
in Ibs ai/A
Sugarcane
aerial
6
6
6
Potato
aerial
1
1
1
1 RQ =
Body
Weight
(g)
15
35
1000
15
35
1000
EEC (me/kg)
%Body
Weight
Consumed
95
66
15
95
66
15
Rat
LD50
mg/kg
2200
2200
2200
2200
2200
2200
EEC
Short
Grass
1440
1440
1440
240
240
240
EEC
Forage &
Small
Insects
810
810
810
135
135
135
EEC
Large
Insects
90
90
90
15
IS
15
Acute
RQ
Short
Grass
0.62
0.43
0.10
0.10
0.07
0.02
Acute RQ
Forage
& Small
Insects
0.35
0.24
0.06
0.06
0.04
0.00
Acute RQ
Large
Insects
0.04
0.03
0.01
0.01
0.00
0.00
LD50 (mg/kg)/ % Body Weight Consumed
Table 32. Mammalian (Granivore) Acute Risk Quotients for Single Application of Nongranular Products (Broadcast)
Based on a rat LD50 of 2200 mg/kg.
Site/
Application
Method/Rate in
Ibs ai/A
Sugarcane
aerial
6
6
6
Potato
aerial
1
1
1
Body
Weight
fe)
15
35
1000
15
35
1000
%Body
Weight
21
15
3
21
15
3
Rat
LD50
(mg/kg)
2200
2200
2200
2200
2200
2200
EEC
Seeds
90
90
90
15
15
15
Acute RQ
Seeds
0.01
0.01
0.00
0.00
0.00
0.00
1 RO = EEC (me/feel
LD50 (mg/kgy % Body Weight Consumed
82
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Table 33. Mammalian (Herbivore/Insectivore) Acute Risk Quotients Multiple Applications of Nongranular Products
(Broadcast) Based on a rat LD50 of 2200 rag/kg.
Site/
App. Method/
Rate in Ibs ai/A
(No. of Apps.)
Sugarcane
aerial
4(2)
4(2)
4(2)
Turf
ground
0.5(2)
0.5(2)
0.5(2)
Body
Weight
(g)
15
35
1000
15
35
1000
% Body
Weight
Consumed
95
66
15
95
66
15
Rat
LD50
mg/kg
2200
2200
2200
2200
2200
2200
EEC
Short
Grass
1836
1836
1836
235
235
235
EEC
Forage &
Small
Insects
1033
1033
1033
132
132
132
EEC
Large
Insects
115
115
115
15
15
15
Acute
RQ
Short
Grass
0.79
0.55
0.13
0.10
0.07
0.02
Acute RQ
Forage
& Small
Insects
0.45
0,31
0.07
0.06
0.04
0.01
Acute RQ
Large
Insects
0.05
0.03
0.01
0.01
0.00
0.00
1 RO = EEC (me/kg)
LD50 (mg/kg)/ % Body Weight Consumed
Table 34. Mammalian (Granivore) Acute Risk Quotients for Multiple Applications Nongranular Products (Broadcast)
Based on a rat LD50 of 2200 mg/kg.
Site/
App. Method/ Rate
in Ibs ai/A
(No. of Apps.)
sugarcane
aerial
4(2)'
4(2)
4(2)
turf
ground
0.5(2)
0.5(2)
0.5(2)
Body
Weight
(g)
15
35
1000
15
35
1000
% Body
Weight
Consumed
21
15
3
21
15
3
Rat
LD50
(mg/kg)
2200
2200
2200
2200
2200
2200
EEC
Seeds
115
115
115
15
15
15
Acute RQ
Seeds
0.01
0.01
0.00
0.00
0.00
0.00
1 RO= EEC(mefke)
LD50 (mg/kg)/ % Body Weight Consumed
The results indicate that for broadcast applications of
nongranular products, acute high risk LOCs are exceeded for small
herbivorous/insectivorous mammals at application rates greater
than or equal to 4.0 Ibs ai/A. Restricted use levels of concern are
83
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also exceeded for small herbivorous/insectivorous mammals at
application rates greater than or equal to 4.0 Ibs ai/A. Endangered
species levels of concern are exceeded for
herbivorous/insectivorous small mammals at application rates
greater than single applications of 1.0 Ib ai/A or multiple
applications of 0.5 Ibs ai/A or greater.
The chronic risk quotients for broadcast applications of
nongranular products are tabulated below.
Table 35. Mammalian Chronic Risk Quotients for Nongranular Products (Broadcast) Based on a rat NOEC of 30 ppm in a 2-generation
reproduction study. EECs were generated using the FATE program, using the aerobic soil metabolism half-life of 106 days.
Site/Application
Method
Application
Rate in Ibs ai/A
(No. of Apps.)
Food Items
Maximum EEC
(ppm)
NOEC (ppm)
Chronic RQ
(EEC/NOEC)
Sugarcane
aerial
4(2)
Potato
ground
Short 1836
grass
Tall 842
grass
Broadleaf 1033
plants/Insects
Seeds 115
Short grass 240
Tall grass 110
Broadleaf plants/Insects 135
Seeds 15
30
30
30
30
30
30
30
30
61.20
28.07
34.43
3.83
8.00
3.67
4.50
0.50
Turf
ground
0.5 (2) Short 235
grass
Tall 107
grass
Broadleaf 132
plants/Insects
15
Seeds
30 7.83
30 3.57
30 4.4
30 0.5
The above results indicate that for broadcast applications of
nongranular products, the chronic level of concern for small
mammals is exceeded at registered application rates equal'to or
above 0.5 Ibs ai/A.
(c) Insects
Currently, the Agency has no procedure for assessing risk
to nontarget insects. Results of acceptable studies are used for
84
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recommending appropriate label precautions.
(1) Exposure and Risk to Nontarget Freshwater Aquatic
Animals
The Agency calculates EECs using the GENeric Expected
Environmental Concentration Program (GENEEC). The resultant
EECs, termed GEECs, are used for assessing acute and chronic
risks to aquatic organisms. Acute risk assessments are performed
using either 0-day GEEC values for single applications or peak
(GEEC) values for multiple applications. Chronic risk assessments
are performed using the 21-day GEECs for invertebrates and 56-
day GEECs for fish.
The GENEEC program uses a few basic environmental fate
chemical parameters and pesticide label application information to
provide a rough estimate of the expected environmental
concentrations following treatment of 10 hectares. The model
calculates the concentration of pesticide in a one hectare, two meter
deep pond, taking into account the following: (1) adsorption to soil
or sediment (2) soil incorporation (3) degradation in soil before
washoff to a water body and (4) degradation within the water body.
The model also accounts for direct deposition of spray drift into the
water body (assumed to be 1% and 5% of the application rate for
ground and aerial applications, respectively). (When multiple
applications are permitted: The interval between applications is
included in the calculations. The environmental fate parameters
used in the model for this pesticide are: soil Koc = 41, solubility =
1200 ppm, aerobic soil metabolism half-life =106 days, hydrolysis
(n/a~"stable"), water photolysis = 4.3 hours, and aquatic
metabolism (n/a). GEECs are tabulated below.
85
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Tabl&36. Estimated Environmental Concentrations (EECs) For Aquatic Exposure
Site
GENEEC
Sugarcane
Sugarcane
Turf
Peas
Application
Method
aerial application of
liquid formulation
ground unincorporated
ground unincorporated
ground incorporated
Application
Rate
(Ibs ai/A)
6.00
4.00
0.50
0.50
# of Apps./
Interval
Between Apps.
1
2 (14 days)
2 (7 days)
1
Initial
(PEAK)
EEC
(ppm)
0.39
0.07
0.024
0.024
21-day
EEC
(ppm)
0.24
0.13
0.043
0.015
56-
day
EEC
(ppm)
0.12
0.10
0.034
0.008
(a) Freshwater Fish
Acute and chronic risk quotients are tabulated
below.
Table 37. Risk Quotients for Freshwater Fish Based On a Rainbow Trout LC50 of 42 ppm and a Rainbow Trout LOEC
of 3.0 ppm.
Site/
Application
Method/Rate in Ibs
ai/A (No. of Apps.)
sugarcanp/aeriai
6(1)
sugarcane/ground
unincorp,
4(2)
turf/ground unincorp.
0.5(2)
peas/ground incorp,
0.5(1)
LCSO
(ppm)
42
42
42
42
LOEC
(ppm)
3
3
3
3
EEC
Initial/Peak
(ppm)
0.39
0.07
0.024
0.024
EEC
56-Day
(ppm)
0.12
0.10
0.034
0.008
Acute RQ
(EEC/LC50)
0.01
0.00
0.00
0.00
Chronic RQ
(EEC/NOEC or
MATC)
0.04
0.03
0.01
0.00
The results indicate that no acute or chronic levels of
concern for freshwater fish are exceeded at any registered
application rate.
(b) Freshwater Invertebrates
The acute and chronic risk quotients are tabulated
below.
