United States Prevention, Pesticides EPA 738-R-06-005
Environmental Protection And Toxic Substances June 2006
Agency (7508C)
Reregistration
Eligibility Decision for
Piperonyl Butoxide
(PBO)
ListB
Case No. 2525
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Reregistration Eligibility Decision (RED) Document
for
Piperonyl Butoxide (PBO)
Approved by: /S/
Debra Edwards, Ph.D.
Director
Special Review and Reregistration
Division
Date: June 14, 2006
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TABLE OF CONTENTS
I. Introduction 12
II. Chemical Overview 13
A. Regulatory History 13
B. Chemical Identification 13
C. Use Profile 14
1. PBO Use Profile 15
III. Summary of PBO Risk Assessments 16
A. Human Health Risk Assessment 16
1. Toxicity Profile 16
2. Drinking Water 23
3. Residential Exposure and Risk 24
4. Cumulative Risk Assessment 30
5. Occupational Risk 30
6. Human Incident Data 36
B. Environmental Risk Assessment 37
1. Environmental Fate and Transport 37
2. Ecological Risk 38
3. Ecological Incidents 47
4. Endangered Species Concerns 47
5. Endocrine Disruption 47
A. Determination of Reregistration Eligibility and Tolerance Reassessment 48
B. Regulatory Position 49
1. Food Quality Protection Act Findings 49
2. Endocrine Disrupter Effects 50
3. Cumulative Risks 51
C. Tolerance Reassessment Summary 51
D. Regulatory Rationale 61
1. Human Health Risk 61
2. Non-Target Organism (Ecological) Risk Management 69
V. What Registrants Need to Do 76
A. Manufacturing Use Products 76
1. Additional Generic Data Requirements 76
2. Labeling Requirements 78
3. Spray Drift Management 78
B. End-Use Products 78
1. Additional Product-Specific Data Requirements 78
2. Labeling for End-Use Products 78
Appendix: Technical Support Documents 110
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Piperonyl Butoxide Reregistration Eligibility Decision Team
Office of Pesticide Programs:
Environmental Fate and Effects Risk Assessment
William Eckel
Michael Davy
Richard Lee
Health Effects Risk Assessment
Rebecca Daiss (Risk Assessor)
Santhini Ramasamy
Thurston Morton
Matthew Crowley
David Hrdy
Biological and Economic Analysis Division
Alan Halvorson
Nikhil Mallampalli
Andrew Lee
John Faulkner
Registration
Richard Gebken
Mark Suarez
Kevin Sweeney
Risk Management
Cathryn O'Connell
Tom Myers
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Glossary of Terms and Abbreviations
AGDCI
ai
aPAD
AR
BCF
CFR
cPAD
CSF
CSFII
DCI
DEEM
DFR
DWLOC
EC
EDWC
EEC
EPA
EUP
FDA
FIFRA
FFDCA
FQPA
FOB
G
GENEEC
GLN
HAFT
IR
LC50
LD50
LOC
LOD
LOAEL
MATC
ug/L
mg/kg/day
mg/L
MOE
MRID
MUP
NA
NAWQA
NPDES
NR
NOAEL
OP
Agricultural Data Call-In
Active Ingredient
Acute Population Adjusted Dose
Anticipated Residue
Bioconcentration Factor
Code of Federal Regulations
Chronic Population Adjusted Dose
Confidential Statement of Formula
USDA Continuing Surveys for Food Intake by Individuals
Data Call-In
Dietary Exposure Evaluation Model
Dislodgeable Foliar Residue
Drinking Water Level of Comparison.
Emulsifiable Concentrate Formulation
Estimated Drinking Water Concentration
Estimated Environmental Concentration
Environmental Protection Agency
End-Use Product
Food and Drug Administration
Federal Insecticide, Fungicide, and Rodenticide Act
Federal Food, Drug, and Cosmetic Act
Food Quality Protection Act
Functional Observation Battery
Granular Formulation
Tier I Surface Water Computer Model
Guideline Number
Highest Average Field Trial
Index Reservoir
Median Lethal Concentration. A statistically derived concentration of a substance that
can be expected to cause death in 50% of test animals. It is usually expressed as the
weight of substance per weight or volume of water, air or feed, e.g., mg/1, mg/kg or ppm.
Median Lethal Dose. A statistically derived single dose that can be expected to cause
death in 50% of the test animals when administered by the route indicated (oral, dermal,
inhalation). It is expressed as a weight of substance per unit weight of animal, e.g.,
mg/kg.
Level of Concern
Limit of Detection
Lowest Observed Adverse Effect Level
Maximum Acceptable Toxicant Concentration
Micrograms Per Gram
Micrograms Per Liter
Milligram Per Kilogram Per Day
Milligrams Per Liter
Margin of Exposure
Master Record Identification (number). EPA's system of recording and tracking studies
submitted.
Manufacturing-Use Product
Not Applicable
USGS National Water Quality Assessment
National Pollutant Discharge Elimination System
Not Required
No Observed Adverse Effect Level
Organophosphate
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OPP
OPPTS
PAD
PCA
PDF
PHED
PHI
ppb
PPE
ppm
PRZM/EXAMS
Qi*
RAC
RED
REI
RfD
RQ
SCI-GROW
SAP
SF
SLC
SLN
TCPSA
TGAI
TRR
USDA
USGS
UF
UV
WPS
EPA Office of Pesticide Programs
EPA Office of Prevention, Pesticides and Toxic Substances
Population Adjusted Dose
Percent Crop Area
USDA Pesticide Data Program
Pesticide Handler's Exposure Data
Preharvest Interval
Parts Per Billion
Personal Protective Equipment
Parts Per Million
Tier II Surface Water Computer Model
The Carcinogenic Potential of a Compound, Quantified by the EP A's Cancer Risk Model
Raw Agriculture Commodity
Reregistration Eligibility Decision
Restricted Entry Interval
Reference Dose
Risk Quotient
Tier I Ground Water Computer Model
Science Advisory Panel
Safety Factor
Single Layer Clothing
Special Local Need (Registrations Under Section 24(c) of FIFRA)
2,3,3-trichloroprop-2-ene sulfonic acid (nitrapyrin Metabolite)
Technical Grade Active Ingredient
Total Radioactive Residue
United States Department of Agriculture
United States Geological Survey
Uncertainty Factor
Ultraviolet
Worker Protection Standard
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Executive Summary
EPA has completed its review of public comments on the human health and environmental risk
assessments and is issuing its reregistration eligibility and tolerance reassessment decisions for
piperonyl butoxide (PBO). There are currently 69 tolerances being reassessed for piperonyl butoxide.
EPA will accept public comments on these decisions and the supporting documents for 60 days.
The revised risk assessments and response documents are based on comments submitted, information
from the PBO Task Force II (PBOTFII), and other information provided to EPA. After considering
the risks identified in the revised risk assessments, comments and mitigation suggestions, EPA
developed its risk management decision for uses of piperonyl butoxide that posed risks of concern.
As a result, the Agency has determined piperonyl butoxide-containing products are eligible for
reregistration provided that risk mitigation measures are adopted and labels are amended accordingly.
Piperonyl butoxide was first registered in the 1950's and acts as a synergist. Synergists are
chemicals that primarily enhance the pesticidal properties of other active ingredients, such as
pyrethrins and synthetic pyrethroids. PBO is a registered active ingredient in over 1500 products used
to control many different types of flying and crawling insects and arthropods, although there are no
products that contain only PBO. It is registered for use in agricultural, residential, commercial,
industrial, and public health sites. Approximately 100,000-200,000 pounds are sold every year for
non-agricultural uses, with only about 5,000-10,000 pounds used in agriculture.
Overall Risk Summary
Dietary Risk (Food and Drinking Water)
Acute dietary (food only) risk does not exceed the Agency's level of concern for the
general US population at 6% of the aPAD. The risk estimate for the most highly exposed
subpopulation, children 1-2, is below the Agency's level of concern at 20% of the aPAD. The
PBO dietary assessments are highly refined using residue data from the USDA Pesticide Data
Program (PDF), actual percent crop treated data where available, and processing factors from
processing study data.
The chronic dietary (food only) risk is below the Agency's level of concern; risk estimates
are 11% cPAD for the general U.S. population, and 32% of the cPAD for children 1-2 years old,
the most exposed subpopulation.
Acute and chronic drinking water levels of concern (DWLOCs) were calculated based on
dietary exposure estimates, default body weight and water consumption figures. The estimated
drinking water concentrations (EDWCs) for both surface water and ground water are well below
both the acute and chronic DWLOCs indicating that combined exposure to PBO in food and
water is not a concern.
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Residential
In the residential handler exposure assessment, a number of scenarios were assessed to
estimate the exposure to homeowners handling products containing piperonyl butoxide. From
the results of the residential handler assessment, there are no residential risks of concern when
piperonyl butoxide is mixed, loaded, applied, or handled by homeowners.
A number of post-application residential scenarios were assessed for adults and children
exposed to piperonyl butoxide indirectly after application. Of these, three were potentially of
concern: 1) broadcast dust applications to carpets; 2) applications from indoor metered release
devices; and 3) applications from outdoor residential misting systems. To address the potential
risks associated with these post-application scenarios, the PBOTFII has agreed to limit dust
application to carpets by allowing spot treatments only, and to add additional label language and
use restrictions to address potential by-stander risks from products used in both metered release
devices and outdoor residential misting systems. The PBOTFII has agreed to prohibit the use of
metered release devices in residential indoor areas and remove the following use sites from their
metered release device product labels: day care centers, nursing homes, schools, and hospitals.
Further, the Agency will require confirmatory exposure and efficacy data for the outdoor misting
systems.
After evaluating both the hazard and exposure data for PBO, EPA reduced the FQPA
safety factor to IX due to the low degree of concern for the fetal susceptibility effects and no
evidence of residual uncertainties for pre- or post-natal toxicity. There were no residual
uncertainties for potential exposures to infants and children.
Aggregate Risks
As noted above, acute and chronic aggregate risk assessments were conducted for exposure
to PBO in food and drinking water and did not indicate risks of concern. The short-term
aggregate exposures from food, water, and residential (incidental oral) routes associated with
application of PBO were also estimated since there is a common toxicity endpoint of decreased
weight gain identified for these routes of exposure.
The short term aggregate risk for PBO was calculated by adding exposure estimates from
dietary, drinking water, and residential incidental oral exposure pathways for children age 1-2
and comparing them with model based EDWCs. The lowest short term DWLOC is 8500|ig/L
for children 1-2 which is substantially higher the surface water EDWC of 60 |ig/L and the
ground water EDWC of 0.26 |ig/L. Thus aggregate short term exposure to PBO does not result
in a risk of concern. Some short term post application risks, as noted above, alone are potentially
of concern. However, because of the conservative exposure assumptions used in the individual
assessments, and with the exposure mitigation requirements described herein, the Agency does
not expect aggregate exposures to pose risks of concern.
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Cumulative
The Food Quality Protection Act (FQPA) requires that the Agency consider available
information concerning the cumulative effects of a particular pesticide and other substances that
have a common mechanism of toxicity. Unlike other pesticides for which EPA has followed a
cumulative risk approach based on a common mechanism of toxicity, EPA has not made a
common mechanism finding as to PBO and any other substances, and PBO does not appear to
produce a toxic metabolite produced by other chemicals. Therefore, for the purposes of this
tolerance reassessment action, EPA has assumed that PBO does not have a common mechanism
of toxicity with other substances.
Occupational Risks
Thirty-four occupational exposure scenarios were assessed for agricultural, forestry,
professional pest control operator, and mosquito control applications of PBO. The exposure of
concern is only inhalation, with target MOEs of 300 for short and intermediate term exposure
due to the lack of a NOAEL in the critical study and 1000 for long term exposures due to
extrapolation from a sub-chronic study. Of the scenarios assessed, several were potentially of
concern assuming baseline clothing. These include: 1) mixing and loading wettable powders for
agricultural handlers and PCOs; 2) applying PBO with handheld foggers indoors; 3) applying
dusts through power duster equipment; 4) mixer/loaders for aerial forestry applications; 5)
PCOs applying indoor crack and crevice treatments with a low pressure handwand; 6) high
pressure handwand applications in greenhouses; and 7) PCOs applying indoor space sprays. To
address these potential risks, the PBO Task Force II has agreed to repackage all wettable powder
formulations in water soluble packages, develop data, reduce application rates in some instances,
prohibit power dusters as an application method, and add additional respiratory protection for
some applications.
There were potential post-application risks estimated for products used in metered release
devices which are commonly used in dairy barns and other sites. EPA believes that the potential
post-application risks are lower for people working in these settings than for residential settings
due to the fact that the occupational areas generally have a greater ventilation capacity. While it
is possible workers could be exposed to PBO from these metered release devices, it is not likely
a worker would be exposed to the full daily amount for 30 or more days, as was assumed in
EPA's assessment. Therefore, no occupational mitigation is being required at this time.
However, data to better characterize the duration and extent of exposure to workers will be
required.
Ecological Risks
Aquatic Organisms
Risk to aquatic organisms can occur through exposure from agriculture, wide area
mosquito abatement, and other non-agricultural (urban) use. Risks to aquatic organisms from
agricultural applications appear to be reduced if typical application rates, frequency, and
numbers of applications are considered. There are possible risks from mosquito abatement
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applications to invertebrates and amphibians, which can be addressed by establishing release
heights, droplets size, and application rates on all PBO mosquito abatement product labels.
There are no risks of concern predicted from down-the-drain use. Non-agricultural (urban) use
was not quantified in this assessment, but there is an on-going effort to develop a model and
work with a number of stakeholders in order to address this source of pesticide exposure in the
near future.
Terrestrial Organisms
There are estimated LOG exceedences for mammals and birds at the maximum
agricultural rate of 0.5 Ibs/ai/A, which is not routinely used for all crops. All agricultural product
labels will be revised to include a maximum of 10 applications per season and a minimum of 1-3
days reapplication interval depending on pest pressure.
Risk Associated with Mixtures
Available evidence indicates that PBO does not effectively act as a pyrethroid synergist
in mammals. It is well know to inhibit microsomal enzymes in insects. It also inhibits
microsomal enzymes in several other species (e.g., rats, rabbits, and mice). However, this
enzyme inhibition in mammals appears to be transient and occurs at high doses. Data for other
species indicate that the toxicity of PBO mixed with pyrethrins or synthetic pyrethroids may be
higher than the toxicity of the individual active ingredients. To address the uncertainty related to
the effects a synergist would have to the environment when mixed with other chemicals, EPA
will require product-specific eco-toxicity data.
Summary of Mitigation Measures
EPA has determined that the currently registered uses of piperonyl butoxide are eligible
for reregi strati on provided the mitigation measures outlined in this document are implemented
through label amendments. Mitigation measures include:
Residential
Restrict carpet dust applications to only spot treatments.
Prohibit use of products in metered release devices in residential areas and remove day-care
centers, nursing homes, schools and hospitals from product labels.
Restrict use of outdoor residential misting systems by establishing a maximum use rate and
precautionary label statements.
Occupational
Require wettable powders to be repackaged in water soluble packages.
Reduce indoor crack and crevice application rate from 2.2 Ibs ai/1000 square feet to 0.56
lbs/ai/1000 square feet
Require all applicators using hand held foggers indoors to wear a dust-mist (PF10) respirator.
Require mixer/loaders supporting forestry applications to wear a dust-mist (PF 5) respirator.
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Require mixer/loader/applicators using high pressure handwands in greenhouses and other
enclosed areas to wear a dust-mist respirator (PF 5).
Prohibit power dusters as an application method.
Ecological
All agricultural product labels must be updated to specify the following application
information:
-No more than 10 applications per season.
-Do not reapply within 3 days, except under extreme pest pressure.
-In case of extreme pest pressure, do not reapply within 24 hours.
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I. Introduction
The Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) was amended in 1988
to accelerate the reregistration of products with active ingredients registered prior to November
1, 1984. The amended Act calls for the development and submission of data to support the
reregistration of an active ingredient, as well as EPA review of all submitted data. Reregistration
involves a thorough review of the scientific database underlying a pesticide's registration. The
purpose of the Agency's review is to reassess the potential risks arising from the currently
registered uses of the pesticide, to determine the need for additional data on health and
environmental effects, and to determine whether or not the pesticide meets the "no unreasonable
adverse effects" criteria of FIFRA.
On August 3, 1996, the Food Quality Protection Act of 1996 (FQPA) was signed into
law. This Act amends FIFRA to require reassessment of all tolerances in effect on the day
before it was enacted. In reassessing these tolerances, the Agency must consider, among other
things, aggregate risks from non-occupational sources of pesticide exposure, whether there is
increased susceptibility among infants and children, and the cumulative effects of pesticides that
have a common mechanism of toxicity. When the Agency determines that aggregate risks are
not of concern and concludes that there is a reasonable certainty of no harm from aggregate
exposure, the tolerances are considered reassessed. EPA decided that, for those chemicals that
have tolerances and are undergoing reregistration, tolerance reassessment will be accomplished
through the reregistration process.
The Food Quality Protection Act (FQPA) requires that the Agency consider available
information concerning the cumulative effects of a particular pesticide's residues and other
substances that have a common mechanism of toxicity. The reason for consideration of other
substances is due to the possibility that low-level exposures to multiple chemical substances that
cause a common toxic effect by a common toxic mechanism could lead to the same adverse
health effect as would a higher level of exposure to any of the substances individually. Unlike
other pesticides for which EPA has followed a cumulative risk approach based on a common
mechanism of toxicity, EPA has not made a common mechanism of toxicity finding as to
piperonyl butoxide (PBO) and any other substances and PBO does not appear to produce a toxic
metabolite produced by other substances that contribute to dietary exposure. For the purposes of
this tolerance action, therefore, EPA has not assumed that PBO has a common mechanism of
toxicity with other substances. For information regarding EPA's efforts to determine which
chemicals have a common mechanism of toxicity and to evaluate the cumulative effects of such
chemicals, see the policy statements released by EPA's Office of Pesticide Programs concerning
common mechanism determinations and procedures for cumulating effects from substances
found to have a common mechanism on EPA's website at
http://www.epa.gov/pesicides/cumulative/.
The Agency made its reregistration eligibility determination based on the required data,
the current guidelines for conducting acceptable studies to generate such data, and published
scientific literature. The Agency has found that currently registered uses of PBO are eligible for
reregistration provided the mitigation and labeling outlined in the RED are implemented. The
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document consists of six sections: Section I, the introduction, contains the regulatory framework
for reregi strati on/tolerance reassessment; Section II provides an overview of the chemical,
including a profile of its use and usage; Section III gives an overview of the human health and
environmental effects risk assessments; Section IV presents the Agency's reregi strati on
eligibility, tolerance reassessment, and risk management decisions; Section V summarizes label
changes necessary to implement the risk mitigation measures outlined in Section IV; and Section
VI includes the appendices, related supporting documents and Data Call-In (DCI) information.
The revised risk assessment documents and related addenda are not included in this document,
but are available on the Agency's web page http://www.epa.gov/pesticides, and in the Public
Docket under docket number EPA-HQ-OPP-2005-0042.
II. Chemical Overview
A. Regulatory History
Piperonyl butoxide (PBO) is a pesticide active ingredient that acts as a synergist.
Synergists are chemicals which, while lacking pesticidal properties of their own, enhance the
pesticidal properties of other active ingredients. PBO was first registered in the United States in
the 1950s. Currently there are approximately 1500 end-use products registered in the United
States containing PBO as a synergist with other active ingredients for use on agricultural and
residential sites. PBO is never used alone. There are 69 tolerances for PBO listed in the Code of
Federal Regulations. The reregi strati on of PBO is being supported by the PBO Task Force II
whose members include: Endura S.P.A., S.C. Johnson & Son, Incorporated, McLaughlin
Gormley King Company, Prentiss Incorporated, Takasago International Corporation USA, and
Valent BioSciences Corporation.
PBO is the only active ingredient in List B reregi strati on case 2525. A Phase IV Data
Call-In was issued for the PBO in January 1991. This DCI mainly required environmental fate
and residue chemistry data. An agricultural re-entry DCI was issued in October of 1995.
This Reregi strati on Eligibility Decision document evaluates risks from all currently
registered uses.
B. Chemical Identification
PBO is a classified as a synergist. As a synergist, PBO works by inhibiting the
detoxification of the pesticide by the insect pests.
Table 1: PBO Nomenclature
Compound
Chemical Structure
OP H
Q^ \<5^ \ /~\ ^ \^/ ^ ^<-"-4n9
Common name
Piperonyl butoxide (PBO)
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Table 1: PBO Nomenclature
IUPAC name
CAS name
CAS#
EPA PC Code
5-[2-(2-butoxyethoxy)ethoxymethyl]-6-propyl-l,3-benzodioxole
or
2-(2-butoxyethoxy)ethyl 6-propylpiperonyl ether
5-[[2-(2-butoxyethoxy)ethoxy]methyl]-6-propyl-l,3-benzodioxole
51-03-6
067501
Table 2: Physicochemical Properties of the Technical Grade of PBO
Parameter
Boiling point
Molecular Weight
PH
Density, bulk density, or specific gravity
Water solubility
Solvent solubility
Vapor pressure
Dissociation constant, pKa
Octanol/water partition coefficient
UV/visible absorption spectrum
Value
202-204ECatl.9mm/Hg
180ECatl.Omm/Hg
338.433
Not applicable because the TGAI has low
solubility in water
1.059g/mLat20°C
14.34ng/mLat25°C
Completely miscible (95% solution) in acetone,
methanol, petroleum distillate, petroleum ether,
methylene chloride, and isooctane
<1 x 10"7 mm Hg at 25 EC (extrapolated from
1.59xlO-7mmHgat60EC
Not applicable because the TGAI has low
solubility in water
4.51xl04
log Kow = 4.95
Not available
Reference
D207185, 1/27/99, T. Morton
2002 Farm Chemicals Handbook
2002 Farm Chemicals Handbook
D172854, 11/30/92, A. Aikens
RD Memorandum, 12/31/90 (cited
under D207185, 1/27/99,1.
Morton)
D207185, 1/27/99, T. Morton
D172854, 11/30/92, A. Aikens
RD Memorandum, 12/31/90 (cited
under D2071 85, 1/27/99, T.
Morton)
D172854, 11/30/92, A. Aikens
c.
Use Profile
PBO comes in many chemical formulations and is found in numerous end-use products
with a wide range of use patterns. PBO is used in combination with a variety of insecticides
such as the natural pyrethrins and synthetic pyrethroids, and is an ingredient in about 1500
registered products. To capture the use parameters for the large number of products and use
sites, the Piperonyl Butoxide Task Force II (PBOTFII) created a master label for PBO. A copy
of the PBO master label is available at http://www.epa.gov/oppsrrdl/reregistration/piperonyl/ucm.pdf.
The following is information on the currently registered uses including an overview of
use sites and application methods. Appendix A contains a detailed table of the uses of PBO
eligible for reregi strati on. There are more than 12 crop groups and several miscellaneous
commodities supported for reregi strati on.
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1. PBO Use Profile
Type of Pesticide: Synergi st
Summary of Use:
PBO is used in these four general ways: (i) preharvest and postharvest
uses on many agricultural crops; (ii) direct and indirect treatments of
livestock animals and premises; (iii) treatments of commercial and
industrial facilities and storage areas where raw and processed food/feed
commodities are stored or processed; and (iv) mosquito abatement areas.
