vvEPA
United States Prevention, Pesticides EPA 73-R-O5-O17
Environmental Protection and Toxic Substances August 2OO5
Agency (75O8C)
Reregistration
Eligibility
Decision (RED) for
Metiram
-------
Reregistration Eligibility Decision
for
Metiram
List A
Case No. 0644
Approved By:
/s/
Debra Edwards, Ph.D.
Director, Special Review and
Reregistration Division
August 29, 2005_
Date
-------
TABLE OF CONTENTS
METIRAM REREGISTRATION ELIGIBILITY DECISION TEAM i
GLOSSARY OF TERMS AND ABBREVIATIONS ii
EXECUTIVE SUMMARY iv
I. INTRODUCTION 1
II. CHEMICAL OVERVIEW 2
A. Regulatory History 2
B. Chemical Identification 3
1. Metiram 3
2. Ethylene thiourea (ETU) 4
C. UseProfile 5
D. Estimated Usage of Metiram 8
III. SUMMARY OF METIRAM RISK ASSESSMENTS 9
A. Human Health Risk Assessment 9
1. Toxicity Assessment of Metiram 10
a. Acute Toxicity Profile for Metiram 10
b. FQPA Safety Factor Considerations for Metiram 11
c. Toxicological Endpoints for Metiram 11
2. Toxicity Assessment of ETU 13
a. Acute Toxicity Profile for ETU 13
b. FQPA Safety Factor Considerations for ETU 13
c. Toxicological Endpoints for ETU 14
3. Metiram andETU Carcinogenicity 16
4. Metiram and ETU Endocrine Effects 17
5. Dietary Risk from Food 17
a. Exposure Assumptions 17
b. Population Adjusted Dose 18
1) Acute Dietary Risk from Food 18
2) Chronic Dietary Risk from Food 19
3) Cancer Dietary Risk from Food 20
6. Dietary Exposure from Drinking Water 21
a. Surface Water 21
b. Ground Water 22
7. Residential Exposure and Risk 22
8. Aggregate Risks from Food, Drinking Water and Residential Uses 22
a. Acute Aggregate 24
-------
b. Short-Term Aggregate 24
c. Chronic (Non-Cancer) Aggregate 25
d. Cancer Aggregate 25
9. Occupational Risks 26
a. Occupational Handler Exposure 27
1) Agricultural and Greenhouse Handler Risks 27
2) Handler Risk for Potato Seed-Piece Treatment 32
b. Post-Application Assessments 34
c. Human Incident Data 36
B. Environmental Risk Assessment 36
1. Environmental Fate and Transport 36
2. Ecological Risk Presumptions 37
3. Risk to Terrestrial Species 38
a. Birds and Mammals Exposure and Toxicity 38
b. Birds and Mammals Risk 40
c. Non-Target Plant Risk 41
d. Non-Target Insect Risk 41
4. Risk to Aquatic Species 41
a. Fish and Invertebrate Exposure and Toxicity 41
b. Fish and Invertebrate Risk 42
c. Non-Target Aquatic Plant Risk 43
5. Risk to Federally Listed Endangered and Threatened Species 44
6. Ecological Incidents 44
IV. RISK MANAGEMENT, REREGISTRATION AND TOLERANCE REASSESSMENT . 45
A. Determination of Reregistration Eligibility 45
B. Public Comments and Responses 46
C. Regulatory Position 46
1. Food Quality Protection Act Findings 46
a. "Risk Cup" Determination 46
b. Determination of Safety for U.S. Population
(including Infants and Children) 46
c. Endocrine Disrupter Effects 47
d. Cumulative Risks 47
2. Tolerances Reassessment Summary 48
a. Tolerances Listed Under 40 CFR § 180.217 48
b. Tolerances To Be Proposed Under 40 CFR § 180.217 48
c. Codex Harmonization 49
D. Regulatory Rationale 49
1. Human Health Risk Management 49
a. Dietary (Food) Risk Mitigation 49
b. Dietary (Drinking Water) Risk Mitigation 50
c. Residential Risk Mitigation 50
-------
d. Aggregate Risk Mitigation 50
e. Occupational Risk Mitigation 51
1) Agricultural and Greenhouse Handler Mitigation 51
2) Potato Seed-Piece Treatment Mitigation 53
3 Post-Application Mitigation 54
2. Environmental Risk Mitigation 55
a. Terrestrial Species Mitigation 55
b. Aquatic Species Mitigation 55
3. Significance of the EBDCs 56
4. Summary of Risk Mitigation Measures 58
E. Other Labeling Requirements 58
1. Endangered Species Considerations 58
2. Spray Drift Management 59
V. WHAT REGISTRANTS NEED TO DO 59
A. Manufacturing Use Products 60
B. End-Use Products 61
C. Labeling Changes Summary Table 61
VI. Appendices 69
Appendix A - Metiram Use Patterns Eligible for Reregistration 70
Appendix B - Data Supporting Guideline Requirements for the Reregistration of Metiram . . 72
Appendix B2 - Data Supporting FIFRA Guideline Requirements for the EBDC Metabolite /
Degradate ETU 78
Appendix C - Technical Support Documents 80
Appendix D - Bibliography 82
Appendix E - Placeholder for Generic Data Call-In (DCI) 99
Appendix F - Placeholder for Product Specific Data Call-In (PDCI) 100
Appendix G - EPA's Batching of Metiram Products for Meeting Acute Toxicity Data
Requirement for Reregistration 101
Appendix H - Placeholder for List of Registrants Sent DCI 103
Appendix I - List of Electronically Available Forms 104
-------
METIRAM REREGISTRATION ELIGIBILITY DECISION TEAM
Biological and Economic Analysis Assessment
Richard Mchell, Plant Pathologist
Bill Phillips, Agronomist
Arnet (Skee) Jones, Branch Chief
David Donaldson, Economist
Tim Keily, Economist
David Widawsky, Branch Chief
Environmental Fate and Effects Risk Assessment
Ronald Parker, RAPL
Gabe Patrick, Eco Tox Risk Assessor
Mohammed Ruhman, Eco Fate
Jean Holmes, Team Leader
Mah Shamim, Branch Chief
Endangered Species
Arty Williams, Associate Director
Health Effects Risk Assessment
Tim Dole, ORE Assessor
Christine Olinger, Residue Chemist
Felicia Fort, Dietary Risk Assessor
Kit Farwell, Toxicologist
Linda Taylor, Toxicologist
Michael Metzger, Branch Chief
Registration Support
Lisa Jones, Senior Reviewer
Mary Waller, PM, Team 21
Cynthia Giles-Parker, Branch Chief
Risk Management
Tawanda Spears, CRM
Kimberly Nesci, Team Leader
Michael Goodis, Branch Chief
Office of General Counsel
Kevin Minoli
Michele Knorr
-------
GLOSSARY OF TERMS AND ABBREVIATIONS
AGDCI
ai
aPAD
AR
ARTF
BCF
CCA
CFR
cPAD
CSF
CSFII
DCI
DEEM
DFR
DNT
DWLOC Drinking
EC
EC
EDWC
EEC
EPA
EUP
FDA
FIFRA
FFDCA
FQPA
FOB
G
GLN
HAFT
IR
LC50
LD50
LOC
LOD
LOAEL
MATC
ug/g
ug/L
mg/kg/day
mg/L
MOE
MRID
MUP
NA
Agricultural Data Call-In
Active Ingredient
Acute Population Adjusted Dose
Anticipated Residue
Agricultural Re-entry Task Force
Bioconcentration Factor
Comparative Cholinesterase Assay
Code of Federal Regulations
Chronic Population Adjusted Dose
Confidential Statement of Formula
USDA Continuing Surveys for Food Intake by Individuals
Data Call-In
Dietary Exposure Evaluation Model
Dislodgeable Foliar Residue
Developmental Neurotoxicity
Water Level of Comparison.
Emulsifiable Concentrate Formulation
Engineering Control
Estimated Drinking Water Concentration
Estimated Environmental Concentration
Environmental Protection Agency
End-Use Product
Food and Drug Administration
Federal Insecticide, Fungicide, and Rodenticide Act
Federal Food, Drug, and Cosmetic Act
Food Quality Protection Act
Functional Observation Battery
Granular Formulation
Guideline Number
Highest Average Field Trial
Index Reservoir
Median Lethal Concentration. A statistically derived concentration of a substance that can be expected to
cause death in 50% of test animals. It is usually expressed as the weight of substance per weight or volume
of water, air or feed, e.g., mg/1, mg/kg or ppm.
Median Lethal Dose. A statistically derived single dose that can be expected to cause death in 50% of the
test animals when administered by the route indicated (oral, dermal, inhalation). It is expressed as a weight of
substance per unit weight of animal, e.g., mg/kg.
Level of Concern
Limit of Detection
Lowest Observed Adverse Effect Level
Maximum Acceptable Toxicant Concentration
Micrograms Per Gram
Micrograms Per Liter
Milligram Per Kilogram Per Day
Milligrams Per Liter
Margin of Exposure
Master Record Identification (number). EPA's system of recording and tracking studies submitted.
Manufacturing-Use Product
Not Applicable
11
-------
NAWQA USGS National Water Quality Assessment
NPDES National Pollutant Discharge Elimination System
NR Not Required
NOAEL No Observed Adverse Effect Level
OP Organophosphate
OPP EPA Office of Pesticide Programs
OPPTS EPA Office of Prevention, Pesticides and Toxic Substances
PAD Population Adjusted Dose
PCA Percent Crop Area
PDF USDA Pesticide Data Program
PHED Pesticide Handler's Exposure Data
PHI Preharvest Interval
ppb Parts Per Billion
PPE Personal Protective Equipment
ppm Parts Per Million
PRZM/EXAMS Tier II Surface Water Computer Model
Q!* The Carcinogenic Potential of a Compound, Quantified by the EPA's Cancer Risk Model
RAC Raw Agriculture Commodity
RED Reregistration Eligibility Decision
REI Restricted Entry Interval
RiD Reference Dose
RQ Risk Quotient
SCI-GROW Tier I Ground Water Computer Model
SAP Science Advisory Panel
SF Safety Factor
SLC Single Layer Clothing
SLN Special Local Need (Registrations Under Section 24©) of FIFRA)
TGAI Technical Grade Active Ingredient
TRR Total Radioactive Residue
USDA United States Department of Agriculture
USGS United States Geological Survey
UF Uncertainty Factor
UFdb Database Uncertainty Factor
UV Ultraviolet
WPS Worker Protection Standard
111
-------
EXECUTIVE SUMMARY
EPA has completed its review of public comments on the revised metiram risk assessments and
is issuing its risk management decision for metiram. There are currently two tolerances being
reassessed for metiram. The revised risk assessments are based on review of the required target data
base supporting the use patterns of currently registered products and additional information received.
After considering the risks identified in the revised risk assessment, comments, and mitigation
suggestions from interested parties, EPA developed its risk management decision for uses of metiram
that pose risks of concern. As a result, the Agency has determined that metiram containing products
are eligible for reregistation provided that data needs are addressed, risk mitigation measures are
adopted, and labels are amended accordingly. The decision is discussed fully in this document.
Metiram was first registered in the United States in 1948 as a broad spectrum fungicide.
Metiram is used on apples, potatoes, and ornamental plants (leatherleaf ferns) in nurseries and
greenhouses. Metiram was previously registered for use on tobacco seedlings and roses, but these
uses have since been voluntarily cancelled. There are no residential labels, and no agricultural uses that
could result in exposure to metiram in residential settings. Approximately 900,000 pounds of metiram
are used for about 125,000 acres treated on an annual basis. Metiram's largest markets in terms of
total pounds of active ingredient (Ibs ai) are allocated to apples (55%) and potatoes (45%).
Metiram is a member of the ethylene bisdithiocarbamate (EBDC) group of fungicides, which
includes the related active ingredients mancozeb and maneb. This document summarizes risk estimates
for both metiram and its metabolite and environmental degradate ethylene thiourea (ETU). Metiram
and two other EBDC fungicides, maneb and mancozeb, are all metabolized to ETU in the body and all
degrade to ETU in the environment. Therefore, EPA has considered the aggregate or combined risks
from food, water and non-occupational exposure resulting from metiram alone, ETU resulting from
metiram use, and ETU from all sources (i.e., the other EBDC fungicides: maneb and mancozeb). The
aggregate risk from ETU from all sources must be considered to reassess the tolerances for metiram,
maneb and mancozeb.
Overall Risk Summary
Metiram dietary risks from food and drinking water sources are low and not of concern. Since
there are no registered residential uses of metiram, no residential risks were assessed. There are some
risk concerns for some occupational handlers, which will be mitigated with additional personal
protective equipment (PPE). In addition, some application restrictions are to be added to product
labels in order to maintain a 24 hour restricted entry interval (REI). For ecological risks, metiram poses
some chronic risk to birds and mammals, which will be reduced with various application reductions.
IV
-------
Dietary Risk
Acute, chronic, and cancer dietary (food only) risk from metiram, metiram-derived ETU, and
ETU from all sources are low and below Agency's level of concern. The drinking water exposure
assessment for metiram addresses concentrations of ETU only, since metiram is not expected to remain
in drinking water long enough to reach a location that would supply water for human consumption,
whether from surface or groundwater sources. Estimated concentrations of ETU, for both surface and
ground water sources of drinking water, are low and not of concern.
Residential Risk
The Agency is not considering residential exposures from metiram, since there are no existing or
proposed residential or other non-occupational sources of exposure, and metiram is not used in or
around public buildings, schools or recreational areas where children or others might be exposed.
Aggregate Risk/ETU
Aggregate risk refers to the combined risk from food, drinking water, and residential (as a
result of residential exposures to ETU from mancozeb uses) exposures. In addition, aggregate risk can
result from one-time (acute), short-term and/or chronic (non-cancer and cancer) exposures, and
considers exposures from metiram-derived ETU and ETU from all sources, depending upon the
scenario assessed. Acute, short-term, and chronic (non-cancer) aggregate risks are low and not of
concern. Aggregate cancer risk estimates are within a negligible risk range, and therefore no mitigation
measures are needed.
For short-term aggregate risks, EPA's original analysis indicated risks above levels of concern
for toddler exposure to transplanted turf for maneb and mancozeb. Recognizing that potential risk, the
maneb and mancozeb registrants voluntarily agreed to reduce the maximum application rate and/or
extend the time between treatment and harvesting of sod from one to three days (i.e., a 3 day PHI for
transplanted turf). The reduced application rate and/or extended PHI, combined with the logistics of
transplanting turf and installation restrictions, effectively reduced the potential contribution from this use
pattern to a level not of concern to the Agency.
Occupational Risk
Workers can be exposed to metiram and metiram-derived ETU through mixing, loading, and/or
applying (handlers) the pesticide to apples, potatoes (foliar and seed piece) and ornamentals (ferns), or
re-entering treated sites. There are some risks of concern to handlers, in particular to mixer/loaders of
dry flowable formulations for aerial/chemigation to apples and potatoes; airblast applicators; Saggers;
and loaders of dust for potato seed treatment. To mitigate these risk concerns, additional personal
protective equipment (PPE) are required on the product labels (i.e., PF5 respirator).
-------
At the current restricted entry interval (REI) of 24 hours and use patterns on current labels,
predicted metiram and ETU exposures exceed levels of concern for post-application high-end
exposure scenarios for apples and leather!eaf ferns. For leather!eaf ferns, by requiring that use be
restricted to a maximum of 1 application per week and 10 applications per year, the Agency has
concluded that the existing 24 hour REI may be retained. For apples, high exposure activities (pruning,
tying, and training) result in predicted exposures that exceed standard levels of concern (MOE of 54) at
the current REI of 24 hours. However, based on information that indicates very low usage in western
states where the short re-entry period is observed and the clear integrated pest management (IPM) and
resistance management advantages from use of metiram, the Agency plans to maintain the current 24
hour REI for apples.
Ecological Risk
For terrestrial species, short-term or acute metiram risks are low to mammals, birds, and non-
target insects. However, the screening-level ecological risk assessment for terrestrial species indicates
some risk quotient (RQ) exceedance of the chronic levels of concern (LOCs), especially from metiram
applications to apples and potatoes. Aquatic species (freshwater fish, freshwater invertebrates, and
non-vascular plants) result in low acute risk. Currently, there is no data on estuarine/marine species and
no toxicity data to assess aquatic chronic risk. The Agency is requiring additional acute and chronic
toxicity data as part of this RED to address these data gaps. Therefore, to be more protective of these
species that may be exposed on a chronic basis, the technical registrant has agreed to additional label
changes to reduce potential risk, including reducing the maximum application rate to apples and the
maximum number of applications to apples and potatoes.
Endangered Species
Based on available screening-level information, there is a potential concern for acute effects on
listed birds and freshwater fish species, and chronic effects on listed birds and mammals should
exposure actually occur. Even though metiram is only slightly acutely toxic to birds, RQs exceed the
endangered species LOG (RQ range from 0.11 to 1.02) at maximum EEC levels. The Agency does
not currently have data to quantify risks for metiram at the screening-level and can not preclude
potential direct effects to the following taxonomic groups; listed non-target terrestrial plants, freshwater
invertebrates, estuarine/marine fish, or vascular aquatic plants. These findings are based solely on
EPA's screening-level assessment and do not constitute "may affect" findings under the Endangered
Species Act (ESA) for any specific listed species. If the Agency determines use of metiram "may
affect" listed species or their designated critical habitat, EPA will employ the provisions in the Services
regulations (50 CFR Part 402).
VI
-------
Mitigation Summary
To address assessed risks of concern, the following mitigation measures will be implemented:
• Add a PF5 respirator to label PPE for some worker scenarios: mixer/loaders of dry flowables
for aerial/chemigation applications; airblast applicators to apples; and flaggers,
• Add the use of engineering controls to labels for aerial applicators (enclosed cockpits),
• Reduce apple pre-bloom maximum application rate from 4.8 to 3.6 Ibs ai/A,
Reduce maximum number of applications for apples from 4 to 3 per year,
Reduce maximum number of applications for potatoes from 7 to 6 per year,
• Limit the number of applications to leather!eaf ferns to 1 per week and 10 per year, and
• Metiram use on roses and dust and wettable powder formulations have been voluntarily
cancelled prior to completion of the RED. Further, as a result of the voluntary cancellation of
the dust formulation by the technical registrant and risks associated with this formulation, the
end-use registrant has requested voluntary cancellation of their active potato seed treatment
fungicide product registration (EPA Registration No. 2935-540).
Next Steps
Numerous opportunities for public comment were offered as this decision was being
developed. Therefore, the Agency is issuing this RED document for metiram without a formal public
comment period, as announced in a Notice of Availability published in the Federal Register:
However, the docket remains open, and any comments submitted in the future will be placed in this
public docket and addressed by the Agency, as appropriate.
EPA will issue a generic DCI for additional data necessary to confirm the conclusions of this
RED for the active ingredient metiram EPA will also issue a product-specific DCI for data necessary to
complete product reregistration for products containing metiram.
vu
-------
I. INTRODUCTION
The Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) was amended in 1988 to
accelerate the reregistration of products with active ingredients registered prior to November 1, 1984.
The amended Act calls for the development and submission of data to support the reregistration of an
active ingredient, as well as a review of all submitted data by the U.S. Environmental Protection Agency
(referred to as EPA or "the Agency"). Reregistration involves a thorough review of the scientific
database underlying a pesticide's registration. The purpose of the Agency's review is to reassess the
potential risks arising from the currently registered uses of the pesticide; to determine the need for
additional data on health and environmental effects; and to determine whether or not the pesticide meets
the "no unreasonable adverse effects" criteria of FIFRA.
On August 3, 1996, the Food Quality Protection Act of 1996 (FQPA) was signed into law.
This Act amends FIFRA and the Federal Food Drug and Cosmetic Act (FFDCA) to require
reassessment of all existing tolerances for pesticides in food. FQPA also requires EPA to review all
tolerances in effect on August 3, 1996 by August 3, 2006. In reassessing these tolerances, the Agency
must consider, among other things, aggregate risks from non-occupational sources of pesticide
exposure, whether there is increased susceptibility to infants and children, and the cumulative effects of
pesticides with a common mechanism of toxicity. When a safety finding has been made that aggregate
risks are not of concern and the Agency concludes that there is a reasonable certainty of no harm from
aggregate exposure, the tolerances are considered reassessed. EPA decided that, for those chemicals
that have tolerances and are undergoing reregistration, tolerance reassessment will be accomplished
through the reregistration process.
As mentioned above, FQPA requires EPA to consider "available information" concerning the
cumulative effects of a particular pesticide's residues and "other substances that have a common
mechanism of toxicity" when considering whether to establish, modify, or revoke a tolerance. Potential
cumulative effects of chemicals with a common mechanism of toxicity are considered because low-level
exposures to multiple chemicals causing a common toxic effect by a common mechanism could lead to
the same adverse health effect as would a higher level of exposure to any one of these individual
chemicals. Metiram belongs to a group of pesticides called dithiocarbamates, which also includes the
ethylene bis-dithiocarbamate (EBDC) fungicides maneb and mancozeb. For the purposes of this
reregistration eligibility decision (RED), EPA has concluded that metiram does not share a common
mechanism of toxicity with other substances. The Agency reached this conclusion after a thorough
internal review and external peer review of the data on a potential common mechanism of toxicity. For
more information, please see the December 19, 2001 memorandum, "The Determination of Whether
Dithiocarbamate Pesticides Share a Common Mechanism of Toxicity,'" which is available on the
internet at http ://www.epa.gov/oppsrrd 1 /cumulative/dithiocarb.pdf However, the EBDCs share a
common metabolite and degradate, ethylene thiourea (ETU), which is considered in this RED.
1 of 108
-------
This document presents EPA's revised human health and ecological risk assessments, its
progress toward tolerance reassessment, and the RED for metiram. The document consists of six
sections. Section I contains the regulatory framework for reregistration/tolerance reassessment.
Section n provides a profile of the use and usage of the chemical. Section m gives an overview of the
revised human health and environmental effects risk assessments based on data, public comments, and
other information received in response to the preliminary risk assessments. Section IV presents the
Agency's reregistration eligibility and risk management decisions. Section V summarizes label changes
necessary to implement the risk mitigation measures outlined in Section IV. Section VT contains the
Appendices, which list related information, supporting documents, and studies evaluated for the
reregistration decision. The preliminary and revised risk assessments for metiram are available in the
Office of Pesticide Programs (OPP) Public Docket, under docket numbers OPP-2004-0078 and
OPP-2005-0177, respectively, on the Agency's web page, http://www.epa.gov/edockets.
II. CHEMICAL OVERVIEW
A. Regulatory History
Metiram was first registered in the United States in 1948 for use on food and ornamental
crops to prevent crop damage in the field and to protect harvested crops from deterioration in storage
or transport. Metiram is a member of the ethylene bisdithiocarbamate (EBDC) group of fungicides,
which includes the related active ingredients mancozeb and maneb. Moreover, it has been determined
that the EBDCs share the common degradate ethylenethiourea (ETU). The EBDCs have been the
subject of two Special Reviews. In 1977, the Agency initiated a Special Review and Continued
Registration of Pesticide Products containing EBDCs based on evidence suggesting that the EBDCs
and ETU, a contaminant, metabolite and degradation product of these pesticides, posed potential risks
to human health and the environment. In 1982, the Agency concluded this Special Review by issuing a
Final Determination (PD 4), which required risk reduction measures to prevent unreasonable adverse
effects pending development and submission of additional data needed for improved risk assessment.
The Agency issued several comprehensive documents summarizing the reregistration status of
metiram. The Metiram Registration Standard Document was issued on 9/8/86, an Addendum to the
Registration Standard on 1/13/87, and an Update to the Metiram Registration Standard on 8/11/92. In
1987, EPA issued a second Notice of Initiation of Special Review of the EBDC pesticides because of
health concerns caused by ETU, including potential carcinogenic, developmental and thyroid effects.
Subsequent Data Call-ins (DCIs) were issued in 1988 and 1995 which included standard and worker
exposure data requests, respectively. The Special Review's Preliminary Determination (PD 2/3) was
published on December 20, 1989 (54 FR 52158) and the Final Determination (PD 4) on March 2,
1992 (57 FR 7484). The Agency concluded that the dietary risks of EBDCs exceeded the benefits for
the following food/feed uses for which one or more of the EBDC pesticides were registered: apricots,
carrots, celery, collards, mustard greens, nectarines, peaches, rhubarb, spinach, succulent beans, and
turnips. Accordingly, EPA canceled all metiram and other EBDC products registered for use on the
2 of 108
-------
above-listed food/feed crops. Currently, the only food/feed uses of metiram eligible for continued
registration are apples and potatoes, provided the label revisions are submitted.
The 1992 Special Review initially set the pre-harvest interval (PHI) for use on potatoes at
fourteen (14) days for most states. The only exceptions to the 14 day PHI were Connecticut, Florida,
Maine, Massachusetts, New Hampshire, New York, Pennsylvania, Vermont, and Wisconsin, where
EPA determined that disease pressures caused by late blight justified a 3 day PHI. Subsequently,
presented with evidence of late blight in additional states, EPA extended the 3 day PHI to Delaware,
Michigan, Rhode Island and Ohio. Recently, EPA received requests for amendments to several EBDC
product registrations and a petition to amend the 1992 cancellation order to allow for a three day PHI
in all states, due to an alleged increase in the occurrence of late blight nationwide. EPA has not
determined whether the petition warrants a hearing under 40 C.F.R. § 164 nor has it determined
whether it will grant the attendant registration amendment requests. Although EPA has not reached any
conclusions on the merits of the petition or the amendment requests, potential risks that would result
from a nationwide reduction in the PHI for potatoes to 3 days have been considered in this RED. That
consideration is for informational purposes only and cannot be interpreted as an indication of the
Agency's position on the petition or amendment requests.
B.
Chemical Identification
1. Metiram
Chemical Structure:
HN—^r
Zn
HN
HN
Common Name:
A mixture of 5.2 parts by weight of ammoniates of
{ethylenebis(dithiocarbamato)} zinc with 1 part by weight ethylenebis
{dithiocarbamic acid} bimolecular and tri molecular cyclic anhydrosulfides and
disulfides
Chemical Name:
Trade Name:
Metiram
Polygram
3 of 108
-------
Chemical Family: Dithiocarbamate
Case Number: 0644
CAS Registry No. : 9006-42-2
OPP Chemical Code: 014601
Moleculer weight: (1088. 6)x
Empirical Formula: (C 16H33N1 i S i6Zn3)x
Basic Manufacturers: BASF Corporation
Metiram is a light yellow solid which decomposes at ~ 140 C, and has a bulk density of 0.33-
0.49 kg/L, an octanol/water partition coefficient of 1.76-2.48 at pH 7 and 21 "C, and vapor pressure of
<1 x 10"7 mbar at 20 "C. Metiram is practically insoluble in water (2 mg/L) and organic solvents, and
decomposes under strong acid and alkaline conditions.
2. Ethylene thiourea (ETU)
Ethylenethiourea (ETU) is a metabolite, environmental degradate, and cooking byproduct of
metiram and the other EBDC fungicides, maneb and mancozeb. Chemical information is provided for
ETU because many of the risk concerns for metiram and the other EBDCs are driven by risk from
ETU.
Chemical Structure:
5
HN NH
Chemical Name: Ethylene thiourea
CAS Registry Number: 96-45-7
OPP Chemical Code: 6000 1 6
Molecular Weight: 1 02.2
Empirical Formula: C3HgN2S
4 of 108
-------
Technical ethylene thiourea (ETU) is a crystalline solid with a white to pale green color, and a
faint amine odor. It has a melting point of 203-204" C. ETU has an octanol/water partition coefficient
of 0.22. ETU is considered soluble in water, with a water solubility of 20,000 ppm at 30 C, but it is
also slightly soluble in methanol, ethanol, ethylene glycol, pyridine, acetic acid and naphtha. When ETU
is heated to decomposition, nitrogen and sulfur oxides are emitted.
C. Use Profile
The following is information on the currently registered uses including an overview of use sites
and application methods. A detailed table of the uses of metiram eligible for reregi station is contained
in Appendix A.
Type of Pesticide: Fungicide
Target organism(s): Downy mildews, anthracnose, rusts, leaf spots and blight.
Mode of action: Contact poison (non-systemic)
Use Sites:
Food/Feed Uses: Metiram is registered for foliar applications to apples and potatoes.
Although not currently registered, exposure from a proposed import use of metiram on grapes
has been assessed. It has also been included in this RED document to assist the Agency in
making a determination of whether to establish an import tolerance for metiram use on wine
grapes. A determination regarding establishment of this import tolerance is outside the scope of
this RED and will be made separately by the Agency.
• Non-Food & Residential Uses: Horticultural use is permitted on ornamental plants (leatherleaf
ferns) in nurseries and greenhouses as a 24(c) registration in Florida only. Metiram was
previously registered for use on tobacco seedlings and roses, but these uses have since been
voluntarily cancelled. There are no residential labels, and no agricultural uses that could result in
exposure to metiram in residential settings.
• Public Health Uses: None.
Use Classification: General Use.
Formulation Types: Metiram is formulated as 80 percent active ingredient dry flowable (water
soluble granules). Metiram was previously formulated into wettable powders and dust, but these
formulations have since been voluntarily cancelled.
5 of 108
-------
Application Methods: Metiram application methods are aerial, groundboom, chemigation, high- and
low-pressure handheld equipment, backpack sprayers, as well as seed and seed-piece treatment
equipment. The application methods for seed and seed-piece treatment are commercial stationary
equipment, on-farm stationary equipment, and tractor drawn planter boxes.
Application Rates: Metiram application rates vary depending on the crop. There are currently 4
active metiram labels and one FIFRA Section 24(c) Special Local Need (SLN) registration. The
maximum rate per application is 1.6 pounds of active ingredient per acre (Ibs ai/A) for potatoes and 4.8
Ibs ai/A for apples. The allowable number of applications per season ranges from 4 for apples to 7 for
potatoes, and the minimum application intervals range from 5 to 14 days. The application rate in
horticulture is 1.6 Ibs ai/A for leatherleaf ferns. Horticultural applications are allowed as much as twice
weekly with no limit on the total number of applications per season. The application rate for potato
seed-piece treatments is 0.105 Ibs ai per 100 pounds of seed-pieces.
Application Timing: Metiram is applied at foliar, pre-bloom, and pre-bloom through foliar stages and
also as a seed-piece treatment.
EBDCs Maximum Application Rates: As a result of Special Review, the Agency set usage
limitations on the EBDC fungicides (mancozeb, maneb, and metiram) to establish consistency between
the EBDCs registrations and Market Basket Survey data. The total poundage of all of the EBDCs
used on each crop must not exceed the maximum seasonal application rate for any one of these
fungicides. The maximum season rate for all of EBDCs used is the same for most of the crops
regardless of which EBDC is used, with the exception of cucurbits (cucumbers, melons, and summer
and winter squash), for which the maximum rate per season depends upon which EBDC is used. The
current maximum seasonal application rates for the EBDCs, by crop, are summarized in Table 1.