86
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Table 38. Risk Quotients for Freshwater Invertebrates Based On a Daphnid EC50 of 4.2 ppm and a Daphnid NOEC of
1.29 ppm.
Site/
Application Method/
Rate in Ibs ai/A
(No. of Apps.)
sugarcane/aerial
6(1)
sugarcane/ground
unincorp.
4(2)
turf/ground unincoip.
0.5 (2)
peas/ground incorp.
0.5(1)
LC50
(ppm)
4.2
4.2
4.2
4.2
NOEC
(ppm)
1.29
1.29
1.29
1.29
EEC
Initial/Peak
(ppm)
0.39
0.07
0.024
0.024
EEC
21-Day
Average
0.12
0.10
0.043
0.008
Acute RQ
(EEC/LC50)
0.09
0.02
0.00
0.01
Chronic RQ
(EEC/NOEC or
MATC)
0.09
0.08
0.01
0.01
The results indicate that no acute or chronic level of
concern is exceeded for freshwater invertebrates at any
registered application rate.
(c) Estuarine and Marine Animals
The acute risk quotients are tabulated below.
Table 39. Risk Quotients for Estuarine/Marine Fish Based on a Sheepshead Minnow LC50 of 85 ppm.
Site/
Application Method
Sugarcane/
aerial
Sugarcane/
ground unincorp.
Turf?
ground
unincorp.
Peas/
ground incorp.
Rate in Ibs ai/A (No. of
Apps.)
6(1)
4(2)
0.5 (2)
0.5 (1)
LC50
(ppm)
85
85
85
85
EEC
Initial/
Peak
(ppm)
0.39
0.07
0.024
0.024
Acute RQ
EEC/LC50
0.00
0.00
0.00
0.00
The results indicate that no acute level of concern is
exceeded for estuarine/marine fish at any registered
application rate.
The acute risk quotients for estuarine/marine
87
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invertebrates are calculated below.
Table 40. Risk Quotients for Estuarine/Marine Aquatic Invertebrates Based on a Oyster EC50 of 40.7 ppm.
Site/
Application Method
Sugarcane/
aerial
Sugarcane/
ground unincorp.
Turf/
ground
unincorp.
Peas/
Rate in Ibs as/A (No. of
Apps.)
6(1)
4(2)
0.5 (2)
0.5 (1)
LC50
(ppm)
40.7
40.7
40.7
40.7
EEC
Initial/
Peak
(ppm)
0.39
0.07
0.024
0.024
Acute RQ
(EEC/LC50)
0.01
0.00
0.00
0.00
The results indicate that no acute level of concern is
exceeded for estuarine invertebrates any registered
application rate.
(2) Exposure and Risk to Nontarget Plants
(a) Terrestrial and Semi-aquatic
Terrestrial and semi-aquatic plants may be exposed
to pesticides from runoff, spray drift or volatilization.
Semi-aquatic plants are those that inhabit low-lying wet
areas that may be dry at certain times of the year. The
Agency's runoff scenario is: (1) based on a pesticide's
water solubility and the amount of pesticide present on the
soil surface and its top one inch (2) characterized as "sheet
runoff' (one treated acre to an adjacent acre) for terrestrial
plants (3) characterized as "channelized runoff (10 treated
acres to a distant low-lying acre) for semi-aquatic plants
and (4) based on % runoff values of 0.01, 0.02, and 0.05 for
water solubility of <10 ppm, 10-100 ppm, and >100 ppm,
respectively.
Spray drift exposure from ground application is
assumed to be 1% of the application rate. Spray drift from
aerial, airblast, forced-air, and chemigation applications is
assumed to be 5% of the application rate.
EECs are calculated for the following application
88
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methods: (1) unincorporated ground applications, (2)
incorporated ground application, and (3) aerial, airblast,
forced-air, andchemigationapplications. Estimated
environmental concentrations for terrestrial and semi-
aquatic plants are tabulated below.
Table 41. Estimated Environmental Concentrations (Ibs ai/A) For Terrestrial and Semi-Aquatic Plants for a Single
Application
Site/ Application
Method/No, of
Apps./Rateof
Application in Ibs
ai/A
Minimum Channelized
Incorporation Runoff Sheet Run-off Run-off Drift
Depth (in) Value (Ibs ai/A) (Ibs ai/A) (Ibs ai/A)
Total
Total Loading to
Loading to Semi-aquatic
Adjacent Area
Area (Channel
(Sheet Run- Run-off+
off+Drift) Drift)
Sugarcane
Unincorporated
aerial
6.0
Peas
Incorporated
Ground
0.5
Tomato,
Chemigation
0.05 0.30
0.05 0.03
0.05 0.05
3.00
0.30
0.50
0.06
0.05
0.36
0.03
0.10
3.06
0.30
0.55
The EC25 value of the most sensitive species in the
seedling emergence study is compared to runoff and drift
exposure to determine the risk quotient for those exposure
scenarios. The EC25 value of the most sensitive species in
the vegetative vigor study is compared to the drift exposure
to determine the risk quotient for that exposure scenario.
EECs and acute high risk quotients for terrestrial and
semi-aquatic plants based on a single application are
tabulated below.
89
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Table 42. Acute High Risk Quotients from a Single Application for Terrestrial and Semi-Aquatic Plants Based On a
Turnip Emergence EC25 of 0.008 Ibs ai/A and a Turnip Vegetative Vigor EC25 of 0.005 Ibs ai/A.
Site, Method
and Rate of
Application
(Ibs ai/A)
Sugarcane
Unincorp,
Ground
6,0
Peas
Incorp.
Ground
0.5
Tomato,
Chemiga-
tion
1
Seedling
Emergence Vegetative
EC25 Vigor EC25
(Ibs ai/A) (Ibs ai/A)
0,008 0.005
0.008 0.005
0.008 0.005
Total
Loading to
Adjacent
Area
Drift (Ibs (Sheet
ai/A) Runoff+
Drift)
0.3 0.36
0.03
0.05 0.1
Total
Loading to
Semi-aquatic
Area
(Channelized
Run-off+
Drift)
3.06
0.30
0.55
Emer-
gence
RQ
Terres-
trial
Plants
45.00
3.75
12.50
Emer-
gence
RQ
Semi-
Aquatic
Plants
382.50
37.50
68.75
Vegeta-
tive Vigor
, RQ
Terrestrial
and Semi-
Aquatic
Plants
60.00
0.00
10.00
The NOEC or EC05 (if a NOEC is unavailable)
value of the most sensitive species in the seedling
emergence study is compared to runoff and drift exposure
to determine the endangered species risk quotient for those
exposure scenarios. The NOEC or EC05 value of the most
sensitive species in the vegetative vigor study is compared
to the drift exposure to determine the endangered species
risk quotient for that exposure scenario.
EECs and acute (endangered species) risk quotients
for terrestrial and semi-aquatic plants based on a single
application are tabulated below.
90
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Table 43. Acute Endangered Species Risk Quotients from a Single Application for Terrestrial and Semi-Aquatic
Plants Based On a Turnip Emergence NOEC of 0.007 Ibs ai/A and a Turnip Vegetative Vigor NOEC of 0.0028 Ibs
ai/A.
Site, Method
and Rate of
Application
(Ibs ai/A)
Sugarcane
Unincorp.
Ground
6
Peas
Incorp.
Ground
0.5
Tomato,
Chemiga-
tion
1
Seedling
Emergence
NOEC or
EC05
(Ifas ai/A)
0.007
0.007
0.007
Vegetative
Vigor
NOEC or Drift
EC05(lbs (Ibs
ai/A) ai/A)
0.0028 0.30
0.0028
0.0028 0.05
Total
Loading to
Adjacent
Area
(Sheet
Runoff+
Drift)
0.36
0.03
0.1
Total
Loading to
Semi-aquatic
Area
(Channelized
Run-off+
Drift)
3.06
0.3
0.55
Emer-
gence
RQ
Terres-
trial
Plants
51.43
4.29
14.29
Emer-
gence
RQ
Semi-
Aquatic
Plants
437.14
42.86
78.57
Vegeta-
tive
Vigor
RQ
Terres-
trial and
Semi-
Aquatic
Plats
107.14
0.00
17.86
The results indicate that for a single application,
acute high risk and endangered species levels of concern
are exceeded for terrestrial plants at a registered maximum
single application rate equal to or above 0.5 Ibs ai/A. For
semi-aquatic plants, acute high risk and endangered species
levels of concern are exceeded at a registered maximum
single application rate equal to or above 0.5 Ibs ai/A. Since
all registered rates for multiple applications are greater than
or equal to 0.5 Ibs ai/A, all registered multiple application
rates will also exceed acute high risk, restricted use and
endangered species levels of concern. Currently, the
Agency does not have a procedure for assessing chronic
risk to terrestrial and semi-aquatic plants.
(b) Aquatic
Exposure to nontarget aquatic plants may occur
through runoff or spray drift from adjacent treated sites or
directly from such uses as aquatic weed or mosquito larvae
control. An aquatic plant risk assessment for acute high
risk is usually made for aquatic vascular plants from the
surrogate duckweed Lemnagibba. Non-vascular high acute
91
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aquatic plant risk assessments are performed using either
algae or a diatom, whichever is the most sensitive species.
