United States Prevention, Pesticides
Environmental Protection and Toxic Substances March 2006
Agency (7508C) EPA738-R-06-015
Interim Reregistration
Eligibility Decision for
Formetanate Hydrochloride
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Interim Reregistration Eligibility Decision (IRED) Document for
Formetanate Hydrochloride
Case Number 0091
Approved by: Date:
Debra Edwards, Ph. D.
Director
Special Review and Reregistration Division
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Table of Contents
Formetanate Hydrochloride Interim Reregistration Eligibility Decision Team i
Glossary of Terms and Abbreviations ii
Abstract iv
I. Introduction 1
II. Chemical Overview 2
A Chemical Identity 2
B Regulatory History 3
B. Use and Usage Profile 3
III. Summary of Risk Assessment 3
A. Human Health Risk Assessment 4
1. Toxicity 4
2. Dietary Exposure and Risk from Food and Drinking Water 6
4. Residential Risk 8
5. Aggregate Risk 9
6. Occupational Exposure and Risk 9
7. Human Incident Summary 12
B. Ecological Risk 12
1. Environmental Fate and Transport 12
Environmental Effects 13
2. Environmental Effect 13
a. Aquatic Organism Risk 13
b. Terrestrial Organism Risk 14
3. Ecological Incidents 15
4. Risk to Endangered Species 16
IV. Interim Risk Management, Reregistration, and Tolerance Reassessment Decision 16
A. Determination or Reregistration Eligibility 16
B. Public Comments and Responses 17
C. Regulatory Position 17
1. Food Quality Protection Act Findings 17
a. "Risk Cup" Determination 17
c. Endocrine Disrupter Effects 18
d. Cumulative Risks 18
2. Interim Tolerance Summary 18
D. Regulatory Rationale 19
1. Human Health Risk Management 19
a. Dietary Risk Mitigation (food and drinking water) 19
b. Residential Risk Mitigation 20
c. Occupational Risk Mitigation 20
2. Ecological Risk Management and Mitigation 22
3. Significance of Formetanate HC1 Use 23
4. Spray Drift 23
5. Endangered Species Considerations 23
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V. What Registrants Need to Do 24
A. Manufacturing-Use Products 25
1. Additional Generic Data Requirements 25
B. End-Use products 25
1. Additional Product-Specific Data Requirements 25
2. Labeling for End-Use Products 25
VI. Appendices 34
A. Table of Use Patterns for Formetanate Error! Bookmark not defined.
C. Technical Support Documents 39
D. Bibliography 41
E. Generic Data Call-In 49
F. Product-Specific Data Call-In 50
G. EPA's Batching of Formetanate HC1 Products for Meeting Acute Toxicity Data
Requirements for Reregistration 51
H. List of Registrants Sent Data Call-Ins 52
I. List of Available Related Documents and Electronically Available Forms 53
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Formetanate Hydrochloride Interim Reregistration Eligibility Decision Team
Biological and Economics Assessment
David Brassard
Environmental Fate and Effects Risk Assessment
Ibrahim Abdel Saheb
Richard Lee
Health Effects Risk Assessment
Danette Drew
John Doherty
Susan Stanton
Seyed Tadayon
Registration Support
Dan Kenny
Risk Management
Demson Fuller
Laura Parsons
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Glossary of Terms and Abbreviations
AGDCI
ai
aPAD
BCF
CFR
cPAD
CSF
CSFII
DCI
DEEM
DFR
DNT
EC
EDWC
EEC
EPA
EUP
FDA
FIFRA
FFDCA
FQPA
GLN
IR
LD5
'50
LOC
LOAEL
MATC
mg/kg/day
mg/L
MOE
MRID
MUP
NOAEL
OPP
Agricultural Data Call-In
Active Ingredient
Acute Population Adjusted Dose
Bioconcentration Factor
Code of Federal Regulations
Chronic Population Adjusted Dose
Confidential Statement of Formulation
USDA Continuing Surveys for Food Intake by Individuals
Data Call-In
Dietary Exposure Evaluation Model
Dislodgeable Foliar Residue
Developmental Neurotoxicity
Emulsifiable Concentrate Formulation
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
Guideline Number
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 a 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
Lowest Observed Adverse Effect Level
Maximum Acceptable Toxicant Concentration
Micrograms Per Gram
Micrograms Per Liter
Milligram Per Kilogram Per Day
Milligram Per Liter
Margin of Exposure
Master Record Identification Number. EPA's system for recording and
tracking studies submitted.
Manufacturing-Use Product
No Observed Adverse Effect Level
EPA Office of Pesticide Programs
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OPPTS
PAD
PCA
PDF
PHED
PHI
ppb
PPE
ppm
PRZM/EXAMS
Q*
RAC
RED
REI
RfD
RQ
SCI-GROW
SAP
SF
SLC
TGAI
USDA
USGS
UF
UV
WPS
EPA Office of Prevention, Pesticides, and Toxic Substances
Population Adjusted Dose
Percent Crop Area
USDA Pesticide Data Program
Pesticide Handler's Exposure Data
Pre-harvest Interval
Parts Per Billion
Personal Protective Equipment
Parts Per Million
Tier II Surface Water Computer Model
The Carcinogenic Potential of a Compound, Quantified by the EPA's
Cancer Risk Model
Raw Agriculture Commodity
Reregi strati on Eligibility Decision
Restricted Entry Interval
Reference Dose
Risk Quotient
Tier I Ground Water Computer Model
Science Advisory Panel
Safety Factor
Single Layer Clothing
Technical Grade Active Ingredient
United States Department of Agriculture
United States Geological Survey
Uncertainty Factor
Ultraviolet
Worker Protection Standard
in
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Abstract
This document presents the Environmental Protection Agency's (hereafter referred to as
EPA or the Agency) interim decision regarding the reregi strati on eligibility of the registered uses
of the insecticide formetanate hydrochloride (formetanate HC1). The Agency has conducted
human health and environmental fate and effects risk assessments for formetanate HC1. EPA has
determined that formetanate HC1 will be eligible for reregi strati on and tolerances will be
assessed provided the mitigation measures outlined in this document are adopted; and cumulative
risks of chemicals sharing a common mechanism of toxicity do not exceed EPA's level of
concern. This compound belongs to a group of pesticides called the N-methyl carbamates which
share a common mechanism of toxicity. While the Agency has not yet completed its cumulative
risk assessment for the N-methyl carbamates, cumulative risks of these chemicals will be
considered in the future. At that time, the Agency's final tolerance reassessment and
reregi strati on decisions for formetanate HC1 and the other N-methyl carbamates will be issued.
The risks from the use of formetanate HC1 alone are considered in this document and mitigation
decisions are included. The Agency may need to pursue further risk mitigation for formetanate
HC1 to address any risks identified in the cumulative assessment for the N-methyl carbamates.
Formetanate HC1 is a carbamate miticide/insecticide used on apples, pears, nectarines,
peaches, oranges, grapefruits, lemons, limes, tangelos, tangerines, and alfalfa grown for seed.
Nectarines are the crop with the highest percent crop treated with formetanate HC1. There are
no residential uses for this chemical. There are currently 10 tolerances established for
formetanate HC1.
In the human health risk assessment, acute dietary risks (from both food and drinking
water) exceed the Agency's level of concern. Chronic dietary risks resulting from food and
drinking water exposure are below the Agency's level of concern for all population subgroups.
To mitigate acute dietary risks, the registrant, Gowan Company, has agreed to delete the late
season use apples from its labels.
There are some short and intermediate term risks to workers that are of concern for use of
formetanate HC1 which can be mitigated by prohibiting aerial applications to orchards and
requiring additional protective equipment or closed cabs for handler scenarios. To address risks
of concern to reentry workers, restricted entry intervals will be revised for alfalfa and deciduous
fruits.
Although, ecological risks to terrestrial animals were identified as a result of formetanate
HC1 use, the exceedances for terrestrial animals are generally minor for this screening level
assessment and risks to aquatic animals (both freshwater and estuarine/marine environments)
were below EPA's level of concern. There are no indications of phytotoxicity from the use of
formetanate HC1 on plants; therefore, a risk assessment for plants was not conducted. The
screening level assessment results in the determination that formetanate HC1 will have no direct
acute effects on threatened and endangered freshwater fish, invertebrates, and estuarine
mollusks. Although there are some assessed ecological risks, the Agency is not proposing
additional mitigation measures to reduce ecological risks at this time.
IV
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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 data submitted to EPA.
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 a 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 amended FIFRA and the Federal Food Drug and Cosmetic Act (FFDCA) to
require EPA to review all tolerances for pesticides in food in effect on August 2, 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 among infants and children, and the cumulative effects of pesticides that have a
common mechanism of toxicity. When the Agency determines that aggregate and cumulative
risks are not of concern and concludes that there is a reasonable certainty of no harm from
aggregate and cumulative exposures, the tolerances are considered reassessed. EPA decided
that, for those chemicals that have tolerances and are undergoing reregistration, tolerance
reassessment would 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. Formetanate HC1 is a member of the N-methyl carbamate class of pesticides. The N-
methyl carbamates, as a group, have been determined to share a common mechanism of toxicity.
The preliminary cumulative risk assessment for the N-methyl Carbamate Cumulative
Assessment Group, which includes formetanate HC1, has been released (July 2005). The FIFRA
Science Advisory Panel reviewed the preliminary cumulative risk assessment in August 2005.
The revised cumulative risk assessment is currently being developed and will be released during
2006. At that time, the Agency's final tolerance reassessment reregistration decisions for
formetanate HC1 and the other N-methyl carbamates will be issued. The Agency may need to
pursue further risk mitigation for formetanate HC1 to address any risks identified in the
cumulative assessment for the N-methyl carbamates.
This document presents EPA's revised human health and environmental fate and effects
risk assessments, its progress toward tolerance reassessment, and the interim reregistration
eligibility decision for formetanate HC1. The document consists of six sections. Section I
contains the regulatory framework for reregi strati on/tolerance reassessment. Section II provides
a description of the chemical identity and a profile of the use and usage of the chemical. Section
III provides a summary of the revised human health and ecological risk assessments based on
data, public comments, and other information received in response to the preliminary risk
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assessments. Section IV presents the Agency's interim risk management, reregi strati on
eligibility, and tolerance reassessment decisions and rationale. Section V summarizes any data
necessary to confirm the reregi strati on eligibility decision as well as label changes necessary to
implement the risk mitigation measures outlined in Section IV. Section VI provides information
on how to access related documents. Finally, the Appendices list related information and
supporting documents. The preliminary and revised risk assessments for formetanate HC1 are
available in the Public Docket and on the internet under docket number EPA-HQ-OPP-2004-
0032.
II. Chemical Overview
A Chemical Identity
Chemical Structure:
V
CR
HC1
Empirical Formula:
Common Name:
CAS Name:
CAS Registry Number:
OPP Chemical Code:
Case Number:
Technical or
Manufacturing-Use
Registrants:
o
CnH16CIN302
Formetanate Hydrochloride
{m-[[dimethyllamino) methylene]amino]phenyl methylcarbamate
hydrochloride}
23422-53-9
097301
0091
Gowan Company
Formetanate HC1 is a white crystalline solid with melting point of 191 - 202°C and a low
vapor pressure. Formetanate HC1 is highly soluble in water and only slightly soluble in organic
solvents (dichloromethane, acetone, toluene, ethyl acetate, and n-hexane). For a complete
review of the product chemistry for formetanate HC1, please see "Formetanate Hydrochloride,
HED Product Chemistry Chapter of the RED" (D. Drew, 3/27/03)
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B Regulatory History
Formetanate HC1 was first registered in 1969. A Registration Standard was completed in
1983. An assessment was completed in 1999 for the formetanate HC1 Interim Reregi strati on
Eligibility Decision (IRED) which showed dietary risks of concern. Based on this dietary
analysis, a Memorandum of Agreement (MOA) between the registrant and EPA was signed in
October 1999. The MOA stipulated labeling amendments aimed at lowering application rates,
increasing pre-harvest intervals and limiting uses to certain crops in an effort to reduce residues
associated with formetanate HC1 uses. As a result, uses on plums and prunes were cancelled,
formetanate HC1 use was prohibited in Florida, application timing was restricted to early season
for most uses and the maximum application rate was lowered. Revised labels were approved in
January and May 2000.
C Use and Usage Profile
The following is information on the currently registered uses of formetanate HC1:
Type of Pesticide: Miticide/Insecticide
Formulations: Formetanate HC1 is formulated as a wettable powder in water soluble
packaging (92 percent active ingredient).
Methods of Application: Formetanate HC1 can be applied with aerial or ground equipment such
as groundboom sprayers and airblast sprayers.
Target Organisms: Rust mite, Thrips, European Red Mite, Two-Spotted Spider Mite,
McDaniel Mite, Lygus Bug, Tentiform Leafminer, White Apple
Leafhopper, and Stink Bugs
Use Sites: Alfalfa grown for seed, Apples, Pears, Nectarines, Peaches,
Grapefruit, Lemon, Lime, Orange, Tangelo, and Tangerine
Application Rates: Formetanate HC1 is labeled for use on tree fruits at 1.15 Ib ai/A and on
alfalfa at 0.92 Ib ai/A.
III. Summary of Risk Assessments
The purpose of this summary is to assist the reader by identifying the key features and
findings of these risk assessments, and to help the reader better understand the conclusions
reached in the assessments. The human health and ecological risk assessments form the basis of
interim regulatory decisions for formetanate HC1. While the risk assessments and related
addenda are not included in this document, they are available from the OPP Public Docket EPA-
HQ-OPP-2004-0032 and may be accessed on the internet at http://www.regulations.gov.
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A. Human Health Risk Assessment
The Agency prepared a revised human health risk assessment, "HED Revised Risk
Assessment for Forme tanate Hydrochloride," (D. Drew, 12/23/05) which addresses toxicology
data and comments submitted during or after Phase 3 of the Public Participation Process for
formetanate HC1. Specifically addressed is the July 2005 submission of a comparative
cholinesterase assay study in pups and adult rats which resulted in the selection of a benchmark
dose for use in this assessment. Also, an updated worker risk assessment was performed which
considers a lower number of estimated acres treated per day for aerial applications to alfalfa
grown for seed. A subsequent dietary analysis was conducted in January 2006 to include United
States Department of Agriculture's (USDA) Pesticide Data Program (PDF) monitoring data.
