United States Prevention, Pesticides EPA 738-R-03-003
Environmental Protection And Toxic Substances September 23, 2003
Agency (7508C)
Reregistration
Eligibility Decision
(RED)
Di-n-propyl
isocinchomeronate
(MGK® Repellent 326)
[Revised: O3/11/O5]
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, D.C. 2O46O
OFFICE OF
PREVENTION, PESTICIDES
AND TOXIC SUBSTANCES
CERTIFIED MAIL
Dear Registrant:
This is to inform you that the U.S. Environmental Protection Agency (hereafter referred to as
EPA or the Agency) has completed its review of the available data and public comments received
related to the risk assessments for the insect repellent di-n-propyl isocinchomeronate (hereafter referred
to as MGK® Repellent 326). Based on its review, EPA has identified risk mitigation measures that the
Agency believes are necessary to address the human health risks associated with the current use of
MGK® Repellent 326. EPA is now publishing its reregistration eligibility, risk management, and
tolerance reassessment decisions for the current uses of MGK® Repellent 326 and its associated human
health and environmental risks. The enclosed "Reregistration Eligibility Decision for Di-n-propyl
isocinchomeronate (MGK® Repellent 326)" contains the Agency's decision on the individual chemical
MGK® Repellent 326, which was approved on September 23, 2003.
A Notice of Availability for this Reregistration Eligibility Decision (RED) for MGK® Repellent
326 is being published in the Federal Register: To obtain a copy of the RED document, please
contact the OPP Public Regulatory Docket at (703) 305-5805. Electronic copies of the RED and all
supporting documents are available on the Internet at the following address:
http//:www.epa.gov/edockets.
This document and the process used to develop it are the result of a process to facilitate greater
public involvement and participation in the reregistration and/or tolerance reassessment decisions for
pesticides. As part of the Agency's effort to involve the public in the implementation of the Food
Quality Protection Act of 1996 (FQPA), the Agency is undertaking a special effort to maintain open
public dockets and to engage the public in the reregistration and tolerance reassessment processes.
Subsequently, the risk assessments for MGK® Repellent 326 were made available to the public for
comment on May 23, 2003. This open process follows the guidance developed by the Tolerance
Reassessment Advisory Committee (TRAC), a large multi-stakeholder advisory body that advised the
Agency on implementing the new provisions of the FQPA. The Agency also conducted a close-out
conference call on September 18, 2003 to discuss the risk management decisions and resultant changes
to the MGK® Repellent 326 labels.
This document contains both generic or product-specific Data Call-ins (DCIs) that outlines
further data requirements for this chemical. Note that a complete DCI, with all pertinent instructions, is
being sent to registrants under separate cover. Additionally, for product-specific DCIs, the first set of
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required responses is due 90 days from receipt of the DCI letter. The second set of required responses
is due eight months from the date of the DCI.
As part of the RED, the Agency has determined that MGK® Repellent is eligible for
reregistration provided that all the conditions identified in this document are satisfied, including
implementation of the risk mitigation measures outlined in Section IV of the RED document. The
Agency believes that current uses of MGK® Repellent may pose unreasonable adverse effects to
human health and that such effects can be mitigated with the risk management measures identified in the
RED document. Accordingly, the Agency recommends that the registrants implement these risk
mitigation measures immediately. Sections IV and V of the RED document describe labeling
amendments for end-use products and data requirements necessary to implement these mitigation
measures.
Should a registrant fail to implement any of the risk mitigation measures outlined in this
document, the Agency will continue to have concerns about the risks posed by MGK® Repellent 326.
Where the Agency has identified any unreasonable adverse effect to human health and the environment,
the Agency may at any time initiate appropriate regulatory action to address this concern. At that time,
any affected person(s) may challenge the Agency's action.
If you have questions on this document or the proposed label changes, please contact the
Chemical Review Manager for MGK® Repellent 326, Tawanda Spears at (703) 308-8050. For
questions about product reregistration and/or the product-specific DCI that accompanies this
document, please contact Barbara Briscoe at (703) 308-8177.
Sincerely,
[signed 09/2 3/04]
Betty Shackleford, Acting Director
Special Review and Reregistration Division
Attachment
111
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Reregistration Eligibility Decision
for
Di-n-propyl isocinchomeronate
(MGK® Repellent 326)
Chemical List B
Case No. 2215
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TABLE OF CONTENTS
MGK® REPELLENT 326 REREGISTRATION ELIGIBILITY DECISION TEAM iii
GLOSSARY OF TERMS AND ABBREVIATIONS iv
EXECUTIVE SUMMARY vi
I. INTRODUCTION 1
II. CHEMICAL OVERVIEW 2
A. Regulatory History 2
B. Chemical Identification 3
C. Use Profile 3
D. Estimated Usage of Pesticide 5
III. SUMMARY OF MGK® REPELLENT 326 RISK ASSESSMENT 5
A. Human Health Risk Assessment 6
1. Dietary Risk from Food 6
2. Dietary Risk from Drinking Water 7
3. Residential Risk 7
a. Toxicity Assessment 7
i. Acute Toxicity 8
ii. Toxicological Endpoints 8
iii. Carcinogenicity 9
iv. FQPA Safety Factor Considerations 10
b. Residential Assessment 10
i. Non-Cancer Residential Risk Summary 11
ii. Cancer Residential Risk Summary 13
4. Aggregate Risk 14
5. Human Incident Reports 14
B. Environmental Risk Assessment 15
1. Ecological Toxicity Data 15
2. Environmental Fate 15
3. Ecological Risk Summary 16
4. Incident Reports 16
5. Endangered Species 16
IV. RISK MANAGEMENT AND REREGISTRATION DECISION 16
A. Determination of Reregistration Eligibility 16
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B. Summary of Public Participation Process 17
C. Regulatory Position 18
1. Determination of Safety for U.S. Population under FQPA 18
a. Tolerance Summary 18
2. Endocrine Disrupter Effects 20
3. Cumulative Risk 20
4. Public Health Benefits 20
D. Regulatory Rationale 21
1. Human Health Risk Mitigation 21
a. Dietary Risk Mitigation 21
b. Residential Risk Mitigation 21
i. Non-Cancer 21
ii. Cancer 21
c. Aggregate Risk Mitigation 24
2. Environmental Risk Mitigation 24
E. Label Amendments 24
V. WHAT REGISTRANTS NEED TO DO 24
A. Data Call-In (DCI) Responses 25
B. Manufacturing-Use Products 26
1. Generic Data Requirements 26
2. Labeling for Manufacturing-Use Products 26
C. End-Use Products 26
1. Additional Product-Specific Data Requirements 26
2. Labeling for End-Use Products 27
D. Existing Stocks 27
E. Labeling Changes Summary Table 27
VI. APPENDICES 31
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MGK® REPELLENT 326 REREGISTRATION ELIGIBILITY DECISION TEAM
Office of Pesticide Programs:
Health Effects Risk Assessment
Rebecca Daiss
David Jacquith
Abdallah Khasawinah
Jerry Stokes
Environmental Fate and Effects Assessment
Henry Craven
James Goodyear
John Jordan
Use and Usage Analysis
Stephen Smearman
Registration Support
Ann Sibold
Joseph Tavano
Risk Management
Neil Anderson
Tawanda Spears
111
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GLOSSARY OF TERMS AND ABBREVIATIONS
ai Active Ingredient
CSF Confidential Statement of Formula
CFR Code of Federal Regulations
DCI Data Call-in
EC50 Effective Concentration for aquatic plants and invertebrates. The concentration of a
chemical in water at which an effect is observed that is 50% of the maximum effect.
EP End-Use Product
EPA U.S. Environmental Protection Agency
FAO Food and Agriculture Organization
FDA Food and Drug Administration
FIFRA Federal Insecticide, Fungicide, and Rodenticide Act
FFDCA Federal Food, Drug, and Cosmetic Act
FQPA Food Quality Protection Act
GLN Guideline Number
LC50 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.
LD50 Median Lethal Dose. A statistically derived single dose that can be expected to cause
death in 50% of the test animals when administered by the route indicated (oral, dermal,
inhalation). It is expressed as a weight of substance per unit weight of animal, e.g.,
mg/kg.
LOG Level of Concern
LOAEL Lowest Observed Adverse Effect Level
mg/kg/day Milligram Per Kilogram Per Day
mg/L Milligrams Per Liter
MOE Margin of Exposure
MP Manufacturing-Use Product
MRID Master Record Identification (number). EPA's system of recording and tracking studies
submitted.
NA Not Applicable
N/A Not Applicable
NAFTA North American Free Trade Agreement
NOEC No Observed Effect Concentration
NOEL No Observed Effect Level
NOAEL No Observed Adverse Effect Level
NR Not Required
OPP (EPA) Office of Pesticide Programs
OPPTS (EPA) Office of Prevention, Pesticides and Toxic Substances
PAM Pesticide Analytical Method
ppb Parts Per Billion
ppm Parts Per Million
PRN Pesticide Registration Notice
Q!* The Carcinogenic Potential of a Compound, Quantified by the EPA's Cancer Risk Model
IV
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RED Reregistration Eligibility Decision
SF Safety Factor
SLN Special Local Need (Registrations Under Section 24(c) of FIFRA)
TGAI Technical Grade Active Ingredient
UF Uncertainty Factor
ug/g Micrograms Per Gram
ug/L Micrograms Per Liter
USDA United States Department of Agriculture
UV Ultraviolet
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EXECUTIVE SUMMARY
The U.S. Environmental Protection Agency (EPA or the Agency) has completed its
reregistration eligibility decision (RED) for the insect repellent di-n-propyl isocinchomeronate (hereafter
referred to as MGK® Repellent 326). The Agency has determined that MGK® Repellent 326
products, labeled and used as specified in this Reregistration Eligibility Decision (RED) document, will
not pose unreasonable risks or adverse effects to humans or the environment. Therefore, the Agency
has determined that MGK® Repellent 326 is eligible for reregistration under the conditions specified in
this RED document.
MGK® Repellent 326 was initially registered by the USDA in 1957 as an insect repellent for
livestock. Tolerances were established for meat and milk and are found in 40 CFR § 180.143.
However, in 1993, McLaughlin Gormley and King Company, the technical registrant, elected to
voluntarily cancel use on livestock intended for slaughter, which resulted in MGK® Repellent 326 being
limited to indoor non-food (i.e., pet living/sleeping quarters) and residential use (i.e., repellents for
humans and companion animals). In addition, in light of the fact that there are no active food uses, the
Agency is recommending that all existing tolerances for MGK® Repellent 326 be revoked. Because
food uses have been cancelled and the Agency is revoking all tolerances, EPA did not perform the
standard FFDCA analyses in this reregistration.
MGK® Repellent 326 is never used as the sole active ingredient (a.i). Rather, it is used to
expand the spectrum of repellency of other formulation components. For instance, when found in
products intended for use on humans, MGK® Repellent 326 is always combined with DEET (N,N-
diethyl-m-toluamide) and MGK® 264. According to current marketing data, the total amount of
MGK® Repellent 326 sold to customers with pesticide labels for use as "personal insect repellents" is
approximately 15,000 to 20,000 pounds (Ibs) of a.i. Whereas use on dogs/cats and horses average
2,100 and 14,000 Ibs of a.i., respectively.
Overall Risk Summary
The Agency's human health risk assessment for MGK® Repellent 326 indicates some risk
concerns. Dietary risk from both food and drinking water are not of concern due to the current use
pattern. Also, individual and combined non-cancer residential risks are not of concern because the
Margin of Exposures (MOEs) are all above the Agency's level of concern (target MOE 100). The
human health risk assessment indicates there is a marginal cancer residential risk of concern, based on
direct application of MGK® Repellent 326 to individuals over a lifetime. However, the Agency's risk
assessment is highly conservative and is believed to overestimate actual risk. The Agency did not
conduct an environmental risk assessment because MGK® Repellent 326 is an "indoor residential" use
pesticide and MGK® Repellent 326 is not likely to result in exposures and risks to non-target
organisms.
VI
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Regulatory Decision
The Agency has concluded, under the Federal Insecticide, Fungicide, and Rodenticide Act
(FIFRA), that MGK® Repellent 326 products, when labeled and used as specified in this document,
will not cause unreasonable adverse effects on human health or the environment. Therefore, MGK®
Repellent 326 products are eligible for reregistration.
Risk Mitigation
For the potential residential cancer risks associated with use of MGK® Repellent 326 over a
lifetime, the Agency is limiting production and distribution of MGK® Repellent 326 for personal insect
repellents to 20,000 Ibs of a.i. per year. Additionally, the Agency is limiting and reducing the maximum
concentration of a.i. to 2.5% for end-use products containing MGK® Repellent 326 intended for use on
humans. The Agency believes these steps are necessary to provide assurance that human exposure to
MGK® Repellent 326 in the U.S. will not increase beyond current levels. Further, to limit potential
overexposure to young children, no more than 3 applications per day of MGK® Repellent 326 are
allowed on children ages twelve and under.
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I. INTRODUCTION
In 1988, the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) was amended to
accelerate the reregistration of products with active ingredients registered prior to November 1, 1984.
The amended Act calls for the development and submission of data to support the reregistration of an
active ingredient, as well as a review of all submitted data by the EPA. Reregistration involves a
thorough review of the scientific database underlying a pesticide's registration. The purpose of the
Agency's review is to reassess the potential hazards arising from the currently registered uses of the
pesticide; to determine the need for additional data on health and environmental effects; and to
determine whether the pesticide meets the "no unreasonable adverse effects" 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 tolerance reassessment during reregistration. The Act also requires
that by 2006, EPA must review all tolerances in effect on the day before the date of the enactment of
the FQPA, which was August 3, 1996. FQPA also amends the Federal Food, Drug, and Cosmetic
Act (FFDCA) to require a safety finding in tolerance reassessment based on factors including an
assessment of cumulative effects of chemicals with a common mechanism of toxicity.
With respect to tolerances for MGK® Repellent 326, the technical registrant voluntarily
cancelled all livestock food uses in a Data Call In (DCI) response dated April 24, 1994. Therefore,
the end-use registrants removed the livestock uses from their labels, either through product
cancellations or label amendments. Because these uses are no longer active, the Agency is proposing
to revoke tolerances for the following commodities: meat, fat, meat byproducts of cattle, goats, hogs,
horses, and sheep; and milk. Upon revocation and removal of these tolerances for combined residues
of MGK® Repellent 326 and its metabolites from 40 CFR 180.143, this insect repellent will no longer
fall under the scope of FQPA with respect to tolerance reassessment. As such, the Agency did not
conduct an aggregate assessment of risk from dietary and residential exposures as a part of this
reregistration eligibility decision (RED).