Target Organisms: PBO is used with insecticides such as the pyrethrins, pyrethroids, and
some organophosphates to target a large numbers of pests including ants,
worms, beetles, mites, flies, gnats, spiders, weevils, caterpillars, grubs,
moths, ticks, lice, wasps, aphids, midges, and fish.
Mode of Action:
Tolerances:
PBO inhibits microsomal enzymes in target organisms by direct binding to
these enzymes and inhibits the breakdown of other pesticides including
pyrethrins and pyrethroids.
PBO currently has 69 tolerances (40 CFR §180.127 and §180.905)
including 62 tolerances on raw agricultural commodities, 3 tolerances for
processed food, 2 for stored dried feed, 1 for milled fractions, and 1
exemption.
Use Classification: General Use
Formulation Types: Aerosol, liquid, ready-to-use solution, dust, wettable powder,
microencapsulate, impregnated material, pressurized gas, pressurized
liquid, pressurized spray, combustible coil, micro-emulsion, dilutable
concentrate, shampoo, towelette, pour-on (spot-on), and water-based
concentrate. PBO is usually formulated with insecticides and other
synergists.
Application Methods: Aerosol can, mist blower, metered aerosol unit, total release aerosol, fixed
wing aircraft, helicopter, truck-mounted ultra low volume (ULV)
equipment, cold aerosol generators, hand held sprayers (high or low
pressure handwands), thermal fogging equipment, conventional dusting
equipment (e.g., power duster, shaker can), gas operated liquid dispenser
systems, and irrigation systems.
Application Rates: Application rates vary significantly by use sites. Maximum rates from
0.56 Ib ai/1000 ft2 (surface applications to commercial and domestic
structures) to 3.5 Ib ai/acre (commercial and domestic outdoor sites).
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Usage of Pyrethrins: An estimated 100,000 to 200,000 pounds are used annually in the U.S. for
non-crop use sites including wide area mosquito adulticide applications.
Approximately 5,000 to 10,000 pounds of PBO are used annually in the
U.S. on agricultural crops, with highest usage on potatoes (30% crop
treated).
III. Summary of PBO Risk Assessments
The following is an overview of EPA's human health and environmental effects risk
assessments and conclusions for PBO. For additional information on the human health risk
assessment, see the Piperonyl Butoxide HED Revised Risk Assessment for Reregistration
Eligibility Document (RED) (Daiss, February 21, 2006). For additional information on the
environmental effects risk assessment, see the Piperonyl Butoxide EFED 's Response to Public
Comments and our Revised Ecological Risk Assessment (Eckel, September 6, 2005).
The purpose of this section is to summarize the key features and findings of the risk
assessment to help the reader better understand EPA's risk management decisions. The revised
risk assessments incorporate input received during the two 60-day public comment periods for
PBO. EPA provided two public comment periods to allow interested stakeholders to provide
feedback on EPA's methodology and results prior to issuing its reregi strati on eligibility and risk
mitigation decisions. This RED and the revised risk assessments can be accessed online at
http://www.regulations.gov, under docket number EPA-HQ-OPP-2005-0042.
A. Human Health Risk Assessment
The Agency evaluated the toxicology, product and residue chemistry, and occupational
and residential exposure studies submitted and determined that the data are adequate to support a
reregi strati on eligibility decision. The risk assessments and separate supporting disciplinary
documents are available in the electronic docket. A summary of the human health risk
assessment findings and conclusions are provided below.
1. Toxicity Profile
The toxicological database is adequate to support the reregi strati on of PBO. Data are
sufficient for all exposure scenarios and for FQPA evaluation.
Acute Toxicity Profile
PBO has a low acute toxicity by oral, inhalation and dermal routes. It has been assigned
toxicity Category III by oral and dermal and Category IV by inhalation exposure routes. In the
acute studies, PBO has been identified as minimally irritating to eyes and skin, and is a dermal
sensitizer. See Table 3 below for a summary of the acute toxicity data.
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Table 3: Acute Toxicity Data on PBO
Study/ Species
870.1100 Acute Oral, Rats
870.1200 Acute Dermal, Rabbits
870.1300 Acute Inhalation, Rats
870.2400 Primary Eye Irritation, Rabbits
870.2500 Primary Skin Irritation,
Rabbits
870.2600 Dermal Sensitization, Guinea
Pig
MRID
41969001
41969002
41990001
41969004
41969003
44194602
Results
LD50 = 4570 mg/kg (m)7220 mg/kg
(f)
LD50 = >2000 mg/kg
LC50 = >5.9 mg/L
Minimally irritating
Minimally irritating
Skin Sensitizer
Classification
Category III
Category III
Category IV
Category IV
Category IV
Skin Sensitizer
Toxic Effects
The major target organ for PBO is the liver. Subchronic studies in rats showed PBO
treatment caused increases in liver weight and clinical parameters such as cholesterol and
enzyme activity compared to controls. Liver histopathological effects such as enlargement of
hepatocytes with glassy cytoplasm, oval cell proliferation, bile duct hyperplasia, and focal
necrosis were observed in treated rats. In ICR mice, similar effects (increased liver weight,
cholesterol and enzyme activity as well as liver histolopathological effects) were observed. A
one-year study in dogs with PBO also resulted in pronounced liver effects, such as increased
liver weight, hepatocyte hypertrophy and elevated serum alkaline phosphatase activity.
Toxic Effects of Mixtures
Because evidence indicates that PBO does not effectively act as a synergist in mammals,
EPA did not assess risks to humans of combined exposures to PBO and other active ingredients.
PBO inhibits microsomal enzymes in insects. It also inhibits the microsomal enzymes in several
other species (e.g., rats, rabbits, mice). However, evidence indicates that enzyme inhibition in
mammals is transient and occurs at high doses. PBO has also been used as a compound in
several pharmacological experiments to compare the toxicological effects of several drugs before
and after metabolism in rodents. These drug interaction studies suggest that the inhibition of
microsomal enzymes is a transient effect in the mammalian system. The kinetics of PBO
inhibition and/or stimulation of microsomal enzymes in humans has not been established.
Developmental
No developmental toxic effects were noted in guideline studies using rats and rabbits. A
few developmental studies in the open literature reported limb deformities, increased resorption
and decreased number of viable fetuses in rodents at doses close to or higher than the highest
dose tested in the guideline studies.
Neurotoxicity
Neurotoxic effects of PBO are not evident from the clinical signs reported in
developmental, reproductive, and chronic studies submitted to the Agency.
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Mutagenicity
PBO tested negative in bacterial gene mutation assays. The in vitro mammalian cell
mutation assays indicate a questionable positive effect for mutation. PBO tested negative for
chromosomal aberration and sister chromatid exchange in CHO cells, and no induction of
unscheduled DNA synthesis was observed in rat primary hepatocytes.
Cancer
PBO is classified as a Group C-possible human carcinogen with no cancer quantification
required for PBO risk assessments.
In a combined chronic/carcinogenic study in rats, positive carcinogenic effects were
reported at doses where a high incidence of ileocecal ulcers were noticed in test mammals. Liver
adenomas and carcinomas were reported in Fischer 344 rats only when tested at very high doses.
A slight increase in thyroid follicular cell tumors was reported in Sprague-Dawley rats. A 1979
National Toxicology Program (NTP) study reported negative effects for carcinogenicity in the
same strain of rats and in B6C3F1 mice. In CD-I mice, PBO tested positive for liver tumor
effects.
Toxicity Endpoints
The toxicological endpoints used in the human health risk assessment for PBO are listed
in Table 4.
Table 4: Endpoints for Assessing Occupational and Residential Risks for PBO
Exposure
Scenario
Dose, Uncertainty Factors
(UFs), and Safety Factors
(SFs)
Population Adjusted Dose
(PAD) or Target Margin of
Exposure (MOE)
Study and Toxicological Effects
Acute Dietary
General Population
NOAEL= 630 mg/kg/day
UF = 100 (inter- and intra-
species UF)
FQPA SF = IX
Total UF = 100
Acute RfD =
6.3 mg/kg/day
aPAD = acute RfD
FQPA SF
aPAD = 6.3 mg/kg/day
Developmental toxicity study, rats
LOAEL = 1065 mg/kg/day based on
decrease in maternal body weight
gain
(Tanaka et al., 1995)
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Table 4: Endpoints for Assessing Occupational and Residential Risks for PBO
Exposure
Scenario
Dose, Uncertainty Factors
(UFs), and Safety Factors
(SFs)
Population Adjusted Dose
(PAD) or Target Margin of
Exposure (MOE)
Study and Toxicological Effects
Chronic Dietary
(All populations)
NOAEL= 15.5 mg/kg/day
UF = 100 (inter- and intra-
species UF)
FQPA SF = IX
Total UF = 100
Chronic RfD =
0.16 mg/kg/day
cPAD = chronic RfD
FQPA SF
cPAD = 0.16 mg/kg/day
Chronic oral toxicity study, dogs
LOAEL = 52.8 mg/kg/day based on
decrease in body weight gain, and
increases in alkaline phosphatase
activity, liver weight and
hepatocellular hypertrophy
(MRID: 42926001, 42926002)
Short-Term
Incidental Oral (1-30 days);
Intermediate-Term
Incidental Oral (1-6 months)
NOAEL= 89 mg/kg/day
UF = 100 (inter- and intra-
species UF)
FQPA SF = IX
Total UF = 100
Residential LOC for MOE =
100
Occupational LOC for MOE
= 100
Two generation reproduction study,
rats
LOAEL = 469 mg/kg/day based on
the decrease in body weight gain of
FI and F2 pups at postnatal day 21
(MRID: 00161118)
Short-Term Dermal
(1 to 30 days);
Intermediate-Term Dermal
(1 to 6 months);
Long-Term Dermal
(>6 months)
No systemic, developmental or neurotoxicity concerns at the limit dose. Therefore, no quantification is
required. PBO is classified as mild irritant. (MRID: 42218201)
Acute Inhalation
(<2hrs)
(inhalation absorption rate =
100 %)
NOAEL= 630 mg/kg/day
UF = 100 (inter- and intra-
species UF)
FQPA SF = IX
Total UF = 100
Residential LOC for MOE =
100
Developmental toxicity study, rats
LOAEL = 1065 mg/kg/day based on
decrease in maternal body weight
gain
(Tanaka et al., 1995)
Short-Term Inhalation
(1 to 30 days);
Intermediate-Term Inhalation
(1 to 6 months)
Respiratory LOAEL= 3.91
mg/kg/day
(0.015 mg/L)
UF = 100 (inter- and intra-
species UF)
FQPA SF = IX
Lack of NOAEL UF = 3X
Total UF = 300
Residential LOC for MOE =
300
Occupational LOC for MOE =
300
Subchronic inhalation toxicity
study, rats
Respiratory LOAEL = 3.91
mg/kg/day (0.015 mg/L) based on
laryngeal hyperplasia and
metaplasia
(MRID: 42477101)
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Table 4: Endpoints for Assessing Occupational and Residential Risks for PBO
Exposure
Scenario
Long-Term Inhalation
(>6 months)
Cancer
Dose, Uncertainty Factors
(UFs), and Safety Factors
(SFs)
Respiratory LOAEL= 3.91
mg/kg/day
(0.015 mg/L)
UF = 100 (inter- and intra-
species UF)
FQPA SF = IX
Lack of NOAEL UF = 10X
Total UF = 1000
Population Adjusted Dose
(PAD) or Target Margin of
Exposure (MOE)
Residential LOC for MOE =
1000
Occupational LOC for MOE =
1000
Study and Toxicological Effects
Subchronic inhalation toxicity
study, rats
Respiratory LOAEL = 3.91
mg/kg/day (0.015 mg/L) based on
laryngeal hyperplasia and
metaplasia
(MRID: 42477101)
Classified as "Group C carcinogen" with no quantification.
NOAEL = no observed adverse effect level, LOAEL = lowest observed adverse effect level, PAD = population
adjusted dose (a = acute, c = chronic), RfD = reference dose, MOE = margin of exposure, LOC = level of concern
2. FQPA Safety Factor
The Food Quality Protection Act (FQPA) directs the Agency to use a tenfold (10X)
safety factor to protect for special sensitivity of infants and children to specific pesticide residues
in food, drinking water, or residential exposures, or to compensate for an incomplete database.
FQPA authorizes the Agency to modify the tenfold safety factor only if reliable data demonstrate
that another factor would be appropriate.
There are no residual uncertainties for potential exposures to infants and children. The
highly refined dietary food exposure assessment uses residue data from the USDA Pesticide Data
Program, actual percent crop treated data from BEAD where available, and processing factors
from processing study data. The drinking water assessment is based on water concentration
values derived from the drinking water model. Modeling parameters were selected to provide
protective, high-end estimates of water concentrations; these estimates are not likely to be
exceeded by actual values. Use of PBO-specific dietary food exposure data enhances the
accuracy of the assessment, and will not result in an underestimation of actual exposures.
Therefore, after evaluating hazard and exposure data for PBO, EPA reduced the 10X
FQPA special safety factor to IX due to low degree of concern for the fetal susceptibility effects
and no evidence of residual uncertainties for pre- and postnatal toxicity.
3. Endocrine disruption
EPA is required under the FFDCA, as amended by FQPA, to develop a screening
program to determine whether certain substances (including all pesticide active and other
ingredients) "may have an effect in humans that is similar to an effect produced by a naturally
occurring estrogen, or other such endocrine effects as the Administrator may designate."
Following recommendations of its Endocrine Disrupter and Testing Advisory Committee
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(EDSTAC), EPA determined that there was a scientific basis for including, as part of the
program, the androgen and thyroid hormone systems, in addition to the estrogen hormone
system. EPA also adopted EDSTAC's recommendation that the Program include evaluations of
potential effects in wildlife. For pesticide chemicals, EPA will use FIFRA and, to the extent that
effects in wildlife may help determine whether a substance may have an effect in humans,
FFDCA authority to require the wildlife evaluations. As the science develops and resources
allow, screening of additional hormone systems may be added to the Endocrine Disrupter
Screening Program (EDSP).
In the database for PBO, there was no lexicologically significant evidence of endocrine
disrupter effects. When additional appropriate screening and/or testing protocols being
considered under the Agency's EDSP have been developed, PBO may be subject to further
screening and/or testing to better characterize effects related to endocrine disruption.
4. Dietary Risk
Dietary risk assessment incorporates both exposure to and toxicity of a given pesticide.
Dietary risk is expressed as a percentage of a level of concern. The level of concern is the dose
predicted to result in no unreasonable adverse health effects to any human population subgroup,
including sensitive members of such population subgroups. This level of concern is referred to
as the population adjusted dose (PAD), which reflects the reference dose (RfD), either acute or
chronic, adjusted to account for the FQPA safety factor. Estimated risks that are less than 100%
of the PAD are below EPA's level of concern.
Acute and chronic dietary exposure assessments were conducted using two models, the
Lifeline model (Version 2.0) and the Dietary Exposure Evaluation Model software with the
Food Commodity Intake Database (DEEM-FCID, Version 2.03), both of which use food
consumption data from the USDA's Continuing Surveys of Food Intakes by Individuals (CSFII)
from 1994-1996 and 1998. USDA Pesticide Data Program (PDF) data were used for
commodities which have pre-harvest registered uses and for cereal grain crops which have a
stored grain use. All other commodities were assigned residues from either the simulated
warehouse space spray experiment or a simulated restaurant experiment. Residue data from
dermal treatment of livestock were used as input values for meat, milk poultry, and eggs because
dermal treatment of livestock could result in dietary exposure for humans.
For risk assessment purposes, the residues of concern for plants include the parent, PBO,
and a two-fold factor to account for metabolites, unless field trial data for metabolites on related
crops indicated a lower factor was appropriate. Percent crop treated data were used for all
commodities for which percent crop treated data are available. Where no percent crop treated
data were available, the dietary analyses assumed 100 percent crop treated.
Acute (Food Only)
The highly refined PBO acute dietary assessment incorporates both exposure to and
toxicity of PBO considering what may be consumed in one day and maximum or high-end
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residue values in food. The acute dietary endpoint, seen at the lowest observed adverse effect
level (LOAEL) of 1065 mg/kg/day, was decrease in maternal body weight gain in rats. The no
observed adverse effect level (NOAEL) was 630 mg/kg/day. An uncertainty factor of 100 (10X
for inter-species extrapolation, 10X for intra-species variation, and IX Special FQPA Safety
Factor) was applied to the NOAEL to calculate the acute Population Adjusted Dose (aPAD).
The aPAD is the highest predicted dose an individual could be exposed to in one day with no
expected adverse health effects. The aPAD was calculated as 630 mg/kg/day + 100 = 6.3
mg/kg/day. Risk is expressed as a percentage of the aPAD. A risk estimate less than 100% of
the aPAD does not exceed the Agency's level of concern.
Dietary risk estimates were calculated for the general U.S. population and various
population subgroups. PBO acute dietary exposure estimates (food + water) for the U.S.
population (6% of the aPAD) and for the most highly exposed population subgroups, children 1-
2 years of age (20% of the aPAD), are below the Agency's level of concern. The dietary
assessment could be further refined with additional residue data and additional percent crop
treated information.
Chronic (Food Only)
A highly refined assessment was conducted to assess the chronic dietary exposure to
PBO. The chronic dietary endpoint, seen at the lowest observed adverse effect level (LOAEL)
of 52.8 mg/kg/day, was decreased weight gain and increased enzyme activity, liver weight and
liver cell size in dogs. The no observed adverse effect level (NOAEL) was 15.5 mg/kg/day. An
uncertainty factor of 100 (1 OX for inter-species extrapolation, 10X for intra-species variation,
and IX Special FQPA Safety Factor) was applied to the NOAEL to calculate the chronic
Population Adjusted Dose (cPAD). The cPAD is the highest predicted dose at which an
individual may be exposed over the course of a lifetime with no expected adverse health effects.
The cPAD was calculated as 15.5 mg/kg/day + 100 = 0.16 mg/kg/day. Risk is expressed as a
percentage of the cPAD. A risk estimate less than 100% of the aPAD does not exceed the
Agency's level of concern. The exposure estimate for the US population is 5% of the c cPAD
and 12 % for the highest exposed subpopulation, children (1-2 years of age).
Table 5: Summary of Dietary1 Exposure and Risk for PBO (Food Only)
Population Subgroup
General U.S. Population
All Infants (< 1 yr)
Children 1-2 yrs
Children 3 -5 yrs
Children 6-12 yrs
Youth 13-19 yrs
Adults 20-49 yrs
Acute Dietary
(99.9th Percentile)
aPAD,
mg/kg/day
6.3
Exposure,
mg/kg/day
0.3761
0.3908
1.2296
0.8027
0.4112
0.3446
0.3030
% aPAD
6
6
20
13
7
5
5
Chronic Dietary
cPAD,
mg/kg/day
0.155
Exposure,
mg/kg/day
0.0075
0.0057
0.0185
0.0163
0.0117
0.0059
0.0064
% cPAD
5
4
12
11
8
4
4
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Table 5: Summary of Dietary1 Exposure and Risk for PBO (Food Only)
Population Subgroup
Adults 50+ yrs
Females 13-49 yrs
Acute Dietary
(99.9th Percentile)
aPAD,
mg/kg/day
Exposure,
mg/kg/day
0.2865
0.3467
% aPAD
5
6
Chronic Dietary
cPAD,
mg/kg/day
Exposure,
mg/kg/day
0.0066
0.0070
% cPAD
4
5
1 Both Lifeline and DEEM-FCID were used to produce exposure values for the dietary risk assessment, but only the
Lifeline values are listed in the table above because they resulted in the most conservative dietary exposure
estimates.
2. Drinking Water
For more detail on the drinking water assessment see the Drinking Water Assessment for PBO
(Eckel, May 17, 2004).
Drinking water exposure to pesticides can occur through groundwater and surface water
contamination. EPA considers both acute (one day) and chronic (lifetime) drinking water risks
and uses either modeling or actual monitoring data, if available, to estimate those risks. To
determine the maximum allowable contribution from water in the diet, EPA first looks at how
much of the overall allowable risk is contributed by food and then determines a "drinking water
level of comparison" (DWLOC) to ascertain whether modeled or monitored concentration levels
exceed this level.
The Agency uses the DWLOC calculation to estimate risk associated with exposure from
pesticides in drinking water. The DWLOCs represent the maximum contribution to the human
diet (in ppb or ug/L) that may be attributed to residues of a pesticide in drinking water after
dietary exposure is subtracted from the aPAD or the cPAD. Risks from drinking water are
assessed by comparing the DWLOCs to the estimated drinking water concentrations (EDWC) in
surface water and groundwater. EDWCs less than the DWLOC are not of concern. Drinking
water modeling is considered to be an unrefined assessment and generally provides high-end
estimates.
The drinking water assessment included the parent PBO, as well as the three major
degradates which are PBO-alcohol, -aldehyde, and -acid. These degradates are expected to be
more soluble in water and therefore more mobile in soil-water systems than the parent, and for
that reason are included in the drinking water assessment. The three major degradates will likely
share the same toxicity as the parent. There are no specific toxicity concerns for all other minor
metabolites. No drinking water monitoring data were available for PBO.
Surface Water
FIRST (FQPA Index Reservoir Screening Tool) was used to estimate surface water
concentrations. FIRST is a Tier I screening level model used to provide high-end values for the
concentrations that might be found in a small drinking water reservoir. FIRST is a single-event
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model (one run-off event), but can account for spray drift from multiple applications. FIRST
makes adjustments for regional percent crop area but makes conservative assumptions including
modeling a runoff-prone watershed, the use of the maximum use rate, no buffer zone, and a
single large rainfall. FIRST input parameters are based on 10 applications at the agricultural use
rate of 0.5 Ib a.i./acre and a re-application interval of 3 days. These parameters result in
calculated acute surface water EDWC of 240 ug/L and a chronic surface water EDWC of 60
ug/L.
Groundwater
The Screening Concentration in Ground Water (SCI-GROW) model was used to estimate
ground water concentrations. The SCI-GROW screening model is a Tier I assessment that
provides a high-end estimate. SCI-GROW generates a single EDWC value of pesticide
concentration in ground water used for drinking water and provides a ground water screening
concentration for use in determining potential risk to human health from drinking water
contaminated with a pesticide. EPA used the Tier I SCI-GROW model and a percent crop area
of 87%, mean soil half-life of 73 days, and a Koc of 599, to calculate an EDWC of 0.26 ug/L in
ground water.
3. Residential Exposure and Risk
For more detail on the residential exposure and risk assessment, see the Revised Occupational
and Residential Exposure Assessment and Recommendations for the Reregistration Eligibility
Decision for PBO, (Daiss, September 8, 2005), and for more detail on the residential outdoor
misting system assessment, see the Occupational and Residential Exposure Assessment for the
Use of PBO in Residential Outdoor Automatic Mister Systems, (Crowley, August 30, 2005).