Table 1. Maximum Label Application Rates for the EBDC Fungicides
Crop Group
Field Crops
Field Crops
Field Crops
Field Crops
Field Crops
Field Crops
Field Crops
Fruits
Fruits
Crop(s)
Barley, Oats, Rye, Triticale,
Wheat
Beans, Dry
Com: hybrid seedcorn
Com: field
Cotton
Peanuts
Sugar Beets
Bananas
Cranberries
EBDC Used
MZ = Mancozeb
MN = Maneb
MT = Metiram
MZ
MN
MZ,MN
MZ
MZ
MZ
MZ,MN
MZ,MN
MZ,MN
Maximum Label Application
Rates
flb ai/acre)
Per Application
1.6
1.6
1.2
1.2
1.6
1.6
1.6
2.4
4.8
Total EBDC
Per Season
4.8
9.6
12
12
6.4
12.8
11.2
24
14.4
6 of 108
-------
Table 1. Maximum Label Application Rates for the EBDC Fungicides
Crop Group
Fruits
Fruits
Fruits
Fruits
Fruits
Miscellaneous
Non-Food
Non-Food
Nut Crops
Ornamentals
Ornamentals
Pome Fruits
Pome Fruits
Turf
Turf
Vegetables
Vegetables
Vegetables
Vegetables
Vegetables
Vegetables
Vegetables
Vegetables
Vegetables
Vegetables
Vegetables
Vegetables
Vegetables
Vegetables
Vegetables
Vegetables
Crop(s)
Figs, Kodota
Grapes - West
Grapes- East
Papayas
Plantains
Christmas Trees, Douglas Fir
Tobacco fields
Tobacco seedlings
Almonds
Ornamentals, Pachysandra
Ornamentals, Variety
Apples
Pears, Crabapples, Quince
Sod Farm
Golf Course, Athletic Fields
Asparagus
Brassica
Corn: sweet/pop/seed: East of
Miss.
Corn: sweet/ pop/seed: West of
Miss.
Cucumbers
Fennel
Gourds: Edible
Lettuce
Melons
Onions: Dry Bulb, Garlic
Onions: Green
Peppers
Potatoes
Pumpkins
Shallots
Squash (winter)
Squash (summer)
EBDC Used
MZ = Mancozeb
MN = Maneb
MT = Metiram
MN
MZ,MN
MZ,MN
MZ,MN
MZ
MZ
MZ
MZ
MN
MZ
MZ,MN
MZ, MN, MT
MZ
MZ,MN
MZ
MZ
MN
MZ,MN
MZ,MN
MZ.MN
MZ
MZ
MN
MZ.MN
MZ,MN
MN
MN
MZ, MN, MT
MN
MZ,MN
MN
MZ.MN
Maximum Label Application
Rates
flb ai/acre)
Per Application
2.4
2
3.2
2
2.4
3.2
1.5
2
6.4
13-14
1.2-1.6
2.4 or 4. 8
2.4 or 4. 8
16.3-19
16.3-19
1.6
1.6
1.2
1.2
MZ = 2.4
MN= 1.6
1.6
2.4
1.6
MZ = 2.4
MN= 1.6
2.4
2.4
1.6(w),2.4(e)
1.6
1.6
2.4
MZ = 2.4
MN= 1.6
Total EBDC
Per Season
2.4
6
19.2
28
24
NA
6
No Max
25.6
NA
NA
16.8 or 19.2
16. 8 or 19.2
NA
NA
6.4
9.6
18
6
MZ=19.2
MN = 12.8
12.8
19.2
6.4 (CA), 9.6 (US)
MZ=19.2
MN = 12.8
24
11.2
9.6 (w), 14.4 (e)
11.2
12.8
24
MZ=19.2
MN = 12.8
7 of 108
-------
Table 1. Maximum Label Application Rates for the EBDC Fungicides
Crop Group
Vegetables
Vegetables
Crop(s)
Tomatoes
Watermelons
EBDC Used
MZ = Mancozeb
MN = Maneb
MT = Metiram
MZ,MN
MZ,MN
Maximum Label Application
Rates
flb ai/acre)
Per Application
2.4 (w), 1.6 (e)
2.4
Total EBDC
Per Season
6.4 (w), 16.8 (e)
19.2
Note - Crops in bold have different rates depending upon which EBDC is used. Also, the not applicable (NA) reference is
because the use was not a part of Special Review.
(w) - West of the Mississippi (e) - East of the Mississippi
D. Estimated Usage of Metiram
Table 2 below summarizes the best available estimates for the pesticide usage of metiram.
Based on Agency data, approximately 900,000 pounds of metiram are used for about 125,000 acres
treated on an annual basis. Metiram's largest markets in terms of total pounds of active ingredient (Ibs
ai) are allocated to apples (55%) and potatoes (45%). Agricultural uses are concentrated in (but not
limited to) the following states: ID, MI, MN, NY, NC, SC, PA, and WA.
Table 2. Metiram Crop Usage Summary
Crop
Apples
Potatoes
Pounds of Active Ingredient
(Ibs a.i.)
500,000
400,000
% Crop Treated
Average
15
10
Maximum
25
10
III. SUMMARY OF METIRAM RISK ASSESSMENTS
The following is a summary of EPA's human health and ecological effects risk findings and
conclusions for the non-systemic fungicide metiram, as presented fully in the documents: Metiram.
Health Effects Division (HED) Human Health Risk Assessment to Support Reregistration, dated
June 13, 2005; ETUfrom EBDCs: Health Effects Division (HED) Human Health Risk
Assessment of the Common Metabolite/Degradate ETU to Support Reregistration, dated June 8,
2005; and Environmental Fate and Ecological Risk Assessment for Metiram, Section 3
Reregistration for Control of Fungal Diseases on Apples, Potatoes, Potato Seed, Certain
Ornamental Plants and Tobacco Seedling Plants (Phase 3 Response), dated June 21, 2005;
hereafter referred to as the Environmental Fate and Effects Risk Assessment.
8 of 108
-------
The purpose of this section is to summarize the key features and findings of the risk assessments
in order to help the reader better understand the conclusions reached in the assessments. Risks
summarized in this RED document are those that result only from the use of metiram. While the risk
assessments and related addenda are not included in this RED document, they are available from the
Office of Pesticide Programs (OPP) Public Docket: OPP-2005-0177 and may also be accessed on the
Agency's website at http://www.epa.gov/edockets. Hard copies of these documents may be found in
the OPP public docket under this same docket number. The OPP public docket is located in Room
119, Crystal Mall n, 1801 South Bell Street, Arlington, VA, and is open Monday through Friday,
excluding Federal holidays, from 8:30 a.m. to 4:00 p.m.
A. Human Health Risk Assessment
EPA released its preliminary risk assessments for metiram for public comment on
November 24, 2004 for a 90 day public comment period (Phase 3 of the public participation process).
The preliminary risk assessments may be found in the OPP public docket at the address given above
and in EPA's electronic docket under docket number OPP-2004-0078. In response to comments
received and new studies submitted during Phase 3, the risk assessments were updated and refined.
The risk assessments were revised again in June 2005 to incorporate comments and additional studies
submitted by the registrant. Revised risk assessments may be found in the OPP dockets under docket
number OPP-2500-0177. Major revisions to the metiram human health risk assessment include the
following:
Deletion of the rose use as a result of the voluntary cancellation of the use.
• Selection of a new NOAEL (No Observed Adverse Effect Level) for short-term dermal
exposures.
New dietary results for a pending import tolerance for use on wine grapes are included;
however, a tolerance has not yet been established and a determination of whether to establish a
tolerance will be made by the Agency separately from this RED.
This document summarizes risk estimates for both metiram and its metabolite and environmental
degradate ethylene thiourea (ETU). Metiram and two other EBDC fungicides, maneb and mancozeb,
are all metabolized to ETU in the body and all degrade to ETU in the environment. Therefore, EPA
has considered the aggregate or combined risks from food, water and non-occupational exposure
resulting from metiram alone, ETU resulting from metiram use, and ETU from all sources (i.e., the other
EBDC fungicides: maneb and mancozeb). The aggregate risk from ETU from all sources must be
considered to reassess the tolerances for metiram, maneb and mancozeb, in accordance with FQPA.
1. Toxicity Assessment of Metiram
Toxicity assessments are designed to predict if a pesticide could cause adverse health
effects in humans (including short-term or acute effects such as skin or eye damage, and lifetime or
chronic effects such as cancer, development and reproduction deficiencies, etc.) and the level or dose
9 of 108
-------
at which such effects might occur. The Agency has reviewed all toxicity studies submitted for metiram
and has determined that the lexicological database is sufficient for reregistation.
For more details on the toxicity and carcinogenicity of metiram see the Metiram: HED
Toxicology Chapter for the Reregistration Eligibility Decision Document (RED), dated December
23, 1999 and the Metiram-Revised Report of the Hazard Identification Assessment Review
Committee, dated April 2, 2003, which are available at http://www.epa.gov/edockets under docket
number OPP-2004-0078.
a. Acute Toxicity Profile for Metiram
Metiram demonstrates low acute toxicity via the oral (Toxicity Category IV), dermal (Toxicity
Category HI) and inhalation (Toxicity Category IV) routes of exposure. Because metiram is not
irritating to the eyes or the skin, it is in Toxicity Categories HI and IV, respectively. However, metiram
is a strong-to-severe skin sensitizer. The acute toxicity profile for metiram is summarized in Table 3.
Table 3. Acute Toxicity Profile for Metiram
Guideline
No.
870.1100
870.1200
870.1300
870.2400
870.2500
870.2600
Study Type
Acute Oral
Acute Dermal
Acute Inhalation
Eye Irritation
Skin Irritation
Dermal Sensitization
MRID
40497002
40497005
40497007
40497008
40497010
40497012
40497004
40497006
Results
LD50 * = >5000 mg/kg
LD50 = >2000 mg/kg
LC,n * = 5.7 mg/L
not an eye irritant
not a skin irritant
strong-to-severe dermal
sensitizer
Toxicity Category
IV
III
IV
III
IV
N/A
* LD50 or LC50 = Median Lethal Dose or Concentration. A statistically derived single dose or concentration that can be
expected to cause death in 50% of the test animals when administered by the route indicated (oral, dermal, inhalation).
b. FQPA Safety Factor Considerations for Metiram
The Federal Food Drug and Cosmetic Act (FFDCA) as amended by the Food Quality
Protection Act (FQPA) directs the Agency to use an additional tenfold (10X) safety factor to take into
account potential pre- and post-natal toxicity and completeness of the data with respect to exposure
and toxicity to infants and children. FFDCA authorizes the Agency to modify the tenfold safety factor
only if reliable data demonstrate that the resulting level of exposure would be safe for infants and
children.
10 of 108
-------
Special FOP A Safety Factor. The Agency concluded that there is qualitative indication of
increased sensitivity to infants and children based on the results of the rat developmental toxicity study
in which pre- and post-implantation loss were observed at a dose level that produced less severe
maternal toxicity [decreased body-weight gain]. An adequate developmental toxicity study in rabbits
and an adequate 2-generation reproduction study in rats are not available with which to assess
susceptibility. The Agency considered the degree of concern for susceptibility within the context of all
available toxicity data, and concluded there is low concern for the observed qualitative susceptibility
based on the following:
• The doses selected for overall risk assessment address concerns seen in the prenatal
developmental toxicity study;
• The dose-response in the rat developmental study was well-characterized;
• There was a clear NOAEL/LOAEL (No/Lowest Observed Adverse Effect Level) for maternal
and developmental toxicity; and
• The doses selected for the risk assessment also address concerns for thyroid toxicity.
Since there are no residual uncertainties for pre- and/or post-natal toxicity, the Special FQPA
Safety Factor was removed (reduced to IX) for metiram.
FOP A Database Uncertainty Factor. The Agency concluded there is a concern for
developmental neurotoxicity following exposure to metiram. Evidence of neurotoxicity and
neuropathology has been seen in rats following oral exposure to metiram in both subchronic and chronic
studies. The metiram metabolite/degradate ETU has been shown to be a teratogen in rats, with effects
seen in the central nervous system, urogenital and skeletal systems. In addition, neurotoxic effects have
been observed in studies with another EBDC, maneb. Therefore, the Agency will be requiring a
developmental neurotoxicity study (DNT) for metiram.
In addition to the required DNT study, the Agency noted data gaps for an acute neurotoxicity
study, a developmental toxicity study in the rabbit, and a 2-generation reproduction study in the rat.
The comparative thyroid assay has been waived for metiram. The requirement for the rabbit
developmental toxicity study is reserved for metiram, contingent on the performance of a rabbit
developmental toxicity on ETU because the developmental effects are expected to be attributable to
ETU. However, a waiver is not granted for the 2-generation reproduction and acute neurotoxicity
studies. The Agency determined that a 10X database uncertainty factor (FQPA UFDB) is needed to
account for the lack of these studies, since the available data provide no basis to support reduction or
removal of the 10XUFDB.
c. Toxicological Endpoints for Metiram
The lexicological endpoints used in the human health risk assessment for metiram are listed in
Table 4. The safety factors used to account for interspecies extrapolation, intraspecies variability, the
potential for special susceptibility to infants and children (FQPA 10X), and database uncertainties
11 of 108
-------
related to FQPA Safety Factor considerations are also described in Table 4 below.
Table 4. Toxicological Endpoints for Metiram
Exposure
Scenario
Dose, Uncertainty Factors (TJFs),
and Safety Factors (SFs)
Population Adjusted Dose
(PAD) or
Target Margin of Exposure
(MOE)
Study and Toxicological
Effects
Metiram Dietary Exposures
Acute Dietary
"emales 13-50
Acute Dietary
General Population
Chronic Dietary
NOAEL = 10 mg/kg/day
UF = 100X (inter and intraspecies)
FQPA SF = IX
FQPAUF=10Xdatabase
rotalUF= 1000X
Acute RfD = 0.01 mg/kg/day
N/A
NOAEL = 0.4 mg/kg/day
UF = 100X (inter and intraspecies)
FQPA SF = IX
FQPAUF^OX^
Total UF=1000X
Chronic RfD=0.0004 mg/kg/day
aPAD = Acute RfD
FQPA SF
aPAD = 0.01 mg/kg/day
Developmental Toxicity
(Rabbit)
LOAEL = 40 mg/kg/day, based
on abortions.
No appropriate endpoint attributable to a single exposure
(dose) was identified.
cPAD = Chronic RfD
FQPA SF
cPAD = 0.0004 mg/kg/day
Subchronic Oral Toxicity (Rat,
bridging study)
LOAEL= 6.7 mg/kg/day based
on decreased forelimb grip
strength
Metiram Dermal Exposures
Short-Term
[1-30 days]
Intermediate-Term,
jOng-Term
>30 days - 6 months,
> 6 months]
NOAEL = 6.7 mg/kg/day
UF = 100X (inter and intraspecies)
TotalUF= 100X
Dermal Absorption: 1%
NOAEL = 0.4 mg/kg/day
UF = 100X (inter and intraspecies)
TotalUF= 100X
Dermal Absorption: 1%
Occupational MOE = 100
Occupational MOE = 100
Subchronic Oral Toxicity (Rat,
bridging study)
LOAEL= 27.3 mg/kg/day
based on decreased forelimb
grip strength at early time
point
Subchronic Oral Toxicity (Rat,
bridging study)
LOAEL= 6.7 mg/kg/day based
on decreased forelimb grip
strength
Metiram Inhalation Exposures
nhalation
(Any Duration, i.e., 1
day to more than 1 80
days)
NOAEL = 0.5 mg/kg/day
UF = 100X (inter and intraspecies)
TotalUF= 100X
Occupational MOE = 100
13-week Inhal. Toxicity, Rat
LOAEL = 5.1 mg/kg/day based
on lung lesions (alveolitis).
SOAEL- No Observable Adverse Effect Level, the highest dose at which no adverse health effect is observed.
LOAEL - Lowest Observable Adverse Effect Level, the lowest dose at which an adverse health effect is observed.
aPAD/cPAD - acute and chronic, respectively, population adjusted dose (PAD), a reference dose which has been adjusted to
account for the FQPA safety factor.
12 of 108
-------
2. Toxicity Assessment for ETU
As previously mentioned, some of the toxicity of the parent EBDCs is attributed to their
common metabolite, ETU. The toxicology database for ETU contains a limited number of FIFRA
guideline studies; therefore, the Agency has relied on a combination of literature studies and unpublished
studies conducted according to the OPPTS testing guidelines. The thyroid is a target organ for ETU,
and thyroid toxicity as a result of ETU exposure has been noted in subchronic and chronic rat, mouse,
and dog studies. Overt liver toxicity was observed in one chronic dog study. Developmental defects in
the rat developmental study included hydrocephaly and related lesions, skeletal system defects, and
other gross defects. These defects showed increased susceptibility to fetuses because they occurred at
a dose that only caused decreased maternal food consumption and body weight gain.
For more details on the toxicity and carcinogenicity of ETU see the ETU- 3rd Report of the
Hazard Identification Assessment Review Committee, dated May 28, 2003, which is available on
the internet and in the public docket.
a. Acute Toxicity Profile for ETU
ETU demonstrates low acute toxicity via dermal (Toxicity Category El) and inhalation (Toxicity
Category IV) routes of exposure. Because ETU is not irritating to the eyes or the skin, it is classified as
a Toxicity Category IV for both. However, acute oral and dermal sensitization studies with ETU were
not available to determine acute toxicity. The acute toxicity profile for ETU is summarized below in
Table 5.
TableS. Acute Toxicity of ETU
Guideline No.
870.1100
870.1200
870.1300
870.2400
870.2500
870.2600
Study Type
Acute Oral - rat
Acute Dermal - rabbit
Acute Inhalation - rat
Primary Eye Irritation
Primary Skin Irritation
Dermal Sensitization
MRID Nos.
None
458881-01
458881-02
458881-04
458881-03
None
Results
N/A
LD50 > 2000 mg/kg
LC50 > 10.4 mg/L
No irritation
No irritation
N/A
Toxicity
Category
N/A
III
IV
IV
IV
N/A
b. FQPA Safety Factor Considerations for ETU
Special FOP A Safety Factor. Since there is evidence of increased susceptibility of fetuses
following exposure to ETU in the rat developmental studies, the Agency evaluated the level of concern
for the effects observed when considered in the context of all available toxicity data. In addition, the
Agency evaluated the database to determine if there were residual uncertainties after establishing
13 of 108
-------
toxicity endpoints and traditional uncertainty factors to be used in the ETU risk assessment. The
Agency determined that the degree of concern for the susceptibility seen in ETU developmental studies
was low because:
The teratogenic effects have been well-characterized in numerous studies in the published
literature, as well as in a guideline study submitted by the registrant;
• There is a clear NOAEL for these effects and the dose-response relationship, although steep, is
well characterized in the numerous developmental studies in rats;
• The developmental endpoint with the lowest NOAEL was selected for deriving the acute RfD;
and
• The target organ toxicity (thyroid toxicity) was selected for deriving the chronic RfD as well as
endpoints for non-dietary exposures (incidental oral, dermal, and inhalation).
Since the ETU doses selected for overall risk assessments will address the concern for
developmental and thyroid toxicity, there are no residual uncertainties with regard to pre- and/or post-
natal toxicity. The Agency concluded that the Special FQPA Safety Factor could be reduced to IX
for ETU.
FOP A Database Uncertainty Factor. The Agency concluded that a developmental
neurotoxicity study for ETU is required, based on severe central nervous system defects observed in
the developmental toxicity study in rats. In addition to the developmental neurotoxicity study, the
following data gaps were identified:
• Developmental toxicity study in rabbits
• 2-Generation reproduction study in rats
• A study evaluating the comparative thyroid toxicity in adults and offspring
The Agency determined that a lOx database uncertainty factor (FQPA UFDB) is needed to account for
the lack of these studies since the available data provide no basis to support reduction or removal of the
10XUFDB.
c. Toxicological Endpoints for ETU
The lexicological endpoints used in the human health risk assessment for ETU are listed in
Table 6. The safety factors used to account for interspecies extrapolation, intraspecies variability, the
potential for special susceptibility to infants and children (FQPA 10X), and database uncertainties
related to FQPA safety factor considerations are also described in Table 6 below.
14 of 108
-------
Table 6. ETU Toxicological Endpoints for Use in Human Health Risk Assessment
Exposure
Scenario
Dose, Uncertainty Factors (UFs),
and Safety Factors (SFs)
Population Adjusted Dose
(PAD) or
Target Margin of Exposure
(MOE)
Study and Toxicological
Effects
ETU Dietary Exposures
Acute Dietary
Females 13-50
Acute Dietary
General Population
Chronic Dietary
NOAEL = 5 mg/kg/day
UF = 100X (inter and intraspecies)
FQPA SF = IX
FQPAUF=10Xdatabase
Total UF=1000X
Acute RID = 0.005 mg/kg/day
Not Applicable
NOAEL = 0.18 mg/kg/day
UF=100X (inter and intraspecies)
FQPA SF = IX
FQPAUF=10Xdatabase
Total UF= 1000X
Chronic RfD=0.0002 mg/kg/day
aPAD = Acute RiD
FQPA SF
aPAD = 0.005 mg/kg/day
Developmental Rat Toxicity
(Khera Study, MRID
45937601)
LOAEL= 10 mg/kg/day,
based on developmental
defects of brain.
No appropriate endpoint attributable to a single exposure
(dose) was identified.
cPAD = Chronic RiD
FQPA SF
cPAD = 0.0002 mg/kg/day
Dog Chronic Oral Toxicity
(MRID No. 42338101)
LOAEL= 1.99 mg/kg/day
based on thyroid toxicity
ETU Incidental Oral Exposures [Residential/PostapplicationJ
Short-Term
[1-30 days]
Intermediate-Term
[>30 days to 6
months]
NOAEL = 7 mg/kg/day
UF = 100X (inter and intraspecies)
FQPAUF=10Xdatabase
FQPA SF = IX
Residential MOE = 1000
Occupational MOE = N/A
4-week range-finding dog
study
LOAEL= 34 mg/kg/day based
thyroid toxicity
ETU Dermal Exposures
Short-Term
[1-30 days]
Females 13-49
Intermediate-Term
[30 days - 6 months]
Long-Term
[> 6 months]
NOAEL = 5 mg/kg/day
UF = 100X (inter and intraspecies)
FQPAUF=10Xdatabase
FQPA SF = IX
Dermal Absorption = 26%
NOAEL = 0.18 mg/kg/day
UF = 100X (inter and intraspecies)
FQPAUF=10Xdatabase
FQPA SF = IX
Dermal Absorption = 26%
Residential MOE = 1000
Occupational MOE = 100
Residential MOE = 1000
Occupational MOE = 100
Same as above for acute
dietary exposures.
Same as above for chronic
dietary exposures.
ETU Inhalation Exposures
15 of 108
-------
Table 6. ETU Toxicological Endpoints for Use in Human Health Risk Assessment
Exposure
Scenario
Short-Term
[1-30 days]
Females 13-49
Intermediate-Term
[30 days - 6 months]
Long-Term
[>6 months]
Dose, Uncertainty Factors (UFs),
and Safety Factors (SFs)
NOAEL = 5 mg/kg/day
UF = 100X (inter and intraspecies)
FQPAUF=10Xdatabase
FQPA SF = IX
Inhalation Absorption = 100%
NOAEL = 0.18 mg/kg/day
UF = 100X (inter and intraspecies)
FQPAUF=10Xdatabase
FQPA SF = IX
Inhalation Absorption = 100%
Population Adjusted Dose
(PAD) or
Target Margin of Exposure
(MOE)
Residential MOE = 1000
Occupational MOE = 100
Residential MOE = 1000
Occupational MOE = 100
Study and Toxicological
Effects
Same as above for acute
dietary exposures.
Same as above for chronic
dietary exposures.
NOAEL- No Observable Adverse Effect Level, the highest dose at which no adverse health effect is observed.
LOAEL - Lowest Observable Adverse Effect Level, the lowest dose at which an adverse health effect is observed.
aPAD/cPAD - acute and chronic, respectively, population adjusted dose (PAD), a reference dose which has been adjusted to
account for the FQPA safety factor.
3. Metiram and ETU Carcinogenicity
In assessing the carcinogenicity of pesticides, the Agency first evaluates evidence that the
pesticide is a carcinogen. If there is evidence, such as tumor formation and the pesticide is classified as
a carcinogen, a quantitative assessment is conducted using either a Qx* (non-threshold) or a Margin of
Exposure (threshold) approach. The mechanism of the tumor formation determines whether or not a
threshold or non-threshold assessment is conducted. Table 7 below provides a comparison of tumor
data for ETU, mancozeb, maneb, and metiram.
Table 7. Tumor Incidence in EBDC/ETU Carcinogenicity Studies in Rats and Mice
Species
Rats
ETU
Thyroid follicular cell
adenomas and
carcinomas at 83 &
250 ppm
Mancozeb
Thyroid follicular cell
adenomas and carcinomas
at 750 ppm (HDT)
[56 ppm ETU]
Maneb
No increase in tumor of
any type at 1000 ppm
(HDT)
[75 ppm ETU]
Metiram
No increase in
tumor of any type
at 320 ppm (HDT)
[24 ppm ETU]
16 of 108
-------
Table 7. Tumor Incidence in EBDC/ETU Carcinogenicity Studies in Rats and Mice
Species
Mice
ETU
Thyroid follicular cell
adenomas and
carcinomas, pituitary
adenomas,
hepatocellular
adenomas and
carcinomas at 1000
ppm
Mancozeb
No increase in tumor of
any type at 1000 ppm
(HDT)
[75 ppm ETU]
Maneb
Increase incidence of
hepatocellular adenomas
and alveogenic adenomas
in the lungs at 2400 ppm
[180 ppm ETU]
Metiram
No increase in
tumor of any type
at 1000 ppm
[75 ppm ETU]
HDT - Highest Dose Tested
[Numbers in brackets represent ETU "dose" levels based on a 7.5% conversion of parent EBDC to ETU]
Historically, it has been assumed that metiram's potential for carcinogen!city (as well as that of
the other EBDCs, maneb and mancozeb) is due to the formation of the metabolite ETU, which is
classified as a probable human carcinogen (B2), with a cancer potency factor (Q/) of 0.0601
(mg/kg/day)"1 for risk assessment. On this basis, metiram cancer risk has been calculated by estimating
exposure to metiram-derived ETU (including that converted from metiram into ETU in the body) and
using the ETU cancer potency factor to provide a quantitative estimate of risk. In a 1999 review, the
Agency concluded that cancer risk for metiram and the other EBDCs should continue to be evaluated
in this way.
4.
Metiram and ETU Endocrine Effects
The available human health and ecological effects data for metiram suggest possible thyroid
effects, which may indicate potential endocrine disruption. EPA has considered these effects in the
human health risk assessment by selecting endpoints based on thyroid effects. To further address these
effects, EPA is requiring a confirmatory comparative thyroid toxicity study for ETU. Data on ecological
effects suggest possible hormonal effects to birds and mammals. These effects will be addressed when
the Agency's Endocrine Disrupter Screening and Testing Advisory Committee develops appropriate
screening and/or testing protocols. At that time, metiram may be subjected to additional screening
and/or testing to better characterize effects related to endocrine disruption.
5. Dietary Risk from Food
a. Exposure Assumptions
EPA conducted acute, chronic, and cancer dietary (food) risk assessments for metiram and its
metabolite ETU using the Dietary Exposure Evaluation Model software with the Food Commodity
Intake Database (DEEM-FCID™, Version 1.3), which incorporates consumption data from USDA's
Continuing Survey of Food Intakes by Individuals (CSFII), 1994-1996 and 1998. Because ETU is
17 of 108
-------
both a metabolite and environmental degradate of maneb and the other two EBDC fungicides, it was
considered in the dietary risk assessment. The Agency conducted a dietary risk assessment for ETU
from all sources, because ETU can be derived from mancozeb, maneb, or metiram.
The acute and chronic dietary (food) risk analyses were conducted using anticipated residue
values from field trial and market basket survey data. The 1989-1990 market basket survey for
EBDCs and ETU was the largest of its kind with 6000 samples (300 samples for each of 10 crops and
food forms). Processing factors, cooking factors, and estimated percent crop treated information were
also incorporated into the dietary risk assessment. EPA derived anticipated residues for ETU from
market basket survey data, ETU formed from metiram during processing, ETU formed by metiram and
ETU from all sources.
b. Population Adjusted Dose
Dietary risk assessment incorporates both exposure and toxicity of a given pesticide. For acute
and chronic dietary assessments, the risk is expressed as a percentage of a level of concern (i.e., the
dose predicted to result in no unreasonable adverse health effects to any human sub-population,
including sensitive members of such sub-populations). This level of concern is referred to as the
Population Adjusted Dose (PAD). Dietary risk is characterized in terms of the PAD, which reflects the
Reference Dose (RfD), either acute or chronic, that has been adjusted to account for the FQPA Safety
Factor.
Estimated dietary (food) risks less than 100% of the Population Adjusted Dose (PAD), either
acute (aPAD) or chronic (cPAD), are not of concern to the Agency. The aPAD is the dose at which a
person could be exposed at any given day with no adverse health effects expected. The cPAD is the
dose at which an individual could be exposed over the course of a lifetime with no adverse health
effects expected.
1) Acute Dietary Risk from Food
As previously mentioned, the acute dietary (food) risk assessment was conducted using the
DEEM-FCID™ computer model, anticipated residues, processing and cooking factors, and estimates
of percent crop treated. A highly refined, probabilistic acute dietary assessment was conducted using a
distribution of residue data for nonblended and partially blended commodities. Acute dietary risk
values for metiram, metiram derived ETU, and ETU from all sources (that is, ETU resulting from the
application of all three EBDC compounds, mancozeb, metiram, and maneb) are presented in Table 8.
(For the acute dietary endpoints see Table 4 for the metiram and Table 6 for the ETU)
18 of 108
-------
Table 8. Summary of Acute Dietary Exposure Analysis
Population
Subgroup
Females 13-
49 years
Metiram3
99.9thPercentile
Exposure
(mg/kg/day)
% aPAD
Metiram-derived ETU*
99.9thPercentile
Exposure
(mg/kg/day)
% aPAD
Apples, Potatoes
0.000786
7.9
0.000108
2.2
Apples, Potatoes, Import Wine Grapes (Proposed)
0.000874
8.7
0.002218
44
ETU from All Sources"
99.9th Percentile
Exposure
(mg/kg/day)
0.002725C
% aPAD
55
a aPAD is 0.01 mg/kg/day b aPAD is 0.005 mg/kg/day c excluding grapes (metiram treated import proposal)
For metiram the estimated acute dietary risk is below the Agency's level of concern. Dietary
exposure comprises 7.9% (without exposure from imported wine grapes) and 8.7% (including potential
exposure from imported wine grapes) of the aPAD for females 13-49 years old. Even with the
proposed use on imported wine grapes, metiram acute dietary (food) risk estimates are below the
Agency's level of concern. Note that a tolerance on imported wine grapes has not yet been established
because the determination of establishing this import tolerance is outside the scope of this RED. The
determination of whether to establish an import tolerance will be made separately by the Agency.
For metiram-derived ETU. the estimated acute dietary risk for ETU is below the Agency's
level of concern when the existing uses and residues from the proposed import tolerance on grapes,
based on field trial and processing studies are included in the assessment. Both metiram and ETU
residues were detected in grapes harvested from the day of treatment (day 0) to 57 days after
treatment. In processing studies with both red and white wine, ETU residues concentrate up to 14X,
while metiram per se residues are reduced by as much as 0.025X. As a result, dietary exposure
comprises 2.2% of the aPAD (without potential exposure from imported wine grapes) and 44%
(including potential exposure from imported wine grapes) of the aPAD for females 13-49 years of age.