Data tables from this analysis are also posted in the docket.
1. Toxicity
(For a complete discussion, see sections 3.0 of the human health risk assessment.)
Formetanate HC1 has high acute toxicity via the oral route, moderate acute toxicity via
the inhalation route and has low acute toxicity via the dermal route. It is not an eye or skin
irritant but is a dermal sensitizer.
Formetanate HC1 is a carbamate pesticide, and its primary mode of toxic action is
through cholinesterase inhibition (ChEI) after single or multiple exposures. In laboratory studies
conducted on animals, exposure to formetanate HC1 resulted in decreased plasma, whole blood
and/or brain cholinesterase (ChE). In most of the toxicity studies in which ChEI was measured,
it was the endpoint used to set the Lowest Observed Adverse Effect Level (LOAEL) and the No
Observed Adverse Effect Level (NOAEL).
A comparative cholinesterase assay (CCA) study in neonates and adult rats was
submitted in lieu of a developmental neurotoxicity study (DNT). The CCA study is appropriate
because the behavioral effects in adult animals were seen at a dose 10-fold higher than the dose
at which ChEI occurred. Importantly, this indicates that behavioral effects in pups measured in
the DNT are likely to occur at higher doses than ChEI. Therefore, EPA determined that
regulating on the ChEI endpoint would protect against potential neurotoxic effects. In order to
evaluate the appropriate point of departure (PoD) for ChEI, EPA performed a benchmark dose
(BMD) analysis which indicated that: (1) brain ChEI is a more sensitive endpoint then red blood
cell (RBC) ChEI, (2) female pups are more sensitive than male pups, and (3) 10% ChE is the
appropriate benchmark response to consider. Based on the CCA study, there was inhibition of
brain ChE at all doses and the female pup brain ChEI data resulted in the lowest BMDLio
(benchmark dose lower limit) of 0.065 mg/kg/day which was selected for the acute and chronic
dietary assessments.
For the dietary assessment, EPA uses the same endpoint for all oral exposures when the
acute BMDLio is lower than the subchronic or chronic value from longer term studies. In the
case of formetanate HC1, the quick acting and reversible nature of carbamate ChE inhibition is
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considered by EPA as justification for using data from the ChEI study following a single acute
dose for the chronic RfD.
For the occupational risk assessment, a dermal toxicity study in rats was used to estimate
occupational risks from dermal exposures. A NOAEL of 10 mg/kg/day was selected with a
LOAEL of 20 mg/kg/day for ChEI in whole blood and plasma. A dermal absorption factor is
not necessary for the risk assessment because a route-specific dermal toxicity study was used for
formetanateHCl.
In considering the dermal endpoints, it should be noted that carbamates are relatively
quick acting reversible inhibitors of cholinesterase and the subchronic and chronic studies do not
usually demonstrate cumulative effects of cholinesterase inhibition. In particular, following a
single dose of formetanate HC1, there is inhibition of cholinesterase that reverses shortly (in the
same day) after exposure, and the consequences of inhibition (unless at extremely high doses)
reverse also. Short-term exposure (up to 30 days) to formetanate HC1 is regarded as multiple
single-dose exposures without a cumulative effect. Thus, the NOAEL and LOAEL from the
single dose study is an appropriate endpoint for the 30-day exposure scenario.
For the inhalation exposure assessment estimating occupational risks, a NOAEL of 0.1
mg/kg/day was selected from an acute neurotoxicity study with a LOAEL of 1 mg/kg/day based
on plasma, whole blood and brain cholinesterase inhibition. This study was used in a previous
assessment ("//ED Revised Risk Assessment for Formetanate Hydrochloride," June 4, 2003) and
EPA determined that the occupational inhalation risk endpoint should be retained since the
NOAEL of 0.1 mg/kg/day is not significantly different from BMDL of 0.065 mg/kg/day.
Therefore, EPA is confident that it is not underestimating toxicity via the inhalation route. An
absorption factor of 100% is assumed for exposure via the inhalation route.
There were no concerns for mutagenicity. There was no indication of a carcinogenic
effect in rats or mice. Formetanate HC1 is classified as a group "E" carcinogen (no evidence of
carcinogenicity). There was no evidence of effects to the immune or endocrine systems.
FQPA Special Safety Factor
The FQPA safety factor is intended to provide an additional safety factor (10X) to
safeguard against potential special sensitivity in infants and children to specific pesticide
residues in food. Exposure to formetanate HC1 did not result in developmental toxicity in either
rats or rabbits or in reproductive effects in the multi-generation reproduction study. There was
no indication of increased offspring susceptibility in these studies. The CCA study demonstrated
that pups were more sensitive than adults to the ChEI effects of formetanate HC1. Because the
endpoint is based on pup sensitivity and the formetanate HC1 dietary and drinking water
assessments are not expected to underestimate exposure, the special FQPA safety factor can be
removed for the formetanate HC1 risk assessment.
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Database Uncertainty Factor
The Agency previously determined that a database uncertainty factor of 10X should be
retained because a study was needed that compares the potential for formetanate HC1 to inhibit
cholinesterase in adult rats with neonatal rats. ^Formetanate Hydrochloride - 4th Report of the
Hazard Identification Assessment Review Committee'" May 21, 2003). The CCA study that was
submitted provided the necessary data which were included in the risk assessment. Therefore,
the 10X uncertainty factor was removed.
Table 1: Formetanate HC1: Summary of lexicological Endpoints
Exposure Scenario
Dose
Endpoint for Risk Assessment
Dietary Risk Assessments
Dietary (Acute and Chronic)
General Population
BMDL10 = 0.065 mg/kg/day
UF = 100
aRfD = 0.00065 mg/kg/day
cRID = 0.00065 mg/kg/day
PAD = 0.00065 mg/kg/day
BMDL10 for female pup brain ChEI
in the Comparative ChE study. The
FQPA SF is removed because an
endpoint based on the most sensitive
effect in the most sensitive
population was used. (MRID #
46618902)
(Occupational) Non-Dietary Risk Assessment
Dermal - Occupational
Short & Intermediate Term
(1 - 30 days)
Inhalation Occupational
Short & Intermediate Term
(1 - 30 days)
Cancer
Dermal NOAEL=
10 mg/kg/day
MOE = 100
Oral NOAEL =
0.1 mg/kg/day
MOE = 100
Special single dose time to peak
effect dermal application study
(2000, MRID #453 11901).
LOAEL = 20 mg/kg/day based on
whole blood and plasma
cholinesterase inhibition.
Acute Neurotoxicity Screen (2000,
MRID #453 14201)
LOAEL = 1 mg/kg/day based on
plasma, whole blood and brain
cholinesterase inhibition.
100% absorption assumed
Classification E: Not Likely
2. Dietary Exposure and Risk from Food and Drinking Water
Acute probabilistic and chronic dietary risk assessments were conducted using the
Dietary Exposure Evaluation Model (DEEM-FCID, Version 2.03) which uses food consumption
data from the United States Department of Agriculture's (USDA's) Continuing Surveys of Food
Intakes by Individuals (CFII) from 1994-1996 and 1998.
Acute Dietary Risk Assessment for Food + Water
A partially refined, Tier 3, acute probabilistic dietary exposure assessment was conducted
for all supported formetanate HC1 food uses and for drinking water. Acute anticipated residues
for all foods were derived using either field trial data reflecting current maximum label rates and
minimum Pre-Harvest Intervals (PHI) or PDF monitoring data. Although the field trial data are
limited in terms of the number of trials and residue samples, it is likely that these data result in
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overestimates of dietary exposure to formetanate HC1 since they reflect current maximum label
rates rather than typical usage. Likewise, PDF data reflect the sampling year of 2001 when the
higher pre-MOA label rates may have been used. Field trial data were used to analyze stone
fruits, lemons, limes, tangelos and juice (orange and grapefruit). PDF data were used to analyze
apples, pears, oranges and grapefruit. Field trial data were used for orange and grapefruit juice
since PDF data reflect residues on peeled fruit and juice is extracted from whole (unpeeled) fruit.
Anticipated residues were further refined using percent crop treated (%CT) data where
appropriate, and, where available, processing factors.
Estimated residues in drinking water were incorporated directly into the acute
assessment. The assessment was conducted using the full distribution of estimated residues in
surface water generated by the PRZM-EXAMS model for the North Carolina apple crop
scenario, the crop scenario resulting in the highest estimated peak surface water concentration
(7.68 ppb).
The resulting acute dietary exposure and risk estimates for food and water exceed EPA's
level of concern for the population subgroups, Infants and Children 1-2 years old. Acute dietary
(food + water) exposure at the 99.9th percentile was estimated at 162% of the Acute Population
Adjusted Dose (aPAD) for the most highly exposed population subgroup (infants). Most of the
estimated acute exposure from food was determined to result from the late season uses of
formetanate HC1 on apples. (See Table 2).
Table 2: Results of Acute Dietary Risk Analysis1
Population Subgroup
General US Population
All Infants (< 1 year old)
Children 1-2 years old
Children 3-5 years old
Children 6-12 years old
Youth 13-19 years old
Adults 20-49 years old
Females 13-49 years old
Adults 50+ years old
Risks Including Late Season Applications
(Food -i- Water)
on Apples
47
162
119
93
51
28
33
33
33
Risks are expressed as a percent of the aPAD. Risks > 100% of the aPAD exceed EPA's Level of Concern.
Deletion of the late season apple applications results in an acute dietary (food + water)
risk of 117% of the aPAD for the most highly exposed population subgroup (infants). Analysis
shows that residues from food only (excluding the late season apple residues) result in an acute
dietary risk of 56% of the aPAD for infants (see Table 3). Therefore, drinking water is a large
contributor to acute dietary exposure when late season uses are excluded.
Drinking water residue estimates are considered to be conservative and unrefined since
residues are estimated from modeling because no water monitoring data were available to refine
the assessment. Modeling estimates are based on conservative assumptions including: (1) that
applications will be made at maximum application rates every year for 30 years and (2) a highly
vulnerable configuration of a reservoir/watershed system is used as the application site.
Additionally, for formetanate HC1, applications were modeled in an apple orchard in North
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Carolina where rainfall is higher than in the west where most formetanate HC1 is used.
Considering that food alone is below the Agency's level of concern for all populations,
an acute dietary risk estimate of 117% of the aPAD including conservative water estimates for
the exposed population of infants is also considered to be below EPA's level of concern.
Table 3: Results of Dietary Risk Analysis1
Population Subgroup
General US Population
All Infants (< 1 year old)
Children 1-2 years old
Children 3-5 years old
Children 6-12 years old
Youth 13-19 years old
Adults 20-49 years old
Females 13-49 years old
Adults 50+ years old
Risks Without Late Season
Applications on Apples
(Food Only)
25
56
56
51
34
19
16
17
17
Risks Without Late Season
Applications on Apples
(Food + Water)
37
117
69
64
41
25
29
31
29
Risks are expressed as a percent of the aPAD
Chronic Dietary Risk Assessment for Food + Water
A partially refined, Tier 3 chronic dietary exposure assessment was also conducted for
the supported food uses of formetanate HC1 and for drinking water. Anticipated residues were
derived using field trial data, %CT data, and, where available, processing factors.
For the chronic assessment, a single point estimate (0.08 ppb) of formetanate HC1
residues in surface water was used to assess exposure from drinking water. The estimated
surface water concentration represents the 90th percentile annual mean concentration generated
by the PRZM-EXAMS model for the Pennsylvania apple crop scenario, the crop scenario
resulting in the highest estimated annual mean concentration.
Chronic dietary risk estimates based on this analysis are below EPA's level of concern
for the U.S. population and all population subgroups. Formetanate HC1 mean dietary (food +
water) exposure is estimated at 4.9% of the Chronic Population Adjusted Dose (cPAD) for the
U.S. population and 28% of the cPAD for the most highly exposed population subgroup (infants,
<1 yr. old).
3. Residential Exposure and Risk
Only agricultural uses are registered for formetanate HC1. There are no uses that would
result in residential or recreational exposures. Assessments addressing residential and
recreational risks are not warranted at this time.
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4. Aggregate Exposure and Risk
(For a complete discussion, see Section 7 of the human health risk assessment.)
The Food Quality Protection Act (FQPA) amendments to the Federal Food, Drug and
Cosmetic Act (FFDCA, Section 408(b)(2)(A) (iii)), require "that there is a reasonable certainty
that no harm will result from aggregate exposure to pesticide chemical residue, including all
anticipated dietary exposures for which there is reliable information." Aggregate exposure will
typically include dietary exposures (food plus drinking water), exposures from residential uses of
a pesticide, and other non-occupational sources of exposure.
There are no residential uses for formetanate HC1. Therefore, when addressing aggregate
exposures, only the dietary pathways of food and drinking water were considered. Since
drinking water was incorporated directly into the acute and chronic dietary assessments, the
dietary risk estimates discussed above reflect total estimated acute and chronic aggregate risks
from formetanate HC1.
Acute aggregate exposure estimates for food and water exceed EPA's level of concern
with the inclusion of late season applications to apples, but are below the level of concern
without this use. Analysis for food only was 56% of the aPAD and food plus conservative water
values resulted in 117% of the Population Adjusted Dose (PAD). Chronic aggregate exposure
estimates for food and water are below the Agency's level of concern.
5. Occupational Exposure and Risk
(For a complete discussion, see section 7.0 of the human health risk assessment.)
People can be exposed to a pesticide while working through mixing, loading, or applying
a pesticide, and reentering a treated site. Handler and worker non-cancer risks are measured by a
Margin of Exposure (MOE) which determines how close the occupational exposure comes to a
NOAEL taken from animal studies. Generally, MOEs greater than 100 do not exceed the
Agency's level of concern.
For formetanate HC1, only short and intermediate-term occupational exposures are
expected based on label-specified use patterns. For the occupational assessment, the dermal
endpoint was selected from a dermal toxicity study in rats. The NOAEL is 10 mg/kg/day and the
LOAEL is 20 mg/kg/day based on whole blood and plasma cholinesterase inhibition. The short-
and intermediate-term endpoints for inhalation exposure are a NOAEL of 0.1 mg/kg/day and a
LOAEL of 1 mg/kg/day based on plasma, whole blood and brain cholinesterase inhibition from
an acute oral neurotoxicity study. Since an oral study was used, an inhalation absorption factor
of 100% is assumed.
