United States Prevention, Pesticides EPA 738-R-06-006
Environmental Protection And Toxic Substances June 2006
Agency (7508C)
xvEPA
Re registration Eligibility
Decision for N-Octyl
bicycloheptene
(MGK-264)
ListB
Case No. 2430
-------
Reregistration Eligibility Decision (RED) Document
for
N-Octyl bicycloheptene dicarboximide
(MGK-264)
Approved by: /S/
Debra Edwards, Ph.D.
Director
Special Review and Reregistration
Division
Date: June 26. 2006
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TABLE OF CONTENTS
Executive Summary 7
I. Introduction 12
II. Chemical Overview 13
A. Regulatory History 13
B. Chemical Identification 13
C. Use Profile 14
III. Summary of MGK-264 Risk Assessments 16
A. Human Health Risk Assessment 16
1. Toxicity Profile 16
2. Dietary Risk 21
3. Drinking Water 22
4. Residential Exposure and Risk 24
5. Aggregate Risk 30
6. Occupational Risk 34
IV. Risk Management, Reregistration, and Tolerance Reassessment Decision 40
A. Determination of Reregistration Eligibility and Tolerance Reassessment 40
B. Regulatory Position 40
1. Food Quality Protection Act Findings 41
2. Endocrine Disrupter Effects 42
3. Cumulative Risks 42
C. Tolerance Reassessment Summary 43
D. Regulatory Rationale 46
1. Human Health Risk 46
2. Non-Target Organism (Ecological) Risk Management 53
V. What Registrants Need to Do 56
A. Manufacturing Use Products 56
1. Additional Generic Data Requirements 56
2. Labeling Requirements 58
3. Spray Drift Management 58
B. End-Use Products 58
1. Additional Product-Specific Data Requirements 58
2. Labeling for End-Use Products 58
Appendix: Technical Support Documents 80
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MGK-264 Reregistration Eligibility Decision Team
Office of Pesticide Programs:
Environmental Fate and Effects Risk Assessment
Michael Davy
William Eckel
Richard Lee
Health Effects Risk Assessment
William Donovan (Risk Assessor)
John Doherty
Steve Weiss
Biological and Economic Analysis Division
Alan Halvorson
Nikhil Mallampalli
Registration
Richard Gebken
Mark Suarez
Kevin Sweeney
Risk Management
Cathryn O'Connell
Tom Myers
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Glossary of Terms and Abbreviations
AGDCI
ai
aPAD
AR
BCF
CFR
cPAD
CSF
CSFII
DCI
DEEM
DFR
DWLOC
EC
EDWC
EEC
EPA
EUP
FDA
FIFRA
FFDCA
FQPA
FOB
G
GENEEC
GLN
HAFT
IR
LC50
LD50
LOC
LOD
LOAEL
MATC
ug/L
mg/kg/day
mg/L
MOE
MRID
MUP
NA
NAWQA
NPDES
NR
NOAEL
OP
Agricultural Data Call-In
Active Ingredient
Acute Population Adjusted Dose
Anticipated Residue
Bioconcentration Factor
Code of Federal Regulations
Chronic Population Adjusted Dose
Confidential Statement of Formula
USDA Continuing Surveys for Food Intake by Individuals
Data Call-In
Dietary Exposure Evaluation Model
Dislodgeable Foliar Residue
Drinking Water Level of Comparison.
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
Functional Observation Battery
Granular Formulation
Tier I Surface Water Computer Model
Guideline Number
Highest Average Field Trial
Index Reservoir
Median Lethal Concentration. A statistically derived concentration of a substance that
can be expected to cause death in 50% of test animals. It is usually expressed as the
weight of substance per weight or volume of water, air or feed, e.g., mg/1, mg/kg or ppm.
Median Lethal Dose. A statistically derived single dose that can be expected to cause
death in 50% of the test animals when administered by the route indicated (oral, dermal,
inhalation). It is expressed as a weight of substance per unit weight of animal, e.g.,
mg/kg.
Level of Concern
Limit of Detection
Lowest Observed Adverse Effect Level
Maximum Acceptable Toxicant Concentration
Micrograms Per Gram
Micrograms Per Liter
Milligram Per Kilogram Per Day
Milligrams Per Liter
Margin of Exposure
Master Record Identification (number). EPA's system of recording and tracking studies
submitted.
Manufacturing-Use Product
Not Applicable
USGS National Water Quality Assessment
National Pollutant Discharge Elimination System
Not Required
No Observed Adverse Effect Level
Organophosphate
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OPP
OPPTS
PAD
PCA
PDF
PHED
PHI
ppb
PPE
ppm
PRZM/EXAMS
Qi*
RAC
RED
REI
RfD
RQ
SCI-GROW
SAP
SF
SLC
SLN
TCPSA
TGAI
TRR
USDA
USGS
UF
UV
WPS
EPA Office of Pesticide Programs
EPA Office of Prevention, Pesticides and Toxic Substances
Population Adjusted Dose
Percent Crop Area
USDA Pesticide Data Program
Pesticide Handler's Exposure Data
Preharvest 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 EP A's Cancer Risk Model
Raw Agriculture Commodity
Reregistration Eligibility Decision
Restricted Entry Interval
Reference Dose
Risk Quotient
Tier I Ground Water Computer Model
Science Advisory Panel
Safety Factor
Single Layer Clothing
Special Local Need (Registrations Under Section 24(c) of FIFRA)
2,3,3-trichloroprop-2-ene sulfonic acid (nitrapyrin Metabolite)
Technical Grade Active Ingredient
Total Radioactive Residue
United States Department of Agriculture
United States Geological Survey
Uncertainty Factor
Ultraviolet
Worker Protection Standard
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Executive Summary
EPA has completed its review of public comments on the human health and
environmental risk assessments and is issuing its reregi strati on eligibility and tolerance
reassessment decisions for MGK-264. There are currently 8 tolerances being reassessed for
MGK-264. EPA will accept public comments on these decisions and the supporting documents
for 60 days. The revised risk assessments and response documents are based on comments
submitted, information from the technical registrant (MGK Company), and other information
provided to EPA. After considering the risks identified in the revised risk assessments,
comments and mitigation suggestions, EPA developed its risk management decision for uses of
MGK-264 that posed risks of concern. As a result, the Agency has determined MGK-264-
containing products are eligible for reregi strati on provided that risk mitigation measures are
adopted, and labels are amended accordingly.
MGK-264 was first registered in the late 1940's and acts as a synergist. Synergists are
chemicals that primarily enhance the pesticidal properties of other active ingredients, such as
pyrethrins and synthetic pyrethroids. MGK-264 is a registered active ingredient in approximately 650
products used to control many different types of flying and crawling insects and arthropods, although
there are no products that contain only MGK-264. It is registered for use in residential, commercial,
and industrial sites. No agricultural crop uses of MGK-264 are being supported, and MGK-264 is
not used in wide area mosquito abatement programs. Less than 300,000 pounds of MGK-264
are sold every year.
Overall Risk Summary
Dietary Risk (Food and Drinking Water)
Acute dietary (food only) risk does not exceed the Agency's level of concern; acute
dietary risk estimates are 13% of the aPAD for females 13 to 49 years old, the only sub-
population that needed to be assessed, because developmental toxicity was the sole endpoint
attributable to a single dose in the available toxicology database.
The chronic dietary (food only) risk is below the Agency's level of concern; risk
estimated are 19% cPAD for the general U.S. population, and 51% of the cPAD for children 1-2
years old, the most exposed sub-population.
The acute and chronic analyses were conducted using maximum and average residue
levels, respectively, from applicable field trials and assumed all food commodities were treated.
Acute and chronic drinking water levels of concern (DWLOCs) were calculated based on
dietary exposure estimates, default body weight and water consumption figures. The estimated
drinking water concentrations (EDWCs) for both surface water and ground water are well below
both the acute and chronic DWLOCs, indicating that combined exposure to MKG-264 in food
and water is not a concern.
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Residential
In the residential handler exposure assessment a number of scenarios were assessed to
estimate the exposure to homeowners handling products containing MGK-264. The results from
the assessed residential handler scenarios indicate there are no residential risks of concern when
MGK-264 is mixed, loaded, applied, or handled by homeowners. Applying dips with MGK-264
to pets was not assessed because there were no application exposure data available. Based on
high risk estimates from a pet shampoo study, there are no interim mitigation measures for
applicators making dips to pets. However, confirmatory applicator exposure data will be
required for pet dip applications.
A number of post-application residential scenarios were assessed for adults and children
exposed to MGK-264 indirectly after application. There were post-application risk concerns for
the following scenarios: 1) indoor spray applications; 2) broadcast dust applications to carpets; 3)
aerosol space sprays indoors; 4) dust applications to pets; 5) insect repellents; and 6) applications
from indoor metered release devices. To address the potential risks associated with these post-
application scenarios, MGK Company has agreed to limit carpet dust applications to spot
treatments only, conduct an aerosol space spray study with MGK-264 at the reduced label rate
and amended application instructions, phase out all dust products applied to pets, and add
additional label language and use restrictions to address potential by-stander risks from products
used in metered release devices. The registrant is conducting a repeat 21-day dermal toxicity
study to the limit dose which will be used to refine the dermal risk assessments. MGK Company
has agreed to prohibit the use of metered release devices in residential indoor areas and remove
the following use sites from their metered release device product labels: day care centers,
nursing homes, schools, and hospitals. MGK Company is not supporting the use of residential
misting systems and labels will be updated to prohibit the use of MGK-264 in these systems.
After evaluating both the hazard and exposure data for MGK-264, EPA reduced the
FQPA safety factor to IX due to the low degree of concern for the fetal susceptibility effects and
no evidence of residual uncertainties for pre- or post-natal toxicity. There were no residual
uncertainties for potential exposures to infants and children.
Aggregate Risk
As noted above, acute and chronic aggregate risk assessments were conducted for exposure
to MGK-264 in food and drinking water and did not indicate risks of concern. The short-term
aggregate exposures from food, water, and residential (incidental oral) routes associated with
application of PBO were also estimated since there is a common toxicity endpoint of slight
decreases in pup body weight identified for these routes of exposure.
The short term aggregate risk for MGK-264 was estimated by comparing model based
EDWCs to DWLOCs, where were determined by adding exposure estimates from food, drinking
water, dermal, and incidental oral exposure pathways for the U.S. population and the highest
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exposed sub-population, children 1-2 years old. The lowest short term DWLOC (38 |ig/L) for
children 1-2 years old is higher than the surface water EDWC (5.2 ppb) and the ground water
EDWC (0.12 ppb), and therefore does not result in a risk of concern.
Cumulative
The Food Quality Protection Act (FQPA) requires that the Agency consider available
information concerning the cumulative effects of a particular pesticide and other substances that
have a common mechanism of toxicity. Unlike other pesticides for which EPA has followed a
cumulative risk approach based on a common mechanism of toxicity, EPA has not made a
common mechanism finding as to MGK-264 and any other substances, and MGK-264 does not
appear to produce a toxic metabolite produced by other chemicals. Therefore, for the purposes
of this tolerance reassessment action, EPA has assumed that MGK-264 does not have a common
mechanism of toxicity with other substances.
Occupational Risks
Occupational exposure assessments were completed by the Agency considering the use
of baseline PPE and, if warranted, for handlers, increasing levels of PPE and engineering
controls in order to estimate the potential impact on exposure and risk. The target MOE for
MGK-264 is 1,000 for both dermal and inhalation exposures due to the lack of a no observable
adverse effect level (NOAEL) in both studies selected for risk assessment. Of the handler
scenarios assessed, two were potentially of concern assuming baseline clothing. These include:
1) applying MGK-264 with a handheld foggers indoors; and 2) applying dusts through power
duster equipment. Pet dips and bulb duster applications were not assessed due to lack of data.
Based on a shampoo scenario the Agency does not believe there will be risks of concern with
applicators using pet dips, and exposure data will be required to confirm this assumption. The
exposure from bulb dusters is not a concern for the Agency due to small amounts of dust used in
this application method; the exposure is expected to be negligible. No additional data or risk
assessments are required for bulb dusters.
There were potential post-application risks for products used in metered release devices
which are commonly used in dairy barns and other sites. EPA believes that the potential post-
application risks are lower for people working in these settings than for residential settings due to
the fact that the occupational areas generally have a greater ventilation capacity. To better
understand the risks from metered release devices in occupational settings the Agency is
requesting additional usage information about the metered release device products.
Ecological Risks
In the ecological risk assessment for MGK-264, applications to turf, ornamentals, and
lawns were considered the most likely use patterns that could lead to exposure to non-target
organisms in the environment. The maximum use rate considered in the risk assessment was 2.2
Ibs a.i./acre for lawn insect control. Since the ecological assessment was completed, MGK
Company has reduced the outdoor spray application rate from 2.2 Ibs a.i./acre to 0.3 Ibs a.i./acre.
This significant reduction in rate decreases the RQs predicted in the risk assessment, and results
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in the majority of RQs for aquatic and terrestrial organisms being below the Agency's level of
concern.
Summary of Mitigation Measures
EPA has determined that the currently registered uses of MGK-264 are eligible for
reregi strati on provided the mitigation measures outlined in this document are implemented
through label amendments. Mitigation measures include:
Residential
• Restrict carpet dust applications to only spot treatments.
• Reduce the rate for aerosol space sprays from 0.001 Ib ai/1,000 ft3 to 0.00015 Ib ai/1,000 ft3
and conduct an aerosol spray study with MGK-264 while following the label specifications
that include a ventilation period of 15 minutes.
• Areas where sensitive populations are present, including day-care centers, nursing homes,
schools and hospitals, will be removed from product labeled for use in metered release
devices. In addition, the use of products in metered release devices in all other residential
areas are prohibited unless required exposure data indicate risks are acceptable.
• Prohibit use of outdoor residential misting systems for MGK-264.
• Phase out all dust products used on pets.
Occupational
• Require applicators using handheld equipment such as handwand, backpack sprayers, or
handgun equipment to wear gloves.
• Require applicators fogging indoors to wear double layers with a respirator.
• Prohibit power dusters as an application method.
Ecological
• Reduce the outdoor spray application rate from 2.2 Ibs a.i./acre to 0.3 Ibs a.i./acre.
Additional rate changes for MGK-264:
Use
General outdoor spray applications
General crack and crevice or spot
spray applications
Ready-to-use trigger pump spray
applications
General surface spray applications
Direct applications of solution to
livestock
Ready-to-use wipe applications to
horses
Old maximum
rate/formulation
2.2 Ib ai/A (0.05 Ib ai/1,000
square feet)
1.6 Ib ai/1,000 ft2
1.6 Ib ai/1,000 ft2
0.4 Ib ai/1,000 ft2
0.2 Ibai/gal
0.00018 Ibai/wipe
New maximum rate/formulation
0.3 Ib ai/A
0.05 Ib ai/1,000 ft2
0. lib ai/1,000 ft2 with the
maximum concentration at 0.5%
0.0 lib ai/1,000 ft2
2 oz of 0.2% spray /animal
(0.00025 Ib ai/animal)
0.0000826 Ib ai/wipe (-37.5 mg
ai/wipe)
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Use
Indoor surface spray applications
Indoor space spray applications with
aerosol can
Dust application to pets
Application of insect repellants
Ready-to-use (RTU) pet collars
RTU aerosol spray can applications
Direct application to pets
RTU paste applications to horses
Dust applied to carpeted and other
indoor surfaces
Metered release products
Surface sprays to pet premises
Aerosol Space Sprays
Old maximum
rate/formulation
0.4 Ib ai/100 ft2
0.006 Ib ai/1,000 ffi
10% product
8% product
NA
NA
NA
NA
NA
NA
NA
NA
New maximum rate/formulation
0.01 Ib ai/1,000 ft2
0.001 Ib ai/1,000 ft3
Voluntary Cancel Use of Dusts on
Pets
5% product
0.0022 Ib ai/per collar
0.01771bai/16ozcan
0.0028 Ib ai/pet
0.0056 Ibs ai per horse
0.011 Ib ai/100 ft2 (and restriction
to spots 3 feet squared)
1.77 mg ai/spray event and
0.002 Ibs ai/1000 cubic feet / day
0.0 lib ai/100 ft2
0.00015 Ib ai/1,000 ft3
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I. Introduction
The Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) was amended in 1988
to accelerate the reregistration of products with active ingredients registered prior to November
1, 1984. The amended Act calls for the development and submission of data to support the
reregistration of an active ingredient, as well as EPA review of all submitted data. Reregistration
involves a thorough review of the scientific database underlying a pesticide's registration. The
purpose of the Agency's review is to reassess the potential risks arising from the currently
registered uses of the pesticide, to determine the need for additional data on health and
environmental effects, and to determine whether or not the pesticide meets the "no unreasonable
adverse effects" criteria of FIFRA.
On August 3, 1996, the Food Quality Protection Act of 1996 (FQPA) was signed into
law. This Act amends FIFRA to require reassessment of all tolerances in effect on the day
before it was enacted. 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 risks are
not of concern and concludes that there is a reasonable certainty of no harm from aggregate
exposure, the tolerances are considered reassessed. EPA decided that, for those chemicals that
have tolerances and are undergoing reregistration, tolerance reassessment will be accomplished
through the reregistration process.
The Food Quality Protection Act (FQPA) requires that the Agency consider available
information concerning the cumulative effects of a particular pesticide's residues and other
substances that have a common mechanism of toxicity. The reason for consideration of other
substances is due to the possibility that low-level exposures to multiple chemical substances that
cause a common toxic effect by a common toxic mechanism could lead to the same adverse
health effect as would a higher level of exposure to any of the substances individually. Unlike
other pesticides for which EPA has followed a cumulative risk approach based on a common
mechanism of toxicity, EPA has not made a common mechanism of toxicity finding as to N-
octyl bicycloheptene dicarboximide (MGK-264) and any other substances. For the purposes of
this tolerance action, therefore, EPA has not assumed that MGK-264 has a common mechanism
of toxicity with other substances. For information regarding EPA's efforts to determine which
chemicals have a common mechanism of toxicity and to evaluate the cumulative effects of such
chemicals, see the policy statements released by EPA's Office of Pesticide Programs concerning
common mechanism determinations and procedures for cumulating effects from substances
found to have a common mechanism on EPA's website at
http://www.epa.gov/pesicides/cumulative/.
The Agency made its reregistration eligibility determination based on the required data,
the current guidelines for conducting acceptable studies to generate such data, and published
scientific literature. The Agency has found that currently registered uses of MGK-264 are
eligible for reregistration provided the mitigation and labeling outlined in the RED are
implemented. The document consists of six sections: Section I, the introduction, contains the
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regulatory framework for reregistration/tolerance reassessment; Section II provides an overview
of the chemical, including a profile of its use and usage; Section III gives an overview of the
human health and environmental effects risk assessments; Section IV presents the Agency's
reregi strati on eligibility, tolerance reassessment, and risk management decisions; Section V
summarizes label changes necessary to implement the risk mitigation measures outlined in
Section IV; and Section VI includes the appendices, related supporting documents and Data Call-
in (DCI) information. The revised risk assessment documents and related addenda are not
included in this document, but are available on the Agency's web page
http://www.epa.gov/pesticides, and in the Public Docket under docket number EPA-HQ-OPP-
2005-0040.
II. Chemical Overview
A. Regulatory History
MGK-264 is a pesticide active ingredient that is classified as a synergist. Synergists are
chemicals which, while lacking pesticidal properties of their own, enhance the pesticidal
properties of other active ingredients. MGK-264 was first registered in the United States in the
late 1940s. Currently there are approximately 650 end-use products registered in the United
States containing MGK-264 as a synergist. There are 8 tolerances for MGK-264 listed in the
Code of Federal Regulations. The reregi strati on of MGK-264 is being supported by the
technical registrant, McLaughlin Gormely King Company.
MGK-264 is the only active ingredient in List B reregi strati on case 2430. A Phase IV
Data Call-In was issued for MGK-264 in June of 1991. This DCI mainly required ecological and
environmental fate data. An agricultural re-entry DCI was issued in October of 1995.
This Reregi strati on Eligibility Decision document evaluates risks from all currently
registered uses of MGK-264.
B. Chemical Identification
MGK-264 is a FIFRA List B pesticide active ingredient classified as a synergist. As a
synergist, MKG-264 works by inhibiting the detoxification of other pesticides by the insect
pests.