At this time, the Agency has not made a decision as to whether MGK® Repellent 326 shares a
common mechanism of toxicity with other pyridine carboxylic acids or any other pesticides.
Nevertheless, a thorough review of the available data is still required before a formal decision is made
on the common mechanism of toxicity. Therefore, for purposes of this RED, the Agency assumes that
MGK® Repellent 326 does not share a common mechanism of toxicity with other pesticides. After a
decision is made regarding common mechanism of toxicity, if it is determined that a cumulative
assessment is necessary, then the Agency will re-evaluate risks posed by MGK® Repellent 326 and
address any outstanding risk concerns at that time.
This document for MGK® Repellent 326 presents the Agency's human health and
environmental risk conclusions, tolerance reassessment, and risk management decision for MGK®
Repellent 326, and consists of five sections. Section I contains the regulatory authority and framework
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for reregistration/tolerance reassessment. Section n provides a profile of the use and usage of the
chemical. Section m gives an overview of the human health and environmental effects risk
assessments. Section IV presents the Agency's reregistration eligibility, tolerance reassessment, and
risk management decisions. Section V identifies label changes necessary to implement the risk
mitigation measures. Finally, among the Appendices is a description of the revised use patterns, generic
and product-specific DCI, and other reference information. The risk assessments and supporting
documents are not included in this document, but are available in the public docket and the electronic
docket at www.epa.gov/edockets.
H. CHEMICAL OVERVIEW
II. A. Regulatory History
MGK® Repellent 326 was first registered in the United States in 1957 by McLaughlin Gormley
King Company (MGK). The chemical was formulated as di-n-propyl isocinchomeronate (EPA Reg
No. 1021-461), a manufacturing-use product to be further formulated into insect repellents for use in
barns or on livestock commodities (i.e., cattle, goats, hogs, horses, sheep). MGK® Repellent 326
works to broaden the spectrum of repellency of other formulation components, such as DEBT (N,N-
diethyl-m-toluamide) or pyrethrins, to repel flies, gnats, and other flying and biting insects.
Since then the technical registrant voluntarily cancelled all outdoor and livestock food uses in
response to DCIs issued in June 1991 and August 1993, respectively. Accordingly, MGK® Repellent
326 technical formulation products have been revised to include the statement "for use in manufacturing
of pesticide products for use in indoor non-food and residential areas only." Based on these actions by
the technical registrant, all end-use registrants were given the option in a DCI issued April 24,1994 of
providing supporting data, amending their labels to include language to prohibit the use of these
products on horses intended for slaughter, or deleting the use on livestock commodities entirely.
In response to the DCI, end-use registrants agreed to delete all livestock food uses from
MGK® Repellent 326 product labels. Therefore, residue chemistry data requirements to support
livestock food uses are no longer applicable and the Agency is proposing to revoke all di-n-propyl
isocinchomeronate tolerances for the following commodities: meat, fat and meat byproducts of cattle,
goats, hogs, horses, and sheep; and milk.
At the present time, EPA's records show there are ninety-one MGK® Repellent 326
products with active registrations. There is one technical product, six formulation intermediates, and the
rest are end-use products. There are no active special local need state registrations (24(c)s).
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II. B. Chemical Identification
Common Name:
Chemical Name:
Chemical Structure:
Dipropyl isocinchomeronate
Di-n-propyl isocinchomeronate
Chemical Family:
Case Number:
CAS Registry Number:
OPP Chemical Code:
Empirical Formula:
Molecular Weight:
Common Trade Name:
Basic Manufacturer:
Pyridine carboxylic acid
2215
136-45-8
047201
C13H17N04
251.3
MGK® Repellent 326
McLaughlin Gormley King Company (MGK)
Technical MGK® Repellent 326 is an amber liquid with a vapor pressure of 4.92x10"7 mm Hg
at 25 °C. The melting point is not applicable, because the technical is a liquid at room temperature.
MGK® Repellent 326 is soluble in petroleum distillates such as kerosene, toluene, xylene, methanol,
ethanol, and isopropanol, and practically insoluble in water.
H. C. Use Profile
Type of Pesticide:
Insect Repellent
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Summary of Use:
• Indoor Residential: Cats (adults/kittens), dogs/canines(adults/puppies),
human body/clothing, horses (not intended for food), pet living/sleeping quarters
Public Health: MGK® Repellent 326 is used to expand the spectrum of repellency of
DEBT for biting flies and ticks, but the Centers for Disease Control and Prevention
(CDC) did not indicate that MGK® Repellent 326 has any significant use in public
health programs.
Target Pests:
On Humans: Biting flies (i.e., black flies, deer flies, stable flies), chiggers, fleas, gnats,
house flies, no-see-ums, mosquitos, and ticks.
• On Companion Animals/Premises: Biting flies (i.e., black flies, bot flies, deer flies, face
flies, horn flies, stable flies, horse flies), chiggers, fleas, gnats, house flies, lice,
mosquitos, and ticks.
Formulation Types Registered:
Technical Grade
Active Ingredient: 97.00%
Manufacturing Use
Active Ingredient: 7.70 to 5 0.00%
• End-Use Products:
For Humans: MGK® Repellent 326 is always co-formulated with DEBT and MGK®
264 when intended for use on humans. Aerosol products range from 1.0-2.5% a.i.
The other products for use on humans are lotions, pump sprays or liquids, which range
from 1.76-4.0% MGK® Repellent 326.
For Companion Animals/Premises: Products used for dip applications to dogs and cats
contain 4.0% MGK® Repellent 326. There are also spray and towelette products with
0.2% and 1.0% a.i., respectively, that are applied to horses. The concentrate products
contain a maximum of 5.0% a.i. for use as surface sprays to the interior of kennels,
barns and other animal premises.
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Methods and Rates of Application
• For Use on Humans: Aerosol product labels specify to "apply to cover exposed skin
or clothing." The other labels for liquid and lotion products direct the user to "apply to
cover exposed skin."
• For Use on Companion Animals: Products used for dip applications to dogs and cats
direct users to dilute at the rate of 1 fl. oz. of product in 1 gallon of water. The
concentrate products directions are to apply undiluted material with a mist applicator at
the rate of 1 fl. oz. of product per 1000 sq. ft. of space in animal premises.
• Timing: All products are applied on an "as needed" basis for both humans and
companion animals.
Use Classification: General Use
II. D. Estimated Usage of Pesticide
This section summarizes the best estimates available for the pesticide uses of MGK® Repellent
326. Because of a lack of available use data, a Quantitative Use Assessment was not conducted for
MGK® Repellent 326. Rather, the Agency relied on estimates derived from the technical registrant.
The data reported reflect annual fluctuations in use patterns.
Based on pesticide usage information from 1997 to 2001, the average total annual domestic
usage of MGK® Repellent 326 was approximately 26,000 Ibs of a.i. According to more recent
marketing data provided by the technical registrant, approximately 15,000 to 20,000 Ibs of a.i. was
sold to customers with pesticide labels for use as "personal insect repellents," 14,000 Ibs a.i for use on
horses, and 2,100 Ibs a.i. for use on dogs and cats.
III. SUMMARY OF MGK® REPELLENT 326 RISK ASSESSMENT
The purpose of this section of the RED document is to summarize the key features and findings
of the risk assessments and to enhance the reader's understanding of the conclusions reached in the
assessments. EPA's human health assessment, environmental risk findings and conclusions for the
pesticide MGK® Repellent 326 are fully presented in the human health risk assessment document
MGK® Repellent 326 (di-n-propyl isocinchomeronate) HED Risk Assessment for Reregistration
Eligibility Decision (RED), dated April 7, 2003; and the environmental fate and effects document,
MGK 326/Disopropyl isochinomerate [sic] RED, dated December 24, 2002.
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Risks summarized in this RED document are those that result only from the use of MGK®
Repellent 326. While the risk assessments and supporting documents are not included in this RED
document, they are available in the electronic docket at http ://www. epa.gov/edocket/.
III. A. Human Health Risk Assessment
EPA issued its risk assessments for MGK® Repellent 326 on May 23, 2003. These risk
assessments were made available for comment and to solicit risk management ideas for this insect
repellent. There is a discussion of these comments in Section IV of this document. Following is a list of
supporting information that was used to formulate the human health risk assessment for MGK®
Repellent 326:
• MGK® Repellent 326: HED Toxicology Chapter for the Reregistration Eligibility
Decision Document (RED) by Abdallah Khasawinah (04/07/03)
• Exposure Assessment for MGK 326 (Dipropyl isocinchomerate) by David Jaquith
(04/07/03)
• Di-N-propyl isocinchomerate (MGK® Repellent 326) Use Closure Memo by
Tawanda Spears (01/16/03)
• MGK® Repellent 326 - Revised Report of the Hazard Identification Assessment
Review Committee by Abdallah Khasawinah (12/20/02)
• Drinking water concentration for Di-N-Propyl isocinchomerate (MGK 326) by
Henry Craven (11/22/02)
• Carcinogenicity Peer Review of MGK® Repellent 326 by Whang Phong and
Esther Rinde (07/21/93)
III. A. 1. Dietary Risk from Food
Dietary food risk assessments are conducted by comparing the inherent toxicity of a pesticide
to the amount of pesticide to which an individual is exposed to in food on a single day (acute) and over
a lifetime (chronic). Estimates of dietary food exposure are derived from the amount of pesticide
residue that is present in and on a food (i.e., the residue level) and the types and amounts of food that
people eat (i.e., food consumption).
For MGK® Repellent 326, there are no proposed or registered food uses. Therefore, there
are no potential dietary (food) exposures from the use of MGK® Repellent 326, and a dietary (food)
risk assessment was not conducted. Further, the Agency proposes to revoke all the following
established tolerances found at 40 CFR § 180.143, because the livestock commodity uses have been
deleted: meat, fat and meat byproducts of cattle, goats, hogs, horses, and sheep; and milk.
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III. A. 2. Dietary Risk from Drinking Water
Drinking water exposure to pesticides can occur through surface and/or ground water
exposure. To assess potential exposures from drinking water, the Agency evaluates the use patterns of
a pesticide to determine its potential to reach ground and surface water against levels of concern to
human health that are computed by the Agency.
When considering the use of products containing MGK® Repellent 326 as a personal repellent,
the Agency assumes that products directed to this market are washed off the human body and released
in household wastewater into a treatment plant. Similarly, those products that are used as surface
sprays of animal premises and pet dips would be discharged as wastewater, often to septic systems or
sewage treatment plants.
Yet, the Agency assumes the amount of MGK® Repellent 326 reaching drinking water sources
from disposal of personal use, surface sprays and pet dip products would be negligible due to low
overall volume of the chemical used and dilution of the compound in water systems. Therefore, the
Agency did not conduct a quantitative assessment and does not expect products containing MGK®
Repellent 326 to contaminate drinking water because of the low potential for MGK® Repellent 326 to
reach drinking water sources in significant concentrations.
III. A. 3. Residential Risk
III. A. 3. a. Toxicity Assessment
Toxicity assessments are designed to determine if a pesticide causes adverse health effects
(including short-term or acute effects such as skin or eye damage; and lifetime or chronic effects such as
cancer, development and reproduction deficiencies, etc.) and the level or dose at which the effects
occur. The Agency has reviewed all toxicity studies submitted and has determined that the toxicity
database is complete.
For more details on the toxicity and carcinogenicity of MGK® Repellent 326, beyond what is
found in IheMGK® Repellent 326 (Di-N-propyl isocinchomeronate) HED Risk Assessment for
Reregistration Eligibility Document (RED), dated April 7, 2003, see particularly the MGK®
Repellent 326: HED Toxicology Chapter for the Reregistration Eligibility Decision Document
(RED) dated April 7, 2003 and the MGK® Repellent 326 - Revised Report of the Hazard
Identification Assessment Review Committee, dated December 20, 2002.
III. A. 3. a. i. Acute Toxicity
MGK® Repellent 326 demonstrates low acute toxicity via the oral (Toxicity Category HI),
dermal (Toxicity Category HI), and inhalation (Toxicity Category IV) routes of exposure.
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Because MGK® Repellent 326 is not irritating to the eyes or the skin, it is in Toxicity Categories HI and
IV, respectively. Also, it is not a dermal sensitizer. The acute toxicity profile for MGK® Repellent 326
is summarized in Table 1.
TABLE 1. ACUTE TOXICITY FOR MGK® REPELLENT 326 (TECHNICAL)
Guideline No.
870.1100
870.1200
870.1300
870.2400
870.2500
870.2600
Study Type
Acute Oral
Acute Dermal
Acute
Inhalation
Eye Irritation
Skin Irritation
Dermal
Sensitization
MRK)
00155068
41648601
41571501
41800501
41826505
41648602
Results
LD50* = 5850 mg/kg, male
LD50 = 4270 mg/kg female
LD50 = 5120 mg/kg male & female
LD50 = > 2000 mg/kg
LC50*= > 6.09 mg/L
Not irritating
Not irritating
Negative
Toxicity Category
III
based on female
toxicity
III
IV
III
IV
NA
*LD50orLC50 =
can be expected to
inhalation).
Median Lethal Dose or Concentration. A statistically derived single dose or concentration that
cause death in 50% of the test animals when administered by the route indicated (oral, dermal,
III. A. 3. a. ii. Toxicological Endpoints
In determining the lexicological endpoints for a chemical, a NOAEL (No Observed
Adverse Effect Level) is identified and/or selected from a study that best approximates the duration and
route of exposure. The NOAEL is the highest dose at which no adverse health effects are observed in
animal studies. The selected lexicological endpoint and NOAEL form the basis of the hazard
component of the risk assessment for each route of human exposure (i.e., oral, dermal, and inhalation).
Residential exposure is the only relevant exposure scenario for MGK® Repellent 326 based on
the current use patterns. Therefore, lexicological doses and endpoints for dietary (food and drinking
water) exposure were not established. However, short- (1-30 days) and intermediate- (1-6 months)
term endpoints for incidental oral, dermal, and inhalation exposures were selected. Because MGK®
Repellent 326 is used seasonally, a long-term (>6 months) exposure endpoint was not selected.