Based on the Master Label, 14 residential exposure scenarios have been assessed for this
RED. Only inhalation and incidental ingestion exposure assessments have been conducted for
the residential scenarios. Dermal exposures were not assessed because no adverse effects were
seen at the highest dose tested (1000 mg/kg/day) in the dermal studies. Acute-, short-, and
intermediate-term exposures were assessed for residential exposure scenarios based on use and
exposure patterns. Acute exposures were assessed for post-application inhalation exposure to
aerial and curbside mosquito abatement applications and for exposures during and after
application of aerosol space sprays indoors. Short- and intermediate-term exposures were
assessed for all other handler and post-application exposure scenarios.
Residential risk is expressed as a Margin of Exposure (MOE), which is a ratio of the
NOAEL selected from a toxicity study to the residential exposure value derived from exposure
studies or standard values. MOEs greater than 100 are considered to be protective for acute
exposure via inhalation and for short- and intermediate-term incidental ingestion exposures.
MOEs greater than 300 (additional 3X uncertainty factor for lack of a NOAEL) are considered
adequate for short- and intermediate-term inhalation exposures.
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Table 6: Target MOEs for Residential Exposure
Residential
Routes of Exposure
Incidental Oral
Inhalation
Duration of Exposures
Acute
-
100
Short
100
300
Intermediate
100
300
a. Toxicity
The toxicological endpoints used in the residential risk assessment for PBO are listed in Table
7 below.
Table 7: Endpoints for Assessing Residential Risks for PBO
Exposure
Scenario
Dose Used in Risk
Assessment, UF
Level of Concern
for Risk Assessment
Study and Toxicological Effects
Short-Term
Incidental Oral (1-30 days);
Intermediate-Term
Incidental Oral (1-6
months)
NOAEL= 89
mg/kg/day
Residential LOC for
MOE = 100
Two generation reproduction study, rats
LOAEL = 469 mg/kg/day based on the decrease
in body weight gain of FI and F2 pups at postnatal
day 21
(MRID: 00161118)
Short-Term Dermal
(1 to 30 days);
Intermediate-Term Dermal
(1 to 6 months)
No systemic, developmental or neurotoxicity concerns at the limit dose. Therefore, no
quantification is required. PBO is classified as mild irritant.
Acute Inhalation
(< 2 hrs)
(inhalation absorption rate
= 100 %)
NOAEL= 630
mg/kg/day
Residential LOC for
MOE = 100
Developmental toxicity study, rats
LOAEL = 1065 mg/kg/day based on decrease
in maternal body weight gain
(Tanaka et al., 1995)
Short-Term Inhalation (1 to
30 days);
Intermediate-Term
Inhalation (1 to 6 months)
Respiratory LOAEL=
3.91 mg/kg/day
(0.015 mg/L)
Residential LOC for
MOE = 300
Subchronic inhalation toxicity study, rats
Respiratory LOAEL = 3.91 mg/kg/day (0.015
mg/L) based on laryngeal hyperplasia and
metaplasia
(MRID: 42477101)
NOAEL = no observed adverse effect level, LOAEL = lowest observed adverse effect level, MOE = margin of
exposure, LOC = level of concern
b. Residential Exposure Scenarios
The residential exposure assessment includes four handler and twelve post-application
residential exposure scenarios. The term "handler" applies to individuals who mix, load, and
apply the pesticide product. The term "post-application" describes individuals who may be
exposed to pesticides after entering areas previously treated with pesticides. Based on
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information for supported uses provided in the Master Label, the Agency assessed the residential
exposure scenarios for PBO.
i. Residential Handler Scenarios
The quantitative residential handler exposure/risk assessment developed for residential
handlers is based on these scenarios:
1) Mixing, loading, and applying liquid spray formulation by low-pressure handwand for
indoor surface spray application
2) Mixing, loading, and applying liquid spray formulation by low-pressure handwand for
indoor crack and crevice treatment
3) Mixing, loading, and applying liquid spray formulation by hose-end sprayer for lawn and
garden application
4) Mixing and loading liquid formulations for the systems' holding tanks for outdoor
automatic mister systems
ii. Residential Post Application Scenarios
The quantitative residential post application exposure/risk assessment developed for
residential handlers is based on these scenarios:
1) Inhalation exposure from application of mosquito adulticide from fixed wing aircraft
and/or helicopter
2) Inhalation exposure from application of mosquito adulticide from ultra-low volume
(ULV) truck mounted sprayer
3) Toddler incidental ingestion of residue from treated turf grass via hand-to-mouth
activities
4) Toddler incidental ingestion of residue via object-to-mouth activity while on treated turf
grass
5) Toddler incidental ingestion of soil from treated area
6) Toddler incidental ingestion of residues deposited on carpet via hand-to-mouth activities
after use of total release foggers
7) Toddler incidental ingestion of residues deposited on vinyl flooring via hand-to-mouth
activities after use of total release foggers
8) Toddler incidental ingestion of residues on pets via hand-to-mouth activities after pet
treatment
9) Inhalation exposure to aerosol spray during and after space spray application
10) Bystander acute inhalation exposure during outdoor automatic mister applications
11) Bystander short-term inhalation exposure during outdoor automatic mister applications
12) Bystander short- and intermediate-term exposure following indoor metered release
applications
Due to lack of data, the risks associated with broadcast dust applications to carpet were
not calculated. A qualitative description of the possible risk concerns is included in Section IV.
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c. Exposure Data and Assumptions
Handler Exposure Data
Data from the Pesticide Handler Exposure Database (PHED) and Occupational
Residential Exposure Task Force (ORETF) database were used to assess residential handler
exposures. Default application assumptions regarding areas treated or amounts applied for
residential handler scenarios are documented in the FIED Science Advisory Committee on
Exposure SOP 12: Recommended Revisions to The Standard Operating Procedures For
Residential Exposure Assessment (February 22, 2001). Other residential exposure standard
operating procedures (SOPs) may be viewed at the following website:
http://www.epa.gov/oscpmont/sap/1997/september/sopindex.htm.
Post Application Exposure Data
The Agency used default factors from the Exposure Science Advisory Committee SOP
12, Non-Dietary Exposure Task Force (NDETF) data, and Spray Drift Task Force exposure data
throughout the post application risk assessment. Refer to the Occupational and Residential
Exposure Assessment for further information.
Exposure Parameters and Assumptions
The parameters and assumptions used in estimating risks from residential exposure to
PBO are described in section 6.2 of the Occupational and Residential Exposure Assessment.
This information was used to assess all scenarios including mosquito abatement, incidental oral,
aerosol space sprays, and outdoor residential misting systems.
d. Residential Risk Estimates
The results of the residential exposure assessment indicate that most residential handler
and post-application exposure scenarios assessed result in MOEs greater than the applicable
target MOEs. All residential handler scenarios are not of concern with MOEs ranging from
2,700 to 51,000.
The quantified post-application risks of concern to the Agency include: (1) the short-term
residential bystander inhalation risk from outdoor residential misting systems; and (2) the short-
term inhalation risk from indoor metered release devices. While exposures are expected from
short-term (1-30 days) durations, the toxicological end point is the same for intermediate-term
exposure (1-6 months), so the risk calculations represent both short- and intermediate-term
exposures.
There were no data to estimate the exposure from applications of dusts to wide areas of
carpet, therefore, this scenario could not be assessed, but is described qualitatively in section IV.
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Outdoor residential misting systems have been modified from existing dairy barn misting
systems and installed in residential areas as likely due to homeowners concerns about West Nile
Virus. These systems are set to dispense pesticide at specific times throughout a day, depending
on how the system is set up.
The outdoor residential misting system scenario triggers bystander short-/intermediate-
term inhalation risk for toddlers when two 1-minute spray durations are estimated (MOEjoddiers =
190). When exposure is to two 30-second spray durations, risk is not of concern (MOEToddiers =
370). Table 8 below summarizes the results of the outdoor residential misting systems
assessment.
Table 8: Short-/Intermediate-Term Inhalation Exposure and Risk Estimates for Residential Bystanders -
Residential Outdoor Misting Systems
Population
Sub-Group
Adult
Toddler
Application Rate
(Ib PBO/ft3-min)
0.000000469
0.000000469
Inhalation
Rate
(m3/hour)
1
0.7
Spray Duration
(minutes)
1
0.5
1
0.5
Air Concentration
(mg PBO/m3)
0.150195
0.0750974
0.150195
0.0750974
Daily Dose
(mg/kg/day)
0.010728
0.005364
0.0210273
0.0105136
MOE
(Target MOE =300)
360
730
190
370
The indoor metered release device scenario was based on the Multi-Chamber
Concentration and Exposure Model (MCCEM) single chamber model to predict the air
concentrations that would result from application to a whole house with multiple units. Products
used in metered release devices are usually formulated in ready to use aerosol cans with a special
nozzle that fits into the device. A battery-powered timer system allows a spray of PBO to
dispense regularly throughout a day. These systems are registered for use to control flying
insects in residential areas, food handling establishments, animal premises, and other areas. The
PBO short- and intermediate-term MOEs for indoor residential metered release devices range
from 12 to 240 and are below the target MOE of 300.
Table 9: PBO Residential Post-Application Inhalation Risks Following Metered Release Devices
Exposed
Population
Adults
Children
Adults
Children
Adults
Children
Adults
Children
MCCEM
Execution Mode
Single Chamber
(Units are installed
throughout house)
Use Interzonal Air
Flow Rates
(Unit installed in
kitchen only)
Air Changes per
Hour
0.18
(Summer House)
0.45
(Fall/Spring House)
0.18
(Summer Houes)
0.45
(Fall/Spring House)
Inhalation
Exposure
(mg/day)
5.7
4.7
3.0
1.95
2.85
1.85
1.15
0.75
Inhalation Dose
(mg/kg/day)
0.081
0.313
0.042
0.130
0.041
0.123
0.016
0.050
Short/
Intemediate
Term MOE
50
12
90
30
100
30
240
80
The application rates are based upon the Clean Air Purge II Label (9444-161). This product contains 1% pyrethrins by weight in
a 232 gram container. One container will apply 3000 sprays per month at fifteen minute intervals and is sufficient for a 6000
cubic feet interior space.
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e. Aggregate Risk
In accordance with the FQPA, the Agency must consider pesticide exposures and risks
from all potential sources when assessing non-occupational sources. These exposures usually
include food, drinking water, and residential exposures. In an aggregate assessment, exposures
from all relevant sources are added together. When aggregating exposures and risks from
various sources, the Agency considers both the route (oral, dermal, and inhalation) and duration
(short-, intermediate-, or long-term) of exposure.
For PBO, aggregate risk assessments were conducted for acute (one day) and chronic
(one year or more) food and drinking water exposures. The short-term aggregate exposures from
food, water, and residential (incidental oral) routes associated with application of PBO were also
calculated for PBO since there was a common toxicity endpoint of decreased weight gain
identified for those routes of exposure.
Acute Aggregate Risk (Food + Drinking Water)
Acute DWLOCs were calculated based on acute dietary exposure estimates and default
body weights and water consumption figures. The EDWCs for both surface water and
groundwater are well below the acute DWLOCs for the general U.S. population and all other
population subgroups indicating that acute aggregate exposure to PBO in food and water is not a
concern. The lowest acute DWLOC is 51000 ug /L for children 1-2 years old, which is higher
than the surface water EDWC of 240 ug/L and the ground water EDWC of 0.26 ug/L.
Short term Aggregate Risk (Food + Drinking Water + Incidental Oral)
Short term aggregate risk is the estimated risk associated with the combined risks from
average food exposures, average drinking water exposures, and short-term oral, dermal and
inhalation exposures. The PBO toxicity endpoints selected for the dietary, drinking water, and
incidental oral routes of exposure may be aggregated because decreased body weight gain was
the common toxicity endpoint for all of these exposure routes.
The inhalation endpoint was different from the other endpoints selected and no endpoint
was identified for dermal exposure, so dermal and inhalation exposures were not considered in
the aggregate assessment.
The short term aggregate risk for PBO was calculated by adding exposure estimates from
dietary, drinking water, and incidental oral exposure pathways for children age 1-2 and
comparing them with model based EDWCs. The lowest short term DWLOC is 8500 ug/L for
children 1-2 years old which is higher than the surface water EDWC of 60 ug/L and the ground
water EDWC of 0.26 ug/L. The aggregate short term exposure to PBO does not result in a risk
of concern. Due to a high degree of uncertainty in the risk assessment some post-application
short-term scenarios, including outdoor residential misting systems and metered release device
scenarios, were not included in the short-term aggregate assessment. However, because of the
conservative exposure assumptions used in the individual assessments, and with the exposure
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mitigation requirements described herein, the Agency does not expect aggregate exposures to
pose risks of concern.
Chronic Aggregate Risk (Food + Drinking Water)
Chronic DWLOCs were calculated based on the chronic dietary exposure estimates and
default body weights and water consumption figures. The EDWCs for both surface water and
groundwater are well below the chronic DWLOCs for the general U.S. population and all other
population subgroups indicating that chronic aggregate exposure to PBO in food and water is not
of concern. The lowest chronic DWLOC is 1400 ug/L for children 1-2 years old, which is higher
than the surface water EDWC of 60 ug/L and the ground water EDWC of 0.26 ug/L.
4. Cumulative Risk Assessment
The Food Quality Protection Act (FQPA) requires that the Agency consider available
information concerning the cumulative effects of a particular pesticide's residues and other
substances that have a common mechanism of toxicity. The reason for consideration of other
substances is due to the possibility that low-level exposures to multiple chemical substances that
cause a common toxic effect by a common toxic mechanism could lead to the same adverse
health effect as would a higher level of exposure to any of the substances individually. Unlike
other pesticides for which EPA has followed a cumulative risk approach based on a common
mechanism of toxicity, EPA has not made a common mechanism of toxicity finding as to PBO
and any other substances and, PBO does not appear to produce a toxic metabolite produced by
other substances. For the purposes of this tolerance reassessment action, therefore, EPA has not
assumed that PBO has a common mechanism of toxicity with other substances. For information
regarding EPA's efforts to determine which chemicals have a common mechanism of toxicity
and to evaluate the cumulative effects of such chemicals, see the policy statements released by
EPA's Office of Pesticide Programs concerning common mechanism determinations and
procedures for cumulating effects from substances found to have a common mechanism on
EPA's website at http://www.epa.gov/pesticides/cumulative/.
5. Occupational Risk
For more detail on the occupational assessment, see the Revised Occupational and Residential
Exposure Assessment and Recommendations for the Reregistration Eligibility Decision for PBO,
(Daiss, September 8, 2005).
Since the last Occupational and Residential PBO risk assessment was available for public
comment on September 21, 2005, the following scenarios were included in the occupational risk
assessment:
Mixing and loading liquids for aerial applications to forestry areas at a rate of 2.5 Ib
ai/acre.
Liquid aerial applications to forestry areas at the rate of 2.5 Ibs ai/acre.
Post-application exposure from metered release devices spraying in institutional or non-
residential areas.
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a. Occupational Toxicity
Table 10 provides a listing of the toxicological endpoints used in the PBO occupational risk
assessment.
Table 10: Endpoints and Doses Used in the Occupational Risk Assessment
Exposure
Scenario
Short-Term Inhalation
(1 to 30 days);
Intermediate-Term
Inhalation (1 to 6 months)
Short-Term Dermal
(1 to 30 days);
Intermediate-Term
Dermal (1 to 6 months)
Dose Used in Risk
Assessment, UF
Respiratory LOAEL=
3.91 mg/kg/day
(0.015 mg/L)
Level of Concern for
Risk Assessment
Occupational LOG for
MOE = 300
Study and Toxicological Effects
Subchronic inhalation toxicity study, rats
Respiratory LOAEL = 3.91 mg/kg/day (0.015
mg/L) based on laryngeal hyperplasia and
metaplasia
(MRID: 42477101)
No systemic, developmental or neurotoxicity concerns at the limit dose. Therefore, no
quantification is required.
NOAEL = no observed adverse effect level, LOAEL = lowest observed adverse effect level, MOE = margin of
exposure, LOG = level of concern
b. Occupational Handler Exposure
Workers can be exposed to a pesticide through mixing, loading, or applying the pesticide,
and through re-entering a treated site. Worker risk is measured by a Margin of Exposure (MOE)
which determines how close the occupational exposure comes to the NOAEL taken from animal
studies. In the case of PBO, MOEs that are greater than 300 for short- and intermediate-term
exposure and 1000 for long-term exposure do not exceed the Agency's level of concern. A
summary of occupational target MOEs is below in Table 11.
Table 11: Target MOEs for Occupational Exposure
Occupational
Routes of Exposure
Inhalation
Duration of Exposures
Acute
100
Short
300
Intermediate
300
Data from the PHED or ORETF databases were used to assess occupational handler
exposures. Standard assumptions regarding areas treated or amounts applied for agriculture and
mosquito abatement handler exposure scenarios are documented in the HED Science Advisory
Committee on Exposure's SOP 9, "Standard Values for Daily Acres Treated in Agriculture"
(July 5, 2000). Information on how pest control operators use pesticide products was obtained
from a survey conducted by the National Pest Management Association (NPMA). NPMA
sponsored a "Pest Control Operators (PCO) Product Use and Usage Information Survey."
Further information on data utilized in the occupational risk assessment can be found in the PBO
occupational risk assessment, (Daiss, September 8, 2005).
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i. Agricultural Handler Scenarios
1) mixing and loading liquids for aerial and/or chemigation application to field crops
2) mixing and loading liquids for groundboom application to field crops
3) mixing and loading liquids for airblast application to field crops
4) mixing and loading wettable powders for aerial and/or chemigation application to field
crops
5) mixing and loading wettable powders for groundboom application to field crops
6) mixing and loading wettable powders for airblast application to field crops
7) applying liquids aerially to field crops
8) applying liquids with ground boom sprayer to field crops
9) applying liquids with airblast sprayer to field crops
10) mixing, loading and applying liquids with high pressure hand wand for greenhouse
application
11) mixing, loading and applying liquids with backpack sprayer or low pressure handwand
for greenhouse application
12) mixing loading and applying wettable powder with backpack sprayer or low pressure
hand wand for greenhouse application
13) mixing, loading and applying liquids with backpack sprayer or low pressure hand wand
for agricultural premise and equipment application
14) flagging for aerial spray application
ii. Forestry Handler Scenarios
1) mixing and loading liquids for aerial forestry applications
2) applying liquids for aerial forestry applications
iii. Pesticide Control Operator Handler Scenarios
1) mixing, loading and applying liquids indoors for surface spray application with low
pressure handwand;
2) mixing, loading and applying liquids indoors for crack and crevice application with low
pressure handwand;
3) mixing, loading and applying wettable powders indoors for surface spray application with
low pressure handwand;
4) mixing, loading and applying wettable powders indoors for crack and crevice application
with low pressure handwand;
5) mixing, loading and applying liquids with backpack sprayer or low pressure hand wand
for general outdoor sites;
6) mixing, loading and applying liquids for hand gun sprayer application to lawns;
7) mixing, loading and applying liquids for groundboom application to golf courses
8) mixing, loading and applying liquids for back pack sprayer or low pressure handwand
application to stored grain
9) mixing, loading and applying liquids for high pressure handwand application to stored
grain
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10) mixing, loading and applying liquids for low pressure handwand application to
warehouse stored produce
11) applying liquids to golf courses with groundboom sprayer
12) aerosol spray application indoors
13) mixing and loading liquid formulations for the systems' holding tanks for outdoor
automatic mister systems
iv. Mosquito Abatement Scenarios
1) mixing, loading liquids for aerial application
2) mixing, loading liquids for ULV truck mounted spray application
3) mixing, loading, applying liquids with truck mounted ULV ground spray (airblast sprayer
unit exposure used as surrogate)
4) mixing, loading, applying liquids with back pack sprayer
v. Direct Application to Pets and Farm Animals
1) spray application by veterinarians and groomers
c. Occupational Handler Risk Summary
Based on the supported uses provided in the Master Label, thirty-four occupational
exposure scenarios were assessed for agricultural, forestry, professional pest control operator,
and mosquito control applications of PBO. Short-, intermediate-, and long-term exposures were
assessed for occupational scenarios based on use patterns. Agricultural and forestry handler
scenarios were assessed as short- and intermediate-term exposures. Pesticide control operator
scenarios were assessed as short-, intermediate- and long-term exposures. Mosquito abatement
scenarios were assessed as short- and intermediate-term exposures for aerial and backpack spray
applications and short-, intermediate-, and long-term exposures for truck mounted ULV spray
applications. Only inhalation exposures have been assessed for each of the occupational
scenarios because no dermal assessment was conducted since no adverse effects were seen at the
highest dose tested in dermal toxicity studies.
The majority of occupational handler scenarios are not of concern at baseline attire (long-
sleeved shirt, long pants, shoes and socks) with MOEs ranging from 300 to 23,000. The
following agricultural, forestry, pesticide control operator, and mosquito abatement scenarios do
not reach their target MOEs (300 for short- and intermediate-term and 1000 for long-term
exposures) at baseline attire, and are potentially of concern.
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Table 12: Scenarios of Potential Concern for Agricultural Handlers
Agricultural Handler Exposure
Scenarios of Concern
Wettable Powders
Mixing/Loading for Aerial application
and/or Chemigation Application
Wettable Powders
Mixing/Loading for Groundboom
Application
Wettable Powders
Mixing/Loading/Applying for Low-
Pressure Handwand or Backpack Sprayer
Application
Liquids
Mixing/Loading/Applying for High-
Pressure Handwand Application
Crop
Field Crops
High Acre
Crops
Field Crops
Greenhouse
Greenhouse
Application
Rate
0.50 Ib ai/acre
0.50 Ib ai/acre
0.50 Ib ai/acre
1.5 Ib ai/acre
1.5 Ib ai/acre
Daily Area
Treated
350 Acres/day
1200 Acres/day
80 Acres/day
2 Acres/day
10 Acres/day
Inhalation
MOE*
(Short & Inter
Term Target =
300)
40
11
160
85
160
* Assumes baseline PPE (long-sleeved shirt, long pants, shoes and socks). No respirator is included in these
calculations.
Table 13: Scenarios of Potential Concern for Handlers for Forestry Application
Forestry Exposure Scenarios
Liquid
Mixing/Loading for aerial application with
baseline PPE (no respirator)
Liquid
Mixing /Loading for aerial application
with PF 5 respirator
Aerial spray application with baseline PPE
(no respirator)
Site
Forestry
Forestry
Forestry
Rate in Assessment
2.5 Ib ai/acre
(Master Label Rate)
2.5 Ib ai/acre
2.5 Ib ai/acre
Daily Area
Treated
1200
acres/day
1200
acres/day
1200
acres/day
Inhalation
MOE
(Short & Inter
Term Target =
300)
160
770
2200
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Table 14: Scenarios of Potential Concern for Pesticide Control Operators
Pesticide Control Operator Exposure
Scenarios
Wettable Powders
Mixing/Loading/Applying for Low
Pressure Handwand application - Surface
Spray
Wettable Powders
Mixing/Loading/Applying for Low
Pressure Handwand application - Crack &
Crevice Treatment
Liquids
Mixing/Loading/Applying for Low
Pressure Handwand application - Crack &
Crevice Treatment
Applying Aerosol Sprays
Use
Indoor Surface
Spray
Indoor Crack
& Crevice
Indoor Crack
and Crevice
Indoor Space
Spray
Application
Rate
0.56 Ib ai per
1000 ft2
2.2 Ib ai per
1000 ft2
2.2 Ib at per
1000 ft2
0.025 Ib ai per
16 oz can
Daily Area
Treated
7 buildings avg
area treated -
1600 ft2
7 buildings avg
area treated -
1600 ft2
7 buildings avg
area treated -
1600 ft2
7 homes per day
2 cans per home
Inhalation
MOE*
(Short & Inter Term
Target = 300)
(Long Term Target =
1000)
40
10
380
615
* Assumes baseline PPE (long-sleeved shirt, long pants, shoes and socks). No respirator is included in these
calculations.