Table 1: MGK-264 Nomenclature
Chemical Structure
Empirical Formula
0
0
C17H25N02
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Common name
EPA PC Code
IUPAC name
CAS name
CAS Registry Number
Chemical Class
N-octylbicycloheptene dicarboximide, MGK-264
057001
N-(2-ethylhexyl)-8,9,10-trinorbom-5-ene-2,3-dicarboximide
4,7-Methano-lH-isoindole-l,3(2H)-dione, 2-(2-ethylhexyl)-3a,4,7,7a-tetrahydro-
113-48-4
Dicarboximide
Table 2; Physicochemical Properties of MGK-264
Parameter
Melting point/range
Molecular Weight
Boiling point/range
PH
Density
Water solubility
Solvent solubility
Vapor pressure
Dissociation constant (pKa)
Octanol/water partition coefficient
Log(Kow)
UV/visible absorption spectrum
Value
N/A
275
155-161ECatlmmHg.
6.9; typical range of 6.8 to 7.2
1.049 + 0.003 g/mL at 20°C
15 + 3|ig/mLat25°C
Miscible in: Acetone, Methanol,
Isopropanol, Petroleum Ether, Concoco LPA
(petroleum distillate), Ethyl Acetate,
Toluene, Chloroform, Acetonitrile, Cyclo
Solv 53 (aromatic petroleum distillate) and
Isopar M (petroleum distillate)
1 .84 + 0.49 x 1CT5 mm Hg at 25°C
N/A
Log P = 3.61 & 3.80 for isomers 1 & 2,
respectively, at 24°C
Data Gap
Reference
Kenneth W. Dockter,
01/07/92: Reregistration of
MGK-264. McLaughlin
Gormley King Product
Chemistry Considerations.
CBRS # 8938; DP Barcode
D171498.
c.
Use Profile
MGK-264 comes in many chemical formulations and is found in numerous end-use
products intended to be used in a wide range of use patterns. MGK-264 is used in combination
with a variety of insecticides such as the natural pyrethrins and synthetic pyrethroids and is an
ingredient in approximately 650 registered products. A Master Label including a list of all uses
supported by the McLaughlin Gormely King Company is available at
http://www.epa.gov/oppsrrdl/reregistration/piperonvl/ucm.pdf. The following is information on the
currently registered uses including an overview of use sites and application methods. A detailed
table of the uses of MGK-264 eligible for reregi strati on is contained in Appendix A.
1. MGK-264 Use Profile
Type of Pesticide: Synergist
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Summary of Use: Commercial uses include application to non-food plants, applications in
food and non-food handling commercial and agricultural structures and
outdoor premises, housing for veterinary and farm animals, and direct
application to veterinary and non-food animals. Residentially, it is used to
control insects both inside the home, as well as outside on gardens, lawns
and ornamentals, patios, and other outdoor structures. No agricultural
crop uses of MGK-264 are being supported, and MGK-264 is not used in
wide area mosquito abatement programs.
Target Organisms: MKG-264 is used with insecticides to target many types of pests,
including various types of ants, worms, beetles, mites, flies, gnats, spiders,
weevils, caterpillars, grubs, moths, ticks, lice, wasps, aphids, midges, and
others.
Mode of Action:
Tolerances:
MGK-264 is known to inhibit microsomal enzymes in insects by binding
directly to these enzymes and thereby inhibiting the breakdown of other
pesticides such as pyrethrins and pyrethroids.
There are currently 8 tolerances established for MGK-264 including six
(6) tolerances for residues in the fat of livestock commodities [40 CFR
180.367(a)(l)], one (1) food-processing use tolerance [40 CFR
180.367(a)(2)(i)], and one (1) exemption when applied to growing crops in
accordance with good agricultural practice [40 CFR 180.905].
Use Classification: General Use
Formulation Types: Liquids, emulsifiable concentrate, dusts, ready-to-use formulations such as
aerosol cans, foggers, trigger pump sprayers, shampoos, pastes, wipes,
metered release devices, insect repellents, and others. MGK-264 is
usually formulated with natural pyrethrins, piperonyl butoxide (PBO)
[another synergist], or synthetic pyrethroids.
Application Methods: Applications to small areas may be made with handheld equipment,
including low-pressure handwand sprayers, high pressure handwand
sprayers, handgun sprayers, hose-end sprayers, thermal misters/foggers,
and with ready-to-use application methods, including pump-trigger
sprayers, foggers, aerosol cans, shampoos, dips, wipes, roll-ons,
impregnated collars, and dust (puffer or shaker) cans.
Application Rates:
Due to the varied number of use sites that MGK-264 is registered to treat,
there is a wide range of application rates that are outlined in detail in the
Use Closure Memo, which can be found at
www.epa.gov/pesticides/reregistration/status.htm. Application rates range
from 0.002 Ibs ai/1,000 ft3 for a space metered release spray to 1.6 Ibs
ai/1,000 ft3 for crack, crevice, or spot surface treatments.
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Usage of MGK-264: Less than 300,000 pounds of MGK-264 are sold every year in the U.S.
III. Summary of MGK-264 Risk Assessments
The following is a summary of EPA's human health and ecological risk findings
conclusions for MGK-264. For more detail on the human health risk assessment, see the Revised
Memo to Incorporate Responses to Phase 5 Public Comments (Donovan, March 20, 2006). For
more detail on the environmental risk assessment, see the Screening Ecological Risk Assessment
for the Reregistration of MGK-264 Insecticide Synergist (Eckel, September 29, 2004).
The purpose of this section is to summarize the key features and findings of the risk
assessment in order to help the reader better understand the Agency's risk management
decisions. The Agency has followed the full 6 phase reregi strati on public participation process
for MGK-264. During this process, two 60-day public comment periods have been completed in
order to allow interested stakeholders to provide feedback on the information and methods
included in the Agency's risk assessments. Since the end of the last 60-day public comment
period, the Agency has responded to the comments received, which are available on the public
docket, along with all of the risk assessments and related addenda pertaining to MGK-264.
These can be accessed through the website, www.regulations.gov, under docket number EPA-
HQ-OPP-2005-0040.
A. Human Health Risk Assessment
The Agency evaluated the toxicology, product and residue chemistry, and
occupational/residential exposure studies submitted and determined that the data are adequate to
support a reregi strati on decision. Details of the risk assessments and separate supporting
disciplinary documents are available in the electronic docket. A summary of the human health
risk assessment findings and conclusions are provided below.
The residues included in the tolerance expression are MGK-264 per se. For further
information on the residue chemistry considerations, see the RevisedN-Octyl bicycloheptene
dicarboximide (MGK-264) Product and Residue Chemistry Considerations, (Donovan,
September 9, 2005).
1. Toxicity Profile
MGK-264 is an insecticide synergist and is incorporated into insecticide formulations to
prevent the breakdown of insecticides by the insect's mixed function oxidase (MFO) system so
the toxic action of the insecticide will be more effective. Data are sufficient to assess all
exposure scenarios and for FQPA evaluation.
Acute Toxicity Profile
MGK-264 is classified as Category IV for acute dermal irritation and Category III for
acute dermal toxicity and eye irritation. No acute inhalation toxicity study or dermal
sensitization study is available. An acute oral study was conducted that indicated toxicity
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Category IV (MRID 41752305), but EPA found the study to be unacceptable because technical
grade MGK-264 was not used (reviewed in memo from M. Lewis, June 16, 2004). See Table 3
below.
Table 3; Acute Toxicity Profile MGK-264
Guideline No.
870.1100
870.1200
870.1300
870.2400
870.2500
870.2600
Study Type
Acute oral - rat
Acute dermal - rabbit
Acute inhalation
Acute eye irritation - rabbit
Acute dermal irritation - rabbit
Skin sensitization
MRID(s)
Results
Toxicity Category
Study unacceptable.
41860601
LD50 > 2 g/kg
III
Study not available.
41860602
92122005
Conjunctival
irritation reversed
by day 7
PDIS= 1.17
III
IV
Study not available.
Subchronic Dermal Toxicity
There was no systemic toxicity demonstrated in the 90-day rabbit dermal toxicity study at
the highest dose tested of 100 mg/kg/day. This study was considered inadequate to establish a
dermal endpoint because animals were not dosed at levels higher than 100 mg/kg/day. These
higher doses might have elicited effects. Therefore, an endpoint for dermal risk assessment was
selected from the 2-generation oral reproduction study in rats, based on offspring effects.
Dermal A bsorption
A study with human volunteers indicated that the dermal absorption factor for MGK-264
is approximately 10% based on the combination of radiolabelled material in the urine (about 1%)
and unaccounted for radioactivity (about 9%, assumed to be retained in the body). The dermal
penetration factor of 10% based on this study with humans has been used for risk assessment
instead of earlier data based on animal studies. EPA's use of a human dermal absorption study
in the MGK-264 risk assessment is in accordance with the Agency's Final Rule promulgated on
January 26, 2006, related to the Protections for Subjects in Human Research, which is codified in
40CFRPart26.
Subchronic Inhalation Toxicity
A 90-day rat inhalation toxicity study demonstrated that at the lowest dose tested, there
were indications of metaplasia/hyperplasia and changes in the larynx. At higher doses,
histopathology of the larynx revealed additional changes and more intense changes in the
epithelium and throat. Thus, inhalation exposure is capable of causing alterations in the
respiratory tract.
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Subchronic and Chronic Oral Toxicity
The liver is the target organ of MGK-264. Liver effects were noted in the adults in the
rat chronic/oncogenicity study, the mouse chronic/oncogenicity study, the rat multi-generation
reproduction study and subchronic and chronic dog studies. The dog appeared to be the most
sensitive species for liver alterations but these alterations were limited to slight to moderate
brown pigment and circulating enzyme changes. The dog study did not include histopathology
of the liver to verify the presence of degenerative conditions. In the mouse, liver changes
include bile duct histological changes including liver tumors, as well as kidney weight effects
and brown pigment.
Carcinogenicity Evaluation
The Carcinogenicity Peer Review Committee (CPRC) classified MGK-264 as a Group C
- Possible Human Carcinogen based on statistically significant increases mainly in benign liver
adenomas in both sexes of mice at doses approaching the limit dose and on increases in benign
thyroid follicular tumors in male rats at doses considered to be adequate to assess carcinogenic
potential. The CPRC determined that a quantification of cancer risk is not required because the
systemic NOAELs established in the chronic/cancer studies would be protective of any tumors
seen at higher doses. Further, as discussed below, there is low concern for mutagenicity.
Developmental Toxicity
The rat and rabbit developmental toxicity studies did not demonstrate developmental
toxicity for MGK-264. Maternal toxicity consisted of body weight and food consumption
decreases. However, at higher doses, abortions, resorptions, and deaths were noted.
Reproductive Toxicity
There were no effects on the reproductive performance of either males or females in the
multi-generation reproduction study. Systemic effects were related to body weight decrease as
well as histopathological changes in the liver similar to those seen in the rat chronic feeding
study. However, offspring for all generations indicated decreased body weight during lactation
at a lower dose than parental systemic effects. The effect was reversible after weaning as pups
regained weight and their weights were comparable to control animal weights after weaning.
The lowest dose tested for the rat multi-generation reproduction study was determined to
demonstrate the lowest LOAEL and was selected as the endpoint of concern for the chronic
reference dose and other exposure scenarios. No NOAEL was established in the study.
Mutagenicity
Mutagenicity and genotoxicity were not evident in the Ames test for bacterial mutations,
in the unscheduled DNA synthesis, or in a chromosome aberration studies. Although MGK-264
was considered weakly positive in the mouse lymphoma assay, there was a low concern for
mutagenic or genetic toxicity.
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Immunotoxicity and Neurotoxicity
There were no indications of immunotoxicity or specific neurotoxicity.
Metabolism
The metabolism and pharmacokinetics data for MGK-264 in rats demonstrated that
MGK-264 is absorbed and excreted with little retention of metabolites.
Toxicity Endpoints
The toxicological endpoints used in the human health risk assessment for MGK-264 are
listed below in Table 4.
Table 4: Summary of Toxicological Doses and Endpoints for MGK-264 for Use in Human Risk Assessments.
Exposure
Scenario
Acute Dietary
(Females 13-49 years of
age)
Acute Dietary
(General population
including infants and
children)
Chronic Dietary
(All populations)
Short-Term (1-30 days)
and Intermediate term (1-6
months) Incidental Oral
Dermal Exposures - all
durations
Doses, Uncertainty
Factors (UFs), and
Safety Factors (SF)
Maternal NOAEL =
100 mg/kg/day
FQPA SF = IX
UF=100
Total UF = 100
Acute RfD = 1
mg/kg/day
Level of Concern:
Population Adjusted
Dose (PAD) or Target
Margin of Exposure
(MOE)
aPAD= 1.0 mg/kg/day
Study and Toxicological Effects
Developmental toxicity study in rabbits
LOAEL = 300 mg/kg/day based on maternal
deaths, abortions and resorptions.
(MRID: 40352301)
An appropriate endpoint attributable to a single dose was not identified in the available toxicology
database.
Offspring
LOAEL= 61 mg/kg/day
FQPA SF = IX
UF=100
Lack of NOAEL UF =
10X
Total UF= 1,000
Chronic RfD =
0.061 mg/kg/day
Offspring
LOAEL = 61mg/kg/day
FQPA SF = IX
UF=100
Lack of NOAEL UF =
10X
Total UF= 1,000
Offspring
LOAEL = 61mg/kg/day
cPAD = 0.061 mg/kg/day
Residential LOC: MOE =
1,000
Residential LOC: MOE =
1,000
Multi generation reproduction-toxicity rat
Offspring LOAEL= 61 mg/kg/day based on
slight decreases in body weight in pups during
lactation.
(MRID: 42155701)
Multi generation reproduction-toxicity rat
Offspring LOAEL = 61mg/kg/day based on
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Table 4: Summary of Toxicological Doses and Endpoints for MGK-264 for Use in Human Risk Assessments.
Exposure
Scenario
Doses, Uncertainty
Factors (UFs), and
Safety Factors (SF)
Level of Concern:
Population Adjusted
Dose (PAD) or Target
Margin of Exposure
(MOE)
Study and Toxicological Effects
FQPA SF = IX
UF=100
Lack of NOAEL UF =
10X
Total UF= 1,000
Used 10% dermal
absorption
Occupational LOG:
MOE = 1,000
slight decreases in body weight in pups during
lactation.
(MRID: 42155701)
MGK-264 Human Dermal Absorption Study
(MRID: 42976701, 42976702)
Inhalation - all durations
LOAEL = 0.01 mg/L
converted to 1.9
mg/kg/day
FQPA SF = IX
UF=100
Lack of NOAEL UF =
10X
Total UF= 1,000
Residential LOG: MOE =
1,000
Occupational LOG:
MOE = 1,000
90 day inhalation study - rat
LOAEL = 0.01 mg/L (1.9 mg/kg/day) based on
hyperplasia and metaplasia in larynx
(MRID: 43309001)
Cancer (oral, dermal,
inhalation)
Group C - Possible Human Carcinogen based on liver tumors in mice and thyroid tumors in rats.
Quantification of cancer risk is not required.
FQPA SF = FQPA safety factor, NOAEL = no observed adverse effect level, LOAEL = lowest observed adverse
effect level, PAD = population adjusted dose (a = acute, c = chronic) RfD = reference dose
2. Safety and Uncertainty Factors
FQPA Safety Factor
The Food Quality Protection Act (FQPA) directs the Agency to use an additional tenfold
(10X) safety factor to protect for special sensitivity of infants and children to specific pesticide
residues in food, drinking water, or residential exposures, or to compensate for an incomplete
database. FQPA authorizes the Agency to modify the tenfold safety factor only if reliable data
demonstrate that another factor would be appropriate. After evaluating hazard and exposure data
for MGK-264, EPA reduced the 10X FQPA safety factor to IX because there are no concerns
and no residual uncertainties with regard to pre- and post-natal toxicity.
There are no residual uncertainties identified in the exposure databases relevant to
potential exposure to infants and children. The dietary food exposure assessment assumes 100%
treatment of all food handling establishments and warehouses. Additionally, the assessment
assumes that all consumed foods have been treated and bear residues of MGK-264. By using
these conservative assumptions, chronic exposures/risks will not be underestimated. The dietary
drinking water assessment (Tier 1 estimates) utilizes values generated by models and associated
modeling parameters which are designed to provide conservative, health protective, high-end
estimates of water concentrations. The residential exposure assumptions are conservative high-
end estimates that are meant to be protective of potential exposure to MGK-264. Therefore,
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these assessments will not underestimate the potential exposure to infants and children resulting
from the use of MGK-264.
Other Uncertainty Factors
An additional 10X uncertainty factor was applied to the chronic dietary assessment and
the incidental oral and dermal exposure scenarios because no NOAEL was identified in the
multi-generation rat study. All inhalation exposure scenarios included an additional 10X
because a NOAEL was not identified in the 90-day rat inhalation study either.
3. Endocrine Disruption
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 such endocrine effects as the Administrator may designate."
Following recommendations of its Endocrine Disrupter 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 the Program include evaluations of
potential effects in wildlife. For pesticide chemicals, EPA will use FIFRA and, to the extent that
effects in wildlife may help determine whether a substance may have an effect in humans,
FFDCA authority to require the wildlife evaluations. As the science develops and resources
allow, screening of additional hormone systems may be added to the Endocrine Disrupter
Screening Program (EDSP).
In the available toxicity studies on MGK-264, there was no estrogen or androgen
mediated toxicity. It is noted, however, that the rat carcinogenicity study demonstrated increased
thyroid tumors that may have been related to perturbation of the thyroid/liver/pituitary axis to
alter thyroid hormone metabolism. EPA believes the endpoints and risk scenarios evaluated are
protective of this potential endocrine effect. When additional appropriate screening and/or
testing protocols being considered under the Agency's EDSP have been developed, MGK-264
may be subjected to further screening and/or testing to better characterize effects related to
endocrine disruption.
2. Dietary Risk
The only MGK-264 food uses presently supported are in food handling establishments
(FHEs) and warehouses. Because no agricultural crop uses or direct animal treatment uses are
being supported, many residue chemistry data requirements are not applicable for the current
uses of MGK-264. A summary of MGK-264 tolerance changes and data requirements is
included in Section IV and V.
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Acute and Chronic (Food Only)
Dietary risk assessment incorporates both exposure to and toxicity of a given pesticide.
Dietary risk is expressed as a percentage of a level of concern. The level of concern is the dose
predicted to result in no unreasonable adverse health effects to any human population subgroup,
including sensitive members of such population subgroups. This level of concern is referred to
as the population adjusted dose (PAD), which reflects the reference dose (RfD), either acute or
chronic, adjusted to account for the FQPA safety factor.
Estimated risks that are less than 100% of the PAD are below EPA's level of concern.
The acute PAD (aPAD) is the highest predicted dose to which a person could be exposed on any
given day with no adverse health effects expected. The chronic PAD (cPAD) is the highest
predicted dose to which a person could be exposed over the course of a lifetime with no adverse
health effects expected.
The acute and chronic analyses were conducted using maximum and average residue
levels, respectively, from applicable field trials and assumed all food commodities were treated.
An acute analysis was conducted only for females 13-49 years old, because an appropriate
endpoint for the general population was not identified. At the 99.9th percentile of exposure for
the acute analysis for females 13-49 years old, the risk was at 13% of the acute population
adjusted dose (aPAD). For the chronic analysis, the most highly exposed population subgroup
was children 1-2 years old with a risk estimate at 51% of the chronic population adjusted dose
(cPAD), while the estimate for the general population was at 19% of the cPAD. Acute and
chronic analyses were conducted using both DEEM (Version 2.0) and Lifeline (Version 2.0).
These analyses are conservative so the actual exposure is likely lower than the estimates
provided.
Table 5; Acute and Chronic Dietary Exposure and Risk Estimates for MGK-264,
Population Subgroup
PAD,
mg/kg/day
DEEM
Exposure,
mg/kg/day
% PAD
Lifeline
Exposure,
mg/kg/day
%PAD
Acute Dietary Estimates (99.9th Percentile of Exposure)
Females 13-49 yrs
1
0.076
7.6
0.13
13
Chronic Dietary Estimates
U.S. Population
All infants (< 1 yr)
Children 1-2 yrs
0.061
0.012
0.016
0.031
19
26
51
0.011
0.015
0.029
19
24
48
The values for the population subgroup with the highest predicted exposure are bolded.