An aquatic plant risk assessment for acute- endangered
species is usually made for aquatic vascular plants from the
surrogate duckweed Lemna gibba. Runoff and drift
exposure is computed from GENEEC. The risk quotient is
determined by dividing the pesticide's initial or peak
concentration in water by the plant EC50 value.
Acute risk quotients for vascular and non-vascular
plants are tabulated below.
Table44, Acute Risk Quotients for Aquatic Plants based upon a Duckweed &mna gibba) EC50 of0.13 ppm and a Marine Diatom
(Skeletonema costotum) EC50 of 0.0087 ppm.
Site/ Application Method/ Rate of
Application in Ibs ai/A (No. of Apps.)
Sugarcane
Aerial
6(1)
Peas
Incorp. Ground
0.5(1)
Turf
Uninc. ground
0,5(2)
Test Species
duckweed
diatom
duckweed
algae or diatom
duckweed
algae or diatom
EC50
(ppm)
0.13
0.0087
0.13
0.0087
0.13
0.0087
EEC
(ppm)
0.39
0.39
0.024
0.024
0.024
0.024
RQ
(EEC/
EC50)
3.00
44.83
0.18
2.76
0.18
2.76
Endangered species risk quotients for vascular
aquatic plants are tabulated below. (Non-vascular
endangered species are not known to exist at this time.)
Table 45. Endangered Species Risk Quotients (RQs) for Aquatic Plants based upon a duckweed I^emna gibba) NOEC of 0.018 ppm.
Site/ Application Method/
Rate of Application in Ibs ai/A
(No. of Apps)
Sugarcane
Aerial
6(1)
Peas
Incorp. Ground
0.5(1)
Turf
0.5 (2)
Test Species
duckweed
duckweed
duckweed
NOECorEQa
(ppm)
0.018
0.018
0.018
EEC
(ppm)
0.39
0.024
0.024
RQ
(EEC/
EC50)
21.67
1.33
1.33
The results indicate that acute high risk levels of
92
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concern are exceeded for vascular plants at application rates
equal to and above 6.0 Ibs ai/A, and endangered species
levels of concern are exceeded for vascular plants at
registered maximum rates equal to or above 0.5 Ibs ai/A.
The results indicate that acute high risk and endangered
species levels of concern are exceeded for nonvascular
aquatic plants at registered maximum rates equal to or
above 0.5 Ibs ai/A. Currently, the Agency does not have a
procedure for assessing chronic risk to aquatic plants.
(3) Endangered Species
Endangered species LOCs for birds, mammals, terrestrial
plants, and aquatic plants are exceeded for metribuzin.
The Endangered Species Protection Program is expected to
become final in the future. Limitations in the use of metribuzin
may be required to protect endangered and threatened species, but
these limitations have not been defined and may be formulation
specific. EPA anticipates that a consultation with the Fish and
Wildlife Service may be conducted in accordance with the species-
based priority approach described in the Program. After
completion of consultation, registrants will be informed if any
required label modifications are necessary. Such modifications
would most likely consist of the generic label statement referring
pesticide users to use limitations contained in county Bulletins.
b. Water Resources Risk Implication for Human Health
(1)
Ground Water
Metribuzin is clearly a compound that leaches to ground
water, but at the present time, the concentrations found in ground
water are low compared to the levels of concern for human health.
However, in some studies, metribuzin residues have been found in
ground water at relatively high levels (14 and 54 ppb).
The lifetime Health Advisory for metribuzin has been
established at 100 ppb. Metribuzin has been placed in Cancer
Group D (not classifiable as to human carcinogenicity). All
metribuzin formulations carry a ground-water advisory on their
labels.
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(2) Surface Water
Metribuzin is not currently regulated under the Safe
Drinking Water Act (SDWA); therefore, no MCL has been
established for it and water supply systems are not required to
sample and analyze for it.- Metribuzin has lifetime and 1- and 10-
day drinking water health advisories of 100 ug/L and 5000 ug/L,
respectively. The low soil/water partitioning of metribuzin and its
major degradates probably makes their removal by the primary
treatment processes employed by most surface water supply
systems ineffective. However, the available data on metribuzin in
surface water indicates that it is unlikely that annual average
concentrations of metribuzin will exceed the lifetime health
advisory or that peak or short term average concentrations will
exceed the 1- to 10-day health advisory in surface water source
drinking water. Also, no drinking water Health Advisories are
available for the major degradates.
(5) Summary Environmental Risk Characterization
A. Avian Species
Acute Risks
Although acute RQs approach, or exceed, the acute
high risk LOG (0.5) and acute endangered species LOG (0.1) for
certain crop/rate scenarios, the Agency concludes that minimal
acute risks exist for these avian species. Our conclusion is based
on the observation that metribuzin's dietary LG50s for bobwhite
quail and mallard duck are > 4000 ppm and > 5000 ppm,
respectively, classifying metribuzin as practically non-toxic.
Typically, herbicides that exhibit such toxicity are expected to have
minimal acute effects on birds. Further, the typical use rate for
metribuzin is 1 Ib ai/acre, a rate that does not result in RQs that
exceed the LOCs.
The certainty of the above assessment is moderate to
high. However, one factor that affects the certainty (and prevents
it from being high) is that the acute oral LD50 for bobwhite quail
exposed to metribuzin is 169.2 mg/kg. This value classifies this
pesticide as moderately toxic to quail and indicates that dietary
ingestion may underestimate potential acute effects to avian
species.
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Chronic Risks
The Agency concludes that chronic risks are likely
for avian species, including endangered species, for rates of 4 Ib
ai/acre or higher. However, for the typical use rate of 1 Ib ai/acre,
RQs do not exceed the LOG of 1.0, and therefore, chronic risks are
not likely to occur under these use situations.
The certainty of the above assessment is moderate.
The following factors affect the utility of the data in a risk
assessment:
1. The avian reproduction studies, using bobwhite quail and
mallard duck, did not result in effects on reproductive
parameters. Instead, there were reductions in body weights
of hatchlings of treated birds.
2. There was some question as to whether the body weight
reductions in the bobwhite quail study were treatment-
related.
3. Since there were no reproductive parameters affected in the
duck study, the highest test concentration, 368 ppm, was
considered to be the No Observed Effect Concentration
(NOEC) and the Lowest Observable Effect Concentration
(LOEC) was not established (i.e., LOEC was > 368 ppm).
Since the LOEC was not determined in this study, it is
possible that the NOEC would be at a higher concentration.
These factors lead to a conclusion that while the
possibility of chronic risk exists, the probability that it will occur
may be relatively low.
B. Mammalian Species
Acute
Use applications of 0.5 Ib ai/acre and higher resulted
in RQs that either exceed the acute endangered species LOG (0.1)
or the acute high risk LOG (0.5). However, considering the factors
discussed below, the Agency concludes that minimal acute risks
exist for these species.
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The certainty of the assessment is moderate. This is
based on the following:
1. The rat acute oral LD50 is > 2000 mg/kg, classifying
metribuzin as practically non-toxic. Typically, herbicides
that exhibit such toxicity are expected to have minimal
acute effects on mammals.
2. However, the laboratory mouse acute oral LD50 is
approximately 700 mg/kg, a value less than half the 2000
mg/kg value for rats. This lower value raises some question
as to differences in sensitivity between species. It is not
known how sensitive wild mammals may be to metribuzin.
If they are substantially more sensitive, they may be at
greater risk than indicated by the RQs.
Therefore, it is only with moderate certainty that the
Agency concludes that mammals are not at acute risk from
metribuzin applications.
Chronic
The Agency concludes that chronic risks are likely
for mammalian species, including endangered species, for rates of
1 Ib ai/acre or higher.
The certainty of the above assessment is high
because:
1.
The available chronic mammalian data appear to be
scientifically sound and provide values (NOEC and LOEC)
related to effects on reproductive parameters.
2. Metribuzin and/or its degradates persist in the environment,
allowing chronic exposure of mammalian species.
C. Aquatic Species
Acute
The Agency concludes that minimal acute risks exist for
nontarget aquatic species, including endangered species. Although
one RQ (0.09) for sugarcane, at an application rate of 6 Ib ai/acre,
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exceeds the acute endangered species LOG (0.05) for aquatic
invertebrates, the Agency concludes that minimal acute risks exist
for these species. This conclusion is based on metribuzin's overall
lack of acute toxicity to a variety of freshwater and
estuarine/marine species, both vertebrate and invertebrate.
Metribuzin ranged from practically non-toxic to slightly toxic for
all species except Daphnia, which ranged from slightly toxic to
moderately toxic. Further, for the typical use rate of 1 Ib ai/acre,
acute RQs do not exceed the LOCs of 0.5 (non-endangered) or 0.05
(endangered), and therefore, acute risks are not likely to occur
under these use situations.