For both incidental oral and dermal routes of exposure, 65 mg/kg/day was selected as the
NOAEL from a two generation reproductive study in the rat based on decreased pup body weight
occurring on lactation days 14-21 at a LOAEL (Lowest Observed Adverse Effect Level) of 250
mg/kg/day. Due to lack of toxicity at the highest dose from a 90-day inhalation rat toxicity study, the
NOAEL was identified as 60 mg/kg/day, which was the highest dose tested for the inhalation route of
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exposure. The cancer endpoint was selected based on a combined chronic toxicity/carcinogenicity
study in rats and a carcinogenicity study in mice. lexicological endpoints used in the residential risk
assessment are summarized in Table 2.
TABLE 2. SUMMARY OF DOSES AND ENDPOINTS SELECTED FOR MGK® REPELLENT 326
RESIDENTIAL RISK ASSESSMENT
Route and
Duration of Exposure
Incidental Oral
Short- and Intermediate- Term
(1 day to 6 months)
Dermal
Short- and Intermediate-Term (1
day to 6 months)
Inhalation
Short- and Intermediate-Term (1
day to 6 months)
Cancer
Dose (mg/kg/day)
&
Uncertainty Factor
(UF)
NOAEL= 65
LOAEL= 250
UF=100
Oral* NOAEL=65
LOAEL=250
UF= 100
NOAEL = 60
LOAEL >60
UF= 100
Toxicological
Endpoint
Decreased pup body
weight on lactation
days 14-21.
Lack of toxic effects at
highest dose tested
Study Type
(MRTO)
2-Generation reproductive
study in the rat
(41547801)
90-day inhalation toxicity
study in the rat
(42990201)
Classification: B2; Probable human carcinogen
Q!* = 1.6x1 0'3 (mg/kg/day)-1
* A 5% dermal absorption factor was applied for conversion from oral to dermal.
Since the dermal exposure endpoint was selected from an oral toxicity study, a dermal
absorption factor (DAF) was required to convert an oral dose to an equivalent dermal dose.
Accordingly, the Agency selected a 5% DAF based on two human dermal absorption studies with a
1% MGK® Repellent 326 product (MRIDs 42974602 and 42732101).
III. A. 3. a. iii. Carcinogenicity
In assessing the carcinogenicity of pesticides, the Agency first evaluates evidence that the
pesticide is a carcinogen. If there is evidence, such as tumor formation and the pesticide is classified as
a carcinogen, a quantitative assessment is conducted using a Q!* (non-threshold) or a Margin of
Exposure (threshold) approach. The mechanism of the tumor formation determines whether or not a
threshold or non-threshold assessment is conducted.
Since 1993, MGK® Repellent 326 has been classified as a probable human carcinogen or
group "B2", based on findings in both the rat and mouse studies during carcinogenicity testing, under the
Agency's 1986 cancer risk assessment guidelines. In light of the findings, the Agency quantified the
cancer risk using a non-threshold approach. The Qx* value for MGK® Repellent 326 is 1.6xlO"3
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(mg/kg/day)"1 based on combined liver tumors in rats. It should be noted that the carcinogenic effects
were seen at the limit dose (1000 mg/kg/day) for the rats and twice the limit dose for the mice.
III. A. 3. a. iv. FQPA Safety Factor Considerations
Determination of the FQPA safety factor is based on an analysis of all the toxicology data
following the approach described in the Agency's 2002 guidance document, Determination of the
Appropriate FQPA Safety Factor(s) in Tolerance Assessment, dated February 28, 2002. Because
all MGK® Repellent 326 registrations for use in/on foods have been cancelled and EPA is proposing to
revoke the tolerances, a FQPA safety factor is not applicable for this pesticide. However, although the
FQPA safety factor does not apply, the toxicity and exposure databases were examined to determine if
any special concerns exist for infants and children. Based on low evidence of increased susceptibility,
the Agency determined that the traditional uncertainty factors (UFs) for MGK® Repellent 326 are
adequately protective of all population subgroups, including infants and children. The traditional UFs
account for differences between test animals and humans (lOx for interspecies extrapolation) and the
differences among different human sub-populations (lOx for intraspecies variation).
HI. A. 3. b. Residential Assessment
The Agency looks at residential exposure by assessing how a person may come in contact with
a pesticide by using the pesticide in and around the home. Accordingly, a residential exposure
assessment was conducted for MGK® Repellent 326 because there is potential exposure and risk due
to direct application of insect repellents containing MGK® Repellent 326 to humans, pets and their
premises. It is assumed that direct application to human skin would result in the highest level of
potential exposures to adults and children, and would exceed those from transfer of residues from any
animal applications. Moreover, the majority of human personal use products contain 2.5% or less of
the a.i., whereas animal products contain 1% a.i. or less. Therefore, the residential risk assessment was
conducted only on exposures resulting from direct application of MGK® Repellent 326 to humans,
since it is considered to be the scenario of greatest potential concern. For a detailed discussion, see the
Exposure Assessment for MGK 326 (Dipropyl isocinchomerate), dated April 7, 2003.
All MGK® Repellent 326 products intended for human use contain DEBT (N, N-diethyl-m-
toluamide) as the primary active ingredient. Therefore, the Agency used frequency and quantity
information from a 1990 survey on consumer use of products containing DEBT to assess exposure to
MGK® Repellent 326, because there are no available data measuring exposures to MGK® Repellent
326 for humans. The DEET survey study was conducted during the months of June and July and was
submitted by the DEET Joint Venture/Chemical Specialties Manufacture Association (MRID
41968001). After analyzing the data, the Agency determined that the DEET survey provides the most
definitive data for estimating human insect repellent exposures for assessing non-cancer and cancer
residential risks of MGK® Repellent 326.
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HI. A. 3. b. i. Non-Cancer Residential Risk Summary
Exposure Scenarios
As personal insect repellents, MGK® Repellent 326 products may be applied as sprays,
lotions, and liquids. There is no standard application rate as the products are applied on an as needed
basis. Accordingly, the Agency identified the following as the three major non-cancer residential
exposure scenarios: 1) incidental oral exposure of children from topical application (i.e., incidental hand
to mouth contact after repellent is applied to a child's skin; 2) dermal exposure from direct application
of MGK® Repellent 326 to human skin and clothing; and 3) inhalation exposure from use of repellent
sprays.
Margins of Exposure (MOEs) and Characterization
Non-cancer residential risk is measured by a Margin of Exposure (MOE) which reflects how
close the residential exposure comes to a NOAEL selected from animal studies. The margin of
exposure (MOE=NOAEL/exposure) is compared to a level of concern, or target MOE. The target
MOE is the same value as the uncertainty factor applied to the NOAEL from the relevant toxicity
study. A MOE less than the target MOE is typically of concern to the Agency. For MGK® Repellent
326, the target MOE is 100 for the incidental oral, dermal, and inhalation routes of exposure for the
non-cancer residential risk assessment.
Although an endpoint for inhalation toxicity was selected, inhalation exposure is expected to be
negligible as explained below; therefore, risks were not quantitatively assessed. The vapor pressure of
MGK® Repellent 326 is very low (4.92xlO"7) so there would be virtually no vapor generated by non-
aerosol products. All MGK® Repellent 326 labels prohibit spraying of the face. Additionally,
inhalation exposure duration from aerosol application is expected to be extremely short (i.e., typically a
few seconds). Based on these considerations, inhalation exposure to MGK® Repellent 326 would not
significantly affect the overall risks.
The Agency assumes that the primary route of exposure will be dermal. Therefore, assuming
average body weights, a mean amount of product applied to skin and clothing per application, a 5%
DAF and 2.5% as the maximum concentration of MGK® Repellent 326 in a product formulation for
human application, the following non-cancer residential MOEs were derived for dermal exposure. The
MOEs estimated for the residential (personal insect repellent use) dermal exposure scenario for all
population subgroups assessed indicate risks are not of concern (i.e., all MOEs are > 100) as indicated
in Table 3.
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TABLE 3. MGK® REPELLENT 326 NON-CANCER RESIDENTIAL MOES - DERMAL EXPOSURE
Population
Subgroup
Child < 12 years
Child 13-17 years
Adult Female
Adult Male
Applied Dose
(mg/kg/day)
120
130
107
130
Body Weight
(kg)
25
56
62
77
Daily Dose
(mg/kg/day)
0.24
0.12
0.09
0.08
MOE1
(Target MOE = 100)
270
565
750
770
1 MOE= Oral NOAEL (65 mg/kg/day) / Daily Dose
where:
Daily Dose = (Applied Dose) x 5% DAF / Body Weight
Applied Dose = Applied Dose of Repellent from DEET Survey x 2.5% MGK® Repellent 326
The above MOEs for dermal exposure assumes MGK® Repellent 326 is applied once a day.
However, because insect repellents containing MGK® Repellent 326 may be applied more than once a
day, the Agency assessed the number of applications that could be applied in a day and not result in
risks of concern. To assess the number of applications allowable per day, the Agency set the MOE to
100 and conducted the calculation in reverse using a set daily dose of 0.65 mg/kg/day, which is the
dermal dose adjusted by uncertainty factors.
Table 4 details the number of dermal applications each population subgroup may make and not
result in risks of concern: children ages twelve and under may use 3 applications; children ages 13-17
may use 6 applications; and adults may use 8 applications. These estimates are considered to be
relatively protective based on the average number of MGK® Repellent 326 applications per year
identified in the DEET survey and its limited use pattern.
TABLE 4. NUMBER OF MGK® REPELLENT 326 APPLICATIONS / DAY WITHOUT EXCEEDING
THE AGENCY'S NON-CANCER RESIDENTIAL LEVEL OF CONCERN 1
Population
Subgroup
Child < 12 years
Child 13-17 years
Adult Female
Adult Male
Applied Dose
(mg/kg/day)
325
735
806
1001
Body Weight
(kg)
25
56
62
77
Daily Dose
(mg/kg/day)
0.65
Number of
Applications / Day
3
6
8
8
'Target MOE = 100
The MOE calculated for incidental oral exposure of children (ages twelve and under) from
topical application is 4100. This MOE is well above the Agency's target of 100; therefore, incidental
oral exposure is not of risk concern. Although incidental oral exposure is expected to be negligible
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when compared to dermal exposure, the Agency assessed combined sources of exposure from direct
application of MGK® Repellent 326 to human skin and incidental oral exposure of children from hand-
to-mouth activity after topical application. Combined risks from different residential exposure pathways
is estimated for the child exposure scenario only, since children are assumed to be exposed via both the
incidental oral and dermal pathways. Whereas adults are assumed to be exposed by the dermal route
only. The combined MOE for the child is calculated by adding exposure estimates from the oral and
dermal pathways. The combined MOE is 250 for children ages twelve and under, which is greater than
the target MOE of 100 and, therefore, not a risk concern.
HI. A. 3. b. ii. Cancer Residential Risk Summary
Exposure Assumptions
To assess the amount of residential cancer exposure an individual will receive over a lifetime
from using MGK® Repellent 326, the following assumptions were applied:
The Agency used its standard assumption that the average adult weighs 70 kg (as agreed
upon by North American Freedom of Trade Agreement (NAFTA) members) over a lifetime. Although
the body weights of exposed individuals vary from children to adults, for a lifetime of exposures adult
body weights are more appropriate for risk assessment purposes.
Standard policy for assessing residential/non-occupational lifetime exposure is 70
years. Therefore, the Agency assumes that an individual is exposed every year for 70 years. Also, in
calculating lifetime exposure, standard policy is to use an average number of applications applied per
year.
• The Agency used the data from a 1990 DEET survey to determine the average
number of applications that are likely to occur over a year. The data gathered revealed repellent
products containing DEET were used an average of 7.5 times during the months of June and July.
Similarly, syndicated market data from 1989-1990 indicated approximately 55-60% of yearly insect
repellent sales occur during the months of June and July.
Using the average of 7.5 applications during the heavy use season and dividing by
60%, which is the volume of insect repellents reportedly sold during the same period from the DEET
survey data, the Agency estimates that an individual will make 12.5 MGK® Repellent 326 applications
per year on average. The Agency conservatively assumed for the risk assessment that each DEET
product reported in the survey also contained MGK® Repellent 326.
• Further, the risk assessment conservatively assumes residues applied to both
clothing and skin are absorbed into the skin. Meaning if an individual sprays an insect repellent
containing MGK® Repellent 326 over their clothes and exposed skin, not only is the amount contacting
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the skin being absorbed, but the residues from the clothing are also being absorbed. Also, it is assumed
that 100% of what is applied is contacting the skin and of the amount applied, 5% is absorbed through
the skin. Moreover, it is assumed that the concentration of MGK® Repellent 326 in all products is
limited to 2.5% a.i. regardless of formulation.
Risk Estimates
Cancer risk estimates are calculated by multiplying the Lifetime Average Daily Dose (LADD),
which represents oral, dermal, inhalation exposure over a lifetime, by the Qx* or unit risk. Because
dermal exposure is the primary route of exposure for MGK® Repellent 326, oral and inhalation routes
exposures were not considered in determining the LADD. Therefore, all the exposure assumptions
discussed above were considered in calculating the LADD for MGK® Repellent 326, which represents
average annual dermal exposure to an individual over a lifetime.
As mentioned in the carcinogenicity section, MGK® Repellent 326 was quantitatively assessed
using a non-threshold (Qi*) approach. The Qx* value for MGK® Repellent 326 is based on combined
tumors in the rat cancer study. Also, the Qx* is based on extrapolating from animal studies, therefore
the Agency used a 3/4 body weight scaling factor to derive a human equivalent. The Qx* value derived
for MGK® Repellent 326 is 1.6xlO'3 (mg/kg/day)-1.
Cancer risk estimates assessed by a Qx* approach are expressed as a probability. For
example, a cancer risk of IxlO"6 means that a person receiving a lifetime exposure to the pesticide
increases his/her risk of developing cancer by one chance in a million. Based on the data and
assumptions discussed above and the Qx* value, EPA estimates that individuals exposed to MGK 326
over a lifetime have a potential cancer risk of 4.7xlO"6. The Agency believes the conservative
assumptions and factors used in the risk assessment provide adequate assurance that actual risks are
lower and do not exceed the Agency's level of concern.
III. A. 4. Aggregate Risk
Although tolerances are proposed for revocation and an aggregate risk assessment is not
required for MGK® Repellent 326, EPA has considered the potential for risk resulting from exposure
via multiple sources. EPA has determined that since there is no potential for exposure through food,
and potential exposure through drinking water would be negligible, risks resulting from combined
sources of exposure (residential, food, and drinking water) would be below EPA's level of concern.
HI. A. 5. Human Incident Reports
In evaluating incidents to humans, the Agency reviews any incident data that may be available
and applicable. Although, there have been incidents reported from other active ingredients formulated
with MGK® Repellent 326, they were not attributed to MGK® Repellent 326. For more details see
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Review of MGK-326 Incident Reports, dated September 3, 2003, which is available on the internet
and in the public docket.