3. Drinking Water
For more detail on the drinking water risk assessment, see the Drinking Water Assessment for
MGK-264 Insecticide Synergist: Surface Water Revision for Ground Spray (Eckel, February 17,
2005).
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Drinking water exposure to pesticides can occur through groundwater and surface water
contamination. EPA considers both acute (one day) and chronic (lifetime) drinking water risks
and uses either modeling or actual monitoring data, if available, to estimate those risks. To
determine the maximum allowable contribution from water allowed in the diet, EPA first looks
at how much of the overall allowable risk is contributed by food and then determines a "drinking
water level of comparison" (DWLOC) to ascertain whether modeled or monitored concentration
levels exceed this level.
The Agency uses the DWLOC calculation to estimate risk associated with exposure from
pesticides in drinking water. The DWLOCs represent the maximum contribution to the human
diet (in ppb or ug/L) that may be attributed to residues of a pesticide in drinking water after
dietary exposure is subtracted from the aPAD or the cPAD. Risks from drinking water are
assessed by comparing the DWLOCs to the estimated drinking water concentrations (EDWC) in
surface water and groundwater. EDWCs less than the DWLOC are below EPA's level of
concern. Drinking water modeling is considered to be an unrefined assessment and generally
provides high-end estimates.
The MGK-264 drinking water assessment for turf was based on a hypothetical Iowa corn
scenario because no exposure model has been developed to estimate pesticide residue from
applications in an outdoor urban setting. Since there are no agricultural or wide area mosquito
abatement uses for MGK-264 and the most likely route of drinking water exposure is from
residential turf use, this is a conservative drinking water risk assessment.
Surface Water
FIRST (FQPA Index Reservoir Screening Tool) was used to estimate surface water
concentrations. FIRST is a Tier I screening level model used to provide high-end values on the
concentrations that might be found in a small drinking water reservoir. FIRST is a single-event
model (one run-off event), but can account for spray drift from multiple applications. FIRST
makes adjustments for the percent-cropped area but makes conservative assumptions including
modeling a runoff-prone watershed, the use of the maximum use rate, no buffer zone, and a
single large rainfall. FIRST input parameters are based on weekly applications (52 per year) at
the turf rate of 2.2 Ib a.i. per acre (the Master Label is 0.05 Ib active ingredient per 1,000 square
feet) and a re-application interval of 7 days. These inputs were used to calculate an acute surface
water concentration of 83 ppb and a chronic surface water concentration of 38 ppb.
During the Phase 5 public comment period, MGK Company, requested a rate reduction
for outdoor application sites, which changes the application rate assumed in the drinking water
assessment. Since there is a linear relationship between application rate and EDWCs, the
calculated EDWCs were scaled to account for the rate reduction from 2.2 Ib a.i. per acre to 0.3 Ib
a.i. per acre. When the application rate is reduced from 2.2 Ibs a.i. per to 0.3 Ibs a.i. per acre, the
estimated acute surface water concentration is reduced to 11 ppb, and the chronic surface water
concentration is reduced to 5.2 ppb.
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Ground Water
The Screening Concentration in Ground Water (SCI-GROW) model was used to estimate
ground water concentrations. The SCI-GROW screening model is a Tier I model that provides a
high-end estimate. SCI-GROW model generates a single EDWC value of pesticide
concentration in ground water used for drinking water and provides a screening concentration for
use in determining potential risk to human health from drinking water contaminated with a
pesticide. EPA used the Tier 1 SCI-GROW model and a hypothetical percent-cropped area of
87%, mean soil half-life of 430 days, and an Organic Carbon Partition coefficient (Koc) of 899
mL/g, to predict a concentration of 0.86 ppb in ground water. When the application rate is
reduced from 2.2 Ibs a.i. per acre to 0.3 Ibs a.i. per acre, the scaled ground water concentration is
reduced to 0.12 ppb.
Table 6: Summary of Estimated Drinking Water Concentrations (EDWCs) for MGK-264.
Exposure
Duration
Acute
Acute: Scaled3
Chronic
Chronic: Scaled a
Surface Water Concentration
(ppb)
83
11
38
5.2
Ground Water Concentration
(ppb)
0.86
0.12
0.86
0.12
a Scaled value based on assumption of direct relationship between application rate and surface or
concentration and a revised application rate of 0.30 Ib ai/A.
ground water
The EDWCs listed above in Table 6 should be considered highly conservative because of
the assumptions made in the modeling. The percent cropped area value used was 87% based on
hypothetical corn use in Iowa. It is unlikely that a chemical with no crop uses and a treatment
rate described in terms of Ibs ai per 1,000 ft2 would be used in 87% of a watershed. Use of the
formulation modeled in the drinking water assessment is intended to be an "area" treatment
rather than a watershed-scale treatment. Available monitoring data in raw ground water and
surface water, and in finished drinking water from four cities, indicate that MGK-264 has not
been found at the detectable limit of 0.1 ppb.
4. Residential Exposure and Risk
For more detail on the residential risk assessment, see the MGK-264: REVISED Occupational
and Residential Exposure Assessment for the Reregistration Eligibility Decision Document
(Weiss, March 10, 2006).
There is potential for residential exposure while applying and handling products
containing MGK-264. There is also a potential for exposure of adults and children entering
MGK-264 treated areas, such as lawns, golf courses, home gardens, and indoor surfaces (carpets
and flooring) and through insect repellents and contact with treated pets. Risk assessments have
been completed for both residential handler and post-application scenarios. Based on the Master
Label provided by MGK Company, 11 residential handler exposure scenarios have been assessed
for this RED.
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Residential risk is expressed as a Margin of Exposure (MOE), which measures how close
the residential exposure comes to a dose selected from toxicity studies. For MGK-264, MOEs
greater than 1,000 are considered protective for all exposure durations (short-, intermediate-, and
long-term) via all routes of exposure (incidental oral, dermal, and inhalation).
a. Toxicity
The toxicological endpoints used in the residential risk assessment for MGK-264 are listed in
Table 7 and summarized below.
Table 7: Summary of Toxicological Doses and Endpoints for MGK-264 for Use in Residential Risk Assessment
Exposure
Scenario
Doses, Uncertainty
Factors (UFs), and Safety
Factors (SF)
Target Level of
Concern:
Margin of Exposure
(MOE)
Study and Toxicological Effects
Short-Term (1-30 days)
and Intermediate term (1-
6 months) Incidental Oral
Offspring
LOAEL = 61 mg/kg/day
FQPA SF = IX
UF=100
LackofNOAELUF=10X
Total UF= 1,000
Residential LOG: MOE
= 1,000
Multi generation reproduction-toxicity rat
Offspring LOAEL= 61 mg/kg/day based on
slight decreases in body weight in pups
during lactation.
(MRID: 42155701)
Dermal Exposures - all
durations
Offspring
LOAEL = 61mg/kg/day
Used 10% dermal absorption
FQPA SF = IX
UF=100
Lack of NOAEL UF = 10X
Total UF= 1,000
Residential LOG: MOE
= 1,000
Multi generation reproduction-toxicity rat
Offspring LOAEL = 61mg/kg/day based on
slight decreases in body weight in pups
during lactation.
(MRID: 42155701)
MGK-264 Human Dermal Absorption
Study (MRID: 42976701, 42976702)
Inhalation - all durations
LOAEL = 0.01 mg/L
converted to 1.9 mg/kg/day
FQPA SF = IX
UF=100
Lack of NOAEL UF = 10X
Total UF= 1,000
Residential LOG: MOE
= 1,000
90 day inhalation study - rat
LOAEL = 0.01 mg/L (1.9 mg/kg/day)
based on hyperplasia and metaplasia in
larynx
(MRID: 43309001)
FQPA SF = FQPA safety factor, NOAEL = no observed adverse effect level, LOAEL = lowest observed adverse
effect level
b. Residential Exposure Scenarios
The residential exposure assessment includes both handler and post-application
residential exposure scenarios. The term "handler" applies to individuals who mix, load, and
apply the pesticide product. The term "post-application" describes individuals who are exposed
to pesticides after entering areas previously treated with pesticides. A post-application scenario
was also assessed for the use of repellents containing MGK-264 that are applied directly to the
skin. Based on information provided in the Master Label regarding current registrant supported
uses, information provided by the registrants in public comments, and information gathered
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through correspondences with the registrants, the Agency assessed the residential exposure
scenarios for MGK-264.
i. Residential Handler Scenarios
The anticipated use patterns and current labeling indicate several residential handler
exposure scenarios based on the types of equipment and techniques that can potentially be used
to make MGK-264 applications. The quantitative residential handler exposure and risk
assessment developed for residential handlers is based on these scenarios:
• Mixing/Loading/Applying liquid formulations with low pressure handwand
(LPH)
• Mixing/Loading/Applying formulations with hose-end sprayer
• Applying ready-to-use dusts with shaker can
• Applying ready-to-use shampoos
• Applying ready-to-use mousse, soap, lotion, gel, comb, or roll-on products
• Applying ready-to-use wipes
• Applying ready-to-use formulations using trigger pump sprayer
• Applying ready-to-use aerosol cans
• Applying ready-to-use foggers
• Applying ready-to-use impregnated collars on dogs
Data were not available to assess applications of MGK-264 for dip applications. Based
on high risk estimates from a pet shampoo study, there are no interim mitigation measures for
applicators making dips to pets. Applicator pet dip exposure data may be required for this
scenario pending the outcome of a 21-day dermal toxicity study.
ii. Residential Post Application Scenarios
The Agency uses the term "post-application" to describe exposures to individuals that
occur as a result of being in an environment that has been previously treated with a pesticide.
MGK-264 can be used in many areas that can be frequented by the general population including
residential areas (e.g., home lawns and gardens). As a result, individuals could be exposed by
entering these areas if they have been previously treated. MGK-264 could also be used on pets,
which can lead to exposures by contact with the treated animal, and through metered release
devices. Products used in metered release devices are usually formulated in ready to use aerosol
cans with a special nozzle that fits into the device. A battery-operated timer system allows a
spray of MGK-264 to dispense regularly throughout a day. These systems are registered for use
to control flying insects in food handling establishments, animal premises, and other areas.
c. Exposure Data and Assumptions
Handler and Post-application Exposure Data
Data from the Pesticide Handler Exposure Database (PHED), the Occupational
Residential Exposure Task Force (ORETF) database, the Chemical Manufacturers Association
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(CMA) Antimicrobial Exposure Assessment Study, and two proprietary studies (trigger pump
spraying with propoxur and shampoo application with carbaryl) were used to assess residential
handler exposures. With the exception of a dog shampoo study, no chemical-specific exposure
data were submitted for MGK-264.
Standard default application assumptions regarding areas treated or amounts applied for
residential handler scenarios were used. See the MGK-264: REVISED Occupational and
Residential Exposure Assessment for the Reregistration Eligibility Decision Document (Weiss,
March 10, 2006) for a complete list of all data and assumptions used in the residential risk
assessment. Other residential exposure standard operating procedures (SOPs) may be viewed at the
following website: http://www.epa.gov/oscpmont/sap/1997/september/sopindex.htm.
The Agricultural Re-entry Task Force (ARTF) database was used for re-entry dermal
exposure to treated foliage. For post-application exposure following indoor treatments, surrogate
data from the Non-Dietary Exposure Task Force (NDETF) and Residential Exposure Joint
Venture (REJV) were used.
Exposure Parameters
The parameters and assumptions used in estimating risks from residential exposure to
MGK-264 can be found in section 3.0 of theMGK-264: Revised Occupational and Residential
Exposure Assessment for the Reregistration Eligibility Decision Document (Weiss, March 10,
2006). The information listed was used to assess all scenarios including incidental oral, aerosol
space sprays, repellent use, and outdoor residential misting systems.
d. Residential Risk Estimates
Handler
It is likely that MGK-264 can be used in multiple ways that have not specifically been
identified in the residential risk assessment. However, EPA believes that the scenarios assessed
represent worse-case exposures and risks resulting from use of MGK-264 in residential
environments.
All of the residential handler scenarios assessed had risks below the Agency's level of
concern. That is, all MOEs calculated were above the target of 1,000. Dermal handler MOEs
ranged from 1,800 (applying pet collars), to 260,000 (applying RTU trigger pump sprays
outside). Handler inhalation MOEs ranged from 2,800 (applying aerosol sprays indoors), to well
over a million (applying soap, hair mousse, lotion, or gel to pets).
Data were not available to assess applications of MGK-264 for dip applications. Based
on relatively high MOEs from a pet shampoo study which would likely present similar exposure,
no interim mitigation measures for residential applicators making dip application to pets will be
required. Applicator pet dip exposure data may be required for this scenario pending the
outcome of a 21-day dermal toxicity study.
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Post-Application
Estimated MOEs for adults and toddlers were calculated for post-application risks
following the application of MGK-264 to home lawns, indoor spaces/surfaces, repellent uses,
and pets. The shampoo post-application dermal scenario is protective of post-application
exposure to pets after dip applications since the dip rate is lower than the shampoo rate. Results
of the post-application assessment are presented in Table 8. MOEs of less than 1,000 are
described further below.
Toddlers
There were post-application dermal risk concerns for toddlers exposed to MGK-264 from
indoor spray applications, indoor fogger applications, indoor dust applications, and from insect
repellents. Aerosol space and metered release applications were a concern for post-application
inhalation exposure. Dusts applied as a broadcast treatment to carpets were a concern for post-
application incidental oral exposure.
Adults
For adults, there were post-application dermal risk concerns from exposure to indoor dust
applications to carpets and from insect repellants. Indoor space and metered release applications
were a concern for post-application inhalation exposure.
Table 8 : Residential Post- Application MOEs
Exposure Scenario
Route of
Exposure
Application Rate
MOEs
Adults
Toddlers
Outdoors
Residential Turf (High Contact Activities)
Residential Turf (Mowing)
Hand to Mouth Activity on Turf
Object to Mouth Activity on Turf
Incidental Soil Ingestion
Dermal
Dermal
Oral
Oral
Oral
0.3 Ib ai/acre
0.3 Ib ai/acre
0.3 Ib ai/acre
0.3 Ib ai/acre
0.3 Ib ai/acre
7,500
30,000
NA
5,200
NA
14,000
54,000
4,100,000
Indoors
Hand to Mouth Activity on Indoor Surfaces
(Spray applications to carpeted surfaces)
Hand to Mouth Activity on Indoor Surfaces
(Fogger applications to carpeted surfaces)
Hand to Mouth Activity on Indoor Surfaces
(Fogger applications to hard surfaces)
Hand to Mouth Activity on Indoor Surfaces (dust
applications to carpeted surfaces) 100% of
surface residue available
Oral
Oral
Oral
Oral
0.011bai/l,000ft2
0.011bai/l,000ft2
0.011bai/l,000ft2
O.Olllbai/lOOft2
NA
4,700
2,500
7,900
430
Page 28 of 81
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Table 8: Residential Post-Application MOEs
Exposure Scenario
Hand to Mouth Activity on Indoor Surfaces (dust
applications to carpeted surfaces) 50% of surface
residue available
Hand to Mouth Activity on Indoor Surfaces (dust
applications to carpeted surfaces) 25% of surface
residue available
Indoor Surfaces
(Spray applications to carpeted/hard surfaces)
Indoor Surfaces
(Fogger applications to carpeted surfaces)
Indoor Surfaces
(Fogger applications to hard surfaces)
Indoor Surfaces (dust applications to carpeted
surfaces) 100% of surface residue available
(dust applications to carpeted surfaces) 50% of
surface residue available
(dust applications to carpeted surfaces) 25% of
surface residue available
Inhalation Exposure from Space Sprays
(aerosol cans)
Inhalation Exposure from Space Sprays in homes
(metered release with 0.18 air changes per hour)
Inhalation Exposure from Space Sprays
(metered release with 2 air changes per hour)
Route of
Exposure
Oral
Oral
Dermal
Dermal
Dermal
Dermal
Dermal
Dermal
Inhalation
Inhalation
Inhalation
Application Rate
O.Olllbai/lOOft2
O.Olllbai/lOOft2
0.011bai/l,000ft2
0.011bai/l,000ft2
0.011bai/l,000ft2
O.Olllbai/lOOft2
O.Olllbai/lOOft2
O.Olllbai/lOOft2
0.001 Ib ai/1,000 ft3
1.77 mg ai/spray event
1.77 mg ai/spray event
MOEs
Adults
1,000
1,200
4,700
100
210
290
170
40
440
Toddlers
850
1700
780
840
3,300
70
140
410
52
13
140
Pets
Hand to Mouth Activity Following Pet Contact
(Dust using Residential-Standard Operating
Procedures)
Pet Contact (Dust using Residential-Standard
Operating Procedures)
Hand to Mouth Activity Following Pet Contact
(Shampoo using MGK-264 data)
Hand to Mouth Activity Following Pet Contact
(Mousse, Soap, Gel, Comb or roll-on using
MGK-264 data)
Pet Contact (Shampoo using MGK-264 data)
Pet Contact (Mousse, Soap, Gel, Comb or roll-on
using MGK-264 data)
Oral
Dermal
Oral
Oral
Dermal
Dermal
0.00248 Ib ai/animal
0.051b ai/animal
0.00088 Ib ai/animal
0.00044 Ib ai/animal
0.00088 Ib ai/animal
0.000441b ai/animal
NA
130
61
6,500
13,000
100,000
50,000
Insect Repellents Applied to Skin
Page 29 of 81
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Table 8: Residential Post-Application MOEs
Exposure Scenario
One Application to 25% of Body Surface Area
Using 1 mg product per cm2 of skin
One Application Based on REJV Survey Data
One Application to 25% of Body Surface Area
Using 1 mg product per cm2 of skin
One Application Based on REJV Survey Data
Route of
Exposure
Dermal
Oral
Dermal
Dermal
Oral
Dermal
Application Rate
8% ai formulation
5% ai formulation
MOEs
Adults
100
NA
88
160
NA
140
Toddlers
70
1,100
24
110
1,800
38
NA = Not Assessed
Bold indicates MOE is less than LOC of 1,000.
5.
Aggregate Risk
In accordance with the FQPA, EPA must consider and aggregate (combine) pesticide
exposures and risks from all sources. For pesticides, these usually include food, drinking water,
and residential exposures. In an aggregate assessment, exposures from relevant sources are
added together and compared to quantitative estimates of hazard (e.g., a NOAEL or PAD), or the
risks themselves can be aggregated. When aggregating exposures and risks from various
sources, EPA considers both the route (oral, dermal, and inhalation) and duration (short-,
intermediate-, or long-term) of exposure.
Model estimates have been used to estimate residues in drinking water (EDWCs). In
order to determine if aggregate risks are of concern, EPA calculates drinking water levels of
comparison, or DWLOCs. The DWLOC is the maximum amount of a pesticide in drinking
water that would be acceptable in light of combined exposure from food and residential
pathways. The calculated DWLOCs are then compared to the EDWCs; if model-derived
EDWCs exceed the DWLOCs for surface or ground water, there may be a concern for dietary
exposure to residues in drinking water, and monitoring data or other refinements may be
required.
Acute Aggregate Risk (Food + Water)
An acute aggregate risk assessment was conducted for MGK-264. The acute assessment
considered exposures from food and water only. Since adequate water monitoring data are not
available to estimate levels of MGK-264 in drinking water, EPA calculated DWLOCs and
compared them to the modeled EDWCs for surface and ground water to determine whether
aggregate acute risks are of concern.
Table 9 summarizes the acute DWLOC calculated for the only population subgroup
(females 13-49 years old) that was relevant based on effects seen in the toxicity database.
Comparison of the acute DWLOC to the maximum EDWCs for surface and ground water shows
that the acute DWLOC is greater than the EDWCs for acute exposure for females 13-49 years
Page 30 of 81
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old. Therefore, the acute aggregate exposures to MGK-264 result in risk estimates below the
Agency's level of concern.
Table 9: Acute Aggregate Risk Assessment for MGK-264
Population
Subgroup
Females 13-49 years
old
1 Maximum acute watei
2 Based on extrapolatio
watershed.