For ETU from all sources, the estimated acute dietary risk for total ETU is also below the
Agency's level of concern. Dietary exposure comprises 55% (excluding proposed import wine grapes)
of the aPAD for females 13-49 years old.
2) Chronic Dietary Risk from Food
Chronic (non-cancer) dietary risk from food is calculated by using the average consumption
value for foods and average residue values on those foods over a 70-year lifetime. The chronic dietary
(food) risk assessment was conducted using the DEEM-FCID™ computer model, anticipated
residues, processing and cooking factors, and estimates of percent crop treated. The chronic
assessment used deterministic methodology to provide point estimates of risk. Chronic dietary risk
19 of 108
-------
values for metiram, metiram-derived ETU, and ETU from all sources are presented in Table 9. (For
the chronic dietary endpoints see Table 4 for the metiram and Table 6 for the ETU)
Table 9. Summary of Chronic (Noncancer) Dietary Exposure Analysis
Population Subgroup
Children (1-2)
Adults (50+)
Metiram3*
Exposure
(mg/kg/day)
0.000025
0.000005
%cPAD
6.2
1.3
Metiram-derived ETC**
Exposure
(mg/kg/day)
0.000007
0.000010
%cPAD
2.5
5.0
ETU from All Sources'"
Exposure
(mg/kg/day)
0.000108
0.000026
%cPAD
54
13
" cPAD is 0.0004 mg/kg/day b cPAD is 0.0002 mg/kg/day * Includes proposed imported wine grape exposure
For metiram the estimated chronic dietary risk is below the Agency's level of concern. Dietary
exposure from metiram comprises 6.2% of the cPAD for children 1-2 years old, the most highly
exposed population subgroup.
For metiram-derived ETU. the estimated chronic dietary risk is below the Agency's level of
concern. The dietary exposure from metiram-derived ETU comprises 5% of the cPAD for adults 50+
years old, the most highly exposed population subgroup.
For ETU from all sources, the estimated chronic dietary risk is also below the Agency's level of
concern. The dietary exposure from ETU from all sources comprises 54% (excluding proposed import
wine grapes) of the cPAD for children 1-2 years old, the most highly exposed population subgroup.
3) Cancer Dietary Risk from Food
Cancer dietary risk from food is calculated by using the average consumption values for food
and average residue values for those foods over a 70-year lifetime. The chronic exposure value is
multiplied by a linear low-dose, or Qj*, based on animal studies, to determine the lifetime cancer risk
estimate. For cancer dietary exposure, risk estimates within the range of an increased cancer risk of 1
x 10"6 (one in a million) are generally not of concern to the Agency.
As mentioned above, metiram's potential for carcinogenicity has been based on its metabolite
ETU. The ETU cancer potency factor has been used for assessing cancer risk associated with metiram
uses.
The Agency evaluated the carcinogenicity potential of ETU and classified ETU as a "probable
human carcinogen" (group B2). Based upon female mouse liver tumors in a National Toxicology
Program (NTP) study, the Qx* for ETU, using a 3/4 scaling factor to account for body weight ratio
from animal to human, was determined to be 6.01 x 10"2 mg/kg/day"1. On this basis, metiram estimated
cancer risk has been calculated by estimating exposure to metiram-derived ETU (including the
20 of 108
-------
metabolic conversion of 0.075) and using the ETU cancer potency factor. Cancer dietary risk values
are listed in Table 10.
The cancer risk for metiram-derived ETU is approximately 7.6 x 10"8 (based on existing uses
on apples and potatoes) and 4 x 10"7 (based on existing uses and a proposed import wine grape
exposure), which both are below the Agency's level of concern for cancer risk. The cancer risk for
ETU from all sources is approximately 1.86 x 10"6, which is within the negligible risk range of 10"6 and
not considered to be of concern.
Table 10. Cancer Dietary Exposure and Risk Summary for Metiram-Derived ETU and ETU from All Sources
Population
Metiram-Derived ETU
Chronic Dietary
Exposure
(mg/kg/day)
Cancer
Risk
Estimate
ETU from All Sources
Chronic Dietary
Exposure
(mg/kg/day)
Cancer
Risk
Estimate
Existing Uses
General U.S. Population
0.000005
7.6 xlO'8
0.000031
1.86 xlO'6
Existing and Proposed Uses
General U.S. Population
0.000007
4.0 xlO'7
Not estimated
6. Dietary Exposure from Drinking Water
Drinking water exposure to pesticides can occur through surface and ground water
contamination. EPA considers acute (one day) and chronic (lifetime) drinking water risks and uses
either modeling and/or monitoring data, if the latter is available and of sufficient quality, to estimate those
exposures. Risks from exposure to ETU in drinking water are further discussed in the section titled
"Aggregate Exposure and Risk."
The Agency prepared a drinking water exposure assessment for ETU only. The parent EBDC
fungicides were not assessed because they are very short-lived in soil and water, and are not expected
to reach water used for human consumption, whether from surface water or groundwater sources.
ETU, however, is highly water soluble, and moderately mobile, and may reach both surface and
groundwater under some conditions. ETU has an aerobic soil half-life of about 3 days; in the absence
of data, the aerobic aquatic metabolism half-life was assumed to be about 6 days, or double the soil
half-life. The measured anaerobic aquatic metabolism half-life, however, is substantially longer (149
days), which may lead to the periodic detections in groundwater. The ETU estimated drinking water
concentrations (EDWCs) were generated using data from both monitoring and modeling. Table 11
shows the EDWCs used to assess exposure to ETU in drinking water from surface water and
groundwater.
21 of 108
-------
Table 11. Estimated Drinking Water Concentrations (EDWCs) for ETU
Drinking water source
Surface Water
Groundwater
Duration
Acute (Peak)
Chronic/Cancer
All Durations
EDWC (ppb)
25.2
0.1
0.21
Data Source
Modeling
Monitoring
Monitoring
a.
Surface Water
Monitoring data for ETU from a targeted surface water monitoring study conducted in several
states by the ETU Task Force were available for use in the risk assessment. In the study, none of the
tested surface water samples had concentrations above the limit of detection of 0.1 ppb. Therefore, the
chronic/cancer EDWC was assigned the value of 0.1 ppb of ETU. The monitoring value of 0.1 ppb of
ETU was also assigned to be the lower limit of the acute EDWC. In addition, the Agency decided that
a higher limit for the acute EDWC value is necessary because monitoring samples were taken every 14
days during the application season in the monitoring study and peak values may have been missed with
this sampling frequency. To obtain the higher limit value, the Agency performed PRZM/EXAMS
simulation modeling for 22 crop scenarios, considering the use patterns for all of the EBDCs and
choosing to model the highest application rate and lowest application intervals. Modeling results
showed the highest one-in-ten year acute surface water EDWC to be 25.2 ppb based on application of
EBDCs to peppers in Florida. Therefore, a range of acute EDWCs was established with a lower limit,
based on monitoring, and an upper limit, based on the PRZM/EXAMS modeling described above.
The established range of acute EDWC values for surface water, at the national level, is expected to be
between the detection limit of 0.1 ppb (from monitoring) and the highest peak value 25.2 ppb (from
modeling after adjustment by the 0.87 national percent crop area factor or PC A). In summary, the
Agency used a combined approach to assess drinking water exposure using both targeted surface
water monitoring and simulation modeling to bracket the expected acute concentrations of ETU in
drinking water between 0.1 and 25.2 ppb. Chronic surface water values were set conservatively at 0.1
ppb, the detection limit for the monitoring data.
b.
Groundwater
A groundwater EDWC was selected from a targeted monitoring study conducted in 2001 to
2003 for seven states chosen to represent the high historic EBDC use areas in the US. Based on the
monitoring results, the highest measured value in a public drinking water well was 0.210 ppb in Lee
County, Florida. Therefore, the groundwater EDWC is assigned the value of 0.21 ppb of ETU. In this
study, ETU was not detected in any of the treated community drinking water sampled from the
monitored 84 sites even when it was detected in the raw water. The absence of ETU in potable water
from community water supplies may be related to its rapid degradation resulting from aeration and
chemical treatment.
22 of 108
-------
7. Residential Exposure and Risk
Metiram has no labeled residential uses. In addition, no residential post-application exposure to
metiram is expected following its use in agricultural or other commercial settings. Therefore, a
residential risk assessment for metiram (and for ETU derived from metiram uses) was not prepared.
However, some residential exposure to ETU may occur from use of the other EBDCs. Therefore,
these exposures have been considered in the ETU (from all sources) aggregate assessment, in
accordance with FQPA.
8. Aggregate Risks from Food, Drinking Water and Residential Uses
The FQPA amendments to the Federal Food, Drug, and Cosmetic Act (FFDCA, Section
408(b)(2)(A)(ii)) require "that there is a reasonable certainty that no harm will result from aggregate
exposure to the pesticide chemical residue," including all anticipated dietary exposures and other
exposures for which there are reliable information. Aggregate exposure will typically include exposures
from food, drinking water, residential uses of a pesticide, and other non-occupational sources of
exposure.
In accordance with the FQPA, the Agency must consider and aggregate pesticide exposures
and risks from three major sources or pathways: food, drinking water and, if applicable, residential or
other non-occupational exposures. For aggregate risk, EPA typically combines exposures from food
and residential sources and calculates a drinking water level of comparison (DWLOC), which
represents the maximum allowable exposure through drinking water after considering food and
residential exposures. If the EDWCs are less than the DWLOCs, EPA does not have concern for
aggregate exposure. If EDWCs are greater than DWLOCs, EPA will conduct further analysis to
characterize the potential for aggregate risk of concern.
Short-term residential and other non-occupational exposure assessment considers all potential
pesticide exposure, other than exposure due to residues in food and/or in drinking water. Each route of
exposure (oral, dermal, inhalation) is assessed, where appropriate, and risk is expressed as a Margin of
Exposure (MOE), which is the ratio of estimated exposure to an appropriate NOAEL dose. A MOE
greater than or equal to the target MOE is considered adequately protective and not a risk of concern.
Note that there is no potential for exposure to metiram or metiram-derived ETU in residential
settings, so metiram aggregate exposure and risk assessments include only dietary food and drinking
water sources of exposure, and are limited to chronic and acute durations. However, there is potential
exposure to ETU from all sources as result of the residential exposures from uses of mancozeb, which
are included in the short-term aggregate risk assessment.
Exposure to metiram per se in drinking water is not expected, and metiram is not registered for
residential uses, so the only exposure and risk for metiram per se is food alone. Therefore, an
aggregate risk assessment for metiram per se was not conducted. Acute and chronic dietary exposures
23 of 108
-------
to metimmper se are not of concern to the Agency, as presented in the dietary food section above.
For ETU resulting from metiram use, the Agency assessed the following aggregate exposure
scenarios:
acute aggregate (food + water)
chronic (non-cancer) aggregate (food + water)
• cancer aggregate (food + water)
For ETU from all sources, the Agency assessed the following aggregate exposure scenarios:
acute aggregate (food + water)
• short-term aggregate (food + water + residential [as a result of the residential exposures from
mancozeb uses])
chronic (non-cancer) aggregate (food + water)
cancer aggregate (food + water + residential [as a result of residential exposures from
mancozeb uses])
a. Acute Aggregate
Potential exposure to metiram-derived ETU from both groundwater and surface water sources
of drinking water, when combined with exposure through food, is below the Agency's level of concern.
EDWCs are significantly less than the DWLOC, as shown in Table 12 below.
Table 12. Acute DWLOC Calculations for Metiram-derived ETU
Population Subgroup
Acute DWLOC (ug/L)
Surface Water EDWC
(PPb)
Groundwater EDWC (ppb)
Existing Uses Only (Apples and Potatoes)
Females 13 -49
147
25.2
0.21
Existing and Proposed Uses (Apples, Potatoes, and Grapes)
Females 13-49
83
25.2
0.21
Unlike for metiram-derived ETU, aggregate (food + drinking water) acute risk to ETU from all
sources was calculated using a more refined assessment on a semi-probabilistic basis using the full
range of food residue data and the acute EDWC estimate of 25.2 ppb for the drinking water
concentration. The acute aggregate risk of 87% of the aPAD at the 99.9th percentile for ETU from all
sources is less than 100% of the aPAD and also below the Agency's level of concern.
b. Short-Term Aggregate
24 of 108
-------
Short-term aggregate (food + drinking water + residential [as a result of residential exposures
from mancozeb uses]) risk for ETU from all sources is below the Agency's level of concern for
residential handlers, and children and adults exposed to ETU from re-entry activities. Short-term
aggregate risks were calculated for adults by aggregating chronic food exposure, chronic drinking water
exposure and golfing or gardening exposures. Short-term aggregate MOEs are significantly greater
than the target MOE of 1000 (see Table 13).
EPA's original ETU analysis indicated risks above levels of concern for toddler exposure to
transplanted turf treated with maneb and mancozeb. Recognizing that potential risk, the maneb and
mancozeb registrants agreed to reduce the maximum application rate and/or extend the time between
treatment and harvesting of sod from one to three days (i.e., 3 day pre-harvest interval [PHI]).
Additionally, given the typical one to three day installation window following harvesting, the minimum
time that would elapse between treatment and installation of sod in a residential setting would be within
the range of four to six days. Further, the frequent and long duration of watering of newly installed sod
and the need to restrict foot traffic for several weeks after planting should also minimize children's
exposure to residues on transplanted turf. The reduced application rate and/or extended PHI,
combined with the logistics of transplanting turf and installation restrictions, effectively reduced the
potential contribution from this use pattern to a level not of concern to the Agency.
Table 13. Short-Term Aggregate Post-Application Risk Estimates for ETU from All Sources.
Exposure Scenario
Golfing
Home Garden Handler (Handwand)
Home Garden Post-Application
Short-Term MOEs
6200
62000
14450
c. Chronic (Non-Cancer) Aggregate
Chronic aggregate (food + drinking water) risk to metiram-derived ETU is below the Agency's
level of concern. The aggregate chronic risk to metiram-derived ETU was calculated using food and
drinking water only, because metiram does not have residential uses. The chronic aggregate risk
estimate of 7.0% (groundwater) and 6.0% (surface water) of the cPAD (with wine grapes) for the most
highly exposed population subgroup, adults 50+ years, is less than 100% of the cPAD.
Aggregate (food + drinking water) chronic risk to ETU from all sources is also below the
Agency's level of concern. The aggregate chronic risks were calculated using food and drinking water
exposure only, because golfing, athletic field and toddler transplanted turf exposure scenarios were
considered to occur only on a short-term basis. The chronic aggregate risk estimate of 56% (surface
water) and 58% (groundwater) of the cPAD for the most highly exposed population subgroup, children
1 to 2 years old, is less than 100% of the cPAD. Note that the ETU chronic exposure estimate from all
sources does not include potential exposure from imported wine grapes.
25 of 108
-------
d. Cancer Aggregate
Cancer aggregate (food + drinking water) risk to metiram-derived ETU for the general U.S.
population is below the Agency's level of concern. Aggregate cancer risk estimates of 3 x 10"7
(groundwater) and 2 x 10"7 (surface water) are considered to be negligible.
If the proposed import tolerance on wine grapes is included, aggregate cancer risks for
metiram-derived ETU are also below the Agency's level of concern; for groundwater the aggregate
cancer risk is 7 x 10"7 and for surface water the aggregate cancer risk is 5 x 10"7.
Aggregate cancer risk estimates for exposure to ETU from all sources are in the range of 2 x
10"6, and food is the largest contributor. The Agency considers cancer risks as high as 3 in 1 million to
be within the negligible risk range. The aggregate cancer risk estimates are within this range of risk, and
therefore are considered negligible. The cancer risks were aggregated using the food and drinking
water exposure estimates for the general population and the food, water and recreational doses for
golfers, home gardeners and athletes. Note that the residential contribution to this risk estimate is a
result of the application of mancozeb. Metiram does not have residential uses.
9. Occupational Risks
Workers can be exposed to metiram and metiram-derived ETU through mixing, loading, and/or
applying the pesticide to apples, potatoes (foliar and seed piece) and ornamentals (ferns), or re-entering
treated sites. Note that rose and tobacco uses have been voluntarily cancelled as a result of risk
concerns, and are no longer included in the risk assessment. Occupational non-cancer risk to workers
is measured by a Margin of Exposure (MOE), which determines how close the occupational exposure
comes to a NOAEL. However, the occupational assessment does not consider an FQPA SF for
sensitive populations (infants or children), nor is it affected by the FQPA database uncertainty factor
being applied to dietary exposures for metiram. Thus, the target MOE for occupational risk is 100, and
MOEs greater than 100 do not exceed the Agency's level of concern. For occupational cancer risks,
as for dietary cancer risk and as described above in Section ni.A.5., risk estimates within the range of
an increased cancer risk of 1 x 10"6 (one in a million) generally do not exceed the Agency's level of
concern. When occupational MOE are less than 100 or occupational cancer risks exceed the range of
an increased risk of 1 x 10"6, EPA strives to reduce worker cancer risks through the use of personal
protective equipment and engineering controls or other mitigation measures. The Agency generally
considers occupational cancer risks within the range of an increased cancer risk of 1 x 10"6 or less to be
negligible, but will consider risks as high as 1 x 10"4 (1 in 10,000 persons) when all mitigation measures
that are feasible have been applied, and when evaluating the advantages associated with the use of the
pesticide. The cancer risks for application of metiram to agricultural crops are as a result of exposure
to ETU, and calculated by estimating 30 days of exposure per year.
References to ETU in the occupational risk section of this document refer to metiram-derived
ETU from three sources, ETU formed in tank mixes, ETU formed in the body by metabolic conversion,
26 of 108
-------
and ETU formed in the environment through degradation. For both handler and post-application
assessments, the metiram dose considered ETU from metabolic conversion of metiram to ETU and
from metiram converted to ETU in tank mixes. Handler assessments addressed combined dermal and
inhalation exposures, but post-application risks were derived solely from dermal exposure.
Occupational risk is assessed based on exposures at the time of application (termed "handler"
exposure) and following application, or post-application exposure. Application parameters are
generally defined by the physical nature of the formulation (e.g., formula and packaging), by the
equipment required to deliver the chemical to the use site, and by the application rate required to
achieve an efficacious dose. Post-application risk is assessed for activities such as scouting, irrigating,
pruning, and harvesting and is based primarily on dermal exposure estimates. Note that occupational
risk estimates are intended to represent pesticide workers, and on this basis assumptions are made
concerning acres treated per day and the seasonal duration of exposure.
For more information on the assumptions and calculations of potential risks to workers handling
metiram or working in metiram treated areas, see the Metiram: Occupational and Residential
Exposure Assessment and Recommendations for the Reregistration Eligibility Decision
Document dated June 8, 2005, which is available in the public docket OPP-2005-0177.
a. Occupational Handler Exposure
For handlers, most exposures were considered to be short-term (1-30 days) or intermediate-
term (1-6 months) in duration, with the exception of greenhouse uses, which may result in chronic
(>180 days) exposure. For handler assessments that consider exposure to ETU, non-cancer short-
term and intermediate-term risks were the same, but chronic risks were assessed using a different
lexicological dose and endpoint. For the metiram handler assessments, metiram dermal and inhalation
exposures could not be combined, since the endpoints (toxic effects) selected for risk assessment were
different. For non-cancer assessments that consider ETU, dermal and inhalation exposures were
combined because the endpoints selected as the basis for risk (thyroid effects) assessment were similar.
No chemical-specific handler exposure studies were submitted in support of the reregistration
of metiram, so Pesticide Handler Exposure Database (PHED, Version 1.1, 1998) data were used to
calculate unit exposure values to estimate occupational handler exposures to metiram and ETU during
application to crops and ornamentals. There are no recent or adequate data (either chemical-specific
or in PHED) that reflect the specifics of the potato seed-piece treatment scenario; therefore, PHED
data for other scenarios were extrapolated to approximate seed-piece treatment. Moreover, standard
assumptions were used for the number of acres treated, body weight, hours worked, etc. for most
handler scenarios. For the potato seed-piece use, assumptions were based on conversations with
experts in the potato industry.
Occupational handler assessments are conducted using increasing levels of protection. The
Agency typically evaluates all exposures with minimal protection and then considers additional
27 of 108
-------
protective measures using a tiered approach (going from minimal to maximum levels of protection) in an
attempt to assess reduction in exposure achieved by each protective measure. The lowest tier is
represented by the baseline clothing scenario (i.e., single layer clothing, socks, and shoes), followed
by, if MOEs are of concern, increasing levels of risk mitigation, such as personal protective equipment
(PPE) and engineering controls (EC). End-use product PPE will be assessed on a product-by-product
basis. Metiram labels currently require double layer PPE and a chemical resistant apron for
mixing/loading and double layer PPE without the apron for application. The labels do not require
respiratory protection.
1) Agricultural and Greenhouse Handler Risks
To assess occupational agricultural and greenhouse handler risks, the Agency conducted the
following risk assessments:
• Metiram - (Non-cancer)
- Short-term dermal (MOEs)
- Intermediate-term dermal (MOEs)
- Inhalation (combined short and intermediate-term MOEs)
• ETU - (Non-cancer - combined dermal and inhalation MOEs)
ETU - (Cancer)
Metiram short-term dermal and ETU non-cancer (combined dermal and inhalation) MOEs are
greater than the target MOE of 100 for all scenarios at baseline protection, and are not of risk concern.
Therefore, to simplify this occupational risk summary, only metiram intermediate-term dermal MOEs,
metiram inhalation (combined short and intermediate-term) MOEs, and ETU cancer risk estimates are
tabulated in this section. Dermal and inhalation metiram risks for occupational agricultural and
greenhouse handlers are summarized in Tables 14 and 15, respectively. ETU cancer risks for
agricultural and greenhouse use are summarized in Table 16.
Table 14. Summary of Metiram Intermediate Term Dermal MOEs for Agricultural Crops
Exposure Scenario
Crop Type
Applicatio
n Rate
Ob
ai/acre)
Acres
per
Day
Dermal MOES
Has
e-
line
PPE
Singl
e
Laye
r
PPE
Doubl
e
Layer
PPE
Eng
Cont
Mixer/Loader
Mix/Load DF for Aerial Application
or Chemigation
Mix/Load DF for Groundboom
apples (pre-bloom)
potatoes
leatherleaf ferns
potatoes
leatherleaf ferns
4.8
1.6
1.6
1.6
1.6
350
350
40
80
40
25
76
660
330
660
25
76
660
331
660
35
106
930
465
930
No Data
No Data
No Data
No Data
No Data
28 of 108
-------
Table 14. Summary of Metiram Intermediate Term Dermal MOEs for Agricultural Crops
Exposure Scenario
Mix/Load DF for Airblast
Mix/Load DF for HP Handwand
Crop Type
apples (pre-bloom)
ferns
Applicatio
n Rate
(Ib
ai/acre)
4.8
1.6
Acres
per
Day
40
10
Dermal MOES
Has
e-
line
PPE
220
>100
0
Singl
e
Laye
r
PPE
220
>100
0
Doubl
e
Layer
PPE
310
>1000
Eng
Cont
No Data
No Data
Applicator
Aerial Application
Groundboom Application
Airblast Application
F1P Handwand Application
apples (pre-bloom)
potatoes
potatoes, ferns
apples (pre-bloom)
ferns
4.8
1.6
1.6
4.8
1.6
350
350
40 to
80
40
10
Not Applicable
>100
0
41
>140
>100
0
100
>450
>1000
120
>600
330
1000
>1000
770
No Data
Mixer/Loader/Applicator
Mix/Load/ Apply DF with LP
Handwand
Mix/Load/Apply DF with Backpack
Sprayer
ferns
ferns
1.6
1.6
0.4
0.4
ND
>500
>700
NA
No Data
Flagger
Flag Aerial Applications (8)
apples (pre-bloom)
potatoes
4.8
1.6
350
350
150
460
140
420
150
450
7600
23000
Note - The target MOE is 100. MOEs less than 100 are of concern and are shown in bold font.
MOE = Margin of Exposure = NOAEL/estimated exposure. The target MOE for metiram and ETU is 100.
PPE = Personal Protective Equipment: The various levels of PPE are defined as follows:
Baseline = long-sleeved shirt, long pants, shoes, socks, and no gloves.
Single Layer = Baseline + gloves.
Double Layer = Single Layer + Coveralls.
Eng. Controls = Enclosed cockpit or cab, water soluble packaging, closed loading systems. Eng. Controls are not
applicable to hand-held application methods.
Table 15. Summary of Metiram Inhalation MOEs for Agricultural Crops
Exposure Scenario
Crop
Application
Rate
(Ib a.i. per
acre)
Acres
Treated
per
Day
Inhalation MOEs
Baselin
e(No
Resp)
PF5
Respirat
or
PF10
Respirat
or
Eng
Contro
1
Mixer/Loader
29 of 108
-------
Table 15. Summary of Metiram Inhalation MOEs for Agricultural Crops
Exposure Scenario
Mix/Load DF for Aerial
Application or Chemigation
Mix/Load DF for Groundboom
Mix/Load DF for Airblast
Mix/Load DF for HP Handwand
Crop
apples
potatoe
s
ferns
potatoe
s
ferns
apples
ferns
Application
Rate
(Ib a.i. per
acre)
4.8
1.6
1.6
1.6
1.6
4.8
1.6
Acres
Treated
per
Day
350
350
40
80
40
40
10
Inhalation MOEs
Baselin
e(No
Resp)
27
81
710
360
710
240
>1000
PF5
Respirat
or
140
420
3600
>1000
>1000
>1000
>1000
PF10
Respirat
or
270
810
7100
>1000
>1000
>1000
>1000
Eng
Contro
1
No
Data
No
Data
No
Data
No
Data
No
Data
No
Data
No
Data
Applicator
Aerial Application
Groundboom Application
Airblast Application
F1P Handwand Application
apples
potatoe
s
potatoe
s
ferns
apples
ferns
4.8
1.6
1.6
1.6
4.8
1.6
350
350
80
40
40
10
Not Applicable
370
>1000
41
>500
>1000
>1000
200
>1000
>1000
>1000
400
>1000
310
920
>1000
>1000
400
No
Data
Mixer/Loader/Applicator (M/L/A)
M/L/A DF with Low Pressure
Handwand
M/L/A DF with Backpack Sprayer
ferns
ferns
1.6
1.6
0.4
0.4
50
250
500
NA
No Data
Flagger
Flag Aerial Applications
apples
potatoe
s
4.8
1.6
350
350
60
180
300
890
600
1800
3000
8900
Note - The target MOE is 100. MOEs less than 100 are of concern and are shown in bold font.
MOE = Margin of Exposure = NOAEL/estimated exposure. The target MOE for metiram and ETU is 100.
PPE = Personal Protective Equipment: The various levels of PPE are defined as follows:
Baseline = long-sleeved shirt, long pants, shoes, socks, and no gloves or respiratory protection.
PF5 = Respirator with 80% protection (dust/mist).
PF10 = Respirator with 90% protection (half face with dust/mist filters).
30 of 108
-------
Metiram Dermal and Inhalation Risks: All of the short-term dermal MOEs for metiram are greater
than 100 and, therefore, the risks are not of concern and not presented in detail in this section. The
intermediate-term dermal MOEs for metiram are of concern with label required PPE for only one
scenario; mixing/loading for aerial application (Table 14). However, Agency information indicates that
the aerial application method is used on apples less than 5% of the time; thus, it is unlikely that
intermediate-term exposures occur. The inhalation MOEs for metiram are of concern with baseline
PPE for two mixer/loader scenarios, one application scenario, one mixer/loader/applicator scenario,
and one flagger scenario (Table 15). These risks can be managed in all cases by the addition of PF5
respiratory protection (dust/mist respirator). Also, the risks for mixing/loading/applying dry flowable
formulations with a low pressure hand-wand are based upon wettable powder data and are considered
to be an overestimate.
ETU Non-Cancer Risks: The short/intermediate-term MOEs are all 1000 or greater for all of the
scenarios at all levels of PPE, which is well above the target MOE of 100. The chronic MOEs for
ETU are 260 or greater for all scenarios, which is also greater than the target MOE and not of risk
concern. Because these risks are not of concern, they are not tabulated in this section.
Table 16. Summary of ETU Cancer Risks for Crop Treatment (30 Days per Year)
Exposure Scenario
Crop
Applicat
ion
Rate
(Ib
ai/acre)
Acres
Treated
per Day
Single
Layer
Double
Layer
Single
Layer
PF5
Single
Layer
PF10
Double
Layer
PFiO
Eng
Control
Mixer/Loader
Mix/Load DF for
Aerial
Mix/Load DF for
Chemigation
Mix/Load DF for
Groundboom
Mix/Load DF for
Airblast
Mix/Load DF for HP
Handwand
apples
potatoes
potatoes
ferns
potatoes
ferns
apples
ferns
2.2
1.5
1.5
1.3
1.5
1.3
2.2
1.3
350
350
350
40
80
40
40
10
3e-06
2e-06
2e-06
3e-07
5e-07
3e-07
4e-07
7e-08
3e-06
2e-06
2e-06
2e-07
5e-07
2e-07
3e-07
6e-08
2e-06
le-06
le-06
2e-07
3e-07
2e-07
3e-07
4e-08
2e-06
le-06
le-06
2e-07
3e-07
2e-07
2e-06
4e-08
le-06
le-06
le-06
le-07
2e-07
le-07
2e-07
3e-08
ND
ND
ND
ND
ND
ND
ND
ND
Applicator
Aerial Application
Groundboom
Application
Airblast Application
apples
potatoes
potatoes
ferns
apples
2.2
1.5
1.5
1.3
2.2
350
350
80
40
40
N/A
3e-07
le-07
2e-06
3e-07
le-07
le-06
le-07
5e-08
7e-07
8e-08
4e-08
6e-07
7e-08
3e-08
5e-07
3e-07
2e-07
4e-08
2e-08
2e-07
31 of 108
-------
HP Handwand
Application
ferns
1.3
10
4e-07
3e-07
3e-07
2e-07
2e-07
NA
Mixer/Loader/Applicator (M/L/A)
M/L/A DF with
Backpack Sprayer
M/L/A DF with LP
Handwand
ferns
ferns
1.3
1.3
0.4
0.4
No Data
2e-06
2e-06
5e-07
3e-07
3e-07
NA
Flagger
Flag Aerial Spray
Applications
apples
potatoes
2.2
1.5
350
350
le-06
7e-07
le-06
7e-07
5e-07
3e-07
4e-07
3e-07
3e-07
2e-07
2e-08
le-08
Note - None of the cancer risks are greater than 1.0x10 at any level of PPE.
ETU Cancer Risks: All of the ETU cancer risk estimates are within the range of an increased cancer
risk of 1 x 10"6 (i.e., negligible) with single layer PPE. The ETU cancer risks are summarized in Table
16 above.