III. B. Environmental Risk Assessment
A summary of the Agency's environmental risk assessment is presented below. For detailed
discussions of all aspects of the environmental risk assessment, seeMGAT 326/Disopropyl
isochinomerate [sic] RED, dated December 24, 2002, which is available on the internet and in the
public docket.
III. B. 1. Ecological Toxicity Data
A limited set of toxicity data for indoor-use pesticides is required to determine precautionary
label statements and to assess environmental hazards in case of spills. MGK® Repellent 326 qualifies
for a reduced data set, because use patterns are limited to indoor non-food and residential uses. The
available data characterize MGK® Repellent 326 as practically nontoxic to birds, slightly toxic to
aquatic invertebrates and highly toxic to fish, and are summarized in the Table 5.
TABLES. SUMMARY OF MGK® REPELLENT 326 ECOLOGICAL TOXICITY ENDPOINTS
Toxicity Study
Test Species
% a.i.
Endpoint (ppm)
Toxicity Category
MRH>
Birds (Subacute: Five days of treated feed)
Avian Dietary
Avian Dietary
Bobwhite Quail
Mallard Duck
98.8
98.8
LC50* = 5,000
LC50 = >5,620
Practically nontoxic
Practically nontoxic
41685502
41685501
Aquatic Species (Acute: Single dose)
Freshwater Invertebrate
Freshwater Fish
Freshwater Fish
Daphnid
Bluegill Sunfish
Rainbow Trout
99.7
99.5
100
EC50**=18
LC50 = 0.44
LC50= 1.0
Slightly toxic
Highly toxic
Highly toxic
41525302
42174501
41911401
*LC50 = Median Lethal Concentration. A statistically derived single concentration that can be expected to cause
death in 50% of the test animals when administered by the oral route.
* *EC50 = Effective Concentration for aquatic plants and invertebrates. The concentration of a chemical in water at
which an effect is observed that is 50% of the maximum effect.
HI. B. 2. Environmental Fate
The Agency develops a profile of the likely fate (persistence and mobility) of an individual
pesticide in the environment based on a combination of standard studies. Because of its limited use
pattern, the only environmental fate study required to be conducted for MGK® Repellent 326 was
hydrolysis. MGK® Repellent 326 remains stable under acidic conditions (pH 5), no degradation was
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observed during the 30 days of the study. However, MGK® Repellent 326 hydrolyzes in neutral (pH 7
half-life=17 days) and alkaline environments (pH 9 half-life=14 hours) (MRS) 43073601).
in. B. 3. Ecological Risk Summary
To assess the potential for significant risk to non-target organisms from use of a pesticide, the
Agency compares the estimated environmental exposure concentration to the toxicity effect level. The
Agency uses surrogate species (i.e., bobwhite quail, rats, rainbow trout, etc.) to represent all terrestrial
and aquatic organism potentially exposed in pesticide use areas.
Ecological risk assessments are not conducted for pesticides with exclusively indoor use
patterns. MGK® Repellent 326 is considered to be an "indoor residential" use rather than an outdoor
use because it is only applied directly to the human body and/or clothing, cats, dogs, horses, pet
quarters, and household/domestic dwellings. Application of MGK® Repellent 326 to these sites is not
likely to adversely affect terrestrial wildlife or aquatic organisms; therefore, an environmental risk
assessment was not conducted for MGK® Repellent 326.
III. B. 4. Incident Reports
The Ecological Incident Information System (EIIS) database recorded no incidents to non-
target species associated with MGK® Repellent 326.
III. B. 5. Endangered Species
Based upon the exclusive "indoor residential" use pattern and unlikelihood of MGK® Repellent
326 to adversely affect terrestrial wildlife or aquatic organisms, MGK® Repellent 326 will have no
effect on federally listed endangered and threatened species from the uses discussed in this RED.
IV. RISK MANAGEMENT AND REREGISTRATION DECISION
IV. A. Determination of Reregistration Eligibility
Section 4(g)(2)(A) of FIFRA calls for the Agency to determine, after submissions of relevant
data concerning an active ingredient, whether pesticides containing the active ingredient are eligible for
reregistration. The Agency has previously identified and required the submission of the generic data
required to support reregistration of products containing MGK® Repellent 326 as the active ingredient.
The Agency has completed its assessment of the residential risks associated with the use of
MGK® Repellent 326 repellency products. Based on a review of these data and public comments on
the Agency's risk assessments for the active ingredient MGK® Repellent 326, EPA has sufficient
information on the human health and ecological effects of MGK® Repellent 326 to make a
16
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reregistration decision under FIFRA, as amended by FQPA. The Agency has determined that MGK®
Repellent 326 is eligible for reregistration provided that: (i) current data gaps and additional data needs
are addressed; and (ii) the risk mitigation measures outlined in this document are adopted, including the
label amendments described in Section IV and limiting production and distribution to 20,000 pounds of
active ingredient annually by all registrants for use as an insect repellent on humans. The technical
registrants) must also submit an annual report certifying that production and distribution of MGK®
Repellent 326 for use in personal insect repellents did not exceed 20,000 Ibs a.L; and (iii) limits the
maximum concentration active ingredient in end-use products for personal insect repellents to 2.5%.
Appendix B identifies the generic data requirements that the Agency reviewed as part of its
determination of reregistration eligibility of MGK® Repellent 326, and lists the submitted studies that the
Agency found acceptable.
Based on its current evaluation of MGK® Repellent 326 alone, the Agency has determined that
MGK® Repellent 326 products, unless labeled and used as specified in this document, would present
risks inconsistent with FIFRA. Accordingly, should a registrant fail to implement any of the risk
mitigation measures identified in this document, the Agency may take regulatory action to address the
risk concerns from use of MGK® Repellent 326. Also, this decision does not preclude the Agency
from making further FQPA determinations and tolerance-related rulemakings that may be required on
this pesticide, or any other, in the future.
IV. B. Summary of Public Participation Process
When making its reregistration decision for MGK® Repellent 326, the Agency took into
account all comments received during the public participation process. The only comments received
were from the technical registrant, McLaughlin Gormley King Company (MGK). In their comments,
MGK indicated that they intend to take certain steps to address the Agency's estimated cancer risk,
including convening a pathology working group to review findings in the kidney and other tissues;
investigate advances presented in the scientific literature; reexamine study tissues (in particular liver
tissue to look for evidence of cell proliferation); and other actions. The registrant also commented on
the cancer risk assessment guidelines and other methods used to derive the cancer risks estimates for
MGK® Repellent 326.
The registrant has not provided the appropriate data to allow the Agency to reconsider the
cancer classification at this time; however, MGK has engaged the Agency to determine the necessary
work to address the identified hazard identification issues, which MGK believes will be responsive to
MGK® Repellent 326 cancer classification and risk concerns. The registrant's comments and the
Agency's response to these comments are available in their entirety on the internet and the public
docket.
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IV. C. Regulatory Position
IV. C. 1. Determination of Safety for U.S. Population under FQPA
As detailed above, all registrations for uses of MGK® Repellent 326 on or in food have been
voluntarily cancelled by the technical registrant. Therefore, the Agency has concluded that a FQPA
safety factor is not applicable for this pesticide. Additionally, EPA is recommending revocation of
tolerances for residues resulting from dermal application in/on livestock commodities that have been
removed from the MGK® Repellent 326 technical label.
Although a FQPA safety factor is not applicable for MGK® Repellent 326, the Agency
considered the available information to determine if there is an increased susceptibility to infants and
children from exposures to MGK® Repellent 326. Based on that evaluation, the Agency concluded
that the MGK® Repellent 326 human health assessment is adequately protective of all population
subgroups, including infants and children.
IV. C. 1. a. Tolerance Summary
Tolerance Reassessment
The tolerances listed under 40 CFR §180.143 are "for negligible residues of the insect repellent
dipropyl isocinchomronate" (MGK® Repellent 326). The Agency is now proposing to revoke
tolerances for residues resulting from dermal application in/on livestock commodities that have been
removed from the MGK® Repellent 326 technical label.
The established tolerances for milk, fat, meat, and meat byproducts of cattle, goat,
hog, horse, and sheep are no longer applicable for MGK® Repellent 326. The Agency's tolerance
reassessment summary is provided in Table 6.
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TABLE 6. TOLERANCE REASSESSMENT SUMMARY FOR MGK® REPELLENT 326
Commodity
Current Tolerance
(ppm)
Reassessed Tolerance
(ppm)
Comment
Tolerances Listed Under 40 CFR §180.143
Cattle, fat
Cattle, meat
Cattle, meat byproducts
Goats, fat
Goats, meat
Goats, meat byproducts
Hogs, fat
Hogs, meat
Hogs, meat byproducts
Horses, fat
Horses, meat
Horses, meat byproducts
Milk
Sheep, fat
Sheep, meat
Sheep, meat byproducts
0.1 (N)
0.1 (N)
0.1 (N)
0.1 (N)
0.1 (N)
0.1 (N)
0.1 (N)
0.1 (N)
0.1 (N)
0.1 (N)
0.1 (N)
0.1 (N)
0.004 (N)
0.1 (N)
0.1 (N)
0.1 (N)
Revoke
Livestock (food) uses have
been deleted, therefore
tolerances to be revoked.
Delete Section 40 CFR
§180.143.
(N) = negligible residues
Codex Harmonization
No Codex Maximum Residue Levels (MRLs) are necessary for MGK® Repellent 326;
therefore, issues of compatibility between Codex MRLs and U.S. tolerances do not exist.
Residue Analytical Methods
The Pesticide Analytical Manual, Volume n lists the available methods for tolerance
enforcement. However, enforcement methods are not required for determining residues of MGK®
Repellent 326 because there are no food uses registered for MGK® Repellent 326 and the tolerances
are to be revoked.
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IV. C. 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 such
endocrine effects as the Administrator may designate." Following the recommendations of its
Endocrine Disrupter Screening and Testing Advisory Committee (EDSTAC), EPA determined that
there were scientific bases 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). When the
appropriate screening and/or testing protocols being considered under the Agency's EDSP have been
developed, MGK® Repellent 326 may be subjected to additional screening and/or testing to better
characterize effects related to endocrine disruption.
IV. C. 3. Cumulative Risk
FQPA of 1996 stipulates that when considering whether to establish, modify, or revoke a
tolerance, the Agency must consider "available information" concerning cumulative effects of a
particular pesticide's residues and "other substances that may have a common mechanism of toxicity."
The Agency did not perform a cumulative risk assessment as part of this assessment for MGK®
Repellent 326 because the Agency has not yet initiated a review to determine if there are any other
chemical substances that have a mechanism of toxicity common with that of MGK® Repellent 326.
Therefore, for purposes of the RED, the Agency assumes that MGK® Repellent 326 does not share a
common mechanism of toxicity with any other substance(s). Should a common mechanism of toxicity
be determined in the future, EPA may need to reconsider the cumulative risks of MGK® Repellent 326...
IV. C. 4. Public Health Benefits
Under section 4(n) of FIFRA, the Agency requested a consultation with the Centers for
Disease Control and Prevention (CDC) for potential public health benefits for the insect repellent
MGK® Repellent 326. CDC responded that because there is little information in the published
literature concerning the effectiveness of the pesticide, CDC found it difficult to evaluate the public
health benefits derived from MGK® Repellent 326. Despite the lack of data, CDC has indicated that
they support the reregistration of MGK® Repellent 326 from a public health perspective. For more
details, see the letter from CDC dated August 25, 2003, which is available on the internet and in the
public docket.
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IV. D. Regulatory Rationale
The following is a summary of the rationale for managing risks associated with the use of
MGK® Repellent 326. Where labeling revisions are warranted, specific language is set forth in the
summary Table of Section V (Table 8) of this document.
IV. D. 1. Human Health Risk Mitigation
IV. D. 1. a. Dietary Risk Mitigation
Dietary risk from food and drinking water are not of concern, based on the current use pattern
and the absence of dietary exposure for the chemical. Therefore, mitigation measures to address
dietary (food and drinking water) risks are not necessary for MGK® Repellent 326.
IV. D. 1. b. Residential Risk Mitigation
IV. D. 1. b. i. Non-Cancer
Non-cancer residential exposures do not pose a risk of concern. The MOEs for individual and
combined routes of exposure from single applications of MGK® Repellent 326 are all greater than 100,
the Agency's level of concern. Therefore, mitigation measures to address non-cancer residential risk
are not necessary for MGK® Repellent 326. However, because MGK® Repellent 326 is an insect
repellent which may be applied multiple times directly to skin of individuals of all age groups including
young children, the Agency assessed the number of dermal applications a population subgroup may
make without resulting in risks of concern (see Table 4). The results of this analysis indicates that
children, ages 12 and under, may make up to 3 applications in a single day without exceeding levels of
concern. Therefore, to limit the potential exposure of MGK® Repellent 326 to children, a statement
shall be added to MGK® Repellent 326 products for human use specifying the number of applications
to children ages twelve and under. The statement will read as follows: "Do not apply more than 3 times
per day to children ages twelve and under."
IV. D. 1. b. ii. Cancer
The Agency conducted a conservative (high-end) cancer risk assessment, which resulted in a
potential lifetime cancer risk estimate of 4.7xlO"6. Although the cancer assessment suggests a risk of
concern (greater than IxlO"6), the Agency believes that the actual risk is lower, in light of the
conservative assumptions used in the Agency's assessment. For instance, although the carcinogenic
effects for MGK® Repellent 326 were identified only at the highest dose tested, using a non-threshold
(Qi*) approach, it is assumed that any dose, however small, can lead to cancer.
21
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Also, in using the DEBT survey data to estimate cancer risk, the Agency assumed that every
DEBT product sold and applied also contains MGK® Repellent 326. This assumption seems to be
highly conservative, because of the significant difference in annual poundage produced and used yearly
(DEET averages about 7-8 million pounds of a.i annually compared to 31,000 to 36,000 Ibs for
MGK® Repellent 326, of which only approximately 15,000 to 20,000 Ibs of MGK® Repellent 326 are
used for personal insect repellent products). Furthermore, insect repellents such as MGK® Repellent
326 are generally used on a seasonal and intermittent basis, as indicated by DEET survey sales data
which denotes 60% of the products are sold in June and July. Based on this information, it is unlikely
an individual would spend 70 years in a seasonally insect populated environment and use the same
DEET repellent products that also contains MGK® Repellent 326 each year.