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Occupational Handler Summary
Based on the registered use patterns, EPA has identified 7 major exposure scenarios for
which there is potential occupational handler exposure during mixing, loading, and applying
products containing formetanate HC1 to agricultural crops. These scenarios are as follows:
(1) mixing/loading wettable powders for aerial application;
(2) mixing/loading wettable powders for airblast application;
(3) mixing/loading wettable powders for groundboom application;
(4) applying sprays with a fixed wing aircraft;
(5) applying sprays with airblast equipment;
(6) applying sprays with a groundboom sprayer; and
(7) flagging for aerial spray applications.
No chemical-specific handler exposure data were submitted, so short-term and
intermediate-term dermal and inhalation exposures for handlers were developed using the
Pesticide Handler Exposure Database (PHED) Version 1.1.
For occupationally exposed workers, combined MOEs (both dermal and inhalation) >100
do not exceed EPA's level of concern. No scenarios resulted in MOEs above 100 for single
layer personal protective equipment (PPE); however, after a respirator was added for applicators
using groundboom equipment in alfalfa for seed production, the risk was below EPA's level of
concern (MOE=130). Most scenarios for applicators had MOEs above 100 at maximum PPE
except for airblast applications to orchards (MOE=73) and aerial applications to alfalfa which are
discussed below. Scenarios for mixing and loading for aerial applications for both orchard crops
(MOE = 51) and for alfalfa grown for seed (MOE = 69) had risks above the Agency's level of
concern even with engineering controls of water soluble bags.
Aerial applications to alfalfa also resulted in risk above the Agency's level of concern for
applicators even when engineering controls (closed cockpits) were considered.
(MOE =54). The mixing/loading and applicator scenarios for aerial application to alfalfa
assumed the default acreage of 1200 acres treated per day. California pesticide application data
for formetanate HC1 applications to alfalfa grown for seed in 2003 showed a maximum acreage
of 328 acres treated in a single day. This daily maximum was split into five separate
applications. Therefore, an additional assessment was performed using a maximum estimate of
328 acres treated per day based on these data submitted by the University of California, Davis
(UC Davis), Western Integrated Pest Management Center.
The following tables summarize the risks to handlers by crop type:
Table 4: Formetanate HC1: Applicator (Spray Application) Short-and Intermediate Term Exposure and Risk Estimates: Single Layer
Protection + Respirator'
Exposure Scenarios
(Scenario #)
Sprays for Groundboom
Application
Crop
Alfalfa for Seed
Application
Rate
(Ib ai/A)
0.92
Daily Area
Treated
200
MOE
130
'A subsequent worker assessment was conducted in January 2006 for this single scenario and has been posted in the docket.
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Table 5: Formetanate HC1: Applicator, Risk Estimates using Double Layer Protection, Gloves, Respirator (and Hood for Airblast
Applicators Only)
Exposure Scenarios
(Scenario #)
Crop
Application
Rate
(Ib ai/A)
Daily Area
Treated
MOE
Applicator
Sprays for Airblast Application
Sprays for Groundboom
Application
Pome, Stone, and Citrus Fruit
Alfalfa for Seed
1.15
0.92
40
200
73
150
Table 6: Formetanate HC1: Mixer-Loader, Applicator, Flagger Risk Estimates using Engineering Controls:
Water Soluble Bags, Closed Cockpit Airplane, Closed Cab Tractors
Exposure Scenarios
(Scenario #)
Crop
Application
Rate
(Ib ai/A)
Daily Area
Treated
MOE
Mixer/Loader
Aerial Application
Aerial Application
Aerial Application
Airblast Application
Groundboom Application
Alfalfa grown for seed
Alfalfa grown for seed
Pome, Stone, and Citrus Fruit
Pome, Stone, and Citrus Fruit
Alfalfa grown for Seed
0.92
0.92
1.15
1.15
0.92
1200*
328
350
40
200
19
69
51
450
110
Applicator
Sprays for Aerial Application
Sprays for Aerial Application
Sprays for Aerial Application
Sprays for Airblast Application
Sprays for Groundboom
Application
Alfalfa grown for seed
Alfalfa grown for seed
Pome, Stone, and Citrus Fruit
Pome, Stone, and Citrus Fruit
Alfalfa grown for seed
0.92
0.92
1.15
1.15
0.92
1200*
328
350
40
200
54
200
150
240
410
Post-Application Occupational Risk
For workers entering a treated site, restricted entry intervals (REIs) are calculated to
determine the minimum length of time required before workers can safely reenter. The
postapplication occupational risk assessment considered exposure to formetanate HC1 from
entering treated fields and orchards. Given the nature of activities in these locations, and that
formetanate HC1 is applied at various times during plant growth, contact with treated surfaces is
likely. Some potential exposure scenarios include scouting, irrigation, harvesting, pruning, and
thinning.
Formetanate HC1 use patterns show that both short-term (1-30 days) and intermediate-
term (1 month to 6 months) exposure is possible for post-application exposures, but because the
endpoint and dose are the same for both exposure durations, so are the results.
No exposure data were submitted for alfalfa. Therefore, data from a citrus study was
translated for alfalfa. The proposed single application rate for alfalfa is 0.92 ai/A. EPA
estimated an alfalfa REI based on the formetanate HC1 citrus data which considers the labeled
rate of 1.15 Ibs ai/A and an estimated transfer coefficient of 2,500 cm2/hr for scouting activities.
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The Agency acknowledges that the citrus residue data are not readily comparable to alfalfa
residues. However, the calculated exposure using the surrogate data is being used as a screening
level assessment and is considered to be a conservative estimate due to the higher rate and leaf
surface area of citrus relative to alfalfa.
For worker reentry risk, the calculated REI represents the day following application on
which the MOE is greater than or equal to 100. For high-end activities, MOEs were acceptable
by day 10 for evergreen fruit trees (citrus), day 8 for deciduous fruit trees (pome and stone
fruits), and day 9 for alfalfa.
Table 7: Formetanate HC1: Occupational Postapplication Risk Estimates
Crops
Alfalfa
Fruit Trees: Deciduous (Pome and Stone Fruits)
Fruit Trees: Evergreen (Citrus)
Re-entry Day with Acceptable MOEs > 100
High exposure activities
9
8
10
Medium exposure activities
6
N/A
7
6. Human Incident Summary
A review of available incident reports on formetanate HC1 was completed in 1997.
Systemic poisoning has been reported in applicators that were not properly protected and skin
rashes were reported in field workers exposed to residues. Incident data supported the need for
additional personal protective equipment for those that handle formetanate HC1 and reentry
intervals for workers returning to orchards or fields where this active ingredient has been
applied. A 2003 review of the EPA incident Data System showed no additional incident reports
since 1996.
B. Ecological Risk Assessment
A summary of the Agency's environmental risk assessment for formetanate HC1 is
presented below. More detailed information associated with environmental risks from the use of
formetanate HC1 can be found in "EFED Science Chapter for the Formetanate Hydrochloride
Reregistration Eligibility Document, " (I. Abdel-Saheb & R. Lee, October 22, 2003). The
complete environmental risk assessment may be accessed in the OPP Public Docket, OPP-2004-
0032.
1. Environmental Fate and Transport
(For a complete discussion, see ecological risk assessment)
Formetanate HC1 is not a persistent pesticide under most normal use conditions. The
primary routes of dissipation appear to be hydrolysis under neutral and alkaline conditions as
well as microbial degradation. Formetanate HC1 hydrolyzes with a half-life of <1 day. The soil
photolysis half-life was <3 days. Metabolism data suggest that formetanate HC1 is also readily
biodegradable, with a half-life of <1 week.
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Formetanate HC1 and degradates were shown to be mobile in the laboratory. Field
studies indicate that formetanate HC1 degrades rapidly and generally remains within the top 6
inches of soil.
Based on the submitted volatility data (vapor pressure = 1.6 X 10"6 torr @ 25 C),
volatilization from soils is not expected to be an important dissipation mechanism. The
relatively high water solubility and low bioconcentration factors in bluegill sunfish suggest that
formetanate HC1 will have a low tendency to bioaccumulate in fish and other exposed organisms.
2. Environmental Effects
(For a complete discussion, see the ecological risk assessment)
To estimate potential ecological risks, EPA integrates the results of exposure and
ecotoxicity information using the quotient method. Risk quotients (RQs) are calculated by
dividing exposure estimates by ecotoxicity values, both acute and chronic, for various wildlife
species. RQs are then compared to levels of concern (LOCs). Generally, the higher the RQ, the
greater the potential risk. Risk characterization provides further information on the likelihood of
adverse effects occurring by considering the fate of the chemical in the environment,
communities and species potentially at risk, their spatial and temporal distributions, and the
nature of the effects observed in studies. The Agency assessed non-target ecological risks at the
maximum labeled single broadcast rates of 1.15 Ibs ai/A for orchard crops and 0.92 Ibs ai/A for
alfalfa.
a. Aquatic Organism Risk
The Agency used modeling to derive estimated environmental concentrations (EECs) for
formetanate HC1 in surface water. 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 PC A factor represent a drinking water 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.
Available acute toxicity data indicate that formetanate HC1 is moderately to slightly toxic
to freshwater fish and highly toxic to freshwater invertebrates on an acute basis. Chronic data
for freshwater fish show that growth/development was the most sensitive endpoint. For
estuarine/marine invertebrates, available acute toxicity data indicate that formetanate HC1 is
moderately toxic. No acute data for estuarine/marine fish or chronic data for invertebrates were
available.
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Aquatic Acute and Chronic Risks
Acute and chronic risks for freshwater fish and freshwater invertebrates are below the
Agency's level of concern for all uses. Acute risks for estuarine/marine invertebrates were also
below EPA's level of concern. Although the Agency has no toxicity data to assess risks to
estuarine fish or chronic risks to estuarine invertebrates, EPA presumes that based on assessed
risks to freshwater fish and invertebrates, estuarine animals are not expected to be at risk from
formetanate HC1 use.
b. Terrestrial Organism Risk
The Agency assessed exposure to terrestrial organisms by first predicting the amount of
formetanate HC1 residues found on animal food items and then by determining the amount of
pesticide consumed by using information on typical food consumption by various weight classes
of birds and mammals. The amounts of residues on animal feed items are based on the Fletcher
nomogram (a model developed by Fletcher, Hoerger, Kenaga, et al.) and the current maximum
application rate for formetanate HC1 which is 1.15 Ibs ai/A.
Formetanate HC1 is classified as highly toxic to birds on an acute basis with an LD50
value of 11.5 mg/kg and slightly toxic with an LC50 of 1413 ppm on a subacute basis. Avian
reproduction data indicate that use of formetanate HC1 has the potential to be of concern for
chronic risks to birds. Chronic toxicity from both bobwhite quail and mallard duck studies
indicate reduced eggs hatched and offspring survival at the 160 ppm treatment level.
Toxicity data for mammals indicate that formetanate HC1 is highly toxic to small
mammals on an acute oral basis. The chronic toxicity endpoint is based on a 52-week dog study
which showed a NOAEC of 10 ppm. Clinical signs associated with this study were salivation,
wheezing, heavy breathing, trembling, vomiting, coughing, and abnormal quietness.
There are no indications that formetanate HC1 is phytotoxic; therefore, plant toxicity
testing is considered unnecessary and a plant risk assessment has not been conducted.
The Agency generally does not conduct non-target insect risk assessments. Data indicate
that formetanate HC1 is practically nontoxic to bees on an acute contact basis. The acute LDso of
formetanate HC1 is greater than 11 jig/bee. However, in the field, formetanate HC1 is known to
be toxic to foraging bees and, therefore, the current bee labeling statements are appropriate.
Terrestrial Acute and Chronic Risks
Birds
Acute risks to birds do not exceed the Agency's LOCs for the screening level assessment
for formetanate HC1. RQs for consumption of short grass were calculated to be 0.2 for the
maximum application rate to orchard fruits. All other acute RQs for birds were < 0.2 and are not
of concern for nonlisted avian species. Chronic avian RQs ranged from 2 to 5 (LOG = 1) for
several foodstuffs when maximum residue values were considered. For further details regarding
assumptions and EECs, please see the EFED risk assessment.
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Table 8: Formetanate HC1: Acute and Chronic Avian Risk Quotients
Site
Citrus, Stone Fruit
Alfalfa grown for
seed
App. Rate
(Ibs ai/A
1.15
0.92
Food Items
Short Grass
Tall Grass
Broadleaf Plant/Small Insects
Fruits/Pods/Large Insects
Short Grass
Tall Grass
Broadleaf Plant/Small Insects
Seeds
Acute RQ
(EEC/LC50) 1
0.20
0.09
0.11
0.01
0.16
0.07
0.09
0.01
Chronic
(EEC/LC50)2
5.21
2.39
2.93
0.33
4.17
1.91
2.34
0.26
'Based on a subacute study where the LC50 is 1413 ppm
2Based on a chronic study where the NOAEC is 53 ppm
Mammals
The LOG for acute risks is triggered by an RQ > 0.5. The acute RQs for orchard and
alfalfa uses are above the Agency's level of concern for all weight classes (15g, 35g, and lOOOg)
foraging on most food categories (grass, forage, and insects) for herbivores/insectivores. Risk
quotients ranged from <1 to 18. For chronic RQs, the mammalian chronic level of concern of
1.0 is exceeded for all foodstuffs at maximum application rates. Risk quotients ranged from 2 to
28. For further details regarding assumptions and EECs, please see the EFED risk assessment.
Table 9: Formetanate HC1: Mammalian Acute Risk Quotients1
Site and Rate in Ibs ai/A
Citrus, Stone, Pome Fruit
1.151bai/A
Alfalfa
0.92 Ib ai/A
Body Weight (g)
15
35
1000
15
35
1000
Acute RQ
Short Grass
17.72
12.31
2.80
14.17
9.85
2.24
Forage & Small
Insects
9.97
6.92
1.57
7.97
5.54
1.26
Large Insect
1.11
0.77
0.17
0.89
0.62
0.14
'Based on a rat LD50 of 14.8 mg/kg
Table 10: Formetanate HC1: Mammalian Chronic Risk Quotients1
Site and Rate in Ibs ai/A
Citrus, Stone, Pome Fruit
1.151bai/A
Alfalfa
0.92 Ib ai/A
Chronic RQ
Short Grass
27.60
22.08
Tall Grass
12.65
10.12
Broadleaf
Plants/insects
15.53
12.42
seeds
1.73
1.38
1 Based on the NOAEC of 10 ppm from a chronic dog study.
4. Ecological Incidents
The Agency has received no reports of formetanate HC1 ecological incidents.