2) Handler Risk for Potato Seed-Piece Treatment
To assess occupational handler potato seed-piece treatment risks, the Agency conducted the
following risk assessments:
• Metiram - (Non-cancer)
- Short-term dermal (MOEs)
- Intermediate-term dermal (MOEs)
- Inhalation (combined short and intermediate-term MOEs)
• ETU - (Non-cancer - combine dermal and inhalation MOEs)
ETU - (Cancer)
32 of 108
-------
Table 17. Metiram Intermediate Term Dermal MOEs for Seed Piece Treatment
Exposure Scenario
Load Dusts for Commercial Seed Piece
Treatment (1)
Load Dusts for On-Farm Seed Piece
Treatment (2)
Apply Dusts During Commercial Seed Piece
Treatment (3)
Apply Dusts During On-Farm Seed Piece
Treatment (4)
Load Treated Seed Pieces for Planting (5)
Plant Treated Seed Pieces (6)
Treatment
Rate
0.105 Ib
a.i./cwt
0.105 Ib
a.i./cwt
2.1 Ib
a.i./acre
Amount
Treated
per day
10000 cwt
800 cwt
10000 cwt
800 cwt
40 acres
Dermal MOEs
Baseline
PPE
1
9
Single
Layer
PPE
16
200
Double
Layer
PPE
21
260
Eng
Control
270
>1000
No Data
>1000
>1000
>1000
>1000
>1000
>1000
No Data
>1000
Table 18. Metiram Inhalation MOEs for Seed Piece Treatment
Exposure Scenario
Load Dusts for Commercial Seed Piece
Treatment (1)
Load Dusts for On-Farm Seed Piece
Treatment (2)
Apply Dusts During Commercial Seed
Piece Treatment (3)
Apply Dusts During On-Farm Seed Piece
Treatment (4)
Load Treated Seed Pieces for Planting (5)
Plant Treated Seed Pieces (6)
Treatment
Rate
0.105 Ib
a.i./cwt
0.105 Ib
a.i./cwt
2.1 Ib
a.i./acre
Amount
Treated
per Day
10000
cwt
800 cwt
10000
cwt
800 cwt
40 acres
Inhalation MOEs
Baseline
(No
Resp)
1
10
PF5
Respirator
4
48
PF10
Respirator
8
97
Eng
Control
140
1700
No Data
No Data
240
350
1200
1700
2400
3500
No Data
1900
Metiram Non-Cancer Risks: All of the metiram short-term dermal exposures exceed the target MOE
with single layer PPE (the current product labels require double layer PPE) and are greater than the
corresponding intermediate-term dermal MOEs, and therefore are not tabulated in this section.
Intermediate-term dermal (see Table 17) and inhalation (see Table 18) risks of concern are indicated
for handlers loading dusts for commercial seed-piece treatment, and would require engineering controls
to achieve the target MOE of 100.
33 of 108
-------
ETUNon-Cancer Risks: The ETU short/intermediate-term dermal and inhalation MOEs for seed
piece treatment are greater than the corresponding MOEs for metiram, and are above 100 for all of the
scenarios if single layer PPE with a PF5 respirator is worn. As such, these risk estimates are not
tabulated in this section. Also, chronic risks were not calculated for the seed piece treatment scenarios,
because the treatment of potato seed-pieces only occurs for several weeks per year during the potato
planting season.
Table 19. Cancer Risks for Metiram Seed Piece Treatment (30 Exposure Days per Year)
Exposure Scenario
Applicatio
nRate
Area
Treated
per day
Single
Layer
Double
Layer
Single
Layer
PF5
Double
Layer
PF10
Eng
Control
Mixer/Loader
Load Dusts for Commercial Seed Piece
Treatment
Load Dusts for On-Farm Seed Piece
Treatment
0.105 Ib
a.i./cwt
10000
cwt
800 cwt
1.3e-04
le-05
1.3e-04
le-05
3e-05
2e-06
5e-06
4e-07
le-06
8e-08
Applicator
Apply Dusts During Commercial or
On-Farm Seed Piece Treatment
0.105 Ib
a.i./cwt
800 to
10000
cwt
no data are available
Secondary Handler
Load Treated Seed Pieces
Plant Treated Seed Pieces
2.1 Iba.i.
40 acres
4e-07
3e-07
4e-07
3e-07
le-07
8e-08
5e-08
le-08
No Data
6e-08
Cancer risks that exceed l.Oe-04 are shown in bold font.
ETU Cancer Risks: The cancer risks for loading dusts for commercial seed-piece treatment exceed 1
x 10"4 with label required PPE (i.e. double layer). Engineering controls would be needed for this
scenario to achieve a cancer risk within the range of 1 x 10"6. The risks of handling the treated seed
pieces is less than 1 x 10"6 with baseline PPE (Table 19).
b. Post-Application Assessments
The post-application occupational risk assessment considers exposure to chemical metiram and
metiram-derived ETU from entering treated fields, orchards, and greenhouses. Given the nature of
activities in these locations and that metiram is applied at various times during plant growth, contact with
treated surfaces is likely. A variety of post-application exposure scenarios were identified by the type
of activity involved and by the range of exposure expected, i.e., low, medium and high exposure
activities. Examples of low exposure activities include irrigation and scouting; medium exposure
activities may involve scouting of mature plants, or in greenhouses, hand pinching certain plants.
Potential high exposure activities include hand harvesting leatherleaf ferns, and thinning and pruning
34 of 108
-------
apples. In the Worker Protection Standard, a Restricted-Entry Interval (REI) is defined as the duration
of time which must elapse before residues decline to a level so entry into a previously treated area and
engaging in any task or activity would not result in exposures which are of concern.
Occupational Post-Application Exposures and Assumptions
One chemical-specific dislodgeable foliar residue (DFR) study was submitted for metiram, and
was used, along with transfer coefficients selected from the Agricultural Re-entry Task Force (ARTF)
data, to estimate post-application exposure and risk for all crops/ornamentals potentially treated with
metiram. The DFR study was conducted on apples in California, and is considered likely to provide
high-end estimates of post-application exposures calculated for ferns, as well as for crops grown under
more humid conditions or with more rainfall.
Metiram Non-Cancer Post-Application Risks: Current label requirements specify a 24 hour REI. All
of the short-term metiram MOEs exceed 100 on day 0 and, as such, are not of concern to the Agency
and not presented in this section. The intermediate/chronic MOEs for metiram are shown below in
Table 20. The time needed to achieve a metiram MOE of 100 is 28 days for high exposure activities
with apples (pruning, training, and tying).
Table 20. Metiram Post-Application Non-Cancer Risks (Intermediate/Chronic)
Crop Group
Leather Leaf Fern Cuttings
Leather Leaf Ferns in Containers
Apples
Potatoes
Application Rate
(Ib ai/acre)
1.6
1.6
2.4
1.6
MOE on Day 0 (Days when MOE> 100)
Very Low
Exposure
NA
NA
1600
NA
Low
Exposure
NA
2200
160
810
Medium
Exposure
NA
1400
NA
160
High
Exposure
90
610
54 (28)
NA
ETU Non-Cancer Post-Application Risks: All of the short/intermediate-term MOEs for ETU exceed
100 at day zero, and, as such, are not of concern and are not presented in this section. EPA also
assessed chronic ETU non-cancer risks for greenhouse grown ferns, which are assumed to have
chronic re-entry exposures. The chronic ETU MOE for fern cutting harvesting is 73 at day zero. This
MOE increases to 100 twenty days after treatment (Table 21).
Table 21. ETU Post-Application Chronic Non-Cancer Risks
Crop Group
Leather Leaf Fern Cuttings
Application Rate
(Ib ai/acre)
1.3
Chronic MOE on Day 0 (Days when MOE>100)
Very Low
Exposure
NA
Low
Exposure
NA
Medium
Exposure
NA
High
Exposure
73(20)
35 of 108
-------
Table 21. ETU Post-Application Chronic Non-Cancer Risks
Crop Group
Leather Leaf Fern Plants
Application Rate
(Ib ai/acre)
1.6
Chronic MOE on Day 0 (Days when MOE>100)
Very Low
Exposure
NA
Low
Exposure
1800
Medium
Exposure
1100
High
Exposure
490
ETU Cancer Post-Application Risks: The ETU cancer risks are < 9 x 10"6 on the day of application
for all of the scenarios, with risks exceeding the range of 1 x 10"6 only in two high exposure scenarios
(Table 22).
Table 22. ETU from Metiram Post-Application Cancer Risks
Crop Group
Leather Leaf Fern
Cuttings
Leather Leaf Fern Plants
Apples
Potatoes
Application
Rate
(Ib ai/acre)
1.3
1.6
2.4
1.5
Cancer Risk on Day 0
Very Low
Exposure
NA
NA
3e-07
NA
Low
Exposure
NA
3e-07
3e-06
6e-07
Medium
Exposure
NA
4e-07
NA
3e-06
High Exposure
4e-06
9e-07
9e-06
NA
c.
Human Incident Data
The most recent assessment of metiram incident reports was completed in 2002.
Information sources consulted included the OPP Incident Data System (IDS); the Poison Control
Centers (1993 -1998); the California Department of Pesticide Regulation survey information collected
from 1982 to present; and the National Pesticide Telecommunications Network (NPTN). In all, only
one occupational incident was reported for metiram, through the Poison Control Centers; the incident
involved exposure to the eye for one adult, and only minor effects were noted.
B.
Environmental Risk Assessment
A summary of the Agency's environmental risk assessment is presented below. For detailed
discussions of all aspects of the environmental risk assessment refer to, Environmental Fate and
Ecological Risk Assessment for Metiram, Section 3 Reregistration for Control of Fungal Diseases
on Apples, Potatoes, Potato Seed, Certain Ornamental Plants and Tobacco Seedling Plants
(Phase 3 Response), dated June 21, 2005, which is available on the internet and in the public docket.
1. Environmental Fate and Transport
36 of 108
-------
Metiram is a high molecular weight polymer composed of repeating single units containing zinc
ions. Parent metiram is nearly insoluble in water, but is expected to decompose rather quickly by
hydrolytic reactions into a multi-species residue (the metiram complex) consisting of transient species
and degradates, including the degradate of concern ETU and its degradates. Most of the species
present in the metiram residue are expected to partition into the soil/sediment particles; with varied
strength of bonding. These soil associated materials are not largely affected by abiotic degradation, but
are susceptible to very slow bio-degradation possibly further producing degradates, including ETU, at a
very slow rate.
Due to rapid hydrolytic decomposition (1 week), parent metiram is expected to exist in most
natural environment for a short duration (few days) when moisture is available. Parent metiram appears
to be stable in alkaline (75 hours at pH 9) compared to neutral (44 hours at pH 7) to acidic (33 hours
at pH 5) conditions. Metiram has low octanol/water partition coefficients (Kow), especially in neutral to
alkaline aqueous environments (pH = 5-8.5), which strongly suggest that it would not be significantly
bio-concentrated by aquatic organisms such as fish. Furthermore, metiram has a very low vapor
pressure, thus indicating that volatilization is not an important dissipation pathway.
The degradate of concern (ETU) is predicted to be susceptible to leaching due to its high
solubility and mobility. In the soil environment, ETU lacks stability which can limit its leaching;
however, its possible slow and steady formation from metiram complex can overcome the lack of
stability and make it available for leaching at low concentrations. ETU has an aerobic soil half-life of
about 3 days; in the absence of data, the aquatic aerobic metabolism half-life was assumed to be about
6 days, or double the soil half life. The measured anaerobic aquatic metabolism half-life, however, is
substantially longer (149 days) possibly leading to the periodic detections in groundwater. ETU is
highly soluble in water (20,000 ppm), highly vulnerable to indirect photolysis (half-life= 1 day), and
moderately mobile (288 L/kg). It also has a high vapor pressure, but high solubility reduces the
possibility of losses from surface water due to volatilization.
2. Ecological Risk Presumptions
The pesticide use profile, exposure data, and toxicity information are used to determine risk
estimates to non-target terrestrial and aquatic organisms. The estimated environmental concentrations
(EECs) are used to calculate RQs. An RQ is the estimated ratio of exposure concentration to the
toxicity endpoint. The calculated RQs use the EECs that are based on the maximum single application
rate of metiram, which would yield the maximum metiram exposure estimates. The RQ is then
compared to the Level of Concern (LOG) to predict if exposure to metiram and its degradates could
pose a risk to non-target organisms. Table 23 outlines the Agency's LOCs and the corresponding risk
presumptions.
37 of 108
-------
Table 23. Agency's LOCs and Risk Presumptions
If RQ > LOC value given below
Terrestrial
Organisms
0.5
0.2
0.1
1
Aquatic
Organisms
0.5
0.1
0.05
1
Plants
1
N/A
1
N/A
Then EPA presumes .. .
Risk Presumption
Acute Risk - there is potential for acute risk; regulatory action
may be warranted in addition to restricted use classification.
Acute Restricted Use - there is potential for acute risk, but
may be mitigated through restricted use classification.
Acute Endangered Species - endangered species may be
adversely affected; regulatory action may be warranted.
Chronic Risk - there is potential for chronic risk; regulatory
action may be warranted.
Note that the following ecological risks are based on parent metiram only. EPA did not
estimate ETU exposure or potential ecological risk from ETU as a result of use of metiram. The
Agency expects ecological ETU exposure and risk resulting from metiram's uses to be encompassed
by ETU exposure and risk resulting from mancozeb's uses because the EBDCs share similar
application patterns. The Agency chose ETU from mancozeb uses as a surrogate assessment to
determine exposure and risk from any ETU because mancozeb has the broadest use pattern of the
EBDCs, thus providing a comprehensive view of risks posed by ETU. ETU exposure and risk as a
result of mancozeb application are addressed in the mancozeb RED.
In summary, chronic mammalian ETU RQs exceed the LOC for most of mancozeb's use
patterns, especially for small- and medium-sized mammals. ETU is practically acutely nontoxic to
mammals, and EPA does not expect acute risks to mammals from ETU exposure. EPA does not have
any toxicity data to evaluate ETU's toxicity to birds. In aquatic habitats, RQs are less than the LOCs
for ETU's acute risk to freshwater fish, freshwater invertebrates, and nonvascular plants from use of
mancozeb. The Agency does not have data to evaluate ETU's acute risks to estuarine/marine fish and
invertebrates, and vascular aquatic plants. Overall, based on available toxicity data, the ETU ecological
risks assessed for mancozeb use are less than the corresponding metiram parent risks. As such,
measures to address ecological risk from metiram parent, as part of this RED, will address potential
metiram-derived ETU exposures as well.
3. Risk to Terrestrial Species
a. Birds and Mammals Exposure and Toxicity
The Agency assessed exposure to terrestrial species by first predicting the amount of metiram
residues found on animal food items and then using information on typical food consumption by various
species of birds and mammals, to predict the amount of pesticide that could be consumed. The amount
38 of 108
-------
of residues on animal feed items are based on the Fletcher nomogram which is a model developed by
Hoerger and Kenaga (1972) and modified by Fletcher (1994). Thus, EPA modeled the maximum and
mean residues of metiram, immediately following a single application at 1 Ib ai/A. EPA's estimates of
metiram residues on various wild animal food items are summarized in Table 24. EPA used these
EECs and standard food consumption values to estimate dietary exposure levels for metiram to birds
and mammals.
Table 24. Estimated Environmental Concentrations on Avian and Mammalian Food Items
Food Items
Short grass
Tall grass
Broadleaf plants and small insects
Fruits, pods, seeds, and large insects
EEC (ppm)
Predicted Maximum Residue1
240
110
135
15
EEC (ppm)
Predicted Mean
Residue1
85
36
45
7
1 Predicted maximum and mean residues are for a 1 Ib ai/a application rate and are based on Hoerger and Kenaga (1972) as
modified bv Fletcher and others. (19941
Metiram is categorized as practically nontoxic to avian species and small mammals on an acute
oral basis. However, metiram as slightly toxic to avian species on a subacute dietary basis. The acute
toxicity profile for birds and mammals is summarized in Table 25.
Table 25. Metiram Acute Toxicity Endpoints for Birds and Mammals
Toxicity Study
Test Species
% a.i.
Endpoint
Toxicity
Category
MRTDor
Accession No.
Acute (Single dose by garage)
Avian Oral
Mammalian Oral
Mammalian Oral
Bobwhite Quail
Laboratory Rat
Laboratory Rat
95
Technical
80
LD50 = >2,150 mg/kg/day
LD50 = >10,000 (male) &
8,000 (female) mg/kg/day
LD50 = >5,000 (male&
female) mg/kg/day
Practically
nontoxic
Practically
nontoxic
Practically
nontoxic
406569901
009768
009926
Subacute (Five days of treated feed}
Avian Dietary
Avian Dietary
Bobwhite Quail
Mallard Duck
80
80
LC50 = 3,712 ppm ai
LC50 = >3,712 ppm ai
Slightly toxic
Slightly toxic
00108005
00108004
In a metiram avian reproduction study using the mallard duck, chronic toxic effects seen
included the following: reduced egg production; reduced mean egg weight; reduced fertility rate;
39 of 108
-------
reduced number of hatched ducklings; reduced number of 14-day old survivors; and an increased rate
of early embryonic deaths. Results from a chronic 3-generation reproduction study in rats for metiram
indicate parental and reproductive toxicity with parental toxicity resulting in decreased body weight
during gestation and lactation for females, and reproductive toxicity resulting in decreased mating
performance (increased precoital time) in the F2 generation (two generations removed from the original
parent generation). The chronic toxicity endpoints for birds and mammals are summarized in Table 26.
Table 26. Metiram Chronic Toxicity Endpoints for Birds and Mammals
Test Species
Mallard Duck
Laboratory rat
%ai
97
96.8
NOAEC
or
NOAEL
(ppm)
50
40
LOAEC
or
LOAEL
(ppm)
300
320
Effects at LOAEC or LOAEL
Reduced hatchling survival at 14 days
Reduced body weight and mating in
offspring
MRIDor
Accession
No.
42539102
247214
NOAEC / LOAEC = No Observable Adverse Effect Concentration, the highest dose at which no adverse health effect is
observed./ Lowest Observable Adverse Effect Concentration, the lowest dose at which an adverse health effect is observed.
NOAEL / LOAEL= No Observable Adverse Effect Level, the highest dose at which no adverse health effect is observed /
Lowest Observable Adverse Effect Level, the lowest dose at which an adverse health effect is observed.
b.
Birds and Mammals Risk
Avian and mammalian RQs exceed the chronic LOCs for almost all use metiram modeled
exposures. Based on multiple applications, the chronic RQs for birds range from 76 on apples to a low
of 1 on ornamentals using a default half-life value of 35 days. The 35-day value is a standard Agency
default value when total foliar dissipation half-life is unknown for a pesticide. Table 27 summarizes the
avian acute (based on maximum EEC values) and chronic (based on maximum and mean EEC values)
RQs, from multiple applications of metiram.
Table 27. Avian Acute/Chronic RQs from Metiram Application
Crop
Apples
Potatoes
Ornamentals (nonflowering plants)
Maximum
Application
Rate
(Ibs a.i./A)
4.8
1.6
1.6
Avian
Acute RQs
(LCSO=3,712 ppm)
Based on
maximum EECs
Avian
Chronic RQs (NOAEC= 50 ppm)
Based on
maximum EECs
Based on
mean EECs
Range = Shortgrass - Seeds
1.02-0.06
0.55-0.03
0.27 - 0.02
76-5
41-3
20 -1
27-2
14-1
7-0.6
40 of 108
-------
Chronic RQs for mammals ranged from a high of 95 on apples to a low of 1 on ornamentals
using a 35 day default half-life. The Agency expects risk to metiram to be below the LOG for acute
risk to mammals, because metiram is practically nontoxic (rat LD50 > 5,000 mg/kg) to mammals on an
acute basis. Thus, RQs for acute mammalian exposure were not calculated. Table 28 summarizes the
mammalian chronic RQs from multiple applications of metiram, based on maximum and mean EEC
values.
Table 28. Mammalian Chronic RQs from Metiram Application
Crop
Apples
Potatoes
Ornamentals (nonflowering plants)
Maximum
Application Rate
(Ibs a.i./A)
4.8
1.6
1.6
Mammalian Chronic RQs
(NOAEL= 40 ppm)
Based on maximum EECs
Based on mean EECs
Range = Shortgrass - Seeds
95-6
51-3
25 -2
34-3
18-1
9-0.7
c. Non-Target Plant Risk
Terrestrial plants inhabiting dry and semi-aquatic areas may be exposed to pesticides from
direct applications via runoff, spray drift, or volatilization. RQs could not be calculated because toxicity
data for plants are not available; however, metiram is applied directly to a wide variety of terrestrial
plants with no adverse effects. The potential for acute risks to terrestrial plants at use sites are
unknown. Currently, the Agency does not perform chronic risk assessments for terrestrial plants.
d. Non-Target Insect Risk
Metiram is practically nontoxic to honeybees from acute contact exposure (acute contact LD50
= 437 jig/bee). The Agency does not expect metiram exposure to pose acute risk to non-target
insects, because metiram is practically nontoxic to honeybees and there are no incident data reporting
adverse effects to honeybees.
4. Risk to Aquatic Species
a. Fish and Invertebrate Exposure and Toxicity
Unlike the drinking water assessment described in the human health risk assessment section of
this document, the ecological water resource assessment does not include the Index Reservoir (IR) and
Percent-Crop Area (PCA) factor refinements. The IR and PCA factors represent a drinking water
41 of 108
-------
reservoir, not the variety of aquatic habitats, such as ponds adjacent to treated fields, relevant to a risk
assessment for aquatic animals. Therefore, the EEC values used to assess exposure to aquatic animals
are not the same as the values used to assess human dietary exposure from drinking water sources.
EECs were estimated using tier n modeling, the linked PRZM and EXAMS models
(PRZM/EXAMS). In modeling, metiram uses on apples and potatoes were chosen, because they are
the major uses for metiram and PRZM-EXAMS modeling scenarios exist for these uses. The EECs
are used for assessing acute and chronic risks to aquatic organisms. Acute risk assessments are
performed using peak EEC values for single and multiple applications. Chronic risk assessments are
performed using the 21-day EECs for invertebrates and 60-day EECs for fish. Table 29 summarizes
the aquatic EECs for metiram.
Table 29. Tier n Estimated Environmental Concentrations (EECs) of Metiram in Surface Water (ppb)
Crop
Apples (NC)
Potatoes (ME)
Rate
(Ibs ai/A)
4.8
1.6
Number of
Application
s
4
7
Interval
7
5
Peak
98.9
54.5
96
Hour
55.4
28.1
21
Day
20.7
10.2
60
Day
9.4
5.6
90
Day
5.3
3.8
Annual
Averag
e
1.6
1.4
Acutely, metiram is highly toxic to coldwater freshwater fish (rainbow trout LC50 = 0.23 ppm
based on measured, filtered samples). The acute daphnid study shows metiram to have a freshwater
aquatic invertebrates EC50 value > 0.358 ppm based on measured, unfiltered samples. The study using
freshwater green algae, Ankistrodesmus bibraianus shows metiram to be toxic to aquatic plants (EC50
= 0.077 ppm based on nominal concentrations). Metiram acute toxicity endpoints for freshwater
aquatic fish and invertebrates are summarized in Table 30.
Table 30. Acute Toxicity Endpoints for Aquatic Species
Toxicity Study
Freshwater Fish (flow-through 96-hr)
Freshwater Invertebrate (static 48-hr)
Test Species
Rainbow Trout
Daphnid
%
a.i.
71.04
70
LCjo °r
EC so
(ppm)
0.23
>0.358
Toxicity
Category
Highly Toxic
Highly Toxic
MRID
43525001
44301101
b.
Fish and Invertebrate Risk
The Agency expects metiram to reach aquatic environments through drift and runoff since
metiram is not labeled for direct application to aquatic environments. Metiram is insoluble in water but
the Agency expects it to decompose rather quickly, by hydrolytic reactions, into a multi-species residue
(metiram complex) consisting of transient species and degradates, including the degradate of concern,
42 of 108
-------
ETU. Once metiram reaches the aquatic environment, the Agency believes the metiram complex will
be the portion of the metiram that is biologically available to aquatic organisms. The Agency expects
most of the transient species present in the metiram complex to partition into the sediment particles with
varied strength of bonding. Over time, ETU is the dominant transformation product of the metiram
complex. These metiram complex residues are short-lived in aquatic media, but ETU is persistent in
this media unless it is subjected to rapid degradation by microbes and/or indirect photolysis.
The Agency did not evaluate acute risks to estuarine/marine animals because of the lack of data
(acute toxicity endpoints). Also, because of a lack of chronic toxicity endpoints data, the Agency did
not evaluate chronic risks for freshwater aquatic animals from exposure to metiram residues. The
Agency is reserving the need for chronic studies for estuarine/marine aquatic organisms at this time, until
acute studies for estuarine/marine organisms are received and reviewed, because the acute toxicity for
estuarine/marine organisms is unknown. Metiram acute risk quotients for freshwater fish and
invertebrates are summarized below in Table 31.
Table 31. Acute RQs for Fish and Invertebrates from Metiram Application
Crop
Apples
Potatoes
Maximum Single
Application Rate
(Ibs a.i./A)
4.8
1.6
Peak EEC
(ppb)
98.9
54.5
Freshwater
Acute RQ
Fish
(LC50=230ppb)
0.43
0.24
Invertebrates
(EC50= >358 ppb)
0.28
0.15
c. Non-Target Aquatic Plant Risk
Like terrestrial plants, non-target aquatic plants may be exposed to pesticide from run-off,
spray drift or volatization of metiram. Available information suggests that metiram may be toxic to
nonvascular aquatic plants. The EC50 for freshwater green algae was 77 ppb based on nominal
concentration, and a nominal NOAEC of 13.0 ppb. The potential for acute risks to terrestrial, semi-
aquatic and aquatic vascular plants exposed to metiram at use sites is unknown. EPA will require plant
data to assess acute risks to terrestrial, semi-aquatic and aquatic plants. Currently, the Agency is not
assessing chronic effects on aquatic plants.
Exposure to non-target aquatic plants may occur through runoff or spray drift from adjacent
treated sites. An acute aquatic plant risk assessment is usually made for aquatic vascular plants from
the surrogate duckweed Lemna gibba. Non-vascular acute risk assessments are performed using
either algae or a diatom, whichever is the most sensitive species. Runoff and drift exposure is
computed from PRZM-EXAMS.
43 of 108
-------
The risk quotient is determined by dividing the pesticide's initial or peak concentration in water
by the plant EC50 value. Acute RQs for freshwater, non-vascular green alga (Ankistrodesmus
bibraianus) plants are presented in Table 32. The results indicate that the non-vascular, non-target
plant acute risk LOG of 1 is slightly exceeded for metiram's maximum application on apples.
Table 32. Acute RQs for Aquatic Non- Vascular Plants from Metiram Application
Crop
Apples
Potatoes
Maximum Single
Application Rate (Ibs a.i./A)
4.8
1.6
Peak EEC
(ppb)
98.9
54.5
Acute RQ
(EC so = 77 ppb)
1.28
0.71
5. Risk to Federally Listed Endangered and Threatened Species
Based on available screening-level information, there is a potential concern for acute effects on
listed birds and freshwater fish species, and chronic effects on listed birds and mammals should
exposure actually occur. Even though metiram is only slightly acutely toxic to birds, RQs exceed the
endangered species LOG (RQ range from 0.11 to 1.02) at maximum EEC levels. The Agency does
not currently have data to quantify risks for metiram at the screening-level and can not preclude
potential direct effects to the following taxonomic groups; listed non-target terrestrial plants, freshwater
invertebrates, estuarine/marine fish, or vascular aquatic plants. These findings are based solely on
EPA's screening-level assessment and do not constitute "may affect" findings under the Endangered
Species Act (ESA) for any specific listed species.
The Agency has developed the Endangered Species Protection Program to identify pesticides
whose use may cause adverse impacts on federally listed endangered and threatened species, and to
implement mitigation measures that address these impacts. The ESA requires federal agencies to
ensure that their actions are not likely to jeopardize listed species or adversely modify designated
critical habitat. To analyze the potential of registered pesticide uses that may affect any particular
species, EPA uses basic toxicity and exposure data developed for the REDs and considers ecological
parameters, pesticide use information, the geographic relationship between specific pesticide uses and
species locations and biological requirements and behavioral aspects of the particular species. When
conducted, this analysis will consider regulatory changes recommended in this RED that are
implemented a that time. A determination that there is a likelihood of potential effects to a listed species
may result in limitations on the use of the pesticide, other measures to mitigate any potential effects, or
consultations with the Fish and Wildlife Service or National Marine Fisheries Service as appropriate. If
the Agency determines use of metiram "may affect" listed species or their designated critical habitat,
EPA will employ the provisions in the Services regulations (50 CFR Part 402). Until that species
specific analysis is completed, the risk mitigation measures being implemented through this RED will
reduce the likelihood that endangered and threatened species may be exposed to metiram at levels of
44 of 108
-------
concern.
6. Ecological Incidents
The Ecological Incident Information System (EIIS) indicated there were no adverse effect
incidents to terrestrial or aquatic non-target organisms reported in association with metiram's use.
IV. RISK MANAGEMENT, REREGISTRATION AND TOLERANCE
REASSESSMENT
A. Determination of Reregistration Eligibility
Section 4(g)(2)(A) of FIFRA calls for the Agency to determine, after submission of relevant
data concerning an active ingredient, whether or not products containing the active ingredient are
eligible for reregistration. The Agency has previously identified and required the submission of the
generic (i.e., active ingredient-specific) data to support reregistration of products containing metiram 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 metiram.
The Agency has completed its assessment of the dietary, occupational, residential (as a result of
exposures from mancozeb), and ecological risk associated with the use of pesticide products containing
the active ingredient metiram, including metiram-derived ETU and ETU from all sources. Based on a
review of these data and on public comments on the Agency's assessments for the active ingredient
metiram, the Agency has sufficient information on the human health and ecological effects of metiram to
make decisions as part of the tolerance reassessment process under FFDCA and reregistration process
under FIFRA, as amended by FQPA. The Agency has determined that metiram containing products
are eligible for reregistration provided that: (i) current data gaps and confirmatory data needs are
addressed; (ii) the risk mitigation measures outlined in this document are adopted; and (iii) label
amendments are made to reflect these measures. Label changes are described in Section V. Appendix
A summarizes the uses of metiram that are eligible for reregistration. Appendix B identifies the generic
data requirements necessary as part of the Agency's determination of reregistration eligibility of
metiram, and lists the submitted studies that the Agency reviewed and found acceptable. Data gaps are
identified as generic data requirements that have not been satisfied with acceptable data.
Based on its evaluation of metiram, the Agency has determined that metiram products, unless
labeled and used as specified in this document, would present risks inconsistent with FIFRA and
FQPA. Accordingly, should a registrant fail to implement any of the risk mitigation measures identified
in this document, the Agency may take regulatory action to address the risk concerns from the use of
metiram. If all changes outlined in this document are incorporated into the product labels, then all
current risks for metiram will be adequately mitigated for the purposes of this reregistration
determination.
45 of 108
-------
Although not currently registered, exposure from a proposed import use of metiram on wine
grapes has been assessed. It has also been included in the risk assessment supporting this RED to
assist the Agency in making a determination of whether to establish an import tolerance for metiram use
on wine grapes. Because the determination of establishing this import tolerance is outside the scope of
this RED, it will be made separately by the Agency.
B. Public Comments and Responses
Through the Agency's public participation process, EPA worked extensively with stakeholders
and the public to reach its regulatory decisions for metiram. During the public comment period on the
risk assessments, which closed on February 22, 2005, the Agency received comments from the
registrant, growers and grower groups. These comments in their entirety and the Agency's response
are available in the public docket (OPP-2005-0078) at http://www.epa.gov/edockets.