Spray-type products, aerosol and pump-types, are the most common forms available for
application of MGK® Repellent 326, and are generally used to treat both skin and clothing to repel
biting flies. The cancer risk estimates were based on the total amount of MGK® Repellent 326 product
measured from typical spray-type applications, which were made to both clothing and skin and
assumed available for absorption into the skin. Yet it is unlikely that the total amount applied to clothing
would be available for absorption into the skin because of the lack of contact between the treated
clothing surface and the individual's skin. Furthermore, because of the nature of spray applications,
particularly aerosol, the amount of product sprayed from a container is not likely to all be deposited on
the target area. In other words, a certain amount of the released spray does not even contact the
individual's skin or clothing. Therefore, the actual dose is expected to be less than the dose used in the
cancer risk calculations.
To present a more realistic estimate of exposure and risk, EPA modified some of the screening-
level assumptions used in the risk assessment, such as the number of years an individual may be
exposed over a lifetime, and the level of MGK® Repellent 326 residues applied to skin only rather than
to both skin and clothing. The range of risks calculated using these different assumptions is presented in
Table 7.
Table 7. ESTIMATED CANCER RISK FROM RESIDENTIAL USE OF MGK* REPELLENT 326
No. of Years Applied
70
50
30
20
15
10
5
Skin and Clothing1
4.7 xlO'6
3.4 xlO'6
2.0 xlO'6
1.3 xlO'6
l.OxlO'6
6.7 xlO'7
3.4 xlO'7
Skin Only2
3.3X10'6
2.4 xlO'6
1.4 xlO'6
9.5 x lO'7
7.1 xlO'7
4.8 xlO'7
2.4 xlO'7
1 Average amount of product per application for skin and clothing (high-end) = 4.!
2 Average amount of product per application for skin only (low-end) = 3.4 g
22
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In Table 7, cancer risks were estimated from a range of 5 to 70 years of exposure. Each
exposure duration was also divided into two categories, skin and clothing (high-end) and skin only
(low-end) exposure. The Agency chose to present a range of estimated cancer risks for MGK®
Repellent 326 for application to skin only and skin and clothing to present more appropriate estimates
of cancer risk, because of the limited use pattern and availability of MGK® Repellent 326 products, and
the conservative exposure assumptions used in the cancer risk assessment. As indicated in Table 7, the
estimated cancer risk decreases proportionally with the reduction in years of exposure. Therefore,
because it is highly unlikely that an individual would use products containing MGK® Repellent 326 over
a period of many years, due to the small proportion of insect repellents available that contain MGK®
Repellent 326, the actual cancer risks associated with this use are likely lower.
As previously discussed, use of product sprays (aerosol and pump-type) are likely to result in
applications to both skin and clothing, which were included in the cancer risk assessment as high-end
exposures. However, the high-end amount of MGK® Repellent 326 applied by sprays to the skin and
clothing is not expected to be fully available to be absorbed into the skin. Further, current product
labels include the statement "do not use under clothing," and not all registered product formulations
containing MGK® Repellent 326 are aerosol sprays. Thus, using more realistic exposure assumptions,
calculations indicate that an individual could be continuously exposed for nearly 30 years without
exceeding the Agency's level of concern. For more details see MGK® Repellent 326 (Di-n-propyl
isocinchomeronate) cancer Risk Estimates for Residential Use of MGK® Repellent 326, dated
August 29, 2003, which is available on the internet and in the public docket.
Thus, based on the Agency's understanding of the use of MGK® Repellent 326 and the
conservative (high-end) assumptions which were used to calculate lifetime exposures, it is the Agency's
position that the estimated cancer risks are an overestimate and that actual risks are not of concern,
provided the following measures are complied with and fully implemented:
• Because the estimated cancer risks are based on an assumption that an individual is
continuously exposed to MGK® Repellent 326 for up to 70 years, which use information
indicates is highly unlikely because of the limited availability of MGK® Repellent 326 products,
the Agency believes it is necessary for production and distribution of MGK® Repellent 326 to
be limited. A limitation on the amount of MGK® Repellent 326 annually produced and
distributed, is imposed to provide assurance that human exposure to MGK® Repellent 326 in
the United States will not increase from current levels, and to reduce the potential of an
individual from encountering long-term exposure to MGK® Repellent 326. Hence, the sole
technical registrant, MGK, has agreed to limit production of MGK® Repellent 326 for human
use products to a total of 20,000 pounds of active ingredient per year.
Pending receipt and review of additional information regarding the cancer risks associated with
the use of MGK® Repellent 326 for human-use products, the Agency may revisit the specified
production limit determination.
23
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Because the cancer risk assessment was conducted based on MGK® Repellent 326 products
containing 2.5% a.i. (for human use, most registered products contain 2.5% a.i. or less,
although there are some products which contain more than 2.5% a.i.), the technical registrant
has agreed to reduce and limit the maximum concentration of a.i. to 2.5% for all manufacturing-
use products containing MGK® Repellent 326 intended for human use only. As a result all
end-use registrations containing MGK® Repellent 326 intended for human use only must also
include this restriction.
IV. D. 1. c. Aggregate Risk Mitigation
Aggregate risk from combined exposure from dietary (food and drinking water) and residential
sources where not considered, because there are no dietary exposures. Therefore, no mitigation is
needed to address aggregate risk.
IV. D. 2. Environmental Risk Mitigation
Environmental risks do not pose a risk of concern, based on the current use pattern and the
absence of exposure to terrestrial wildlife or aquatic organisms for the chemical. Therefore, mitigation
measures to address environmental risks are not necessary for MGK® Repellent 326.
IV. E. Label Amendments
A number of label amendments, in addition to the existing label requirements, are necessary in
order for MGK® Repellent 326 products to be reregistered. The listing below identifies the label
statements/amendments needed on MGK® Repellent 326 labels in order for products to be
reregistered:
Label Statements for Human Products:
"Do not apply more than 3 times per day to children ages twelve (12) and under."
Label Statements for Companion Animal/Premise Products:
• "Do not use on horses or foals intended for slaughter"
"For use in companion animal quarters only, do not broadcast outdoors."
"Remove animals from quarters before treating premises."
V. WHAT REGISTRANTS NEED TO DO
In order for MGK® Repellent 326 to be eligible for reregistration, registrants need to implement
the risk mitigation measures outlined in sections IV and V, which include, among other things,
submission of the following:
24
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V. A. Data Call-In (DCI) Responses
For MGK® Repellent 326 technical grade active ingredient products, registrants need to
submit the following items:
Within 90 days from receipt of the generic data call-in (DCI): (1) completed response
forms to the generic DCI (i.e., DCI response form and requirements status and registrant's response
form); and (2) submit any time extension and/or waiver requests with a full written justification.
Within the time limit specified in the generic DCI: cite any existing generic data which
address data requirements or submit new generic data responding to the DCI.
Please contact Tawanda Spears at (703) 308-8050 with questions regarding generic
reregistration and/or the DCI. All materials submitted in response to the generic DCI should be
addressed:
Bv US mail:
Document Processing Desk (DCI/SRRD)
Tawanda Spears
US EPA (7508C)
1200 Pennsylvania Ave., NW
Washington, DC 20460
By express or courier service:
Document Processing Desk (DCI/SRRD)
Tawanda Spears
Office of Pesticide Programs (7508C)
Crystal Mall 2, Room 266A
1801 South Bell St.
Arlington, VA 22202
For end-use products containing the active ingredient MGK® Repellent 326. registrants need to
submit the following items for each product:
Within 90 days from the receipt of the product-specific data call-in (PDCI): (1)
completed response forms to the PDCI (i.e., PDCI response form and requirements status and
registrant's response form); and (2) submit any time extension or waiver requests with a full written
justification.
Within eight months from the receipt of the PDCI: (1) two copies of the confidential
statement of formula (EPA Form 8570-4); (2) a completed original application for reregistration (EPA
Form 8570-1). Indicate on the form that it is an "application for reregistration"; (3) five copies of the
draft label incorporating all label amendments outlined in Table 21 of this document; (4) a completed
form certifying compliance with data compensation requirements (EPA Form 8570-34); (5) if
applicable, a completed form certifying compliance with cost share offer requirements (EPA Form
8570-32); and (6) the product-specific data responding to the PDCI.
25
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Please contact Barbara Briscoe at (703) 308-8177 with questions regarding product
reregistration and/or the PDCI. All materials submitted in response to the PDCI should be addressed:
Bv US mail:
Document Processing Desk (DCI/PRB)
Barbara Briscoe
US EPA (7508C)
1200 Pennsylvania Ave., NW
Washington, DC 20460
By express or courier service:
Document Processing Desk (DCI/PRB)
Barbara Briscoe
Office of Pesticide Programs (7508C)
Crystal Mall 2, Room 266A
1801 South Bell St.
Arlington, VA 22202
V. B. Manufacturing-Use Products
V. B. 1. Generic Data Requirements
The generic database supporting the reregistration of di-n-propyl isocinchomeronate (MGK®
Repellent 326) has been reviewed and determined to be complete. However, the following product
chemistry data requirements have been identified by the Agency as outstanding (required in a previous
DCI, therefore will not be included in the generic DCI for this RED) or confirmatory (included in the
generic DCI for this RED):
Outstanding:
830.1700 Preliminary Analysis
830.1750 Certified Limits
830.1800 Enforcement Analytical Method
Confirmatory:
830.7050 UV/Visible Absorption
V. B. 2. Labeling for Manufacturing-Use Products
To remain in compliance with FIFRA, manufacturing-use product (MUP) labeling should be
revised to comply with all current EPA regulation, PR Notices and applicable policies. The MUP
labeling should bear the labeling contained in Table 8 at the end of this section.
V. C. End-Use Products
V. C. 1. Additional Product-Specific Data Requirements
Section 4(g)(2)(B) of FIFRA calls for the Agency to obtain any needed product-specific data
regarding the pesticide after a determination of eligibility has been made. Registrants must review
26
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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.
V. C. 2. Labeling for End-Use Products
Labeling changes are necessary to implement the mitigation measures outlined in Section IV
above. Specific language to incorporate these changes is specified in Table 8 at the end of this section.
V. D. Existing Stocks
Registrants may generally distribute and sell products bearing old labels/labeling for 26 months
from the date of the issuance of this RED document. Persons other than the registrant may generally
distribute or sell such products for 50 months from the date of the issuance of this RED. However,
existing stocks time frames will be established case-by-case, depending on the number of products
involved, the number of label changes, and other factors. For more information, refer to "Existing
Stocks of Pesticide Products; Statement of Policy"; Federal Register., Volume 56, No. 123, June 26,
1991.
The Agency has determined that registrants may distribute and sell MGK® Repellent 326
products bearing old labels/labeling for 26 months from the date of issuance of this RED. Persons other
than the registrants may distribute or sell such products for 50 months from the date of the issuance of
this RED. Registrants and persons other than the registrant remain obligated to meet pre-existing label
requirements and existing stocks requirements applicable to products they sell or distribute.
V. E. Labeling Changes Summary Table
In order to be eligible for reregistration, all product labels shall be amended to incorporate the
risk mitigation measures outlined in Section IV. Table 8 describes how language on the labels should
be amended. Label language in Table 8 enclosed in quotation marks represents exact language that
should appear on the label. Instructions that are not enclosed in quotation marks represent actions that
the registrant must take to amend their labels or product registrations in order for products to be
reregistered.
27
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Table 8. SUMMARY OF LABELING CHANGES FOR MGK* REPELLENT 326
Description
Labeling Language
Manufacturing-Use Products
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
Maximum Concentration
for Formulations Intended
for Human Use
Environmental Hazard
Statements
"Only for formulation into an insect repellent for the following use(s) [fill blank only with
those uses that are being supported by MP registrant]."
"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)."
"For formulations of this product intended for human use, the maximum percent of active
ingredient in any formulation type is 2.5."
"This pesticide is toxic to fish. 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."
Directions for Use
Directions for Use
Directions for Use
Precautionary Statements under:
Environmental Hazards
End-Use Products
Directions for Use on
Humans
"Read and Follow all Directions and Precautions on this Product Label."
Directions For Use: Following
the Misuse Statement (It is a
violation if Federal Law..)
28
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Table 8. SUMMARY OF LABELING CHANGES FOR MGK* REPELLENT 326
Description
Labeling Language
General Precautions and
Restrictions for Use on
Humans
"Do not apply over cuts, wounds, or irritated skin."
"Do not apply near eyes and mouth. Apply sparingly around ears."
"Do not allow children to handle this product, and do not apply to children's hands"
"When using on children, apply to your own hands and then put it on the child."
"Do not apply more than 3 times per day to children ages twelve (12) and under."
"Use just enough repellent to cover exposed skin and/or clothing. Avoid overexposure"
"Do not use under clothing."
"After returning indoors, wash treated skin with soap and water."
"Wash treated clothing before wearing it again."
"Do not spray directly onto face. Spray hands first and then use hands to wipe spray onto
face."
Directions for Use under the
heading "General Precautions
and Restrictions."
Replacement First Aid
Statement for Dermal Route
of Exposure
The following text must be added to the label as per PR Notice 2001-1 and replaces the "If
On Skin Or On Clothing" statements:
"If you suspect a reaction to this product:
-Discontinue use.
-Rinse skin immediately with plenty of water for 15-20 minutes.
-Call a poison control center or doctor for treatment advice."
First Aid Statement
29
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Table 8. SUMMARY OF LABELING CHANGES FOR MGK* REPELLENT 326
Description
Directions for Use on
Companion Animals
General Precautions and
Restrictions for Use in
Companion Animal Quarters
Environmental Hazard
Labeling Language
"Do not use on horses or foals intended for slaughter."
"Do not apply over cuts, wounds, or irritated skin."
"Do not apply near eyes and mouth. Apply sparingly around ears."
Include all statements consistent with PR Notice 96-6.
"For use in companion animal quarters only, do not broadcast outdoors."
"Remove animals from quarters before treating premises."
"This pesticide is toxic to fish. Do not apply directly to water, or to areas where surface
water is present or to intertidal areas below the mean high water mark. Do not contaminate
water when disposing of equipment washwaters or rinsate."