TablelS: Scenarios of Potential Concern for Mosquito Abatement Handlers
Mosquito Abatement Exposure Scenarios
of Concern
Liquids
Mixing/Loading for Aerial Application
Mix/Load/Apply Sprays for ULV truck
mounted spray (Airblast Surrogate Unit
Exposure)
Use
Mosquito
Control
Mosquito
Control
Application
Rate
0.08 Ib ai per
acre
0.08 Ib ai per
acre
Daily Area
Treated
7500 acres per
day
3000 acres per
day
Inhalation
MOE
(Short & Inter Term
Target = 300)
(Long Term Target =
1000)
390
260
There were no risks of concern with professional applications to pets or other animals.
Due to lack of data, application of dust with bulb duster, and power dusters were not assessed.
Also, handlers applying with handheld foggers could not be assessed due to lack of use and
application information.
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d. Occupational Post-Application Risk Summary
Inhalation exposures are thought to be negligible in outdoor post-application scenarios,
since PBO has low vapor pressure and the dilution factor outdoors is considered infinite. As a
result, inhalation post-application exposures from outdoor applications were not considered in
this assessment. There is potential for post-application inhalation exposure from indoor metered
release applications.
According to the Master Label, PBO is used as a space spray in a wide variety of indoor
areas such as barns, greenhouses, food storage areas, food processing areas, restaurants and
residences. A scenario that involves a metered release into a dairy barn was evaluated to assess
these exposures because PBO is commonly used in dairy barns and because the ventilation
characteristics of dairy barns are relatively well defined. The MOE for short- and intermediate-
term exposure is 62, which does not reach the target MOE of 300 as shown in Table 16.
The indoor metered release device scenario used the same model, the MCCEM single
chamber model, as the residential metered release device scenario, except the occupational
assessment assumed a ventilation rate of six air changes per hour, while the residential scenario
assumed less than half an air change per hour. The risk estimates for the metered release
scenarios are conservative because it was assumed that the aerosol particles would remain
airborne until they were removed by ventilation and the effect of aerosol particle settling was not
considered. Aerosol particle settling could be a major factor depending upon the aerosol particle
size and rate of evaporation. Data will be required to better characterize this exposure.
Table 16: PBO Occupational Post-Application Estimated Risks Following Metered Release
Exposure Scenario
Metered Release Space Spray
Location
Dairy Barns
Short/Intermediate Term MOE
(Target MOE = 300)
62
The restricted entry interval (REI) for PBO will remain at 12 hours for all post-
application scenarios that fall under the Worker Protection Standard. In addition, under the
Worker Protection Standard for Agricultural Pesticides - WPS-(40 CFR 170) greenhouses must
be appropriately ventilated following pesticide applications so that post-application inhalation
exposures are minimal.
6. Human Incident Data
Based on data from Poison Control Centers, there appears to be a greater risk of moderate
or major symptoms among those exposed to products containing PBO and pyrethrins than those
exposed to pyrethrins alone. A detailed review of symptoms found that respiratory symptoms
(bronchospasm, cough/choke, and dyspnea) and selected dermal symptoms (dermal
irritation/pain, itching, and rash) were more likely reported if the exposure included PBO. These
symptoms are likely the reason for increased risk of moderate effects which typically would
require medical attention. The findings from analysis of symptoms from Poison Control Centers
suggest that PBO added to a product with pyrethrins increases the reported effects.
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However, other evidence indicates that PBO does not effectively act as a synergist in
mammals. PBO is well known to inhibit microsomal enzymes in insects. It also inhibits the
microsomal enzymes in several other species (e.g., rats, rabbits, mice) based on available
toxicological data. However, evidence indicates that enzyme inhibition in mammals is transient
and occurs at high doses. These studies also indicates that initial inhibition in mammals is
followed by stimulations of microsomal enzymes upon continues exposure. PBO has also been
used as a classical compound in several pharmacological experiments to compare the
therapeutical or toxicological effects of several drugs before or after metabolism in rodents.
These drug interactions studies also suggest that the inhibition of microsomal enzymes in a
transient effect in mammalian systems. The kinetics of PBO inhibition and stimulation of
microsomal enzymes in humans is not established. However, one study in humans reports no
inhibition or microsomal enzymes at a relatively low dose.
B. Environmental Risk Assessment
A summary of the Agency's environmental risk assessment for PBO is presented below. More
detailed information associated with the environmental risk from the use of PBO can be found in
the document PBO EFED 's Response to Public Comments and our Revised Ecological Risk
Assessment (Davy, September 6, 2005).
Agricultural and public health (mosquito control) uses were estimated to result in the
most likely environmental exposure for PBO. Exposure analyses focused on the use of PBO in
post-crop emergence sprays to control insects. Both ground and aerial spray applications were
considered. The use of PBO in mosquito control was examined with the standard Rice Paddy
Model, which estimates environmental concentrations from direct water applications.
PBO was evaluated for its ecological and environmental effects independently from any
other active ingredient, but because PBO is never used alone, its adverse effects should be
considered in light of the other active ingredients with which it is formulated, typically
insecticides like pyrethroids or natural pyrethrins. PBO alone is generally less toxic to the
species of concern, such as aquatic invertebrates, than pyrethrins and pyrethroids. Depending on
the different fate characteristics of PBO and other active ingredients in formulated products, the
chemicals may separate in the environment, affecting the potential for adverse effects to species
at risk. Risk quotients (RQs) discussed in this section reflect PBO alone. The available toxicity
data from PBO plus other active ingredients like pyrethrins or pyrethroids show greater toxicity
to invertebrates than if exposure was to the pyrethrin/pyrethroid alone.
1. Environmental Fate and Transport
The environmental fate database is adequate to characterize the environmental fate,
drinking water, and ecological exposure of PBO. However, EPA does intend to issue a Data
Call-in as part of this RED to address remaining areas of uncertainty.
PBO degrades rapidly (8.4-hour half-life) in the environment by photolysis in water, and
is metabolized by soil microorganisms. Other tested routes of degradation, such as hydrolysis,
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aerobic and anaerobic aqueous metabolism, are very slow or have questionable rates due to
experimental difficulties, as in the case of soil photodegradation. The estimated atmospheric
half-life of PBO is 3.4 hours, based on the estimated reaction rate with hydroxyl radicals. PBO
is moderately mobile in soil-water systems (Koc = 399 - 830 ). Little volatilization from soil or
water is expected, but PBO may enter the atmosphere as an aerosol when applied by spraying.
The major degradates PBO-alcohol, PBO-aldehyde, and PBO-acid are expected to be
more soluble in water than the parent and therefore more mobile in soil-water systems. Exposure
to both parent PBO and its major degradates (PBO-alcohol, PBO-aldehyde, and PBO-acid) were
considered in the assessment. The toxicity of the degradates was considered to be equivalent to
that of the parent in the absence of data.
2. Ecological Risk
The Agency's ecological risk assessment compares toxicity endpoints from ecological
toxicity studies to estimated environmental concentrations (EECs) based on environmental fate
characteristics and pesticide use data. PBO lacks pesticide properties of its own, and must be
used with other active ingredients to be effective, but in this assessment PBO alone was
considered. To evaluate the potential risk to non-target organisms from the use of PBO alone,
the Agency calculates a Risk Quotient (RQ), which is the ratio of the EEC to the most sensitive
toxicity endpoint values, such as the median lethal dose (LD50) or the median lethal
concentration (LCso). These RQ values are then compared to the Agency's levels of concern
(LOCs), which are listed below in Table 17 and indicate whether a pesticide, when used as
directed, has the potential to cause adverse effects to non-target organisms. When the RQ
exceeds the LOG for a particular category, the Agency presumes a risk of concern. These risks
of concern may be addressed by further refinements of the risk assessment or risk mitigation
measures. Use, toxicity, fate, and exposure are considered when characterizing the risk, as well
as the uncertainty in the assessment. EPA further characterizes ecological risk based on any
reported incidents to non-target terrestrial or aquatic organisms in the field (e.g., fish or bird
kills).
Table 17: EPA's Levels of Concern and Associated Risk Presumptions
Risk Presumption
Acute Risk - there is potential for acute risk
Acute Endangered Species - endangered species may be
adversely affected
Chronic Risk - there is potential for chronic risk
LOC
Terrestrial
Animals
0.5
0.1
1
LOC
Aquatic
Animals
0.5
0.05
1
LOC Plants
1
1
N/A
The ecological risk assessment for PBO focuses on maximum application rates for
agricultural and mosquito abatement uses, which combined make up roughly about 20% of the
total PBO use. Consideration was also given to PBO entering water from sources like lice
shampoos and flea sprays that may contaminate water going down the drain and run into water
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treatment facilities. This "Down-the-Drain" scenario was included in a response memo from
EFED addressing water quality concerns (Davy, January 30, 2006). However, no analogous
exposure model has been developed to allow a similar screening assessment for pesticides
applied in an outdoor urban setting. As a result, the Agency has taken a qualitative approach to
characterize the potential aquatic risk from urban and suburban use of PBO.
a. Risk to Aquatic Organisms
i. Fish and Invertebrate Toxicity and Exposure
1. Toxicity
A summary of the toxicity results for aquatic organisms exposed to PBO is below in
Table 18.
Freshwater Fish
PBO is moderately toxic to freshwater fish on an acute basis (LCso = 1.9 ppm).
A no observed effect concentration (NOEC) of 0.04 ppm was estimated from a chronic
early life stage offish study with fathead minnow in which embryo survival at hatch and length
and weight of larvae was observed at the lowest observed effect concentration (LOEC) of 0.11
ppm.
Freshwater invertebrates
PBO ranges from moderately toxic (LCso = 12.0 ppm) to highly toxic (LCso = 0.51 ppm)
to freshwater invertebrates on an acute basis. The species selected for RQ calculation was
Daphnia magna with an LCso of 0.51 ppm.
A NOEC of 0.030 ppm was estimated from a chronic life cycle study where Daphnia
magna exhibited reproduction affects at the lowest observed effect concentration (LOEC) of
0.047 ppm.
Estuarine fish
PBO is moderately toxic (LCso = 3.94 ppm) to estuarine/marine fish based on observed
effects to sheepshead minnow on an acute basis.
There are no chronic data available for estuarine fish.
Estuarine'/Marine invertebrates
PBO is highly toxic to estuarine invertebrates (LC50 = 0.49 ppm). There are no chronic
data available for estuarine/marine invertebrates.
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Amphibians
PBO is highly toxic to amphibians on an acute basis (LC50 = 0.21 ppm).
Table 18: Toxicity reference values for aquatic organisms exposed to PBO
Exposure Scenario
Species
Toxicity
Reference Value
Freshwater Fish
Acute
Chronic
Rainbow trout
(Oncorhynchus mykiss)
Fathead minnow
(Pimephales promelas)
LC50a=1.9ppm
NOEC b= 0.04 ppm
LOECC= 0.11 ppm
Effect: Survival and growth
Freshwater Invertebrates
Acute
Chronic
Waterflea
(Daphnia magna)
Waterflea
(Daphnia magna)
LC50= 0.51 ppm
NOEC = 0.03 ppm
LOEC = 0.047 ppm
Effect: reproduction
Esutarine/Marine Fish
Acute
Sheepshead minnow
(Cyprinodon variegatus)
LC50 = 3.94ppm
Estuarine/Marine Invertebrates
Acute
Mysid shrimp (Mysidopsis bahia)
LC50 = 0.49 ppm
Amphibians
Acute
Western chorus frog tadpole
(Pseudacris triseriata)
LC50 = 0.210ppm
aLC50 = Median Lethal Concentration
bNOEC = No Observed Effect Concentration
0 LOEC = Lowest Observed Effect Concentration
2. Exposure
Environmental exposure from PBO was modeled in four ways. Exposures from
terrestrial agricultural applications were assessed using the standard farm pond scenario in the
PRZM-EXAMS models. All PRZM-EXAMS exposure analyses were done at maximum
application rates and frequency. The EFED Interim Rice Paddy Model was used to calculate
acute exposure due to direct application to water from mosquito abatement uses. Spray drift
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from terrestrial agricultural applications was assessed using the AgDrift model to calculate
exposures in the EFED standard farm pond and standard wetland models. Finally, the Down-
the-Drain model in E-FAST was used to address water quality impacts from disposal of PBO
down drains.
Comments were submitted from PBOTFII stating that the aquatic exposure assessment
for PBO should include only the parent compound and no degradates. To demonstrate the effect
of considering only parent PBO, a revised assessment for Florida peppers was run considering
the parent compound only. Although the results of the revised parent only Florida peppers
assessment, which is found in the PiperonylButoxide: EFED's Response to Public Comments
and Revised Ecological Risk Assessment (Davy, September 6, 2005), resulted in lower RQs, the
results were not large enough to change the original risk conclusions for acute or chronic levels-
of-concern for any organism. Considering the parent only or the parent plus degradates, did not
change the risk conclusions for PBO.
Agricultural Exposure
For exposure to fish and aquatic invertebrates, EPA considers surface water only, since
most aquatic organisms are not found in ground water. The aquatic exposure assessment for
PBO relied on the PRZM and EXAMS Tier II models. The Pesticide Root Zone Model (PRZM
version 3.12) simulates fate and transport on the agricultural field, while the water body is
simulated with Exposure Analysis Modeling System (EXAMS version 2.98). Simulations are
run for multiple (usually 30) years and the reported EECs represent the values that are expected
once every ten years based on the thirty years of daily values generated during the simulation.
The half-life values used in the PRZM/EXAMS model reflect the combined residues of parent
PBO and its major degradates PBO-alcohol, PBO-aldehyde, and PBO-acid, expressed as PBO
equivalents.
PRZM/EXAMS modeling of PBO was done for 23 crop scenarios using the current
maximum label rate of 0.5 Ibs a.i. per acre, ten applications per year, and a 3-day re-application
interval. The peak EECs ranged from 22.1 ppb (CA grapes) to 160 ppb (FL peppers) for aerial
application. For ground application, the peak EECs ranged from 8.4 ppb (CA grapes) to 159 ppb
(FL peppers). A complete listing of EECs, including those used for PBO RQ calculations can be
found in table 6a and 6b in the EFED risk assessment (September 2005).
Mosquito Abatement Exposure
The EFED interim standard Rice Paddy Model (October 29, 2002) was used as a measure
of exposure for mosquito abatement applications. This model estimates the exposure
concentration in a four-inch deep water body at the time of application, and accounts for
partitioning to sediment, but not dissipation. Overall, the model yields a conservative measure of
exposure. The PBO Master Label indicates that the application rate of PBO for mosquito
abatement applications can be up to 0.08 Ib/acre to control Aedes taeirorhynchus and other
difficult species. No maximum number of applications is indicated. The minimum soil-water
distribution coefficient (Kd = 0.98) measured for PBO was used to provide maximum
partitioning to the water phase, and resulting in a conservative measure of exposure in the water
column. The Rice Paddy EEC for a single application is 75 ppb.
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Spray Drift
Ground Application
The AgDrift model was used to calculate aquatic exposures in the EPA standard pond
and standard wetland, from spray drift from a single agricultural application. A ground spray
Tier I aquatic assessment was performed, assuming high boom application with very fine to fine
spray, 90th percentile drift, and a zero-foot buffer, at an application rate of 0.5 Ib a.i./acre.
AgDrift calculated that 6.16% of the applied mass would reach the pond or wetland, resulting in
an initial average concentration of 1.7 ppb in the pond, and 23 ppb in the wetland.
Aerial Application
Tier 1 aerial analysis, assuming fine to very fine spray and a zero-foot buffer, resulted in
the pond and wetland EECs of 6.8 ppb and 90.6 ppb, respectively.
Aquatic Exposure - "Down-the-Drain " Assessment
In order to address the issue of PBO release to domestic wastewater treatment, the
Agency relied on the Office of Pollution Prevention and Toxics (OPPT) consumer exposure
model, Exposure and Fate Assessment Screening Tool (E-FAST) (USEPA, 1999). This
screening level Down-the-Drain model E-FAST is specifically designed to address all sources of
PBO, such as from pet shampoos and other uses that could potentially contribute to domestic
wastewater from a "down-the-drain" application.
The model uses input parameters to estimate the highest amount of PBO that could be
released down a drain before a significant concentration of PBO is reached. In this case, it was
assumed that synergistic effects from PBO would be insignificant at levels less than 1 ppb. The
model assumes that in a given year, a certain amount of PBO is parceled out on a daily per capita
basis to the U.S. population and diluted into the average daily volume of wastewater prior to
entering a treatment facility. It is assumed that the sewage treatment removal efficiency is zero
for PBO, and that it is instantaneously diluted when mixing with surface water. Two dilution
scenarios were modeled assuming low (75 times) and average (980 times) dilution into surface
water.
Assuming a sewage treatment removal efficiency of 0%, then 6,033,688 pounds PBO per
year disposed down a drain would be required to reach 1 ppb in receiving waters for the low
dilution case (75 times), and 79,568,289 pounds PBO per year are required for the average
dilution case (980 times). The annual production of PBO, estimated at 210,000 Ibs per year for
agricultural and non-agricultural applications, is well below this level and the Agency concluded
that there was no risk of concern from the Down-the-Drain scenario.
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ii. Aquatic Risk
A summary of the RQs for acute exposure to PBO is summarized in Table 19 below. The
LOG for endangered species was slightly exceeded for most species and application methods.
The RQ for amphibians exposed to PBO from agricultural applications was the highest estimated
RQ at 0.76.
Table 19: Acute Aquatic Risk Quotient (RQ) Summary
Species
Freshwater fish
Freshwater invertebrates
Estuarine/Marine Fish
Estuarine/Marine Invertebrates
Amphibians
Application Type
Agriculture
0.05 - 0.08
0.05 - 0.31
O.05
0.05 - 0.33
O.05 - 0.76
Mosquito Use
0.05
0.15
O.05
0.15
0.36
Spray Drift
0.05 - 0.05
0.05 - 0.18
O.05
0.05 - 0.18
O.05 - 0.43
Bold values indicate exceedance for Endangered Species LOG (RQ > 0.05).
Data were only available to assess chronic risk to freshwater fish and invertebrates
exposed to PBO from agricultural applications. Some RQs exceeded the target LOG of 1.0, with
the highest RQ estimated for freshwater invertebrates at 5.1. There were no data available to
assess chronic risk to other species. The chronic RQ summary is in Table 20 below.
Table 20: Chronic Aquatic Risk Quotient (RQ) Summary
Species
Freshwater fish
Freshwater invertabrates
Esturaine/Marine Fish
Esturaine/Marine Invertebrates
Amphibians
Agricultural Applications
<1.0-3.6
<1.0-5.1
Not assessed because no data were
available.
Bold values indicate exceedance for chronic LOG (RQ > 1.0).
Wide Area Mosquito Adulticide Monitoring Data
In a Sacramento County monitoring study for PBO and pyrethrins, water samples were
collected after mosquito adulticide applications in the Sacramento metropolitan area. In samples
collected up to 10 hours after application there were detections of PBO and pyrethrins in the ppb
range, that were similar to modeling predictions in the PBO and the pyrethrins mosquito
adulticide assessment. Samples were also collected the day after application and measured lower
or no concentrations for both active ingredients. This indicates both chemicals appear to
dissipate fairly rapidly in the water column. The co-occurrence of PBO and pyrethrins in some
of these first samples is an indication of direct transport to water from pesticide application and
not transport by runoff.
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Birds
b. Risk to Terrestrial Organisms
i. Birds, Mammals, and Insects Toxicity and Exposure
1. Toxicity
PBO is practically nontoxic to birds on an acute basis. There were no mortalities
observed at the highest concentration tested for acute oral (2250 mg/kg bw) or for the sub-acute
dietary studies (5620 ppm). EPA did not calculate RQs from the acute toxicity data because no
mortality was seen at very high concentrations indicting minimal adverse acute effects to birds.
From chronic avian toxicity data, aNOEC of 300 ppm was estimated from an avian
reproduction study in which adult and hatchling body weight and food consumption, number of
eggs laid, number of eggs cracked, and eggshell thickness effects were observed at the lowest
observed effect concentration (LOEC) of 1200 ppm.
Mammals
PBO is practically nontoxic to mammals on an acute basis. At higher concentrations
mortalities were observed; therefore, RQs were calculated based on the LD50 of 4570 mg/kg bw.
From chronic mammal toxicity data, a NOAEC of 1,000 ppm (89 mg/kg bw) was
estimated from a 2-generation rat reproductive study in which decreased body weight gain in the
maternal rats and offspring was observed at the LOAEC of 5,000 ppm (469 mg/kg bw).
Beneficial insects
PBO is practically nontoxic to honey bees on an acute oral basis (LD50 > 25 jig/bee).
Due to the uncertainty of estimating environmental exposure to the honey bee, EPA did not
attempt to calculate an RQ.
Table 21: Toxicity reference values for mammals and birds exposed to PBO
Exposure Scenario
Species
Toxicity
Reference Value
Mammals
Acute
Chronic
Rat
(Rattus norvegicus)
Rat
(Rattus norvegicus)
LD50 = 4570 mg/kg bw
Maternal NOAEC = 1000 ppm (89 mg/kg bw)
Maternal LOAEC = 5000 ppm (469 mg/kg)
Offspring NOAEC = 1000 ppm (89 mg/kg bw)
Offspring LOAEC = 5000 ppm (469 mg/kg)
Birds
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Table 21: Toxicity reference values for mammals and birds exposed to PBO
Exposure Scenario
Acute
Acute
Chronic
Species
Bobwhite quail (Colinus
virginianus)
Bobwhite quail (Colinus
virginianus) and
Mallard duck (Anas
platyrhynchos)
Mallard duck
(Anas platyrhynchos)
Toxicity
Reference Value
LD50 > 2250 mg a.i./kg bw
(no mortalities at highest dose)
NOEC = 486 mg a.i./kg bw
Dietary LC50 > 5620 ppm (no mortalities)
NOEC = 1000 ppm (toxicosis)
NOEC = 300 ppm
LOEC = 1200 ppm (adult and hatchling body
weight and food consumption, number of eggs
laid, number of eggs cracked, and eggshell
thickness)
Insects
Acute
Honey Bee
LD50> 25 ug /bee; NOAEC = 25 ug/bee
2. Exposure
Birds and mammals may be exposed after application through oral or dietary exposure to
vegetative plant material or insects when foraging in the treated fields for nesting material or
food. The EFED terrestrial exposure model, T-REX, Version 1.1, is used to estimate exposures
and risks to avian and mammalian species. Input values for avian and mammalian toxicity as
well as use parameters and foliar half-life data are required to run the model. The model
provides estimates of both exposure concentrations and risk quotients (RQs). Specifically, the
model provides estimates of concentrations (maximum and average) of chemical residues in
different types of food sources that may be sources of dietary exposure to avian, mammalian,
reptilian, or terrestrial-phase amphibian receptors. By comparing these estimated concentrations
to acute and chronic toxicity reference values, acute and chronic RQs are calculated.