C. Regulatory Position
1. Food Quality Protection Act Findings
a. "Risk Cup" Determination
As part of the FQPA tolerance reassessment process, EPA assessed the risks associated with
this pesticide. EPA has determined that risk from dietary (food sources only) exposure to metiram is
within its own "risk cup." An aggregate assessment was conducted for exposures to metiram through
food and drinking water only, since there are no registered residential uses of metiram. Because
metiram and the other EBDC fungicides (maneb and mancozeb) degrade to ETU in the environment
and metabolize to ETU in the body, the aggregate assessment considered ETU derived from metiram
and other EBDCs. The Agency has determined that the human health risks from these combined
exposures to both metiram and ETU are within acceptable levels, provided the mitigation measures
stipulated in this document are implemented. In other words, EPA has concluded that the tolerances
for metiram meet FQPA safety standards. In reaching this determination, EPA has considered the
available information on the special sensitivity of infants and children, as well as aggregate exposure
from metiram and ETU.
b. Determination of Safety to U.S. Population (including Infants and
Children)
The Agency has determined that the established tolerances for metiram, with amendments and
changes as specified in this document, meet the safety standards under the FQPA amendments to
section 408(b)(2)(D) of the FFDCA, and that there is a reasonable certainty no harm will result to the
general population or any subgroup from the use of metiram. In reaching this conclusion, the Agency
has considered all available information on the toxicity, use practices and exposure scenarios, and the
46 of 108
-------
environmental behavior of metiram and its ETU metabolite and degradate. EPA has also considered
information on the toxicity of ETU, and the aggregate exposure to ETU, resulting both from the use of
metiram and from the use of the other EBDC fungicides.
As discussed in Chapter m, acute, chronic and cancer dietary (food alone) risks from metiram
are not of concern. Aggregate risk, which combined food, drinking water and residential exposures,
where applicable, from metiram, metiram-derived ETU, and ETU from all sources are also not of
concern. The aggregate risk assessment for ETU considers residential scenarios, because mancozeb
has uses that may result in residential exposure, and degrade to ETU.
c. Endocrine Disrupter Effects
EPA is required under the FFDCA, as amended by FQPA, to develop a screening program to
determine whether certain substances (including all pesticide active and other ingredients) "may have an
effect in humans that is similar to an effect produced by a naturally occurring estrogen, or other
endocrine effects as the Administrator may designate." Following recommendations of its Endocrine
Disrupter Screening and Testing Advisory Committee (EDSTAC), EPA determined that there was a
scientific basis for including, as part of the program, the androgen and thyroid hormone systems, in
addition to the estrogen hormone system. EPA also adopted EDSTAC's recommendation that EPA
include evaluations of potential effects in wildlife. For pesticides, EPA will use FIFRA and, to the
extent that effects in wildlife may help determine whether a substance may have an effect in humans,
FFDCA authority to require the wildlife evaluations. As the science develops and resources allow,
screening of additional hormone systems may be added to the Endocrine Disrupter Screening Program
(EDSP).
The available human health and ecological effects data for metiram suggest possible thyroid
effects, which may indicate potential endocrine disruption. EPA has considered these effects in the
human health risk assessment by selecting endpoints based on thyroid effects. To further address these
effects, EPA is requiring a confirmatory comparative thyroid toxicity study for ETU. Data on ecological
effects suggest possible hormonal effects to birds and mammals. These effects will be addressed when
the Agency's Endocrine Disrupter Screening and Testing Advisory Committee develops appropriate
screening and/or testing protocols. At that time, metiram may be subjected to additional screening
and/or testing to better characterize effects related to endocrine disruption.
d. Cumulative Risks
Risks summarized in this document are those that result only from the use of metiram and its
metabolite, ETU. The FFDCA, as amended by FQPA, requires that the Agency consider "available
information" concerning the cumulative effects of a particular pesticide's residues and "other substances
that have a common mechanism of toxicity." The reason for consideration of other substances is due to
the possibility that low-level exposures to multiple chemical substances that cause a common toxic
effect by a common toxic mechanism could lead to the same adverse health effect as would a higher
47 of 108
-------
level of exposure to any of the substances individually. Metiram belongs to a group of pesticides called
dithiocarbamates, which also includes the EBDC fungicides maneb and mancozeb. For the purposes of
this RED, EPA has concluded that metiram does not share a common mechanism of toxicity with other
substances. The Agency reached this conclusion after a thorough internal review and external peer
review of the data on a potential common mechanism of toxicity. For more information, please see the
December 19, 2001 memorandum, "The Determination of Whether Dithiocarbamate Pesticides
Share a Common Mechanism of Toxicity, "which is available on the internet at
http://www.epa.gov/oppsrrdl/cumulative/dithiocarb.pdf However, the EBDCs share a common
metabolite and degradate, ethylene thiourea (ETU), which is considered in this RED.
2. Tolerance Reassessment Summary
Metiram tolerances are established under 40 CFR §180.217 and are currently expressed in
terms of residues of a fungicide that is a mixture of 5.2 parts by weight of ammoniates of
[ethylenebis(dithiocarbamato)]zinc with 1 part by weight ethylenebis [dithiocarbamic acid] bimolecular
and trimolecular cyclic anhydrosulfides and disulfides, calculated as zinc ethylenebisdithiocarbamate.
Based on a reevaluation of the available plant and livestock metabolism studies, the Agency has
reaffirmed that the residues of lexicological concern, i.e. to be included in risk assessment, are the
parent EBDC.
For regulatory/enforcement purposes, the Agency recommends that tolerances in plant and
livestock commodities at 40 CFR §180.217(a) be established for residues of metiram per se. The
Agency has further proposed that EBDC (including metiram) tolerances be calculated as carbon
disulfide rather than as zineb. The only established metiram tolerances are for apple (2.0 ppm) and
potato (0.5 ppm). No metiram tolerances have been established for animal and processed food/feed
commodities.
a. Tolerances Listed Under 40 CFR §180.217
Adequate residues of metiram and ETU in/on apple and potato have been submitted/evaluated
to reassess the established tolerances. The maximum combined residues of metiram and ETU in/on
apples following treatments were 0.5299 ppm, which is below the established tolerance of 2 ppm.
Considering the conversion factor to CS2 as 0.56x, the available residue data suggest expected
combined residues of about 0.3 ppm and, therefore, the established apple tolerance should be lowered
from 2 ppm to 0.5 ppm.
The maximum combined residues of metiram and ETU in/on potato tubers following treatments
at Ix were <0.03 ppm, which is below the established tolerance of 0.5 ppm. The available residue
data suggest that the established potato tolerance may be lowered from 0.5 ppm to 0.2 ppm to achieve
numerical compatibility with the Codex's maximum residue limit (MRL) for dithiocarbamates on potato.
b. Tolerances To Be Proposed Under 40 CFR §180.217
48 of 108
-------
The available apple data indicates that the combined residues of metiram and ETU
concentrated 5x in wet pomace processed from whole apples bearing detectable residues. Based on a
Highest Average Field Trial (HAFT) of 0.53 ppm and the observed concentration factor of 5x, the
maximum expected combined residue in wet apple pomace is 2.65 ppm. Considering the conversion
factor to CS2 as 0.56x, the data suggest expected combined residues of about 1.7 ppm and, therefore,
a tolerance for residues in wet apple pomace should be established at 2 ppm.
Table 33. Tolerance Reassessment Summary for Metiram.
Commodity
Tolerance Listed
Under 40 CFR (ppm)
Maximum
Residue Value 1
(ppm)
Reassessed
Tolerance2 (ppm)
Comment
[Correct Commodity
Definition/
Tolerance Listed Under 40 CFR §180.217
Apple
Potato
2
0.5
0.5299
<0.03
0.5
0.2
Harmonized
Tolerance To Be Proposed Under 40 CFR §180.217
Apple, pomace, wet
None
0. 53 (HAFT) x 5
(average
concentration
factor) = 2.65
2
1 Maximum combined residues of metiram and ETU (including ETU conversion factor for Metiram) in/on treated RAC
sample(s) following applications of metiram formulation according to maximum registered use patterns.
2 To be residues of metiram calculated as CS2 (0.56 conversion factor is accounted for within).
c.
Codex Harmonization
There are no established or proposed Codex MRLs for metiram residues per se, however,
Codex limits for dimethyldithiocarbamates fungicides are grouped under dithiocarbamates. Maximum
residue limits (MRLs) for the dithiocarbamates are established for several commodities resulting from
the use of mancozeb, maneb, metiram, propineb, thiram, and ziram and are currently expressed as ppm
carbon disulfide. The Agency is recommending harmonization of the tolerance expression with the
Codex residue definition. A numerical comparison of the Codex MRLs and the corresponding
reassessed U.S. tolerances for metiram are presented on the internet at the Food and Agricultural
Organization database website: http://faostat.fao.org/faostat/collections?version=ext&hasbulk=0. The
tolerance value for potatoes will be harmonized with the Codex MRL.
D. Regulatory Rationale
The following is a summary of the rationale for the mitigation measures necessary for
reregistration eligibility and for managing risks associated with the use of metiram. Where labeling
revisions are warranted, specific language is set forth in the summary table of Section V (Table 36 of
this RED document).
49 of 108
-------
1. Human Health Risk Management
a. Dietary (Food) Risk Mitigation
Acute, chronic, and cancer dietary (food only) exposure and risk from metiram, metiram-
derived ETU, and ETU from all sources are below the Agency's level of concern. Acute, chronic, and
cancer risks were also not of concern for metiram or metiram derived-ETU, even when residues from
the proposed import use on wine grapes were included in the dietary assessment. Since there are no
acute, chronic, cancer dietary (food only) risks of concern, no mitigation measures are necessary.
b. Dietary (Drinking Water) Risk Mitigation
The drinking water exposure assessment for metiram addresses concentrations of ETU only,
since metiram is not expected to remain in water long enough to reach a location that would supply
drinking water for human consumption, whether from surface or groundwater sources. Estimated
concentrations of ETU, for both surface and ground water sources of drinking water, are low and not
of concern; therefore, no mitigation is needed.
c. Residential Risk Mitigation
The Agency is not considering residential mitigation options for metiram, since there are no
existing or proposed residential or other non-occupational sources of exposure, and metiram is not
used in or around public buildings, schools or recreational areas where children or others might be
exposed.
d. Aggregate Risk Mitigation
Aggregate risk refers to the combined risk from food, drinking water, and residential (as a
result of residential exposures from mancozeb uses) exposures. In addition, aggregate risk can result
from one-time (acute), short-term and/or chronic (non-cancer and cancer) exposures. Below is a
discussion of the risk for each duration of exposure and any risks of concern.
Acute Aggregate: Since residues of metiram per se are not expected in drinking water, acute
aggregate risks for metiram consist of acute exposures to metiram-derived ETU and ETU from all
sources. Potential concentrations of metiram-derived ETU and ETU from all sources in drinking water,
when combined with exposure through food, are below Agency's level of concern for acute aggregate
risk (see Table 12). No mitigation measures are necessary for acute aggregate risk.
Short-term Aggregate: Short-term aggregate (food + drinking water + residential [as a result
of residential exposures from mancozeb uses]) risk for ETU from all sources is below the Agency's
level of concern for residential handlers, and children and adults exposed to ETU from re-entry
activities (see Table 13). Therefore, no mitigation is required.
50 of 108
-------
Chronic (Non-Cancer) Aggregate: The chronic aggregate risk to metiram-derived ETU and
ETU from all sources were calculated using food and drinking water exposures only, because
residential mancozeb exposure scenarios were considered to occur only on a short-term basis.
Aggregate (food + drinking water) chronic risk to metiram-derived ETU and ETU from all sources are
below the Agency's level of concern; therefore, no mitigation is required.
Cancer Aggregate: Aggregate (food + drinking water) cancer risk to metiram-derived ETU
for the general U.S. population is below the Agency's level of concern. The cancer risks from ETU
from all sources were aggregated using food, drinking water and residential/recreational (as a result of
mancozeb uses) exposures. These risks range from 2.0 x 10"6 to 2.3 x 10"6 depending upon the
drinking water source and the type of residential exposure, with the food exposure being the largest
contributor of cancer risk (1.86 x 10"6), followed by drinking water from groundwater sources. The
Agency considers cancer risks as high as 3 in 1 million are within the negligible risk range; thus, cancer
aggregate risks are not of concern. Therefore, the Agency believes no further mitigation is required for
metiram.
e. Occupational Risk Mitigation
It is the Agency's policy to mitigate occupational risk to the greatest extent necessary and
feasible. Mitigation measures may include reducing application rates, adding personal protective
equipment (PPE) to end product labels, requiring the use of engineering controls, and other measures.
A wide range of factors is considering in making risk management decisions for worker risks. These
factors include, estimated margins of exposure (MOEs), cancer risk estimates, incident data, the nature
and severity of adverse effects observed in animal studies, uncertainties in the risk assessment,
alternative registered pesticides, the importance of the chemical in integrated pest management (IPM)
programs, and other similar factors.
1) Agricultural and Greenhouse Handler Mitigation
Handler exposure assessments are completed by EPA considering the use of baseline PPE,
and, if warranted, increasing levels of PPE and engineering controls in order to estimate their potential
impact on exposure. The target MOE for occupational risk is 100, and MOEs greater than 100 do not
exceed the Agency's level of concern. For occupational cancer risks, estimates in the general range of
1 x 10"6 (one in a million) generally do not exceed the Agency's level of concern. When occupational
MOEs are less than 100 or occupational cancer risks exceed the general range of 1 x 10"6, EPA strives
to reduce worker cancer risks through the use of personal protective equipment and engineering
controls or other mitigation measures. The Agency generally considers occupational cancer risks in the
general range of 1 x 10"6 or less to be negligible, but may accept estimated risks as high as 1 x 10"4 (1 in
10,000 persons) when all mitigation measures that are feasible have been applied, particularly when
there are critical pest management needs associated with the use of the pesticide. Levels of PPE
considered and applicable to the proposed mitigation are described below:
51 of 108
-------
Baseline - long-sleeved shirt, long pants, and shoes and socks
Single layer - baseline plus gloves
• Double layer - baseline plus gloves and coveralls
• PF5 - a dust/mist filtering respirator
PF10 - a half face respirator with appropriate cartridges
Section 3 Use on Apples and Potatoes
As described in Section m.A.6. of this document, non-cancer (inhalation and dermal) and
cancer risks to handlers mixing and loading and applying metiram are not of concern for several
exposures at baseline PPE (MOEs and cancer risk estimates are also described below). The Agency
is requiring the use of baseline PPE for these scenarios, as follows:
Handlers mixing and loading dry flowable for groundboom application to potatoes
(dermal and inhalation MOEs are 330 and 360; cancer risks are 5 x 10"7);
• Handlers mixing and loading dry flowable for airblast application to apples (dermal and
inhalation MOEs are 220 and 240; cancer risks are 4 x 10"7);
Handlers applying via groundboom to potatoes (dermal and inhalation MOEs are
>1000 and 370; cancer risks are 3 x 10'7);
For other exposure scenarios, risks to handlers are above the Agency's level of concern at
baseline PPE, as described in Section m.A.6. of this document. The Agency is requiring the use of
additional PPE for these scenarios and other mitigation measures for these scenarios, as described in
the paragraphs below.
For handlers mixing and loading dry flowable for aerial or chemigation application to apples or
potatoes, the Agency is requiring the use of double-layer PPE and a PF5 respirator. Considering the
use of this PPE, the dermal and inhalation MOEs for apples are 35 and 140 and for potatoes are 106
and 420, respectively. In addition, to help further mitigate the dermal risk associated with apples, the
registrants have agreed to reduce the maximum application rates from 4.8 Ib ai/A to 3.6 Ib ai/A. This
results in a dermal MOE of approximately 50, which is still less than the target MOE of 100; however,
Agency information indicates that the aerial application method is an infrequent occurrence and used on
apples less than 5% of the time (e.g., when it is too wet to use ground application equipment for this
scenario). Thus, it is unlikely that intermediate-term exposures occur. Since the short-term dermal
MOE is 420 at baseline, the Agency believes that the mitigation described here mitigates any risk of
concern.
For handlers applying via airblast application to apples, the Agency is requiring single layer PPE
plus a PF5 respirator. MOEs were both 41 with baseline PPE. The dermal MOE with the use of
single layer PPE increases to 100 and the inhalation MOE with the use of a respirator is 200. The
cancer risk estimate considering the use of the PPE being required is 7 x 10"7. Considering the
mitigation, there are no remaining risks of concern to the Agency.
52 of 108
-------
For aerial applicators, the Agency is requiring the use of engineering controls (closed cockpits).
With the use of engineering controls, dermal and inhalation MOEs are 330 and 310 for apples and
1000 and 920 for potatoes, respectively, and cancer risk estimates are 3 x 10"7 for apples and 2 x 10"7
for potatoes. Considering the mitigation, there are no remaining risks of concern to the Agency.
For Saggers, the Agency is requiring the use of baseline PPE (no gloves) plus a PF5 respirator.
For use on apples, the dermal MOE for Saggers at baseline PPE is 150 and the inhalation MOE at
baseline PPE is 60. MOEs for potatoes are all greater than 100. With the addition of a PF5
respirator, the inhalation MOE increases to 300. The cancer risk estimates with the use of a PF5
respirator are 5 x 10"7 for apples and 3 x 10"7 for potatoes; therefore, there are no remaining risks of
concern to the Agency.
Short-term, intermediate term and non-cancer chronic risks were not of concern for metiram-
derived ETU; MOEs were above 100 for all of the handler scenarios evaluated.
Section 24(c) Use on Leatherleaf Ferns
As described in Section m.A.6. of this document, non-cancer (inhalation and dermal) risks to
handlers mixing, loading, and applying metiram to leatherleaf ferns with a low pressure handwand are
not of concern at single layer PPE (baseline plus gloves) with a dermal MOE greater than 500, but
resulted in an inhalation MOE of 50. Related to dermal exposure, MOEs could not be calculated
without gloves due to the lack of data; however, the Agency understands that the use of gloves is
common use practice for these handlers. The Agency believes that the inhalation MOE of 50 is not a
risk of concern, because wettable powder unit exposure data were used to substitute for the dry
flowable formulation; data specific to dry flowable formulations are not available for this scenario. The
use of wettable powder data to substitute for the dry flowable formulation is highly conservative,
because dry flowable formulations are significantly less dusty than wettable powders and, therefore,
result in much less inhalation exposure.
Dermal and inhalation MOEs and cancer risk estimates were not able to be calculated for
handlers mixing, loading, and applying metiram to ferns with a backback sprayer. The Agency believes
that single layer PPE will mitigate any risks of concern for this scenario as well, because backpack
sprayer and low pressure handwand are comparable application methods; the low pressure handwand
dermal MOE is five times greater than the target MOE of 100; and inhalation exposures will not be
greater than for handlers using the low pressure handwand.
Short-term, intermediate term and non-cancer chronic risks were not of concern for metiram-
derived ETU; MOEs were above 100 for all of the handler scenarios evaluated.
2) Potato Seed-Piece Treatment Mitigation
As described in Section m.A.6. of this document, risks to handlers loading dust formulation for
53 of 108
-------
commercial and on-farm potato seed-piece treatment are of concern to the Agency for dermal,
inhalation, and cancer risks. As such, the end-use registrant has requested to voluntarily cancel the
potato seed-piece treatment product registration and this scenario is no longer a risk of concern.
3) Post-Application Mitigation
When preparing post-application risk assessments, EPA considers dislodgeable foliar residue
(DFR) data, application rates, transfer coefficients based on crop type and exposure scenario (low,
medium, or high contact activities), and assumptions about average occupational workdays and adult
body weight. In the case of metiram, both metiram and its degradate ETU were considered in the
assessment. For the ETU cancer risk assessment, the Agency assumed that workers would be
exposed for 30 days each year.
At the current REI of 24 hours, for high-end intermediate/chronic exposure scenarios,
estimated MOEs are <100 only for apples and leather-leaf fern cuttings. For the ETU high-end chronic
exposure scenario, the estimated MOE is <100 for leather-leaf fern cuttings. The only two post-
application cancer risk scenarios with predicted risks exceeding the range of 1 x 10"6 are the high-end
exposure scenarios for apples and leather-leaf fern cuttings; however, neither of these exceed 9 x 10"6
For leatherleaf ferns, the Agency is requiring that use be restricted to a maximum of 1
application per week and 10 applications per year, but maintaining the existing 24 hour REI. Based on
these restrictions, if 10 applications per year are made at weekly intervals, the expected use pattern
based on information available from the user community, the exposure would be considered an
intermediate-term duration and not a chronic duration. Thus, the chronic MOE as a result of ETU
exposure (MOE of 74 at day 0 after treatment) is no longer applicable, considering these restrictions.
The intermediate-term MOEs for metiram exposure are 90 at day 0 and 92 at day 1 after treatment,
and for ETU the intermediate term MOE is greater than 100. MOEs of 90 and 92 are not significantly
different than 100 and not of concern to the Agency.
For apples, a MOE of 54 is predicted for high intermediate-term exposure activities (pruning,
tying, and training) at the current REI of 24 hours. Based on information provided to the Agency from
the user community, these high exposure activities do not begin until several weeks after the last
metiram application for apples grown in the East, including New England, and the central states. At 20
days after application, the metiram intermediate/chronic MOE is 84. For apples grown in the
Southwest, West, and Pacific Northwest, high exposure activities can occur immediately after
treatment, and may extend for greater than 30 days. This results in an intermediate-term MOE of 54.
However, the Agency does not believe that there is a risk of concern to workers reentering treated
apple orchards. The major metiram usage states are Michigan, New York, Virginia, North Carolina,
Pennsylvania, Ohio, and South Carolina; and National Agricultural Statistical Services (NASS) data
available to the Agency indicate very low metiram usage in the West. Further, IPM and resistance
54 of 108
-------
management advantages from the use of this chemical as described in the Significance of the EBDCs
section of this document (Section IV.E.3) are significant. Therefore, the Agency plans to maintain the
current 24 hour REI for all apples.
2. Environmental Risk Mitigation
It is the Agency's policy to mitigate ecological risks to the greatest extent necessary and
feasible. Mitigation measures may include lowering application rates, reducing the number of
applications, restricting the timing of applications, minimizing runoff potential, and others.
a. Terrestrial Species Mitigation
From a short-term or acute metiram exposure, the Agency expects low risk to mammals and
birds. However, the screening-level ecological risk assessment indicates some exceedance of the
chronic screening LOCs for risk to birds and small mammals. In particular, the highest chronic RQs
result from metiram use on apples. With a total of four applications at a rate of 4.8 Ibs ai/A to apples,
the corresponding avian chronic RQs based on mean EECs range from 27-2 and the mammalian
chronic RQs range from 34-3. Predicted exposures from use of metiram on potatoes also exceed
screening levels of concern for birds and mammals, with RQs ranging from 14-1 for birds and 18-1 for
mammals, again based on mean EECs. These RQs are screening-level estimates, incorporating
modeled estimated environmental concentrations. Nevertheless, to be more protective of terrestrial
species that may be exposed on a chronic basis, the technical registrant has agreed to additional label
changes to reduce potential risk. For example, the maximum application rate (pre-bloom) to apples is
being reduced from 4.8 to 3.6 Ibs ai/A, and the maximum number of applications is also being reduced
from 4 to 3 times per year. Moreover, the maximum number of applications to potatoes is also being
reduced from 7 to 6 times per year, thus reducing the yearly maximum application rate. Refer to Table
34 for summary of revisions to use site parameters.
The Agency does not expect metiram exposure to pose acute risk to non-target insects,
because metiram is practically nontoxic to honeybees and there are no incident data reporting adverse
effects to honeybees. Therefore, no bee precautionary labeling is required on metiram product labeling.
b. Aquatic Species Mitigation
Predicted acute risk to aquatic species (freshwater fish, freshwater invertebrates, and non-
vascular plants) is low. Currently, there are no toxicity data on estuarine/marine species and no toxicity
data to assess chronic risk to freshwater fish or freshwater invertebrates. The Agency is requiring
additional acute and chronic toxicity data as part of this RED to address these data gaps.
Although the assessed acute RQs to aquatic species are relatively low, some LOG
55 of 108
-------
exceedances exist. The same mitigation measures addressing terrestrial risks will also reduce these
risks, including reducing single maximum application rates, and reducing maximum number of
applications per year and maximum seasonal application rates. Refer to Table 34 for summary of
revisions to use site parameters. For acute risks to aquatic non-vascular plants, the reduction of the
maximum application rate for apples reduces the corresponding RQ below the LOG.
Table 34. Revised Use Site Parameters and Requirements for Metiram
Crop
Apples
Potatoes
Leatherleaf
Ferns
Single Application
Rates (Ib ai/A)
Previous
4.8
1.6
1.6
Revised
3.6
1.6
1.6
Minimum
Retreatment
Interval
(days)
7
5
7
Maximum Number of
Applications Per Year
Previous
4
7
Unlimited
Revised
3
6
10
Yearly Maximum Rate
(Ib ai/A)
Previous
19.2
11.2
Unlimited
Revised
10.8
9.6
16
3. Significance of the EBDCs
As mentioned above, EPA received many comments in response to the Federal Register
Notice published on November 24, 2004 (OPP-2004-0078) announcing the availability of the EBDC
risk assessments and requests for risk reduction options. The majority of the comments supported the
continued use of the EBDC products and data supporting the usefulness of the EBDCs to control plant
diseases. The Agency also obtained information from internal expertise, USDA's Office of Pesticide
Management and Policy (OPMP), and proprietary sources on several use sites.
Based on the information provided by a variety of resources, the Agency has determined that
the EBDCs are a class of fungicides that are particularly significant to agriculture and integrated pest
management (1PM) programs due to the use of the EBDCs in disease resistance management
programs. The EBDCs have a multi-site mode of action, and, as such, are not considered susceptible
to resistance development. This is supported by the fact that there has been no confirmed case of
fungal resistance to the EBDCs after over 50 years of use. Because of these characteristics, the
EBDCs are important resistance management partner chemicals for tank mixing or rotation with newer
and lower risk fungicides that have single-site modes of action such as the sterol inhibitors and the
strobilurins. This property helps to prolong the life of the newer and lower risk fungicides.
The Agency is committed to long-term pest resistance management strategies, and an important
pesticide resistance management strategy is to avoid the repeated use of pesticides with the same or
similar mode/target site of action in the same field (OPP PR Notice 2001-5). Because of this, the
Agency has considered the advantages from the use of EBDCs as an important tool in fungicide
resistance management programs while making its reregistration decision for all 3 EBDCs, mancozeb,
56 of 108
-------
maneb, and metiram.
Further, comparing the cost per treatment of EBDCs with other fungicides, cost information
demonstrated that the EBDCs are generally lower. The following paragraphs are summaries for
specific use sites.
Mancozeb, maneb and metiram are registered to control several important fungal diseases on
apples. The key alternatives to EBDCs include captan, strobilurins (e.g., trifloxystrobin), sterol
inhibitors, and benzimidazoles. Copper, dodine, ziram, and cyprodinil are also used. However, none
of these fungicides are considered to be a universal substitute for the EBDC fungicides. Fungal
resistance to dodine, sterol inhibitor fungicides and benzimidazoles has developed, reducing the ability
of these systemic fungicides to control apple diseases in orchards.
Dormant oil is used to decrease early season mite populations. This early mite population
control reduces the total number of miticide applications needed during the course of the apple growing
season. The advantage of mancozeb and metiram compared to captan is that captan cannot be used
with dormant oil because this combination is phytotoxic to apple foilage. This phytotoxicity is not seen
with mancozeb and metiram. Thus, indirectly, the use of EBDC fungicides in lieu of captan typically
reduces the total number of miticide applications needed.
Potatoes
Mancozeb, maneb, and metiram are used to control early blight and late blight as well as
several potato seed-piece diseases. The alternative fungicides include strobilurins (e.g. azoxystrobin,
trifloxystrobin), chlorothalonil, propamocarb, dimethomorph, cymoxanil, copper, triphenylin hydoxide
(TPTH), iprodione, and zoxamide fluazinam. However, there is no one alternative fungicide registered
to control all the potato diseases for which EBDCs are registered. Because there has been reduced
sensitivity of the strobilurins towards early blight on potatoes in some areas, rotational applications of
strobilurins with fungicides with a different mode of action are required after every application.
Along with the EBDCs, chlorothalonil has been considered the standard early blight and late
blight treatments for years. However, EBDCs are needed for use when the seasonal allowance of
chlorothalonil per acre has been reached. Copper and tin products are less efficacious for early blight
in some areas. Lastly, applications of TPTH may result in injury to foilage of sensitive varieties, but
injury is reduced and efficacy is improved when TPTH is combined with an EBDC fungicide.
Leatherleaf Ferns 24(c) in Florida
Metiram is used to control anthracnose. Typically application occurs during high incidence of
anthracnose (June through September). The key alternatives are chlorothalonil, mancozeb,
57 of 108
-------
tebuconazole, cloroneb, fosetyl-aluminum, mefenoxam, thiophanate-methyl. Metiram and mancozeb
provide an extra component of zinc in addition to disease control. The EBDCs' source of zinc fertilizer
allows growers to apply a reduced number of zinc micro-nutrients, making the EBDCs favorable to
growers due to the dual benefits.
4. Summary of Risk Mitigation Measures
The technical registrant has agreed to the following bulleted list that summarizes all mitigation
measures necessary for the reregi station of metiram:
• Add a PF5 respirator to label PPE for some worker scenarios: mixer/loaders of dry flowables
for aerial/chemigation applications; airblast applicators to apples; and Saggers,
Add the use of engineering controls to labels for aerial applicators (enclosed cockpits),
• Reduce apple pre-bloom maximum application rate from 4.8 to 3.6 Ibs ai/A,
• Reduce maximum number of applications for apples from 4 to 3 per year,
Reduce maximum number of applications for potatoes from 7 to 6 per year, and
Limit the number of applications to leatherleaf ferns to 1 per week and 10 per year.
• Metiram use on roses and dust and wettable powder formulations have been voluntarily
cancelled prior to completion of the RED. Further, as a result of the voluntary cancellation of
the dust formulation by the technical registrant and risks associated with this formulation, the
end-use registrant has requested voluntary cancellation of their active potato seed treatment
fungicide product registration (EPA Registration No. 2935-540).
E. Other Labeling Requirements
In order to be eligible for reregistration, various use and safety information will be included in
the labeling of all end-use products containing metiram. For the specific labeling statements and a list of
outstanding data, refer to Section V of this RED document.
1. Endangered Species Considerations
Based on available screening-level information, there is a potential concern for acute effects on
listed birds and freshwater fish species, and chronic effects on listed birds and mammals should
exposure actually occur. Even though metiram is only slightly acutely toxic to birds, RQs exceed the
endangered species LOG (RQ range from 0.11 to 1.02) at maximum EEC levels. The Agency does
not currently have data to quantify risks for metiram at the screening-level and can not preclude
potential direct effects to the following taxonomic groups; listed non-target terrestrial plants, freshwater
invertebrates, estuarine/marine fish, or vascular aquatic plants. These findings are based solely on
EPA's screening-level assessment and do not constitute "may affect" findings under the Endangered
Species Act (ESA) for any specific listed species.