Directions for Use
Precautionary Statements
Precautionary Statements
30
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APPENDICES
31
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Appendix A. MGK® Repellent 326 (Case 2215): Use Patterns Eligible for Reregistration
Application Type
Timing
Equipment
Cats (Adults/Kittens)
Animal Treatment (spray)
When Needed
Aerosol Can
Animal Treatment
(lotion/ointment)
When Needed
By Hand
Dip Treatment (shampoo)
When Needed
Dip
Formulation
Pressurized
Liquid
Ready To Use
Emulsifiable
Concentrate
Max. Single
App. Rate
Not Specified
Not Specified
1 fl.oz /
1 gal of water
Max. Seasonal
App. Rate
Not
Specified
Not
Specified
Not
Specified
Minimum
Retreatment
Interval
(days)
Not
Applicable
Not
Applicable
Not
Applicable
Restrictions/Comments
Dogs (Adults/Puppies)
Animal Treatment (spray)
When Needed
Aerosol Can
Animal Treatment
(lotion./ointment)
When Needed
By Hand
Dip Treatment (shampoo)
When Needed
Dip
Pressurized
Liquid
Ready To Use
Emulsifiable
Concentrate
Not Specified
Not Specified
1 fl.oz /
1 gal of water
Not
Specified
Not
Specified
Not
Specified
Not
Applicable
Not
Applicable
Not
Applicable
32
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Appendix A. MGK® Repellent 326 (Case 2215): Use Patterns Eligible for Reregistration
Application Type
Timing
Equipment
Horses
Animal Treatment
When Needed
Towelette
Animal Treatment (spray)
When Needed
Pump Sprayer/Bottle
Formulation
Impregnated
Material
Pressurized
Liquid
Max. Single
App. Rate
Not Specified
Not Specified
Max. Seasonal
App. Rate
Not
Specified
Not
Specified
Minimum
Retreatment
Interval
(days)
Not
Applicable
Not
Applicable
Restrictions/Comments
Do not use on horses or foals intended for
slaughter.
Do not use on horses or foals intended for
slaughter.
Human Body/Clothing While Being Worn
Clothing Treatment
When Needed
Aerosol Can
Clothing Treatment
When Needed
Sprayer
Skin Contact Treatment
When Needed
Aerosol Can
Pressurized
Liquid
Pressurized
Liquid
Pressurized
Liquid
Not Specified
Not Specified
Not Specified
Not
Specified
Not
Specified
Not
Specified
Not
Applicable
Not
Applicable
Not
Applicable
Do not apply more than 3 times per day to
children ages twelve (12) and under.
Do not apply more than 3 times per day to
children ages twelve (12) and under.
Do not apply more than 3 times per day to
children ages twelve (12) and under.
33
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Appendix A. MGK® Repellent 326 (Case 2215): Use Patterns Eligible for Reregistration
Application Type
Timing
Equipment
Skin Contact Treatment
(lotion/ointment)
When Needed
By Hand
Formulation
Ready
To Use
Max. Single
App. Rate
Not Specified
Max. Seasonal
App. Rate
Not
Specified
Minimum
Retreatment
Interval
(days)
Not
Applicable
Restrictions/Comments
Do not apply more than 3 times per day to
children ages twelve (12) and under.
Interior of Pet Living/Sleeping Quarters
Animal Bedding/Litter
Treatment
When Needed
Mist Applicator
Spot Treatment
When Needed
Mist Applicator
Pressurized
Liquid
Pressurized
Liquid
1 fl. oz/
1000 sq. ft
1 fl. oz/
1000 sq. ft
Not
Specified
Not
Specified
Not
Applicable
Not
Applicable
For use in companion animal quarters only, do
not broadcast outdoors. Remove animals
from quarters before treating premises
34
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Appendix B. Data Supporting Guideline Requirements for the Reregistration of MGK®
Repellent 326
GUIDE TO APPENDIX B
Appendix B contains a listing of data requirements which support the reregistration for active
ingredients within the chemical case covered by this RED. It contains generic data requirements that
apply in all products, including data requirements for which a "typical formulation" is the test substance.
The data table is organized in the following formats:
1. Data Requirement (Columns 1, 2 & 3). The data requirements are listed in the order of New
Guideline Number and appear in 40 CFR §158. The reference numbers accompanying each
test refer to the test protocols set in the Pesticide Assessment Guidance, which are available
from the National Technical Information Service, 5285 Port Royal Road, Springfield, VA
22161-0002, (703) 487-4650.
2. Use Pattern (Column 4). This column indicates the use patterns for which the data
requirements apply. The following letter designations are used for the given use patterns.
1. Terrestrial food
2. Terrestrial feed
3. Terrestrial nonfood
4. Aquatic food
5. Aquatic nonfood outdoor
6. Aquatic nonfood industrial
7. Aquatic nonfood residential
8. Greenhouse food
9. Greenhouse nonfood
10. Forestry
11. Residential
12. Indoor food
13. Indoor nonfood
14. Indoor medical
15. Indoor residential
3. Bibliographical Citation (Column 5). If the Agency has acceptable data in its files, this column
lists the identification number of each study. Normally, this is the Master Record Identification
(MRID) Number, but may be a "GS" number if no MRID number has been assigned. Refer to
the Bibliography (Appendix D) for a complete citation of the study.
35
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New
Guideline
Number
Old
Guideline
Number
Requirement
Use
Pattern
Bibliographical Citation(s)
PRODUCT USE CHEMISTRY
830.1550
830.1600
830.1620
830.1670
830.1700
830.1750
830.1800
830.6302
830.6303
830.6304
830.7050
830.7220
830.7300
830.7840
830.7860
830.7950
830.7370
830.7550
830.7000
830.6313
830.6315
830.6316
830.6317
830.7100
830.6319
830.6320
61-1
6 1-2 A
61-2B
62-1
62-2
62-3
63-2
63-3
63-4
None
63-6
63-7
63-8
63-9
63-10
63-11
63-12
63-13
63-15
63-16
63-17
63-18
63-19
63-20
Product Identity and Composition
Starting Materials and Manufacturing
Process
Description of Production Process
Discussion of Formation of Impurities
Preliminary Analysis
Certification of Limits
Enforcement Analytical Method
Color
Physical State
Odor
UV/Visible Absorption
Boiling Point/Boiling Range
Density, Relative Density, Bulk Density
Solubility
Vapor Pressure
Dissociation Constant in Water
Octanol/Water Partition Coefficient
pH of Water Solutions or Suspensions
Stability
Flammability
Explodability
Storage Stability
Viscosity
Miscibility
Corrosion Characteristics
All
All
All
All
All
All
All
All
All
All
M, O
All
All
All
All
All
All
All
All
All
All
All
All
All
All
41605101, 42321101, Data Gap
41605101,42321101
41605102, 42321101, 43015101,
Data Gap
41605101-2, 42321101, Data Gap
41605102, 42321101, 42757901,
Data Gap
41605103
Data Gap
41605103
41548301,41605103
42230401,42321101
41520602,41605103
41605103
41605103, 43452501, 44190201
41605103
ECOLOGICAL EFFECTS
850.2100
71-1A
Avian Acute Oral Toxicity, Bobwhite
Ouail
M, O
Reserved
36
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New
Guideline
Number
850.2200
850.1075
850.1010
Old
Guideline
Number
71-1B
7 1-2 A
71-2B
72-1A
72- 1C
72-2A
Requirement
Avian Acute Oral Toxicity, Mallard Duck
Avian Subacute Dietary Toxicity,
Bobwhite Quail
Avian Subacute Dietary Toxicity, Mallard
Duck
Fish Toxicity, Bluegill Sunfish
Fish Toxicity, Rainbow Trout
Invertebrate Toxicity
Use
Pattern
M, O
M, O
M, O
M, 0
M, O
M, 0
Bibliographical Citation(s)
Reserved
41685502
41685501
42174501
41911401
41525302
TOXICOLOGY
870.1100
870.1200
870.1300
870.2400
870.2500
870.2600
870.3100
870.3200
870.3465
870.4100
870.4200
870.3700
870.3800
870.4300
870.5100
870.5300
870.7485
870.7600
81-1
81-2
81-3
81-4
81-5
81-6
82-1A
82-2
82-4
83-1B
83-2B
83-3A
83-3B
83-4
83-5
84-2
85-1
85-2
Acute Oral Toxicity, Rat
Acute Dermal Toxicity, Rabbit/Rat
Acute Inhalation Toxicity, Rat
Primary Eye Irritation, Rabbit
Primary Skin Irritation
Dermal Sensitization
90-Day Subchronic Feeding, Rodent
21 -Day Dermal, Rabbit/Rat
90-Day Inhalation, Rat
Chronic Feeding Toxicity, Nonrodent (Dog)
Chronic Carcinogenicity (Feeding), Mouse
Prenatal Developmental Toxicity, Rat
Prenatal Developmental Toxicity, Rabbit
2-Generation Reproduction and Fertility
Effects, Rat
Combined Chronic
Toxicity /Carcinogenicity Study, Rat
Bacterial Reverse Gene Mutation Assay
Test
Detection of Gene Mutations in Somatic
Cells in Culture, Mammalian
General Metabolism, Rat
Dermal Absorption (Penetration), Rat
M, O
M, O
M, O
M, 0
M, O
M, O
M, O
M, 0
M, 0
M, O
M, O
M, O
M, 0
M, 0
M, O
M, 0
M, O
M, O
M, O
00155068
41648601
41571501
41800501
41826505
41648602
42093901,42100101
42427202
42990201
42320602
42100102
41987802
40433301
41547801
42093902,42973501
40382101
40382102,40382103-4
42305701,42246501-2
42246503
37
-------
New
Guideline
Number
None
Old
Guideline
Number
None
Requirement
Dermal Absorption & Mass Balance,
Humans
Use
Pattern
M,0
Bibliographical Citation(s)
42732101, 42974601-2, 43099401
ENVIRONMENTAL FATE
835.2120
161-1
Hydrolysis
M, 0
43073601, Reserved
38
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Appendix C. Technical Support Documents
Additional documentation in support of this RED is maintained in the OPP docket, located in
Room 119, Crystal Mall #2, 1921 Jefferson Davis Highway, Arlington, VA. It is open Monday through
Friday, excluding legal holidays, from 8:30 am to 4 pm.
The docket initially contained preliminary risk assessments and related documents as of May,
2003. Sixty days later the first public comment period closed. The EPA then considered comments,
revised the risk assessment, and added the formal "Response to Comments" document and the revised
risk assessment to the docket on April, 2004.
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.epa.gov/oppsrrdl/reregistration/dipropyliso/
These documents include:
1. Review of MGK 326 Incident Reports
2. MGK® Repellent 326 (Di-N-propyl isocinchomeronate) Cancer Risk
Estimates for Residential Use of MGK® Repellent 326
3. MGK® Repellent 326 (Di-N-propyl isocinchomeronate) HED Response to
Public Comment on HED's Risk Assessment for Reregistration Eligibility
Document (RED)
39
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Appendix D. Citations Considered to Be Part of the Data Base Supporting the
Reregistration Eligibility Decision (Bibliography)
GUIDE TO APPENDIX D
1. CONTENTS OF BIBLIOGRAPHY. This bibliography contains citations of all studies
considered relevant by EPA in arriving at the positions and conclusions stated elsewhere in the
Interim Reregistration Eligibility Document. Primary sources for studies in this bibliography
have been the body of data submitted to EPA and its predecessor agencies in support of past
regulatory decisions. Selections from other sources including the published literature, in those
instances where they have been considered, are included.
2. UNITS OF ENTRY. The unit of entry in this bibliography is called a "study." In the case of
published materials, this corresponds closely to an article. In the case of unpublished materials
submitted to the Agency, the Agency has sought to identify documents at a level parallel to the
published article from within the typically larger volumes in which they were submitted. The
resulting "studies" generally have a distinct title (or at least a single subject), can stand alone for
purposes of review and can be described with a conventional bibliographic citation. The
Agency has also attempted to unite basic documents and commentaries upon them, treating
them as a single study.
3. IDENTIFICATION OF ENTRIES. The entries in this bibliography are sorted numerically by
Master Record Identifier, or "MRID" number. This number is unique to the citation, and
should be used whenever a specific reference is required. It is not related to the six-digit
"Accession Number" which has been used to identify volumes of submitted studies (see
paragraph 4(d)(4) below for further explanation). In a few cases, entries added to the
bibliography late in the review may be preceded by a nine character temporary identifier.
These entries are listed after all MRID entries. This temporary identifying number is also to be
used whenever specific reference is needed.
4. FORM OF ENTRY. In addition to the Master Record Identifier (MRID), each entry consists
of a citation containing standard elements followed, in the case of material submitted to EPA, by
a description of the earliest known submission. Bibliographic conventions used reflect the
standard of the American National Standards Institute (ANSI), expanded to provide for certain
special needs.
a Author. Whenever the author could confidently be identified, the Agency has chosen to
show a personal author. When no individual was identified, the Agency has shown an
identifiable laboratory or testing facility as the author. When no author or laboratory
could be identified, the Agency has shown the first submitter as the author.
b. Document date. The date of the study is taken directly from the document. When the
40
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date is followed by a question mark, the bibliographer has deduced the date from the
evidence contained in the document. When the date appears as (????), the Agency
was unable to determine or estimate the date of the document.
c. Title. In some cases, it has been necessary for the Agency bibliographers to create or
enhance a document title. Any such editorial insertions are contained between square
brackets.
d. Trailing parentheses. For studies submitted to the Agency in the past, the trailing
parentheses include (in addition to any self-explanatory text) the following elements
describing the earliest known submission:
(1) Submission date. The date of the earliest known submission appears
immediately following the word "received."
(2) Administrative number. The next element immediately following the word
"under" is the registration number, experimental use permit number, petition
number or other administrative number associated with the earliest known
submission.
(3) Submitter. The third element is the submitter. When authorship is defaulted to
the submitter, this element is omitted.
(4) Volume Identification (Accession Numbers). The final element in the trailing
parentheses identifies the EPA accession number of the volume in which the
original submission of the study appears. The six-digit accession number
follows the symbol "CDL," which stands for "Company Data Library." This
accession number is in turn followed by an alphabetic suffix which shows the
relative position of the study within the volume.
41
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BIBLIOGRAPHY
MRID
CITATION
00155068 Costello, B. (1985) Acute Oral Toxicity, LD50 Rats: MGK Repellent 326«<: Project
No. 85-4781 A. Unpublished study prepared by Biosearch, Inc. 14 p.
40382101 Lawlor, T. (1986) Salmonella/Mammalian-microsome Plate Incorporation
Mutagenicity Assay (Ames Test): MGK Repellent 326, Lot No. 3716: Laboratory
Study No. T5204.501014. Unpublished study prepared by Microbiological
Associates, Inc. 61 p.
403 82102 Putman, D. (1987) Chromosome Aberrations in Chinese Hamster Ovary (CHO) Cells
with a Confirmatory Assay: MGK Repellent 326, Lot No. 3716: Laboratory Study
No. T5204.337001: Final Report. Unpublished study prepared by Microbiological
Associates, Inc. 28 p.