It was assumed that PBO was applied ten times at the maximum agricultural use rate (0.5
Ib/acre) with 3-day intervals. In the absence of foliage residue data, the default assumption for
the decay rate on foliage (35-day half-life) was used. The maximum EEC on food items
available for wildlife ranged from 58 ppm to 932 ppm. The Hoerger-Kenaga nomogram also has
mean values for residues on food items. The mean EEC on food items available for wildlife
ranges from 17 ppm to 330 ppm.
ii. Bird Risk
Since PBO is practically non-toxic to birds and no mortality was observed at the highest
concentrations, no RQ calculation is necessary for acute exposures to birds.
Chronic risk quotients for birds range from less than 1.0 to 3.1, and exceed the Agency's
level of concern of 1.0 for chronic risks. The EECs used to calculate the RQs are based on an
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application rate of 0.5 Ib ai/A applied ten times during a season at 3-day intervals between
applications.
Using the maximum Kenaga residue EEC, chronic LOCs are exceeded for birds that
consume short grass, tall grass, and broadleaf plants/small insects (RQs range 1.4 to 3.1). Using
the mean Kenaga residue EEC, chronic LOCs are exceeded for birds that consume short grasses
(RQ = 1.1).
iii. Mammal Risk
Acute risk quotients for mammals are all below the Agency's level of concern of 0.1 for
endangered mammalian species.
Chronic risk quotients for mammals range from less than 1.0 to 4.5 for maximum Kenaga
EEC values and from less than 1.0 to 1.6 for mean Kenaga EEC values. The Agency's level of
concern is 1.0 for chronic exposures to mammals.
Using the maximum Kenaga residue EEC, chronic LOCs are exceeded for all mammal
weight classes except for those animals that only consume the fruit/pods/large insects food
category. Using the mean Kenaga residue EEC, chronic LOCs are exceeded for only 15-gram
and 35-gram mammal weight classes that only consume short grass food category.
iv. Non-Target Insect Risks
Currently, the Agency does not estimate RQs for terrestrial non-target insects.
v. Synergistic Risk Effects
Antagonistc Effects with Organophosphate Insecticides
Table 10 in the EFED Risk Assessment (Eckel, September 2005) lists 12
organophosphate (OP) insecticides and one carbamate insecticide that have been tested for PBO
antagonism, that is, whether they are made toxic by simultaneous exposure to PBO.
Nine OP insecticides (azinphos-methyl, chlorpyrifos, diazinon, dioxabenzophos,
fenitrothion, malathion, methyl parathion, parathion, and phenthoate) that require metabolic
activation were less toxic when PBO was present in most sensitive species. The remaining three
OP insecticides (chlorfenvinphos, dichlorvos, mevinphos) did not require metabolic activation,
and did not exhibit decreased toxic effects when mixed with PBO.
PBO's mechanism of action increases the toxicity of insecticides by preventing them
from breaking down by blocking the action of mixed-function oxidase (MFO) enzymes. By the
same mechanism, PBO blocks the action of OP insecticides that require activation by MFO
enzymes to convert them to their more-toxic forms.
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Synergistic Effects with PyrethroidInsecticides
A study comparing the toxic effects to fish of the pyrethroid resmethrin alone, compared
to the toxic effects from resmethrin mixed with PBO concluded that PBO increases the toxicity
of resmethrin to fish following short exposures (6 hours). No differences in toxicity between
synergized and non-synergized resmethrin were detected with longer exposures (24 hours or
longer).
In another study with permethrin it appears that PBO does not increase the toxicity of
permethrin to fish. Any mortality offish in the study seems to be due to permethrin rather than
PBO.
The presence of PBO in a water body may either increase or decrease the toxicity of a
mixture of insecticides, depending on which ones are present. PBO increases the toxicity of
pyrethroids/pyrethrins, decreases the toxicity of OP insecticides that require metabolic activation,
and has no effect on OP insecticides that do not require activation.
3. Ecological Incidents
According to the Ecological Incident Information System (EIIS) database summarizing
6(a)2 incident reports, for PBO, there are three alleged terrestrial animal incidents (bee,
butterflies, and birds), seven alleged plant incidents (mostly ornamental flowers) and one alleged
aquatic organisms incident (fish and invertebrates). The PBO products involved in the incidents
were all applied as co-formulated sprays or through tank mixed mist blowers with pyrethrins,
pyrethroids or rotenone. The Agency can not attribute any of the incidents to PBO by itself since
as an insecticide synergist, it is never used by itself but always with another insecticide.
However, the incidents do show that PBO in conjunction with an insecticide has the potential to
cause adverse effects to aquatic species and to beneficial insect.
4. Endangered Species Concerns
The Agency's screening level assessment results in the determination that PBO will have
no direct acute effects on threatened and endangered estuarine fish, mammals, and birds.
Chronic RQs were estimated up to 3.1 for birds and 4.5 for mammals, and chronic RQs were not
calculated for estuarine/marine fish due to lack of chronic data. The preliminary risk assessment
for endangered species indicates that RQs exceed endangered species LOCs for freshwater fish,
freshwater invertebrates, freshwater amphibians, and estuarine/marine invertebrates. Further,
potential indirect effects to any species dependent upon a species that experiences effects from
use of PBO can not be precluded based on the screening level ecological risk assessment. These
findings are based solely on EPA's screening level assessment and do not constitute "may affect"
findings under the Endangered Species Act.
5. Endocrine Disruption
EPA is required under the FFDCA, as amended by FQPA, to develop a screening
program to determine whether certain substances (including all pesticide active and other
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ingredients) "may have an effect in humans that is similar to an effect produced by a naturally
occurring estrogen, or other such endocrine effects as the Administrator may designate."
Following recommendations of its Endocrine Disrupter and Testing Advisory Committee
(EDSTAC), EPA determined that there was a scientific basis for including, as part of the
program, the androgen and thyroid hormone systems, in addition to the estrogen hormone
system. EPA also adopted EDSTAC's recommendation that the Program include evaluations of
potential effects in wildlife. For pesticide chemicals, EPA will use FIFRA and, to the extent that
effects in wildlife may help determine whether a substance may have an effect in humans,
FFDCA authority to require the wildlife evaluations. As the science develops and resources
allow, screening of additional hormone systems may be added to the Endocrine Disrupter
Screening Program (EDSP).
In the available ecological toxicity studies on PBO, an avian reproduction study shows
that PBO may cause decreases in adult and hatchling body weight and food consumption,
number of eggs laid, and eggshell thickness. In addition, PBO may cause increases in number of
eggs cracked. When additional appropriate screening and/or testing protocols being considered
under the Agency's EDSP have been developed, PBO may be subjected to further screening
and/or testing to better characterize effects related to endocrine disruption.
IV. Risk Management, Reregistration, and Tolerance Reassessment Decision
A. Determination of Reregistration Eligibility and Tolerance Reassessment
Section 4(g)(2)(A) of FIFRA calls for the Agency to determine, after submission of
relevant data concerning an active ingredient, whether or not products containing the active
ingredient are eligible for reregi strati on. The Agency has previously identified and required the
submission of the generic data to support reregi strati on of products containing PBO. The
Agency has completed its review of these generic data, and has determined that the data are
sufficient to support reregi strati on of all products containing PBO.
The Agency has completed its assessment of the dietary, occupational, residential, and
ecological risk associated with the use of pesticide products containing the active ingredient
PBO. Based on a review of these data and on public comments on the Agency's assessments for
the active ingredient PBO, the Agency has sufficient information on the human health and
ecological effects to make decisions as part of the tolerance reassessment process under FFDCA
and reregi strati on process under FIFRA, as amended by FQPA. The Agency has determined that
products containing PBO are eligible for reregi strati on provided that: (i) the risk mitigation
measures outlined in this document are adopted and (ii) label amendments are made to reflect
these measures. Label changes are described in Section V. Appendix A summarizes the uses of
PBO that are eligible for reregi strati on. Appendix B identifies the generic data requirements that
the Agency reviewed as part of its determination of reregi strati on eligibility of PBO, and lists the
submitted studies that the Agency found acceptable. Data gaps are identified as generic data
requirements that have not been satisfied with acceptable data.
Based on its evaluation of PBO, the Agency has determined that PBO products, unless
labeled and used as specified in this document, would present risks inconsistent with FIFRA and
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FQPA. Accordingly, should a registrant fail to implement any of the reregi strati on requirements
identified in this document, the Agency may take regulatory action to address the risk concerns
from the use of PBO. If all changes outlined in this document are incorporated into the product
labels, then all current risks for PBO will be adequately mitigated for the purposes of this
determination. Once an Endangered Species assessment is completed, further changes to these
registrations may be necessary as explained under "Endangered Species Concerns" above.
B. Regulatory Position
Through the Agency's public participation process, EPA worked with stakeholders and
the public to reach the regulatory decisions for PBO. EPA released its PBO preliminary risk
assessments for public comment on April 27, 2005 for a 60-day public comment period (Phase 3 of
the 6 Phase public participation process). Where appropriate, the PBO risk assessments were revised
in response to the comments received, and the assessments were released for an additional 60 day
public comment period on September 21,2005 (Phase 5 of the 6 Phase public participation process).
During both public comment periods, the Agency received comments from the PBO Task Force
II, stakeholder groups, such as the American Mosquito Control Association, State and Local
government entities in California, California Water Boards, Publicly Owned Treatment Works,
Mosquito and Vector Control Districts, and several private citizens. All of the preliminary and
revised PBO risk assessments, public comments, response to comments, and this RED document
are available in the public docket (OPP-2005-0043) at EPA's docket and in the EPA's electronic
docket at www.regulations.gov.
1. Food Quality Protection Act Findings
a. "Risk Cup" Determination
As part of the FQPA tolerance reassessment process, EPA assessed the risks associated
with PBO. EPA has determined that risk from dietary (food + water) exposure is within its own
"risk cup." An aggregate assessment was conducted for PBO for exposures through dietary and
residential exposures. The Agency has determined that the human health risks from these
combined exposures are within acceptable levels. In other words, EPA has concluded that the
tolerances for PBO meet FQPA safety standards. In reaching this determination, EPA has
considered the available information on the special sensitivity of infants and children, as well as
aggregate exposure from food, drinking water, and residential sources.
b. Determination of Safety to U.S. Population
The Agency has determined that the established tolerances for PBO, with amendments
and changes as specified in this document, meet the safety standards under the FQPA
amendments to section 408(b)(2)(D) of the FFDCA, as amended by FQPA, and that there is a
reasonable certainty no harm will result to the general population or any subgroup from the use
of PBO. In reaching this conclusion, the Agency has considered all available information on the
toxicity, use practices, and the environmental behavior of PBO. As discussed in Section III, the
acute, chronic, short-term, intermediate-term, and long-term risks from food, drinking water, and
residential exposures do not exceed the Agency's level of concern.
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c. Determination of Safety to Infants and Children
EPA has determined that the established tolerances for PBO, with amendments and
changes as specified in this document, meet the safety standards under the FQPA amendments to
section 408(b)(2)(C) of the FFDCA, that there is a reasonable certainty of no harm for infants
and children. The safety determination for infants and children considers the toxicity, use
practices and environmental behavior of a chemical for the general population, but also takes
into account the possibility of increased dietary exposure due to the specific consumption
patterns of infants and children, as well as the possibility of increased susceptibility to the toxic
effects of PBO residues in this population subgroup.
In determining whether or not infants and children are particularly susceptible to toxic
effects from exposure to residues of PBO, the Agency considered the completeness of the hazard
database for developmental and reproductive effects, the nature of the effects observed, and other
information. The FQPA Safety Factor has been reduced to IX, because there are no residual
uncertainties for pre- and/or post-natal toxicity, exposure is not underestimated, and there is no
evidence of increased susceptibility.
2. Endocrine Disrupter Effects
EPA is required under the FFDCA, as amended by FQPA, to develop a screening
program to determine whether certain substances (including all pesticide active and other
ingredients) "may have an effect in humans that is similar to an effect produced by a naturally
occurring estrogen, or other endocrine effects as the Administrator may designate." Following
recommendations of its Endocrine Disrupter Screening and Testing Advisory Committee
(EDSTAC), EPA determined that there was a scientific basis for including, as part of the
program, the androgen and thyroid hormone systems, in addition to the estrogen hormone
system. EPA also adopted EDSTAC's recommendation that EPA include evaluations of
potential effects in wildlife. For pesticides, EPA will use FIFRA and, to the extent that effects in
wildlife may help determine whether a substance may have an effect in humans, FFDCA
authority to require the wildlife evaluations. As the science develops and resources allow,
screening of additional hormone systems may be added to the Endocrine Disrupter Screening
Program (EDSP).
In the available human health toxicity studies on PBO, there was no lexicologically
significant evidence of endocrine disrupter effects. In the available ecological toxicity studies on
PBO, an avian reproduction study shows that PBO may cause decreases in adult and hatchling
body weight and food consumption, number of eggs laid, and eggshell thickness. In addition,
PBO may cause increases in number of eggs cracked.
When the appropriate screening and/or testing protocols being considered under the
EDSP have been developed, PBO may be subject to additional screening and/or testing.
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3. Cumulative Risks
The Food Quality Protection Act (FQPA) requires that the Agency consider available
information concerning the cumulative effects of a particular pesticide's residues and other
substances that have a common mechanism of toxicity. The reason for consideration of other
substances is due to the possibility that low-level exposures to multiple chemical substances that
cause a common toxic effect by a common toxic mechanism could lead to the same adverse
health effect as would a higher level of exposure to any of the substances individually. Unlike
other pesticides for which EPA has followed a cumulative risk approach based on a common
mechanism of toxicity, EPA has not made a common mechanism of toxicity finding for PBO and
any other substances. For information regarding EPA's efforts to determine which chemicals
have a common mechanism of toxicity and to evaluate the cumulative effects of such chemicals,
see the policy statements released by EPA's Office of Pesticide Programs concerning common
mechanism determinations and procedures for cumulating effects from substances found to have
a common mechanism on EPA's website at http://www.epa.gov/pesticides/cumulative/.
C. Tolerance Reassessment Summary
Table 22, 23, and 24 provide a summary of the PBO tolerance reassessment decision.
Further tolerance explanation is provided after the table.
All references that indicate use in combination with another active ingredient, such as
pyrethrins or n-octyl bicycloheptene dicarboximide (MGK-264), are removed, or decoupled from
the tolerance expressions for PBO. All tolerances established for use on bags are being revoked
as the last active product supporting this use was cancelled on October 10, 1989, and there are no
data to support this use. The 40 CFR should be updated to reflect all of these changes as
summarized below.
Table 22: 40 CFR Changes for PBO
Current 40 CFR Citation
§ 180. 127(a)(2)(i) all parts
§ 180. 127(a)(2)(ii) all parts
§180.127(a)(2)(iii)(A)
§180.127(a)(2)(iii)(B)
§180.127(a)(2)(iii)(C)
Action
Remove
Remove
Retain
Remove
Retain
Comment
This section refers to PBO being used in conjunction with
pyrethrins. All references to use with multiple chemicals
is being removed from the CFR.
This section refers to PBO being used in conjunction with
pyrethrins and MGK-264. All references to use with
multiple chemicals is being removed from the CFR.
This tolerance for cereal grain will be kept as indicated in
Table 23 below.
Recodify under §180.127 (a)(2)
This is a tolerance for use on bags. The last registration
for this use was cancelled in 1989 and there are no data to
support this use.
This citation refers to another part of the CFR for MGK-
264 that is being revised. In order to clarify the statement
it will be stated in its entirety here. The exact statement
and section number are indicated in Table 23 below.
Recodify under §180.127 (a)(3)
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§180.127(a)(2)(iii)(D)
§180.127(a)(2)(iii)(E)
§180.127(a)(2)(iv)
§180.127(a)(2)(v)
§ 180. 127(a)(3) all parts
Remove
Remove
Remove
Retain
Remove
This is a tolerance for use on bags. The last registration
for this use was cancelled in 1989 and there are no data to
support this use.
This refers to other sections that are being removed, so
this section is not relevant once the other parts are revised.
Old language not used in the CFR currently.
Recodify under §180.127 (a)(4)
This is a tolerance for use on bags. The last registration
for this use was cancelled in 1989 and there are no data to
support this use.
Table 23: Tolerance Reassessment Summary for PBO
Commodity
Current
Tolerance
(ppm)
Tolerance
Reassessment
(ppm)
Comment
[Correct Commodity Definition]
Tolerances Listed Under 40 CFR §180.127 (a)(l)
Almond, postharvest
Apple, postharvest
Barley, postharvest
Bean, postharvest
Birdseed, mixtures, postharvest
Blackberry, postharvest
Blueberry (huckleberry),
postharvest
Boysenberry, postharvest
Buckwheat, grain, postharvest
Cattle, fat
Cattle, meat byproducts
Cattle, meat
Cherry, postharvest
Cocoa bean, postharvest
Coconut, copra, postharvest
Corn (including popcorn),
postharvest
Cottonseed, postharvest
Crabapple, postharvest
Currant, postharvest
Dewberry, postharvest
Egg
Fig, postharvest
Flaxseed, postharvest
8
8
20
8
20
8
8
8
20
0.1 (N)
0.1 (N)
0.1 (N)
8
8
8
20
8
8
8
8
1
8
8
TBD1
TBD
TBD
TBD
TBD
TBD
TBD
TBD
TBD
TBD
TBD
TBD
TBD
TBD
TBD
TBD
TBD
TBD
TBD
TBD
TBD
TBD
TBD
[Barley, grain, postharvest}
[Bean, succulent, postharvest]
[Blueberry, postharvest}
[Cocoa bean, dried bean, postharvest}
[Corn, field and pop, grain, postharvest}
[Cotton, undelinted seed, postharvest}
[Flax, seed, postharvest}
1 TBD = To be determined. EPA notes that while additional data are needed to support certain tolerances,
conservative assumptions have been used in the risk assessment and no dietary risks have been identified. Thus,
EPA considers the tolerances reassessed.
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Table 23: Tolerance Reassessment Summary for PBO
Commodity
Goat, fat
Goat, meat byproducts
Goat, meat
Gooseberry, postharvest
Grape, postharvest
Guava, postharvest
Hog, fat
Hog, meat byproducts
Hog, meat
Horse, fat
Horse, meat byproducts
Horse, meat
Loganberry, postharvest
Mango, postharvest
Milk fat (reflecting negligible
residues in milk)
Muskmelon, postharvest
Oat, postharvest
Oranges, postharvest
Peach, postharvest
Peanut (with shell removed),
postharvest
Pear, postharvest
Pea, postharvest
Pineapple, postharvest
Plum, prune, fresh, postharvest
Potato, postharvest
Poultry, fat
Poultry, meat byproducts
Poultry, meat
Raspberry, postharvest
Rice, postharvest
Rye, postharvest
Sheep, fat
Sheep, meat byproducts
Current
Tolerance
(ppm)
0.1 (N)
0.1 (N)
0.1 (N)
8
8
8
0.1 (N)
0.1 (N)
0.1 (N)
0.1 (N)
0.1 (N)
0.1 (N)
8
8
0.25
8
8
8
8
8
8
8
8
8
0.25
3
3
3
8
20
20
0.1 (N)
0.1 (N)
Tolerance
Reassessment
(ppm)
TBD
TBD
TBD
TBD
TBD
TBD
TBD
TBD
TBD
TBD
TBD
TBD
TBD
TBD
TBD
TBD
TBD
TBD
TBD
TBD
TBD
TBD
TBD
TBD
0.25
TBD
TBD
TBD
TBD
TBD
TBD
TBD
TBD
Comment
[Correct Commodity Definition]
[Oat, grain, postharvest}
[Orange, sweet, postharvest]
[Peanut, nutmeat, postharvest}
[Pea, dry, seed, postharvest}
The reassessed tolerance is based on data
reflecting residues of PBO per se.
Additional data may be required if PBO
metabolites are included in the tolerance
expression
[Rice, grain, postharvest}
[Rye, grain, postharvest}
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Table 23: Tolerance Reassessment Summary for PBO
Commodity
Sheep, meat
Sorghum, grain, postharvest
Sweet potato, postharvest
Tomato, postharvest
Walnut, postharvest
Wheat, postharvest
Current
Tolerance
(ppm)
0.1 (N)
8
0.25
8
8
20
Tolerance
Reassessment
(ppm)
TBD
TBD
0.25
TBD
TBD
TBD
Comment
[Correct Commodity Definition]
The preharvest use on stored raw sweet
potatoes are supported by residue data
translated from potatoes.
[Wheat, grain, postharvest}
Tolerance Listed Under 40 CFR §180.127(a)(2)(iii)(A)
Grains, Cereal, Milled Fractions
10
10
Tolerance Listed Under 40 CFR §180.127(a)(2)(iii)(B)
Stored Dried Food (Multiwall
paper bags (50 Ibs +))
10
Revoke
This is a tolerance for use on bags. The last
registration for this use was cancelled in
1989 and there are no data to support this
use.
Tolerance Listed Under 40 CFR §180.127(a)(2)(iii)(C)
Processed Food (food handling
establishments)
10
10
Decouple pyrethrins tolerance from MGK-
264 and PBO.
The new tolerance should be stated as:
"A tolerance of 10 ppm is established for
residues of the insecticide synergist
piperonyl butoxide in or on all food items in
food handling establishments where food
and food products are held, processed,
prepared and/or served. Food must be
removed or covered prior to use."
Tolerance Listed Under 40 CFR §180.127(a)(2)(iii)(D)
Processed Food (Cotton bags (50
Ibs +) with waxed paper liners
containing Stored Dried Food
(4% fat or less))
10
Revoke
This is a tolerance for use on bags. The last
registration for this use was cancelled in
1989 and there are no data to support this
use.
Tolerance Listed Under 40 CFR §180.127(a)(3)(iii)(A)
Processed Food (Stored Feed
(Dried Feed from use on outer
ply of multiwall paper bags 50
Ibs or more))
10
Revoke
This is a tolerance for use on bags. The last
registration for this use was cancelled in
1989 and there are no data to support this
use.
Tolerance Listed Under 40 CFR §180.127(a)(3)(iii)(B)
Stored Feed (Dried Feed
(containing 4% fat or less) from
use on cotton bags with waxed
paper liners 50 Ibs or more)
10
Revoke
This is a tolerance for use on bags. The last
registration for this use was cancelled in
1989 and there are no data to support this
use.
Tolerances Listed Under 40 CFR §180.905(a)(6)
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Table 23: Tolerance Reassessment Summary for PBO
Commodity
Raw Agricultural Commodities
Current
Tolerance
(ppm)
Exemption
Tolerance
Reassessment
(ppm)
Revoke
Comment
[Correct Commodity Definition]
Formerly established under 180.1001 (b).
The Agency will not revoke this tolerance
immediately, but will issue a DCI for the
data. When the data have been reviewed
and approved by the Agency, the
appropriate crop group tolerances will be
established concomitant with revocation of
the exemption.