58 of 108
-------
The Agency has developed the Endangered Species Protection Program to identify pesticides
whose use may cause adverse impacts on federally listed endangered and threatened species, and to
implement mitigation measures that address these impacts. The ESA requires federal agencies to
ensure that their actions are not likely to jeopardize listed species or adversely modify designated
critical habitat. To analyze the potential of registered pesticide uses that may affect any particular
species, EPA uses basic toxicity and exposure data developed for the REDs and considers ecological
parameters, pesticide use information, the geographic relationship between specific pesticide uses and
species locations and biological requirements and behavioral aspects of the particular species. When
conducted, this analysis will consider regulatory changes recommended in this RED that are
implemented a that time. A determination that there is a likelihood of potential effects to a listed species
may result in limitations on the use of the pesticide, other measures to mitigate any potential effects, or
consultations with the Fish and Wildlife Service or National Marine Fisheries Service as appropriate. If
the Agency determines use of metiram "may affect" listed species or their designated critical habitat,
EPA will employ the provisions in the Services regulations (50 CFR Part 402). Until that species
specific analysis is completed, the risk mitigation measures being implemented through this RED will
reduce the likelihood that endangered and threatened species may be exposed to metiram at levels of
concern.
2. Spray Drift Management
The Agency has been working closely with stakeholders to develop improved approaches for
mitigating risks to human health and the environment from pesticide spray and dust drift. As part of the
reregistration process, we will continue to work with all interested parties on this important issue.
From its assessment of metiram, as summarized in this document, the Agency concludes that no
drift management measures are needed for metiram. In the future, metiram product labels may need to
be revised to include additional or different drift label statements. Current, drift label statements are
listed in the "spray drift management" section of the label table (Table 36) in Chapter V of this RED
document.
V. WHAT REGISTRANTS NEED TO DO
The Agency has determined that metiram is eligible for reregistration provided that: (i) additional
data are submitted to confirm this decision; (ii) the risk mitigation measures outlined in this document are
adopted; and (iii) label amendments are made to reflect these measures. To implement the risk
mitigation measures, the registrants will be required to amend their product labeling to incorporate the
label statements set forth in the Label Summary Table (Table 36). In the near future, the Agency
intends to issue Data Call-In Notices (DCIs) requiring product-specific data and additional generic
(technical grade) data at which time required label amendments will be submitted. Generally, registrants
will have 90 days from receipt of a DCI to complete and submit response forms or request time
extension and/or waiver requests with a full written justification. For product-specific data, the
registrant will have eight months to submit data and amended labels. For generic data, due dates can
59 of 108
-------
vary depending on the specific studies being required. Below are additional generic data and label
amendments that the Agency intends to require for metiram to be eligible for reregistration.
A. Manufacturing-Use Products
Generic Data Requirements
The generic data base supporting the reregistration of metiram for the above eligible uses has
been reviewed and determined to be substantially complete. However, the data listed below are
necessary to confirm this RED.
Table 35. Outstanding and Confirmatory Generic Data Requirements for Metiram and ETU
Guideline Study Name
New OPPTS
Guideline No.
Old Guideline
No.
Human Health
Preliminary Analysis (technical)
Confined Accumulation in Rotational Crops
2-Generation Reproduction - Rat*
Developmental Toxicity - Rabbit**
Acute Neurotoxicity - Rat
Developmental Neurotoxicity - Rat**
Comparative Thyroid Assay **
U V/Visible Absorption
830.1700
860.1850
870.3800
870.3700
870.6200
870.6300
Special Study
830.7050
62-1
165-1
83-4
83-3
81-8
83-6
None
Ecological
Acute Fish Toxicity Bluegill
Acute Aquatic Invertebrate Toxicity
Whole Sediment Acute Toxicity Invertebrates, Freshwater
Acute Estuarine/Marine Toxicity - Fish
Acute Estuarine/Marine Toxicity - Mollusk
Acute Estuarine/Marine Toxicity - Shrimp
Whole Sediment Acute Toxicity Invertebrates, Estuarine/Marine
850.1075
850.1010
850.1735
850.1075
850.1025
850.1025
850.1740
72-1 A
72-2A
None
72-3A
72-3B
72-3C
None
60 of 108
-------
Table 35. Outstanding and Confirmatory Generic Data Requirements for Metiram and ETU
Guideline Study Name
Early Life Stage Fish - Estuarine/Marine
Life Cycle Aquatic Invertebrate - Estuarine/Marine
Aquatic Plant Growth - Tier I
Seedling Germination and Seedling Emergence - Tier I
Vegetative Vigor - Tier I
Aquatic Plant Growth - Tier II
New OPPTS
Guideline No.
850.1350
850.1350
850.5400
850.4225
850.4250
850.4400
Old Guideline
No.
72-4A
72-4B
122-2
122-1A
122-1B
123-2
* The study must be conducted under the current protocol.
** ETU data requirement
Labeling for Manufacturing-Use Products
To ensure compliance with FIFRA, manufacturing-use product (MUP) labeling must be revised
to comply with all current EPA regulations, PR Notices, and applicable policies. The MUP labeling
must bear the labeling contained in Table 36.
B.
End-Use Products
Additional Product-Specific Data Requirements
Section 4(g)(2)(B) of FIFRA calls for the Agency to obtain any needed product-specific data
regarding the pesticide after a determination of eligibility has been made. Registrants must review
previous data submissions to ensure that they meet current EPA acceptance criteria and if not, commit
to conduct new studies. If a registrant believes that previously submitted data meet current testing
standards, then the study MRID numbers should be cited according to the instructions in the
Requirement Status and Registrants Response Form provided for each product. The Agency intends to
issue a separate product-specific data call-in (PDCI), outlining specific data requirements.
Labeling for End-Use Products
To be eligible for reregi station, labeling changes are necessary to implement measures outlined
in Section IV above. Specific language to incorporate these changes is specified in Table 36.
Generally, conditions for the distribution and sale of products bearing old labels/labeling will be
established when the label changes are approved. However, specific 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.
61 of 108
-------
C. Labeling Changes Summary Table
In order to be eligible for reregistration, amend all product labels to incorporate the risk
mitigation measures outlined in Section IV. The following table (Table 36) describes how language on
the labels should be amended.
62 of 108
-------
Table 36. Summary of Labeling Changes for Metiram
Description
Amended Labeling Language
Placement on Label
Manufacturing Use Products
For all Manufacturing Use
Products
"Only for formulation as a dry flowable fungicide for use on apples and potatoes.
Only for formulation as a dry flowable fungicide for Section 24(c) — Special Local
Need use on leatherleaf ferns in Florida (FL980001).
Technical and end-use product labels must be revised to delete all references to and
use directions for all other formulations and use patterns."
Directions for Use
One of these statements
may be added to a label to
allow reformulation of the
product for a specific use
or all additional uses
supported by a formulator
or user group
"This product may be used to formulate products for specific use(s) not listed on
the manufacturing use product label if the formulator, user group, or grower has
complied with U.S. EPA submission requirements regarding support of such
use(s)."
"This product may be used to formulate products for any additional use(s) not listed
on the manufacturing use product label if the formulator, user group, or grower has
complied with U.S. EPA submission requirements regarding support of such use."
Directions for Use
Environmental Hazards
Statements Required by
the RED and Agency
Label Policies
"Do not discharge effluent containing this product into lakes, streams, ponds,
estuaries, oceans, or other waters unless in accordance with the requirements of a
National Pollutant Discharge Eliminations System (NPDES) permit and the
permitting authority has been notified in writing prior to discharge. Do not discharge
effluent containing this product to sewer systems without previously notifying the
local sewage treatment plant authority. For guidance, contact your State Water
Board or Regional Office of the Environmental Protection Agency."
Precautionary
Statements
End-Use Products Intended for Occupational Use (WPS and non-WPS)
63 of 108
-------
Table 36. Summary of Labeling Changes for Metiram
Description
Amended Labeling Language
Placement on Label
PPE Requirements
Established by the RED
for Dry Flowable (DF)
Formulation for Section 3
use on Apples and
Potatoes
"Personal Protective Equipment (PPE)"
"Some materials that are chemical-resistant to this product are [registrant inserts
correct material(s)]. If you want more options, follow the instructions for category
[insert A, B, C, D, E, F, G or H] on an EPA chemical-resistance category selection
chart."
"Mixers and loaders supporting aerial applications or use in chemigation systems
and handlers cleaning up spills must wear:
- coveralls over long-sleeved shirt and long pants
- chemical-resistant gloves,
- chemical-resistant footwear plus socks,
- chemical-resistant apron, and
- a dust/mist filtering respirator (MSHA/NIOSH approval number prefix TC-21C),
or a NIOSH approved respirator with any N*, R, P, or FIE filter."
*Instructions to registrant: Drop the "N" type filter from the respirator statement if
the pesticide product contains or is used with oil.
"All other handlers must wear:
- long-sleeved shirt,
- long pants,
- shoes and socks,
- chemical resistant gloves when applying by airblast sprayer, and
- a dust/mist filtering respirator (MSHA/NIOSH approval number prefix TC-
21C), or a NIOSH approved respirator with any N*, R, P, or HE filter when
Immediately
following/below
Precautionary
Statements: Hazards to
Humans and Domestic
Animals
64 of 108
-------
Table 36. Summary of Labeling Changes for Metiram
Description
Amended Labeling Language
Placement on Label
applying by airblast sprayer and when flagging."
*Instructions to registrant: Drop the "N" type filter from the respirator statement if
the pesticide product contains or is used with oil.
"See engineering controls for additional options and requirements"
PPE Requirements
Established by the RED
for Dry Flowable (DF)
Formulations labeled for
the 24(c) Special Local
Need Use on Leatherleaf
Ferns
"Personal Protective Equipment (PPE)"
"Some materials that are chemical-resistant to this product are [registrant inserts
correct material(s)]. If you want more options, follow the instructions for category
[insert A, B, C, D, E, F, G or H] on an EPA chemical-resistance category selection
chart."
"Mixers, loader, applicators, and other handlers must wear:
- long-sleeved shirt,
- long pants,
- shoes and socks, and
- chemical-resistant gloves.
"See engineering controls for additional options and requirements"
Immediately
following/below
Precautionary
Statements: Hazards to
Humans and Domestic
Animals
65 of 108
-------
Table 36. Summary of Labeling Changes for Metiram
Description
Amended Labeling Language
Placement on Label
Engineering Controls:
Enclosed Cockpits for
Aerial Applicators
Handlers for Section 3
(apples and potatoes) and
Section 24(c) (leatherleaf
ferns) labels
Enclosed Cockpits
"Engineering Controls: Pilots must use an enclosed cockpit that meets the
requirements listed in the Worker Protection Standard (WPS) for agricultural
pesticides [40 CFR 170.240(d)(6)] and must wear a long-sleeve shirt, long pants,
shoes, and socks.
Immediately
following/below
Precautionary
Statements: Hazards to
Humans and Domestic
Animals
Engineering Controls:
Optional Use by Handlers
for Section 3 (apples and
potatoes) and Section
24(c) (leatherleaf ferns)
labels
Engineering Control Statement for Optional Use (WPS Only)
"Engineering Controls: When handlers use enclosed cabs in a manner that meets
the requirements listed in the Worker Protection Standard (WPS) for agricultural
pesticides [40 CFR 170.240(d)(5)], the handler PPE requirements may be reduced
or modified as specified in the WPS."
Immediately
following/below
Precautionary
Statements: Hazards to
Humans and Domestic
Animals
User Safety Requirements
"Follow manufacturer's instructions for cleaning/maintaining PPE. If no such
instructions for washables exist, use detergent and hot water. Keep and wash PPE
separately from other laundry."
"Discard clothing or other absorbent materials that have been drenched or heavily
contaminated with this product's concentrate. Do not reuse them."
Precautionary
Statements: Hazards to
Humans and Domestic
Animals immediately
following the PPE
requirements
66 of 108
-------
Table 36. Summary of Labeling Changes for Metiram
Description
Amended Labeling Language
Placement on Label
User Safety
Recommendations
"USER SAFETY RECOMMENDATIONS"
"Users should wash hands before eating, drinking, chewing gum, using tobacco, or
using the toilet."
"Users should remove clothing/ PPE immediately if pesticide gets inside, then wash
thoroughly and put on clean clothing."
"Users should remove PPE immediately after handling this product. Wash the
outside of gloves before removing. As soon as possible, wash thoroughly and
change into clean clothing."
Precautionary
Statements under:
Hazards to Humans and
Domestic Animals
(Must be placed in a
box.)
Restricted-Entry Interval
for the Section 3 label
(apples and potatoes)
"Do not enter or allow worker entry into treated areas during the restricted entry
interval (RET) of 24 hours."
Directions for Use, in
Agricultural Use
Requirements box
Restricted-Entry Interval
for the (24(c) Special
Local Need Use on
Leatherleaf Ferns)
"Do not enter or allow worker entry into treated areas during the restricted entry
interval (REI) of 24 hours."
Directions for Use, in
Agricultural Use
Requirements box
Early Reentry Personal
Protective Equipment
Interval for the Section 3
label (apples and potatoes)
and for the (24(c) Special
Local Need Use on
Leatherleaf Ferns)
"PPE required for early entry to treated areas that is permitted under the Worker
Protection Standard and that involves contact with anything that has been treated,
such as soil or water, is:
Coveralls,
Shoes and socks, and
Chemical-resistant gloves made of any waterproof material.
Directions for Use, in
Agricultural Use
Requirements Box
67 of 108
-------
Table 36. Summary of Labeling Changes for Metiram
Description
Amended Labeling Language
Placement on Label
General Application
Restrictions
"Do not apply this product in a way that will contact workers or other persons,
either directly or through drift. Only protected handlers may be in the area during
application."
Place in the Directions
for Use directly above
the Agricultural Use
Box
Application Restrictions
for Section 3 labels
(apples and potatoes)
Apples: Limit to 3 applications per year. Maximum application rate per application
is 3.6 Ib ai/A. (Label also must list this as pounds of formulated product per acre)
Potatoes: Limit to 6 applications per year.
Directions for Use
Application Restrictions
for Section 24(c) labels
(leatherleaf ferns)
Leatherleaf Fern: Limit to a maximum of 1 application per week and 10
applications per year.
Directions for Use
Environmental Hazards
Statements Required by
the RED and Agency
Label Policies
"This pesticide is toxic aquatic organisms. Do not apply directly to water, or to
areas where surface water is present, or to inter-tidal areas below the mean high
water mark. Do not contaminate water when cleaning equipment or disposing of
equipment washwaters or rinsate. Apply this product only as specified on the
label."
Precautionary
Statements: Hazards to
Humans and Domestic
Animals
Spray Drift Label
Language for Products
Applied as a Spray
"SPRAY DRIFT MANAGEMENT"
"A variety of factors including weather conditions (e.g., wind direction, wind speed,
temperature, relative humidity) and method of application (e.g., ground, aerial, airblast,
chemigation) can influence pesticide drift. The applicator must evaluate all factors
and make appropriate adjustments when applying this product."
Wind Speed
"Do not apply at wind speeds greater than 15 mph.
Temperature Inversions
"If applying at wind speeds less than 3 mph, the applicator must determine if a)
Directions for Use
under General
Precautions or
Restrictions and/or
Application Instructions
68 of 108
-------
Table 36. Summary of Labeling Changes for Metiram
Description
Amended Labeling Language
Placement on Label
conditions of temperature inversion exist, or b) stable atmospheric conditions exist at
or below nozzle height. Do not make applications into areas of temperature
inversions or stable atmospheric conditions."
Other State and Local Requirements
"Applicators must follow all state and local pesticide drift requirements regarding
application of metiram. Where states have more stringent regulations, they must be
observed."
Equipment
"All aerial and ground application equipment must be properly maintained and
calibrated using appropriate carriers or surrogates."
Additional requirements for aerial applications:
1. "The boom length must not exceed 75% of the wingspan or 90% of the rotor blade
diameter."
2. "Release spray at the lowest height consistent with efficacy and flight safety. Do
not release spray at a height greater than 10 feet above the crop canopy unless a
greater height is required for aircraft safety."
3. "When applications are made with a crosswind, the swath must be displaced
downwind. The applicator must compensate for this displacement at the up and
downwind edge of the application area by adjusting the path of the aircraft upwind."
Additional requirements for ground boom application:
1. "Do not apply with a nozzle height greater than 4 feet above the crop canopy."
69 of 108
-------
APPENDICES
70 of 108
-------
Appendix A: METIRAM (CASE 0644): USE PATTERNS ELIGIBLE FOR REREGISTRATION
Application Type
Timing
Equipment
Formulation
[EPA Reg. No.]
Max. Single
App. Rate
Max. No.
of Apps.
Per
Year
Minimum
Retreatment
Interval
Pre-harvest
Interval
(PHI)
Restrictions/Comments
Apple
Foliar
Pre-bloom schedule
Aerial or
Ground (Broadcast)
Foliar
Extended schedule
Aerial or
Ground (Broadcast)
80% AI
Dry Flowable
[7969-105]
80% AI
Dry Flowable
[7969-105]
3.6
Ibai/A
2.4
Ibai/A
3
7
7
7
Not Specified
(MS)
77
Do not combine or integrate the 'pre-bloom' and
'extended application' schedules. Applications after
bloom are prohibited. Ground applications may be
made in a minimum of 20 gal/A; aerial applications
may be made in a minimum of 1 0 gal/A.
Do no apply more than 24 pounds of active
ingredient per season. Do not graze livestock in
treated areas.
Do not combine or integrate the 'pre-bloom' and
'extended ' application schedules. Ground
applications may be made in a minimum of 20 gal/A;
aerial applications may be made in a minimum of 10
gal/A. Do no apply more than 21 pounds of active
ingredient per season.
Do not graze livestock in treated areas.
Potato
Foliar
Aerial, Ground
(Broadcast) or
Chemigation
80% AI
Dry Flowable
[7969-105]
1.6
Ibai/A
6
5
14;
3 in CT, DE,
FL, MA, ME,
MI, NH, NY,
OH, PA, RI,
VT
Vine kill should occur 14 days prior to harvest.
Grazing of livestock in treated areas is prohibited.
Ground applications may be made in a minimum of
15 gal/A; aerial applications may be made in minimum
of 5 gal/A; and chemigation may be made only by
sprinkler irrigation systems.
71 of 108
-------
Appendix A: METIRAM (CASE 0644): USE PATTERNS ELIGIBLE FOR REREGISTRATION
Application Type
Timing
Equipment
Seed Treatment
Formulation
[EPA Reg. No.]
80% AI
Dry Flowable
[7969-105]
Max. Single
App. Rate
0.105
Ib ai/lOOlbs of
seed pieces
Max. No.
of Apps.
Per
Year
1
Minimum
Retreatment
Interval
5
Pre-harvest
Interval
(PHI)
NS
Restrictions/Comments
In addition to the maximum number of foliar
applications permitted, a single seed treatment
application may be made on potatoes.
Leatherleaf Ferns
Foliar
Ground (Broadcast)
80% AI
Dry Flowable
[7969-105]
1.6
Ibai/A
10
7
NS
Limit to a maximum of 1 application per week and 10
applications per year.
24(c) Special Local Need (SLN) use in Florida only.
72 of 108
-------
Appendix B
Data Supporting Guideline Requirements for the Reregistration of Metiram
GUIDE TO APPENDIX B
Appendix B contains a listing of data requirements which support the reregistration for active
ingredients within the chemical case covered by this RED. It contains generic data requirements that
apply in all products, including data requirements for which a "typical formulation" is the test substance.
The data table is organized in the following formats:
1. Data Requirement (Columns 1, 2 & 3). The data requirements are listed in the order of New
Guideline Number and appear in 40 CFR §158. The reference numbers accompanying each
test refer to the test protocols set in the Pesticide Assessment Guidance, which are available
from the National Technical Information Service, 5285 Port Royal Road, Springfield, VA
22161-0002, (703) 487-4650.
2. Use Pattern (Column 4). This column indicates the use patterns for which the data requirements
apply. The following letter designations are used for the given use patterns.
A. Terrestrial food
B. Terrestrial feed
C. Terrestrial nonfood
D. Aquatic food
E. Aquatic nonfood outdoor
F. Aquatic nonfood industrial
G Aquatic nonfood residential
H. Greenhouse food
I. Greenhouse nonfood
J. Forestry
K. Residential
L. Indoor food
M. Indoor nonfood
N. Indoor medical
O. Indoor residential
3. Bibliographical Citation (Column 5). If the Agency has acceptable data in its files, this column
lists the identification number of each study. Normally, this is the Master Record Identification
(MRID) Number, but may be a "GS" number if no MRID number has been assigned. Refer to
the Bibliography (Appendix D) for a complete citation of the study.
73 of 108
-------
Appendix B. Data Supporting Guideline Requirements for the Rere
New
Guideline
Number
Old
Guideline
Number
Requirement
gistration of Metiram
Use
Pattern
Bibliographical Citation(s)
PRODUCT USE CHEMISTRY
830.1550
830.1600
830.1620
830.1670
830.1700
830.6302
830.6303
830.6304
830.7050
830.7200
830.7300
830.7840
830.7860
830.7950
830.7370
830.7550
830.7000
830.6313
61-1
6 1-2 A
61-2B
62-1
63-2
63-3
63-4
None
63-5
63-7
63-8
63-9
63-10
63-11
63-12
63-13
Product Identity and Composition
Starting Materials and Manufacturing
Process
Description of Production Process
Discussion of Formation of Impurities
Preliminary Analysis (Technical)
Color
Physical State
Odor
UV/Visible Absorption
Melting Point/Melting Range
Density, Relative Density, Bulk Density
Solubility
Vapor Pressure
Dissociation Constant in Water
Octanol/Water Partition Coefficient
pH of Water Solutions or Suspensions
Stability
All
All
All
All
All
All
All
All
All
All
All
All
All
All
All
All
All
Not Applicable *
40507102
40507102
Data Gap*
00149526
New Data Requirement
(Confirmatory)
00149526
00149526
40507101, 40507102, 00157997
00149526
40507102
00157997
40507102
00149526
ECOLOGICAL EFFECTS
850.2100
850.2200
850.2300
71-1A
7 1-2 A
71-2B
7 1-4 A
71-4B
Avian Acute Oral Toxicity, Bobwhite
Quail
Avian Subacute Dietary Toxicity,
Bobwhite Quail
Avian Subacute Dietary Toxicity,
Mallard Duck
Avian Reproduction, Bobwhite Quail
Avian Reproduction, Mallard Duck
A,B, C
A,B, C
A,B, C
A,B, C
A,B,C
40656901
00108004
00108005
41082001
42539102
74 of 108
-------
Appendix B. Data Supporting Guideline Requirements for the Rere
New
Guideline
Number
850.1075
850.1010
None
850.1025
850.1035
850.1300
850.1350
854.1450
850.1500
850.1735
850.1740
850.4100
850.4150
850.4225
850.4250
850.5400
850.4400
850.3020
Old
Guideline
Number
72-1A
72-1C
72-2A
72-3A
72-3B
72-3C
72-4A
72-4B
72-4D
72-5
None
None
122-1A
122-1B
123-1A
123-1B
122-2A
123-2B
141-1
Requirement
Fish Acute Toxicity, Bluegill Sunfish
Fish Acute Toxicity, Rainbow Trout
Invertebrate Toxicity
Acute Estuarine/Marine Toxicity, Fish
Acute Estuarine/Marine Toxicity,
Mollusk
Acute Estuarine/Marine Toxicity,
Shrimp
Early Life Stage Fish, Freshwater
Life Cycle Aquatic Invertebrate,
Freshwater
Early Life Stage, Estuarine/Marine Fish
Life Cycle Fish
Whole Sediment Acute Toxicity
Invertebrates, Freshwater
Whole Sediment Acute Toxicity
Invertebrates, Estuarine/Marine
Seedling Emergence, Tier 1
Vegetative Vigor, Tier 1
Seedling Germination and Seedling
Emergence, Tier 2 on TEP
Vegetative Vigor, Tier 2 on TEP
Aquatic Plant Growth, Tier 1 on TEP
Aquatic Plant Toxicity Test Using
Lemma spp., Tier 2
Honey Bee Acute Contact Toxicity
eistration of Metiram
Use
Pattern
A,B,C
A,B,C
A,B,C
A,B,C
A,B,C
A,B, C
A,B,C
A,B,C
A,B,C
A,B,C
A,B,C
A,B, C
A,B,C
A,B, C
A,B,C
A,B,C
A,B,C
A,B, C
A,B, C
Bibliographical Citation(s)
Data Gap*
43525001,45933402
44301 101, Data Gap*
New Data Requirement
(Confirmatory)
New Data Requirement
(Confirmatory)
New Data Requirement
(Confirmatory)
New Data Requirement
(Confirmatory)
Data Gap*
Reserved
Reserved
New Data Requirement
(Confirmatory)
New Data Requirement
(Confirmatory)
New Data Requirement
(Confirmatory)
New Data Requirement
(Confirmatory)
Reserved
Reserved
Data Gap New Data Requirement
(Confirmatory)
43 199601, Data Gap*
66220 (Duplicate of 132710)
TOXICOLOGY
870.1100
81-1
Acute Oral Toxicity, Rat
A,B,C
40497002, 40497005
75 of 108
-------
Appendix B. Data Supporting Guideline Requirements for the Rere
New
Guideline
Number
870.1200
870.1300
870.2400
870.2500
870.2600
870.6200
870.3100
870.3150
870.3200
870.3465
870.4100
870.4200
870.3700
870.3800
870.4300
870.6300
870.5100
870.5300
870.5385
870.5900
Old
Guideline
Number
81-2
81-3
81-4
81-5
81-6
81-8
82-1A
82- IB
82-2
82-4
83-1A
83-1B
83-2B
83-3A
83-3B
83-4
83-5
83-6
84-2
Requirement
Acute Dermal Toxicity, Rabbit/Rat
Acute Inhalation Toxicity, Rat
Primary Eye Irritation, Rabbit
Primary Skin Irritation
Dermal Sensitization
Acute Neurotoxicity Screening Battery
90-Day Subchronic Feeding, Rodent
90-Day Subchronic Feeding, Nonrodent
21 -Day Dermal, Rabbit/Rat
90-Day Inhalation, Rat
Chronic Feeding Toxicity, Rodent
Chronic Feeding Toxicity, Nonrodent
(Dog)
Chronic Carcinogenicity (Feeding),
Mouse
Prenatal Developmental Toxicity, Rat
Prenatal Developmental Toxicity, Rabbit
2-Generation Reproduction and Fertility
Effects, Rat
Combined Chronic
Toxicity /Carcinogenicity Study, Rat
Developmental Neurotoxicity Study, Rat
Bacterial Reverse Gene Mutation Assay
Test
Detection of Gene Mutations in Somatic
Cells in Culture, Mammalian
Structural Chromosomal Aberrations
Cytogenics
eistration of Metiram
Use
Pattern
A,B,C
A,B,C
A,B,C
A,B, C
A,B, C
A,B, C
A,B,C
A,B, C
A,B, C
A,B, C
A,B,C
A,B,C
A,B,C
A,B,C
A,B, C
A,B,C
A,B,C
A,B,C
A,B,C
A,B,C
A,B,C
A,B,C
Bibliographical Citation(s)
40497007, 40497008
40497010
40497012
40497004
40497006
New Data Requirement
(Confirmatory)
126738 (Ace. No 249885), 40290601,
42539101,42595001
31591 (Ace. No 242190)
40497001
164083 (Ace. Nos. 263914, 263915),
40044701,40713301
98449, 98450 (Ace. Nos.247209-
247213), 41 163101
42133101,42491401
30245 (Ace. Nos. 242192, 242193)
30565 (Ace. No. 242188)
4071 1401, Reserved
98431 (Ace. No. 247214), Data Gap*
24720913,41163101
Reserved
0148682
00148680
00163786
00148681
76 of 108
-------
Appendix B. Data Supporting Guideline Requirements for the Rere
New
Guideline
Number
870.5500
870.7485
870.7600
Old
Guideline
Number
84-4
85-1
85-2
Requirement
Other Genotoxic Effects
(Unscheduled DNA Synthesis)
General Metabolism, Rat
Dermal Absorption (Penetration), Rat
eistration of Metiram
Use
Pattern
A,B, C
A,B,C
A,B, C
Bibliographical Citation(s)
00149528
155160, 155161 (Ace. No 259892)
155160, 155161 (Ace. No 259892)
OCCUPATIONAL/RESIDENTIAL EXPOSURE
875.2100
132-1A
Foliar Residue Dissipation
A,B,C
41339901 (Apple DFR)
ENVIRONMENTAL FATE
835.2120
835.2240
835.2410
835.4100
835.4200
835.4400
835.4300
835.1240
835.6100
835.1950
161-1
161-2
161-3
162-1
162-2
162-3
162-4
164-1
165-4
Hydrolysis
Photodegradation, Water
Photodegradation, Soil
Aerobic Soil Metabolism Study
Anaerobic Soil Metabolism Study
Anaerobic Aquatic Metabolism Study
Aerobic Aquatic Metabolism Study
Leaching
Terrestrial Field Dissipation Study
Bioaccumulation in Fish
A,B, C
A,B, C
A,B, C
A,B,C
A,B, C
A,B, C
A,B, C
A,B,C
A,B,C
A,B, C
00146764, 00155189, 00161937
00155190,00161938
00157031
45906901, 45145203, 00155288
00155288, Reserved
Reserved
459334401
40576301,00155288
00161935, 41440801, 41440802
Waived
RESIDUE CHEMISTRY
860.1100
860.1200
860.1300
171-2
171-3
171-4A
171-4B
Chemical Identity
Directions for Use
Nature of the Residue, Plants
Nature of the Residue, Livestock
A,B, C
A,B,C
A,B,C
A,B, C
40507102
Product Labels
00088894, 00160789, 00160790,
41695901, 41695902, 41695907,
41695908, 41695909, 41695910,
43064001
00088894, 00157034, 00160534,
00161338,41171601,41695903,
41695904, 41695905, 41695906,
43064001
77 of 108
-------
Appendix B. Data Supporting Guideline Requirements for the Rere
New
Guideline
Number
860.1340
860.1360
860.1380
860.1480
860.1850
860.1900
Old
Guideline
Number
171-4C
171-4D
171-4M
171-4E
171-4J
165-1
165-2
Requirement
Residue Analytical Method, Plants
Residue Analytical Method, Animals
Multiresidue Methods
Storage Stability, Plants
Storage Stability, Livestock
Magnitude of Residues in Meat, Milk,
Poultry and Eggs
Confined Rotational Crops
Field Rotational Crops
gistration of Metiram
Use
Pattern
A,B, C
A,B,C
A,B, C
A,B, C
A,B, C
A,B, C
A,B, C
A,B,C
Bibliographical Citation(s)
00063821, 00098644, 00098677,
00098689, 00157032, 00157033,
00160784, 00160785, 40540009,
40540010, 40587401, 40587402,
40587403, 40587404, 40581405,
40587406, 41076201, 41076202,
41076203, 41076204, 41076205,
41076206, 42078601, 43357201
00098685, 00160639, 00160786,
00161939,42078601
40730001,40730002
40540001, 40540002, 40540003,
40540004, 40540005, 40540006,
40540007, 40540008, 40540010,
40587407, 40587601, 40617401,
40617402, 40642101, 40642102,
40655101, 40655102, 40838901,
40962801, 41 1 12201, 411 12202,
41112203,41112204,41137601,
41188601,41188602,41188603,
41188604,41188605,41188606,
41188607,41294401,43064001,
43357201
40587601,40962801
40062801,40063802
4 1904801, Data Gap*
Reserved
Pome Fruits Group
860.1500
171-4K
Crop Field Trials (Apple)
A,B,C
40587406, 41076203, 41731801,
41831501, 42036901, 43357201
Root and Tuber Vegetables Group
860.1500
171-4K
Processed Food/Feed Grou
860.1520
171-4L
Crop Field Trials (Potato J
A,B,C
40540009
p
Processed Food (Apple)
Processed Food (Potato)
A,B, C
A,B,C
40587402
40540010
1 Data are not required for the unregistered TGAI.
* These studies were required under a previous DCI (GDCI-014601-16149), therefore data remain outstanding.