The certainty of the above assessment is moderate to high.
However, one factor that affects the certainty (and prevents it from
being high) is the sensitivity of Daphnia to metribuzin relative to
other aquatic organisms. The EG50 value of 4.2 ppm is significantly
lower than other aquatic LC50/EC50 values. This lower value raises
some question as to differences in sensitivity between species. It
is not known how sensitive wild aquatic organisms may be to
metribuzin. If they are substantially more sensitive, they may be
at greater risk than indicated by the RQs.
Chronic
The Agency concludes that minimal chronic risks
exist for nontarget aquatic species, including endangered species.
All RQs are well below the chronic LOC of 1.0.
The certainty of the above assessment is moderate to
high because:
1. The available chronic aquatic data appear to be
scientifically sound and provide values (NOEC and LOEC)
related to effects on reproductive parameters. Although a
NOEC was not determined in the rainbow trout early life-
stage study, use of the LOEC in developing RQs still
resulted in values well below the LOC of 1.0.
2. However, metribuzin and its degradates persist in the
aquatic environment, allowing for chronic exposure of
aquatic species. Because of this persistence and lack of
available chronic aquatic data on degradates, the Agency
cannot determine the chronic risks for metribuzin
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degradates. This factor affects the certainty and prevents it
from being high. However, one chronic aquatic
invertebrate study using Daphnia and DADK, a degradate
of metribuzin, is available. The results from this study are
comparable to those using parent compound.
D. Plants
The Agency concludes that risks are likely for
nontarget terrestrial and aquatic plant species, including
endangered species, for rates of 0.5 Ib ai/acre or higher.
Routes of exposure include drift and runoff (both
channelized and sheet runoff) for such organisms.
The certainty of the above assessment is high
because metribuzin is a herbicide and as such is intended to
adversely affect plants.
IV. RISK MANAGEMENT AND REREGISTRATION DECISION
A. Determination of Eligibility
Section 4(g)(2)(A) of FIFRA calls for the Agency to determine, after submission
of relevant data concerning an active ingredient, whether products containing the active
ingredients are eligible for 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 metribuzin as an active ingredient. The
Agency has completed its review of these generic data, and has determined that the data
"are sufficient to support reregistration of all products containing metribuzin under the
conditions specified in the RED. Appendix B identifies the generic data requirements that
the Agency reviewed as part of its determination of reregistration eligibility of metribuzin,
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 metribuzin and to determine that metribuzin can be used without
resulting in unreasonable adverse effects to humans and the environment if used
according to the labels as amended by this RED. The Agency therefore finds that all
products containing metribuzin as the active ingredients are eligible for reregistration
under the conditions specified in this RED. 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
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studies to generate such data, published scientific literature, etc. and the data identified
in Appendix B. Although the Agency has found that all uses of metribuzin are eligible
for reregistration under the conditions specified in this RED, it should be understood that
the Agency may take additional appropriate regulatory action, and/or require the
submission of additional data to support the registration of products containing
metribuzin, if new information comes to the Agency's attention or if the data requirements
for registration (or the guidelines for generating such data) change.
B. D etermination of Eligibility D ecision
1. Eligibility Decision
Based on the reviews of the generic data for the active ingredient
metribuzin, the Agency has sufficient information on the health effects of
metribuzin and on its potential for causing adverse effects in fish and wildlife and
the environment. The Agency has determined that metribuzin products, labeled
and used as specified in this Reregistration Eligibility Decision, will not pose
unreasonable risks or adverse effects to humans or the environment. Under the
Food Quality Protection Act of 1996, the Agency has determined that there is a
reasonable certainty that no harm will result to infants, children or to the general
population from aggregate exposure to metribuzin. Significant non-occupational
exposures are unlikely, therefore, the only risks considered in the aggregate
exposure assessment were those from dietary and drinking water sources. EPA
has concluded that consideration of a common mode of toxicity is not appropriate
at this time since EPA does not have information to indicate that toxic effects
produced by metribuzin would be cumulative with those of any other chemical
compounds. Therefore, the Agency concludes that products containing jtnetribuzin
for all uses are eligible for reregistration under the conditions specified in the
RED.
2. Eligible and Ineligible Uses
The Agency has determined that all uses of metribuzin are eligible for
reregistration under the conditions specified in the RED.
C. Regulatory Position
The following is a summary of the regulatory positions and rationales for
metribuzin. Where labeling revisions are imposed, specific language is set forth in
Section V of this document.
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1. Food Quality Protection Act Consideration
Determination of Safety for Metribuzin
EPA has determined that the established tolerances for metribuzin meet the
safety standards under the FQPA amendments to section 40S(b)(2)(D) for the
general population. In reaching this determination, EPA has considered available
information on the aggregate exposures (both acute and chronic) from non-
occupational sources, food and drinking water, as well as the possibility of
cumulative effects from metribuzin and other chemicals with a similar mechanism
of toxicity.
Determination of safety includes consideration of special sensitivity to
children, potential cumulative effects with pesticides that have a common mode
of toxicity and aggregate risks resulting from exposure to dietary residues,
residues in drinking water, and residential sources.
The available toxicological database for metribuzin does not indicate any
special sensitivity for infants and children to metribuzin. Therefore, the Agency
concludes that an additional uncertainty factor is not warranted, that the RfD
established at 0.013 mg/kg/day is appropriate for assessing aggregate chronic
dietary risk to infants and children, and that the NOEL of 15 mg/kg/day used in
calculating acute dietary exposure is also appropriate.
EPA does not have, at this time, available data to determine whether
metribuzin has a common mechanism of toxicity with other substances or how to
include this pesticide in a cumulative risk assessment. Unlike other pesticides for
which EPA has followed a cumulative risk approach based on a common
mechanism of toxicty, metribuzin does not appear to produce a toxic metabolite
produced by other substances. For the purposes of this tolerance action, therfore,
EPA has not assumed that metribuzin has a common mechanism of toxicity with
other substances.
The Agency has determined that significant non-occupational exposures
are unlikely. The only risks which must be considered are those from dietary and
drinking water sources. There are no chronic homeowner exposure scenarios;
therefore, the aggregate acute or chronic risk would be the total dietary risk (food
source + drinking water).
The total acute dietary (food and drinking water source) risk assessment
was performed for the sub-population females (13+ years). The MOE was 1200
(rounded to two significant digits). Metribuzin's acute dietary MOE greatly
exceeds 100; therefore, the Agency considers the MOE to be sufficiently
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protective for the acute total dietary (food source and drinking water) risk.
Using the previously described exposure assumptions, the Agency has
concluded that for the general population 1% of the RfD will be reserved for
exposure to residues of metribuzin in drinking water and 36% of the RfD will be
utilized by exposure to residues of metribuzin in food commodities. Thus, the
total chronic dietary risk is 37% of the RfD.
When total chronic dietary risk is assessed for the population sub-group
with the highest %RfDs (children 1 - 6), the Agency has concluded that 4% of the
RfD will be reserved for exposure to residues of metribuzin in drinking water and
75% of the RfD will be utilized by exposure to residues of metribuzin in food
commodities. The total chronic dietary risk is 79% of the RfD, thus not exceeding
the Agency's risk concern level.
2. Tolerance Reassessment
Tolerances Listed Under 40 CFR ง180.332
The tolerances listed under 40 CFR ง180.332 are expressed in terms of the
combined residues of metribuzin and its triazinone metabolites. A summary of
metribuzin tolerance reassessments is presented in Table 46. Tolerance
reassessments were prepared for metribuzin and its metabolites DADK, DK, and
DA. It should be noted that the registrant has requested that the current tolerance
expression be amended to consider only metribuzin and its DADK metabolite.
However, the Agency has not received a formal proposal containing additional
data and/or discussion concerning this request.
Sufficient data are available to ascertain the adequacy of the tolerances
established in 40 CFR ง180.332 for the following commodities: barley, grain;
barley, straw; carrots; corn, stover (fodder); com, forage; grass; grass, hay; lentils
(dried); lentils, forage; peas; peas (dried); peas, forage; sainfoin; sainfoin, hay;
soybeans; soybeans, forage; soybeans, hay; sugarcane; tomatoes; wheat, forage;
wheat, grain; and wheat straw. Additional confirmatory data/information are
needed before the established tolerances for animal commodities can be
reassessed. When tolerances for animal commodities are reassessed, a separate
dietary exposure assessment should be made to determine the necessity of
including any of these animal metabolites in the tolerance expression.
Tolerances for residues in alfalfa chaff, alfalfa seed, and cannery waste of
fresh corn (previously proposed in PP#8F3683/FAP#8H6663) are not needed.
There are presently no registered uses of metribuzin on popcorn. When
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acceptable field corn grain data have been submitted and evaluated, the
established tolerance for "corn, grain (inc. popcorn)" should be revoked
concomitant with the establishment of a tolerance for "corn, field, grain." There
are also no registered uses of metribuzin on sweet corn; therefore, the established
tolerance for this commodity will be revoked.