3 Acute DWLOC(ug/L
Acute Scenario
aPAD
mg/kg/day
1
Acute
Food Exp
mg/kg/day
0.128
Max
Allowable
Acute Water
Exp
mg/kg/day1
0.872
Ground
Water
EDWC
(ppb)2
0.12
Surface
Water
EDWC
(ppb)2
11
Acute
DWLOC
(ppb)3
26,160
- exposure (mg/kg/day) = [(aPAD (mg/kg/day) - acute food exposure (mg/kg/day)]
n of the maximum single application outdoor use rate of 0.05 Ib ai/1,000 ft2 to 87% of a
) = [maximum acute water exposure (ms/ks/dav) x body weight (ks)l
[water consumption (L) x 10"3 mg/ug]
Short-Term Aggregate Risk (Food + Water + Dermal + Incidental Oral)
Short-term aggregate exposure takes into account residential exposure plus average
exposure through food and water. Some MGK-264 residential uses represent short-term
exposure scenarios. Toxicity endpoints were selected for short-term incidental oral, dermal, and
inhalation exposures, and the acceptable MOE for short-term exposure was 1,000 for all
exposures. Inhalation exposures were not included since the toxicological effects through the
inhalation exposure route, changes in the larynx, are different from the toxicological effects
through the oral and dermal routes, slight decreases in pup body weight. Indoor scenarios were
selected because they could potentially lead to higher risk to adults and toddlers than outdoor
scenarios.
This short-term aggregate risk assessment was conducted adding dermal, oral non-dietary
exposure, and average food and water exposures as shown in Table 10. The aggregate MOE
takes into account average food consumption values (calculated from the chronic dietary
assessment), and oral and dermal exposures (from the indoor fogger scenario on hard floors at
the rate of 0.01 Ib ai/1,000 ft2).
Residue values from water monitoring data were not available for MGK-264; therefore,
as with the acute dietary aggregate risk estimate, DWLOCs were calculated for comparison with
EDWCs. For the U.S. population and children 1-2 years old, the estimated ground (0.12 ppb)
and surface water (0.2 ppb) EDWC values do not exceed the DWLOC value for the U.S.
population (1,261 ppb) or children 1-2 years old (38 ppb), the highest exposed subpopulation.
Therefore, short-term aggregate risk does not exceed the Agency's level of concern.
Many of the indoor residential post-application use scenarios resulted in predicted risk
levels that exceeded the Agency's level of concern by themselves (i.e., without aggregating).
Page 31 of 81
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Thus, the following scenarios were not included in the aggregate assessment indoor spray
applications, fogger applications to carpets, dust applications to pets, insect repellents applied to
humans, aerosol space sprays, metered release applications, and dusts applied as a broadcast
treatment to carpets.
In general, the potential exposure to MGK-264 from residential scenarios exceeds that
expected from food and water sources. Because the exposure contributions from food and water
sources are relatively low in the aggregate risk assessment, mitigation adequate to address
residential exposure scenarios of potential concern will also be protective for the short-term
aggregate risk from MGK-264. Further, there are several conservative assumptions in the
dermal risk assessment, including the use of 10% as the dermal absorption factor, and reliance on
an oral study with a 10X uncertainty factor for lack of a NOAEL, which tend to overstate the
dermal component of the aggregate calculation. For more details and data required to refine
dermal estimates, see discussion in Section IV, under Insect Repellents.
Table 10: Short-Term Aggregate Risk and DWLOC Calculations for MGK-264
Population
Subgroup
U.S.
Population
Children 1-2
years old
1 Aggregate M(
2WaterMOE =
3 Allowable wa
4 The highest la
5 DWLOC(ug/I
Short-Term Scenario
Aggregate
MOE
(food and
residential)1
2,442
1,066
MOE
Water2
1,693
16,152
Allowable
water
exposure3
(mg/kg/day)
0.036
0.0038
Ground
Water
EDWC4
(ppb)
0.12
0.12
Surface
Water
EDWC4
(ppb)
5.2
0.2
Short-term
DWLOC5
(Hg/L)
1,261
38
3E (food and residential) = H[(RMOE food) + (RMOE oral) + (RMOE dermal) ]
K [(H Target Aggregate MOE) - (^Aggregate MOE (food and residential)]
ter exposure = Short Term Oral NOAEL -^ MOE Water
bel rate for outdoor area treatments was extrapolated to a watershed area for modeling purposes.
.,) = [allowable water exposure (ms/ks/dav) x body weight (ks)l
[water consumption (L) x 10~3 mg/ug]
Chronic Aggregate Risk (Food + Water)
A long-term (chronic) aggregate risk assessment was conducted for MGK-264. The
chronic assessment considered exposures from food and water only because there were no
residential uses expected to contribute to chronic exposures for this chemical. DWLOCs were
calculated and compared to the modelled EDWCs for surface and ground water to determine
whether aggregate chronic risks are of concern.
The results of the dietary exposure assessment indicate that chronic dietary exposures to
MGK-264 in food are below the Agency's level of concern (100% of the cPAD). MGK-264
food exposure was estimated at 0.012 mg/kg/day for the U.S. population (19% of the cPAD) and
0.031 mg/kg/day (51% of the cPAD) for the most highly exposed population subgroup (children
Page 32 of 81
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1-2 years old) based on the most conservative estimates for each population subgroup from the
LifeLine and DEEM-FCID models. The calculated DWLOCs ranged from 1800 ppb for adults
to 300 ppb for children. The Tier 1 chronic surface water EDWC (5.2 ppb) was below the
Agency's calculated DWLOCs for chronic exposure to MGK-264 for the U.S. population and
each population subgroup. The Tier 1 ground water EDWC (0.12 ppb) is also less than the
Agency's calculated chronic DWLOCs for all population subgroups. The chronic aggregate risk
associated with the use of MGK-264 does not exceed the Agency's level of concern for any
population subgroup.
Table 11: Aggregate Risk Assessment for Chronic Exposure to MGK-264
Population
Subgroup1
U.S. Population
All Infants (<1
year old)
Children 1-2 years
Children 3 -5 years
Children 6-12
Youth 13-19
Adults 20-49
Females 13+
Adults 50+ years
'DWLOC values cal
2Maximum Chronic A
(mg/kg/day)]
3 Based on extrapola
watershed.
4 Chronic DWLOC((,
Chronic Scenario
cPAD
mg/kg/day
0.061
0.061
0.061
0.061
0.061
0.061
0.061
0.061
0.061
Chronic
Food Exp
mg/kg/day
0.0118
0.0161
0.0309
0.0289
0.0196
0.0126
0.00953
0.0111
0.0089
Max
Chronic
Water Exp
mg/kg/day2
0.0492
0.0449
0.0301
0.0321
0.0414
0.0484
0.05147
0.0499
0.0521
Ground
Water
EDWC
(ppb)3
0.12
Surface
Water
EDWC
(ppb)3
5.2
Chronic
DWLOC
(ppb)4
1,722
449
301
321
414
1,452
1,801
1,497
1,824
culated assuming standard body weights (70 kg adult male; 60 kg adult female; 10 kg child).
\Vater Exposure (mg/kg/day) = [Chronic PAD (mg/kg/day) - Chronic Dietary Exposure
tion of the maximum single application outdoor use rate of 0.05 Ib ai/1,000 ft2 to 87% of a
is/L) = [maximum chronic water exposure (ms/ks/dav) x body weight (ks)l
[water consumption (L) x 10"3 mg/ug]
Page 33 of 81
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6. Occupational Risk
For more detail on the occupational risk assessment, see section 2.0 of the MGK-264: REVISED
Occupational and Residential Exposure Assessment for the Reregistration Eligibility Decision
Document (Weiss, March 10, 2006).
a. Occupational Toxicity
Table 12 provides a listing of the toxicological endpoints used in the MGK-264 occupational
risk assessment.
Table 12: Summary of Toxicological Doses and Endpoints for MGK-264 for Use in Occupational Risk Assessment
Exposure
Scenario
Doses, Uncertainty Factors
(UFs), and Safety Factors (SF)
Level of Concern:
Target Margin of
Exposure (MOE)
Study and Toxicological Effects
Dermal Exposures -
all durations
Offspring
LOAEL = 61mg/kg/day
UF=100
Lack of NOAEL UF = 10X
Total UF= 1,000
Used 10% dermal absorption
Occupational LOG:
MOE = 1,000
Multi generation reproduction-toxicity rat
Offspring LOAEL = 61 mg/kg/day based on
slight decreases in body weight in pups during
lactation
(MRID: 42155701)
MGK-264 Human Dermal Absorption Study
(MRID: 42976701, 42976702)
Inhalation - all
durations
LOAEL = 0.01 mg/L converted
to 1.9 mg/kg/day
UF=100
Lack of NOAEL UF=10X
Total UF= 1,000
Occupational LOG:
MOE = 1,000
90 day inhalation study - rat
LOAEL = 0.01 mg/L (1.9 mg/kg/day) based
on hyperplasia and metaplasia in larynx
(MRID: 43309001)
NOAEL = no observed adverse effect level, LOAEL = lowest observed adverse effect level
The level of concern MOEs for occupational exposure include the conventional
uncertainty factor of 100X (10X for interspecies extrapolation and 10X for intraspecies
variation) and an additional 10X for the use of a LOAEL (i.e, lack of a NOAEL in the selected
study) for dermal and inhalation exposure risk assessments for all durations.
Workers can be exposed to a pesticide through mixing, loading, or applying the pesticide,
and through reentering a treated site. Worker risk is measured by a Margin of Exposure (MOE)
which determines how close the occupational exposure comes to the NOAEL taken from animal
studies. In the case of MGK-264, MOEs greater than 1,000 for short- and intermediate-term
exposures are not a concern. No long term exposures (> 6 months) are expected.
b. Occupational Handler Exposure
The quantitative exposure and risk assessment developed for occupational handlers is
based on the following scenarios:
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Mixing/Loading/Applying (M/L/A):
• M/L/A liquids with low pressure hand-wand (LPH)
• M/L/A liquids with backpack sprayer
• M/L/A liquid with handgun
• M/L/A liquids with high pressure hand-wand (HPH)
Applying:
• Applying ready-to-use (RTU) paste
• Applying RTU wipes
• Applying pour-on or spot-on
• Applying RTU formulations via trigger-pump sprayer
• Applying RTU formulations to pet via hair mousse, soap, lotion, gel, comb, or roll-on
• Applying RTU shampoo
• Applying RTU formulations with aerosol cans
• Applying RTU formulations with fogger cans
• Applying fogs with hand-held equipment
• Applying liquid formulations for handheld fogger application
Due to lack of applicator exposure data, MOEs were not calculated for handlers applying
liquids for dip applications. Based on high MOEs from a pet shampoo study which likely pose
similar exposure, there are no interim mitigation measures for applicators making dips to pets.
Applicator pet dip exposure data may be required for this scenario pending the outcome of a
confirmatory 21-day dermal toxicity study.
c. Occupational Handler Risk Summary
With the exception of the four occupational handler scenarios in Table 13 below,
estimated MOEs were below EPA's level of concern for most scenarios at baseline protection,
which includes a single layer of clothes plus shoes and socks, with no gloves, and no respirator.
Dermal MOEs ranged from 1,400 (applying paste or shampoo to animals) to over a million
(mixing and loading for dip applications) for most scenarios. Possible dermal risks were
identified for four scenarios. The addition of gloves elevated the estimated MOEs to greater than
1,000 for mixer, loader, and applicator scenarios using handheld equipment, such as handwand,
backpack, or handgun spray equipment. There were additional concerns for applicators using
hand-held fogging equipment, which is further explained below.
Most occupational handler scenarios did not required additional inhalation protection
with a respirator. Inhalation MOEs for most scenarios ranged from 1,900 (applying dusts with
shaker can) to over a million (applying shampoo to pets).
Table 13: MGK-264 Occupational Handler Scenarios of Concern
Exposure Scenario
M/L/A Liquids w/ LPH
Application Rate
0.00005 Ib ai/ft2
Area Treated
11,200ft2
Baseline
Dermal MOE
654
Baseline
Inhalation
MOE
7,800
PPE-Gloves
Dermal
MOE
150,000
Page 35 of 81
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Table 13: MGK-264 Occupational Handler Scenarios of Concern
Exposure Scenario
M/L/A Liquids w/
Backpack
M/L/A Liquids w/
Backpack
M/L/A Liquid w/
Handgun
Application Rate
0.00005 Ib ai/ft2
0.3 Ib ai/A
0.00025 Ib ai/
animal
0.07 Ib ai/A
0.3 Ib ai/A
0.00005 Ib ai/ft2
0.00025 Ib ai/
animal
Area Treated
11,200ft2
1 A
25 animals
5A
5 A
11,200ft2
25 animals
Baseline
Dermal MOE
No data
No data
No data
No data
No data
No data
No data
Baseline
Inhalation
MOE
7,800
14,000
690,000
12,000
46,000
120,000
> 1,000,000
PPE-Gloves
Dermal
MOE
26,000
49,000
2,300,000
42,000
90,000
240,000
> 1,000,000
Indoor Handheld Fogging
The Agency does not have data to estimate risk to applicators fogging with hand-held
equipment indoors. Due to insufficient information, two different handheld fogging studies that
were submitted for other chemicals were used for inhalation and dermal risk assessment for
MGK-264.
The exposure values estimated from the two studies differ greatly depending on the type
of equipment, duration of application, size of fogging area, and air flow. One study with the
pyrethroid prallethrin (MRID 45869301) was conducted to estimate exposure from a short (6
minute) fogging application in a small space. Another study conducted in a Florida greenhouse
(MRID 40350501) may be more appropriate to estimate exposure for greenhouse and warehouse
applications. The estimated MOE from inhalation exposure using the prallethrin study was 12,
while the MOE was 5,700 using the Florida greenhouse study. Additional information is needed
to assess handheld fogging exposure for MGK-264. Until data are submitted that satisfy the
Agency's concerns for applicators using handheld foggers, additional PPE, including double
layers and a respirator, are required.
d. Occupational Post-Application Summary
The Agency uses the term "post-application" to describe exposures to individuals that
occur as a result of being in an environment that has been previously treated with a pesticide.
MGK-264 uses that may result in foliar contact were identified in the following crop groupings
based on EPA's review of current MGK-264 uses:
• Floriculture crops grown for cutting;
• Floriculture crops not grown for cutting;
• Evergreen trees (Christmas trees);
• Turf/sod (e.g., golf courses, sod farms); and
• Nursery crops (e.g., container and balled and burlapped ornamentals).
For MGK-264, the exposure durations for post-application risk assessment were short-
term (up to 30 days) and intermediate-term (greater than 30 days up to several months).
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However, since the dermal toxicological endpoint was the same for short- and intermediate-term
exposures, the short- and intermediate-term post-application risks are the same.
Inhalation exposures are thought to be negligible in outdoor post-application scenarios,
since MGK-264 has low vapor pressure and the dilution with outdoor air is considered infinite.
For indoor scenarios, under the Worker Protection Standard (WPS) for Agricultural Pesticides
(40 CFR 170) greenhouses must be appropriately ventilated following pesticide applications so
that post-application inhalation exposures are minimal. As a result, post-application inhalation
exposures from outdoor applications were not considered in this assessment and ventilation
requirements will be in place for greenhouse applications.
None of the scenarios assessed have a risk concern on day 0, or 12 hours after
application. Transplanting many crops, including in the ornamental and forestry industry and
various operations with Christmas trees, such as pruning or balling, do not involve substantial
foliar contact; therefore they have not been evaluated in this risk assessment. Post-application
risk at the current reentry interval (REI) of 12 hours is below EPA's level of concern for all post-
application scenarios that fall under the Worker Protection Standard. This REI does not apply to
occupational handlers that are not covered by the WPS.
III. MGK-264 Ecological Fate and Effects Risk Assessment
The Agency has conducted an environmental assessment for MKG-264 for the purposes
of making a reregi strati on decision. The Agency evaluated environmental fate, wildlife, and
aquatic organism toxicity studies submitted for MGK-264 and determined that the data are
adequate to support a reregi strati on decision. More in depth details of the toxicity to aquatic and
terrestrial organisms, as well as fate and persistence studies used to develop the risk assessments
are provided in the Screening Ecological Risk Assessment for the Reregistration of MGK-264
Insecticide Synergist (Lee, September, 29, 2004). A summary of the environmental risk
assessment findings and conclusions is provided below.
1. Environmental Fate and Transport Properties
The physical properties and fate characteristics of MGK-264 indicate that it is a persistent
compound, and that it will be mobile in coarse soils (Koc=636 in sand). MGK-264 is immobile
in clay soils (Koc=3106 in clay loam), which may serve as a sink. MGK-264 may partition to
particulate matter in water. MGK-264 is stable to hydrolysis, direct photolysis, and soil
photolysis. Aerobic and anaerobic soil metabolism are very slow (mean aerobic half-life was
341 days). The expected half-life in air is short (half-life =1.4 hours), so long-range transport is
not expected, and it is expected to be an aerosol rather than a gas. The combined persistence and
mobility would predict MGK-264 being found in surface and ground water, however, limited
monitoring shows no detections above the limit of detection (LOD) of 0.1 ppb.
2. Ecological Risk Assessment
To estimate potential ecological risk, EPA integrated the results of exposure and
ecotoxicity studies using the risk quotient method. Risk quotients (RQs) are calculated by
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dividing exposure estimates by ecotoxicity values, both acute and chronic, for various wildlife
species. RQs are then compared to the Agency's levels of concern (LOCs), which are listed
below in Table 14. 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.
Table 14: EPA's Levels of Concern and Associated Risk Presumptions
Risk Presumption
Acute Risk - there is potential for acute risk
Acute Endangered Species - endangered species may be
adversely affected
Chronic Risk - there is potential for chronic risk
LOC
Terrestrial
Animals
0.5
0.1
1
LOC
Aquatic
Animals
0.5
0.05
1
LOC Plants
1
1
N/A
According to use information available to the Agency and information provided by the
technical registrant, most of the use of MGK-264 is for residential insect control, direct
application to animals, and veterinary use. Since there are no agricultural or wide area mosquito
abatement uses for MGK-264, applications to turf, ornamentals, and lawns were considered the
most likely uses that could lead to exposure to non-target organisms in the environment. Two
turf scenarios were used in the ecological risk assessment. There were no frequency or
reapplication directions on the MGK-264 Master Label, so for the risk assessment it was
assumed that MGK-264 was applied up to 20 times at 7-day intervals. The maximum use rate
considered was 2.2 Ibs a.i./acre for lawn insect control. The registrant has since agreed to reduce
the outdoor spray application rate from 2.2 Ibs a.i./acre to 0.3 Ibs a.i./acre, which will decrease
the RQs estimated in this risk assessment.
3. Risk to Aquatic Animals
Freshwater
MGK-264 is considered to be "moderately toxic" to freshwater fish and invertebrates on
an acute basis. The median lethal concentrations (LCso) for freshwater fish range from 1.4 to 2.4
ppm and the effects concentration level (ECso) is 2.3 ppm for freshwater invertebrates. There
were screening level endangered species risk exceedences for listed freshwater fish with RQs
ranging up to 0.40 and listed freshwater invertebrates with RQs ranging up to 0.24 at an
application rate of 2.2 Ibs a.i./acre.
There were no aquatic chronic studies available for this risk assessment.
Page 38 of 81
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Estuarine/Marine
There were no data available to complete a risk assessment for estuarine/marine species;
however, the possible risk to freshwater species the rate of 2.2 Ibs a.i./acre suggests a potential
risk concern for estuarine/marine species at this rate as well.
4. Risk to Terrestrial Animals
Birds
For birds, MGK-264 is practically nontoxic on an acute basis as no deaths were observed
at any dose level. Therefore, no risk assessment was conducted for birds.
Mammals
For mammals, MGK-264 is practically nontoxic on an acute basis as no deaths were
observed at any dose level. No risk assessment was conducted for acute risk to mammals.
For chronic exposure in mammals, the multi-generation rat study produced a LOAEL of
1,250 mg/kg diet, with an endpoint of reduced body weight gain in the pups. A NOAEL was not
observed.