Table 24: PBO Tolerances to be Established Under 40 CFR §180.127
Commodity
Current
Tolerance
(ppm)
Tolerance
Reassessment
(ppm)
Comment
[Correct Commodity Definition]
Tolerances to be Established Under CFR §180.127(a)(l)
Aspirated grain fractions
None
TBD1
1 TBD = To be determined. EPA notes that while additional data are needed to support certain tolerances,
conservative assumptions have been used in the risk assessment and no dietary risks have been identified.
Tolerance exemption under CFR S180.1001(b)(4)
PBO is currently exempt from the requirements of tolerances when applied to growing
crops in accordance with good agricultural practices [40 CFR §180.1001(b)(4)]. Based on the
results of limited field trials reflecting preharvest uses, EPA recommends for the revocation of
this tolerance exemption. The results of preharvest trials show detectable and variable residues
of PBO per se (or PBO plus PBO metabolites, assayed collectively as hydroxymethyl
dihydrosafrol) in/on nearly all raw agricultural commodities following applications of one
formulation class (EC) at l.OX the maximum seasonal rate the PBO Task Force II wishes to
support for preharvest uses. Additional residue data reflecting preharvest uses will be required to
confirm the tolerance reassessment. When the requested data have been evaluated, EPA will
recommend for the revocation of the tolerance exemption in 40 CFR § 180.100 l(b)(4)
concomitant with the establishments of crop group tolerances, if appropriate, in 40 CFR
§180.127 to support all uses.
Tolerances Established Under CFR §180.127
Tolerances are established in 40 CFR §180.127 for residues of PBO per se
[(butylcarbityl)(6-propyl piperonyl)ether] in/on: (i) plant commodities resulting from
postharvest uses; (ii) livestock commodities; and (iii) food/feed items while in storage areas.
The CAS name for PBO is: 5-[[2-(2-butoxyethoxy)ethoxy]methyl]-6-propyl-l,3-benzodioxole.
EPA recommends the chemical name of PBO listed in 40 CFR §180.127 be changed to the CAS
name. The tolerance expression will be updated in the CFR to read as follows: "Tolerances for
residues of the insecticide synergist piperonyl butoxide [5-[[2-(2-butoxyethoxy)ethoxy]methyl]-
6-propyl-l,3-benzodioxole] are established in or on the following food commodities:". A list of
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tolerances established for PBO along with our recommendations of changes to correct
commodity definitions are presented in Table 22, 23, and 24.
The qualitative nature of the residue in plants has not yet been determined although the
registrants have submitted acceptable plant metabolism studies conducted on three dissimilar
crops (lettuce, cotton, and potatoes). The nature of the residue in livestock (poultry and
ruminants) remains inadequately understood because additional data are required to upgrade
previously submitted studies. The EPA Metabolism Assessment Review Committee (MARC)
concluded the terminal residue of concern in plants and livestock (i.e., residues that need to be
regulated or included in the tolerance expression) is PBO/>er se.
An improved method, HPLC/fluorescence method has been proposed to replace the
existing colorimetric method listed in PAM Volume II for the enforcement of plant commodity
tolerances. The new method can separately measure residues of PBO/>er se and PBO
metabolites collectively determined as hydroxymethyl dihydrosafrol (HMDS). The
HPLC/fluorescence method has been subjected to a successful independent laboratory validation
and has been forwarded to ACL/BEAD for a method validation by Agency chemists. There are
also several methods listed in PAM Volume II which can measure residues of PBO/>er se in
livestock commodities.
The PBO tolerances for plant commodities, resulting from post-harvest uses [40 CFR
§180.127(a)(l)], range from 0.25 ppm (potato and sweet potato) to 20 ppm (most cereal grains).
The available data are inadequate to support many of the established tolerances resulting from
post-harvest uses (except those uses for potato and sweet potato), and additional data are
required for tolerance reassessment. The required post-harvest data for cereal grains will be
translated to birdseed mixture since the use rate for birdseed mixture and cereal grains are
identical.
PBO tolerances of 0.25 ppm for milk fat, reflecting negligible residues in milk, and 0.1
ppm for the fat, meat, and meat byproducts of cattle, goats, hogs, horses, and sheep are
established [40 CFR §180.127(a)(l)]. Tolerances of 1 ppm for eggs and 3 ppm for the fat, meat,
and meat byproducts of poultry are also established [40 CFR §180.127(a)(l)]. Additional data
are required to confirm the livestock commodity tolerances and to estimate residues expected
from all possible exposure scenarios which include direct application to livestock, premise
treatment, and oral treatment.
The remainder of tolerances and tolerance exemptions established in CFR §180.127
pertain to uses of PBO in food/feed storage areas.
- According to 40 CFR §180.127(a)(2)(i), PBO may be safely used in combination with
pyrethrins for control of insects when used according to conditions specified in the same 40
CFR section.
- According to 40 CFR §180.127(a)(2)(ii), PBO may be safely used in combination with
pyrethrins and N-octylbicycloheptene dicarboximide for insect control in accordance with 21
CFR 178.3730.
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- According to 40 CFR §180.127(a)(2)(iii), a tolerance of 10 ppm is established for residues
of PBO/?er se in/on: (A) milled fractions derived from cereal grains when present therein as
a result of its use in cereal grain mills and in storage areas for milled cereal grain products;
(B) dried foods when present as a result of migration from its use on the outer ply of
multiwall paper bags of 50 pounds or more capacity; (C) foods treated in accordance with 21
CFR 178.3730; (D) dried foods that contain 4 % fat, or less, when present as a result of
migration from its use on the cloth of cotton bags of 50 pounds or more capacity constructed
with waxed paper liners; and (E) foods from treated food processing and storage areas
provided the food is removed or covered prior to such use.
- According to 40 CFR §180.127(a)(2)(iv), to assure safe use of the pesticide, its label and
labeling shall conform to that registered with the U.S. Environmental Protection Agency, and
it shall be used in accordance with such label and labeling.
- According to 40 CFR §180.127(a)(2)(v), where tolerances are established on both raw
agricultural commodities and processed foods made therefrom, the total residues of PBO
in/on the processed food shall not be greater than that permitted by the larger of the two
tolerances.
- According to 40 CFR §180.127(a)(3), PBO may be safely used in accordance with the
following prescribed conditions: (i) It is used or intended for use in combination with
pyrethrins for control of insects: (A) On the outer ply of multiwall paper bags of 50 pounds
or more capacity in amounts not exceeding 60 milligrams per square foot; or (B) On cotton
bags of 50 pounds or more capacity in amounts not exceeding 55 milligrams per square foot
of cloth. Such treated bags are constructed with waxed paper liners and are to be used only
for dried feeds that contain 4 percent fat or less; or (ii) It is used in combination with
pyrethrins, whereby the amount of PBO is equal to 10 times the amount of pyrethrins in the
formulation. Such treated bags are to be used only for dried feeds.
The tolerance regulations contained in 40 CFR §180.127(a)(2)(i) and 40 CFR
§180.127(a)(2)(ii) establish that PBO may be safely used in combination with pyrethrins and N-
octylbicycloheptene dicarboximide, respectively, for control of insects in food/feed processing
areas and food/feed storage areas provided that the food/feed is removed or covered prior to use
of the products. EPA concludes that no additional data for PBO are required to maintain the
above tolerance regulations. This conclusion does not apply to pyrethrins and N-
octylbicycloheptene dicarboximide because the labels for these pesticide chemicals were not
examined in the generation of this Residue Chapter.
Adequate data depicting the magnitude of residues of PBO per se in food-handling
establishments and food storage areas are available. These data indicate that the established
tolerance of 10 ppm will not be exceeded in representative food commodities and surfaces that
had been covered during space, contact, and intermittent spray aerosol treatments using
representative soluble concentrate/liquid and pressurized liquid formulations. The submitted
PBO master label provides adequate instructions which specify that food should be removed or
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covered during treatment, and that all food processing surfaces should be covered during
treatment or thoroughly cleaned before use.
No data are available to support uses of PBO on foods stored in multi-walled paper or
cloth bags. The last active product with this use was cancelled in October 15, 1989. Therefore,
the stored dried food tolerance in section 180.127(a)(2)(iii)(B), the two processed food tolerances
in sections 180.127(a)(2)(iii)(D) and 180.127(a)(3)(iii)(A), and the stored feed tolerance in
section 180.127(a)(3)(iii)(B) should be revoked.
Tolerances to be Established Under 40 CFR §180.127
The data requirements to support pre-harvest uses, that are recommended in this RED
Chapter, are designed to support the establishments of crop group tolerances. Therefore, several
crop group tolerances, if appropriate, will likely be proposed when the requested data have been
reviewed. In addition, a tolerance for aspirated grain fraction needs to be proposed upon receipt
of the requested residue data for this commodity.
Codex/International Harmonization
The Codex Alimentarius Commission has established several maximum residue limits
(MRLs) for residues of PBO. The Codex MRLs are expressed in terms of PBO per se which is
identical to the current U.S. tolerance expression. A numerical comparison of the Codex MRLs
and the corresponding current U.S. tolerances for PBO is presented in Table 25. Canadian
MRLs are presented in Table 26. Following completion of the RED the Agency will take steps
to determine if harmonization of U.S. tolerances and certain Codex and Canadian MRLs can be
achieved.
Table 25: Codex MRLs and Applicable U.S. Tolerances for PBO
Codex
Commodity, As Defined
Cattle, kidney
Cattle liver
Cattle meat
Cereal grains
Citrus fruits
Citrus juice
Dried fruits
Eggs
MRL (mg/kg)
0.3
1
5 (fat)
30 (Po 2)
5
0.05
0.2 (Po)
1
Current U.S.
Tolerance, ppm
0. 1 for meat byproducts of cattle, goat,
hog, horse, and sheep
0.1 for meat of cattle, goat, hog, horse,
and sheep
8 ppm for oat and sorghum resulting
from postharvest uses; 20 ppm for
barley, buckwheat, corn, (including
popcorn), rice, rye, and wheat
resulting from postharvest uses
8 ppm for oranges resulting from
postharvest uses
1
2 Po = Postharvest
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Table 25: Codex MRLs and Applicable U.S. Tolerances for PBO
Codex
Commodity, As Defined
Fruiting vegetables, cucurbits
Kidney of cattle, goats, pigs, and sheep
Lettuce, leaf
Liver of cattle
Maize, oil, crude
Meat (mammalian) fat
Milks
Mustard greens
Pea hay
Pea vines (green)
Peanut, whole
Peppers
Poultry meat
Poultry, edible offal
Pulses
Radish leaves
Root and tuber vegetables
Spinach
Tomato
Tomato juice
Wheat
Wheat bran, unprocessed
Wheat flour
Wheat germ
Wheat wholemeal
MRL (mg/kg)
1
0.2 (excluding cattle)
50
1
80 (Po)
2 (excluding cattle meat)
0.05
50
200
400
l(Po)
2
7 (fat)
10
0.2 (Po)
50
0.5
50
2
0.3
10 (Po)
80 (Po)
10 (Po)
90 (Po)
30 (Po)
Current U.S.
Tolerance, ppm
0. 1 for meat byproducts of cattle, goat,
hog, horse, and sheep
0. 1 for meat byproducts of cattle, goat,
hog, horse, and sheep
0. 1 for fat of cattle, goat, hog, horse,
and sheep
0.25 ppm for milk fat
8 ppm for pea resulting from
postharvest uses
8 ppm for peanut resulting from
postharvest uses
o
J
o
J
0.25 ppm for potato and sweet potato
resulting from postharvest uses
8 ppm resulting from postharvest uses
20 ppm for barley, buckwheat, corn
(including popcorn), rice, rye, and
wheat resulting from postharvest uses
Po = Postharvest
Table 26: Canadian MRLs for PBO
Commodity, As Defined
Raw Cereals
MRL (ppm)
20
Current U.S.
Tolerance, ppm
8 ppm for oat and sorghum resulting
from postharvest uses; 20 ppm for
barley, buckwheat, corn, (including
popcorn), rice, rye, and wheat
resulting from postharvest uses
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Table 26: Canadian MRLs for PBO
Commodity, As Defined
Almonds, apples, beans, blackberries,
blueberries, boysenberries, cherries, cocoa
beans, copra, crabapples, currants,
dewberries, figs, gooseberries, grapes,
guavas, huckleberries, loganberries,
mangoes, muskmelons, oranges,
peaches/nectarines, peanuts, pears, peas,
pineapple, plums, raspberries, tomatoes,
and walnuts.
Dried codfish
MRL (ppm)
8
1
Current U.S.
Tolerance, ppm
8 ppm from postharvest uses
none
Updated 40 CFR
The 40 CFR should be updated to incorporate all the changes specified above. Once
these changes are made the CFR should be in the format listed below.
§180.127 Piperonyl butoxide; tolerances for residues
(a)General.
(1) Tolerances for residues of the insecticide synergist piperonyl butoxide [5-
[[2-(2-butoxyethoxy)ethoxy]methyl]-6-propyl-l,3-benzodioxole] are established
in or on the following food commodities:
[Insert list as specified in the tables above after all data to support these
tolerances have been submitted and reviewed.]
(2) A tolerance of 10 ppm is established for residues of the insecticide synergist
piperonyl butoxide in or on milled fractions derived from Grain, cereal when
present as a result of its use in cereal grain mills and in storage areas for milled
cereal grain products.
(3) A tolerance of 10 ppm is established for residues of the insecticide synergist
piperonyl butoxide in or on all food items in food handling establishments where
food and food products are held, processed, prepared and/or served. Food must
be removed or covered prior to use.
(4) Where tolerances are established on both the raw agricultural commodities
and processed foods made there-from, the total residues of piperonyl butoxide in
or on the processed food shall not be greater then that permitted by the larger of
the two tolerances.
(b) Section 18 emergency exemptions.
[Reserved]
(c) Tolerances with regional registrations.
[Reserved]
(d) Indirect or inadvertent residues.
[Reserved]
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D. Regulatory Rationale
The Agency has determined that PBO is eligible for reregi strati on provided that the risk
mitigation measures and label amendments specified in this RED are implemented. The
following is a summary of the rationale for managing risks associated with the use of PBO.
1. Human Health Risk
a. Dietary (Food Only) Risk Mitigation
Acute Risk
Acute dietary (food only) risk does not exceed the Agency's level of concern; acute
dietary risk estimates are 6% of the aPAD for the general U.S. population, and 20% for children
1-2 years old, the subgroup most exposed. Therefore, no mitigation is necessary for this
scenario.
Chronic Risk
The chronic dietary (food and drinking water) risk is below the Agency's level of
concern; risk estimated are 5% of the cPAD for the general U.S. population, and 12% of the
cPAD for children 1-2 years old, the most exposed subpopulation. Therefore, no mitigation is
necessary for this scenario.
b. Residential Risk Mitigation
i. Handler
In the residential handler exposure assessment a number of scenarios were assessed to
estimate the exposure to homeowners handling products containing PBO. From the results of the
residential handler assessment, there are no residential risks of concern when PBO is mixed,
loaded, applied, or handled by homeowners. Therefore, no mitigation is necessary for these
scenarios.
ii. Post-Application
A number of post-application residential scenarios were assessed either quantitatively or
qualitatively for adults and children exposed to PBO indirectly after application. Of these
scenarios, three post-application residential scenarios assessed were potentially of concern to the
Agency including: 1) broadcast dust applications to carpets, 2) applications from indoor metered
release devices, and 3) applications from outdoor residential misting systems. To address the
potential risks associated with these post-application scenarios, the following mitigation
measures are to be implemented.
Dusts - Broadcast Applications to Carpets
Applying dusts to carpets over a wide area can lead to exposure to children through
incidental oral exposures. Most of the labels containing this type of application indicate that
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the dust needs to be vacuumed after application. The Agency has concerns form the potential
incidental oral exposure children could have from this type of broadcast application to large
carpeted areas since there is no information to determine how much PBO is removed from the
carpet after vacuuming and an unknown amount of dust available for exposure to children. To
reduce exposure to children from broadcast dust applications to carpets, the PBOTF II has
agreed to restrict carpet applications to spot treatments no greater than 3 feet by 3 feet in area.
PBO is also used on turf, and so an incidental oral assessment was conducted for use on
turf which is considered a conservative risk estimate including 3 separate incidental oral
exposure activities and assumes the exposures occur simultaneously. The turf scenario
methodology, which has been peer reviewed and is better understood than the carpet dust
scenario, includes incidental oral exposure to pesticide on turf from (1) hand to mouth
activities, (2) object to mouth activities, and (3) ingesting soil particles. The aggregate of all
three of these incidental oral turf exposures is above the Agency's target MOE of 100 with an
MOE of 4800. Given the conservative nature of the turf exposure scenario, it is unlikely that
the magnitude and frequency of exposure to small spot treatments (3 sq ft) of dust formulations
of PBO would result in exposure estimates equal or greater than estimated for the residential
lawns. Since there are no incidental oral risks of concern from the turf scenario, and the
PBOTFII has agreed to reduce the amount of potential exposure to children by restricting
applications to spots only, the Agency is not requiring and additional data at this time.
Indoor Metered Release Devices
There are potential risk concerns for post-application short- and intermediate-term
exposures following indoor applications with metered release devices. The MOEs range from 12
to 240 and are less than the target MOE of 300. The risk calculations for the metered release
scenarios are conservative because it was assumed that the aerosol spray would remain airborne
until they were removed by ventilation and the effect of aerosol spray settling was not
considered. Aerosol spray settling could be a major factor depending upon the aerosol droplet
size and rate of evaporation. Information regarding the aerosol droplet size and evaporation rate
could be used to refine the risks, particularly for the residential scenarios where the ventilation
removal rate is probably slower than the settling rate.
The master label indicates that the metered release system application rate of 0.05 Ib
ai/1000 ft3/day can be used in domestic dwellings and indoor sites. Commercially available
aerosol dispensers that appear to be intended for the residential areas apply much less than the
master label rate. These dispensers apply aerosols from 6.4 oz cans at 15 minute intervals and
each can will deliver approximately 3000 applications in a month to a 6000 ft3 space. The
application rate for these dispensers is approximately 0.00013751b ai/1000 ft3/day if continuous
operation is assumed.
Therefore, to reduce the risks to bystanders of sensitive population, the PBOTFII has
agreed to prohibit the use in residential areas and remove the following use sites from their
metered release device product labels: day care centers, nursing homes, and schools.
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Outdoor Residential Misting Systems
As stated in Section 3, the Agency considered post-application exposure to adults and
toddlers who are exposed to PBO from an outdoor residential misting system pesticide
application. These systems are fairly new to the pesticide market, and vary in their system
design. Based on available information at the time and outreach to the PBO registrants, other
stakeholders, and review of labels currently registered for use in these systems, the Agency used
the following assumptions in the PBO risk assessment:
The spray droplets would be inhaled over a period of 5 hours for adults or 3 hours for
toddlers, based on information from the Exposure Factors Handbook (EPA, 1997) on how
much time individuals spend outside.
The initial concentration is based upon instantaneous release and mixing into a fixed space
with a height of 8 feet.
The exposure is assumed to encompass 2 spray events that occur in the morning or evening.
Based on these assumptions, the Agency has identified a potential risk of concern for
toddlers over the short-/intermediate-term exposure duration. The target short-/intermediate-
term inhalation MOE is 300, and the toddler bystander assessment calculated an MOE of 190.
The inhalation exposure durations used for the mosquito mister scenarios (5 hours/day for
adults, 3 hours/day for toddlers) represent the 95th percentile values for time spent outdoors at a
restaurant/picnic area (USEPA, 1997). During this exposure period the individual is assumed to
be exposed to 2 spray events each lasting a period of 1 minute. Although this spray duration is
considered reasonable, lower spray durations (i.e., 20- or 30-second durations) may be more
representative of actual system rates, particularly for extended exposure durations. Standard
label language for use rates could provide a more refined risk assessment. Currently, the labels
do not specify the maximum daily application rates.
The Consumer Specialty Products Association (CSPA) submitted a discussion paper
outlining some use information associated with these outdoor residential misting systems.
Mosquito mister risks were calculated based on automatic applications of 4 sprays per day. It
was noted in the CSPA discussion paper that the systems could be manually activated by the
homeowner to apply additional sprays. Although re-filling and maintenance costs would likely
limit homeowner use, label language indicating appropriate daily spray cycles and maximum
daily application rates is also needed to address current concerns over excessive use.
Therefore, to mitigate the risks for toddler bystander exposure from intermediate-term
outdoor residential misting systems, the PBOTF II has agreed to restrict the maximum allowable
daily rate to 0.00058 Ibs PBO/1000 cubic feet/day, which is the rate where risks to children are
not a concern to the Agency. Further, the PBOTF II has agreed to submit data to allow the
Agency to better understand these systems and refine the risk assessment. Information on use
and usage of outdoor residential misting systems, as well as air concentration and droplet size
data will be submitted. The PBOTF II has also agreed to add the label statements listed in the
label table in Section V of this document. These label statements will restrict the maximum
allowable daily rate that can be applied, specify how the systems should be installed to reduce
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off-site drift, and specify measures to make the system reservoirs less accessible to children or
other individuals.
Future Steps for Outdoor Residential Misting Systems
The distribution or sale, and use of pesticides in outdoor residential misting systems are
subject to several statutory requirements. At this time, PBO, pyrethrins, and permethrin appear
to be the only chemicals known to be used in outdoor residential misting systems; however, it is
possible that other pesticide registered for residential outdoor use might also be used in similar
systems. Section 2(ee)(3) of FIFRA permits the use of any application methods that are not
prohibited by the pesticide's labeling; however, the application must only be to sites specified by
the labeling and at no more than the maximum dosage rates specified by the labeling. Since
most pesticide labels do not explicitly prohibit use in outdoor residential misting systems, other
chemicals that target similar pests could be used in these misting systems. The Agency is not
aware of other pesticides being used in outdoor residential misting systems, and therefore, has
not assessed the potential risks to homeowners associated with use of pesticides other than PBO,
pyrethrins, and permethrin.
All PBO, pyrethrins, and permethrin registrants that do not support outdoor residential
misting systems use for their products will be expected to amend their Manufacturing Use
Product label to state the following, "This product must not be formulated into an end use
product for use in outdoor misting systems." Additionally, all registrants of PBO end-use
products must either include a statement prohibiting use in an outdoor residential misting system,
for example, "This product must not be used in an outdoor residential misting system," or
include separate and specific instructions for use in outdoor residential misting systems,
including the maximum application rate per day, use directions, and restrictions specified in
Section V. Although this action will only address PBO, pyrethrins, and permethrin products, the
Agency plans to issue broader guidance pertaining to use of outdoor misting systems and the
pesticides which can be used in these systems as part of its on-going effort to standardize the
way in which these systems are used.
By definition in FIFRA Section 2(e)(l) and (gg), leaving unapplied pesticide at a use site
constitutes the distribution or sale of a pesticide. In order to be in compliance with FIFRA,
companies which sell, install, and service outdoor residential misting systems must ensure that
one of the following transactions occur when providing these services:
The unopened registered pesticide is distributed or sold to the use-site owner prior to
mixing and loading into the equipment; or
The diluted registered pesticide is distributed or sold as a custom blend in accordance
with EPA's custom blending policies at FIFRA Compliance Program Policies Nos. 3.4
and 7.1 of the FIFRA Compliance Program Policy Compendium; or
The diluted pesticide is registered and is distributed or sold to the use-site owner prior to
loading into the equipment.