The livestock feeds table for Subdivision O (9/95) no longer considers
lentil hay, lentil forage, or barley forage to be significant livestock feed stuffs.
The established tolerances for lentil vine hay, lentil forage, and barley forage will
therefore be revoked.
Tolerances That Need To Be Proposed Under 40 CFR SI 80.332
The Agency has recently determined that tolerances for aspirated grain
fractions should be established based on the use of a pesticide on corn, wheat,
sorghum, and soybeans; there are presently registered uses of metribuzin on corn,
wheat, and soybeans. The available field corn grain dust data indicate that
residues of metribuzin and its metabolites DA and DADK were nondetectable
(<0.01 ppm each) and residues of DK were nondetectable (<0.03 ppm) following
treatment at 5x. An adequate level for a tolerance for metribuzin residues of
concern in/on aspirated grain fractions will be determined when the outstanding
data for wheat aspirated grain fractions are submitted.
Food/Feed Additive Issues Under 40 CFR ง185.250 and 40 CFR S186.250
Adequate processing studies have been submitted for field corn, potatoes,
and soybeans. The field corn and soybean processing studies suggest that no
food/feed additive tolerances are needed on the processed commodities of these
crops; nondetectable residues in the raw agricultural and processed commodities
of these crops-were obtained following applications of metribuzin at exaggerated
rates. The potato processing study suggests that the established food/feed additive
tolerances on processed potato commodities are appropriate.
The livestock feeds table for Subdivision O (9/95) no longer considers
sugarcane forage to be a major raw agricultural commodity of sugarcane.
Therefore, no tolerance or feeding restrictions are required for this commodity.
The registrant has indicated that additional processing studies on
sugarcane, tomatoes, and wheat have been initiated and the results, once
completed, will be submitted to EPA for evaluation. The wheat processing study,
once completed and evaluated, will be translated to fulfill the reregistration
requirements for a barley processing study.
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The listing in 40 CFR ง186.250 of 0.3 ppm for sugarcane molasses is in
error. The Metribuzin Residue Chemistry Science Chapter, dated 12/84, noted
that an increase in the feed additive tolerance for sugarcane molasses from 0.3 to
2 ppm was accepted as proposed in FAP#5H5151. This higher tolerance had been
established (43 FR 157:35915, 8/24/78).
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Alfalfa meal is no longer regulated as a processed feed item of alfalfa (per
livestock feeds table for Subdivision O - 9/95). Therefore, a tolerance and
supporting residue data are not required for this commodity. Alfalfa meal should,
however, be considered in the calculation of livestock diet using the alfalfa hay
tolerance level.
Table 46: Tolerance Reassessment Summary
Current
Tolerance
Tolerance
Reassessment
Comment/fCorrecf Commodity Definition ]
Tolerances Listed Under 40 CFR ง180.332
Alfalfa, green
Alfalfa, hay
Asparagus
Barley, straw
Carrots
Cattle, fat
Cattle, mbyp
Cattle, meat
Com, fodder
Corn, forage
Corn, fresh (inc. sweet
K + CWHR)
Corn, grain (inc.
popcorn)
Eggs
Goats, fat
Goats, mbyp
Goats, meat
Grass
2
7
0.05
0.75
1
0.3
0.7
0.7
0.7
0.1
0.1
0.05
0.05
0.01
0.7
0.7
0.7
2
7
TBDa
TBDa
0.1
0.75
1
0.3
TBDa
TBDa
TBDa
0.1
0.1
Revoke
TBDa
TBDa
TBDa
TBDa
TBDa
2
7
[Alfalfa, forage ]
Previously proposed at a different tolerance
level in PP#8F3683.
[Corn, field, fodder]
[Corn, field, forage ]
There are no registered uses of metribuzin on
sweet corn; therefore, the established tolerance
should be revoked.
There are presently no registered uses of
metribuzin on popcorn. When acceptable field
corn grain data have been submitted and
evaluated, the established tolerance for "corn,
grain (inc. popcorn)" should be revoked
concomitant with the establishment of tolerance
for "Corn, field, grain".
[Grass, forage ]
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Commodity
Hogs, fat
Hogs, mbyp
Hogs, meat
Horses, fat
Horses, mbyp
Horses, meat
Lentils (dried)
Lentils, forage
Lentils, vine hay
Milk
Peas
Peas (dried)
Peas, forage
Peas, vine hay
Potatoes
Poultry, fat
Poultry, mbyp
Poultry, meat
Sainfoin
Sainfoin, hay
Sheep, fat
Sheep, mbyp
Sheep, meat
Soybeans
Soybeans, forage
Soybeans, hay
Sugarcane
Tomatoes
Wheat, forage
Current
Tolerance
(ppm)
0.7
0.7
0.7
0.7-
0.7
0.7
0.05
0.5
0.05
0.05
0.1
0.05
0.5
0.05
0.6
0.7
0.7
0.7
2
7
0.7
0.7
0.7
0.1
4
4
0.1
0.1
2
Tolerance
Reassessment
(ppm)
TBDa
TBDa
TBDa
TBDa
TBDa
TBDa
0.05
Revoke
Revoke
TBDa
0.1
0.05
0.5
4.0
TBDa
TBDa
TBDa
TBDa
2
7
TBDa
TBDa
TBDa
0.3
4
. 4
0.1
0.1
2
Comment/[ Correct Commodity Definition ]
{Lentils']
Lentil forage is no longer considered to be a
significant livestock feed stuff per Table II
(9/95).
Lentil hay is no longer considered to be a
significant livestock feed stuff per Table II
(9/95).
[Peas, succulent]
[Peas, seed]
[Peas, field, forage ]
Previously proposed at a different tolerance
level in PP#8F3683.
[Peas, field, hay]
[Sainfoin, forage ]
Previously proposed at a different tolerance
level in PP#2F2677.
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Com in od ity
Wheat, grain
Wheat, straw
Current
Tolerance
(ppm)
0.75
1
Tolerance
Reassessment
(ppm)
0.75
1
Comment/[ Correct Commodity Definition ]
Tolerances That Need To Be Established Under 40 CFR ง180.332
Aspirated grain
fractions
Barley, hay
Wheat, hay
None
established
None
established
None
established
TBDa
7
7
A tolerance level for aspirated grain fractions
may need to be established when the
outstanding data for wheat aspirated grain
fractions are submitted and evaluated.
Previously proposed in PP#8F3683.
TOLERANCESLlSTED UNDER 40 CFR ง185.250
Barley, milled fractions
(except flour)
Potatoes, processed
Wheat, milled fractions
(except flour)
3
3
2
3
TBD"
3
TBD"
TBDa
The wheat processing study, once completed
and evaluated, will be translated to fulfill the
reregistration requirements for a barley
processing study.
[Barley, milled fractions (exc. flour) ]
[Sugarcane, molasses ]
[Wheat, milled fractions (exc. flour) ]
Tolerances Listed Under 40 CFR ง186.250
Barley, milled fractions
(except flour)
Potato waste, processed
(dried)
Sugarcane bagasse
Sugarcane molasses
3
3
0.5
0.3 (in
error);
2.0 (correct
TBDa
3
Revoke
TBDa
The wheat processing study, once completed
and evaluated, will be translated to fulfill the
reregistration requirements for a barley
processing study. [Barley, milled fractions (exc.
flour)}
[Potatoes, waste from processing ]
Sugarcane, bagasse is no longer considered to
be a significant livestock feed stuff per Table II
(9/95).
[Sugarcane, molasses ]
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Commodity
Tomato pomace, dried
Wheat, milled fractions
(except flour)
Current
Tolerance
(ppm)
2
3
Tolerance
Reassessment
(ppm)
Revoke
TBDa
Comment/[ Correct Commodity Definition ]
Dried tomato pomace is no longer considered to
be a significant livestock feed stuff per Table II
(9/95).
[Wheat, milled fractions (exc flour) ]
TBD = These tolerance(s) will be evaluated once confirmatory data is submitted and reviewed.
The currently established tolerance of 0.3 ppm as published in 40 CFR 186.250 for sugarcane molasses is
in error. The appropriate tolerance should be 2 ppm (See 43 FR 157:35915, 8/24/78).
CODEX HARMONIZATION
There are no Codex MRLs established or proposed for residues of
metribuzin and its triazinone metabolites. Therefore, there are no questions with
respect to compatibility of U.S. tolerances with Codex MRLs.
There is a Canadian tolerance of 0.05 ppm for metribuzin and its
metabolites for potatoes. Canada also has a negligible residue limit for
metribuzin, per se, on alfalfa, asparagus, barley, corn, fava beans, lentils, lupine,
peas, rapeseed (canola oil), soybeans, sunflowers, tomatoes, wheat, fruit tree
orchards (fruit), meat, milk, and eggs.