A range of applications from 1 to 20 per year, with an application interval of 7 days was
assessed at a rate of 2.2 Ibs a.i./acre. There were chronic risk exceedences depending on the
number of applications made in a year. For mammals feeding on short grass, RQs range from
0.42 (1 application) to 3.03 (20 applications), for tall grass RQs range from 0.19 (1 application)
to 1.39 (20 applications), and for broadleaf plants/small insects RQs range from 0.24 (1
application) to 1.7 (20 application). There were no chronic LOG exceedences for mammals
feeding on fruits/pods/large insects. Many of these RQs are expected to be substantially reduced
when labels are amended to reflect a maximum application rate of 0.3 Ibs a.i./acre.
5. Risk to Plants
No data were required for plants; therefore, no assessment was conducted to evaluate
risks to terrestrial or aquatic plants. It is unlikely that MGK-264 would cause phytotoxicity in
plants.
6. Endangered Species
The Agency's screening level assessment indicated that MGK-264 is practically nontoxic
to birds and mammals on an acute basis. No deaths were observed at any dose level and no risk
assessments were conducted for acute risk to mammals or birds. These results suggest that
MGK-264 will have no direct acute effects on threatened and endangered mammals or birds.
There are no data or reported incidents on plant effects from MGK-264. The preliminary risk
assessment for endangered species indicates that RQs exceed endangered species LOCs for
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aquatic organisms. However, this preliminary assessment will be modified as proposed label
changes limiting applications to 0.3 Ibs a.i./acre are implemented. Further, potential indirect
effects to any species dependent upon a species that experiences effects from use of MGK-264
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. Risk Management, Reregistration, and Tolerance Reassessment Decision
A. Determination of Reregistration Eligibility and Tolerance Reassessment
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 data to support reregi strati on of products containing MGK-264. The
Agency has completed its review of these generic data, and has determined that the data are
sufficient to support reregi strati on of all products containing MGK-264.
The Agency has completed its assessment of the dietary, occupational, residential, and
ecological risk associated with the use of pesticide products containing the active ingredient
MGK-264. Based on a review of these data and on public comments on the Agency's
assessments for the active ingredient MGK-264, the Agency has sufficient information on the
human health and ecological effects to make decisions as part of the tolerance reassessment
process under FFDCA and reregi strati on process under FIFRA, as amended by FQPA. The
Agency has determined that products containing MGK-264 are 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. Label changes are described in Section V.
Appendix A summarizes the uses of MGK-264 that are eligible for reregi strati on. Appendix B
identifies the generic data that the Agency reviewed as part of its determination of reregi strati on
eligibility of MGK-264, and lists the submitted studies that the Agency found acceptable. Data
gaps are identified as generic data requirements that have not been satisfied with acceptable data.
Based on its evaluation of MGK-264, the Agency has determined that MGK-264
products, unless labeled and used as specified in this document, would present risks inconsistent
with FIFRA and FQPA. Accordingly, should a registrant fail to implement any of the
reregi strati on requirements identified in this document, the Agency may take regulatory action to
address the risk concerns from the use of MGK-264. If all changes outlined in this document are
incorporated into the product labels, and all required data are acceptable, then all current risks for
MGK-264 will be adequately mitigated for the purposes of this determination. Once an
Endangered Species assessment is completed, further changes to these registrations may be
necessary as explained under "Endangered Species Concerns" above.
B. Regulatory Position
Through the Agency's public participation process, EPA worked with stakeholders and
the public to reach the regulatory decisions for MGK-264. EPA released its MGK-264
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preliminary risk assessments for public comment on April 27, 2005, for a 60-day public comment
period (Phase 3 of the 6 Phase public participation process). Where appropriate, the MGK-264 risk
assessments were revised in response to the comments received, and the assessments were released for
an additional 60 day public comment period on September 21, 2005 (Phase 5 of the 6 Phase public
participation process). During both public comment periods, the Agency received comments from
MGK Company, stakeholder groups such as the State and Local government entities in
California, California Water Boards, and Publicly Owned Treatment Works. The comments
included concerns about synergistic effects with MGK-264, water quality concerns with urban
runoff, and other water quality concerns from residential uses including pet shampoos. All of the
preliminary and revised MGK-264 risk assessments, public comments, response to comments,
and this RED document are available in the public docket (OPP-2005-0040) at EPA's docket and
in the EPA's electronic docket at www.regulations.gov.
1. Food Quality Protection Act Findings
a. "Risk Cup" Determination
As part of the FQPA tolerance reassessment process, EPA assessed the risks associated
with MGK-264. EPA has determined that risk from dietary (food + water) exposure is within its
own "risk cup." An aggregate assessment was conducted for MGK-264 for exposures through
dietary and residential exposures. The Agency has determined that with the mitigation measures
outlined below the human health risks from these combined exposures are within acceptable
levels. In other words, EPA has concluded that the tolerances for MGK-264 meet FQPA safety
standards. In reaching this determination, EPA has considered the available information on the
special sensitivity of infants and children, as well as aggregate exposure from food, drinking
water, and residential sources.
b. Determination of Safety to U.S. Population
The Agency has determined that the established tolerances for MGK-264, with
amendments and changes as specified in this document, meet the safety standards under the
FQPA amendments to section 408(b)(2)(D) of the FFDCA, as amended by FQPA, and that there
is a reasonable certainty no harm will result to the general population or any subgroup from the
use of MGK-264. In reaching this conclusion, the Agency has considered all available
information on the toxicity, use practices, and the environmental behavior of MGK-264. The
acute, chronic, short-term, intermediate-term, and long-term risks from food, drinking water, and
residential exposures do not exceed the Agency's level of concern either individually or
aggregated, after mitigation measures outlined below are considered.
c. Determination of Safety to Infants and Children
EPA has determined that the established tolerances for MGK-264, with amendments and
changes as specified in this document, meet the safety standards under the FQPA amendments to
section 408(b)(2)(C) of the FFDCA, that there is a reasonable certainty of no harm for infants
and children. The safety determination for infants and children considers factors on the toxicity,
use practices and environmental behavior noted above for the general population, but also takes
into account the possibility of increased dietary exposure due to the specific consumption
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patterns of infants and children, as well as the possibility of increased susceptibility to the toxic
effects of MGK-264 residues in this population subgroup.
In determining whether or not infants and children are particularly susceptible to toxic
effects from exposure to residues of MGK-264, the Agency considered the completeness of the
hazard database for developmental and reproductive effects, the nature of the effects observed,
and other information. The FQPA Safety Factor has been reduced to IX because there are no
residual uncertainties for pre- and/or post-natal toxicity, exposure is not underestimated, and
there is no evidence of increased susceptibility.
2. Endocrine Disrupter Effects
EPA is required under the FFDCA, as amended by FQPA, to develop a screening
program to determine whether certain substances (including all pesticide active and other
ingredients) "may have an effect in humans that is similar to an effect produced by a naturally
occurring estrogen, or other endocrine effects as the Administrator may designate." Following
recommendations of its Endocrine Disrupter Screening and Testing Advisory Committee
(EDSTAC), EPA determined that there was a scientific basis for including, as part of the
program, the androgen and thyroid hormone systems, in addition to the estrogen hormone
system. EPA also adopted EDSTAC's recommendation that EPA include evaluations of
potential effects in wildlife. For pesticides, EPA will use FIFRA and, to the extent that effects in
wildlife may help determine whether a substance may have an effect in humans, FFDCA
authority to require the wildlife evaluations. As the science develops and resources allow,
screening of additional hormone systems may be added to the Endocrine Disrupter Screening
Program (EDSP).
In the available toxicity studies on MGK-264, there was no estrogen or androgen
mediated toxicity. It is noted, however, that the rat carcinogenicity study demonstrated increased
thyroid tumors that may have been related to perturbation of the thyroid/liver/pituitary axis to
alter thyroid hormone metabolism. EPA believes the endpoints and risk scenarios evaluated are
protective of this potential endocrine effect. When additional appropriate screening and/or
testing protocols being considered under the Agency's EDSP have been developed, MGK-264
may be subjected to further screening and/or testing to better characterize effects related to
endocrine disruption.
3. Cumulative Risks
The Food Quality Protection Act (FQPA) requires that the Agency consider available
information concerning the cumulative effects of a particular pesticide's residues and other
substances that have a common mechanism of toxicity. The reason for consideration of other
substances is due to the possibility that low-level exposures to multiple chemical substances that
cause a common toxic effect by a common toxic mechanism could lead to the same adverse
health effect as would a higher level of exposure to any of the substances individually. Unlike
other pesticides for which EPA has followed a cumulative risk approach based on a common
mechanism of toxicity, EPA has not made a common mechanism of toxicity finding for MGK-
264 and any other substances. Therefore, for purpose of this decision, EPA has not assemmed
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that MGK-264 shares a common mechanism of toxicity with other substances. For information
regarding EPA's efforts to determine which chemicals have a common mechanism of toxicity
and to evaluate the cumulative effects of such chemicals, see the policy statements released by
EPA's Office of Pesticide Programs concerning common mechanism determinations and
procedures for cumulating effects from substances found to have a common mechanism on
EPA's website at http://www.epa.gov/pesticides/cumulative/.
C. Tolerance Reassessment Summary
Table 16 provides a summary of the MGK-264 tolerance reassessment decision. Further
tolerance explanation is provided after the table.
All references that indicate use in combination with another active ingredient, such as
pyrethrins or PBO, are removed, or decoupled from the tolerance expressions for MGK-264.
EPA will propose to update 40 CFR part 180 to reflect all of these changes as summarized in
Table 15 below.
Table 15: 40 CFR Changes for MGK-264
Current 40 CFR Citation
§180.367(a)(2)(i)
§180. 367 (a)(2)(ii)
§180.127(a)(2)(iii)
Action
Remove
Retain
Remove
Comment
This section refers MGK-264 being used in conjunction
with pyrethrins and piperonyl butoxide in food-processing
areas. All references to use with multiple chemicals will
be removed from the CFR.
This tolerance for food areas will be retained as specified
in Table 16 below.
Recodify under §180. 367(a)(l)
Old language not used in the CFR currently.
Table 16: Tolerance Reassessment Summary for MGK-264
Commodity
Current
Tolerance
(ppm)
Tolerance
Reassessment
(ppm)
Comment
Tolerances Listed Under 40 CFR §180. 367(a)(l)
Cattle, fat
Goat, fat
Hog, fat
Horse, fat
0.3
0.3
0.3
0.3
Revoke
Revoke
Revoke
Revoke
Direct dermal uses are no longer being
supported for uses on livestock intended for
food uses.
Direct dermal uses are no longer being
supported for uses on livestock intended for
food uses.
Direct dermal uses are no longer being
supported for uses on livestock intended for
food uses.
Direct dermal uses are no longer being
supported for uses on livestock intended for
food uses.
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Table 16: Tolerance Reassessment Summary for MGK-264
Commodity
Milk, fat
Sheep, fat
Current
Tolerance
(ppm)
0.3
0.3
Tolerance
Reassessment
(ppm)
Revoke
Revoke
Comment
Direct dermal uses are no longer being
supported for uses on livestock intended for
food uses.
Direct dermal uses are no longer being
supported for uses on livestock intended for
food uses.
Tolerances Listed Under 40 CFR §180.905(a)(6)
Raw Agricultural Commodities
Exemption
Revoke
Formerly established under 180.1001 (b).
The registrant has agreed to drop all
agricultural uses of MGK-264 on growing
crops
Tolerances Listed Under 40 CFR §180. 367(a)(2)(ii)
Processed Food (food handling
establishments)
10
5
Decouple MGK-264 tolerance from
pyrethrins and PBO.
The new tolerance should be stated as:
"A tolerance of 5 ppm is established for
residues of the insecticide synergist MGK-
264 in or on all food items in food handling
establishments where food and food
products are held, processed, prepared
and/or served."
Tolerance exemption under CFR S180.1001(b)(2)
MGK-264 is currently exempt from the requirement of a tolerance when applied to growing
crops in accordance with good agricultural practice [40 CFR §180.1001(b)(2)]. Based on the
decision of the registrant to drop all agricultural uses of MGK-264 on growing crops, EPA will
propose to revoke this tolerance exemption.
Tolerances Established Under CFR §180.367
Tolerances are established in 40 CFR §180.367(a)(l) for residues of n-octyl
bicycloheptene dicarboximide (MGK-264) per se, resulting from dermal applications to
livestock, in/on the fat of cattle, goat, sheep, hog, horse, and milk at 0.3 ppm. Because direct
dermal uses are no longer being supported for uses on livestock intended for food uses, EPA will
propose to revoke these tolerances.
The remainder of tolerances and tolerance exemptions established in CFR §180.367
pertain to uses of MGK-264 in food handling establishments and warehouses.
• According to 40 CFR § 180.367(a)(2)(i), MGK-264 may be safely used in combination
with piperonyl butoxide (PBO) and pyrethrins for control of insects in food-processing
and food-storage areas, provided that the food is removed or covered prior to such use.
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• According to 40 CFR §180.367(a)(2)(ii), residues in food resulting from the use
described in the preceding paragraph shall not exceed 10 ppm of MGK-264, 10 ppm of
PBO, and 1 ppm of pyrethrins.
• According to 40 CFR §180.367(a)(2)(iii), to assure the safe use of MGK-264, the label
and labeling shall conform to that registered with the U.S. EPA, and MGK-264 shall be
used in accordance with such label and labeling.
EPA will propose that the tolerance level of 10 ppm for MGK-264 in all foods be reduced
to 5.0 ppm to better reflect the likely residue levels expected based on the residue data and use
pattern. Presently, 40 CFR §180.367(a)(2)(i) specifies that MGK-264 may be used in
combination with PBO and pyrethrins for insect control in food-processing and food-storage
areas, provided that the food is removed or covered prior to such use.
However, MGK Company plans to market use of MGK-264-containing products in
warehouses without removing or covering food items which are packaged in cloth, paper, or foil
bags. Adequate residue data were submitted for MGK-264 reflecting residue levels based on this
use pattern. Consequently, EPA will propose that a paragraph be added to 40 CFR §180.367
specifying that bagged foods in warehouse storage need not be removed or covered prior to
applications of formulations containing MGK-264. The residue data indicate that these
uncovered bagged foods in warehouse storage are likely to exhibit finite levels of MGK-264
residues (<5.0 ppm) following treatment. In contrast, the covered or removed foods in food
processing/handling establishments are not likely to have detectable residue levels. This
determination does not apply to piperonyl butoxide and pyrethrins because the labels for these
pesticide chemicals were not examined in this decision, but are considered in separate
Reregi strati on Eligibility Decision documents. Products containing multiple active ingredients
will need to be labeled in accordance with the most protective provisions of any single
component active ingredient.
Codex/International Harmonization
There are no Codex, Canadian, or Mexican tolerances/MRLs for MGK-264.
Updated 40 CFR
The 40 CFR should be updated to incorporate all the changes specified above. Once
these changes are made the CFR should be in the format listed below.
§180.367 «-Octyl bicycloheptenedicarboximide; tolerances for residues.
(^General.
(1) A tolerance of 5 ppm is established for residues of the insecticide synergist
n-octyl bicycloheptene-dicarboximide in or on all food items in food handling
establishments where food and food products are held, processed, prepared
and/or served.
(b) Section 18 emergency exemptions.
[Reserved]
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(c) Tolerances with regional registrations.
[Reserved]
(d) Indirect or inadvertent residues.
[Reserved]
D. Regulatory Rationale
The Agency has determined that MGK-264 is eligible for reregi strati on provided that the
risk mitigation measures and label amendments specified in this RED are implemented. The
following is a summary of the rationale for managing risks associated with the use of MGK-264.
Additional label restrictions that were assumed in the risk assessments for MGK-264 are
included in the label changes summary table (Table 17).
1. Human Health Risk
a. Dietary (Food Only) Risk Mitigation
Acute Risk
Acute dietary (food only) risk does not exceed the Agency's level of concern; acute
dietary risk estimates are 13% of the aPAD for females 13 to 49 years old, the only sub-
population that needed to be assessed. Therefore, no mitigation is necessary for this scenario.
Chronic Risk
The chronic dietary (food only) risk is below the Agency's level of concern; risk
estimated are 19% cPAD for the general U.S. population, and 51% of the cPAD for children 1-2
years old, the most highly exposed subpopulation. Therefore, no mitigation is necessary for this
scenario.
b. Residential Risk Mitigation
i. Handler
In the residential handler exposure assessment a number of scenarios were assessed to
estimate the exposure to homeowners handling products containing MGK-264. The results from
the assessed residential handler scenarios indicate there are no residential risks of concern when
MGK-264 is mixed, loaded, applied, or handled by homeowners. Therefore, no mitigation is
necessary for these scenarios.
There were no dermal or inhalation handler data available for handlers applying liquids
for dip applications to pets. However, a scenario was assessed for residential handlers applying
shampoos to pets, which resulted in risks well above the Agency's level of concern for both
dermal (MOE is about 2,300) and inhalation (MOE is well over a million) exposures. Since the
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MOEs in the shampoo scenario are high, no additional steps are necessary to address risk from
dips while confirmatory data are being developed.
The dermal exposure from dips is expected to be higher than inhalation exposure. The
dermal risk assessment contains several conservative assumptions, as described below in the
insect repellent section, which may exaggerate the possible dermal risk from dips. The registrant
has agreed to conduct a 21 day dermal toxicity study in rats with MGK-264 up to the limit dose
of 1,000 milligrams per kilogram per day to confirm the Agency's assumption that risk from dips
are not above the Agency's level of concern. Exposure data for applicators using dips will be
held in reserve pending the outcome of the dermal toxicity study.
ii. Post-Application
A number of post-application residential scenarios were assessed for adults and children
exposed to MGK-264 indirectly after application. There were post-application dermal risk
concerns for toddlers exposed to MGK-264 from indoor spray applications, indoor fogger
applications, indoor dust applications, and from application of insect repellents. Aerosol space
and metered release applications were potentially a concern for post-application inhalation
exposure. Dusts applied as a broadcast treatment to carpets were potentially a concern for post-
application incidental oral exposure. For adults, there were post-application dermal risk
concerns from exposure to indoor dust applications to carpets and from use of insect repellants.
Indoor space and metered release applications were a concern for post-application inhalation
exposure.
Indoor Spray Applications - Surface and Fogger Applications
There are potential post-application dermal concerns for toddlers exposed to MGK-264
after indoor surface spray to both carpeted and hard surfaces (MOE is 780) and fogger
applications to carpeted surfaces (MOE is 840). The toxicity studies selected for the dermal risk
assessment contain several conservative assumptions which may exaggerate the toddler dermal
risk estimated for post-application exposure from indoor surface and fogger applications. These
assumptions, which are described further under the insect repellent section below, include
selecting an oral study instead of a route-specific dermal study for the risk assessment, adding an
additional 10X safety factor to the target MOE due to lack of a NOAEL in the oral study, plus a
conservative dermal absorption factor. Considering all of these factors together, the Agency
does not believe there is a post-application dermal risk of concern from use of surface or fogging
sprays indoors. The registrant has agreed to conduct a 21 day dermal toxicity study in rats with
MGK-264 up to the limit dose of 1,000 milligrams per kilogram per day to confirm this
conclusion. This study will allow the Agency to assess any possible dermal effects from MGK-
264 through a route-specific study more appropriate for dermal risk assessment.
Dusts - Broadcast Applications to Carpets
Applying dusts to carpets over a wide area can lead to exposure to children through
incidental oral exposures. Most of the labels containing this type of application indicate the dust
needs to be vacuumed after application. Since there is no information to determine how much
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MGK-264 is removed from the carpet while vacuuming, there is an unknown amount of dust
available for exposure to children. Using various assumptions in the assessment, the MOEs
range from 70 to 410. The Agency has concerns from the potential incidental oral exposure
children could have from this type of broadcast application to large carpeted areas. To reduce
exposure to children from broadcast dust applications to carpets, the registrants have agreed to
restrict carpet applications to spot treatments no greater than 3 feet by 3 feet in area.
In addition to the use on carpets, MGK-264 is also used on turf, and so an incidental oral
assessment was conducted for use on turf which is considered a conservative risk estimate for
oral exposures. This assessment includes 3 separate incidental oral exposure activities and
assumes the exposures occur simultaneously. The turf scenario methodology, which has been
peer reviewed and is better understood than the carpet dust scenario, includes incidental oral
exposure to pesticide on turf from (1) hand to mouth activities, (2) object to mouth activities, and
(3) ingesting soil particles. MOEs from all three of these incidental oral turf scenarios are
greater than the Agency's target MOE of 1,000 with MOEs ranging from 14,000 to 4 million.