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Several issues, in addition to those discussed above, have been raised to EPA Regions
through State FIFRA Issues Research and Evaluation Group (SFIREG) issue papers, stakeholder
forums and comments, and other sources regarding the use of these systems. These issues
include, but are not limited to, the potential for inadvertent exposure and risks to residents,
misuse of the systems and pesticide products, offsite drift and potential exposure to non-target
organisms, and pest resistance issues. The Agency is aware of a cooperative effort lead by the
National Pest Management Association involving state and industry stakeholders, and pest
management professionals to standardize these systems and address the issues raised above, and
intends to continue to address these on-going issues through continued involvement and
discussions with the States, industry and stakeholder groups.
The Agency will have a 60-day comment period after the publication of the RED to
solicit feedback on the label language in Section V and the issues discussed above.
c. Aggregate Risk Mitigation
For PBO, aggregate risk assessments were conducted for acute (one day) and chronic
(one year or more) food and drinking water exposures. The short-term aggregate exposures from
food, water, and residential routes associated with application of PBO was also calculated since
there was a common toxicity endpoint of decreased weight gain identified for those routes of
exposure.
i. Acute and Chronic Aggregate Risk (Food + Water)
Acute DWLOC
Acute DWLOCs were calculated based on acute dietary exposure estimates and default
body weights and water consumption figures. The EDWCs for both surface water and
groundwater are well below the acute DWLOCs for the general U.S. population and all other
population subgroups indicating that acute aggregate exposure to PBO in food and water is not a
concern. Therefore, no mitigation is necessary for this scenario.
Chronic DWLOC
Chronic DWLOCs were calculated based on the chronic dietary exposure estimates and
default body weights and water consumption figures. The EDWCs for both surface water and
groundwater are well below the chronic DWLOCs for the general U.S. population and all other
population subgroups indicating that chronic aggregate exposure to PBO in food and water is
below the Agency's level of concern for these populations. Therefore, no mitigation is necessary
for this scenario.
ii. Short-Term Aggregate (Food + Water + Residential)
The short term aggregate risk for PBO was calculated by adding exposure estimates from
dietary, drinking water, and incidental oral exposure pathways for children age 1-2, the highest
exposed sub-population, and comparing them with model based EDWCs. The lowest short term
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DWLOC (8500 ug/L) for children 1-2 years old, which is higher than the surface water EDWC
(60 ug/L) and the ground water EDWC (0.26 ug/L), and therefore does not result in a risk of
concern. Therefore, no mitigation is necessary for this scenario.
d. Occupational Risk Mitigation
Occupational exposure assessments are completed by the Agency considering the use of
baseline PPE and, if warranted, for handlers, increasing levels of PPE and engineering controls
in order to estimate the potential impact on exposure and risk. The target MOEs for PBO are
300 for short- and intermediate-term inhalation exposures, and 1000 for long-term inhalation
exposures.
i. Handler Risk Mitigation
Wettable Powders - Agricultural
There are inhalation risk concerns for agricultural mixers and loaders using wettable
powder PBO products at baseline attire. Therefore, to mitigate the risks to mixers and loaders of
wettable powders in agricultural settings, the PBOTFII has agreed to package wettable powders
only in water soluble bags. When wettable powder products are packaged in water soluble bags,
there are no risks of concern for mixers and loaders in agricultural settings. At this time, the
Agency is not aware of any wettable powder products being actively marketed in the U.S. If
wettable powders are sold in the future all products must comply with the water soluble bag and
other requirements established in this decision document.
Wettable Powders - PCO Handlers
There are inhalation risk concerns for pest control operators (PCO) mixers and loaders
handling wettable powder PBO products at baseline attire. Therefore, to mitigate the risks to
PCO mixers and loaders of wettable powders, the PBOTFII has agreed to repackage wettable
powders in water soluble bags. Even when water soluble packages are used by PCOs, there is
still a risk of concern for crack and crevice applications with wettable powders. Therefore, to
mitigate this risk, the PBOTFII has agreed to reduce the indoor crack and crevice treatment rate
from 2.2 Ibs ai/1000 square feet, to 0.56 Ibs ai/1000 square feet. At this lower rate and with
water soluble bags, there will be no risks of concern for PCO mixing, loading, and applying
wettable powders.
Indoor Handheld Equipment (including thermal, cold, and ULV foggers)
Hand held fogging equipment was not included in the Phase 5 PBO risk assessment.
Two studies measuring exposure from fogging have since been considered by the Agency. The
exposure values estimated from the two studies differ greatly depending on the type of
equipment, duration of application, size of fogging area, and air flow. One study with the
pyrethroid prallethrin (MRID 45869301) was conducted to estimate exposure from a short (6
minute) fogging application in a small space. Another study conducted in a Florida greenhouse
(MRID 40350501) reflected applications in greenhouses, and may be more appropriate to
estimate exposure for greenhouse and warehouse applications. Due to the uncertainty in fogging
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practices with PBO, the Agency is requiring use and usage information to show if the existing
data is satisfactory to calculate exposure values from fogging with PBO. Based on the review of
this use and usage data, the Agency will determine if further fogging exposure data is needed.
Therefore, to further characterize the inhalation risk to applicators using handheld
fogging equipment, the Agency is requiring use and usage data on fogging applications. Based
on review of this data the Agency may require additional exposure data in the future. A dust-
mist respirator (PF10) will be required in the interim to address the Agency's immediate
inhalation risk concerns.
Dusts Applied through Power Dusters - Agricultural and PCO Handlers
The Agency was not able to assess scenarios involving dust applications with power
dusters because there are no exposure data to represent this application method. Power dusters
could potentially pose inhalation risk. Due to a lack of data on this exposure scenario and no
interest in supporting this application method from the PBOTFII, EPA has determined that this
application scenario is not eligible for reregi strati on. If data are submitted to support this
application method, EPA will reconsider this decision in the future. Dust product labels must
prohibit use of power dusters.
Dusts Applied through Bulb Dusters
The Agency was not able to assess scenarios involving dust applications with bulb
dusters because of a lack of data. Bulb dusters are only used for crack and crevice treatments,
which reduces the possible exposure to an applicator. Due to small amounts of dust used in this
application method, the exposure is expected to be negligible. Therefore, no mitigation or data
are required for this scenario.
Forestry Applications
Applications to forest areas are made at a higher rate than was assessed for any other
scenario. Other agricultural applications are made at the rate of 0.5 Ibs ai/acre, while
applications to forest areas are made at the rate of 1.25 Ibs ai/acre. There are inhalation risks of
concern for mixers and loaders supporting aerial applications with liquid and wettable powder
formulations at baseline attire. The addition of a dust-mist (PF5) respirator would eliminate
inhalation concerns from this scenario. Therefore, the Agency is requiring all mixers and loaders
supporting aerial application to forests with liquids to wear a dust-mist (PF5) respirator. All
applications to forest areas with wettable powder formulations will be prohibited.
Indoor Crack and Crevice Treatments with Low Pressure Handwand
There are inhalation risks of concern for PCO mixers, loaders, and applicators using a
low pressure handwand making indoor crack and crevice treatments. Therefore, to mitigate
these concerns the PBOTFII has agreed to reduce the rate from 2.2 Ibs ai/1000 square feet to
0.56 Ibs ai/1000 square feet. At this new rate, there will be no risks of concern for PCO handlers
of making crack and crevice applications.
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High Pressure Handwand Applications in Enclosed Areas (Greenhouses) - Agricultural
There are inhalation risks of concern for agricultural mixers, loaders, and applicators
using a high pressure handwand for applications to enclosed areas like greenhouses. Therefore,
to mitigate these concerns the PBOTFII has agreed to require applicators to wear a dust-mist
(PF5) respirator when making applications in enclosed areas like greenhouses. With this
additional PPE, there will be no risks of concern for agricultural handlers making high pressure
handwand applications in enclosed areas.
PCO Long-Term Handler Assessments
There are inhalation risks of concern for PCO handlers in some of the assessed long-term
scenarios including making applications with low pressure handwands for crack and crevice
treatments, and aerosol applications for indoor space spray applications.
PBO is used to control a large number and a wide variety of pests and labels do not
restrict or preclude repeated applications or long-term use. Given the potential for multiple
applications and long-term use for occupational handlers, inclusion of a repeated use/long-term
exposure for pest control operator and mosquito abatement scenarios is considered reasonable.
The results of the worker exposure assessment indicate that certain pest control operator
scenarios (i.e., mixing/loading/applying and/or aerosol application) result in MOEs less than the
target MOE of 1000 for long-term exposure.
However, it is important to note that for pest control operators and mosquito abatement
scenarios, assuming full day, long-term application for each application method is likely to
significantly overestimate actual exposure. Based on data on usage of likely PBO containing
pesticides presented in the National Pest Management Association Survey, these assumptions
would result in a significant overestimate of exposure for PCOs. Similarly, assuming continuous
usage of PBO containing pesticides for mosquito abatement applications would also significantly
overestimate total exposure based on personal communication with mosquito control district
officials regarding current usage of these products. Therefore, no mitigation is necessary for
these scenarios.
Aerosol Applications for Indoor Space Sprays - PCO Handlers
The registrants have requested a rate increase for aerosol cans applied by PCOs, from
0.025 Ibs ai/ 16 oz can, to 0.05 Ibs ai/ 16 oz can.
At this higher rate, the MOE for the aerosol space spray scenario would still fall above
our target for short-term risk. No intermediate-term exposure is expected from this use based on
use information provided by the PBOTFII. The assessment assumed each PCO handler applied
14 cans of PBO pesticide containing PBO everyday for both a short-term (30 day) and an
intermediate-term (30 day to 6 month) duration. This is a conservative estimation of the amount
of PBO a PCO handles over the intermediate term. Therefore, for the aerosol application
scenario the Agency will allow the PBOTFII to raise the rate to 0.05 Ibs ai/16 oz can.
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The 0.025 Ibs ai/16 oz can rate for the aerosol application was also used in the residential
post-application assessment. The MOE for this scenario was 600 for children. A rate increase
would still result in an MOE above our target of 100 and not a concern for the Agency.
ii. Post-Application Worker Risk Mitigation
Metered Release Devices - Dairy Barns
The Agency has similar concerns for post-application short- and intermediate-term
exposures from these systems as described in the occupational post-application section of this
chapter. According to the PBO Master Label, PBO is used as space sprays in a wide variety of
indoor areas such as barns, greenhouses, food storage areas, food processing areas, restaurants
and residences. A scenario that involves a metered release into a dairy barn was evaluated to
assess these exposures because PBO is commonly used in dairy barns and because the ventilation
characteristics of dairy barns are relatively well defined. The MOE for metered release devices
in occupational areas like dairy barns was calculated to be 62 with a target of 300 for both short-
and intermediate-term exposures. Risks are lower for these occupational scenarios than for
residential settings due to the fact that the occupational areas generally have a greater ventilation
capacity and the risk assessment assumes a higher number of air changes per hour in these
settings.
Therefore, in order to refine the risk assessment for metered release devices in
occupational settings, the Agency is requiring additional usage information about metered
release device products, as well as requiring label changes which are included in Section V.
Some products labeled for use in occupational areas are also labeled for use in residential
settings and areas where children may be present. Therefore, as mentioned in the residential
metered release device section above, the PBOTF II has agreed to remove the following use sites
from metered release device product labels: day-care centers, nursing homes, schools, and
hospitals.
2. Non-Target Organism (Ecological) Risk Management
a. Aquatic Organisms
Agriculture
There were exceedences for acute exposure for several aquatic species exposed to PBO
from agricultural applications including amphibians (RQs 0.76 to 1.1), estuarine/marine
invertebrates (RQs <0.05 to 0.33), freshwater fish (RQs <0.05 to 0.08), and freshwater
invertebrates (RQs <0.05 to 0.31).
There were also chronic exceedences for aquatic organisms exposed from agricultural
applications including freshwater fish (RQs <1.0 to 3.6) and freshwater invertebrates (RQs <1.0
to 5.1).
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A sensitivity analysis was conducted with the scenario that produced the highest EECs
(Florida peppers with aerial application). The EEC appears to be proportional to both the
application rate (Ib/acre) and the number of applications. A decrease from 0.5 Ib/acre to 0.25
Ib/acre decreased the EEC by about half. Similarly, a decrease in number of application from 10
to 5 decreased the EEC by about half.
An increase in the application interval from 3 to 6 days had little effect on the EEC, but
the longer time averages dropped somewhat (21-day average from 153 ppb to 140, and 60-day
average from 142 ppb to 120). An increase to ten-day application intervals reduced the 21-day
average EEC to 104 ppb, and the 6-day average to 90.5 ppb. The relatively small changes in
time-averaged concentrations versus changed application intervals are likely due to the large
number of applications allowed (10).
The maximum rate for all agricultural crops (0.5 Ibs ai/acre) is not expected to be
typically applied at this rate on all crops. PBO is used on a wide variety of crops, and the typical
application parameters can vary greatly depending on the commodity, but will never exceed the
modeled maximum agricultural rate of 0.5 Ibs ai/acre. Applying PBO at rates and re-application
intervals lower than the maximum assessed values will decrease the potential risk to aquatic
organisms.
Currently there are label restrictions on some, but not all product labels indicating the
application frequency and rate. All product labels will be revised to include the following
information:
No more than 10 applications per season.
Do not reapply within 3 days except under extreme pest pressure.
In case of extreme pest pressure, do not reapply within 24 hours.
Stating these imitations on all product labels will promote more judicious use and will
likely reduce the amount of PBO in the environment.
Wide Area Mosquito Abatement
There were slight exceedences for acute exposure for several aquatic species exposed to
PBO from mosquito abatement applications including freshwater invertebrates (RQ = 0.15),
estuarine/marine invertebrates (RQ = 0.15), and amphibians (RQ = 0.36).
Currently there are label restrictions on some, but not all product labels with specific
application parameters. Therefore, to address the risks from wide area mosquito adulticide
applications, the PBOTFII agreed to the following restrictions in accordance with PR 2005-1:
Droplet size for aerial applications: DV0.5 < 60 microns and DvO.9 < 80 microns
Droplet size for ground applications: DV0.5 < 30 microns and DvO.9 < 50 microns
Release height: 100 feet for airplane, 75 feet for helicopter
Yearly application rate: 2.0 Ibs ai/acre/year
Wind Speed: Apply only when wind speed is greater than or equal to 1 mph.
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Down the Drain
There were no risks of concern identified in EPA's assessment attributed to PBO in
domestic wastewaters. Therefore, no mitigation is needed.
Spray Drift
As a result of AgDrift modeling for aerial applications to both pond and wetland
scenarios, there were listed species LOG exceedences for freshwater invertebrates (RQ = 0.18),
amphibians (RQ = 0.43), and estuarine invertebrates (RQ = 0.18). There was also an exceedence
for listed amphibian species from ground spray applications (RQ = 0.11).
All labels are being required to be updated with the following spray drift language to
address concerns of drift to non-target organisms:
Wind speed: "Do not apply at wind speeds greater than 10 mph at the application site."
Droplet size: "Apply as a medium or coarser spray (ASABE standard 572)."
Temperature inversions: "Do not make any type of application into temperature
inversions."
Release height for ground applications: "Do not release spray at a height greater than
4 feet above the ground or crop canopy."
Release height for aerial applications: "Do not release spray at a height greater than
10 feet above the ground or crop canopy."
Other Non-Agricultural Uses
The Office of Pesticide Programs (OPP) generally tries to estimate pesticide exposure
through all significant routes of exposure from both agricultural and non-crop uses. However,
the ecological risk assessments for pyrethrins, pyrethroids, and the synergists like PBO, focus
predominantly on the agricultural uses for these insecticides, because pesticide transport models
are available to estimate potential aquatic exposure. Based on laboratory toxicity tests with
terrestrial and aquatic animals, aquatic exposure would be more likely to cause adverse effects in
the environment.
However, sales data indicate that non-crop uses of PBO comprise a much larger fraction
of total use than agricultural uses. The use of pyrethrins, pyrethroids, and synergists in urban
and suburban settings has increased since the phase-out of these uses of the organophosphate
insecticides diazinon and chlorpyrifos. Outdoor non-crop uses of PBO include landscape
maintenance and homeowner lawn and garden use. Indoor uses include insect control, and
treatment of pets and clothing.
The Agency uses a "Down-the-Drain" model to perform a screening aquatic risk
assessment for indoor uses of pesticides. In these simulations, waste water containing pesticide
residue from pet shampoos or treated clothing flows into a building drain and passes through a
sanitary sewer and publicly owned treatment works (POTW) before being discharged to surface
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water. However, no analogous exposure model has been developed to allow a similar screening
assessment for pesticides applied in an outdoor urban setting. As a result, the Agency has had to
take a qualitative approach to characterize the potential aquatic risk from urban and suburban use
of pyrethrins, pyrethroids, and synergists.
For outdoor urban uses it is assumed that runoff water from rain and/or lawn watering
may remove pesticide to storm sewers and then directly to surface water. Conceptually, a greater
contribution to contamination of surface water bodies would be expected from application to
impervious surfaces such as walkways, driveways or the sides of buildings than to lawns or bare
ground. This is especially so for the pyrethrins and pyrethroids, given their strong affinity to
bind to organic carbon in soils. However, the Agency has not identified a model which can
simulate the different application methods for urban use and the physical representation of the
urban landscape, storm sewer and receiving water configuration.
There are models available that can be calibrated to simulate sites and pesticides for
which extensive flow and pollutant data have been collected in advance. The HSPF/NPSM
model, for instance, which is included in the Office of Water's BASINS shell, has been used to
calibrate stream flow and copper pesticide use data to simulate loading of these pesticides
consistent with concentrations measured in surface water monitoring. Risk assessors with the
California Department of Environmental Protection confirmed in conversations with the Agency
that they also have used watershed models calibrated to previously collected flow and pesticide
monitoring data, but that they did not know of any models capable of predicting concentrations
of pyrethrins and pyrethroids that might occur because of outdoor urban uses.
Development of a screening model which could simulate the fate and transport of
pesticides applied in an urban setting would require a large body of data which is currently
unavailable. For instance, an urban landscape cannot be simulated as easily as an agricultural
field. The PRZM model simulates runoff from an agricultural field using readily available data
describing surface soil characteristics and laboratory data detailing the persistence and mobility
of pesticides in these soils. The agricultural field simulated is homogenously planted to a single
crop, and soil and water are transported from the field to a receiving water body with dimensions
consistent with USDA farm-pond construction guidelines.
By contrast, an urban landscape or suburban housing development consists of impervious
surfaces such as streets and sidewalks, and permeable surfaces such as lawns and parkland. One
could expect much greater mobility for pesticides applied to impervious surfaces, but laboratory
soil metabolism studies may not provide an accurate measure of the persistence of pesticides on
these surfaces. The path runoff water and eroded sediment might take is less obvious for an
urban setting than an agricultural field. First, an urban landscape cannot be considered
homogeneous, as the proportion of impervious and pervious surfaces varies for different
locations. In addition, the flow path of runoff water and sediment is not necessarily a direct path
over land, but can pass below ground through storm sewer networks, or be directed or slowed by
pumping stations or temporary holding ponds.
The timing and magnitude of urban uses is less well defined than agricultural uses.
While agricultural uses would occur within a predictable window during the growing season, the
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need for urban uses could occur at different times each year, and might occur at different times
within the same watershed. In addition, since records of how and to what extent pyrethrins and
pyrethroids are applied by homeowners are less well defined than for professional applications, it
is harder to estimate the total load to model.
Monitoring Data
The Agency considers surface water monitoring data in addition to modeling results
when they are available. However, surface water monitoring for PBO has been limited. PBO is
always used with another chemical, commonly either pyrethrins or the synthetic pyrethroids.
In a Sacramento County monitoring study targeting PBO and pyrethrins, water samples
were collected after mosquito adulticide applications in the Sacramento metropolitan area. In
samples collected up to 10 hours after application there were detects of PBO and pyrethrins from
in the ppb range, similar to modeling predictions in the PBO and the pyrethrins mosquito
adulticide assessment. Samples were also collected the day after application and measured lower
or no concentrations for both active ingredients. This indicates both chemicals appear to
dissipate fairly rapidly in the water column. The co-occurrence of PBO and pyrethrins in some
of these first samples is an indication of direct application to water and not transport by runoff.
There has been limited monitoring for the pyrethroids, but recently researchers from the
University of California- Berkeley have published studies which reported transport of
pyrethroids to stream bed sediment as a result of urban uses. In 2004, Weston, et al. collected
sediment from creeks draining a residential area in Rosedale, California. The sediments were
analyzed for 7 pyrethroids (including two currently in the reregi strati on process), as well as for
other insecticides. All of the pyrethroids were detected in the bed sediment from at least one
sampling location. The researchers exposed the aquatic amphipod Hyalella azteca to the 21
sediment samples they collected; pesticide concentrations in 9 of these samples were sufficient to
cause 90% mortality in the amphipods after a 10-day exposure. The concentrations of
pyrethroids detected in the sediments were above the level expected to cause 50% mortality in H.
azteca, suggesting that the pyrethroids were responsible for the observed toxicity.
In a subsequent study, Weston, et al. collected samples from 15 urban creeks in
California and 12 in Tennessee. Toxicity to H. azteca was observed at least once with sediments
taken from 12 of the 15 California sampling sites. In most cases, the toxicity could be accounted
for by the concentrations of pyrethroids detected in the sediment. Pyrethroids were rarely
detected in the Tennessee sediment samples, and exposure to the Tennessee sediments did not
prove to be toxic to H. azteca. The Weston studies did not sample for PBO.
The Weston, et al. studies indicate that urban uses of pesticides can lead to surface-water
contamination, including contamination by pesticides that would bind almost completely to soil
in an agricultural setting. Since PBO is commonly formulated with the pyrethrins or the
synthetic pyrethroids, efforts to better understand the conditions under which pyrethroids and
pyrethrins might be transported to surface water would help improve our assessment of the
scenarios in which PBO might contribute to increased risk to aquatic organisms.
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The results of the Weston, et al. studies have led a number of organizations, such as the
California State Water Resources Control Board (SWRCB) to submit comments to the Agency
calling for mitigation measures to prevent surface-water contamination. However, the lack of
data and information to develop an urban pesticide transport model also makes it difficult to
identify whether risks may exceed some LOCs, and appropriate mitigation at this time. The
Agency is committed to develop mitigation options during the reregi strati on process, and to
identify steps which can be taken to allow a greater understanding of potential ecological risk
from urban use.
One reason that broad mitigation measures cannot be adopted during reregi strati on is that
not all of the chemicals of concern are going through reregi strati on at this time. If use
restrictions were placed on only a few of these chemicals, it would likely be replaced with
another chemical with a similar registered use. It would be useful, as some commenters have
suggested, performing a risk assessment for all of the pyrethrins, pyrethroids, and synergists at
the same time. The Weston papers indicated that the sediments which proved toxic to the tested
aquatic invertebrate were contaminated not only with the chemicals undergoing reregi strati on,
but also pyrethroids such as bifenthrin and lambda-cyhalothrin.