3. Tolerance Revocations and Import Tolerances
As part of EPA's reregistration eligibility decision for metribuzin, food
additive tolerances are no longer needed. Under the new law (FQPA, H.R. 1627),
the residues on processed food/feed items will be regulated Section 408. Once a
pesticide use is no longer registered in the United States, the related pesticide
residue tolerance and/or food/feed additive regulation generally is no longer
needed. It is EPA's policy to propose revocation of a tolerance, and/or food/feed
additive regulation, following the deletion of a related food use from a registration,
or following the cancellation of a related food-use registration. EPA has the
responsibility under the Federal Food, Drug, and Cosmetic Act (FFDCA) to
revoke a tolerance/regulation on the grounds that the Agency cannot conclude that
the tolerance/regulation is protective of the public health.
The Agency recognizes, however, that interested parties may want to retain
a tolerance and/or food/feed additive regulation in the absence of a U.S.
registration, to allow legal importation of food into the U.S. To assure that all
food marketed in the U.S. is safe, under FFDCA, EPA requires the same technical
chemistry and toxicology data for such import tolerances (tolerances without
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related U.S. registrations) as are required to support U.S. food use registrations
and any resulting tolerances. See 40 CFR Part 158 for EPA's data requirements
to support domestic use of a pesticide and establishment and maintenance of a
tolerance and/or food/feed regulation. In addition, EPA requires residue chemistry
data (crop field trials) that are representative of growing conditions in exporting
countries in the same manner that EPA requires representative residue chemistry
data from different U.S. regions to support domestic use of the pesticide and the
tolerance and/or regulation. Additional guidance on the Agency's import tolerance
policy will be published in an upcoming Federal Register Notice.
Parties interested in supporting an existing metribuzin tolerance as an
import tolerance should ensure that all of the data noted above are available to
EPA during its further assessments of existing tolerances and regulations, so that
the Agency may determine whether maintenance of the tolerance and/or regulation
would be protective of the public health."
4. Summary of Risk Management Decisions
The Agency has determined that the current uses of metribuzin exceed
levels of concern for, 1) acute and chronic avian and mammalian effects; 2)
nontarget terrestrial and aquatic plant species; 3) endangered species; 4) ground
water contamination, which could potentially impact drinking water and
ecological endpoints; and 5) occupational inhalation exposure.
Several risk mitigation measures to address these concerns have been
proposed by the technical registrant, Bayer Corporation. They were considered
by the Agency, and are being required. It must be noted that risk mitigation
measures are required for all metribuzin registrants.
Below is a brief summary of the Agency's concerns arid associated risk
mitigation measures.
o There is potential acute and chronic risk concern for avian species,
including endangered species, for rates of 4 Ib ai/acre or higher. Also, acute and
chronic risks are likely for mammalian species, including endangered species, for
rates of 1 Ib ai/acre or higher. In addition, metribuzin and its degradates are
mobile and persist in the environment. Risks are likely for nontarget terrestrial
and aquatic plant species, including endangered species, for rates of 0.5 Ib ai/acre
or higher. Routes of exposure include drift and runoff for such organisms.
Mitigation measures which specifically reduce the exposure of metribuzin
to nontarget organisms are: 1) prohibiting aerial application on asparagus and
tomatoes; 2) reducing the application rate of metribuzin being applied to
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sugarcane via aerial and chemigation methods from 6.0 Ib ai/acre to 2.0 Ib ai/acre;
and 3) spray drift labeling requirements, specified in Section V of this document,
Actions Required of Registrants.
o Although presently there are ground water advisories on metribuzin
product labels, the Agency is still concerned with potential ground water
contamination with metribuzin use. Data currently available to the Agency
indicate that metribuzin and its degradates are very mobile and highly persistent
and thus have the potential to contaminate ground water and surface water;
however, the persistence of parent metribuzin in surface water may be lessened by
its susceptibility to photolytic degradation. Metribuzin use could adversely affect
ground-water quality, especially in vulnerable areas. Detections have been
reported in the "Pesticides in Ground Water Database" (Hoheisel et al., 1992) and
other studies. These ground water contamination concerns are enhanced by the
widespread use patterns.
Mitigation measures that will reduce the likelihood of metribuzin and its
primary degradates contaminating ground and surface water are: 1) specifying
Best Management Practices; and 2) determining areas that are vulnerable to
ground-water contamination by metribuzin and recommending risk mitigation
measures. This information, once submitted and reviewed, will determine the
need for additional labeling. Other actions proposed by the registrant include: 1)
providing additional information on how levels of detects and nondetects were
handled in the small-scale retrospective study which was conducted in Portage
County, Wisconsin on potatoes; and 2) providing available historic data on
accumulations of metribuzin in surface water over time.
o There is an inhalation toxicity concern for mixer and loaders of the
wettable powder formulation for chemigation and aerial application at 6 Ibs.
ai/acre.
Mitigation measures which specifically reduce potential human health risk
of metribuzin use are: 1) reducing the application rate of metribuzin being applied
to sugarcane by chemigation and aerial application methods from 6.0 Ib ai/acre to
2.0 Ib ai/acre; and 2) prohibiting the use of low-pressure or high volume hand
wand equipment. As noted previously, although the 70 kg default male body
weight was used in calculating the MOEs, if the MOEs were to be re-calculated
using the 60 kg default female body weight, the MOEs would only be slightly
smaller. Therefore, the acceptable MOEs with mitigation measures all sufficiently
exceed 100 so that all MOEs estimated using the default female body weight
would also be acceptable.
Based on the Agency's overall risk assessment and risk characterization of
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metribuzin, and the mitigation measures required in this document, the Agency
believes that human risks associated with metribuzin use will be minimal and that
the risks to the environment from metribuzin and its degradates are relatively low.
The required rate reductions will adequately reduce the exposure of metribuzin to
occupational workers. Although the risk mitigation measures may not
quantitatively bring the risks below the level of concern for birds, mammals, and
plants; the Agency believes that these measures will substantially reduce the risks.
Minimizing spray drift will greatly reduce the risk to nontarget plants. Also, the
restrictions placed on the high use rate crop (sugarcane), will greatly reduce the
level of concern for birds, mammals and plants.
5. 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.
6. Occupational Labeling Rationale
The Worker Protection Standard (WPS)
Scope of the WPS
On August 21, 1992 the Agency issued worker protection regulations
affecting all pesticide products whose labeling reasonably permits use in the
production of agricultural plants on any farm forest, nursery or greenhouse. These
regulations established certain worker protection requirements (personal protective
equipment, restricted entry intervals, etc.). In general, products within the scope
of the Worker Protection Standard(WPS) had to bear complying labeling when
sold or distributed by the registrant after April 21, 1994.
At this time some of the registered uses of metribuzin are within the scope
of the Worker Protection Standard for Agricultural Pesticides (WPS) and some
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uses are outside the scope of the WPS, Those that are outside the scope of the
WPS include use:
on pastures or rangelands,
on plants grown for other than commercial or research purposes,
which may include plants in habitations, home fruit and vegetable
gardens, and home greenhouses,
on plants that are in ornamental gardens, parks, golf courses, and
public or private lawns and grounds and that are intended only for
decorative or environmental benefit,
in a manner not directly related to the production of agricultural
plants, including, for example, control of vegetation along
rights-of-way and in other noncrop areas.
Personal Protective Equipment/Engineering Controls for
Handlers
At this time there are no engineering control requirements, such as
closed systems, currently required on labeling for end-use products
containing metribuzin, though some metribuzin products are formulated
in water-soluble packaging, which is an engineering control for mixing and
loading.
B. Occupational-Use Products
EPA has determined that occupational handler exposures and risks
generally are the same for WPS and nonWPS uses of metribuzin.
Therefore, occupational handler exposures and risks are evaluated jointly.
As a result of the reregistration evaluation of the acute and other adverse
effects of metribuzin, the Agency has determined that risks to handlers do
not warrant the establishment of active-ingredient-based minimum
personal protective equipment or engineering-control requirements that
would apply to all metribuzin end-use products. Handler PPE
requirements for metribuzin are to be based solely on the acute toxicity of
individual end-use products.
C. Post-Application/Entry Restrictions
1) Occupational-Use Products (WPS Uses)
Restricted-Entry Interval:
Under the Worker Protection Standard (WPS), interim restricted
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entry intervals (REIs) for all uses within the scope of the WPS are based
on the acute toxicity of the active ingredient. The toxicity categories of the
active ingredient for acute dermal toxicity, eye irritation potential, and skin
irritation potential are used to determine the interim WPS REI. If one or
more of the three acute toxicity effects are in toxicity category I, the
interim WPS REI is established at 48 hours. If none of the acute toxicity
effects are in category I, but one or more of the three is classified as
category n, the interim WPS REI is established at 24 hours. If none of the
three acute toxicity effects are in category I or II, the interim WPS REI is
established at 12 hours. In addition, the WPS specifically retains two types
of REI's established by the Agency prior to the promulgation of the WPS:
(1) product-specific REI's established on the basis of adequate data, and (2)
interim REI's that are longer than those that would be established under the
WPS.