Given the conservative nature of the turf exposure scenario, it is unlikely that the magnitude and
frequency of exposure to small spot treatments (3 sq ft) of dust formulations of MGK-264 would
result in exposure estimates equal to or greater than those estimated for the residential lawns.
Since there are no incidental oral risks of concern from the turf scenario, and the registrants have
agreed to reduce the amount of potential exposure to children by restricting applications to spots
only, the Agency is not requiring any additional data at this time.
Aerosol Space Sprays
There are potential inhalation risks from post-application exposure to MGK-264 from
aerosol space sprays. This scenario was evaluated with data from a Non-Dietary Exposure Task
Force (NDETF) study that measured the air concentration after an aerosol application of a
pyrethrins and piperonyl butoxide product assuming no deposition and no ventilation. The study
application rate was adjusted to reflect the MGK-264 application rate of 0.001 Ib ai/1,000 ft3.
With these assumptions the MOE for inhalation post-application exposure to MKG-264 was
estimated to be 170 for adults and 52 for children. MGK Company has agreed to reduce the rate
for aerosol space sprays from 0.001 Ib ai/1,000 ft3 to 0.00015 Ib ai/1,000 ft3. Using this new
application rate the MOEs are expected to be about 10 times higher.
In addition, there are currently label statements on some MGK-264 products that contain
the instructions: "When using indoors, do not remain in treated area. Ventilate the area for 15
minutes following treatment. Allow treated surfaces to thoroughly dry before use." Since
ventilation was not factored into the assessment, it can be expected that requiring a ventilation
period before entering a treated area would further reduce the potential exposure to adults and
children. Therefore, all MGK-264 aerosol space spray products will be required to include a 15
minute ventilation reentry restriction. In addition, MGK Company has agreed to conduct a
repeat aerosol study with MGK-264 with the lower rate and to follow the specific label
directions for ventilation periods in the study.
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Pet Applications with Dusts
There are both incidental oral (MOE is 130) and dermal (MOE is 61) risk concerns with
post-application exposure for toddlers exposed to pets treated with dust products. Therefore,
MGK Company has agreed to phase out all dust products used on pets.
Insect Repellents
There are potential dermal concerns for MGK-264 products applied to both adults and
children as insect repellents with MOEs ranging from 24 to 160. The toxicity studies selected
for the dermal risk assessment contain several conservative assumptions which may exaggerate
the dermal risk from repellents. A dermal toxicity study in rabbits was conducted for MGK-
264, but was not selected for risk calculation because the highest dose tested (100 mg/kg/day)
did not elicit systemic toxicity. Since animals were not dosed at levels above 100 mg/kg/day in
the dermal study an oral study was selected for the dermal risk assessment.
The dermal risk assessment for MGK-264 is based on a LOAEL of 61 mg/kg/day from a
multi-generation reproduction study in rats. The LOAEL was based on slight decreases in
maternal body weight. An additional 10X safety factor was added to the LOAEL, because a
NOAEL was not reached in this study. In addition, a dermal absorption factor of 10 percent
from a study using human volunteers was factored into the dermal calculation. The dermal
absorption factor of 10% that was factored into the dermal assessment includes the portion of
radioactive material that was not recovered in the human dermal absorption study (MRID:
42976701, -02). About 1% of the radiolabelled material was recovered in the human volunteers,
with about 9% assumed to be retained in the body. It is an upper bound assumption to include all
of the unaccounted for radioactivity in the dermal absorption factor.
Considering all of these factors together and that no systemic effects were observed in the
rabbit dermal study at 100 milligrams per kilogram per day, the Agency does not believe there is
a risk of concern from use of repellents with MGK-264. MGK Company has agreed to conduct a
21-day dermal toxicity study in rats with MGK-264 up to the limit dose of 1,000 milligrams per
kilogram per day to confirm this conclusion. This study will allow the Agency to assess any
possible dermal effects from MGK-264 insect repellents through a route-specific study more
appropriate for dermal risk assessment. Depending on the results of this study, further mitigation
could be required in the future for insect repellents.
Indoor Metered Release Devices - Residential
There are potential risk concerns for post-application short- and intermediate-term
exposures following indoor applications with metered release devices. The MOEs range from 13
to 440 and are less than the target MOE of 1,000. The risk calculations for the metered release
scenarios are conservative because it was assumed that the aerosol sprays would remain airborne
until they were removed by ventilation and the effect of aerosol spray settling was not
considered. Aerosol spray settling could be a major factor depending upon the aerosol droplet
size and rate of evaporation. Information regarding the aerosol droplet size and evaporation rate
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could be used to refine the risks, particularly for the residential scenarios where the ventilation
removal rate is probably slower than the settling rate.
In the absence of such data, to reduce the risks to potentially sensitive bystander
populations, MGK Company has agreed to remove use sites where sensitive populations could
be present from their metered release device product labels including day care centers, nursing
homes, schools, and hospitals. In addition, EPA is requiring air concentration and particle size
data for indoor metered release devices. Use of metered release device in residential areas will
be prohibited unless acceptable data are submitted that show there are no risks of concern to
residential populations.
Outdoor Residential Misting Systems
MGK Company is not supporting the use of MGK-264 in outdoor residential misting
systems, and has agreed to include a statement on all technical labels prohibiting use in these
systems. All end-use product labels will also be required to include a label statement prohibiting
use in outdoor residential misting systems. Table 17 contains a list of all label statements
required for the reregi strati on of MGK-264.
c. Aggregate Risk Mitigation
Food and drinking water exposures were aggregated for acute (one day) and chronic (one
year or more) durations. A short-term aggregate assessment was also completed since some
MGK-264 residential uses represent short-term exposure scenarios. The short-term aggregate
risk assessment added dermal, oral non-dietary exposure, and average food and water exposures
since there was a common toxicity endpoint of decreased pup body weight for these routes of
exposure.
i. Acute and Chronic Aggregate Risk (Food + Water)
Acute DWLOC
Acute DWLOCs were calculated based on acute dietary exposure estimates and default
body weights and water consumption figures. The EDWCs for both surface water (EDWC =11)
and groundwater (EDWC = 0.12) are well below the acute DWLOCs (DWLOC = 26,160) for the
only population subgroup (females 13-49 years old) that was relevant from the toxicity endpoints
selected, indicating that acute aggregate exposure to MGK-264 in food and water is not a
concern. Therefore, no mitigation is necessary for this scenario.
Chronic DWLOC
Chronic DWLOCs were calculated based on the chronic dietary exposure estimates and
default body weights and water consumption figures. The EDWCs for both surface water
(EDWC = 5.2) and groundwater (EDWC = 0.12) are well below the chronic DWLOCs for the
general U.S. population (DWLOC = 1,722) and the most highly exposed sub-population,
Children 1 to 2 years old (DWLOC Children 1-2 years = 301), indicating that chronic aggregate
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exposure to MGK-264 in food and water is below the Agency's level of concern for these
populations. Therefore, no mitigation is necessary for this scenario.
ii. Short-Term Aggregate (Food + Water + Residential)
The short term aggregate risk for MGK-264 was calculated by adding exposure
estimates from food, drinking water, dermal, and incidental oral exposure pathways for the U.S.
population and the highest exposed sub-population, children 1-2 years old, and comparing them
with model based EDWCs. The aggregate MOE takes into account average food consumption
values (calculated from the chronic dietary assessment), and oral and dermal exposures (from the
indoor fogger scenario on hard floors at the rate of 0.01 Ib ai/1,000 ft2). The lowest short term
DWLOC (38 ppb) for children 1-2 years old is higher than the surface water EDWC (0.2 ppb)
and the ground water EDWC (0.12 ppb), and therefore does not result in a risk of concern for
this scenario (indoor fogging to hard surfaces). Therefore, no mitigation is necessary.
Many of the indoor residential post-application use scenarios resulted in predicted risk
levels that exceeded the Agency's level of concern by themselves (i.e., without aggregating).
Thus, the following scenarios were not included in the aggregate assessment indoor spray
applications, fogger applications to carpets, dust applications to pets, insect repellents applied to
humans, aerosol space sprays, metered release applications, and dusts applied as a broadcast
treatment to carpets.
In general, the potential exposure to MGK-264 from residential scenarios exceeds that
expected from food and water sources. Because the exposure contributions from food and water
sources are relatively low in the aggregate risk assessment, mitigation for residential exposure
scenarios of potential concern will be protective for the short-term aggregate risk from MGK-
264.
d. Occupational Risk Mitigation
Occupational exposure assessments were completed by the Agency considering the use
of baseline PPE and, if warranted, for handlers, increasing levels of PPE and engineering
controls in order to estimate the potential impact on exposure and risk. The target MOE for
MGK-264 is 1,000 for both dermal and inhalation exposures.
i. Handler Risk Mitigation
Handheld Equipment
There are possible dermal risk concerns for occupational applicators mixing, loading, and
applying MGK-264 for scenarios using handheld equipment such as handwands, backpack, or
handgun spray equipment. The addition of gloves while using handheld equipment increases the
estimated MOEs to greater than 1,000. Therefore, MGK Company has agreed to add gloves to
the baseline PPE requirement which includes long pants, long sleeved shirt, shoes and socks for
all scenarios that involve occupational handlers applying MGK-264 with handheld equipment.
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Handheld Foggers Applied Indoors (including thermal cold, and ULV foggers)
The Agency does not have data to estimate risk to applicators fogging with hand-held
equipment indoors. Due to insufficient information, two different handheld fogging studies that
were submitted for other chemicals were used for inhalation and dermal risk calculation for
MGK-264 that resulted in MOE estimates that ranged from 12 to 5711 for inhalation risk, and
2179 for dermal risk. Due to the great uncertainty in fogging practices with MGK-264, the
Agency is requiring use and usage information to determine if the existing data are appropriate to
calculate exposure values for fogging with MGK-264. Based on review of these use and usage
data, the Agency will determine if further fogging exposure data are needed.
To mitigate potential inhalation and dermal risks to applicators using handheld fogging
equipment, a dust-mist respirator (PF10) will be required in the interim to address inhalation risk
concerns. Double layers, including gloves, coveralls over long-pants and a long sleeved shirt,
shoes and socks, are required to address the dermal risk concerns. Based on review of the
use/usage data the Agency may require additional exposure data in the future.
Dusts Applied through Power Dusters - Agricultural and Pest Control Operator (PCO) Handlers
The Agency was not able to assess scenarios involving dust applications with power
dusters because there are no exposure data to represent this application method. Power dusters
could potentially create a significant inhalation risk. Due to a lack of data on this exposure
scenario and no interest in supporting this application method from MGK Company, labels will
be amended to prohibit power dusters as an application method for MGK-264 for agricultural or
PCO handlers. If there is interest in supporting this application method, acceptable handler
exposure data with power dusters need to be submitted to the Agency.
Dusts Applied through Bulb Dusters
The Agency was not able to assess scenarios involving dust applications with bulb
dusters because of a lack of data. Bulb dusters are only used for crack and crevice treatments,
which reduces the possible exposure to an applicator. Due to small amounts of dust used in this
application method, the exposure is expected to be negligible. Therefore, no mitigation or data
are required for this scenario.
Pet Dip Applications
As stated above under the residential handler section, there is a data gap for handlers
making dip applications to pets. There were no dermal or inhalation handler data available for
handlers mixing/loading/applying liquids for dip applications. Based on high MOEs from a pet
shampoo study, there are no interim mitigation measures for applicators making dips to pets.
The dermal exposure from dips is expected to be higher than inhalation exposure; therefore,
applicator pet dip exposure data may be required for this scenario pending the outcome of a 21-
day dermal toxicity study that could change the dermal risk assessment for MGK-264.
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ii. Post-Application Worker Risk Mitigation
Metered Release Devices - Occupational Settings
The Agency has similar concerns for post-application short- and intermediate- term
exposures from these systems as described in the residential post-application section on this
chapter. The risk estimates from these occupational uses are expected to be less of a concern due
to the fact that occupational areas where these devices are installed generally have a greater
ventilation capacity.
Therefore, to better understand the risks from metered release devices in occupational
settings the Agency is requiring air concentration and particle size data for these products, as
well as requiring the label changes included in Section V. Some products labeled for use in
occupational areas are also labeled for use in residential settings and areas where children may
be present. Therefore, as mentioned in the residential metered release device section above,
MGK Company will remove the following use sites where potentially sensitive populations may
be present from their metered release device product labels: day-care centers, nursing homes, and
schools. Use of metered release device in residential areas will be prohibited unless acceptable
data are submitted that show there are no risks of concern to residential populations.
2. Non-Target Organism (Ecological) Risk Management
For aquatic organisms, there were slight exceedences for endangered species for
freshwater fish (maximum RQ = 0.40) and freshwater invertebrates (maximum RQ = 0.24).
There were no data available for estuarine/marine species; however, the risk to freshwater
species suggests a potential risk concern for estuarine/marine species as well. The maximum use
rate considered in the assessment was 2.2 Ibs a.i./acre for lawn insect control. The registrant has
since agreed to reduce the outdoor spray application rate from 2.2 Ibs a.i./acre to 0.3 Ibs a.i./acre,
which will decrease the RQs approximately 7 fold. This will also decrease the potential loading
and exposure to aquatic organisms. The majority of RQs for aquatic organisms will be below the
Agency's level of concern, with the highest RQ for freshwater fish about 0.06.
For terrestrial organisms, there were chronic risk exceedences for most mammals with
RQs ranging up to 3.03. Again, the maximum use rate considered in the assessment was 2.2 Ibs
a.i./acre for lawn insect control. The registrant has since agreed to reduce the outdoor spray
application rate from 2.2 Ibs a.i./acre to 0.3 Ibs a.i./acre, which will decrease the potential the
RQs approximately 7 fold. As a result, all of the chronic RQs for terrestrial organisms are
expected to fall below the Agency's level of concern at the rate of 0.3 Ibs a.i./acre.
Other Urban Uses
In the MGK-264 ecological risk assessment two turf scenarios were used to estimate the
potential risk from MGK-264 to the environment and resulted in slight potential risk
exceedances for aquatic organisms. Although MGK-264 is registered for use on turf, it is also
used on other sites including outdoor residential areas and a wide variety of indoor sites. The
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Agency does not currently have a model available to assess the urban contribution to the residues
of MGK-264 in the environment, but EPA is working to develop a model for this scenario.
Comments from a variety of stakeholders and recent studies focusing on the contribution of
pyrethroid residues used in urban settings to the estimated environmental concentration of
pesticides have lead to further exploration of this area of pesticide contribution.
Development of a screening model which could simulate the fate and transport of
pesticides applied in an urban setting would require a large body of data which is currently
unavailable. For instance, an urban landscape cannot be simulated as easily as an agricultural
field. The PRZM model simulates runoff from a field using readily available data describing
surface soil characteristics and laboratory data detailing the persistence and mobility of
pesticides in these soils. The field simulated is homogenously planted to a single crop, and soil
and water are transported from the field to an adjacent receiving water body with dimensions
consistent with USDA farm-pond construction guidelines.
By contrast, an urban landscape or suburban housing development consists of impervious
surfaces such as streets and sidewalks, and permeable surfaces such as lawns and parkland. One
could expect much greater mobility for pesticides applied to impervious surfaces, but laboratory
soil metabolism studies may not provide an accurate measure of the persistence of pesticides on
these surfaces. The path runoff water and eroded sediment might take is less obvious for an
urban setting than an agricultural field. First, an urban landscape cannot be considered
homogeneous, as the proportion of impervious and pervious surfaces varies for different
locations. In addition, the flow path of runoff water and sediment is not necessarily a direct path
over land, but can pass below ground through storm sewer networks, or be directed or slowed by
pumping stations or temporary holding ponds.
The timing and magnitude of urban applications is less well defined than turf uses. While
turf uses could occur within a predictable window during the growing season, the need for urban
uses could occur at different times for different locations each year, and might occur at different
times within the same watershed. In addition, since records of how and to what extent MGK-264
is applied by homeowners are less well defined than for professional applications, it is harder to
estimate the total load to model.
Monitoring Data
The Agency considers surface water monitoring data in addition to modeling results
when they are available. Available monitoring data in raw ground water and surface water, and
in finished drinking water from four cities, indicate that MGK-264 has not been found at the
detectable limit of 0.1 ppb.
There has been limited monitoring for the pyrethroids, but recently researchers from the
University of California- Berkeley have published studies which reported transport of
pyrethroids to stream bed sediment as a result of urban uses. In 2004, Weston, et al. collected
sediment from creeks draining a residential area in Rosedale, California. The sediments were
analyzed for 7 pyrethroids (including two currently in the reregi strati on process), as well as for
other insecticides. All of the pyrethroids were detected in the bed sediment from at least one
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sampling location. The researchers exposed the aquatic amphipod Hyalella azteca to the 21
sediment samples they collected; pesticide concentrations in 9 of these samples were sufficient to
cause 90% mortality in the amphipods after a 10-day exposure. The concentrations of
pyrethroids detected in the sediments were above the level expected to cause 50% mortality in H.
azteca, suggesting that the pyrethroids were responsible for the observed toxicity.
In a subsequent study, Weston, et al. collected samples from 15 urban creeks in
California and 12 in Tennessee. Toxicity to H. azteca was observed at least once with sediments
taken from 12 of the 15 California sampling sites. In most cases, the toxicity could be accounted
for by the concentrations of pyrethroids detected in the sediment. Pyrethroids were rarely
detected in the Tennessee sediment samples, and exposure to the Tennessee sediments did not
prove to be toxic to H. azteca. The Weston studies did not sample for MGK-264.
The Weston, et al. studies indicate that urban uses of pesticides can lead to surface-water
contamination, including contamination by pesticides that would bind almost completely to soil
in an agricultural setting. In general MGK-264 is more mobile in soils than the pyrethrins or the
pyrethroids. Since MGK-264 is commonly formulated with these types of insecticides, efforts to
better understand the conditions under which pyrethroids and pyrethrins might be transported to
surface water would help improve our assessment of the scenarios in which MGK-264 might
contribute to increased risk to aquatic organisms.
The results of the Weston, et al. studies have led a number of organizations, such as the
California State Water Resources Control Board (SWRCB) to submit comments to the Agency
calling for mitigation measures to prevent surface-water contamination. However, the lack of
data and information to develop an urban pesticide transport model also makes it difficult to
identify whether risks may exceed some LOCs, and appropriate mitigation at this time. The
Agency is committed to develop mitigation options during the reregi strati on process, and to
identify steps which can be taken to allow a greater understanding of potential ecological risk
from urban use of pesticides.
It would be useful, as some commenters have suggested, performing a risk assessment for
all of the pyrethrins, pyrethroids, and synergists at the same time. The Weston papers indicated
that the sediments which proved toxic to the tested aquatic invertebrate were contaminated not
only with the chemicals undergoing reregi strati on, but also pyrethroids such as bifenthrin and
lambda-cyhalothrin.
The Agency will also continue in its efforts to develop a screening model for urban
pesticide uses. Advances in the resolution of GIS databases may allow better representation of
the impervious and pervious portions of a typical urban landscape. As it becomes clearer which
uses are most likely to lead to transport of MGK-264 to surface water, the conceptual model of
how urban transport should be simulated will be more focused.
The Agency plans to evaluate available published literature and call-in data to resolve
data gaps to ensure a robust comparison of the potential ecological risk of all the pyrethrins,
pyrethroids, and synergists during Registration Review. Toxicity data cited by several
commenters from published literature are included in the Agency's ECOTOX database. The
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Agency will evaluate the quality of studies to identify those to be included in the risk
assessments during Registration Review.
V. What Registrants Need to Do
The Agency has determined that MGK-264 is eligible for reregi strati on provided that the
mitigation measures and label changes identified in this RED are implemented. Registrants will
need to amend their product labeling to incorporate the label statements set forth in the Label
Changes Summary Table (Table 17). The Agency intends to issue Data Call-Ins (DCIs)
requiring generic and product specific data. Generally, the registrant will have 90 days from
receipt of a DCI to complete and submit response forms or request time extensions and/or
waivers with a full written justification. For product-specific data, the registrant will have eight
months to submit data and amended labels.