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5. Risk to Endangered Species
The Agency's screening level assessment results in the determination that formetanate
HC1 will have no direct acute effects on threatened and endangered freshwater fish,
invertebrates, and estuarine mollusks. The preliminary risk assessment for endangered species
indicates that RQs exceed endangered species LOCs for birds and mammals with acute RQs
ranging up to 0.2 for birds and up to 18 for mammals. Chronic RQs ranged up to 5 for birds and
28 for mammals. Further, potential indirect effects to any species dependent upon a species that
experiences effects from use of formetanate HC1 can not be precluded based on the screening
level ecological risk assessment. These findings are based solely on EPA's screening level
assessment and do not constitute "may affect" findings under the Endangered Species Act.
IV. Interim Risk Management, Reregistration, and Tolerance Reassessment Decision
A. Determination of Reregistration Eligibility
Section 4(g)(2)(A) of FIFRA calls for the Agency to determine, after submission of
relevant data concerning an active ingredient, whether or not products containing the active
ingredient are eligible for reregi strati on. The Agency has previously identified and required the
submission of the generic (technical or manufacturing-use grade) data required to support
reregi strati on of products containing formetanate HC1 as an active ingredient.
The Agency has completed its review of submitted data and its assessment of the dietary,
occupational, and ecological risks associated with the use of pesticide products containing the
active ingredient formetanate HC1. Based on these data, the Agency has sufficient information
on the human health and ecological effects of formetanate HC1 to make its interim decisions as
part of the tolerance reassessment process under FFDCA and the reregi strati on process under
FIFRA, as amended by FQPA, pending completion of the cumulative assessment of the N-
methyl carbamates class of pesticides, of which formetanate HC1 is a member. Additional
mitigation may be necessary after this cumulative assessment is completed. The Agency has
determined that products containing formetanate HC1 will be eligible for reregi strati on provided
that (i) the risk mitigation measures outlined in this document are adopted; and (ii) label
amendments are made to reflect these measures and (iii) any additional measures needed to
reduce cumulative risks are adopted. Needed label changes and language are listed in Section V.
Appendix A is a detailed table listing all uses that are eligible for formetanate HC1, or uses which
require tolerances or tolerance consideration, that were considered for reregi strati on. Appendix
B identifies generic data requirements that the Agency reviewed as part of its determination of
the interim reregi strati on eligibility of formetanate HC1, and lists the submitted studies the
Agency found acceptable. Data gaps are identified as either outstanding generic data
requirements that have not been satisfied with acceptable data or additional data necessary to
confirm the decision presented here.
Based on its evaluation of formetanate HC1, the Agency has determined that formetanate
HC1 products, unless labeled and used as specified in this document, would present risks
inconsistent with FIFRA and FFDCA. Accordingly, should a registrant fail to implement any of
the risk mitigation measures identified in this document, the Agency may take regulatory action
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to address the risk concerns from the use of formetanate HC1. If all changes outlined in this
document are incorporated into the product labels, then all current risks for formetanate HC1 will
be adequately mitigated for the purposes of this interim determination under FIFRA.
Additionally, once an endangered species assessment is completed, further changes to these
registrations may be necessary as explained in Section IV.D.S.a of this document.
B. Public Comments and Responses
Through the Agency's public participation process, EPA worked extensively with
stakeholders and the public to reach the regulatory decisions for formetanate HC1. During the
public comment period on the risk assessments, which closed on May 24, 2004, the Agency
received five comments: one comment from a grower, three comments from grower associations,
and one from the registrant, Gowan Company. The comments by growers cited the importance
of formetanate HC1 in their resistance management programs to control pests, particularly thrips.
Gowan commented on issues concerning both the human health and ecological risk assessments
and the Agency's policies in conducting these analyses. The Agency addressed these issues and
incorporated the comments, as appropriate, in the risk assessment. These comments in their
entirety are available in the public docket EPA-HQ-OPP-2004-0032 at http://www
regulations.gov. A detailed Response to Comments document is available in the public docket as
well.
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 formetanate HC1. This assessment is for this individual carbamate and does not fully
reassess these tolerances as required under FQPA. FQPA requires the Agency to evaluate food
tolerances on the basis of cumulative risk from substances sharing a common mechanism of
toxicity, such as the toxicity expressed by the structurally-related N-methyl carbamates that have
the capacity to inhibit cholinesterase enzymes. The preliminary cumulative risk assessment for
the N-methyl carbamates, which includes formetanate HC1, has been released. The revised
cumulative risk assessment is currently being developed and will be released during 2006. At
that time, the Agency's final tolerance reassessment and reregi strati on decisions for formetanate
HC1 and the other N-methyl carbamates will be issued.
The Agency has made an interim conclusion that if the risk mitigation measures
described in this document are adopted, tolerances for formetanate HC1 meet the FQPA safety
standards and that the aggregate exposure (from food and drinking water) is within the "risk
cup." The Agency has determined that the human health risks from these combined exposures
are within acceptable levels. In reaching this determination, EPA has considered the available
information on the special sensitivity of infants and children.
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b. 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 for additional hormone systems may be added to the Endocrine Disrupter Screening
Program (EDSP).
In the available toxicity studies on formetanate HC1, there was no evidence of endocrine
disrupter effects. When additional appropriate screening and/or testing protocols being
considered under the Agency's EDSP have been developed, formetanate HC1 may be subjected
to further screening and/or testing to better characterize effects related to endocrine disruption.
c. Cumulative Risks
The Food Quality Protection Act of 1996 (FQPA) requires that, when considering
whether to establish, modify, or revoke a tolerance, the Agency consider "available information"
concerning the cumulative effects of a particular pesticide's residues and other substances that
have a common mechanism of toxicity with other pesticides. Formetanate HC1 belongs to a
group of pesticides called the N-methyl carbamates, which share a common mechanism of
toxicity. The Agency has not yet completed its cumulative risk assessment for the N-methyl
carbamates, but the cumulative risks of these chemicals will be considered in the future. At that
time, the Agency's final tolerance reassessment decision for formetanate HC1 and the other N-
methyl carbamates will be issued. The Agency may need to pursue further risk mitigation for
formetanate HC1 to address any risks identified in the cumulative assessment for the N-methyl
carbamates.
2. Interim Tolerance Summary
An interim tolerance summary and interim tolerance reassessment is presented for
formetanate HC1 in Table 11 below. The nature of the residue of formetanate HC1 in livestock
and plants has been adequately demonstrated. The residue of concern for tolerance enforcement
and risk assessment is parent formetanate HC1. The tolerances levels were lowered based on
limited residue data from field trials. Additional residue data are necessary to establish
formetanate HC1 tolerance values. At such time as the additional field trial data are received and
deemed adequate these tolerance levels will be reevaluated. However, because the Agency has
no dietary, drinking water, residential, or aggregate risk concerns (based on the exclusion of late
season applications to apples) the data are adequate to conduct the reassessment summary for
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formetanate HC1. No maximum residue limits (MRLs) for formetanate HC1 have been
established by Codex for any agricultural commodity.
For a detailed discussion of this section, please refer to section 860.1550, Proposed
Tolerances, in the document "Formetanate Hydrochloride HED Revised Chemistry Chapter of
the RED: Summary of Analytical Chemistry & Residue Data (Phase ¥") ( D. Drew, 12/14/2005).
This document is located in the public docket (EPA-HQ-OPP-2004-0032 at http://www
regulations.gov.)
Table 11: Formetanate HC1: Interim Tolerance Reassessment Summary
Commodity
Current Tolerance
(ppm)
Tolerance Reassessment
(ppm)1
Comment/
[Correct Commodity Definition]
Tolerances Listed Under 40 CFR §180.276
Apple
Pear
Grapefruit
Lemon
Lime
Oranges
Tangerine
Nectarine
Peach
Plum, prune, fresh
o
J
3
4
4
4
4
4
4
5
2
0.50
0.50
1.5
0.60
0.03
1.5
0.03
0.40
0.40
revoke
[orange]
no longer a registered use
Tolerances To Be Proposed Under 40 CFR §180.276
Apple, wet pomace
Tangelo
None
None
1.5
0.03
Reassessed tolerances are based on limited field trial data. When additional field trial data are received, the tolerance reassessment will be
reevaluated.
D. Regulatory Rationale
1. Human Health Risk Management
a. Dietary Risk Mitigation (food and drinking water)
Acute dietary risks (from both food and drinking water) exceed the Agency's level of
concern (162% of the aPAD for the most sensitive subgroup, infants). Most of the estimated
acute exposure from food was determined to result from the late season use of formetanate HC1
on apples.
Although labels specifically allow only one application per season (1.15 Ibs. ai/A) for
most uses, there are some late season applications permitted on labeling for pome fruits for
special local concerns from California and other states located in the Northwest part of the
country. Residues from these applications result in dietary risks of concern. Removing the late
season use for apples resulted in a dietary risk of 56% (for food only) and 117% (food plus
water) of the aPAD for infants, the most highly exposed subgroup. All other populations have
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risks below EPA's level of concern (69% or less of the aPAD occupied after late season apples
are removed).
Drinking water estimates are a major source of residues for formetanate dietary analysis
when modeling results were used probabilistically in the acute dietary analysis. Water
monitoring data are not available to estimate residues of formetanate HC1 in drinking water. The
availability and use of monitoring data would have resulted in a more refined estimate of
drinking water exposure. The drinking water estimates used to conduct the acute assessment are
considered conservative for the reasons discussed earlier in chapter 3. Therefore, the dietary risk
estimate of 117% of the aPAD for infants based on food plus water is considered to be below the
Agency's level of concern.
To reduce acute dietary risk the following mitigation is necessary:
• Amend labels to prohibit late season application to apples
Chronic dietary estimates from food plus drinking water do not result in dietary risks of
concern and therefore, no mitigation is necessary to address chronic dietary risks.
b. Residential Risk Mitigation
There are no residential uses for formetanate HC1 and no residential exposure is
anticipated from current uses; therefore, no mitigation is necessary at this time.
c. Occupational Risk Mitigation
There were some occupational risks identified from current labeled uses of formetanate
HC1.
Formetanate HC1 is currently sold only as a wettable powder packaged in water soluble
bags. The Agency's handler risk assessment included scenarios which considered the protection
factors for water soluble bags (an engineering control) plus maximum protective clothing and a
respirator. Although this resulted in an MOE greater than 200 for mixers and loaders supporting
aerial applications on alfalfa, the Agency does not recommend the use of engineering controls
plus additional PPE. This calculated MOE of 200 was achieved by applying protection factors
and does not actually result in significant risk reduction. Further, use of engineering controls
plus maximum protection would conflict with the Worker Protection Standard (WPS). The WPS
allows workers to reduce their PPE when using engineering controls, which in this case the
resulting PPE would be single layer clothing, chemical resistant gloves/apron and no respirator.
Although these scenarios with engineering controls and additional PPE were assessed, the results
are not appropriate for regulatory purposes and are not considered here.
Handler Risks from applications to Alfalfa:
The current label requires applicators spraying alfalfa grown for seed using groundboom
equipment to wear double layer PPE, eyewear, gloves, and a respirator. The risk for this
Page 20 of 64
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scenario did not exceed the Agency's level of concern (MOE=150). However, EPA assessed this
scenario again using only single layer PPE and a respirator. The risk associated with exposure to
the active ingredient was still acceptable (MOE=130).
The mixing/loading and the applicator scenarios for aerial application on alfalfa grown
for seed resulted in MOEs (57 and 54, respectively) that were above the Agency's level of
concern when large acreage (1200 acres treated per day) is considered.
However, data were submitted by the UC Davis, Western Integrated Pest Management
Center which provided evidence of lower acreage values (328 acres treated per day) for alfalfa
grown for seed. In addition, Agency data suggest that majority of the alfalfa acreage treated with
formetanate HC1 in the United States is in California. Therefore, this assessment was refined to
reflect the lower acreage. When the new acreage is considered, the risk for aerial application on
alfalfa for seed is below the Agency's level of concern (MOE=200). However, there is still a
potential risk of concern for the mixer/loader scenario for aerial application (combined dermal
and inhalation MOE= 69).
Although the Agency is concerned with the MOE for the mixing/loading scenario for
aerial application on alfalfa grown for seed, EPA recognizes the inputs used to calculate the risk
are based on conservative assumptions. The NOAEL used in the inhalation assessment was
derived from an oral endpoint from an acute neurotoxicity study (0.1 mg/kg/day), and an
inhalation absorption factor of 100% was used as a high end default value in lieu of an inhalation
study. The Agency is requiring as a condition of this interim decision, the submission of an
inhalation study which will provide a more refined estimate of the inhalation risks for workers
handling formetanate HC1. The Agency believes these data will confirm the conclusion that no
mitigation is appropriate for the mixer/loader scenario for aerial applications to alfalfa.
Handler Risks for Applications to Orchard Fruits:
The risk for the mixer/loader scenario using aerial application on orchard fruit exceeds
EPA's level of concern using engineering controls (MOE=51). No other level of protection can
be added to reduce this risk. In addition, based on Agency data, there are virtually no aerial
applications of formetanate HC1 to tree crops (less than 1%). Therefore, EPA has determined that
aerial applications must be prohibited for orchard crops for reregi strati on eligibility.
The risk for applicator scenarios using airblast sprayers on orchard fruit exceeded the
Agency's level of concern at Baseline PPE (MOE=19) and with double layer protection
(MOE=73). When engineering controls (single layer clothing and closed cabs) are added, the
risk was below the Agency's level of concern (MOE=240).
Flagger Risks for all aerial applications:
MOEs for flaggers are at an acceptable level with double layer PPE and a respirator.
However, the Agency has concerns with requiring additional protective clothing for these
workers due to the potential for heat stress with additional PPE. The Agency believes that most
aerial applicators have either GPS systems or can use closed cabs for flagger protection.