403 82103 Curren, R. (1987) Unscheduled DNA Synthesis in Rat Primary Heptocytes: MGK
Repellent 326, Lot NO. 3716: Laboratory Study No. T5204.380009: Final Report.
Unpublished study prepared by Microbiological Associates, Inc. 29 p.
40382104 Rogers-Back, A. (1986) L5178Y TK+/- Mouse Lymphoma Mutagenesis Assay:
MGK Repplent 326, Lot No. 3716: Laboratory Study No. T5204.701020.
Unpublished study prepared by Microbiological Associates, Inc. 58 p.
40433301 Schardein, J. (1987) Teratological Study of MGK Repellant 326 Administered Orally
to Albino Rabbits: 551-008. Unpublished study prepared by International Research
and Development Corp. 86 p.
41520602 Pesselman, R. (1990) Octanol/Water Partition Coefficient Determination of MGK
Repellent 325: Final Report: Lab Project ID.: HLA 6001-500. Unpublished study
prepared by Hazleton Laboratories America, Inc. 39 p.
41525302 Blakemore, G; Burgess, D. (1990) Acute Flow-through Toxicity of MGK Repellent
326 to Daphnia magna: Final Report # 38501. Unpublished study prepared by
Analytical Bio-Chemistry Laboratories, Inc. 161 p.
41547801 Schardein, J. (1990) Two Generation Reproduction Study of MGK Repellant 326 in
the 83-4/2-generation repro.-rat Albino Rat: Laboratory Project ID. 551-009.
Unpublished study prepared by International Research and Development Corp. 658 p.
42
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BIBLIOGRAPHY
MRID
CITATION
41548301
41571501
41605101
41605102
Bowman, B. (1990) Vapor Pressure of MGK R-326: Laboratory Project Number:
38356. Unpublished study prepared by Analytical Bio-Chemistry Laboratories, Inc.
220 p.
Hershman, R. (1990) MGK Repellent 326 Code No. 392-90: Acute Inhalation
Toxicity, Single Level, 4-Hour Exposure-Rats: Lab Project No: 90-6990A.
Unpublished study prepared by Biosearch, Inc. 26 p.
Meinen, V. (1990) Product Identity and Composition of MGK Repellent 326.
Unpublished study prepared by McLaughlin Gormley King Co. 150 p.
Meinen, V. (1990) Analysis and Certification of Product Ingredients for MGK
Repellent 326. Unpublished study prepared by McLaughlin Gormley King Co. 33 p.
41605103 Meinen, V. (1990) Product Chemistry of MGK Repellent 326: Physical and Chemical
Characteristics. Unpublished study prepared by McLaughlin Gormley King Co. 35 p.
41648601 Gabriel, D. (1990) MGK Repellent 326 Code No. 392-90: Acute Dermal
Toxicity, Single Level—Rabbits: Lab Project Number: 90/6990A. Unpublished study
prepared by Biosearch Inc. 12 p.
41648602 Romanelli, P. (1990) MGK Repellent 326 Code No. 392-90: Guinea Pig
Dermal Sensitization-Modified Buehler Method: Lab Project Number: 90/6990A.
Unpublished study prepared by Biosearch Inc. 20 p.
41685501 Long, R.; Foster, J.; Hoxter, K.; et al. (1990) MGK 326: A Dietary LC50 Study with
the Mallard: Lab Project Number: 163-108. Unpublished study prepared by Wildlife
International Ltd. 29 p.
41685502 Long, R.; Foster, J.; Hoxter, K.; et al. (1990) MGK 326: A Dietary LC50 Study with
the Northern Bobwhite: Lab Project Number: 163-107. Unpublished study prepared
by Wildlife International Ltd. 30 p.
41800501 Bielucke, J. (1990) MGK Repellent 326 Code No. 392-90: Primary Eye
Irritation-Rabbits: Lab Project Number: 90-6990A. Unpublished study prepared by
Biosearch Inc. 13 p.
43
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BIBLIOGRAPHY
MRID
CITATION
41826505 Romanelli, P. (1990) MGK Insect Repellent Spray 2559 Code No. 705-90: Primary
Skin Irritation - Rabbits: Lab Project No: 90-7129A. Unpublished study prepared by
Biosearch Inc. 10 p.
41911401 Bowman, J. (1991) Acute Flow-Through Toxicity of MGK Repellent 326 to Rainbow
Trout (Oncorhynchus mykiss): Lab Project Number: 385-00. Unpublished study
prepared by Analytical Bio-Chemistry Laboratories, Inc. 192 p.
41987802 Irvine, L. (1991) MGK Repellant 326: Rat Teratology Study: Laboratory Project
Number: MGK/8/R. Unpublished study prepared by Toxicol Labs Ltd. 177 p.
42093901 Blair, M. (1991) 13 Week Dietary Range-finding Toxicity Study in Rats (Amended):
Lab Project Number: 551-002. Unpublished study prepared by International Research
and Development Corp. 237 p.
42093902 Blair, M. (1991) 24 Month Dietary Chronic Toxicity and Oncogenicity Study in the
Rat: Lab Project Number: 551-005. Unpublished study prepared by International
Research and Development Corp. 2319 p.
42100101 Blair, M. (1991) 13 Week Dietary Range-Finding Toxicity Study in Mice: Lab Proj ect
Number: 551-001. Unpublished study prepared by International Research and
Development Corp. 156 p.
42100102 Blair, M. (1991) Eighteen Month Dietary Oncogenicity Study in Mice: Lab Project
Number: 551-004. Unpublished study prepared by International Research and
Development Corp. 1413 p.
42174501 Sword, M.; Bucksath, J. (1991) Acute Flow-Through Toxicity of MGK Repellent 326
to Bluegill (Lepomis macrochirus): Lab Proj ect Number: 39572. Unpublished study
prepared by ABC Laboratories, Inc. 177 p.
42230401 Pesselman, R. (1992) Dissociation Constant Determination of R-326: Lab Project
Number: 6399-100. Unpublished study prepared by Hazleton, Wise. 31 p.
42246501 Braun, R. (1990) Determination of Expired CO2-14 Following Oral Dosing of
pyridine-4-carbon 14 MGK Repellent 326 in the Rat: Lab Proj ect Number: P01939.
Unpublished study prepared by Biological Test Center. 46 p.
44
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BIBLIOGRAPHY
MRID
CITATION
42246502 Selim, S. (1992) Addendum to Report Entitled "Absorption, Distribution, Metabolism
and Excretion Studies of pyridine-4-carbon 14 MGK Repellent 326 in the Rat: Lab
Project Number: P01938. Unpublished study prepared by Biological Test Center. 45
P-
42246503 Selim, S. (1992) Pharmacokinetic and Distribution Studies of Pyridine-4-carbon 14
MGK Repellent 326 in the Rat Following Dermal Administration: Lab Project Number:
P01990. Unpublished study prepared by Biological Test Center. 161 p.
42305701 Selim, S. (1991) Absorption, Distribution, Metabolism and Excretion Studies of
pyridine-4-carbon 14 MGK Repellent 326 in the Rat: Lab Project Number: P01938.
Unpublished study prepared by Biological Test Center. 212 p.
42320602 Blair, M. (1989) One Year Dietary Toxicity Study in Dogs: MGK Repellent 326: Lab
Project Number: 551-006. Unpublished study prepared by International Research and
Development Corp. 362 p.
42321101 Meinen, V. (1992) Product Chemistry: Discussion of Impurities, Analytical Method,
and Dissociation Constant re MGK Repellent 326: Supplementary Information.
Unpublished study prepared by McLaughlin Gormley King Co., 29 p.
42427202 Lancaster, S.; Husband, R (1992) MGK Repellent 326-13-week Dermal Toxicity
Study in the Rabbit: Lab Project Number: MCA/16/C. Unpublished study prepared
by Toxicol Laboratories, Ltd. 341 p.
42732101 Selim, S. (1993) A Multiple Dose Open Label Study on the Percutaneous Absorption
and the Excretion of Formulated MGK 326 after Dermal Application in Healthy Male
Volunteers: Lab Project Number: P0492003: PBR-910530-2: 92-0916. ETC.
Unpublished study prepared by Biological Test Center. 211 p.
42757901 Meinen, V. (1993) Product Chemistry: MGK's Reply to EPAs Request for Additional
Information Concerning MGK's Response for Product Chemistry for MGK Repellent
326. Unpublished study prepared by MGK Co. 77 p.
42973501 Blair, M. (1993) 24 Month Dietary Chronic Toxicity and Oncogenicity Study in the
Rat: Supplement to the Final Report: MGK Repellant 326: Lab Proj. No. 551-005.
Unpublished study prepared by International Research and Development Corp. 32 p.
45
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BIBLIOGRAPHY
MRID
CITATION
42974601 Selim, S. (1992) Absorption and Mass Balance of (carbon 14)-MGK 326 After
Topical Administration to Healthy Volunteers: Lab Project Number: PO2034:
PBR-900425-3: 920114. Unpublished study prepared by Biological Test Center.
180 p.
42974602 Selim, S. (1990) ABsorption and Mass Balance of Formulated (carbon 14)-MGK 326
After Topical Administration to Healthy Volunteers: Lab Project Number: PO2035:
PBR-900426-2: 92-0208. ETC. Unpublished study prepared by Biological Test
Center. 189 p.
42990201 Newton, P. (1993) A Subchronic (3-Month) Inhalation Toxicity Study of MGK
Repellent 326 in the Rat via Whole-Body Exposures: Final Report: Lab Project
Number: 91-8363. Unpublished study prepared by Bio/Dynamics, Inc. 769 p.
43015101 Meinen, V. (1993) Product Chemistry Data Regarding Preliminary Analysis of MGK
Repellent 326 (R-326) and Method Validation for Capillary-GLC Analysis of
Technical MGK Repellent 326: Lab Project Number: GLP/726. Unpublished study
prepared by MGK Co. 115 p.
43099401 Selim, S. (1993) Isolation and Identification of Major Metabolites in the Urine of
Human Volunteers Administered (carbon 14)-MGK 326: Lab Project Number:
P0992004. Unpublished study prepared by Biological Test Center. 336 p.
43452501 Meinen, V. (1994) Product Chemistry Data Regarding Storage Stability of MGK
Repellent 326 and Method Validation for Packed Column~GLC Analysis of Technical
MGK Repellent 326: Lab Project Number: GLP/724. Unpublished study prepared by
McLaughlin Gormley King Co. 192 p.
44190201 Meinen, V. (1996) MGK Repellent 326 Product Chemistry Data Regarding EPA
Guideline #63-13 (Stability): Lab Project Number: GLP-1087. Unpublished study
prepared by McLaughlin Gormley King Co. 60 p.
46
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Appendk E. GENERIC DATA CALL-IN
See the following table for a list of generic data requirements. Note that a complete Data Call-
in (DCI), with all pertinent instructions, is being sent to registrants under separate cover.
47
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48
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Appendix F. PRODUCT SPECIFIC DATA CALL-IN
See attached table for a list of product-specific data requirements. Note that a complete Data
Call-in (DCI), with all pertinent instructions, is being sent to registrants under separate cover.
49
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50
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Appendix G. EPA's Batching of MGK® Repellent 326 Products for Meeting Acute Toxicity
Data Requirements for Reregistration
In an effort to reduce the time, resources and number of animals needed to fulfill the acute
toxicity data requirements for reregistration of products containing MGK® Repellent 326 as the active
ingredient, the Agency has batched products which can be considered similar for purposes of acute
toxicity. Factors considered in the sorting process include each product's active and inert ingredients
(identity, percent composition and biological activity), type of formulation (e.g., emulsifiable
concentrate, aerosol, wettable powder, granular, etc.), and labeling (e.g., signal word, use classification,
precautionary labeling, etc.). Note that the Agency is not describing batched products as "substantially
similar" since some products within a batch may not be considered chemically similar or have identical
use patterns.
Using available information, batching has been accomplished by the process described in the
preceding paragraph. Not withstanding the batching process, the Agency reserves the right to require,
at any time, acute toxicity data for an individual product should the need arise.
Registrants of products within a batch may choose to cooperatively generate, submit or cite a
single battery of six acute lexicological studies to represent all the products within that batch. It is the
registrants' option to participate in the process with all other registrants, only some of the other
registrants, or only their own products within a batch, or to generate all the required acute lexicological
studies for each of their own products. If a registrant chooses to generate the data for a batch, he/she
must use one of the products within the batch as the test material. If a registrant chooses to rely upon
previously submitted acute toxicity data, he/she may do so provided that the data base is complete and
valid by today's standards (see acceptance criteria attached), the formulation tested is considered by
EPA to be similar for acute toxicity, and the formulation has not been significantly altered since
submission and acceptance of the acute toxicity data. Regardless of whether new data is generated or
existing data is referenced, registrants must clearly identify the test material by EPA Registration
Number. If more than one confidential statement of formula (CSF) exists for a product, the registrant
must indicate the formulation actually tested by identifying the corresponding CSF.
In deciding how to meet the product specific data requirements, registrants must follow the
directions given in the Data Call-In Notice and its attachments appended to the RED. The DCI Notice
contains two response forms which are to be completed and submitted to the Agency within 90 days of
receipt. The first form, "Data Call-in Response," asks whether the registrant will meet the data
requirements for each product. The second form, "Requirements Status and Registrant's Response,"
lists the product specific data required for each product, including the standard six acute toxicity tests.
A registrant who wishes to participate in a batch must decide whether he/she will provide the data or
depend on someone else to do so. If a registrant supplies the data to support a batch of products,
he/she must select one of the following options: Developing Data (Option 1), Submitting an Existing
Study (Option 4), Upgrading an Existing Study (Option 5) or Citing an Existing Study (Option 6). If a
registrant depends on another's data, he/she must choose among: Cost Sharing (Option 2), Offers to
51
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Cost Share (Option 3) or Citing an Existing Study (Option 6). If a registrant does not want to
participate in a batch, the choices are Options 1, 4, 5 or 6. However, a registrant should know that
choosing not to participate in a batch does not preclude other registrants in the batch from citing his/her
studies and offering to cost share (Option 3) those studies.
Ninety one products were found which contain MGK® Repellent 326 as the active ingredient.
These products have been placed into twelve batches and a no batch group in accordance with the
active and inert ingredients and type of formulation.
Batching Instructions:
Batch 1: EPA Reg. No. 498-148 may cite data from EPA Reg. No. 10807-127.