78 of 108
-------
APPENDIX B2
Data Supporting FIFRA Guideline Requirements for the EBDC Metabolite/Degradate ETU
Guideline Requirement
Guideline Number
New
850.1010
850.1075
850.1025
850.1075
850.1075
850.1300
850.1400
850.4400
Old
72-2A
72-1
72-3B
72-3 C
72-1 A
72- 1C
72-4B
72-4
122-2
123-2
Study Title
Use Pattern
MRID Citation
ECOLOGICAL EFFECTS
Acute Aquatic Invertebrate Toxicity -
Daphnia magna
Acute Toxicity - Estuarine/Marine Fish
Acute Toxicity - Estuarine/Marine
Mollusk
Acute Toxicity - Estuarine/Marine
Shrimp
Acute Fish Toxicity - Bluegill
Fish Toxicity Rainbow - Trout
Life Cycle Aquatic Invertebrate for
freshwater and estuarine/marine
Fish Early Life Stage for freshwater
and estuarine/marine
Aquatic Plant Growth, Tier I
Aquatic Plant Growth, Tier II
All
All
All
All
All
All
All
All
All
All
405910402, 46020901
New Data Requirement (Confirmatory)
New Data Requirement (Confirmatory)
New Data Requirement (Confirmatory)
New Data Requirement (Confirmatory)
45910401, 46020903
Reserved - Potential New Data Requirement
Reserved - Potential New Data Requirement
Data Gap*
45910403, 46020902 (supplemental), Data Gap*
79 of 108
-------
Guideline Requirement
Guideline Number
New
Old
870.3700
870.3800
870.4100
870.4100
870.6300
None
83-3
83-4
83-1A
83-1B
None
None
Study Title
Use Pattern
TOXICOLOGY
Developmental Toxicity Study in
Rabbits
2 Generation Reproductive Toxicity
Study
Chronic Feeding Toxicity - Rodent
Chronic Feeding Toxicity -
Non-Rodent
Developmental Neurotoxicity Study
Comparative Thyroid Toxicity Study in
Young and Adult Rats
All
All
All
All
All
All
MRID Citation
New Data Requirement (Confirmatory)
New Data Requirement (Confirmatory)
NTP Bioassay
42338101,42338102
New Data Requirement (Confirmatory)
New Data Requirement (Confirmatory)
ENVIRONMENTAL FATE
835.2120
835.2240
835.2410
835.4100
835.4400
835.1240
835.6100
None
161-1-SS
161-2-SS
161-3-SS
162-1-SS
162-3-SS
163-1-SS
164-1-SS
165-4-SS
Hydrolysis
Photodegradation - Water
Photodegradation - Soil
Aerobic Soil Metabolism
Anaerobic Aquatic Metabolism
Leaching/Adsorption/Desorption
Terrestrial Field Dissipation
Bioaccumulation in Fish
All
All
All
All
All
All
All
All
40466103
40466102
40466101
40838701, 45156401, 45225101 (all supplemental) t
00163335t
40588301 (supplemental)
00088923 (supplemental)
Waived
These studies were required under a previous DCI, GDCI-014504-16148, which was issued in April 1987. Data remain outstanding.
Registrants must completely characterize bound species to fulfill these guideline requirements.
80 of 108
-------
Appendix C
TECHNICAL SUPPORT DOCUMENTS
Additional documentation in support of this RED is maintained in the OPP docket, located in
Room 119, Crystal Mall #2, 1801 South Bell Street, Arlington, VA. It is open Monday through Friday,
excluding legal holidays, from 8:30AM to 4PM.
Public docket OPP-2004-0078 initially contained preliminary risk assessments and related
documents as of November 24, 2004. Ninety days later the first public comment period closed. The
EPA then considered comments, revised the risk assessment, and added the formal "Response to
Comments" document and the revised risk assessment to docket OPP-2005-0177 in December 2005.
All documents, in hard copy form, may be viewed in the OPP docket room or downloaded
and/or viewed via the Internet at the following Federal Docket Management Docket (FDMS) site:
http://www.regulations.gov
These documents include:
HEP Documents:
1. Kit Farwell. Metiram. Health Effects Division (HED) Human Health Risk
Assessment to Support Reregistration. June 13, 2005.
2. Christine Olinger. ETU'from EBDCs: Health Effects Division (HED)
Human Health Risk Assessment for the Common Metabolite/Degradate
ETU to Support Reregistration. June 8, 2005.
3. FeleciaFort. Mancozeb, Maneb, and Metiram: Revised Aggregate Dietary
Assessment of the Common Metabolite/Degradate Ethylene Thiourea
(ETU) to Support the Reregistration including the Aggregate ETU
Drinking Water Assessment. May 26, 2005.
4. FeleciaFort. Metiram Acute, Chronic, and Cancer Dietary Exposure
Assessments for the Reregistration Eligibility Decision. June 1, 2005.
5. Christine Olinger. Metiram. Revised Residue Chemistry Chapter of the
Reregistration Eligibility Decision. June 23, 2005.
6. Timothy Dole. Metiram. 2nd Revised Occupational and Residential
Exposure Assessment and Recommendations for the Reregistration
Eligibility Decision Document. June 8, 2005.
7. Linda L. Taylor. Metiram. Reregistration Branch 1/Health Effects
Division Response to Comments by BASF Corporation - Agricultural
Products [datedFebruary 22, 2005, March 14, 2005, April 7, 2005]. July
6, 2005.
81 of 108
-------
EFED Documents:
1. Gabe Patrick, Mohammed Ruhman, and Ronald Parker. Environmental Fate
and Ecological Risk Assessment for Metiram, Section 4 Reregistration for
Control of Fungal Diseases on Apples, Potatoes, Potato seed, Certain
Ornamental Plants and Tobacco Seedling Plants (Phase 3 Response). June
21,2005.
2. Gabe Patrick, Mohammed Ruhman, and Ronald Parker. Environmental Fate
and Ecological Risk Assessment for Ethylenethiourea (ETU) a Common
Degradate of the Ethylenebisdithiocarbamate Fungicides (EBDCs):
Metiram, Mancozeb, andManeb. A Part of EFED Section 4
Reregistrations for Control of Fungal Diseases on Various Crops, A
Forestry Use on Douglas Firs, Ornamental Plantings, and Turf. June 21,
2005.
BEAD Documents:
1. Richard Michell, Bill Phillips, and David Donaldson. BEAD Deliverables for
theEBDCRED. May 23, 2005.
2. Jenna Carter. Usage Report in Support of the Metiram Reregistration.
March 31,2005.
82 of 108
-------
Appendix D
CITATIONS CONSIDERED TO BE PART OF THE DATA BASE SUPPORTING THE
METIRAM REREGISTRATION DECISION (BIBLIOGRAPHY)
GUIDE TO APPENDIX D
1. CONTENTS OF BIBLIOGRAPHY. This bibliography contains citations of all studies
considered relevant by EPA in arriving at the positions and conclusions stated elsewhere in the
Reregistration Eligibility Document. Primary sources for studies in this bibliography have been
the body of data submitted to EPA and its predecessor agencies in support of past regulatory
decisions. Selections from other sources including the published literature, in those instances
where they have been considered, are included.
2. UNITS OF ENTRY. The unit of entry in this bibliography is called a "study". In the case of
published materials, this corresponds closely to an article. In the case of unpublished materials
submitted to the Agency, the Agency has sought to identify documents at a level parallel to the
published article from within the typically larger volumes in which they were submitted. The
resulting "studies" generally have a distinct title (or at least a single subject), can stand alone for
purposes of review and can be described with a conventional bibliographic citation. The
Agency has also attempted to unite basic documents and commentaries upon them, treating them
as a single study.
3. IDENTIFICATION OF ENTRIES. The entries in this bibliography are sorted numerically by
Master Record Identifier, or "MRID" number. This number is unique to the citation, and should
be used whenever a specific reference is required. It is not related to the six-digit "Accession
Number" which has been used to identify volumes of submitted studies (see paragraph 4(d)(4)
below for further explanation). In a few cases, entries added to the bibliography late in the
review may be preceded by a nine character temporary identifier. These entries are listed after
all MRID entries. This temporary identifying number is also to be used whenever specific
reference is needed.
4. FORM OF ENTRY. In addition to the Master Record Identifier (MRID), each entry consists
of a citation containing standard elements followed, in the case of material submitted to EPA, by
a description of the earliest known submission. Bibliographic conventions used reflect the
standard of the American National Standards Institute (ANSI), expanded to provide for certain
special needs.
a Author. Whenever the author could confidently be identified, the Agency has chosen to
show a personal author. When no individual was identified, the Agency has shown an
identifiable laboratory or testing facility as the author. When no author or laboratory
could be identified, the Agency has shown the first submitter as the author.
83 of 108
-------
b. Document date. The date of the study is taken directly from the document. When the
date is followed by a question mark, the bibliographer has deduced the date from the
evidence contained in the document. When the date appears as (1999), the Agency
was unable to determine or estimate the date of the document.
c. Title. In some cases, it has been necessary for the Agency bibliographers to create or
enhance a document title. Any such editorial insertions are contained between square
brackets.
d. Trailing parentheses. For studies submitted to the Agency in the past, the trailing
parentheses include (in addition to any self-explanatory text) the following elements
describing the earliest known submission:
(1) Submission date. The date of the earliest known submission appears
immediately following the word "received."
(2) Administrative number. The next element immediately following the word
"under" is the registration number, experimental use permit number, petition
number, or other administrative number associated with the earliest known
submission.
(3) Submitter. The third element is the submitter. When authorship is defaulted to
the submitter, this element is omitted.
(4) Volume Identification (Accession Numbers). The final element in the trailing
parentheses identifies the EPA accession number of the volume in which the
original submission of the study appears. The six-digit accession number
follows the symbol "CDL," which stands for "Company Data Library." This
accession number is in turn followed by an alphabetic suffix which shows the
relative position of the study within the volume.
84 of 108
-------
BIBLIOGRAPHY
MRID
30245
30565
31591
63821
88894
98431
98449
98450
CITATION
Hunter, B.; Barnard, A.V.; Prentice, D.E.; et al. (1979) Metiram
Tumorigenicity to Mice in Long Term Dietary Administration. Final rept.
(Unpublished study received Apr 10, 1980 under 279- 2514; prepared by
Huntingdon Research Centre, submitted by FMC Corp., Philadelphia, Pa.;
CDL:242192-A, 242193)
Palmer, A.K.; Simons, R. (1979) Effect of Metiram Technical on Pregnancy
of the Rat: BSF 302/79616. (Unpublished study includ- ing submitter
summary, received Apr 10, 1980 under 279-2514; prepared by Huntingdon
Research Centre, submitted by FMC Corp., Philadelphia, Pa.; CDL:242188-
A)
Sortwell, R.J.; Allen, D.G.; Heywood, R.; et al. (1979) Metiram: (Containing
2.2% Ethylenethiourea) Oral Toxicity Study in Rhesus Monkeys: BSF
267/78263. Final Report. (Unpublished study in- eluding submitter summary,
received Apr 10, 1980 under 279-2514; prepared by Huntingdon Research
Centre, submitted by FMC Corp., Philadelphia, Pa.; CDL:242190-A)
Shuttleworth, J.M. (1974) Letter sent to Route List dated Nov 14, 1974:
Determination of polyram residues on apples resulting from a polyram-
benlate program: M-3589. (Unpublished study received Feb 6, 1975 under
279-2032; submitted by FMC Corp., Philadel phia, Pa.; CDL:227773-A)
Lyman, W.R. (1977) The Fate of Ethylenebisdithiocarbamate Fungicides in
the Environment. (Unpublished study received Dec 9, 1981 under 707-78;
submitted by Rohm & Haas Co., Philadelphia, Pa.; CDL:070520-A)
Cozens, D.D.; Simons, R; Clark, R; et al. (1981) Effect of Metiram
Technical on Reproductive Function of Multiple Genera- tions in the Rat: BSF
200/80692. (Unpublished study received Apr 8, 1982 under 279-2032;
prepared by Huntingdon Research Centre, England, submitted by FMC
Corp., Philadelphia, Pa.; CDL: 247214-A)
Hunter, B.; Barnard, A.V.; Street, A.E.; et al. (1981) Metiram Toxicity and
Tumorigenicity in Prolonged Dietary Administration to the Rat: BSF
199/80391; WNT No. 77/951. Final rept. (Unpublished study received Apr
8, 1982 under 279-2032; prepared by Huntingdon Research Centre,
England, submitted by FMC Corp., Philadelphia, Pa.; CDL:247211-A;
247209; 247210; 247212; 247213)
FMC Corporation (1981) Two-year Dietary Toxicity/Oncogenicity Study:
Metiram (Technical): DEN/2038A/3. (Unpublished study prepared by FMC
85 of 108
-------
BIBLIOGRAPHY
MRID
98644
98677
98685
98689
108004
108005
148680
148681
148682
149526
CITATION
Corp. and Huntingdon Research Center, received Apr 8, 1982 under 279-
2032; CDL:247212-A)
Cullen, I.E. (1964) Spectrophotometric determination of dithio- carbamate
residues on food crops. Analytical Chemistry 36(1): 221-224.
(Also~In~unpublished submission received Nov 16, 1965 under unknown
admin, no.; submitted by FMC Corp., Philadelphia, Pa.; CDL: 120299-A)
FMC Corporation (1973) Polyram 80 Wettable Powder: Residues. (Un-
published study received Feb 20, 1974 under 279-2032; CDL: 023021-B)
Munger, D.M.; Berger, E.; Stanovick, R.P. (1967) Determination of Polyram
Residues in or on Cows Milk and Tissues: M-2128. (Un- published study
received on unknown date under 7F0550; submitted by Niagara Chemical,
Div. of FMC Corp., Los Fresnos, Tex.; CDL:092839-A)
Devine, J.M. (1970) Polyram Metabolite Method Development: Con- tract
No. L1045-06. Final rept. (Unpublished study received on unknown date
under 1F1088; prepared by Syracuse Univ. Re- search Corp., submitted by
Niagara Chemical, Div. of FMC Corp., Los Fresnos, Tex.; CDL:098619-B)
Fink, R. (1974) Final Report: Eight-day Dietary LCI50A~Bobwhite Quail:
Project No. 104-105. (Unpublished study received Apr 2, 1974 under 279-
2032; prepared by Truslow Farms, Inc., submitted by FMC Corp.,
Philadelphia, Pa.; CDL: 132451-A)
Fink, R. (1974) Final Report: Eight-day Dietary LCI50A~Mallard Ducks:
Project No. 104-106. (Unpublished study received Apr 2, 1974 under 279-
2032; prepared by Truslow Farms, Inc., submitted by FMC Corp.,
Philadelphia, Pa.; CDL: 132451-B)
Jagannath, D. (1985) Mouse Host-mediated Assay of Metiram Tech K38/
33 A: Final Report: LBI Project No. 20988. Unpublished study prepared by
Litton Bionetics, Inc. 15 p.
Ivett, J. (1985) Mutagenicity Evaluation of Metiram Technical K38/ 33 A in
an in vitro Sister Chromatid Exchange Assay in Chinese Hamster Ovary
(CHO) Cells: Final Report: LBI Project No. 20990. Unpublished study
prepared by Litton Bionetics, Inc. 28 p.
Jaeckh, R. (1985) Report on a Point Mutation Test Carried Out on CHO
Cells (HGPRT Locus) with the Test Substance Metiram (Techn. Purity).
Unpublished study prepared by BASF AG. 20 p.
BASF (1985) [Product Chemistry Data for Metiram]. Unpublished
86 of 108
-------
BIBLIOGRAPHY
MRID
149528
155160
155161
155288
157032
157033
157034
157997
160534
160639
160784
CITATION
compilation prepared by FMC Corporation. 48 p.
Cifone, M. (1984) Evaluation of Metiram Tech. in the Rat Primary
Hepatocyte Unscheduled DNA Synthesis Assay: Final Report: Pro-jectNo.
20991. Unpublished study prepared by Litton Bionetics, Inc. 14 p.
Hawkins, D.; Elsom, L.; Mdgley, L; et al. (1985) The Biokinetics and
Metabolism of [Carbon-14]-Metiram in the Rat: HRC Report No. BSF
410/85720. Unpublished study prepared by Huntingdon Re- search Centre
Ltd. 184 p.
Hawkins, D.; Elsom, L.; Girkin, R.; et al. (1984) Dermal Absorption of
Metiram in Rats: HRC Report No. BSF 411/84694. Unpublished study
prepared by Huntingdon Research Centre pic. 75 p.
Keller, E.; Huber, R. (1985) [The Fate of Metiram in Soil]: Rep. No. 2208.
Unpublished compilation prepared by BASF AG. 29 p.
Novak, R. (1986) Determination of Residues of Polyram and Ethylene-
thiourea in Apples: NPC Project No. 86-2001: FMC-01-85. Unpub- lished
study prepared by NPC, Inc. and Enviro-Bio-Tech, Ltd. 27 p.
Novak, R. (1986) Determination of Residues of Polyram and Ethylene-
thiourea in Potatoes: NPC Project No. 86-2001: FMC-02-85. Un-
published study prepared by NPC, Inc. and Enviro-Bio-Tech, Ltd. 20 p.
Holloway, C.; Kargarotos, B.; Kurth, B.; et al. (1986) The Bioki- netics and
Metabolism of Metiram Complex in Lactating Goats: NATEC Projects NA
85 9658, NA 85 9668, NA 85 9676 and NA 85 9678. Unpublished study
prepared by NATEC Institute. 131 p.
BASF Wyandotte Chemical Corp. (1985?) Product Chemistry [Data]:
Metiram. Unpublished compilation. 73 p.
Cameron, D.; Gummer, J.; Gillard, D. (1986) Residues of Metiram in Milk
and Tissues of Dairy Cows: Rept. No. BSF/443/86353. Un- published study
prepared by Huntingdon Research Centre. 51 p.
Cameron, D.; Gummer, J. (1986) Residues of ETU (Ethylene Thiourea) in
Milk and Tissues of Dairy Cows following Oral Administration of Metiram:
HRC Report No. BSF/443/86353/b. Unpublished study prepared by
Huntingdon Research Centre. 34 p.
Novak, R. (1986) Determination of Residues of Polyram and Ethylene-
thiourea in Apples and Process Fractions: Project No.: G237. Ill: PC-0050.
Unpublished compilation prepared by Enviro-Bio-Tech, Ltd. 30 p.
87 of 108
-------
BIBLIOGRAPHY
MRID
160785
160786
160789
160790
161338
161939
163786
164083
40044701
40062801
CITATION
Novak, R. (1986) Determination of Residues of Polyram and Ethyl-
enethiourea in Potato Process Samples: Project No. G237. Ill: NPC Project
No.: 86-2001. Unpublished study prepared by FMC Corp. 30 p.
Roberts, R.; Cameron, D.; Gummer, J. (1986) Residues of Metiram in Milk
and Tissues of Dairy Cows: HRC Study No.: BSF/443/86353. Unpublished
study prepared by Huntingdon Research Centre. 40 p.
Bieber, W.; Kroehn, R. (1986) Study on the Metabolism of the Metiram
Complex (Ethylene-[Carbon-14-labeled]) in Apples: Proj.: NA 85 9620/H.
Unpublished study prepared by BASF, AG. 68 p.
Bieber, W.; Kroehn, R. (1986) Study on the Metabolism of the Metiram
Complex (Ethylene-[Carbon-14-labeled]) in Potatoes: Proj.: NA 85 9620/1.
Unpublished study prepared by BASF, AG. 67 p.
Holloway, C.; Kargarotos, B.; Baustian, M.; et al. (1986) The Bio- kinetics
and Metabolism of Metiram Complex in Laying Hens: Part I: Biokinetics:
[Part II: Metabolism]. Unpublished compilation prepared by Institut fur
Naturwissenschaftiichtechnische Dienste GmbH. 157 p.
Roberts, N; Fairley, C.; Gummer, J.; et al. (1986) The Determination of
Residues of Metiram in the Eggs and Tissues of the Laying Hen following Oral
Gavage of Metiram: BSF 449BR/86777b. Unpublished study prepared by
Huntingdon Research Centre Ltd. 133 p.
Ivett, J. (1986) Mutagenicity Evaluation of Metiram Technical K38/ 33 A in
the Rat Bone Marrow: Cytogenetic Assay: Amended Final Rept: LBI Proj.
No. 22202. Unpublished study prepared by Lit- ton Bionetics, Inc. 29 p.
Ulrich, C. (1986) Thirteen Week Subchronic Inhalation Toxicity Study on
Metiram in Rats - Final Report: Study No. 312-015. Un- published study
prepared by International Research and Develop- ment Corporation. 371 p.
Ulrich, C. (1986) Thirteen Week Subchronic Inhalation Toxicity Study on
Metrim in Rats - Final Report: Laboratory Project ID: 312-015: BASF Doc.
No. 86/0407. Unpublished study prepared by International Research and
Development Corp. 385 p.
Roberts, N.; Fairley, C.; Emerson, E.; et al. (1987) The Determination of
Residues of Metiram in the Eggs and Tissues of the Laying Hen Following
Oral Gavage of Metiram Complex: Laboratory Project Identification:
BSF/449/RB(b): Final Report. Unpublish- ed study prepared by Huntingdon
Research Centre Ltd. 47 p.
88 of 108
-------
BIBLIOGRAPHY
MRID
40062802
40290601
40497001
40497002
40497004
40497005
40497006
40497007
40497008
40497010
CITATION
Roberts, N.; Fairley, C.; Emerson, E.; et al. (1987) The Determi- nation of
Ethylenethiourea (ETU) Residues in the Eggs and Tissues of the Laying Hen
Following Oral Administration of Metiram Complex: Laboratory Project
Identification: BSF/449/RBR/(a): Final Report. Unpublished study prepared
by Huntingdon Research Centre Ltd. 97 p.
Offer, 1; Gopinath, C. (1987) Metiram: Toxicity to Rats in Dietary
Administration for 13 Weeks Followed by a 6-week Withdrawal Per- iod:
HRC Report No. BSF 197/8713, Addendum to BSF 197/77612.
Unpublished study prepared by Huntingdon Research Centre, Ltd. lip.
Ullmann, L.; Sacher, R.; Porricello, T.; et al. (1986) Subacute 21-day
Repeated-dose Dermal Toxicity Study with Polyram DF in Rabbits:
Registration Document No. BASF 87/0260. Unpublished study prepared by
Research & Consulting Co. AG. 167 p.
Hofmann, H. (1975) Metiram Technical—Acute Oral Toxicity in the Rat:
Laboratory Project ID XXIV/318: Reg. Doc. #BASF 75/0005. Unpublished
study prepared by BASF Aktiengesellschaft. 9 p.
Kirsch, ?. (1987) Report on the Acute Dermal Irritation/Corrosivity to the
Intact Dorsal Skin of the White Rabbit Based on OECD and EPA:
Laboratory Project ID 14H314/86: Reg. Doc. #BASF 87/0093.
Unpublished study prepared by BASF Aktiengesellschaft. 12 p.
Hofmann, H. (1974) Polyram Combi—Acute Oral Toxicity in Rats:
Laboratory Project ID 85/121 (XIII/100): Reg. Doc. #BASF 85/0121.
Unpublished study prepared by BASF Aktiengesellschaft. 9 p.
Jackh, R. (1981) Report on the Study of the Sensitizing Effect of Metiram
Techn. (Project No. 30H171/81) in the Guinea Pig— Maximization Test:
Laboratory Project ID 30H171/81: Reg. Doc. #BASF 82/0068.
Unpublished study prepared by BASF Aktiengesell- schaft. 29 p.
Grundler, O. (1979) Metiram Technical with 2% ETU-Acute Dermal
Toxicity in the Rat: Laboratory Project ID 79/443: Reg. Doc. #BASF
79/0032. Unpublished study prepared by BASF Aktiengesell-schaft. 8 p.
Grundler, O. (1979) Metiram-complex—Acute Dermal Toxicity in the Rats:
Laboratory Project ID 79/442: BASF 85/0026. Unpublished study prepared
by BASF Aktiengesellschaft. 8 p.
Kirsch, ?. (1987) Report on the Acute Irritation to the Eye of the White
Rabbits Based on OECD and EPA: Laboratory Project ID 13H314/86: Reg.
89 of 108
-------
BIBLIOGRAPHY
MRID
40497012
40507101
40507102
40540001
40540002
40540003
40540004
40540005
40540006
40540007
40540008
CITATION
Doc. #BASF 87/0095. Unpublished study prepared by BASF
Aktiengesellschaft. lip.
Kirsch, ?. (1987) Report on the Acute Irritation to the Eye of the White
Rabbit Dated on OECD and EPA (FIFRA): Laboratory Project ID
13H314/86: Reg. Doc. #BASF 87/0095. Unpublished study pre- pared by
BASF Aktiengesellschaft. lip.
Schneider, A.; Redeker, J. (1988) Solubility of Metiram in Ethanol and
DMSO: Reg. Document No. BASF 88/5006. Unpublished study prepared
by BASF Aktiengesellschaft. 7 p.
Ohnsorge (1988) Amendment on Product Chemistry Submission Based on
Discission ?sic| with EPA on September 11, 1987: Reg. Document No.
88/5007. Unpublished study prepared by BASF Aktiengesell-schaft. lip.
Larese, J. (1988) Storage Stability of Metiram and Ethylenethiourea in Frozen
Potato Processed Commodities: Laboratory Project IDs FMC-22-87,
FMC-23-87. Unpublished study prepared by Enviro-Bio- Tech, Ltd. 163 p.
Larese, J. (1988) Storage Stability of Metiram and Ethyl enethiourea in Frozen
Apple Processed Commodities: Laboratory Project IDs FMC-15-87, FMC-
16-87. Unpublished study prepared by Enviro-Bio- Tech, Ltd. 269 p.
Larese, J. (1988) Storage Stability of Metiram and Ethyl enethiourea in Frozen
Tomatoes: Laboratory Project ID FMC-03-87. Unpub- lished study
prepared by Enviro-Bio-Tech, Ltd. 92 p.
Larese, J. (1988) Storage Stability of Metiram and Ethyl enethiourea in Frozen
Potatoes: Laboratory Project ID FMC-04-87. Unpub- lished study prepared
by Enviro-Bio-Tech, Ltd. 106 p.
Larese, J. (1988) Storage Stability of Metiram and Ethyl enethiourea in Frozen
Apples: Laboratory Project ID FMC-05-87. Unpublished study prepared by
Enviro-Bio-Tech, Ltd. 101 p.
Larese, J. (1988) Storage Stability of Metiram and Ethyl enethiourea in Frozen
Sugar Beets: Laboratory Project ID FMC-06-87. Unpub- lished study
prepared by Enviro-Bio-Tech, Ltd. 102 p.
Novak, R. (1988) Metiram and Ethylenethiourea: Summary of Storage
Stability Studies in Animal Commodities Including Sample Histories for
Metiram Dairy Cattle and Poultry Feeding Studies: Project ID METIRAM-
88-1000. Unpublished study. 17 p.
Novak, R. (1988) Metiram and Ethylenethiourea: Summary of Storage
90 of 108
-------
BIBLIOGRAPHY
MRID
40540009
40540010
40576301
40587401
40587402
40587403
40587404
40587405
CITATION
Stability in Frozen Raw Agricultural Commodities and Processed
Commodities: Project ID METIRAM-88-1001. Unpublished study. 17 p.
Bookbinder, M. (1988) Metiram and Ethylene Thiourea: Magnitude of the
Residue in Potatoes Treated by Ground Equipment in Colarado, Idaho,
Maine, Michigan, North Dakota, Oregon, and Wisconsin, 1987. Unpublished
study prepared by Enviro-Bio-Tech, Ltd. 223 p.
Bookbinder, M. (1988) Metiram and ETU: Residues in Commodities
Processed from Potatoes Treated by Grounded Equipment. Unpub- lished
study prepared by Orius Associates, Inc. in cooperation with Enviro-Bio-
Tech, Ltd. 183 p.
Spare, W. (1988) Leaching Characteristics of Parent Metiram: Pro-jectNo.
2501. Unpublished study prepared by Agrisearch Inc. 118 p.
Bookbinder, M. (1988) Metiram and Ethylene Thiourea: Magnitude of the
Residue in Pecans Treated by Ground Equipment in Arizona, Louisiana, and
Oklahoma, 1987: File/Issue 28-MET/88006. Unpublished study prepared by
Orius Associates in association with Enviro-Bio-Tech, Ltd. 126 p.
Bookbinder, M. (1988) Metiram and ETU: Residues in Commodities
Processed from Apples Treated by Ground Equipment in Washington, 1987:
File/Issue 28-MET/88007. Unpublished study prepared by Orius Associates
Inc. in association with Enviro-Bio-Tech, Ltd. 173 p.
Bookbinder, M. (1988) Metiram and Ethylene Thiourea: Magnitude of the
Residue in Peanuts Treated by Ground Equipment in Georgia, North
Carolina, Oklahoma, South Carolina, Texas, and Virginia, 1987: File/Issue
28-MET/88008. Unpublished study prepared by Orius Associates in
association with Enviro-Bio-Tech , Ltd. 213 p.
Bookbinder, M. (1988) Metiram and Ethylene Thiourea: Magnitude of the
Residue in Tomatoes Treated by Ground Equipment in Califor- nia, Florida,
Indiana, Ohio, New Jersey, and South Carolina, 1987: File/Issue 28-
MET/88012. Unpublished study prepared by Orius Associates Inc. in
association with Enviro-Bio-Tech, Ltd. 208 p.
Bookbinder, M. (1988) Metiram and Ethylene Thiourea: Magnitude of the
Residue in Sugar Beets Treated by Ground Equipment in California, Idaho,
Michigan, North Dakota, and Nebraska, 1987: File/Issue 28-MET/88013.
Unpublished study prepared by Orius Associates Inc. in association with
Enviro-Bio-Tech, Ltd. 205 p.
91 of 108
-------
BIBLIOGRAPHY
MRID
40587406
40587407
40587601
40617401
40617402
40642101
40642102
40655101
40655102
CITATION
Bookbinder, M. (1988) Metiram and Ethylene Thiourea: Magnitude of the
Residue in Apples Treated by Ground Equipment in California, Michigan,
North Carolina, New York, Oregon, Virginia and Washington, 1987:
File/Issue 28-MET/88014. Unpublished study prepared by Orius Associates
Inc. in association with Enviro- Bio-Tech, Ltd. 239 p.
Bookbinder, M. (1988) Metiram: Storage Stability of Weathered Residues in
Apples Treated by Ground Equipment in North Carolina and New York,
1987: File/Issue 28-MET/88026. Unpublished study prepared by Orius
Associates Inc. in association with Enviro- Bio-Tech, Ltd. 73 p.