Page 21 of 64
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Therefore to be eligible for reregistration, the following mitigation is required to reduce
risk for handlers:
• Revise labels to prohibit aerial application for orchard crops.
• Revise labels to require closed cabs for applicators using airblast sprayers on orchard
fruit.
• Revise labels to require closed cabs for human flaggers for aerial applications.
• Additionally, based on results of the risk assessment for the active-ingredient, the
registrant may be able to revise labels by reducing the PPE to a single layer with a PF5
respirator for applicators using groundboom equipment for alfalfa for seed, depending
on end-use product toxicity.
Post Application Risks from Alfalfa and Or chard Fruits:
Based on the formetanate HC1 occupational assessment for postapplication, MOEs for
high exposure activities are below levels of concern by day 10 for evergreen fruit trees, day 8 for
deciduous fruit trees, and day 9 for alfalfa.
It was determined that high exposure activities (hand harvesting) are not appropriate for
alfalfa, and therefore, a 6-day REI is considered appropriate to protect post application workers
performing medium-exposure activities.
Therefore to be eligible for reregistration, the following mitigation is required to reduce
risk for postapplication workers:
• Revise labels to require a 10 day re-entry interval (REI) for citrus, an 8 day REI for pome
and stone fruits, and a 6 day REI for alfalfa.
2. Ecological Risk Management and Mitigation
Although the screening level ecological risk assessment shows risks of concern, the risks
are relatively low in comparison with other N-methyl carbamates. For formetanate HC1, the
highest RQ estimates were identified for chronic mammals when maximum estimated residues
are considered (RQ's were as high as 28). Chronic risk to birds was low (highest RQ was 5).
There were no risks of concern to aquatic organisms.
The Agency is not proposing additional mitigation for ecological risks at this time since
considerable reductions in rates and uses were made in 1999 in accordance with the MO A.
Additionally, some of the dietary and worker mitigation will result in slightly lower ecological
exposures.
Page 22 of 64
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3. Significance of Formetanate HC1 Use
There are advantages to the use of formetanate HC1 as an insecticide. EPA has received
comments supporting the continued use of formetanate HC1 to control thrip outbreaks on stone
fruit and citrus crops. USD A, private citizens, and grower organizations have expressed their
need for the use of formetanate HC1 as a rotational partner with other insecticides, as part of an
efficacious integrated pest management program.
Formetanate HC1 is a niche pesticide for growers needing the chemical to control thrips
which can severely damage the skin of orchard fruits. Formetanate HC1 is used extensively in
California for treatment of orchard crops, particularly nectarines. Since California orchard crops
are grown primarily for the fresh market, the appearance of the fruit dramatically affects the
grower's ability to sell the fruit.
Alfalfa grown for seed is a relatively minor, but high value crop. Based on Agency data,
approximately 48,000 acres nationally are grown for seed on an annual basis. Alfalfa growers
use formetanate HC1 as part of their integrated pest management programs.
4. Spray Drift
The Agency has been working with the Spray Drift Task Force, EPA Regional Offices
and State Lead Agencies for pesticide regulation and other parties to develop the best spray drift
management practices. The Agency has completed its evaluation of the new data base submitted
by the Spray Drift Task Force, a membership of U.S. pesticide registrants, and is developing a
policy on how to appropriately apply the data and the AgDRIFT computer model to its risk
assessments for pesticides applied by air, orchard airblast and ground hydraulic methods. After
the policy is in place, the Agency may impose further refinements in spray drift management
practices to reduce off-target drift and risks associated with aerial as well as other application
types where appropriate.
From its assessment of formetanate HC1, as summarized in this document, the Agency
concludes that no additional drift mitigation measures are needed for formetanate HC1. The
deletion of aerial application of all orchard crops from the formetanate HC1 labels will reduce the
potential for drift. In the future, formetanate HC1 product labels may need to be revised to
include additional or different drift label statements. Additionally, the Agency encourages the
inclusion of best management practices on labels to reduce spray drift.
5. Endangered Species Considerations
From the screening level assessment, RQs exceeded the LOCs for endangered species for
some of the representative exposure scenarios considered. The Agency's screening level
assessment results in the determination that formetanate HC1 will have no direct acute effects on
threatened and endangered freshwater fish, invertebrates, and estuarine mollusks.
The preliminary risk assessment for endangered species indicates that RQs exceed
endangered species LOCs for birds and mammals with RQs ranging up to 0.2 for birds and up to
Page 23 of 64
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18 for mammals. Chronic RQs for all uses exceeded LOCs for endangered birds using a single
application (RQs for birds ranged from 2 to 5). Additionally, chronic RQs were exceeded LOCs
for mammals from all uses at a single application rate (RQ's ranged from 2 to 28).
Further, potential indirect effects to any species dependent upon a species that
experiences effects from use of formetanate HC1 can not be precluded based on the screening
level ecological risk assessment. These findings are based solely on EPA's screening level
assessment and do not constitute "may affect" findings under the Endangered Species Act.
The Agency has developed the Endangered Species Protection Program to identify
pesticides whose use may cause adverse impacts on endangered and threatened species, and to
implement mitigation measures that address these impacts. The Endangered Species Act (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 IREDs and considers it in relation to individual species and their locations by evaluating
important ecological parameters, pesticide use information, geographic relationship between
specific pesticide uses and species locations, and biological requirements and behavioral aspects
of the particular species, as part of a refined species-specific analysis. When conducted, this
species-specific analysis will take into consideration any regulatory changes recommended in
this IRED that are being implemented at that time.
Following this future species-specific analysis, a determination that there is a likelihood
of potential impact to a listed species or its critical habitat may result in: limitations on the use of
formetanate HC1, other measures to mitigate any potential impact, or consultations with the Fish
and Wildlife Service or the National Marine Fisheries Service as necessary. If the Agency
determines use of formetanate HC1 "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 IRED will reduce the likelihood that endangered and threatened species may be exposed to
formetanate HC1 at levels of concern. EPA is not requiring specific formetanate HC1 label
language at the present time relative to threatened and endangered species. If, in the future,
specific measures are necessary for the protection of listed species, the Agency will implement
them through the Endangered Species Protection Program.
V. What Registrants Need to Do
The Agency has made an interim determination that formetanate HC1 is eligible for
reregi strati on provided that product specific data are submitted and the mitigation measures
stated in this document are included in upcoming label submissions. In the near future, the
Agency intends to issue Data Call-In (DCIs) notices requiring product specific data and generic
confirmatory (technical grade) data. Generally, registrants will have 90 days from receipt of a
DCI to complete and submit response forms or request time extensions and/or waiver requests
with a full written justification. For product specific data, the registrant will have 8 months to
submit data and amended labels. For generic data, due dates can vary depending on the specific
Page 24 of 64
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studies being required. Listed below is the additional generic data that the Agency intends to
require.
A. Manufacturing-Use Products
1. Additional Generic Data Requirements
The generic data base supporting the interim reregi strati on of formetanate HC1 for the
above eligible uses has been reviewed and determined to be substantially complete. However,
the data listed below are necessary to confirm the interim reregi strati on eligibility decision
documented in this RED.
830.7050 UV-Visible Absorption
830.1550 Product Identity and Composition
830.1750 Certified Limits
830.1800 Enforcement of Analytical Method
835.4100 Aerobic Soil Metabolism
835.4200 Anaerobic Soil Metabolism
860.1300 Nature of the Residue
860.1500 Crop Field Trials
870.1200 Acute Dermal Toxicity
870.1300 Acute Inhalation Toxicity
870.2500 Primary Dermal Irritation
870.3465 28-Day Inhalation Toxicity Study
B. End-Use Products
1. Additional Product-Specific Data Requirements
Section 4(g) (2) (B) of FIFRA calls for the Agency to obtain any needed product-specific
data regarding the pesticide after a determination of eligibility has been made. The registrant
must review previous data submissions to ensure 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 Registrations Response Form provided for each
product. The Agency intends to issue a separate product-specific Data Call-In outlining specific
data requirements.
2. Labeling for End-Use Products
Labeling changes are necessary to implement measures outlined in Section IV above.
The specific changes and language required are presented in Table 8 below.
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. Please refer to "Existing
Page 25 of 64
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Stocks of Pesticide Products; Statement of Policy," Federal Register, Volume 56, No. 123, June
26, 1991.
Page 26 of 64
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Labeling Changes Summary Table
[Attachment III]
In order to be eligible for reregi strati on, amend all product labels to incorporate the risk mitigation measures outlined in Section IV.
The following table describes how language on the labels should be amended.
Table 12: Summary of Labeling Changes for Formetanate Hydrochloride
Description
Manufacturing Use Products
Placement on Label
For all Manufacturing
Use Products
AOnly for formulation into an insecticide for the following use(s)
nectarines, peaches, pome fruits, citrus, and alfalfa grown for seed.@
"This product may be used only to formulate wettable powder end use
products that are packaged in water soluble packets".
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
AThis product may be used to formulate products for specific use(s) not
listed on the MP label if the formulator, user group, or grower has
complied with U.S. EPA submission requirements regarding support of
suchuse(s).@
AThis product may be used to formulate products for any additional
use(s) not listed on the MP label if the formulator, user group, or grower
has complied with U.S. EPA submission requirements regarding support
of such use(s).@
Directions for Use
Environmental Hazards
Statements Required
by the RED and
Agency Label Policies
"This pesticide is toxic to fish and aquatic invertebrates. Do not
discharge effluent containing this product into lakes, streams, ponds,
estuaries, oceans, or other waters unless in accordance with the
requirements of a National Pollution Discharge Elimination System
(NPDES) permit and the permitting authority has been notified in writing
prior to discharge. Do not discharge effluent containing this product to
Precautionary Statements
Page 27 of 64
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Table 12: Summary of Labeling Changes for Formetanate Hydrochloride
sewer systems without previously notifying the local sewage treatment
plant authority. For guidance contact your State Water Board or
Regional Office of the EPA. Do not contaminate water when disposing of
equipment washwaters."
End Use Products Intended for Occupational Use
PPE Requirements
Established by the
RED'ForWettable
Powder
Formulations
(Note: Only products
packaged in water
soluble bags will be
eligible for
reregistration)
APersonal Protective Equipment (PPE)
Some materials that are chemical-resistant to this product are (registrant
inserts correct chemical-resistant material). If you want more options,
follow the instructions for category [registrant inserts A,B,C,D,E,F,G,or
H\ on an EPA chemical-resistance category selection chart."
AMixers, loaders, applicators, flaggers, and other handlers must wear:
> Long-sleeved shirt and long pants,
> Shoes plus socks,
> Chemical resistant gloves and apron for mixers and other handlers
exposed to the concentrate.
> Applicators using groundboom equipment must wear a NIOSH-
approved respirator with:
- a dust/mist filter with MSHA/NIOSH approval number prefix TC-21C
or
- any N, R, P, or HE filter@
"See Engineering Controls for Additional
Requirements"
Instruction to Registrant: Drop the AN@ type prefilter from the
respirator statement, if the pesticide product contains, or is used with, oil.
Immediately following/below
Precautionary Statements: Hazards to
Humans and Domestic Animals
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Table 12: Summary of Labeling Changes for Formetanate Hydrochloride
User Safety
Requirements
ADiscard clothing and other absorbent materials that have been drenched
or heavily contaminated with this product=s concentrate. Do not reuse
them.@
"Follow manufacturers' instructions for cleaning and maintaining PPE.
If no such instructions for washables exist, use detergent and hot water.
Keep and wash PPE separately from other laundry."
Precautionary Statements: Hazards to
Humans and Domestic Animals
immediately following the PPE
requirements
Engineering Controls
for wettable powder
formulations
"Engineering Controls
Applicators using airblast equipment and flaggers must use an enclosed
cab that meets the definition in the Worker Protection Standard for
Agricultural Pesticides [40 CFR 170.240(d)(5)] for dermal protection. In
addition, applicators must:
~ wear the personal protective equipment required in the PPE section of
this labeling for applicators,
~ either wear the type of respirator specified in the PPE section of this
labeling or use an enclosed cab that is declared in writing by the
manufacturer or by a government agency to provide at least as much
respiratory protection as the type of respirator specified in the PPE
section of this labeling,
~ be provided and have immediately available for use in an emergency
when they must exit the cab in the treated area: coveralls, chemical-
resistant gloves, chemical-resistant footwear, chemical-resistant
headgear, if overhead exposure, and, if using an enclosed cab that
provides respiratory protection, a respirator of the type specified in the
PPE section of this labeling,
~ take off any PPE that was worn in the treated area before reentering the
cab, and
Precautionary Statements: Hazards to
Humans and Domestic Animals
(Immediately following PPE and User
Safety Requirements.)
Page 29 of 64
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Table 12: Summary of Labeling Changes for Formetanate Hydrochloride
~ store all such PPE in a chemical-resistant container, such as a plastic
bag, to prevent contamination of the inside of the cab.@
"Water-soluble packets when used correctly qualify as a closed
mixing/loading system under the Worker Protection Standard for
Agricultural Pesticides [40 CFR 170.240(d)(4)]. Mixers and loaders
using water-soluble packets must:
~ wear the personal protective equipment required in the PPE section of
this labeling for mixers and loaders, and
~ be provided and must have immediately available for use in an
emergency, such as a broken package, spill, or equipment breakdown:
chemical-resistant footwear and the respirator as specified in the PPE
section of this label.
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)].
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)(4-5), the handler PPE
requirements may be reduced or modified as specified in the WPS.0
User Safety
Recommendations
AUser 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.
Precautionary Statements under:
Hazards to Humans and Domestic
Animals immediately following
Engineering Controls
(Must be placed in a box.)
Page 3 Oof 64
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Table 12: Summary of Labeling Changes for Formetanate Hydrochloride
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.@
Environmental Hazards
"This product is toxic to aquatic invertebrates. Do not apply directly to
water, to areas where surface water is present or to intertidal areas below
the mean high water mark. Drift and runoff may be hazardous to aquatic
organisms in water adjacent to treated areas. Do not contaminate water
when disposing of equipment washwaters or rinsate."
"This chemical can contaminate surface water through spray applications.
Under some conditions, it may also have a potential for runoff into
surface water after application."