A. Manufacturing Use Products
1. Additional Generic Data Requirements
The generic data base supporting the reregi strati on of MGK-264 for currently registered
uses has been reviewed and determined to be substantially complete. However, the data listed
below are necessary to confirm the reregistration eligibility decision documented in this RED.
Human Health Data Requirements
Toxicity Data
• 870.1100: Acute oral toxicity data on the technical grade product.
• 870.1300: Acute inhalation data on the technical grade product.
• 870.2600: Skin sensitization data on the technical grade product.
• 870.3200: 21-day dermal toxicity study in rats up to the limit dose of 1,000 mg/kg/day.
Chemistry
• 830.7050: UV/Vis data on the technical grade product.
Occupational and Residential Data
• 875.1700: Metered release devices. Use and usage information, as well as air
concentration and particle size data.
• 875.1700: Applicators using handheld fogging equipment. Use and usage data on
application practices.
• 875.1400: Aerosol Space Sprays. A repeat aerosol study with MGK-264 with ventilation
periods included in the study.
• 875.2400 & 875.2500: Exposure data for pet dip applications.
• 875.2400 & 875.2500: Shampoo application exposure data (used carbaryl study in risk
assessment).
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• 875.2400 & 875.2500: Trigger pump spray exposure data (used propoxur study in risk
assessment).
Environmental Fate and Ecological Effects Data
The following ecological studies are required for MGK-264:
• 850.2300: Avian reproduction study.
The potential chronic risks to birds would be clearer if a study on avian reproductive
effects was available. Chronic risk to birds may exist because the chronic RQ for
mammals exceeds the Level of Concern. The avian reproduction study is required to
remove or confirm the presumption of risk to birds.
• 850.1035 (mysid shrimp), 805.1025 (oyster), 850.1075 (fish) Acute toxicity studies.
Acute toxicity data on estuarine/marine fish, invertebrates, and mollusks are required to
clarify the potential ecological risks to aquatic estuarine/marine organisms. In the risk
assessment uncertainty exists regarding risk to estuarine/marine species because of the
presumed risk to freshwater species. These studies will remove uncertainty regarding the
presumption of risk.
The following studies are reserved and may be required to refine the Environmental Fate and
Ecological Effects assessment of MGK-264:
• 835.4300: Aerobic aquatic metabolism.
The Agency's understanding of the exposure of aquatic and estuarine/marine organisms
would be improved by submission of data on aerobic aquatic metabolism. This study will
allow refinement of the modeled aquatic EECs, and possibly remove the presumption of
risk to aquatic estuarine/marine organisms.
• 850.1730: Fish bioaccumulation study.
The measured log Kow value (3.70) indicates a potential for bioaccumulation in fish.
Since fish are expected to be exposed to MGK-264, a fish bioaccumulation study
(guideline 165-4) will indicate if there is any potential for food-chain effects in species
that consume fish.
In addition to the ecological and fate data requirements listed above for MGK-264, there
may be uncertainties about how the synergists effects from chemicals like MGK-264 and
piperonyl butoxide could impact the risk to certain non-target organisms, specifically aquatic
invertebrates, fish, and non-target insects. Since products formulated with piperonyl butoxide
are registered for use in more outdoor areas than products containing MGK-264, additional
confirmatory data for typical end-use products formulated with piperonyl butoxide will be
required in the piperonyl butoxide RED and Data Call-In. Some of the data required for the
piperonyl butoxide products will include products containing MGK-264.
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2. Labeling Requirements
To ensure compliance with FIFRA, manufacturing use product (MUP) labeling should be
revised to comply with all current EPA regulations, PR Notices, and applicable policies. The
MUP labeling should bear the labeling contained in Table 17.
3. Spray Drift Management
The Agency has been working closely with stakeholders to develop improved approaches
for mitigating risks to human health and the environment from pesticide spray drift. As part of
the reregi strati on process, the EPA will continue to work with all interested parties on this
important issue.
Specific spray drift language for ground applications of MGK-264 are outlined in the
"spray drift management" section of Table 17.
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 that they meet current EPA acceptance criteria
and if not, commit to conduct new studies. If a registrant believes that previously submitted data
meet current testing standards, then the study MRID numbers should be cited according to the
instructions in the Requirement Status and Registrants Response Form provided for each
product. The Agency intends to issue a separate product-specific data call-in (PDCI), outlining
specific data requirements. For any questions regarding the PDCI, please contact Bonnie Adler
at (703) 308-8523.
In addition, efficacy data for all applications that target public health pests must be
submitted, including data for insect repellents and metered release devices. Additional
information on the efficacy data can be found in the Series 810 Product Performance Test
Guidelines on the Agency's website.
(http://www.epa.gov/opptsfrs/publications/OPPTS_Harmonized/810_Product_Performance_Test_Guidelines/index.
html)
2. Labeling for End-Use Products
To be eligible for reregi strati on, labeling changes are necessary to implement measures
outlined in Section IV above. Specific language to incorporate these changes is specified in
Table 17. Generally, conditions for the distribution and sale of products bearing old
labels/labeling will be established when the label changes are approved. However, specific
existing stocks time frames will be established case-by-case, depending on the number of
products involved, the number of label changes, and other factors.
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Labeling Changes Summary Table 17
In order to be eligible for reregi strati on, all product labels must be amended to incorporate the risk mitigation measures outlined in
Section IV. The following table describes how language on the labels should be amended.
Description
MGK-264 Required Labeling Language
Placement on Label
Manufacturing-Use Products
Required on all MUPs
"Only for formulation into a synergist for the following use(s) [fill blank only with those uses that
are being supported by MP registrants]."
"Not for formulation into an end use product with directions for use permitting use in power
dusters."
"Not for formulation into a dust end use product for use on pets."
Outdoor Residential Misting Systems
The following statement must appear on the MUP label of all liquid products that could feasibly be
formulated into end-use products (e.g. liquid concentrates) for use in outdoor residential misting
systems:
"Not for formulation into an end use product for use in outdoor residential misting systems."
Pet Care
Ready-to-use formulated products for use on pets eligible for reregistration must not contain a
percentage of a.i. that exceeds the following:
Shampoos - 1.0 % ai
Sprays - 2.5% ai
Spot-on or Pour-on - 1.0 % ai
Mousse, soap, lotion, roll-on, or gel - 0.5 % ai
Comb-0.5 %ai
Wipe or rub - 1.5 % ai
Directions for Use
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Description
MGK-264 Required Labeling Language
Placement on Label
Towelettes-2% ai
In addition for collars and dips, products must not contain a percentage of a.i. of MGK-264 that
exceeds the following:
Collar - 0.0022 Ibs ai/collar
Dip - 0.3 % ai per ounce of dip
Direct Application to Non-domestic Animals (non-food livestock only, i.e. donkeys, horses,
ponies, mules)
Formulated products must not contain a percentage of a.i. that exceeds the following:
Towelettes for application to horses- 37.5 mg ai/ towelette (or 0.0000826 Ibs ai/wipe)
Repellent Applied to Humans
Formulated products eligible for reregistration must not contain a percentage of a.i. that exceeds the
following:
On skin or clothing - 5.0 % ai
One of these statements
may be added to a label to
allow reformulation of the
product for a specific use or
all additional uses
supported by a formulator
or user group.
"This product may be used to formulate products for specific use(s) not listed on the MP label if the
formulator, user group, or grower has complied with U.S. EPA submission requirements regarding
support of such use(s)."
"This product may be used to formulate products for any additional use(s) not listed on the 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
"Do not discharge effluent containing this product into lakes, streams, ponds, estuaries, oceans or
other waters unless in accordance with the requirements of a National Pollutant Discharge
Elimination System (NPDES) permit and the permitting authority has been notified in writing prior
to discharge. Do not discharge effluent containing this product to sewer systems without previously
notifying the local sewage treatment plant authority. For guidance contact your State Water Board
or Regional Office of the EPA. Do not contaminate water when disposing of equipment wash-
waters."
Directions for Use
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Description
MGK-264 Required Labeling Language
Placement on Label
End-Use Products Intended for Occupational Use (WPS andnon-WPS)
Handler PPE Requirements1
for Liquid Products that are
registered for use in
handheld fogging
equipment or could
potentially be used in
handheld fogging
equipment.
[including:
microencapsulated
concentrates and liquid
concentrates]
Notes:
(1) If the use of handheld
equipment such as
handwands, backpack
sprayers, or foggers is not
feasible or is prohibited on
the label, the statement
requiring gloves for those
uses may be omitted.
(2) If dip applications are
not feasible or are
prohibited on the label, the
statement requiring gloves
and aprons for those uses
may be omitted.
Handler PPE Requirements1
for Liquid Formulations
"Personal 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."
"Applicators using hand held foggers in an enclosed area must wear:
- coveralls over long-sleeved shirt and long pants,
- chemical-resistant footwear plus socks,
- chemical-resistant gloves,
- chemical-resistant headgear, and
- a half -face, full-face, or hood-style NIOSH-approved respirator with:
~ a dust/mist filtering cartridge (MSHA/NIOSH approval number prefix TC-21C), or
~ a canister approved for pesticides (MSHA/NIOSH approval number prefix TC-14G), or
~ a cartridge or canister with any N, R, P or HE filter."
"All other mixers, loaders, applicators, and other handlers must wear the following:
- long-sleeve shirt,
- long pants,
- shoes plus socks,
- chemical-resistant gloves for applicators using handheld equipment (other than handheld foggers)
or participating in dip treatments, and
- chemical-resistant apron when participating in dip treatments."
Instruction to Registrant:
Drop the "N" type filter from the respirator statement, if the pesticide product contains, or is used
with, oil.
"Personal Protective Equipment (PPE)"
"Some materials that are chemical-resistant to this product are (registrant inserts correct chemical-
Precautionary
Statements: Hazards to
Humans and Domestic
Animals
Precautionary
Statements: Hazards to
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Description
MGK-264 Required Labeling Language
Placement on Label
that prohibit the use of
handheld fogging
equipment or for products
that could NOT feasibly be
used in handheld fogging
devices
[including: total release
foggers, or ready to use
products such as foams,
aerosols, gels, pastes, and
pressurized liquids]
Notes:
(1) This entire statement
may be omitted if the end-
use product is labeled only
for use on pets or humans.
(2) If the use of handheld
equipment such as
handwands, backpack
sprayers, or foggers is not
feasible or is prohibited on
the label, the statement
requiring gloves for those
uses may be omitted.
(3) If dip applications are
not feasible or are
prohibited on the label, the
statement requiring gloves
and aprons for those uses
may be omitted.
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."
"Mixers, loaders, applicators, and other handlers must wear the following:
- long-sleeve shirt,
- long pants,
- shoes plus socks,
- chemical-resistant gloves for applicators using handheld equipment or participating in dip
treatments, and
- chemical-resistant apron when participating in dip treatments."
Humans and Domestic
Animals
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Description
MGK-264 Required Labeling Language
Placement on Label
Handler PPE Requirements
for Dusts J
"Personal Protective Equipment (PPE)"
"Loaders, applicators, and other handlers must wear the following:
- long-sleeve shirt,
- long pants,
- shoes plus socks."
Precautionary
Statements: Hazards to
Humans and Domestic
Animals
User Safety Requirements
"Follow manufacturer's instructions for cleaning/maintaining PPE. If no such instructions for
washables exist, use detergent and hot water. Keep and wash PPE separately from other laundry.'
"Discard clothing and other absorbent material that have been drenched or heavily contaminated
with the product's concentrate. Do not reuse them."
Precautionary
Statements: Hazards to
Humans and Domestic
Animals immediately
following the PPE
requirements
User Safety
Recommendations
for all products
"USER SAFETY RECOMMENDATIONS"
"Users should wash hands before eating, drinking, chewing gum, using tobacco, or using the toilet.'
Precautionary
Statements under:
Hazards to Humans and
Domestic Animals
immediately following
Engineering Controls
(Must be placed in a
box.)
User Safety
Recommendations
for all products EXCEPT
those labeled solely for use
on pets and humans.
"USER SAFETY RECOMMENDATIONS"
"Users should remove clothing/PPE immediately if pesticide gets inside. Then wash thoroughly
and put on clean clothing."
"Users should remove PPE immediately after handling this product. Wash the outside of gloves
before removing. As soon as possible, wash thoroughly and change into clean clothing."
Precautionary
Statements under:
Hazards to Humans and
Domestic Animals
immediately following
Engineering Controls
(Must be placed in a
box.)
Environmental
Hazards Statements for
products labeled for outdoor
"ENVIRONMENTAL HAZARDS"
"This product may contaminate water through runoff. This product has a potential for runoff for
Precautionary
Statements under
Environmental Hazards
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Description
MGK-264 Required Labeling Language
Placement on Label
uses
several months or more after application. Poorly draining soils and soils with shallow water tables
are more prone to produce runoff that contains this product. Do not apply directly to water, to areas
where surface water is present or to intertidal areas below the mean high water mark. Do not
contaminate water when disposing of equipment wash-waters or rinsate."
Environmental Hazards for
Products labeled only for
Indoor Use EXCEPT ready
to use impregnated
materials (e.g. flea collars,
ear tags, coils, mats)
(Note: Products used on
domestic animals like flea
collars and ear tags,
generally do not require an
Environmental Hazards
statement.)
"ENVIRONMENTAL HAZARDS"
"Do not contaminate water when disposing of equipment, washwater, or rinsate. See Directions for
Use for additional precautions and requirements."
For indoor products packaged in containers equal to or greater than 5 gallons or 50 Ibs add
the following statement:
"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 sewer systems without previously
notifying the local sewage treatment plant authority. For guidance contact your State Water Board
or Regional Office of the EPA."
Precautionary
Statements under
Environmental Hazards
Restricted-Entry Interval
for products with WPS uses
"Do not enter or allow worker entry into treated areas during the restricted entry interval (REI) of
12 hours."
Directions for Use,
Agricultural Use
Requirements Box
Early Entry Personal
Protective Equipment for
products with WPS uses
"PPE required for early entry to treated areas that is permitted under the Worker Protection
Standard and that involves contact with anything that has been treated, such as soil or water, is:
- coveralls,
- chemical-resistant gloves made of any waterproof material, and
- shoes plus socks."
Directions for Use,
Agricultural Use
Requirements Box
Entry Restrictions
for products with non-WPS
uses on the label
Note: This excludes
products labeled for use
when people are permitted
Entry Restriction for products applied as a spray (does not apply to products applied directly
to humans or domestic animals or applied when people are permitted to be present):
"Do not enter or allow others to enter until sprays have dried."
Entry Restriction for products applied dry:
If no WPS uses on the
product label, place the
appropriate statement
in the Directions for
Use Under General
Precautions and
Restrictions. If the
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Description
MGK-264 Required Labeling Language
Placement on Label
to be present (e.g. metered
release devices, pet
applications, and repellents
applied to humans)
"Do not enter or allow others to enter until dusts have settled."
Entry Restriction for total release foggers or products applied as a space spray:
"Do not allow adults, children, or pets to enter the treated area for at least 15 minutes, until vapors,
mists, and aerosols have dispersed, and the treated area has been thoroughly ventilated."
product also contains
WPS uses, then create a
Non-Agricultural Use
Requirements box as
directed in PR Notice
93-7 and place the
appropriate statement
inside that box.
Entry Restrictions for
products labeled solely for
use when people are present
(e.g. metered release
devices, applications to
pets, and repellents applied
to humans)
Note to Registrants: No entry restrictions are required. See below under Use Restrictions for
further requirements.
Entry Restrictions for
products labeled for use
when people are present
(e.g. metered release
devices, applications to
pets, and repellents applied
to humans) and for use on
other sites as a directed or
space spray.
Products labeled for use as a directed spray (does not apply to products applied directly to
domestic animals):
"Except when (insert application method or site that allows people to be present), do not enter or
allow others to enter until sprays have dried."
Products labeled for use as a space spray:
"Except when (insert application method or site that allows people to be present), do not enter or
allow others to enter until vapors, mists, and aerosols have dispersed, and the treated area has been
thoroughly ventilated."
Note to Registrant: An example is as follows: Except when applying in a metered release system,
do not enter or allow others to enter until sprays have dried.
If no WPS uses on the
product label, place the
appropriate statement
in the Directions for
Use Under General
Precautions and
Restrictions. If the
product also contains
WPS uses, then create a
Non-Agricultural Use
Requirements box as
directed in PR Notice
93-7 and place the
appropriate statement
inside that box.
General Application
Restrictions for products
with WPS or non-WPS uses
on the label
"Do not apply this product in a way that will contact workers or other persons, either directly or
through drift."
Place in the Direction
for Use.
Page 65 of 81
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Description
MGK-264 Required Labeling Language
Placement on Label
Note: This excludes
products that contain any
directions for uses when
people are permitted to be
present in the treated area
(e.g. metered release
devices, applications to
pets, and repellents applied
to humans)
''Only protected handlers may be in the area during application."
General Application
Restrictions for Ready-to-
use (RTU) Total Release
Fogger products
"Do not apply this product in a way that will contact workers or other persons, either directly or
through drift."
"Only protected handlers may be in the area during application."
"Do not remain in treated area. Exit area immediately and remain outside the treated area until
aerosols, vapors, and/or mists have dispersed."
Place in the Direction
for Use.
General Application
Restrictions for products
with WPS and non-WPS
uses on the label AND
contain directions for uses
when people are permitted
to be present in the treated
area (e.g. metered release
devices, applications to
pets, and repellents applied
to humans)
"Except when" (insert application method or site that allows people to be present) "do not apply this
product in a way that will contact workers or other persons, either directly or through drift."
"Except when" (insert application method or site that allows people to be present) "only protected
handlers may be in the area during application."
Place in the Direction
for Use.
General Application
Restrictions for products
labeled for use solely when
Note to Registrants: No entry restrictions are required. See below under Use Restrictions for
further requirements.
Place in the Direction
for Use.
Page 66 of 81
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Description
MGK-264 Required Labeling Language
Placement on Label
people are permitted to be
present in the treated area
(e.g. metered-release
devices, applications to
pets, and repellents applied
to humans)
Other Application
Restrictions
Note to Registrants: Delete any reference to tolerance exemptions on labels.
In addition add the following restrictions depending on the registered product uses and formulation:
Dust formulations:
"Aerial applications are prohibited."
"Applications with power duster equipment are prohibited."
"Applications to pets are prohibited."
Products labeled for spray applications to plants:
"Do not wet plants to point of runoff or drip."
Products labeled for spray applications to articles:
"Do not wet articles to point of runoff or drip."
"Do not use treated article until spray has dried."
Products labeled for applications to clothing articles:
"Dry clean treated clothes before wearing."
Products labeled for dip applications to articles:
"Do not use treated article before it is dry."
Products labeled for crack and crevice, surface or space spray, fogging or dust applications
indoors:
"Remove or cover exposed food and drinking water before application."
Directions for Use
under General
Precautions and
Restrictions and/or
Application
Instructions
Page 67 of 81
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Description
MGK-264 Required Labeling Language
Placement on Label
"Remove or cover dishes, utensils, food processing equipment, and food preparation surfaces, or
wash them before use."
Products labeled for applications to non-residential indoor sites:
"Do not use in aircraft cabins except in compliance with PR Notice 96-3."
"When used in dairy barns or facilities: Close milk bulk tank lids to prevent contamination from
spray and from dead or falling insects. Remove or cover milking utensils before application. Wash
teats of animals before milking."
Products labeled for use in food handling and processing facilities:
"Do not make space spray applications when facility is in operation."
"Prior to space spray applications, cover or remove food."
"Prior to space spray applications, cover food processing surfaces or clean after treatment with a
suitable detergent and rinse with potable water before use."
Products labeled for applications to indoor areas including pet areas:
"Remove or cover exposed food and water before application."
"Remove or cover dishes, utensils, food processing equipment, and food preparation surfaces, or
wash them thoroughly before use."