Christman, P. (1988) Determination of the Stability of Metiram and
Ethylenethiourea in/on Animal Products: HLA 6001-180. Unpub- lished
study prepared by Hazleton Laboratories America, Inc. 72 p.
Larese, J. (1988) Storage Stability of Metiram and Ethylenethiourea in Frozen
Apples: Addendum: Three Month Ethylenethiourea Stability: Laboratory
Project ID FMC-05-87. Unpublished study prepared by Enviro-Bio-Tech,
Ltd. 18 p.
Larese, J. (1988) Storage Stability of Metiram and Ethylenethiourea in Frozen
Sugar Beets: Addendum: Three Month Ethylenethiourea Stability: Laboratory
Project ID FMC-06-87. Unpublished study prepared by Enviro-Bio-Tech,
Ltd. 19 p.
Larese, J. (1988) Storage Stability of Metiram and Ethylenethiourea in Frozen
Potatoes: Addendum: One and Three Month Ethylenethio- urea Stability:
Laboratory Project ID: FMC-04-87. Unpublished study prepared by Enviro-
Bio-Tech, Ltd. 23 p.
Larese, J. (1988) Storage Stability of Metiram and Ethylenethiourea in Frozen
Potato Processed Commodities: Addendum: Three Month Metiram and
Ethylenethiourea Stability Potato Chips and Granules: Laboratory Project ID:
FMC-22-87, -23-87. Unpublished study prepared by Enviro-Bio-Tech, Ltd.
37 p.
Larese, J. (1988) Storage Stability of Metiram and Ethylenethiourea in Forzen
Apple Processed Commodities: Laboratory Project ID: FMC-15-87.
Unpublished study prepared by Enviro-Bio-Tech, Ltd. 18 p.
Larese, J. (1988) Storage Stability of Metiram and Ethylenethiourea in Frozen
Apple Processed Commodities: Laboratory Project IDs: FMC-16-87 and -
17-87. Unpublished study prepared by Enviro-Bio- Tech, Ltd. 48 p.
92 of 108
-------
BIBLIOGRAPHY
MRID
40656901
40711401
40713301
40730001
40730002
40838901
40962801
41076201
41076202
CITATION
Fletcher, D. (1988) Metiram Technical: 21-day Acute Oral LD50 Study in
Bobwhite Quail: Laboratory Project ID: 87 QD 99. Unpublished study
prepared by Bio-Life Associates, Ltd. 25 p.
Hellwig, J. (1988) Report on the Study of the Prenatal Toxicity of Metiram
Premix 95% in Rabbits after Oral (Gavage) Administra- tion: Reg. Doc.
#BASF 88/0154. Unpublished study prepared by BASF Aktiengeschaft. 290
P-
Ulrich, C. (1987) Thirteen Week Subchronic Inhalation Toxicity Study on
Metiram in Rats—Addendum to Final Report Covering Re- covery Phase:
Laboratory Project ID: 312-015. Unpublished study prepared by
International Research and Development Corp. 264 p.
Rhoads, W. (1988) Determination of the Characteristics of Metiram When
Subjected to Aanlysis by the United States food and Drug Administration
(FDA) Multi-Residue Protocols I, II, HI, and IV (40CFR 158.125): Study
No. NPC/BASF 1082. Unpublished study prepared by Colorado Analytical
Research & Development Corp. 80 p.
Rhoads, W. (1988) Determination of the Characteristics of Ethylene- thiourea
When Subjected to Analysis by the United States Food and Drug
Administration (FDA) Multi-Residue Protocols I, H, m and IV (40 CFR
158.125): Study No. NPC/BASF 1082A. Unpublished study prepared by
Colorado Analytical Research & Development 147 p.
Larese, J. (1988) Storage Stability of Metiram and Ethylenethiourea in Frozen
Peanut Nutmeat and Hulls: Laboratory Project ID FMC- 28-87: FMC-29-
87. Unpublished study prepared by Enviro-Bio- Tech, Ltd. 130 p.
Christman, P. (1988) Determination of the Stability of Metiram and
Ethylenethiourea Residues in/on Anaimal Products: Final Report: Project ID:
HLA 6001-180. Unpublished study prepared by Hazle- ton Laboratories
America, Inc. 72 p.
Bookbinder, M. (1989) Metiram and ETU: Residues in Commodities
Processed from Sugar Beets Treated by Ground Equipment in North Dakota
and Idaho, 1987: Addendum to: File/Issue No. 28-MET/ 89025.
Unpublished study prepared by Orius Associates Inc., in cooperation with
Morse Laboratories, Inc., and others. 130 p.
Bookbinder, M. (1989) Metiram and ETU: Residues in Peanuts Treated at
Exaggerated Rates by Ground Equipment in Georgia, 1987: Addendum to:
93 of 108
-------
BIBLIOGRAPHY
MRID
41076203
41076204
41076205
41076206
41082001
41112201
41112202
41112203
CITATION
File/Issue No. 28-MET/89026. Unpublished study prepared by Orius
Associates Inc., in cooperation with Enviro- Bio-Tech, Ltd. 62 p.
Bookbinder, M. (1989) Metiram and Ethylene Thiourea: Magnitude of the
Residue in or on Apples Treated by Aerial and Ground Equip- ment in
California, 1988: File/Issue No. 40-MET/89057. Unpu- blished study
prepared by Orius Associates Inc., in cooperation with McKenzie
Laboratories and others. 76 p.
Bookbinder, M. (1989) Metiram and ETU: ResiduesIN Commodities
Processed from Tomatoes Treated by Ground Equipment in Califor- nia,
1988: Addendum to: File/Issue No. 28-MET/89058. Unpublish- ed study
prepared by Orius Associates Inc., in cooperation with Morse Laboratories,
Inc. 224 p.
Bookbinder, M. (1989) Metiram and ETU: Magnitude of the Residues in
Pecans Treated by Ground Equipment in Georgia, 1988: Addendum to:
File/Issue No. 40-MET/89059. Unpublished study prepared by Orius
Associates Inc., in cooperartion with McKenzie Labora- tories Inc. 88 p.
Bookbinder, M. (1989) Metiram and Ethylene Thiourea: Magnitude of the
Residue in or on Tomatoes Treated by Aerial and Ground Equipment in
California, 1988: File/Issue No. 40-MET/89061. Un- published study
prepared by Orius Associates Inc., in coopera- tion with McKenzie
Laboratories and others. 80 p.
Fletcher, D.; Pedesen, C. (1989) Metiram Premix 95%: Toxicity and
Reproduction Study in Bobwhite Quail: BLAL No. 87 QR 29. Unpub- lished
study prepared by Bio-Life Associates, Ltd. 90 p.
Larese, J. (1989) Storage Stability ...Addendum: Metiram And
Ethylenethiouria Stability up to One Year in Wet and Dry Apple Pomace:
Project IDS FMC-25-87 and FMC-30-87. Unpublished study prepared by
Enviro-Bio-Tech, Ltd. 64 p.
Larese, J. (1989) Storage Stability ... Addendum: Twelve Month Meti ram
and Ethylenethiourea Stability: Project IDs FMC-28-87 and FMC-29-87.
Unpublished study prepared by Enviro-Bio-Tech, Ltd. 43 p.
Larese, J. (1989) Storage Stability ... Addendum: Metiram and Ethy-
lenethiourea Stability in Wet & Dry Potato Peel: Project IDs FMC-26-87
and FMC-31-87. Unpublished study prepared by Enviro- Bio-Tech, Ltd. 65
P-
94 of 108
-------
BIBLIOGRAPHY
MRID
41112204
41137601
41163101
41171601
41188601
41188602
41188603
41188604
41188605
CITATION
Westburg, G. (1989) Metiram And Ehtylene Thiourea: Storage Stabi- lity of
Residues in Sugar Beet Processed Commodities: File/Issue No. 89R-MET-
001. Unpublished study prepared by Morse Labora- tories, Inc. 127 p.
Larese, J. (1989) Storage Stability of Metiram and Ethylenethiourea in Frozen
Pecan Nutmeat: Laboratory Project ID No. FMC-01-89: Metiram Task
Force Protocol No. 87-1002. Unpublished study prepared by Enviro-Bio-
Tech, Ltd. 69 p.
Hunter, et. al. (1976) Preliminary Assesment of Metiram Toxicity to Mice in
Dietary Administration for 4 Weeks: Registration Docu- ment No. BASF 76-
0014. Unpublished study prepared by Huntington Research Centre. 36 p.
Wu, J. (1989) Metabolism of ?carbon 14|-Metiram Complex in Lacta- ting
Goats—Analysis and Quantitation of Metabolite and/or the Corresponding
Natural Products in Milk and Tissues: Project ID: Xenobiotic Laboratories,
Inc. 260 p.
Larese, J. (1989) Storage Stability of Metiram and Ethyl enethiourea in Frozen
Apples: Addendum: Twelve Month Ethylenethiourea and Metiram Stability:
Laboratory Project ID FMC-05-87. Unpublished study prepared by Enviro-
Bio-Tech, Ltd. 38 p.
Larese, J. (1989) Storage Stability of Metiram and Ethylenethiourea in Frozen
Sugar Beets: Addendum: Twelve Month Metiram and Ethylenethiourea
Stability: Laboratory Project ID FMC-06-87. Unpublished study prepared
by Enviro-Bio-Tech, Ltd. 40 p.
Larese, J. (1989) Storage Stability of Metiram and Ethylenethiourea in Frozen
Potatoes: Addendum: Twelve Month Ethylenethiourea and Metiram Stability:
Laboratory Project ID FMC-04-87. Unpublished study prepared by Enviro-
Bio-Tech, Ltd. 39 p.
Larese, J. (1989) Storage Stability of Metiram and Ethylenethiourea in Frozen
Tomatoes: Addendum: Twelve Month Metiram and Ethylene- thourea
Stability: Laboratory Project ID FMC-03-87. Unpublished study prepared
by Enviro-Bio-Tech, Ltd. 35 p.
Larese, J. (1989) Storage Stability of Metiram and Ethylenethiourea in Frozen
Apple Processed Commodities: Addendum: Metiram and Ethylenethiourea
Stability Up to One Year in Apple Juice, Sauce and Baby Food: Laboratory
Project ID FMC-15-87: FMC-16-87. Unpublished study prepared by
Enviro-Bio-Tech, Ltd. 90 p.
95 of 108
-------
BIBLIOGRAPHY
MRID
41188606
41188607
41294401
41339901
41440801
41440802
41695901
41695902
CITATION
Larese, J. (1989) Storage Stability Study: Determination of the Stability of
Weathered Metiram Residues on Apples: Analysis of NC Apples after Siz
and Twelve Months of Frozen Storage: Addendum: Laboratory Project ID
FMC-12-87. Unpublished study prepared by Enviro-Bio-Tech, Ltd. 37 p.
Larese, J. (1989) Storage Stability of Metiram and Ethylenethiourea in Frozen
Potato Processed Commodities: Addendum: Twelve Month Metiram and
Ethylenethiourea Stability: Potato Chips and Granules: Laboratory Project
IDs FMC-22-87: FMC-23-87. Unpub- lished study prepared by Enviro-
Bio-Tech, Ltd. 64 p.
Westberg, G.; Novak, R. (1989) Metiram and Ethylene Thiourea: Storage
Stability of Residues in Tomato Processed Commodities: Lab Project
Number: 89R/MET/002. Unpublished study prepared by Morse
Laboratories, Inc. 139 p.
Ravitz, S.; Bookbinder, M. (1989) Dislodgeable Foliar Residues of Polyram
80WP Fungicide Applied to Apples in California, 1988: Lab Project No.
28288; File No. 37-MET/89121; Lab No. 48923, etc. Unpublished study
prepared by Orius Associates, Inc. in cooperation with Research for Hire and
Morse Laboratories, Inc. 171 p.
Bookbinder, M. (1990) Metiram and Ethylenethiorea: Dissipation in Soil
After Application to Sugar Beets in California by Ground Equipment: Lab
Project Number: 42-MET/90014. Unpublished study prepared by Orius
Associates Inc., in cooperation wtih Morse Laboratories, Inc., and others.
200 p.
Bookbinder, M. (1990) Metiram and Ethylenethiourea: Dissipation in Soil
After Application to Sugar Beets in New York by Ground Equipment, 1988-
1989: Lab Project Number: 42-MET/90029. Unpub- lished study prepared
by Orius Associates Inc., in cooperation with Morse Laboratories, Inc., and
others. 132 p.
Hubert, T. (1990) Metiram: Nature of the Residue in Apples: Final Report:
Lab Project Number: HLA 6101-106A. Unpublished study Prepared by
Hazleton Laboratories America, Inc. 236 p.
Hubert, T. (1990) Metiram: Nature of Residues in Apples: Metiram and
Ethylenethiourea Residues: Final Report: Lab Project Number: HLA 6101-
106B. Unpublished study prepared by Hazleton Labora- tories America, Inc.
73 p.
96 of 108
-------
BIBLIOGRAPHY
MRID
41695903
41695904
41695905
41695906
41695907
41695908
41695909
41695910
41731801
41831501
CITATION
Marco, G.; Novak, R. (1990) Executive Summary of Metiram Hen
Metabolism Studies Conducted by the Metiram Task Force. Unpublished
study prepared by NPC, Inc. 15 p.
Merricks, L. (1988) Metabolism Feeding Study in Laying Hens Using
?Carbon 14|-Metiram: Lab Project Number: 2507. Unpublished study
prepared by Agrisearch Inc. 57 p.
Wu, J. (1990) Metabolism of ?Carbon 14|-Metiram Complex in Laying Hens
Analysis and Quantitation of Metabolites and/or the Corros- ponding Natural
Products in Eggs and Tissues: Lab Project Num- ber: XBL RPT0011: 90
5080. Unpublished study prepared by Xeno- Biotica Laboratories, Inc. 113
P-
Christman, P. (1989) Metiram and Ethylenethiourea Residue Analysis:
Analysis of Tissues and Eggs from Laying Hens Dosed with ?Carbon 14|-
Metiram: Lab Project Number: HLA 6001-355B: 89 5083. Unpub- lished
study prepared by Hazleton Laboratories America, Inc. 72 p.
Marco, G.; Novak, R. (1990) Executive Summary of Metiram Potato Me-
tabolism Studies Conducted by the Metiram Task Force. Unpub- lished study
prepared by NPC, Inc. 13 p.
Hubert, T. (1989) Metiram: Nature of the Residue in Potatoes: Final Report:
Lab Project Number: HLA 6101-105A: 89 5167. Unpublished study
prepared by Hazleton Laboratories America, Inc. 55 p.
Wu, J. (1990) Metabolism of ?Carbon 14|-Metiram Complex in Pota- toes:
Nature of the Residue in Potatoes: Analysis and Quantita- tion of Metabolites:
Lab Project Number: XBL RP0013: 90 5081. Unpublished study prepared
by XenoBiotic Laboratories, Inc. 74 p.
Hubert, T. (1989) Metiram: Nature of Residues in Potatoes; Metiram and
Ethylenethiourea Residues: Lab Project Number: HLA 6101- 105B: 89
5082. Unpublished study prepared by Hazleton Laborato- lies America, Inc.
68 p.
Loftus, M. ; Kovacs, M. (1990) 1990 Mancozeb and Metiram Apple Field
Study-Early Season Treatments Through Full Bloom: Lab Project Number:
ETU 90-13. Unpublished study prepared by Rohm and Haas Co. 582 p.
Loftus, M. (1991) 1990 Mancozeb and Metirm Apple Field Study: Lab
Project Number: ETU 91-02. Unpublished study prepared by Rohm and
Haas Co. 691 p.
97 of 108
-------
BIBLIOGRAPHY
MRID
41904801
42036901
42078601
42133101
42539101
42539102
42595001
43064001
43199601
43357201
CITATION
Merricks, L.; Lantz, L. (1991) Carbon 14-Metiram Confined Rotation- al
Crop Study: Lab Project Number: 2503. Unpublished study pre- pared by
Agrisearch Inc. 73 p.
Leparulo, M. (1991) 1990 Mancozeb and Metiram Apple Field Study:
Storage Stability Study: Lab Project Number: ETU 91-06. Unpublished study
prepared by Technical Assessment Systems, Inc. 216 p.
Mao, J. (1991) Analysis of Ethylenebisdithiocarbamate Fungicides by High
Performance Liquid Chromatography: Final Report: Lab Project Number:
91-10-3950: 986.0991.6114.250. Unpublished study prepared by
Springborn Labs., Inc. 38 p.
Corney, S.; Allen, T.; Frei, T.; et al. (1984) 52-Week Oral Toxi- city
(Feeding) Study with Metiram Premix 95% in the Dog: Lab Project Number:
206627: ZST 33 DO 636/899005. Unpublished study prepared by RCC
Research and Consulting Company Ltd., RCC Um- weltchemie AG, and
others. 767 p.
Mellert, W. (1992) Study of the Oral Toxicity of Metiram Premix 95% in the
Wistar Rat—Administration in the Diet for 3 Months including the
Examinamtion of Neurotoxicology: Lab Project Number: 99C0331/90037:
92/11224. Unpublished study prepared by BASF Aktiengesellschaft. 589 p.
Munk, R. (1992) 1-generation Reproduction Study with Metiram Premix on
the Mallard Duck by Administration in the Diet: Lab Project Number:
72W0698/90059: 92/11151. Unpublished study prepared by BASF
Aktiengesellschaft. 214 p.
Mellert, W. (1992) Study of the Oral Toxicity of Metiram Premix 95% in the
B6C3F1 Mice—Administration in the Diet for 3 Months: Lab Project
Number: 92/11223: 35C0331/90036. Unpublished study prepared by BASF
Aktiengesellschaft. 341 p.
Novak, R. (1993) Metiram Metabolism in Plants and Animals: Comparability
to Metabolism of Other Ethylenebisdithiocarbamate Fungicides: Lab Project
Number: 93/5160. Unpublished study prepared by NPC, Inc. lip.
Dohmen, G. (1990) Effects of BAS 222 28 F on the Growth of the Green
Alga Ankistrodesmus bibraianus: Lab Project Number: P90/E008: 90/0114:
2985. Unpublished study prepared by BASF Aktiengesellschaft. 27 p.
Honey curt, R.; DeGeare, B. (1994) 1992 Mancozeb and Metiram Apple
Residue Studies: Lab Project Number: 92/203RA: ETU/92/APP: 93/310.
98 of 108
-------
BIBLIOGRAPHY
MRID
44301101
45145203
45906901
45933401
45933402
CITATION
Unpublished study prepared by Morse Lab., Inc., 1464 p.
Maisch (1997) Determination of the Acute Effect of BAS 222 28 F
(Metiram) on the Swimming Ability of the Water Flea, Daphnia magna Straus:
Final Report: Lab Project Number: 97/10538: PCP04287: 96/0599/50/1.
Unpublished study prepared by BASF Aktiengesellschaft. 27 p.
Wright, M. (2000) Aerobic Soil Metabolism of (carbon-14) Metiram in Soil:
Lab Project Number: XBL99042: RPT00597. Unpublished study prepared
by XenoBiotic Laboratories, Inc. 171 p.
Staudenmaier, H. (2002) Aerobic Metabolism of BAS 222 F (Metiram) in
Cashmere Soil: Final Report: Lab Project Number: 121479: 2002/1011913.
Unpublished study prepared by BASF Aktiengesellschaft. 61 p.
Ebert, D. (2003) Degradation of BAS 222 F (Metiram) in Water/Sediment-
Systems Under Aerobic Conditions: Final Report: Lab Project Number:
115885: 2003/1001011. Unpublished study prepared by BASF
Aktiengesellschaft. 93 p.
Junker, M. (2002) Effect of Multiple Applications of BAS 222 28 F on the
Rainbow Trout (Oncorhynchus mykiss) in a Chronic, Juvenile Growth Test:
Final Report: Lab Project Number: 140305: 2002/1005264. Unpublished
study prepared by BASF Aktiengesellschaft. 55 p. (OPPTS 850.1400}
99 of 108
-------
Appendix E
PLACEHOLDER FOR GENERIC DATA CALL-IN (DCI)
This is a placeholder for the generic data call-in, which lists confirmatory studies for the
active ingredient metiram that must be conducted as a condition ofmetiram 's continued
registration. The DCI will be issued at a future date.
100 of 108
-------
Appendix F
PLACEHOLDER FOR PRODUCT SPECIFIC DATA CALL-IN (PDCI)
This is a placeholder for the product specific generic data call-ins, which list studies
necessary for the reregistration of products containing the active ingredient metiram. The PDCI
will be issued at a future date.
101 of 108
-------
Appendix G
EPA'S BATCHING OF METIRAM PRODUCTS FOR MEETING ACUTE
TOXICITY DATA REQUIREMENTS FOR REREGISTRATION
In an effort to reduce the time, resources and number of animals needed to fulfill the acute
toxicity data requirements for reregistration of products containing METIRAM as the active ingredient,
the Agency has batched products which can be considered similar for purposes of acute toxicity.
Factors considered in the sorting process include each product's active and inert ingredients (identity,
percent composition and biological activity), type of formulation (e.g., emulsifiable concentrate, aerosol,
wettable powder, granular, etc.), and labeling (e.g., signal word, use classification, precautionary
labeling, etc.). Note that the Agency is not describing batched products as "substantially similar" since
some products within a batch may not be considered chemically similar or have identical use patterns.
Using available information, batching has been accomplished by the process described in the
preceding paragraph. Notwithstanding the batching process, the Agency reserves the right to require, at
any time, acute toxicity data for an individual product should the need arise.
Registrants of products within a batch may choose to cooperatively generate, submit or cite a
single battery of six acute lexicological studies to represent all the products within that batch. It is the
registrants' option to participate in the process with all other registrants, only some of the other
registrants, or only their own products within a batch, or to generate all the required acute lexicological
studies for each of their own products. If a registrant chooses to generate the data for a batch, he/she
must use one of the products within the batch as the test material. If a registrant chooses to rely upon
previously submitted acute toxicity data, he/she may do so provided that the data base is complete and
valid by today's standards (see acceptance criteria attached), the formulation tested is considered by
EPA to be similar for acute toxicity, and the formulation has not been significantly altered since
submission and acceptance of the acute toxicity data. Regardless of whether new data is generated or
existing data is referenced, registrants must clearly identify the test material by EPA Registration
Number. If more than one confidential statement of formula (CSF) exists for a product, the registrant
must indicate the formulation actually tested by identifying the corresponding CSF.
In deciding how to meet the product specific data requirements, registrants must follow the
directions given in the Data Call-in Notice and its attachments appended to the RED. The DCI Notice
contains two response forms which are to be completed and submitted to the Agency within 90 days of
receipt. The first form, "Data Call-In Response," asks whether the registrant will meet the data
requirements for each product. The second form, "Requirements Status and Registrant's Response,"
lists the product specific data required for each product, including the standard six acute toxicity tests.
A registrant who wishes to participate in a batch must decide whether he/she will provide the data or
depend on someone else to do so. If a registrant supplies the data to support a batch of products,
he/she must select one of the following options: Developing Data (Option 1), Submitting an Existing
Study (Option 4), Upgrading an Existing Study (Option 5) or Citing an Existing Study (Option 6). If a
102 of 108
-------
registrant depends on another's data, he/she must choose among: Cost Sharing (Option 2), Offers to
Cost Share (Option 3) or Citing an Existing Study (Option 6). If a registrant does not want to
participate in a batch, the choices are Options 1, 4, 5 or 6. However, a registrant should know that
choosing not to participate in a batch does not preclude other registrants in the batch from citing his/her
studies and offering to cost share (Option 3) those studies.
Two products were found which contain Metiram as the active ingredient. These products have been
placed a no batch group in accordance with the active and inert ingredients and type of formulation.
Batching Instructions:
No Batch: Each product in this Batch should generate their own data.
NOTE: The technical acute toxicity values included in this document are for informational purposes
only. The data supporting these values may or may not meet the current acceptance criteria.
No Batch
EPA Reg. No.
7969-105
Percent Active Ingredient
80.0
103 of 108
-------
Appendix H
LIST OF REGISTRANTS SENT DATA CALL-IN (DCI)
This is a placeholder for the list of registrants, which will be generated at a future date,
just before the DCI is mailed.
104 of 108
-------
Appendix I
LIST OF ELECTRONICALLY AVAILABLE FORMS
Pesticide Registration Forms are available (in PDF format and require the Acrobat reader) at the EPA
internet site: http ://www.epa. gov/opprdOO 1 /forms/.
Instructions
2.
3.
Print out and complete the forms. (Note: Form numbers that are bolded can be filled
out on your computer then printed.)
The completed form(s) should be submitted in hardcopy in accord with the existing
policy.
Mail the forms, along with any additional documents necessary to comply with EPA
regulations covering your request, to the address below for the Document Processing
Desk.
DO NOT fax or e-mail any form containing 'Confidential Business Information' or 'Sensitive
Information.'
If you have any problems accessing these forms, please contact Nicole Williams at (703) 308-5551 or
by e-mail at williams.nicole@epa.gov.
The following Agency Pesticide Registration Forms are currently available via the internet:
at the following locations:
8570-1
8570-4
8570-5
8570-17
8570-25
8570-27
8570-28
8570-30
8570-32
8570-34
8570-35
Application for Pesticide Registration/Amendment
Confidential Statement of Formula
Notice of Supplemental Registration of Distribution of a
Registered Pesticide Product,
Application for an Experimental Use Permit
Application for/Notification of State Registration of a
Pesticide To Meet a Special Local Need
Formulator's Exemption Statement
Certification of Compliance with Data Gap Procedures
Pesticide Registration Maintenance Fee Filing,
Certification of Attempt to Enter into an Agreement
with other Registrants for Development of Data
Certification with Respect to Citations of Data (PR
Notice 98-5)
Data Matrix (PR Notice 98-5)
ittD://www.eDa.20v/ODDrd001/forms/8570-l.Ddf
ittp://www.epa.aov/opprd001/forms/8570-4.pdf
ittD://www.eDa. gov/ODDrdOO l/forms/8570-5 .pdf
ittoV/www.eDa. aov/ODDrdOO l/forms/8570- 1 7.Ddf
ittp://www.epa. aov/opprdOO l/forms/8570-25 .pdf
ittD://www.epa.gov/opDrd001/forms/8570-27.pdf
httD://www.eDa.aov/ODDrd001/forms/8570-28.Ddf
ittD://www.eDa.gov/ODDrd001/forms/8570-30.Ddf
ittD://www.epa.gov/opprd001/forms/8570-32.pdf
ittp://www.epa.aov/opppmsdl/PR Notices7pr98-5.pdf
ittD://www.epa.gov/opppmsdl/PR Notices/Dr98-5.pdf
105 of 108
-------
8570-36
8570-37
Summary of the Physical/Chemical Properties (PR
Notice 98-1)
Self-Certification Statement for the Physical/Chemical
Properties (PRNotice98-l)
ittD://www.eDa.aov/ODDDmsdl/PR Notices/Dr98-l .Ddf
ittD://www.eDa.gov/ODDDmsdl/PR Notices/Dr98-l .pdf
Pesticide Registration Kit
Dear Registrant:
www.epa.gov/pesticides/registrationkit/
For your convenience, we have assembled an online registration kit which contains the following
pertinent forms and information needed to register a pesticide product with the U.S. Environmental
Protection Agency's Office of Pesticide Programs (OPP):
1. The Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) and the Federal Food,
Drug and Cosmetic Act (FFDCA) as Amended by the Food Quality Protection Act
(FQPA)of 1996.
2. Pesticide Registration (PR) Notices
a. 83-3 Label Improvement Program—Storage and Disposal Statements
b. 84-1 Clarification of Label Improvement Program
c. 86-5 Standard Format for Data Submitted under FIFRA
d. 87-1 Label Improvement Program for Pesticides Applied through Irrigation
Systems (Chemigation)
e. 87-6 Inert Ingredients in Pesticide Products Policy Statement
f 90-1 Inert Ingredients in Pesticide Products; Revised Policy Statement
g. 95-2 Notifications, Non-notifications, and Minor Formulation Amendments
h. 98-1 Self Certification of Product Chemistry Data with Attachments (This
document is in PDF format and requires the Acrobat reader.)
Other PR Notices can be found at http://www.epa.gov/opppmsdl/PR_Notices
3. Pesticide Product Registration Application Forms (These forms are in PDF format and will
require the Acrobat reader).
a. EPA Form No. 8570-1, Application for Pesticide Registration/Amendment
b. EPA Form No. 8570-4, Confidential Statement of Formula
c. EPA Form No. 8570-27, Formulator's Exemption Statement
d. EPA Form No. 8570-34, Certification with Respect to Citations of Data
e. EPA Form No. 8570-35, Data Matrix
4. General Pesticide Information (Some of these forms are in PDF format and will require the
Acrobat reader).
a. Registration Division Personnel Contact List
b. Biopesticides and Pollution Prevention Division (BPPD) Contacts
c. Antimicrobials Division Organizational Structure/Contact List
106 of 108
-------
d. 53 F.R. 15952, Pesticide Registration Procedures; Pesticide Data Requirements
(PDF format)
e. 40 CFR Part 156, Labeling Requirements for Pesticides and Devices (PDF
format)
f 40 CFR Part 158, Data Requirements for Registration (PDF format)
g.. 50 F.R. 48833, Disclosure of Reviews of Pesticide Data (November 27, 1985)
Before submitting your application for registration, you may wish to consult some additional sources
of information. These include:
1. The Office of Pesticide Programs' website.
2. The booklet "General Information on Applying for Registration of Pesticides in the United
States", PB92-221811, available through the National Technical Information Service
(NTIS) at the following address:
National Technical Information Service (NTIS)
5285 Port Royal Road
Springfield, VA 22161
The telephone number for NTIS is (703) 605-6000.
3. The National Pesticide Information Retrieval System (NPIRS) of Purdue University's
Center for Environmental and Regulatory Information Systems. This service does charge
a fee for subscriptions and custom searches. You can contact NPIRS by telephone at
(765) 494-6614 or through their website.
4. The National Pesticide Telecommunications Network (NPTN) can provide information on
active ingredients, uses, toxicology, and chemistry of pesticides. You can contact NPTN
by telephone at (800) 858-7378 or through their website: ace.orst.edu/info/nptn.
The Agency will return a notice of receipt of an application for registration or amended
registration, experimental use permit, or amendment to a petition if the applicant or
petitioner encloses with his submission a stamped, self-addressed postcard. The postcard
must contain the following entries to be completed by OPP:
a. Date of receipt;
b. EPA identifying number; and
c. Product Manager assignment.
Other identifying information may be included by the applicant to link the acknowledgment
of receipt to the specific application submitted. EPA will stamp the date of receipt and
provide the EPA identifying file symbol or petition number for the new submission. The
identifying number should be used whenever you contact the Agency concerning an
application for registration, experimental use permit, or tolerance petition.
107 of 108
-------
To assist us in ensuring that all data you have submitted for the chemical are properly
coded and assigned to your company, please include a list of all synonyms, common and
trade names, company experimental codes, and other names which identify the chemical
(including "blind" codes used when a sample was submitted for testing by commercial or
academic facilities). Please provide a chemical abstract system (CAS) number if one has
been assigned.
108 of 108
------- |