"This product is toxic to bees exposed to direct treatment. Do not apply
this product while bees are actively visiting the treatment area. Do not
allow animals to graze in treated orchard areas."
Precautionary Statements immediately
following the User Safety
Recommendations
Restricted-Entry
Interval (REI)
ADo not enter or allow worker entry into treated areas during the
restricted entry interval (REI) of:
10 days for citrus
8 days for pome and stone fruits
6 days for alfalfa grown for seed"
Directions for Use, Under Agricultural
Use Requirements Box
Early Entry Personal
Protective Equipment
APPE required for early entry to treated areas that is permitted under the
Worker Protection Standard and that involves contact with anything that
Direction for Use
Agricultural Use Requirements box
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Table 12: Summary of Labeling Changes for Formetanate Hydrochloride
has been treated, such as plants, soil, or water, is:
coveralls,
shoes plus socks
chemical-resistant gloves made of any waterproof materials
"Notify workers of the application by warning them orally and by posting
warnings signs at entrances to treated area."
General Application
Restrictions
ADo not apply this product in a way that will contact workers or other
persons, either directly or through drift. Only protected handlers may be
in the area during application. @
Place in the Direction for Use directly
above the Agricultural Use Box.
Other Application
Restrictions (Risk
Mitigation)
"Late season applications to apples is prohibited; Only apply at
petal fall"
"Aerial applications to orchard crops is prohibited"
"Hand harvesting for alfalfa is prohibited"
Directions for Use in the appropriate
site/crop instructions
1 PPE that is established on the basis of Acute Toxicity of the end-use product must be compared to the active ingredient PPE in this document.
The more protective PPE must be placed in the product labeling. For guidance on which PPE is considered more protective, see PR Notice 93-7.
2 Label requirements in quotes are to be specified on the label.
Page 32 of 64
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Page 3 3 of 64
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VI. Appendices
Appendix A: Formetanate HC1 Use Patterns Eligible for Reregistration
Application
Type, Equipment
Formulation
Max, Single
App, Rate (Ibs
ai/A)
Seasonal
Maz
(Ibs ai/A/Yr.)
PHI
(Days)
REI
(Days)
Restrictions/Comments
Alfalfa
Aerial &
Groundboom
Wettable
Powder
0.92
0.92
21
6
Apple
Airblast
Wettable
Powder
1.15
1.15
One application can
be made through
petal fall.
8
Late season uses are
prohibited. Use of
aerial application in
apple orchards is
prohibited.
Grapefruit, Orange
Airblast
Wettable
Powder
1.15
1.15
Applications may be
made to overcropped
grapefruits and
Valencia oranges
above one inch in
diameter, provided
that a preharvest
interval (PHI) of 30
days is obaserved.
10
Use of aerial
applications in
grapefruit and orange
orchards is prohibited.
Lemon, Limes, Tangelos, Tangerines
Airblast
Wettable
Powder
1.15
1.15
One application may
be made prior to
fruit reaching one
inch in diameter.
10
Use of aerial
applications in these
orchards is prohibited.
Nectarine, Peach
Airblast
Wettable
Powder
1.15
1.15
One application may
be made through
shuck fall.
8
Use of aerial
applications in
nectarine and peach
orchards is prohibited.
Pear
Airblast
Wettable
Powder
1.15
1.15
One application may
be made through
petal fall. One
additional
application for pears
may be made in the
late season to control
pest in CA, OR, WA
and ID upon written
approval on a case-
by-case basis by the
State Agency
responsible for
enforcement of
FIFRA, or
authorized by that
state agency.
8
Use of aerial
application in pear
orchards is prohibited.
Page 3 4 of 64
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Appendix B
Data Supporting Guideline Requirments for the Reregistration of Formetnate HC1
GUIDE TO APPENDIX B
Appendix B contains a listing of data requirements which support the reregi strati on 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.
Page 3 5 of 64
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Appendix B. Data Supporting Guideline Requirments for the Registration of
Formetanate HC1
New
Guideline
Number
Old
Guideline
Number
Requirement
Use
Pattern
Bibliographical Citation
PRODUCT USE CHEMISTRY
830.1550
830.1600
830.1620
830.1650
830.1670
830.1700
830.1750
830.1800
830.6302
830.6303
830.6304
830.6313
830.6314
830.6316
830.6317
830.6320
830.7000
830.7050
830.7200
830.7300
830.7370
830.7550
830.7560
830.7570
830.7840
830.7860
830.7950
61-1
6 1-2 A
61-2B
62-1
62-2
62-3
63-2
63-3
63-4
63-13
63-14
63-16
63-17
63-20
63-12
63-5
63-7
63-10
63-11
63-8
63-9
Product Identity and
Disclosure of Ingredients
Starting Materials and
Manufacturing Process
Discussion of Formation
Impurities
Preliminary Analysis
Certification of Ingredient
Limits
Analytical Methods to Verify
the Certified Limits
Color
Physical State
Odor
Stability
Oxidation/Reduction
Explodability
Storage Stability
Corrosion Characteristics
pH
UV/Visible Absorption
Melting Point/Melting Range
Density /Relative
Density /Bulk Density
Dissociation Constant in
Water
Partition Coefficient
(Octanol/Water)
Solubility
Vapor Pressure
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
Confirmatory Data Needed
00144899, 42089807, 42155401,
43489402
00144899, 42089807, 42155401,
43489404
00144899, 42089801, 42155401,
43489407, 43489408
Confirmatory Data Needed
Confirmatory Data Needed
00064035,42155402
00064035, 42155402
00064035, 42155402
00064035, 42155402
00144899
00144899
00064035, 42155402
00144899
00142494
Confirmatory Data Needed
00064035, 42155402
00142494
00142494
00142494
00064035, 42155402
00064035, 42155402
ECOLOGICAL EFFECTS
850.2100
850.2200
850.2200
850.2300
850.2300
850.1075
850.1075
71-1A
7 1-2 A
71-2B
7 1-4 A
71-4B
72-1A
72-1C
Acute Avian Oral,
Quail/Duck
Acute Avian Dietary,
Bobwhite Quail
Acute Avian Dietary,
Mallard Duck
Avian Reproduction,
Bobwhite Quail
Avian Reproduction, Mallard
Duck
Acute Fish Toxicity, Bluegill
Acute Fish Toxicity,
A,B,C
A,B,C
A,B,C
A,B,C
A,B,C
A,B,C
A,B,C
00077751
00164338
00164337
42841001
42841002
00164340
00164339
Page 3 6 of 64
-------
New
Guideline
Number
850.1010
850.1025
850.1035
850.1300
850.1350
850.1710
850.3020
Old
Guideline
Number
72-2A
72-3B
72-3C
72-4A
72-4B
72-6
141-1
Requirement
Rainbow Trout
Acute Aquatic Invertebrate
Toxicity
Acute Estuarine/Marine
Toxicity, Mollusk
Acute Estuarine/Marine
Toxicity, Shrimp
Daphnia Chronic Toxicity
Test
Mysid (Shrimp) Chronic
Toxicity
Aquatic Organism
Accumulation Study
Honey Bee Acute Contact
Toxicity
Use
Pattern
A,B,C
A,B,C
A,B,C
A,B,C
A,B,C
A,B,C
A,B,C
Bibliographical Citation
00160118
42306601
00131846
42980601
43228701
00077656
00077766
TOXICOLOGY
870.3100
870.3200
870.3700
870.3700
870.3800
870.4100
870.4200
870.4300
870.6200
870.6200
870.6300
870.7485
82-1A
82-2
83-3A
83-3B
83-4
83-1B
83 -2 A
83-5
81-8
82-7
83-6
85-1
90-Day Oral Toxicity -
Rodent
90 Day Oral Toxicity -Non-
rodents
Prenatal Developmental in
Rats
Prenatal Developmental in
Non-rodents
Reproduction and Fertility
Effects
Chronic Toxicity - Dogs
Carcinogenicity - Rat
Carcinogenicity - Mouse
Acute Neurotoxicity
Screening Battery
Subchronic Neurotoxicity
Screening Battery
Special Non-Guideline
Comparative ChEI Study
Metabolism and
Pharmacokinetics
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
42664401
44948501
00151570
00151571
40411801,-02and-03
00164341
40640901
40707101
45314201
45314202
46618901
42684601,42684602,42684603,42684604,
and 42909701
OCCUPATIONAL/RESIDENTIAL EXPOSURE
875.2100
132-1A
Foliar Residue Dissipation
A,B,C
44151201
ENVIRONMENTAL FATE
835.2120
835.2240
835.2410
835.4100
835.4200
835.1240
835.6100
860.1950
161-1
161-2
161-3
162-1
162-2
163-1
164-1
165-4
Hydrolysis
Photolysis
Photodegradation in Soil
Aerobic Soil Metabolism
Study
Anaerobic Soil Metabolism
Soil Column Leaching
Terrestrial Field Dissipation
Study
Accumulation
(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
00141498
00164331,42155403
00164331,42155403
Confirmatory Data Needed
Confirmatory Data Needed
42089805, 43034002
41192301,41192302,
00077656
Page 3 7 of 64
-------
New
Guideline
Number
Old
Guideline
Number
Requirement
Use
Pattern
Bibliographical Citation
RESIDUE CHEMISTRY
860.1200
860.1300
860-1300
860.1340
860.1340
860.1360
860.1380
171-3
171-4A
171-4B
171-4C
171-4D
171-4M
171-4E
Directions for Use
Nature of Residue - Plants
Nature of Residue -
Livestock
Residue Analytical Method -
Plants
Residue Analytical Method-
Livestock
Multiresidue Methods
Storage Stability Data
A,B,C
A,B
A,B
A,B
A,B
A,B
A,B
Confirmatory Data Needed
00164328, 00164329, 42664414,
42664417, 43329001, 43329002
00029161, 00035917, 40411802
40557601
42664406, 42983201
00077702, 40411803, 42664407,
42664408, 42723601, 43329003,
43384401, 43384405, 43610401,
43610403
Citrus Fruits Group
860.1500
860.1500
860.1500
860.1500
860.1500
860.1500
171-4K
171-4K
171-4K
171-4K
171-4K
171-4K
Crop Field Trials
(Grapefruit)
Crop Field Trials (Lemon)
Crop Field Trials (Lime)
Crop Field Trials (Orange)
Crop Field Trials (Tangelo)
Crop Field Trials (Tangerine)
A,B
A,B
A,B
A,B
A,B
A,B
Confirmatory Data Needed
Confirmatory Data Needed
Confirmatory Data Needed
Confirmatory Data Needed
Confirmatory Data Needed
Confirmatory Data Needed
Pome Fruits Group
860.1500
860.1500
171-4K
171-4K
Crop Field Trials (Apple)
Crop Field Trials (Pear)
A,B
A,B
Confirmatory Data Needed
Confirmatory Data Needed
Stone Fruits Group
860.1500
860.1500
171-4K
171-4K
Crop Field Trials (Nectarine)
Crop Field Trials (Peach)
A,B
A,B
Confirmatory Data Needed
Confirmatory Data Needed
Non-Grass Animal Feeds
860.1500
171-4K
Crop Field Trials (Alfalfa
For Seed)
A,B
40534301
Processed Food/Feed
860.1520
860.1520
171-4L
171-4L
Processed Food (Apple)
Processed Food (Citrus)
A,B
A,B
00077721
00073455, 00077665, 00077702
Meat, Milk, Poultry, Eggs
860.1480
171-4J
Magnitude of Residues in
Meat, Milk, Poultry, and
Eggs
A,B
41299601,41299603
Confined Rotational Crops
860.1850
165-1
Confined Rotational Crops
A,B,C
43170401,43583101
Page 3 8 of 64
-------
C. Technical Support Documents
Appendix C. Technical Support Documents
Additional documentation in support of this IRED is maintained in the OPP
Regulatory Docket, located in One Potomac Yard (South Building), 2777 S. Crystal
Drive, Arlington, VA. It is open Monday through Friday, excluding legal holidays, from
8:30 am to 4:00 pm.
The docket initially contained preliminary human health and ecological effects
risk assessments and related documents that were published March 24, 2004. The public
comment period closed sixty (60) days later on May 24, 2004. The EPA then considered
comments and revised the risk assessments where appropriate. Final human health and
ecological risk assessments, as well as additional support documents, will be published in
the docket with this RED. These documents include the following:
Phase 3 Public Comment Documents:
HED Documents
Formetanate Hydrochloride, Addendum to Acute (Probablistic) and Chronic Dietary
Exposure Assessment. 6/4/2003.
Formetanate Hydrochloride: The Occupational and Residential Exposure Assessment &
Recommendations for the RED. 5/21/2003.
Formetante Hydrochloride, HED Revised Chemistry Chapter of the RED: Summary of
Analytical Chemistry & Residue Data. 3/27/2003.
Formetanate Hydrochloride Toxicology Chapter for the RED. 4/14/2003.
Formetanate Hydrochloride (97301) HED Product Chemistry Chapter of the RED.
3/27/2003.
Formetante Hydrochoride - 4th Report of the Hazard Identification Assessment Review
Committee. 5/21/2003.
Formetanate Hydrochloride - Acute & Chronic Dietary Exposure Assessment for the
RED. 4/28/2003.
HED Revised Risk Assessment for Formetanate Hydrochloride. 6/4/2003.
HED Preliminary Risk Assessment for Formetanate Hydrochloride. 4/6/1999.
Formetanate Hydrochloride - Report of the Hazard Identification Assessment Review
Committee. 7/22/2002.
Page 3 9 of 64
-------
HED Revised Risk Assessment for Formetanate Hydrochloride. 12/23/2005.
Formetanate Hydrochloride FED Revised Chemistry Chapter of the RED: Summary of
Analytical Chemistry and Residue Data. 12/14/2005.
Formetanate Hydrochloride: Revised Acute Probablistic and Chronic Dietary Exposure
Assessments for the Reregistration Eligibility Decision. 12/16/2005.
EFED Documents
EFED Science Chapter for the Formetanate Hydrochloride RED. 10/22/2003.
EFED Science Chapter for the Formetanate Hydrochloride RED. 8/29/1997.
Revised Tier II Drinking Water Assessment for Formetanate HC1. 3/27/2003.