Since at this tune there are no dermal toxicological endpoints of
concern and metribuzin is classified as toxicity category IV for acute
dermal toxicity, eye irritation potential, and skin irritation potential, EPA
is establishing a 12-hour restricted-entry interval for all uses within the
scope of the WPS. The Agency believes that the 12 hour REI provides
adequate protection for workers reentering treated sites, and that a longer
REI is not needed. Although there are no active ingredient specific data
on which to base a quantitative estimate of post-application exposure, in
the Agency's judgement such workers are not likely to have substantially
greater exposure than pesticide handlers (those who mix, load or apply
pesticides). The Agency is not calling in post application exposure data at
this time, because EPA concludes that there is unlikely to be any
significant benefit to users from a shorter REI. In addition, EPA believes
that workers reentering a treated site much sooner than 12 hours after
application could experience significantly higher dermal exposure through
contact with wet surfaces on which the sprays have not completely dried.
The Agency doubts that post application exposure studies would support
much reduction in the REI for metribuzin products, however, if the
registrant would like to reduce the 12 hours REI, post application exposure
data would need to be provided to the Agency for review.
The WPS interim REI in effect is. 12 hours. EPA notes that the 12-
hour interim WPS REI was established because EPA data indicates that
metribuzin is classified as toxicity category IV for acute dermal toxicity,
eye irritation potential, and skin irritation potential.
EPA notes that the WPS places very specific requirements for
persons entering areas during restricted-entry intervals when that entry
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involves contact with treated surfaces. EPA believes that existing WPS
protections are sufficient to mitigate post-application exposures of workers
who contact surfaces treated with metribuzin.
EPA also notes that if metribuzin has been correctly incorporated
in soil, the WPS permits workers to enter the treated area during the
restricted-entry interval without personal protective equipment or any other
restriction if they are performing tasks that do not involve contact with the
soil surface.
Early-Entry PPE:
The WPS establishes very specific restrictions on entry by workers
to areas that remain under a restricted-entry interval if the entry involves
contact with treated surfaces. Among those restrictions are a prohibition
on routine entry to perform hand labor tasks and a requirement that
personal protective equipment be worn. Personal protective equipment
requirements for persons who must enter areas that remain under a
restricted-entry interval are based on the toxicity concerns for the active
ingredient.
During the reregistration process, EPA considers all relevant
product-specific information to decide whether there is reason to set
personal protective equipment requirements that differ from those set
through the WPS. The RED requirements for early-entry personal
protective equipment are set in one of two ways:
1. If EPA determines that no regulatory action must be taken as the
result of the acute effects or other adverse effects of an active
ingredient, it establishes the early-entry PPE requirements on the
basis of the acute dermal toxicity category, skin irritation potential
category, and eye irritation potential category of the active
ingredient.
2. If EPA determines that regulatory action on an active ingredient
must be taken as the result of very high acute toxicity or to certain
other adverse effects, such as allergic effects or delayed effects
(cancer, developmental toxicity, reproductive effects), it may
establish early-entry PPE requirements that are more stringent than
would be established otherwise.
Since metribuzin is classified as category IV for skin irritation
potential and IV for acute dermal toxicity, and EPA has determined that no
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regulatory action must be taken due to the acute effects or other adverse
effects of metribuzin active ingredient, the PPE for dermal protection
required for early entry is the minimum early-entry PPE permitted under
the WPS. Since metribuzin is classified as toxicity category IV for eye
rritation potential, no protective eyewear is required.
WPS Notification Statement
Under the WPS, the labels of some pesticide products must require
employers to notify workers about pesticide-treated areas orally as well as
by posting of the treated areas. Also, during the reregistration process,
EPA may decide that a product requires this type of "double notification."
EPA has determined that double notification is not required for metribuzin
end-use products.
2) Occupational-Use Products (NonWPS Uses)
Since EPA has concerns about post-application exposures to
persons immediately following nonWPS occupational applications of
metribuzin, it is establishing entry restrictions for all nonWPS occupational
uses of metribuzin end-use products. For specific language refer to
Section V of this document.
D. Additional Labeling Requirements
The Agency is requiring additional labeling statements to be located
on all end-use products containing metribuzin. There are also- several
clarifications that need to be made to the labels. For the specific labeling
statements, refer to Section V of this document.
7. Spray Drift Advisory
The Agency has been working with the Spray Drift Task Force, EPA
Regional Offices and State Lead Agencies for pesticide regulation to develop the
best spray drift management practices. The Agency is now requiring interim
measures that must be placed on product labels/labeling as specified in Section V.
Once the Agency completes its evaluation of the new data base submitted by the
Spray Drift Task Force, a membership of U.S. pesticide registrants, the Agency
may impose further refinements in spray drift management practices to further
reduce off-target drift and risks associated with this drift.
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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
1. Additional Generic Data Requirements
The generic data base supporting the reregistration of metribuzin for the
above eligible uses has been reviewed and determined to be substantially
complete. All uses of metribuzin are eligible for reregistration, however, the
Agency is requiring that the following confirmatory data be submitted to fulfill the
generic data requirements for reregistration of metribuzin.
1) Magnitude of residue studies (alfalfa and field corn trials, and field
rotational crop studies, additional field trials for field corn and potatoes,
and outstanding data for wheat aspirated grain fractions must be
submitted).
2) Processing studies for sugarcane and wheat are in progress. These
data must be submitted. A processing study for tomatoes was submitted
and is currently under review.
3) Certified limits (GLN 62-2) and analytical methods to verify
certified limits (GLN 62-3) are required for three impurities related to the
active ingredient in the 90% T.
4) Storage stability data for animal commodity samples from the
previously evaluated poultry and ruminant feeding studies are required.
If the storage intervals and conditions for livestock commodities are not
supported by adequate data, additional feeding study data may be required.
5) Confined rotational crop and field rotational crop studies are
required.
6) Ground water information. (GLN 166-17)
2. Labeling Requirements for Manufacturing-Use Products
To remain in compliance with FIFRA, manufacturing use product (MP)
labeling must be revised to comply with all current EPA regulations, PR Notices
and applicable policies. The MP labeling must bear the following statement under
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Directions for Use:
"Only for formulation into an Herbicide for those uses that are being
supported by MP registrant."
An MP registrant may, at his/her discretion, add one of the following statements
to an MP label under
"Directions for Use" to permit the reformulation of the product for
a specific use or all additional uses supported by a forrnulator or
user group:
(a) "This product may be used to formulate products for specific use(s)
not listed on the MP label if the forrnulator, 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 forrnulator, user group, or
grower has complied with U.S. EPA submission requirements
regarding support of such use(s)."
B. End-Use Products
1. Additional Product-Specific Data Requirements
Section 4(g)(2)(B) of FIFRA calls for the Agency to obtain any needed
product-specific data regarding the pesticide after a determination of eligibility
has been made. Registrants must review previous data submissions to ensure that
they meet current EPA acceptance criteria and if not, commit to conduct new
studies. If a registrant believes that previously submitted data meet current testing
standards, then study MRID numbers should be cited according to the instructions
in the Requirement Status and Registrants Response Form provided for each
product.
2. Labeling Requirements for End-Use Products
a. 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
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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 mis 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 ง 156.10 and other applicable
notices.
b. Occupational/Residential Labeling
PPE Requirements for Pesticide Handlers
Sole-active-ingredient end-use products that contain metribuzin must
be revised to adopt the handler personal protective equipment requirements set
forth in this section. Any conflicting PPE requirements on their current labeling
must be removed.
Multiple-active-ingredient end-use products that contain metribuzin
must compare the handler personal protective equipment requirements set forth
in this section to the PPE requirements on their current labeling and retain the
more protective. For guidance on which PPE is considered more protective, see
PR Notice 93-7.
1. WPS and nonWPS uses
a) Minimum (baseline) PPE requirements
For all formulations: EPA is not establishing active-ingredient-based
minimum (baseline) PPE or engineering control requirements for
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2.
metribuzin end-use products.
b) Actual end-use product PPE requirements Minimum PPE
requirements must be'compared with the PPE that would be designated on
the basis of the acute toxicity of the end-use product. The most protective
PPE must be placed on the product labeling. For guidance on which PPE
is considered more protective, see PR Notice 93-7.
c) Placement in labeling The personal protective equipment must be
placed on the end-use product labeling in the location specified in PR
Notice 93-7 and the format and language of the PPE requirements must be
the same as is specified in PR Notice 93-7.
d) Entry Restrictions
Sole-active-ingredientend-use products that contain metribuzin
must be revised to adopt the entry restrictions set forth in this section. Any
conflicting entry restrictions on their current labeling must be removed.
Multiple-active-ingredient end-use products that contain
metribuzin must compare the entry restrictions set forth in this section to
the entry restrictions on their current labeling and retain the more
protective. A specific time-period in hours or days is considered more
protective than "sprays have dried" or "dusts have settled."
WPS uses
Restricted-entryinterval - A 12-hour restricted entry interval (REI) is required
for uses within the scope of the WPS (see PR Notice 93-7) on all end-use products
with WPS uses (see tests in PR Notices 93-7 and 93-11).