Batch 4: EPA Reg. No. 270-301 and EPA Reg. No. 68688-26 may not cite data from EPA Reg. No.
37425-21.
Batch 5: EPA Reg. No. 11715-173 may not cite data from EPA Reg. No. 10806-17 or EPA Reg.
No. 13799-8.
Batch 6: EPA Reg. No. 11715-23 may not cite data from EPA Reg. No. 67517-24.
No Batch: Each product in this Batch should generate their own data.
NOTE: The technical acute toxicity values included in this document are for informational purposes
only. The data supporting these values may or may not meet the current acceptance criteria.
Batch 1
EPA Reg. No.
498-148
10807-127
Percent Active Ingredient
MGK® Repellent 326: 2.5
MGK 264: 5.0
Deet: 25.0
MGK® Repellent 326: 2.5
MGK 264: 5.0
Deet: 25.0
Batch 2
EPA Reg. No.
Percent Active Ingredient
305-40
MGK® Repellent 326: 2.5
MGK 264: 5.0
Deet: 17.5
769-606
MGK® Repellent 326: 2.5
MGK 264: 5.0
Deet: 17.5
52
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Batch:
EPA Reg. No.
Percent Active Ingredient
270-300
37425-17
68688-22
MGK® Repellent 326: 1.0
MGK 264: 2.0
Pyrethrins: 0.2
Piperonyl Butoxide: 0.5
Permethrin: 0.2
Butoxy Polypropylene glycol: 5.0
MGK® Repellent 326: 1.0
MGK 264: 2.0
Pyrethrins: 0.2
Piperonyl Butoxide: 0.5
Permethrin: 0.2
Butoxy Polypropylene glycol: 5.0
MGK® Repellent 326: 1.0
MGK 264: 2.0
Pyrethrins: 0.2
Piperonyl Butoxide: 0.5
Permethrin: 0.2
Butoxy Polypropylene glycol: 5.0
Batch 4
EPA Reg. No.
270-301
37425-21
68688-26
Percent Active Ingredient
MGK® Repellent 326: 2.50
MGK 264: 3. 10
Pyrethrins: 0.50
Piperonyl Butoxide: 1.85
Permethrin: 1.00
MGK® Repellent 326: 1.25
MGK 264: 3. 10
Pyrethrins: 0.50
Piperonyl Butoxide: 1.85
Permethrin: 1.00
MGK® Repellent 326: 2.50
MGK 264: 3. 10
Pyrethrins: 0.50
Piperonyl Butoxide: 1.85
Permethrin: 1.00
53
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Batch 5
EPA Reg. No.
Percent Active Ingredient
10806-17
11715-173
13799-8
MGK® Repellent 326: 1.33
MGK 264: 0.67
Pyrethrins: 0.20
Piperonyl Butoxide: 0.40
MGK® Repellent 326: 1.84
MGK 264: 0.67
Pyrethrins: 0.20
Piperonyl Butoxide: 0.40
MGK® Repellent 326: 1.33
MGK 264: 0.67
Pyrethrins: 0.20
Piperonyl Butoxide: 0.40
Batch 6
EPA Reg. No.
11715-23
67517-24
Percent Active Ingredient
MGK® Repellent 326: 1.20
MGK 264: 0.60
Pyrethrins: 0.18
Piperonyl Butoxide: 0.36
MGK® Repellent 326: 1.20
MGK 264: 0.60
Pyrethrins: 0.18
Piperonyl Butoxide: 0.36
Batch 7
EPA Reg. No.
270-305
769-583
Percent Active Ingredient
MGK® Repellent 326: 1.00
MGK 264: 0.50
Pyrethrins: 0.15
Piperonyl Butoxide: 1.00
MGK® Repellent 326: 1.00
MGK 264: 0.50
Pyrethrins: 0.15
Piperonyl Butoxide: 1.00
54
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40849-73
67572-20
68688-31
MGK® Repellent 326: 1.00
MGK 264: 0.50
Pyrethrins: 0.15
Piperonyl Butoxide: 1.00
MGK® Repellent 326: 1.00
MGK 264: 0.50
Pyrethrins: 0.15
Piperonyl Butoxide: 1.00
MGK® Repellent 326: 1.00
MGK 264: 0.50
Pyrethrins: 0.15
Piperonyl Butoxide: 1.00
Batch 8
EPA Reg. No.
9468-31
37425-12
43591-2
Percent Active Ingredient
MGK® Repellent 326: 0.50
MGK 264: 0.50
Pyrethrins: 0.15
Piperonyl Butoxide: 1.50
MGK® Repellent 326: 0.50
MGK 264: 0.50
Pyrethrins: 0.15
Piperonyl Butoxide: 1.50
MGK® Repellent 326: 0.50
MGK 264: 0.50
Pyrethrins: 0.15
Piperonyl Butoxide: 1.50
Batch 9
EPA Reg. No.
Percent Active Ingredient
270-306
769-579
MGK® Repellent 326: 0.50
MGK 264: 0.50
Pyrethrins: 0.15
Piperonyl Butoxide: 1.00
MGK® Repellent 326: 0.50
MGK 264: 0.50
Pyrethrins: 0.15
Piperonyl Butoxide: 1.00
55
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68688-30
68688-32
69061-4
MGK® Repellent 326: 0.50
MGK 264: 0.50
Pyrethrins: 0.15
Piperonyl Butoxide: 1.00
MGK® Repellent 326: 0.50
MGK 264: 0.50
Pyrethrins: 0.15
Piperonyl Butoxide: 1.00
MGK® Repellent 326: 0.50
MGK 264: 0.50
Pyrethrins: 0.15
Piperonyl Butoxide: 1.00
Batch 10
EPA Reg. No.
769-615
40849-58
Percent Active Ingredient
MGK® Repellent 326: 0.50
MGK 264: 0.50
Pyrethrins: 0.15
Piperonyl Butoxide: 1.00
MGK® Repellent 326: 0.50
MGK 264: 0.50
Pyrethrins: 0.15
Piperonyl Butoxide: 1.00
Batch 1 1
EPA Reg. No.
40322-2
51651-1
Percent Active Ingredient
MGK® Repellent 326: 1.17
Pyrethrins: 0.22
MGK® Repellent 326: 1.17
Pyrethrins: 0.22
Batch 12
EPA Reg. No.
Percent Active Ingredient
4691-153
MGK® Repellent 326: 0.200
MGK 264: 1.000
Piperonyl Butoxide: 0.500
Permethrin: 0.150
ESBIOL: 0.100
Pyriproxyfen: 0.125
56
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28293-289
MGK® Repellent 326: 0.200
MGK264: 1.000
Piperonyl Butoxide: 0.500
Permethrin: 0.150
ESBIOL: 0.100
Pyriproxyfen: 0.125
No Batch
EPA Reg. No.
270-37
270-103
270-107
270-250
270-253
270-326
Percent Active Ingredient
MGK® Repellent 326: 1.0
Pyrethrins: 0.2
Piperonyl Butoxide: 0.5
Butyoxy Propypropylene Glycol: 20.0
MGK® Repellent 326: 1.0
Pyrethrins: 0.2
Piperonyl Butoxide: 0.5
MGK® Repellent 326: 1.0
MGK 264: 0.4
Pyrethrins: 0.4
Piperonyl Butoxide: 1.0
MGK® Repellent 326: 2.0
Pyrethrin: 0.8
Piperonyl Butoxide: 6.4
Butoxy Polypropylene Glycol: 20.0
Cypermethrin: 0.80
MGK® Repellent 326: 0.50
Pyrethrin: 0.20
Piperonyl Butoxide: 1.63
Butoxy Polypropylene Glycol: 4.85
Cypermethrin: 0.15
MGK® Repellent 326: 2.50
MGK 264: 3. 10
Piperonyl Butoxide: 1.85
Permethrin: 1.0
Prallethrin: .033
57
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270-327
MGK® Repellent 326: 1.0
Piperonyl Butoxide: 0.5
Butoxy Polypropylene Glycol: 20.0
Prallethrin:0.13
270-328
498-175
769-580
769-581
769-582
1021-461
1021-501
1021-537
1021-567
MGK® Repellent 326: 1.00
MGK 264: 2.00
Piperonyl Butoxide: 0.50
Butoxy Polypropylene Glycol: 5.00
Permethrin: 0.20
Prallethrin:0.13
MGK® Repellent 326: 2.5
MGK 264: 5.0
Deet: 25.0
MGK® Repellent 326: 0.50
MGK 264: 0.50
Pyrethrin: 0.15
Piperonyl butoxide: 1.00
MGK® Repellent 326: 0.20
MGK 264: 0.20
Pyrethrin: 0.06
Piperonyl butoxide: 0.40
MGK® Repellent 326: 0.20
MGK 264: 0.20
Pyrethrin: 0.06
Piperonyl butoxide: 0.40
MGK® Repellent 326: 97.0
MGK® Repellent 326: 50.0
MGK 264: 50.0
MGK® Repellent 326: 33.33
MGK 264: 66.67
MGK® Repellent 326: 10.0
MGK 264: 20.0
Deet: 70.0
58
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1021-579
MGK® Repellent 326: 39.22
MGK264: 19.60
Pyrethrin: 5.88
Piperonyl butoxide: 11.77
1021-788
MGK® Repellent 326: 26.67
MGK 264: 22.00
Pyrethrin: 6.67
Piperonyl butoxide: 13.34
1021-1208
MGK® Repellent 326: 40.0
MGK 264: 20.0
Pyrethrin: 4.0
Piperonyl butoxide: 20.0
1021-1290
MGK® Repellent 326: 7.70
MGK 264: 15.38
Deet: 76.92
1021-1600
MGK® Repellent 326: 2.5
MGK 264: 5.0
Deet: 25.0
1317-83
MGK® Repellent 326: 0.40
MGK 264: 0.20
Pyrethrin: 0.06
Piperonyl butoxide: 0.12
2382-89
MGK® Repellent 326: 4.0
MGK 264: 6.0
Pyrethrin: 1.0
Piperonyl butoxide: 4.0
2382-129
MGK® Repellent 326: 0.500
MGK 264: 0.500
Pyrethrin: 1.000
Piperonyl butoxide: 0.500
Pyriproxfen: 0.005
2781-9
MGK® Repellent 326: 1.0
Pyrethrin: 0.2
Piperonyl butoxide: 0.5
59
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3546-39
MGK® Repellent 326: 4.0
MGK 264: 8.0
Deet: 28.0
5481-16
MGK® Repellent 326: 0.330
MGK 264: 0.330
Pyrethrin: 0.099
Piperonyl butoxide: 0.198
5481-52
MGK® Repellent 326: 0.400
MGK 264: 0.501
Pyrethrin: 0.150
Piperonyl butoxide: 0.300
5481-153
MGK® Repellent 326: 0.20
MGK 264: 0.17
Pyrethrin: 0.05
Piperonyl butoxide: 0.10
7754-40
MGK® Repellent 326: 1.0
MGK 264: 2.0
Deet: 7.0
7754-41
MGK® Repellent 326: 2.5
MGK 264: 5.0
Deet: 25.0
9444-28
MGK® Repellent 326: 1.20
MGK 264: 0.60
Pyrethrin: 0.18
Piperonyl butoxide: 0.36
10088-97
MGK® Repellent 326: 1.76
MGK 264: 3.52
Deet: 12.33
10806-34
MGK® Repellent 326: 1.5
MGK 264: 3.0
Deet: 10.5
10900-72
MGK® Repellent 326: 2.5
MGK 264: 5.0
Deet: 25.0
60
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11715-85
MGK® Repellent 326: 1.92
MGK 264: 7.67
Deet: 28.76
11715-230
MGK® Repellent 326: 0.998
Piperonyl butoxide: 0.796
Butoxy Polypropylene Glycol: 20.0
S-Bioallethrin: 0.178
11715-234
MGK® Repellent 326: 1.00
Butoxy Polypropylene Glycol: 20.00
Sumithrin:0.10
Neo-Pynamin: 0.21
11715-235
MGK® Repellent 326: 1.00
Pyrethin: 0.25
Piperonyl butoxide: 0.50
11715-332
MGK® Repellent 326: 1.55
MGK 264: 3.09
Deet: 15.46
34704-597
MGK® Repellent 326: 0.20
MGK 264: 0.33
Pyrethrin: 0.10
Piperonyl butoxide: 0.20
34704-768
MGK® Repellent 326: 0.20
Pyrethin: 0.03
Piperonyl butoxide: 0.25
35138-79
MGK® Repellent 326: 5.0
Pyrethin: 2.0
Piperonyl butoxide: 20.0
37425-14
MGK® Repellent 326: 1.00
MGK 264: 0.50
Pyrethrin: 0.15
Piperonyl butoxide: 1.50
37425-16
MGK® Repellent 326: 1.00
MGK 264: 1.00
Pyrethrin: 0.15
Piperonyl butoxide: 0.37
61
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37425-19
MGK® Repellent 326: 1.94
MGK 264: 5.70
Pyrethrin: 0.97
Piperonyl butoxide: 3.74
37425-22
MGK® Repellent 326: 4.00
MGK 264: 5.70
Pyrethrin: 0.97
Piperonyl butoxide: 3.63
Permethrin: 3.00
37425-32
MGK® Repellent 326: 0.5
MGK 264: 0.5
Esbiothrin: 0.30
40849-57
MGK® Repellent 326: 0.50
MGK 264: 0.50
Pyrethrin: 0.15
Piperonyl butoxide: 1.00
44446-48
MGK® Repellent 326: 2.50
MGK 264: 5.00
Deet: 23.75
46813-22
MGK® Repellent 326: 2.5
MGK 264: 5.0
Deet: 25.0
47000-54
MGK® Repellent 326: 0.20
MGK 264: 0.15
Pyrethrin: 0.05
Piperonyl butoxide: 0.10
Dichlorvos: 0.50
50830-3
MGK® Repellent 326: 3.0
MGK 264: 5.0
Deet: 25.0
54287-8
MGK® Repellent 326: 2.5
MGK 264: 5.0
Deet: 17.5
54287-13
MGK® Repellent 326: 2.5
MGK 264: 5.0
Deet: 17.5
62
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67517-5
MGK® Repellent 326: 0.70
MGK 264: 0.35
Pyrethrin: 0.10
Piperonyl butoxide: 0.20
67517-11
MGK® Repellent 326: 0.500
MGK 264: 1.175
Pyrethrin: 0.200
Piperonyl butoxide: 0.400
68543-27
MGK® Repellent 326: 2.5
MGK 264: 5.0
Deet: 25.0
63
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