Other Documents
Formetanate Hydrochloride, Addendum to the HED Revised Risk Assessment for
Formetanate Hydrochloride dated May 23, 2005
Page 40 of 64
-------
D. Bibliography
Bibliography
MRTO Citation Reference
29161 Nor-Am Agricultural Products, Incorporated (1969) 332/30: Colorimetric
Determination of Formetanate HC1. (Nor-Am EP-332) in Plant Material:
(Schering 36 056/5 Revised). Method dated May 22, 1969. (Unpublished
study received May 22, 1980 under OE2363; submitted by Interregional
Research Project No. 4, New Brunswick, N.J.; CDL:099438-B)
35917 Jenny, N.A. (1969) Gas Chromatographic Residue Determination of
Formetanate HC1 (Nor-Am Carzol) in Plant Material: Report 332/41. Method
dated Nov 7, 1969. (Unpublished study received Feb 1, 1973 under 3F1351;
submitted by Nor-Am Agricultural Products, Inc., Naperville, 111.;
CDL:096476-F)
64035 Nor-Am Agricultural Products, Incorporated (19??) Formetanate hy-
drochloride. (Unpublished study received Mar 18, 1970 under OF0961;
CDL:093273-M)
73455 Morton Chemical Company (1968) ?Residues of Formetanate on Oranges,
Grapefruit and Lemons). (Compilation; unpublished study re- ceived Nov 29,
1968 under 9G0746; CDL:091290-E)
77656 Michigan State University (1968?) Residues of CA14I Formetanate-
hydrochloride in Green Sunfish following a Subacute Exposure. (Unpublished
study received May 18, 1973 under 2139-99; CDL: 124298-A)
77665 Nor-Am Agricultural Products, Incorporated (1975) Residues of Formetanate
Hydrochloride in Citrus Treated with Carzol SP by Air. Includes method
332/30 dated May 22, 1969. (Compilation; unpublished study received Mar
12, 1975 under 2139-99; CDL: 110595-A)
77702 Nor-Am Agricultural Products, Incorporated (1970) ?Residue Data on Carzol
SP in Citrus Fruits). (Compilation; unpublished study received Apr 12, 1970
under OF0961; CDL: 091643-D)
77721 Nor-Am Agricultural Products, Incorporated (1973) Residues of For-
metanate Hydrochloride in Apple Products. (Compilation; unpub- lished
study, including letter dated Oct 8, 1973 from M. Lambert to Edward Gross,
received Apr 25, 1973 under 3H5029; CDL: 221762-F)
77751 Nor-Am Agricultural Products, Incorporated (19??) ?Toxicity of Carzol to
Bobwhite Quail and Mallard Ducks). (Compilation; unpublished study
received May 27, 1970 under OF0989; CDL: 093298-D)
77766 Nor-Am Agricultural Products, Incorporated (1972) ?Formetanate Hy-
Page41 of 64
-------
drochloride Residues in Almonds]. (Compilation; unpublished study received
Jul 12, 1973 under 4F1419; CDL:093790-B)
131846 Rausina, G. (1975) Report to Four-day Static Aquatic Toxicity Studies with
Carzol SP in Grass Shrimp and Shore Crabs: IBT No. 621-06936.
(Unpublished study received Aug 11, 1983 under 2139-99; prepared by
Industrial Bio-Test Laboratories, Inc., submitted by Nor-Am Agricultural
Products, Inc., Naperville, IL; CDL:250994-A)
141498 Rehme (1982) Investigation of the Hydrolysis of Carzol in Agueous
Solutions: Report Nr. 36/82. Unpublished study prepared by Schering AG. 6
P-
142494 Nor-Am Chemical Co. (1984) [Chemistry Data for Formetanate HCL].
Unpublished compilation. 17 p.
144899 Nor-Am Chemical Co. (1984) [Chemistry Data for Formetanate HCL].
Unpublished compilation. 18 p.
151570 Tesh, J.; Willoughby, C.; Lambert, E.; et al. (1985) Technical For- metanate-
HC1: Effects of Oral Administration (Gavage) upon Preg- nancy in the Rat
(Teratology Study): LSR Report No. 84/SCE004/ 318. Unpublished study
prepared by Life Science Research. 100 p.
151571 Tesh, J.; Ross, F.; Wightman, T.; et al. (1985) Technical Formeta- nate-HCl:
Effects of Oral Administration (Gavage) upon Pregnancy in the Rabbit
(Teratology Study): LSR Report No. 84/SCE002/319. Unpublished study
prepared by Life Science Research. 95 p.
160118 Barrett, K.; Arnold, D. (1986) Determination of the Acute Toxicity of
Formetanate to Daphnia magna: Report No. METAB/85/40: Study No. 59D.
Unpublished study prepared by FBC Ltd. 12 p.
164328 Campbell, J.; Needham, D. (1986) Metabolism and Residues of Forme- tanate
Hydrochloride in Laying Hens: Proj. ID. No. METAB/86/36. Unpublished
study prepared by Schering Agrochemicals Ltd. 24 p.
164329 Campbell, J.; Needham, D. (1986) Excretion and Tissue Residues of
Formetanate Hydrochloride in a Lactating Goat: Proj. ID. No. METAB/86/28.
Unpublished study prepared by Schering Agrochemi- cals Ltd. 24 p.
164331 Brehm, M. (1986) Photodegradation of Formetanate Hydrochloride (...) on
Soil Surfaces: Proj. ID. APC/41/86. Unpublished study prepared by Schering
AG. 43 p.
164337 Roberts, N.; Fairley, C. (1986) Technical Formetanate Hydrochlo- ride:
Subacute Dietary Toxicity (LC50) to the Mallard Duck: HRC Study No. FSB
187BT/851171. Unpublished study prepared by Huntingdon Research Centre.
23 p.
164338 Roberts, N.; Fairley, C. (1986) Technical Formetanate Hydrochlo- ride:
Page 42 of 64
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Subacute Dietary Toxicity (LC50) to the Bobwhite Quail: HRC Study No.
FSB 186BT/851172. Unpublished study prepared by Huntingdon Research
Centre. 22 p.
164339 Barrett, K.; Arnold, D. (1986) The Acute Toxicity of Formetanate
Hydrochloride to Rainbow Trout (Salmo gairdneri): Proj. ID No.
METAB/86/31. Unpublished study prepared by Schering Agrochemi- cals
Ltd. 19 p.
164340 Hill, R. (1986) Determination of Acute Toxicity to Bluegill Sunfish (Lapomis
macrochirus): Formetanate Hydrochloride: Proj. ID No. BL/B/2940.
Unpublished study prepared by Imperial Chemical Industries Ltd. 18 p.
164341 Massey, I; Harling, R.; Buist, D.; et al. (1986) Dietary Toxicity Study in
Beagle Dogs (Final Report - Repeated Administration for 52 Weeks):
Formetanate Hydrochloride: HRC Rept. No. FSB ISO/ 86477. Unpublished
study prepared by Huntingdon Research Centre Ltd. 278 p.
40411801 Tesh, J. (1987) T83 Technical Formetanate Hydrochloride: The Reproductive
Performance of Rats Treated Continuously Through Two Successive
Generations: Laboratory Project ID TOX 85002. Unpublished study prepared
by Life Science Research Ltd. 1242 p.
40411802 Scheuermann, H. (1987) R155/Formetanate HCL: GLC Method of Analysis
for Major Formetanate Derived Residues in Nectarines (10 970 1/87):
Laboratory Project ID UPSR 32/87 PA 10 970.5/11. Unpublished study
prepared by Schering AG. 28 p.
40411803 Scheuermann, H. (1987) R156 Formetanate HCL: Residues of Formetanate X
HCL and Major Metabolites in Stone Fruits Follow- ing Foliar Application of
CARZOL (92 SP) in the USA 1985 and 1986 (10 970 11/87): Laboratory
Project ID UPSR 36/87 PA 10 970.6/11. Unpublished study prepared by
Schering AG. 43 p.
40534301 Scheuermann, H. (1988) R157 Formetanate: Residue Decline of Formetanate
x HCL and Major Metabolites in Alfalfa Following Foliar Application of
Carzol (90SP) in the USA 1985 (10970 III/ 87): Laboratory Project ID UPSR
50/87. Unpublished study prepared by Schering AG, Germany. 52 p.
40557601 Manley, J.; Snowdon, P. (1988) R154 Formetanate: Analytical Method for the
Determination of Residues of Formetanate and Major Metabolites
Hydrolysing to 3-Aminophenol in Animal Tissues, Milk and Eggs by Gas
Chromatography: Laboratory Project ID RESID/87/82. Unpublished study
prepared by Schering Agrochemicals Limited, England. 38 p.
40640901 Mallyon, B. (1988) T87 Technical Formetanate Hydrochloride: An Eva-
luation of Dietary Oncogenic and Chronic Toxicity Potential in the Rat: Final
Report: Project ID: TOX 84083. Unpublished study prepared by Schering
Agrochemicals Ltd. 1919 p.
Page 43 of 64
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40707101 Mallyon, B. (1988) T85 Technical Formetanate Hydrochloride: An
Evaluation of Dietary Oncogenic Potential in the Mouse: Labora- tory Project
ID: TOX/87/197-64. Unpublished study prepared by Schering Agrochemicals
Ltd. 1146 p.
41192301 Scheuermann, H. (1989) W75/2 Formetanate: Dissipation of Formeta- nate X
HC1 and Relevant Metabolites in Soil Following Maximum Recommended
Use Rates in an Orchard in the USA, 1987: Laboratory Project ID UPSR
27/89. Unpublished study prepared by Schering AG. 107 p.
41192302 Scheuermann, H. (1989) W76/2 Formetanate: Dissipation of Formeta- nate X
HC1 and Relevant Metabolites in Soil Following Maximum Recommended
Use Rates in Alfalfa Trials in the USA 1987: Labora- tory Project ID UPSR
30/89. Unpublished study prepared by Schering AG. 187 p.
41299601 Roberts, N.; Cameron, D.; Emerson, E. (1988) R163A Formetanate
Hydrochloride: Residues in Milk & Tissues of Dairy Cows—Animal Phase:
Lab Project Number RESID/88/44; FSB 275/861445; 101/05/001.
Unpublished study prepared by Huntingdon Research Centre. 23 p.
41299603 Manley, I; Snowdon, P. (1989) C49 Formetanate: Analytical Method for the
Determination of Dietary Concentrations of Formetanate Hydrochloride in
Maize Oil by High Performance Liquid Chromatography: Lab Project
Number RESID/88/46; 101/01/002. Unpublished study prepared by Schering
Agrochemicals Ltd. 20 p.
42089801 Muller, T.; Steib, C.; Lehne, V. (1991) Formetanate Hydrochloride: Product
Chemistry: Lab Proj ect Number: C-55: C-56: C-57. Unpub- lished study
prepared by Schering AG. 83 p.
42089805 Forster, V. (1990) W-83, Formetanate Hydrochloride: The Sorption of
Formetanate Hydrochloride on German Standard Soils 2.1 and 2.3 and
Schering Soils 175 and 179: Lab Proj ect Number: 62/90-PA 10 970.7/18.
Unpublished study prepared by Schering AG. 40 p.
Vukich, J. (1991) Formetanate Hydrochloride: Preliminary Discussion of
Proposed Alternative Manufacturing Process: Lab Project Numb- er.
Unpublished study prepared by Nor-Am Chemical Co. 38 p.
42155401 Steib, C.; Muller, T.; Klehr, M.; et al. (1991) Formetanate Hydrochloride:
Product Chemistry: Lab Proj ect Number: C-53: C-61: C-8. Unpublished study
prepared by Schering Ag. 306 p.
42155402 Steib, C.; Muller, T.; Lehne, V. (1991) Formetanate Hydrochloride: Product
Chemistry: Lab Proj ect Number: C-62: C-65: C-59. Unpublished study
prepared by Schering Ag. 153 p.
42155403 Brehm, M. (1991) W67, Addendum 1-Formetanate-HCL: Photodegradation
of Formetanate Hydrochloride (...) on Soil Surfaces: Lab Proj ect Number:
00164331. Unpublished study prepared by Schering Ag. 28 p.
Page 44 of 64
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42306601 Sved, D.; Smith, G. (1992) Formetanate Hydrochloride: a 96-Hour Shell
Deposition Test with the Eastern Oyster (Crassostrea virginica): Final Report:
Lab Project Number: 244A-103: W-90. Unpublished study prepared by
Wildlife Intl. 41 p.
42664401 Wason, S. (1992) Investigational Study into the Effects on Acetylo-
cholinesterase in the Rat following Treatment for 3 Months: T97
Formetanate: Technical Formetanate Hydrochloride: Lab Project Nos.
020901: TOX/91/197-71: 91/197-71. Unpublished study pre- pared by
Schering Agrochemical Ltd. 77 p.
42664406 Bowman, M. (1992) Testing of Formetanate HCL (R187) through U.S. FDA
Multiresidue Methods: U.S.A., 1992: Lab Project Number: MCB-NOR-
AM/MR-5: Y-92R-03. Unpublished study prepared by M.C. Bowman &
Associates. 76 p.
42664407 Wrede-Rucker, A. (1992) Stability of Formetanate X HCL and its Metabolite
ZK 10 714 during Deep Freeze Storage in Peaches: Interim Report: (R191
Formetanate HCL): Lab Project Number: U/R 43/92: 020906: PF-R 92 029.
Unpublished study prepared by Schering AG. 27 p.
42664408 Wrede-Rucker, A. (1992) Stability of Formetanate HCL and its Metabolite
ZK 10714 during Deep Freeze Storage in Apples: Interim Report: (R191
Formetanate HCL): Lab Project Number: U/R/ 45/92: 020907. Unpublished
study prepared by Schering AG. 27 p.
42664410 Brady, S. (1992) At-harvest Formetanate-derived Residues in or on
Nectarines following Treatment with Carzol SP (Aerial and Ground) at
Maximum Use Rates: USA, 1991: Lab Project Number: Y-91R-01.
Unpublished study prepared by NOR-AM Chemical Co. 42 p.
42664414 Reynolds, C. (1993) The Nature of the Residues of Formetanate HCL in the
Edible Tissues and Milk of a Cow following Oral Administration for 7 days at
a Dose Equivalent of 30 ppm in the Diet: Lab Project Number: TOX 92/197-
76: 020910: TOX 91044. Unpublished study prepared by Schering
Agrochemical Ltd. 170 p.