Use Restrictions
(Note: The maximum
application rate and
maximum seasonal rates
specified in this table must
be listed as pounds or
gallons of formulated
product per acre/square
ft/ppm/cubic feet etc., not
just as pounds active
ingredient)
Trigger Pump Sprayers
Products must be formulated to deliver no more than this maximum rate when used according
to directions:
All trigger pump sprayers - 0.1 Ibs ai/1000 square feet (maximum concentration is 0.5 % ai)
Indoor Aerosol Space Sprays (Residential Areas)
Products must be formulated to deliver no more than this maximum rate when used according
to directions:
All aerosol pump sprayers used in residential areas- 0.00015 Ibs ai/1000 cubic foot
Non-food (ornamentals, flowering, and foliage plants) plants in Commercial Greenhouses
Maximum application rates:
Greenhouse surface spray - 0.01 Ibs per 1000 square feet
Directions for Use
under General
Precautions and
Restrictions and/or
Application
Instructions
Page 68 of 81
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Description
MGK-264 Required Labeling Language
Greenhouse space sprays - 0.001 Ibs ai/1000 cubic feet
Use restrictions:
"Do not apply more than 1 time per day."
Direct Application to Non-domestic Animals (non-food livestock only, i.e. donkeys, horses,
ponies, mules)
Products must be formulated to deliver no more than this maximum rate when used according
to directions:
Application to non-food livestock- 0.00025 Ibs ai/animal (or 2 oz of 0.2% spray /animal)
Ready-to-use paste applications to horses - 0.0056 Ibs ai/horse
Use restrictions:
"Do not apply more than 1 time per day."
Indoor Agricultural Premises and Commercial Animal Housing and Equipment (animals not
present)
Products must be formulated to deliver no more than this maximum rate when used according
to directions:
Crack/crevice or spot- 0.05 Ibs ai/1000 square feet
Surface applications - 0.01 Ibs ai/1000 square feet
Space sprays - 0.001 Ibs ai/1000 cubic feet
Metered release device sprays - 0.002 Ibs ai/ 1000 cubic feet per day and 1.77 mg ai/spray
event
Use Restrictions:
"Do not apply more than 1 time per day."
Indoor Food Handling/Processing Facilities
Products must be formulated to deliver no more than the maximum rate when used according
to directions:
Placement on Label
Page 69 of 81
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Description
MGK-264 Required Labeling Language
Surface applications - 0.01 Ibs ai/1000 square feet
Crack/crevice or spot - 0.05 Ibs ai/1000 square feet
Space sprays- 0.001 Ibs ai/1000 cubic feet
Metered release device space sprays - 0.002 Ibs ai/1000 cubic feet/day and 1.77 mg ai/spray
event
Use Restrictions:
"Do not apply more than 1 time per day."
In addition, these label statements should be deleted from all products registered for food
handling and processing facilities:
"Except in Federally inspected meat and poultry plants, food processing operations may
continue when the product is applied as a general surface spray with care and in accordance
with the directions and precautions on the label, at a maximum rate of 0.01 pounds of MGK-
264 per 1000 square feet."
"Except in Federally inspected meat and poultry plants, food processing operations may
continue when the product is applied as a crack and crevice treatment with care and in
accordance with the directions and precautions on the label, at a maximum rate of 0.05 pounds
of MGK-264 per 1000 square feet."
Outdoor Agriculture Premises and Equipment
Products must be formulated to deliver no more than this maximum rate when used according
to directions:
Surface applications - 0.01 Ibs ai/1000 square feet
Crack/crevice or spot- 0.05 Ibs ai/1000 square feet
Use Restrictions:
"Do not apply more than 1 time per day."
Pet Care
Products must be formulated to deliver no more than this maximum rate when used according
to directions:
Placement on Label
Page 70 of 81
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Description
MGK-264 Required Labeling Language
Placement on Label
The use directions must not allow more than 0.0028 Ibs ai/pet for all pet applications,
including those listed above.
Use restrictions:
"Do not apply to pets less than 12 weeks old."
"Consult a veterinarian before applying this product on medicated, debilitated, aged, pregnant,
or nursing animals."
"Sensitivities may occur after using any pesticide product for pets. If signs of sensitivity occur
bathe your pet with mild soap and rinse with large amounts of water. If signs continue,
consult a veterinarian immediately."
Registrant Note: Follow instructions in PR Notice 96-6, Pet Pesticide Product Label
Statements, for including reapplication restrictions on the end-use product label.
Pet Premise Treatment (pets are not present)
Products must be formulated to deliver no more than this maximum rate when used according
to directions:
Surface - 0.01 Ibs per 100 square feet
Space spray - 0.001 Ibs per 1000 square feet
Outdoor Residential Ornamental and Lawns
Maximum application rates:
Surface applications - 0.3 Ibs ai/A
User Restrictions:
"Do not apply more than 1 time per day."
Residential Dwellings and Commercial, Institutional Indoor Sites
Products must be formulated to deliver no more than this maximum rate when used according
to directions:
Surface applications -0.01 Ibs ai/1000 square feet
Crack/crevice or spot - 0.05 Ibs ai/1000 square feet
Space sprays- 0.001 Ibs ai/1000 cubic feet
Page 71 of 81
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Description
MGK-264 Required Labeling Language
Placement on Label
Metered release device space sprays (except for residential dwellings which are prohibited)-
0.002 Ibs ai/1000 cubic feet/day and 1.77 mg ai/spray event
Residential Indoor Dust Applications to Carpet and Other Indoor Surfaces
Products must be formulated to deliver no more than this maximum rate when used according
to directions:
Dust - 0.011 Ibs ai/100 square feet
User Restrictions:
"Do not apply more than once a day."
"Only apply as a spot treatment to areas no greater than 3 feet by 3 feet per room."
General Outdoor Sites (including non-agricultural rights-of-way,
commercial/institutional/industrial premises, residential sites, and outdoor eating
establishments)
Products must be formulated to deliver no more than this maximum rate when used according
to directions:
Surface applications - 0.01 Ibs ai/1000 square feet
Crack/crevice or spot - 0.05 Ibs ai/1000 square feet
Metered release device space sprays (except for residential sites which are prohibited) - 0.002
Ibs ai/1000 cubic feet/day and 1.77 mg ai/spray event
Manholes
Products must be formulated to deliver no more than this maximum rate when used according
to directions:
Surface applications to manholes - 0.07 Ibs ai per manhole over a length of 200 feet
Use restrictions:
"Do not apply more than 1 time per day."
Food Stored in Bags
Page 72 of 81
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Description
MGK-264 Required Labeling Language
Placement on Label
Products must be formulated to deliver no more than this maximum rate when used according
to directions:
Space sprays may be made to the surfaces of bags of stored food products at the rate of 0.001
Ibs ai/1000 cubic foot.
Use restrictions:
"Direct application to food contact surfaces is prohibited."
Application Restrictions for
products used in Metered
Release Devices
Note to Registrants: Delete nurseries, day care centers, schools, hospitals, and nursing homes as
registered use sites on all product labels for this use pattern.
Add the following statements:
"Not for use in residential areas."
"Do not use in nurseries or rooms where infants, ill, or aged persons are present."
"Do not place metering device directly over or within 8 feet of exposed food, dishes, utensils, food
processing equipment, and food handling or preparation."
"Do not install within 3 feet of air vents."
"Carefully follow directions for the dispenser unit when installing the dispenser and replacing cans
or conducting maintenance."
Directions for Use
under General
Precautions and
Restrictions and/or
Application
Instructions
Use-Specific Application
Restrictions for all liquid
products that could feasibly
be used in an outdoor
residential misting system
Note to registrants: No
products for use in outdoor
residential misting systems
will be eligible for
reregistration
Outdoor Residential Misting Systems
Products that could be feasibly used in outdoor residential misting systems (e.g., liquid
concentrates) must contain the following statement:
"Not for use in outdoor residential misting systems."
Directions for Use
under General
Precautions and
Restrictions and/or
Application
Instructions
Page 73 of 81
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Description
MGK-264 Required Labeling Language
Placement on Label
Products Primarily Used by Consumers/Homeowners
Application Restrictions for
products applied as a space
spray or by a fogger
"Do not remain in treated area. Exit area immediately and remain outside the treated area until
aerosols, vapors, and/or mists have dispersed."
Place in the Direction
for Use.
Entry Restrictions
for products except those
products that contain any
directions for uses when
people are permitted to be
present in the treated area
(e.g. pet applications and
repellents)
Entry Restriction for products applied as a surface or crack and crevice spray except for
sprays applied directly to domestic animals:
"Do not allow adults, children, or pets to enter the treated area until sprays have dried."
Entry Restriction for products applied dry:
"Do not allow adults, children, or pets to enter the treated area until dusts have settled."
Entry Restriction for products applied as a space spray or by fogger:
"Do not allow adults, children, or pets to enter the treated area for at least 15 minutes, until vapors,
mists, and aerosols have dispersed, and the treated area has been thoroughly ventilated."
Directions for use
under General
Precautions and
Restrictions
Entry Restrictions for
products products that only
contain directions for uses
when people are permitted
to be present (e.g. pet
applications and repellents)
Note to Registrants: No entry restrictions are required. See below under Use Restrictions for
further requirements.
Directions for use
under General
Precautions and
Restrictions
Entry Restrictions for
products that contain
directions for uses when
people are permitted to be
present in the treated area
(e.g. applications to pets
and repellents) AND for use
on other sites as a surface
and/or crack and crevice
spray.
Products labeled for use as a surface spray (does not apply to products applied directly to
domestic animals):
"Except when applying directly to pets, do not allow adults, children, or pets to enter until sprays
have dried."
Directions for use
under General
Precautions and
Restrictions
Page 74 of 81
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Description
MGK-264 Required Labeling Language
Placement on Label
General Application
Restrictions for all products
except those products that
contain any directions for
uses when people are
permitted to be present in
the treated area (e.g. pet
applications and repellents)
"Do not apply this product in a way that will contact adults, children, or pets, either directly or
through drift."
"Remove pets, birds, and cover fish aquariums before spraying."
Place in the Direction
for Use
General Application
Restrictions for products
that only contain directions
for uses when people are
permitted to be present (e.g.
pet applications and
repellents)
Note to Registrants: No entry restrictions are required. See below under Use Restrictions for
further requirements.
Place in the Direction
for Use
General Application
Restrictions for products
that contain directions for
uses when people are
permitted to be present in
the treated area (e.g. pet
applications)
AND for use on other sites.
"Except when applying directly to pets, do not apply this product in a way that will contact adults,
children, or pets, either directly or through drift. Remove pets, birds, and cover fish aquariums
before spraying."
Place in the Direction
for Use
Homeowner User Safety
Recommendations
Statements
"User Safety Recommendations
Users should wash hands with plenty of soap and water before eating, drinking, chewing gum, using
tobacco, or using the toilet."
Precautionary
Statements under:
Hazards to Humans and
Domestic Animals
immediately following
Engineering Controls
(Must be placed in a
box.)
Homeowner User Safety
Recommendations
"Users should remove clothing immediately if pesticide gets inside. Then wash thoroughly and put
on clean clothing."
Precautionary
Statements under:
Page 75 of 81
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Description
MGK-264 Required Labeling Language
Placement on Label
for all products EXCEPT
those labeled solely for use
on pets and humans.
Hazards to Humans and
Domestic Animals
immediately following
Engineering Controls
(Must be placed in a
box.)
Residential Use Restrictions
(Note: The maximum
allowable application rate
and maximum allowable
seasonal rate must be listed
as pounds or gallons of
formulated product per acre
or per square feet or per
cubic feet, not just as
pounds active ingredient per
unit area.)
Trigger Pump Sprayers
Products must be formulated to deliver no more than this maximum rate when used according
to directions:
All trigger pump sprayers -0.1 Ibs ai/1000 square feet (maximum concentration is 0.5 % ai
MGK-264)
Indoor Aerosol Space Sprays (Residential Areas)
Products must be formulated to deliver no more than this maximum rate when used according
to directions:
All aerosol pump sprayers used in residential areas- 0.00015 Ibs ai/1000 cubic foot
Non-food (ornamentals, flowering, and foliage plants) plants in Residential Greenhouses
Maximum application rates:
Greenhouse surface spray - 0.01 Ibs per 1000 square feet
Greenhouse space sprays - 0.001 Ibs ai/1000 cubic feet
Use restrictions:
"Do not apply more than 1 time per day."
Pet Premise Treatment (pets are not present)
Products must be formulated to deliver no more than this maximum rate when used according
to directions:
Surface - 0.01 Ibs per 100 square feet
Space spray - 0.001 Ibs per 1000 square feet
Directions for Use
under General
Precautions and
Restrictions and/or
Application
Instructions
Page 76 of 81
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Description
MGK-264 Required Labeling Language
Placement on Label
Outdoor Residential Ornamental and Lawns
Maximum application rates:
Surface applications - 0.3 Ibs ai/acre
User Restrictions:
"Do not apply more than once a day."
Indoor Residential Dwellings
Products must be formulated to deliver no more than this maximum rate when used according
to directions:
Surface applications - 0.01 Ibs ai/1000 square feet
Crack/crevice or spot- 0.05 Ibs ai/1000 square feet
Space sprays- 0.001 Ibs ai/1000 cubic feet
Residential Indoor Dust Applications to Carpet and other indoor surfaces
Products must be formulated to deliver no more than this maximum rate when used according
to directions:
Dust- 0.011 Ibs ai/100 square feet
User Restrictions:
"Do not apply more than once a day."
"Do not apply as a broad carpet treatment. Only spots less than 3 feet by 3 feet per room may
be applied with this product."
Repellent Applied to Humans
Use restrictions:
"Do not use under clothing."
"Avoid over application."
"Do not apply over cuts, wounds, or irritated skin."
"Do not spray directly on face."
Page 77 of 81
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Description
MGK-264 Required Labeling Language
Placement on Label
"To apply to face, spray into hands first and then apply sparingly and avoid eyes."
"Do not apply near eyes and mouth."
"Apply sparingly around ears."
"Do not allow children to handle product."
"Do not apply to children's hands."
"When using on children, apply to your own hands first and then put it on a child."
Pet Care
Products must be formulated to deliver no more than this maximum rate when used according
to directions:
The use directions must not allow more than 0.0028 Ibs ai/pet for all pet applications,
including those listed above.
Use restrictions:
"Do not apply to pets less than 12 weeks old."
"Consult a veterinarian before applying this product on medicated, debilitated, aged, pregnant,
or nursing animals."
"Sensitivities may occur after using any pesticide product for pets. If signs of sensitivity occur
bathe your pet with mild soap and rinse with large amounts of water. If signs continue,
consult a veterinarian immediately."
Registrant Note: Follow instructions in PR Notice 96-6, Pet Pesticide Product Label
Statements, for including reapplication restrictions on the end-use product label.
General Outdoor Sites (including outdoor residential sites, automobiles, and manure)
Products must be formulated to deliver no more than this maximum rate when used according
to directions:
Surface applications - 0.01 Ibs ai/1000 square feet
Crack/crevice or spot- 0.05 Ibs ai/1000 square feet
Use-Specific Application
Restrictions
Requirement for Liquid Formulations (except for Ready to Use) with outdoor uses:
"Do not apply directly to or near water, storm drains, or drainage ditches. Do not apply when
Directions for Use
under General
Precautions and
Restrictions and/or
Page 78 of 81
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Description
MGK-264 Required Labeling Language
Placement on Label
For products with directions
for residential uses
windy. To prevent product run-off, do not over water the treated area(s) or apply when heavy rain
is expected. Rinse applicator over lawn or garden area only."
Requirement for Ready to Use Liquid or Dust Formulations with outdoor uses:
"Do not apply directly to or near water, storm drains, or drainage ditches. Do not apply when
windy. To prevent product run-off, do not over water the treated area(s) or apply prior to heavy
rainfall."
Application
Instructions
Use-Specific Application
Restrictions for all liquid
labels that could feasibly be
used in an outdoor
residential misting system
Note to registrants: No
products for use in outdoor
residential misting systems
will be eligible for
reregistration
Outdoor Residential Misting Systems
Products that could be feasibly used in outdoor residential misting systems (e.g., liquid
concentrates) must contain the following statement:
"Not for use in outdoor residential misting systems."
Directions for Use
under General
Precautions and
Restrictions and/or
Application
Instructions
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. In the case of multiple
active ingredients, the more protective PPE must be placed on the product labeling. For guidance on which PPE is considered more protective, see PR Notice 93-7.
All references to the active ingredient (a.i.) in this table refer to MGK-264.
Page 79 of 81
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Appendix: Technical Support Documents
Additional documentation in support of this RED is maintained in the OPP
docket, located in room S-4400, One Potomac Yard (South Building), 2777 S. Crystal Drive,
Arlington, VA 22202. It is open Monday through Friday, excluding legal holidays, from 8:30
am to 4 pm.
All documents, in hard copy form, may be viewed in the OPP docket room or
downloaded or viewed via the Internet at the following site: http://www.regulations.gov
These documents include:
HED Documents:
Revised Memo to Incorporate Reponses to Phase 5 Public Comments. N-Octyl
bicycloheptene dicarboximide (MGK-264): HED Chapter of the Reregi strati on Eligibility
Decision Document (RED). Donovan, W.; D327167; March 20, 2006.
MGK-264 Indoor Handheld Fogger Applicator Scenario: Comparison of Prallethrin
Inhalation Study and Florida Greenhouse Study. Weiss, S.; D327961; July 5, 2006.
MGK-264: REVISED Occupational and Residential Exposure Assessment for the
Reregistration Eligibility Decision Document. Weiss, S.; D324674; March 10, 2006.
Revised Memo to Incorporate Responses to Phase 3 Public Comments. N-Octyl
bicycloheptene dicarboximide (MGK-264) RED - Reregistration Eligibility Decision.
Product and Residue Chemistry Considerations. Donovan, W.; D318874; September 9,
2005.
Review of MGK-264 Incident Reports. Blondell, J.; D306591; October 6, 2004.
N-Octyl bicycloheptene dicarboximide (MGK-264) Acute and Chronic Dietary Exposure
Assessments for the Reregistration Eligibility Decision. Donovan, W.; D295639;
September 21,2004.
MGK-264: First Report of the Hazard Identification Assessment Review Committee.
Eiden, C.; TXRNo. 0052650; June 25, 2004.
HED Response to Comments Documents:
MGK-264. Health Effects Division (HED) Phase 6 Response to Phase 5 Comments on
the MGK-264 Preliminary Reregistration Eligibility Decision (RED) and Supporting
Memos. Donovan, W., Doherty, J., Weiss, S.; D324672; May 11, 2006.
MGK-264. Health Effects Division (HED) Phase 4 Response to Phase 3 Public
Comments on the MGK-264 Preliminary Reregistration Eligibility Decision (RED) and
Page 80 of 81
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Supporting Memos. Donovan, W., Doherty, J., Weiss, S.; D321193; September 15,
2005.
Piperonyl Butoxide (PBO), Pyrethrins and MGK-264: Health Effects Division's
response to the Registrant's concerns for using metaplasia seen in the larynx in
subchronic inhalation studies as an endpoint for inhalation risk assessment. Ramasamy,
S., et al.; D319913, D319914, andD320298; September 8, 2005.
MGK-264. HED Response to Error-Only Registrant Comments on the MGK-264
Preliminary RED. Donovan, W., Doherty, J., Weiss, S.; D311280; March 2, 2005.
EFED Documents:
Revised Screening Ecological Risk Assessment for the Reregi strati on of MGK-264
Insecticide Synergist. Eckel, W.; D329617; July 14, 2006.
Drinking Water Assessment for MGK-264 Insecticide Synergist: Surface Water Revision
for Ground Spray. Eckel, W.; D305104; February 17, 2005.
EFED Response to Comments Documents:
Response to Comments of Phase 5 Period About Water Quality, and Other Issues on the
Revised Draft EFED RED Chapters for Pyrethrins, PBO and MGK-264. Davy, M., et al.;
D324663, D324664, D324667, D324662, D324671, and D324673; January 30, 2006.
Response to Pubic Comments on Drinking Water Assessment for MGK-264 Insecticide
Synergist. Eckel, W.; D318870; August 31, 2005.
Response to Public Comments on Ecological Risk Assessment for MGK-264 Insecticide
Synergist. Eckel, W., and Lee, R.; D318871; August 31, 2005.
Response to Error-Only Review of Ecological Risk Assessment and Drinking Water
Assessment for MGK-264 Insecticide Synergist. Eckel, W.; D295633; February 17,
2005.
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