Early-Entry Personal Protective Equipment (PPE)- The PPE required for
early entry is:
coveralls,
chemical-resistant gloves,
shoes plus socks.
Placement on the Labeling- The REI must be inserted into the standardized REI
statement required by Supplement Three of PR Notice 93-7. The PPE required for
early entry must be inserted into the standardized early entry PPE statement
required by Supplement Three of PR Notice 93-7.
3. NonWPS uses
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Entry restrictions --
Spray Applications: The entry restriction for all nonWPS uses applied as a spray
is:
"Do not enter or allow others to enter the treated area until sprays have dried. If
soil incorporation is required following the application, do not enter or allow
others to enter the treated area (except those persons involved in the incorporation)
until the incorporation is complete. If the incorporation is accomplished by
watering-in, do not enter or allow others to enter the treated area until the surface
is dry following the watering-in."
Dry (Fertilizer) Applications: The entry restriction for all nonWPS uses applied
dry is:
"Do not enter or allow others to enter the treated area until dusts have settled. If
soil incorporation is required following the application, do not enter or allow
others to enter the treated area (except those persons involved in the incorporation)
until the incorporation is complete. If the incorporation is accomplished by
watering-in, do not enter or allow others to enter the treated area until the surface
is dry following the watering-in."
Placement in labeling ~
If WPS uses are also on label: Follow the instructions in PR
Notice 93-7 for establishing a Non-Agricultural Use Requirements box and
place the appropriate nonWPS entry restriction in that box.
If no WPS uses are on label: Add the appropriate nonWPS entry
restriction to the labels of all end-use products, except products primarily intended
for homeowner use, in a section in the Directions For Use with the heading: "Entry
Restrictions:"
The Agency is requiring the following labeling statements to
be located on all end-use products containing metribuzin that are
intended primarily for occupational use.
Application restrictions
"Do not apply this product in a way that will contact workers or
other persons, either directly or through drift. Only protected
handlers may be in the area during application."
Engineering controls
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"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."
User safety requirements
"Follow manufacturer's instructions for cleaning and maintaining PPE. If
no such instructions are available for washables, use detergent and hot
water. Keep and wash PPE separately from other laundry."
User safety recommendations
' "Users should wash hands before eating, drinking, chewing
gum, using tobacco, or using the toilet."
" "Users should remove clothing immediately if pesticide gets
inside. Then wash thoroughly and put on clean clothing."
"Users should remove PPE immediately after handling this
product. Wash the outside of gloves before removing. As
soon as possible, wash thoroughly and change into clean
clothing."
Optional Soil incorporation statement
"Exception: if the product is soil-incorporated or watered-in, the Worker
Protection Standard, under certain circumstances, allows workers to enter the
treated area if there will be no contact with anything that has been treated."
c.
Environmental Hazard Statements
"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
disposing of equipment wash water or rinsate."
d. Application Restrictions
The labels of all metribuzin end-use products must be revised to bear the
following application restrictions under the Directions for Use Section:
For asparagus and tomato uses:
"Aerial application is prohibited"
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For aerial application on sugarcane:
"To assure that spray will not adversely affect adjacent sensitive nontarget
plant, apply this product by aircraft at a minimum upwind distance of 400
ft from sensitive plants."
For all uses:
"low-pressure and high volume hand wand equipment is prohibited"
e. Application Rates
The labels of metribuzin end-use products must be revised to bear the
following application rates under the Crop Uses Section for the respective
crops:
For the aerial and chemigation application methods of metribuzin on
sugarcane:
" A maximum application rate of 2.0 Ib ai/acre.
C. Spray Drift Labeling
The following language must be placed on each product label that can be applied
aerially:
Avoiding spray drift at the application site is the responsibility of the applicator.
The interaction of many equipment-and-weather-related factors determine the
potential for spray drift. The applicator and the grower are responsible for
considering all these factors when making decisions.
The following drift management requirements must be followed to avoid off-target
drift movement from aerial applications to agricultural field crops. These
requirements do not apply to forestry applications, public health uses or to
applications using dry formulations.
1. The distance of the outer most nozzles on the boom must not exceed 3/4
the length of the wingspan or rotor.
2. Nozzles must always 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
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covered in the Aerial Drift Reduction Advisory Information.
The following aerial drift reduction advisory information must be contained in the
product labeling:
[This section is advisory in nature and does not supersede the mandatory label
requirements.]
INFORMATION ON DROPLET SIZE
The most effective way to reduce drift potential is to apply large droplets. The
best drift management strategy is to apply the largest droplets that provide
sufficient coverage and control. Applying larger droplets reduces drift potential,
but will not prevent drift if applications are made improperly, or under
unfavorable environmental conditions (see Wind, Temperature and Humidity, and
Temperature Inversions).
CONTROLLING DROPLET SIZE
Volume - Use high flow rate nozzles to apply the highest practical spray
volume. Nozzles with higher rated flows produce larger droplets.
Pressure - Do not exceed the nozzle manufacturer's recommended
pressures. For many nozzle types lower pressure produces larger droplets. When
higher flow rates are needed, use higher flow rate nozzles instead of increasing
pressure.
Number of nozzles - Use the minimum number of nozzles that provide
uniform coverage.
Nozzle Orientation - Orienting nozzles so that the spray is released parallel
to the airstream produces larger droplets than other orientations and is the
recommended practice. Significant deflection from horizontal will reduce droplet
size and increase drift potential.
Nozzle Type - Use a nozzle type that is designed for the intended
application. With most nozzle types, narrower spray angles produce larger
droplets. Consider using low-drift nozzles. Solid stream nozzles oriented straight
back produce the largest droplets and the lowest drift.
BOOM LENGTH
For some use patterns, reducing the effective boom length to less than 3/4 of the
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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 in low relative humidity, set up equipment to produce
larger droplets to compensate for evaporation. Droplet evaporation is most severe
when conditions are both hot and dry.
TEMPERATURE INVERSIONS
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
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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).
D. OTHER LABELING REQUIREMENTS
Clarifications that need to be made to the label are:
1) On several labels the maximum Ib per acre application rate when applied
once a year is different from the application rate per year.
2) Labels should include registration number/site/rate/appl. method, etc
for items such as aerial application.
3) Labels should clearly state approved methods of application.
Label revisions are required for alfalfa and winter wheat. For alfalfa, the
registrant must amend all pertinent labels to specify a maximum seasonal rate
which must be consistent with the available (and required) residue data. A
previous recommendation to establish a 180-day PHI (pre-harvest interval) for
alfalfa grown for seed based on available data is no longer applicable since
presently there are no registered uses of metribuzin on alfalfa grown for seed. For
whiter wheat, the registrant must amend all pertinent labels to specify an
appropriate PHI consistent with that reflected in the residue data used to support
the tolerance.
Because finite residues were observed at all plantback intervals tested in
the confined rotational study, field rotational crop studies (GLN 165-2) are
required. The available field rotational crop studies must be replaced. In the
absence of adequate field rotational crop studies a label restriction stating "Do not
rotate to any crop not on the metribuzin label" must be added to all pertinent
labels.
When end-use product DCIs are developed (e.g., at issuance of the RED),
the Agency should require that all end-use product labels (e.g., MAI labels, SLNs,
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and products subject to the generic data exemption) be amended such that the uses
on these labels are consistent with the uses on the basic producer labels.
D. Existing Stocks
Registrants may generally distribute and sell products bearing old labels/labeling
for 26 months from the date of the issuance of this Reregistration Eligibility Decision
(RED). 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 metribuzin
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.
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VI. APPENDICES
APPENDIX A. Table of Use Patterns Subject to Reregistration
Appendix A is 126 pages long and is not being included. Copies of Appendix A are available upon request per the instructions in Appendix D
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GUIDE TO APPENDIX B
Appendix B contains listings of data requirements which support the reregistration for active ingredients within the case
Metribuzin covered by this Reregistration Eligibility Decision Document. It contains generic data requirements that
apply to Metribuzin in all products, including data requirements for which a "typical formulation" is the test substance.
The data table is organized in the following format:
1. Data Requirement (Column 1). The data requirements are listed in the order in which they appear in 40 CFR
Part 158. the reference numbers accompanying each test refer to the test protocols set in the Pesticide Assessment
Guidelines, which are available from the National Technical Information Service, 5285 Port Royal Road, Springfield,
VA 22161 (703)487-4650.
2. Use Pattern (Column 2). This column indicates the use patterns for which the data requirements apply. The
following letter designations are used for the given use patterns:
A Terrestrial food
B Terrestrial feed
C Terrestrial non-food
D Aquatic food
E Aquatic non-food outdoor
F Aquatic non-food industrial
G Aquatic non-food residential
H Greenhouse food
I Greenhouse non-food
J Forestry
K Residential
L Indoor food
M Indoor non-food
N Indoor medical
O Indoor residential
3. Bibliographic citation (Column 3). If the Agency has acceptable data in its files, this column lists the
identifying number of each study. This normally is the Master Record Identification (MRED) 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.
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