42664417 Reynolds, C. (1992) The Excretion and Distribution of Formetanate HCL and
its Metabolites in the Laying Hen following Daily Oral Administration at a
Dose Rate Equivalent to 10 ppm in the Diet: Lab Project Number: TOX
92/197-74: 020911: TOX 91045. Unpublished study prepared by Schering
Agrochemical Ltd. 27 p.
42684601 O'Boyle, F. (1993) M-18: The Distribution and Excretion of Radiolabelled
Residues in the Rat Following Oral Dosing with (carbon 14)-Formetanate
Hydrochloride at 10 mg/kg Body Weight: Lab Project Number: TOX/92/197-
75: TOX 91043A: M-18. Unpublished study prepared by Schering
Agrochemicals Ltd. 16 p.
42684602 Elson, L. (1993) M-17: The Metabolism of Formetanate HC1 in the Rat: Lab
Page 45 of 64
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Project Number: SMS 437A/921189: TOX 91043: TOX/92/197-78.
Unpublished study prepared by Huntingdon Research Center, Ltd. 65 p.
42684603 O'Boyle, F. (1993) M-24: The Metabolism of Formetanate Hydrochloride in
the Rat Following Oral Dosing at 10 mg/kg Body Weight: Lab Project
Number: TOX/93/197-79: TOX/91330: M-24. Unpublished study prepared
by Schering Agrochemicals Ltd. 60 p.
42684604 Girkin, R. (1993) M-25: The Metabolism of Formetanate Hydrochloride in
the Rat Following Dosing with (carbon 14)-Formetanate Hydrochloride at 0.1
mg/kg Body Weight: Lab Project Number: SMS 437B/930480: TOX 91043:
M-25. Unpublished study prepared by Huntingdon Research Center, Ltd. 49
P-
42841001 Mansell, P. (1993) Technical Formetanate HC1: Bobwhite Quail Dietary
Reproduction and Tolerance Studies: Lab Project Number: SMS 351: SMS
309/93057: TOX 91041. Unpublished study prepared by Huntingdon
Research Center, Ltd. 263 p.
42841002 Mansell, P. (1993) Technical Formetanate HC1: Mallard Duck Dietary
Reproduction and Tolerance Studies: Lab Project Number: SMS 352: SMS
310/930571: TOX 91040. Unpublished study prepared by Huntingdon
Research Center, Ltd. 216 p.
42723601 Scheuermann, H. (1990) Stability of Formetanate X HC1 in Alfalfa during
Deep Freeze Storage: Lab Project Number: UPSR 56/90: 4010. Unpublished
study prepared by Schering AG. 20 p.
42983201 Williams, L. (1993) Testing of Formetanate.HCL Through Protocol A of US
FDA Multiresidue Methods: Lab Project Number: Y-92R-08. Unpublished
study prepared by NOR-AM Chemical Co. 26 p.
42909701 O'Boyle, F.; Elson, L.; Girkin, R. (1993) Supplement 1: Metabolism of
Formetanate Hydrochloride in the Rat: Lab Project Number: M-18: M-17: M-
24. Unpublished study prepared by NOR-AM Chemical Co. 34 p.
42980601 Kelly, L; Schupner, J. (1993) Formetanate W-91, Supplement 1: The Toxicity
of Formetanate-HCL Early Life Stages of Fathead Minnow, Pimephales
promelas, in a Flow Through System: Lab Project Number: 501Y.
Unpublished study prepared by NOR-AM Chemical Co. 32 p.
43034002 Bruhl, R. (1986) W65-Formetanate HC1: Mobility of Formetanate
Hydrochloride in a Sandy Loam After Aging (Schering Soil No. 152): Lab
Project Number: UPSR 26/86-PA 36 056: 26/86-PA 36 056.73/6.
Unpublished study prepared by Schering Ag. 23 p.
43170401 Smith, S. (1994) Uptake of (carbon 14)-Formetanate Residues in Soil by
Rotational Crops under Confined Conditions: Lab Project Number: 503Y.
Unpublished study prepared by Nor-Am Chemical Co. 167 p.
43228701 Fischer, R.; Young, B.; Schupner, J. (1994) Supplement 2: A Daphnia magna
Page 46 of 64
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21-Day Reproduction Study of Formetanate-HCl Technical in a Flow
Through System: Lab Project Number: 500 Y. Unpublished study prepared by
NOR-AM Chemical Co. 8 p.
43329001 Reynolds, C. (1994) The Nature of Residues of Formetanate HC1 in the
Edible Tissues and Milk of a Cow Following Oral Administration for 7 Days
at a Dose Equivalent of 30 ppm in the Diet: Ml9-Addendum 1: Lab Project
Number: TOX/92/197/76. Unpublished study prepared by Schering
Agrochemicals Ltd. 99 p.
43329002 O'Boyle, F. (1994) The Nature of Residues of Formetanate HC1 in the Edible
Tissues of the Laying Hen Following Oral Administration for 14 Days at a
Dose Equivalent to 10 ppm in the Diet: M20-Addendum 1: Lab Project
Number: TOX/92/197/77'. Unpublished study prepared by Schering
Agrochemicals Ltd. 69 p.
43329003 Czochor, L. (1994) Response to EPA Review of Formetanate Hydrochloride
Storage Stability Data Base. Unpublished study prepared by AgrEvo USA
Co. 17 p.
43384401 Wrede, A. (1994) Formetanate HC1 R165-Addendum to Report: Residues of
Formetanate x HC1 and Major Metabolites in Citrus Following Application of
CARZOL 92 SP in the USA 1988: Lab Project Number: UPSR 89/88: PF-
R88056. Unpublished study prepared by Schering AG and Hoechst Schering
AgrEvo GmbH. 13 p.
43384405 Wrede, A. (1994) Formetanate HC1 Rl 79-Addendum to Report: Residues of
Formetanate x HC1 and Major Metabolites in Citrus Following Application of
CARZOL 92 SP in the USA 1989: Lab Project Number: UPSR 11/90: PF-
R90007. Unpublished study prepared by Schering AG and Hoechst Schering
AgrEvo GmbH. 13 p.
43489402 Cichy, M. (1994) Formetanate Hydrochloride: Description of Beginning
Materials and Manufacturing Process: Report Number C73: Lab Project
Number: 94/030. Unpublished study prepared by Hoechst Schering AgrEvo
GmbH. 59 p.
43489404 Cichy, M. (1994) Formetanate Hydrochloride: Discussion of the Formation of
Impurities: Report Number C74: Lab Project Number: 94/034. Unpublished
study prepared by Hoechst Schering AgrEvo GmbH. 19 p.
43489407 Mueller, H.; Laass, H.; Cichy, M. (1994) Formetanate Hydrochloride-
Preliminary Analysis of 5 Product Samples: Report Number C72 and
Amendment: Lab Project Number: 94 02420 55: 94/029. Unpublished study
prepared by Hoechst Schering AgrEvo GmbH. 28 p.
43489408 Repenthin, W. (1994) Determination of the Total Content of N-Nitroso
Compounds in Formetanate-HCl: Report Number C75: Lab Project Number:
AZ 205 340: SPA 05/94. Unpublished study prepared by Schering AG. 31 p.
Page 47 of 64
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43583101 Smith, S.; Meyer, B. (1994) Uptake of Residues of (Carbon 14)-Formetanate
Residues in Soil by Rotational Crops Under Confined Conditions: Addendum
1 to Report: Lab Project Number: 503 Y. Unpublished study prepared by
AgrEvo USA Co. 95 p.
43610401 Wrede, A. (1995) Stability of Formetanate x HC1 and Its Metabolite ZK
10714 During Deep Freeze Storage of 33 Months in Apples: Lab Project
Number: PF-R 92061: R216: R/V41/94.3/16. Unpublished study prepared by
Hoechst Schering AgrEvo GmbH. 75 p.
43610403 Wrede, A. (1995) Stability of Formetanate x HC1 and Its Metabolite ZK
10714 During Deep Freeze Storage of 2 Years in Citrus Peel and Citrus Flesh:
Lab Project Number: PF-R 92030: R218: R/V 40/94-PA 10 970.3/16.
Unpublished study prepared by Hoechst Schering AgrEvo GmbH. 87 p.
44054800 AgrEvo USA Co. (1996) Submission of Environmental Fate Data in Support
of Reregi strati on Data Call-In for Formetanate Hydrochloride. Transmittal of
1 Study.
44151201 Cole, M. (1996) Dissipation of Foliar Dislodgeable Residues of Formetanate
Hydrochloride Following Application of Carzol SP to Apples and Citrus,
USA, 1995: (Interim Report): Lab Project Number: U044/R742: Y-94R-03:
95519. Unpublished study prepared by AgrEvo USA Co. 121 p.
44948501 McAlinden, D. (1999) Rat 21-Day Dermal Toxicity Study Formetanate
Hydrochloride: Lab Project Number: TOX 98178: C004820: TOX/99/197-87.
Unpublished study prepared by Quintiles England Ltd. 384 p. (OPTS
870.3200}
45314201 Beyrouty, P. (2000) Rat Acute Oral Neurotoxicity Study: Formetanate
Hydrochloride: Lab Project Number: 97553: TOX20009. Unpublished study
prepared by ClinTrials BioResearch Ltd. 519 p. (OPPTS 870.6200}
45314202 Beyrouty, P. (2000) Rat 13-Week Dietary Neurotoxicity Study: Formetanate
Hydrochloride: Lab Project Number: 97554: TOX20010. Unpublished study
prepared by ClinTrials BioResearch Ltd. 526 p. {OPPTS 870.6200}
46618901 Barnett, J. (2005) Oral (Gavage) Acute Relative Sensitivity Study of
Formetanate HC1 in Neonatal and Adult Rats: Final Report. Project Number:
WJI00007, WJI00005, WJI00006. Unpublished study prepared by Charles
River Laboratories. 648 p.
Page 48 of 64
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E. Generic Data Call-In
Note that the complete generic Data Call-In (DCI), with all pertinent instructions,
will be sent to registrants under separate cover.
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F. Product-Specific Data Call-In
Note that the complete product-specific Data Call-In (DCI), with all pertinent
instructions, will be sent to registrants under separate cover.
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G. EPA's Batching of Formetanate HC1 Products for Meeting Acute Toxicity
Data Requirements for Reregistration
The Agency has determined that batching is not needed for formetanate HC1 due
to the low number of products.
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H. List of Registrants Sent Data Call-Ins
A list of registrants sent this data-call in will sent at a later date.
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I. List of Available Related Documents and Electronically Available Forms
Pesticide Registration Forms are available at the following EPA internet site:
http://www.epa.gov/opprd001/forms
Pesticide Registration Forms (these forms are in PDF format and require the
Acrobat reader)
Instructions
1. Print our and complete the forms. (Note: Form numbers that are bolded
can be filled out on your computer than printed.)
2. The completed form(s) should be submitted in hardcopy in accord with the
existing policy.
3. Mail the forms, along with any additional documents necessary to comply
with EPA regulations covering your request, to the address below or 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 email atwilliams.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
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 (in PR
Notice 98-5)
http://www.cpa.aov/opprd001/rorms/8570-l.pdf
http://www.cpa.aov/opprd001/romis/8570-4.pdf
http://www.epa.gov/opprd001/fornis/8570-5.pdf
http : //www . epa. aov/o pprdOO 1 /forms/8 5 70 - 1 7 . pdf
http://www.epa.gov/opprd001/rorms/8570-25.pdr
http://www.epa.gov/opprdOO l/fornis/8570-27. pdf
http : //www .epa. gov/o pprdOO 1 /f orms/8 5 70 -2 8 . pdf
http://www.cpa.gov/opprd001/rorms/8570-30.pdr
http://www.cpa.gov/opprd001/romis/8570-32.pdr
http://www.cpa.gov/opppmsdl/PR Notices/pr98-
5.pdf
Page 5 3 of 64
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8570-35
8570-36
8570-37
Data Matrix (in PR Notice 98-5)
Summary of the Physical/Chemical Properties (in PR
Notice 98-1)
Self-Certification Statement for the Physical/Chemical
Properties (in PR Notice 98-1)
http ://www . epa. gov/o pppmsd 1 /PR N otice s/pr9 8 -
http ://www .epa. gov/o pppmsd 1 /PR N otice s/pr9 8 -
Ij2df
http ://www .epa. gov/o pppmsd 1 /PR N otice s/pr9 8 -
Ij2df
Pesticide Registration Kit:
Dear Registrant:
For your convenience, we have assembled an online registration kit that 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 httrj7/www^erja.goy/ojrjrjrnsdJ/p_R_J^ojicgs.
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
Page 54 of 64
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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
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' Web Site
2. The booklet "General Information on Applying for Registration of Pesticides
in the United States", PB92-221811, available through the National Technical
Information Service (NTIS) 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. Please note that EPA is
currently in the process of updating this booklet to reflect the changes in the registration
program resulting from the passage of the FQPA and the reorganization of the Office of
Pesticide Programs. We anticipate that this publication will become available during the
Fall of 1998.
3. The National Pesticide Information Retrieval System (NPIRS) of Purdue
University's Center for Environmental and Regulatory Information Systems.
This service does charge a fee for subscriptions and custom searches. You can
contact NPIRS by telephone at (765) 494-6614 or through their Web site.
4. The National Pesticide Telecommunications Network (NPTN) can provide
information on active ingredients, uses, toxicology, and chemistry of
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pesticides. You can contact NPTN by telephone at (800) 858-7378 or through
their Web site: 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:
Date of receipt
EPA identifying number
Product Manager Assignment
Other identifying information may be included by the applicant to link the
acknowledgment of receipt to the specific application submitted. EPA will stamp the date
of receipt and provide the EPA identifying File Symbol or petition number for the new
submission. The identifying number should be used whenever you contact the Agency
concerning an application for registration, experimental use permit, or tolerance petition.
To assist us in ensuring that all data you have submitted for the chemical are properly
coded and assigned to your company, please include a list of all synonyms, common and
trade names, company experimental codes, and other names which identify the chemical
(including "blind" codes used when a sample was submitted for testing by commercial or
academic facilities). Please provide a CAS number if one has been assigned.
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