A number of steps are planned for the intervening years which should improve the
Agency's ability to assess the level of aquatic exposure to pesticides such as pyrethrins,
pyrethroids, and synergists from urban use. One step is to better identify what conditions in an
urban setting might lead to greater vulnerability to transport to urban water bodies. Although the
Weston paper reported sediment toxicity from samples from California but not Tennessee, the
authors could only speculate what differences in use or geography made an area more vulnerable
to exposure than the other.
Further investigation into the dominant urban uses and application practices of
pyrethroids and pyrethrins, and PBO by association, around the country would also help provide
a clearer picture of relative vulnerability. The California SWRCB commented that structural
pest control is likely a major source of pyrethroids in urban runoff, and suggested best
management practices (BMP). The Pyrethroid Working Group (PWG) indicated that irrigation
of lawns in areas of California with little rainfall during the application season could be a major
contributor, and has contacted organizations such as Responsible Industry for a Sound
Environment (RISE) and the Coalition for Urban/Residential Environmental Stewardship
(CURES) to develop BMPs as part of their product stewardship plan. As further sediment
monitoring studies are published reflecting various parts of the country with different weather
and pest pressures, more detailed usage data will make it easier to correlate the causes of
pyrethrins, pyrethroids, and synergist contamination of surface water with use practices.
The Agency will also continue in its efforts to develop a screening model for urban
pesticide uses. Advances in the resolution of GIS databases may allow better representation of
the impervious and pervious portions of a typical urban landscape. As it becomes clearer which
uses are most likely to lead to transport of pyrethrins, pyrethroids, and synergists to surface
water, the conceptual model of how urban transport should be simulated will be more focused.
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The Agency will evaluate available published literature and call-in data to resolve data
gaps to ensure a robust comparison of the potential ecological risk of all the pyrethrins,
pyrethroids, and synergists during Registration Review. Toxicity data cited by several
commenters from published literature are included in the Agency's ECOTOX database. The
Agency will evaluate the quality of studies to identify those to be included in the risk
assessments during Registration Review.
Stewardship Language
While the Agency cannot currently assess the potential risks to aquatic organisms from
non-agricultural uses of PBO, the Agency is still seeking to reduce the potential drift and run-off
of PBO into aquatic habits through explicit directions for use on both professional and consumer
use products for use in residential settings. These use directions include best management and
stewardship practices which are formulation specific, and will serve to reduce the potential run-
off and drift that can occur from applications of these products. Label statements implementing
these measures are listed in the "direction for use" section of the label table in Section V of this
RED document.
b. Terrestrial Organisms
There are LOG exceedences using the maximum application rate of 0.5 Ibs ai/acre for
chronic exposure to birds (RQs <1.0 to 3.1), and chronic exposures for mammals using both the
maximum Kenaga EEC values (RQs <1.0 to 4.5) and the average Kenaga EEC values (RQs <1.0
to 1.6).
All product labels will be revised to include the maximum application rate, application
frequency, and maximum applications per season. These measures will reduce the amount of
PBO in the environment.
c. Ecological Risk from Mixtures
The Agency has reviewed data that show the toxicity and risk from PBO formulated with
other insecticides, specifically the pyrethrins or synthetic pyrethroids, appeared to be higher than
the toxicity or risk from either of the individual active ingredients separately for certain species.
When PBO is mixed with organophosphate insecticides, the toxic effect observed depends upon
the mechanism that causes the OP to break down. In some cases the toxicity of the OP
insecticide can be either increased or decreased in the presence of PBO. Due to the uncertainty
in predicting the possible effects a synergist would have to the environment when mixed with
another chemical, the Agency is requiring product specific ecotoxicity data on formulated
products of PBO.
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V. What Registrants Need to Do
The Agency has determined that PBO is eligible for reregi strati on provided that the
mitigation measures and label changes identified in this RED are implemented. Registrants will
need to amend their product labeling to incorporate the label statements set forth in the Label
Changes Summary Table (Table 27). The Agency intends to issue Data Call-Ins (DCIs)
requiring generic and product specific data. Generally, the registrant will have 90 days from
receipt of a DCI to complete and submit response forms or request time extensions and/or
waivers with a full written justification. For product-specific data, the registrant will have eight
months to submit data and amended labels.
A. Manufacturing Use Products
1. Additional Generic Data Requirements
The generic data base supporting the reregi strati on of PBO for currently registered uses
has been reviewed and determined to be substantially complete. However, the data listed below
are necessary to confirm the reregi strati on eligibility decision documented in this RED.
Environmental Fate and Ecological Effects Data Needs
Guideline 72-5 Full Life Cycle Fish (freshwater) is required to understand the chronic
toxicity of PBO to fish beyond that found in the fish early life stage study.
Eco-toxicity data on fish, invertebrates, and sediment dwelling organisms, and honeybees
must be submitted in order to address concerns for synergistic toxic effects for typical
end use products containing PBO.
The exposure of birds and mammals is required to better understand the dissipation of
total foliar residues (guideline 132-la). Due to lack of this data, a default half-life of 35
days on foliage has been assumed. A measured foliar dissipation rate, if shorter than 35
days, might remove the presumption of chronic risk to mammals.
72-4 Life-cycle estuarine invertebrate using shrimp.
122-1 Tier I Terrestrial Plant Study - Field incidents reported under section 6(a)(2)
indicate that PBO with pyrethrin and pyrethroid insecticides may cause plant mortality.
Since this is an area of great uncertainty due to lack of data, Tier I terrestrial plant studies
with typical end use products (Vegetative Vigor) are needed to decrease this uncertainty.
In the avian reproduction toxicity studies on PBO, there was lexicologically significant
evidence for PBO to be a potential candidate to test for endocrine disrupter effects once
the endocrine disrupter program is formalized.
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Human Health Data Requirements
The following product and residue chemistry data are required to support the registration of
PBO:
Product Chemisty
Product chemistry data as listed in the Product Chemistry Chapter is needed for TGAI of
PBO.
Residue Chemistry
Label revisions and clarifications will be required for some crops in order to reflect the
use pattern parameters for which adequate residue data are available.
Further analytical work to upgrade the previously submitted oral metabolism studies with
ruminant and poultry. Representative egg, milk, and tissue samples from the dermal or
oral ruminant/poultry metabolism studies must be analyzed using the enforcement
method or any preferred data-collection method to determine whether the method(s)
adequately recover PBO residues of concern. Data are under review.
Additional storage stability data for plant (and processed) and livestock commodities to
upgrade previously submitted studies or to support new studies.
Data to support uses of PBO on foods stored in multi-walled paper or cloth bags.
A magnitude of the residue study with ruminants reflecting premise treatment and further
analysis on milk samples from the dermal and oral studies.
A magnitude of the residue study with poultry reflecting direct applications to laying
hens using a 10% dust formulation.
Magnitude of the residue studies reflecting preharvest uses on representative
commodities of all crop groups (and a few miscellaneous commodities) which are being
supported for reregi strati on.
Magnitude of the residue studies reflecting postharvest uses for all crops (except potato
and sweet potato) which are being supported for reregi strati on
Processing studies on apple, barley, coconut, corn (field), fig, flax, oat, peanut, pineapple,
plum, potato, rice, rye, sorghum, and wheat.
A confined rotational crop study. A field accumulation study in rotational crops (OPPTS
860.1900) is required if the level of the total radioactive residue in the confined rotational
crops is equal to or exceeds 0.01 ppm at the desired rotational interval or at 12 months,
and once the nature of the residue in the rotational crops is understood.
Occupational and Residential Exposure
Metered release devices: use and usage information, as well as air concentration and
particle size data.
Outdoor residential misting systems: use and usage information, as well as air
concentration and droplet size data.
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Applicators using handheld fogging equipment: use and usage data on application
practices, as well as exposure data held in reserve pending review of the use and usage
data.
2. Labeling Requirements
To ensure compliance with FIFRA, manufacturing use product (MUP) labeling should be
revised to comply with all current EPA regulations, PR Notices, and applicable policies. The
MUP labeling should bear the labeling contained in Table 27.
3. Spray Drift Management
The Agency has been working closely with stakeholders to develop improved approaches
for mitigating risks to human health and the environment from pesticide spray drift. As part of
the reregi strati on process, the EPA will continue to work with all interested parties on this
important issue.
Specific spray drift language for PBO is outlined in the "spray drift management" section
of Table 27.
B. End-Use Products
1. Additional Product-Specific Data Requirements
Section 4(g)(2)(B) of FIFRA calls for the Agency to obtain any needed product-specific
data regarding the pesticide after a determination of eligibility has been made. The Registrant
must review previous data submissions to ensure that they meet current EPA acceptance criteria
and if not, commit to conduct new studies. If a registrant believes that previously submitted data
meet current testing standards, then the study MRID numbers should be cited according to the
instructions in the Requirement Status and Registrants Response Form provided for each
product. The Agency intends to issue a separate product-specific data call-in (PDCI), outlining
specific data requirements. For any questions regarding the PDCI, please contact Veronica
Dutch at (703) 308-8585.
In addition, efficacy data for all applications that target public health pests must be
submitted, including data for outdoor residential misting systems. Additional information on the
efficacy data can be found in the Series 810 Product Performance Test Guidelines on the
Agency's website.
(http://www.epa.gov/opptsfrs/publications/OPPTS_Hamionized/810_Product_Perfomiance_Test_Guidelines/index.html)
2. Labeling for End-Use Products
To be eligible for reregi strati on, labeling changes are necessary to implement measures
outlined in Section IV above. Specific language to incorporate these changes is specified in
Table 27. Generally, conditions for the distribution and sale of products bearing old
labels/labeling will be established when the label changes are approved. However, specific
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existing stocks time frames will be established case-by-case, depending on the number of
products involved, the number of label changes, and other factors.
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Labeling Changes Summary Table 27
In order to be eligible for reregi strati on, all product labels must be amended to incorporate the risk mitigation measures outlined in
Section IV. The following table describes how language on the labels should be amended.
Description
PBO Required Labeling Language
Placement on Label
Manufacturing-Use Products
Required on all MUPs
"Only for formulation into a synergist for the following use(s) [fill blank only with those uses that
are being supported by MP registrants]."
"Not for formulation into wettable powder end use products (EUP), unless the EUP is packaged in
water soluble bags."
"Not for formulation into granular End Use Products."
»Delete any reference to tolerance exemptions on labels.
If Registrants are not supporting outdoor residential misting systems use for their products, the
following statement must appear on the MUP label of all liquid or wettable powder products:
"Not for formulation into an end use product for use in outdoor residential misting systems."
Direct Application to Non-domestic Animals/Livestock
Formulated products eligible for reregistration may not contain a percentage of a.i. that
exceeds the following:
Dusts for application to livestock only- 10% ai
Liquids for application to livestock only - 0.35 Ib ai/gallon
Towelettes for application to livestock only - 2% ai
Spot-on applications - 10% ai
Liquids for applications to poultry only - 0.1% ai
Directions for Use
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Description
PBO Required Labeling Language
Placement on Label
Pet Care
Formulated products eligible for reregistration may not contain a percentage of a.i. that
exceeds the following:
Shampoos - 3% ai
Sprays -0.1%ai
Spot-on or Pour-on - 10% ai
Dust - 10% ai
Towelettes-2% ai
One of these statements
may be added to a label to
allow reformulation of the
product for a specific use or
all additional uses
supported by a formulator
or user group.
"This product may be used to formulate products for specific use(s) not listed on the MP label if the
formulator, user group, or grower has complied with U.S. EPA submission requirements regarding
support of such use(s)."
"This product may be used to formulate products for any additional use(s) not listed on the MP label
if the formulator, user group, or grower has complied with U.S. EPA submission requirements
regarding support of such use(s)."
Directions for Use
Environmental Hazards
Statements Required by the
RED and Agency Label
Policies
"This product is toxic to aquatic organisms, including fish and invertebrates. Do not discharge
effluent containing this product into lakes, streams, ponds, estuaries, oceans or other waters unless
in accordance with the requirements of a National Pollutant Discharge Elimination System
(NPDES) permit and the permitting authority has been notified in writing prior to discharge. Do not
discharge effluent containing this product to sewer systems without previously notifying the local
sewage treatment plant authority. For guidance contact your State Water Board or Regional Office
of the EPA. Do not contaminate water when disposing of equipment wash-waters."
Directions for Use
End-Use Products Intended for Occupational Use (WPS and non-WPS) and Wide Area Mosquito Adulticide Applications
Handler PPE Requirements
for Wettable Powders
Formulations Packaged in
Water Soluble Packaging
[Note: Wettable Powders
"Personal Protective Equipment (PPE)"
"Mixers, loaders, applicators, and other handlers must wear:
- long-sleeve shirt,
- long pants, and
- shoes and socks."
"In addition to the above PPE, applicators using a high pressure handwand in an enclosed area must
Precautionary
Statements: Hazards to
Humans and Domestic
Animals
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Description
PBO Required Labeling Language
Placement on Label
must be packaged in water
soluble bags to be eligible
for reregistration.]
wear at least a NIOSH-approved respirator with:
- a dust/mist filter with MSHA/NIOSH approval number prefix TC-21C or
- any N, R, P, or HE filter."
"In addition to the above PPE, applicators using hand held foggers in an enclosed area must wear at
least a half face NIOSH-approved respirator with:
~ a dust/mist filtering cartridge (MSHA/NIOSH approval number prefix TC-21C), or
~ a canister approved for pesticides (MSHA/NIOSH approval number prefix TC-14G), or
~ a cartridge or canister with any N,R,P or HE filter.
"See engineering controls for additional requirements."
Instruction to Registrant:
Drop the "N" type prefilter from the respirator statement, if the pesticide product contains, or is
used with, oil.
Handler PPE Requirements
for Liquid Formulations1
[including: liquid
concentrates, total release
foggers, microencapsulated
concentrates, foams,
aerosols, gels, pastes, and
pressurized liquids]
Note: The statement may
be omitted if the end-use
product is labeled only for
use on pets.
Note: If aerial application
to forests or use of a high
"Personal Protective Equipment (PPE)"
"Mixers, loaders, applicators, and other handlers must wear the following:
- long-sleeve shirt,
- long pants,
- shoes and socks."
"In addition to the above PPE, mixers and loaders supporting aerial applications to forests and/or
applicators using a high pressure handwand in an enclosed area must wear at least a NIOSH-
approved respirator with:
- a dust/mist filter with MSHA/NIOSH approval number prefix TC-21C or
- any N, R, P, or HE filter."
"In addition to the above PPE, applicators using hand held foggers in an enclosed area must wear a
half-face, full-face, or hood-style NIOSH-approved respirator with:
Precautionary
Statements: Hazards to
Humans and Domestic
Animals
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Description
PBO Required Labeling Language
Placement on Label
pressure handwand sprayer
is not permitted or not
feasible for the end-use
product, the statement
requiring respirators for
those uses may be omitted.
Note If aerial application is
not permitted or not feasible
for the end-use product, the
reference to engineering
control statements may be
omitted.
Note: If the use of
handheld foggers in
enclosed areas is not
permitted or not feasible for
the end-use product, the
statement requiring
respirators for those uses
may be omitted.
~ a dust/mist filtering cartridge (MSHA/NIOSH approval number prefix TC-21C), or
~ a canister approved for pesticides (MSHA/NIOSH approval number prefix TC-14G), or
~ a cartridge or canister with any N,R,P or HE filter.
"See engineering controls for additional requirements."
Instruction to Registrant: Drop the "N" type filter from the respirator statement, if the pesticide
product contains, or is used with, oil.
Products that prohibit aerial applications may omit the reference to engineering control statements.
Handler PPE Requirements
for Dusts
"Personal Protective Equipment (PPE)"
"Loaders, applicators, and other handlers must wear the following:
- long-sleeve shirt,
- long pants,
- shoes and socks."
" In addition, applicators using power duster equipment must wear a half-face, full-face, or hood-
style NIOSH-approved respirator with:
a dust/mist filtering cartridge (MSHA/NIOSH approval number prefix TC-21C), or
Precautionary
Statements: Hazards to
Humans and Domestic
Animals
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Description
PBO Required Labeling Language
Placement on Label
a canister approved for pesticides (MSHA/NIOSH approval number prefix TC-14G), or
a cartridge or canister with any N,R, P, or HE filter."
User Safety Requirements
"Follow manufacturer's instructions for cleaning/maintaining PPE. If no such instructions for
washables exist, use detergent and hot water. Keep and wash PPE separately from other laundry.
"Discard clothing and other absorbent material that have been drenched or heavily contaminated
with the product's concentrate. Do not reuse them."
Precautionary
Statements: Hazards to
Humans and Domestic
Animals immediately
following the PPE
requirements
Engineering Controls:
Wettable Powders packaged
in Water-Soluble Bags
[Note: Wettable Powders
must be packaged in water
soluble packages to be
eligible for reregistration.]
Note If aerial application is
not permitted or not feasible
for the end-use product, the
to engineering control
statements referring to
pilots or human flaggers
may be omitted.
"Engineering Controls:"
"Water-soluble packets when used correctly qualify as a closed mixing/loading system under the
Worker Protection Standard for Agricultural Pesticides [40 CFR 170.240(d)(4)]. Mixers and
loaders using water-soluble packets must:
~ wear the personal protective equipment required in the PPE section of this labeling for mixers and
loaders, and
~ be provided and must have immediately available for use in an emergency, such as a broken
package, spill, or equipment breakdown a half-face, full-face, or hood-style NIOSH-approved
respirator with:
~ a dust/mist filtering cartridge (MSHA/NIOSH approval number prefix TC-21C), or
~ a canister approved for pesticides (MSHA/NIOSH approval number prefix TC-14G), or
~ a cartridge or canister with any N,R,P or HE filter.
"Pilots must use an enclosed cockpit that meets the requirements listed in the Worker Protection
Standard (WPS) for agricultural pesticides [40 CFR 170.240(d)(6)]."
"Human flagging is prohibited. Flagging to support aerial application is limited to use of the Global
Positioning System (GPS) or mechanical flaggers."
Instructions to Registrant:
Drop the "N" type prefilter from the respirator statement, if the pesticide product contains, or is
used with, oil.
Precautionary
Statements: Hazards to
Humans and Domestic
Animals (Immediately
following PPE and
User Safety
Requirements.)
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Description
PBO Required Labeling Language
Placement on Label
Engineering Controls for all
liquid formulations.
Note if aerial application is
not permitted or not feasible
for the end-use product, the
to engineering control
statements referring to
pilots or human flaggers
may be omitted.
"Engineering Controls:"
"Pilots must use an enclosed cockpit that meets the requirements listed in the Worker Protection
Standard (WPS) for agricultural pesticides [40 CFR 170.240(d)(6)]."
"Human flagging is prohibited. Flagging to support aerial application is limited to use of the Global
Positioning System (GPS) or mechanical flaggers."
Precautionary
Statements: Hazards to
Humans and Domestic
Animals (Immediately
following PPE and
User Safety
Requirements.)
User Safety
Recommendations
"USER SAFETY RECOMMENDATIONS"
"Users should wash hands before eating, drinking, chewing gum, using tobacco, or using the toilet."
"Users should remove clothing/PPE immediately if pesticide gets inside. Then wash thoroughly
and put on clean clothing."
"Users should remove PPE immediately after handling this product. Wash the outside of gloves
before removing. As soon as possible, wash thoroughly and change into clean clothing."
Precautionary
Statements under:
Hazards to Humans and
Domestic Animals
immediately following
Engineering Controls
(Must be placed in a
box.)
Environmental
Hazards Statements for
products labeled for outdoor
uses other than as a wide
area mosquito adulticide:
(PR Notice 2005-1
recommends separating
labels intended for wide
area mosquito adulticide
applications.)
"ENVIRONMENTAL HAZARDS"
"This product is toxic to aquatic organisms, including fish and invertebrates. Drift and runoff may
be hazardous to aquatic organisms in water adjacent to treated areas. This product may contaminate
water through runoff. This product has a potential for runoff for several weeks after application.
Poorly draining soils and soils with shallow water tables are more prone to produce runoff that
contains this product."
"Do not apply directly to water, to areas where surface water is present or to intertidal areas below
the mean high water mark. Do not contaminate water when disposing of equipment wash-waters or
rinsate."
Precautionary
Statements under
Environmental Hazards
Environmental
"ENVIRONMENTAL HAZARDS"
Precautionary
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Description
PBO Required Labeling Language
Placement on Label
Hazards Statements for
products labeled solely for
use as a wide area mosquito
adulticide:
(PR Notice 2005-1
recommends separating
labels intended for wide
area mosquito adulticide
applications.)
"This pesticide is toxic to aquatic organisms, including fish and invertebrates. Runoff from treated
areas or deposition of spray droplets into a body of water may be hazardous to fish and aquatic
invertebrates."
"Before making the first application in a season, it is advisable to consult with the state or tribal
agency with primary responsibility for pesticide regulation to determine if other regulatory
requirements exist."
"Do not apply over bodies of water (lakes, rivers, permanent streams, natural ponds, commercial
fish ponds, swamps, marshes or estuaries), except when necessary to target areas where adult
mosquitoes are present, and weather conditions will facilitate movement of applied material away
from the water in order to minimize incidental deposition into the water body. Do not contaminate
bodies of water when disposing of equipment rinsate or washwaters."
Statements under
Environmental Hazards
Environmental
Hazards Statements for
products labeled as a wide
area mosquito adulticide
and is labeled for other
outdoor uses as well:
(PR Notice 2005-1
recommends separating
labels intended for wide
area mosquito adulticide
applications.)
"ENVIRONMENTAL HAZARDS for TERRESTRIAL APPLICATIONS"
"This product is toxic to aquatic organisms, including fish and invertebrates. Drift and runoff may
be hazardous to aquatic organisms in water adjacent to treated areas. This product may contaminate
water through runoff. This product has a potential for runoff for several weeks after application.
Poorly draining soils and soils with shallow water tables are more prone to produce runoff that
contains this product."
"Except as specified in the directions for use, do not apply directly to water, to areas where surface
water is present or to intertidal areas below the mean high water mark. Do not contaminate water
when disposing of equipment wash-waters or rinsate."
"ENVIRONMENTAL HAZARDS for WIDE AREA MOSQUITO ADULTICIDE
APPLICATIONS"
"This pesticide is toxic to aquatic organisms, including fish and invertebrates. Runoff from treated
areas or deposition of spray droplets into a body of water may be hazardous to fish and aquatic
invertebrates."
"When applying as a wide area mosquito adulticide, before making the first application in a season,
Precautionary
Statements under
Environmental Hazards
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Description
PBO Required Labeling Language
Placement on Label
it is advisable to consult with the state or tribal agency with primary responsibility for pesticide
regulation to determine if other regulatory requirements exist."
"When applying as a wide area mosquito adulticide, do not apply over bodies of water (lakes,
rivers, permanent streams, natural ponds, commercial fish ponds, swamps, marshes or estuaries),
except when necessary to target areas where adult mosquitoes are present, and weather conditions
will facilitate movement of applied material away from the water in order to minimize incidental
deposition into the water body.
Environmental Hazards for
Products labeled only for
Indoor Use EXCEPT ready
to use impregnated
materials (e.g. flea collars,
ear tags, coils, mats)
(Note: Products used on
domestic animals like flea
collars and ear tags,
generally do not require an
Environmental Hazards
statement.
In addition, products
containing the statement:
"For indoor use only," may
also omit the environmental
hazards statement.)
"ENVIRONMENTAL HAZARDS"
"This product is toxic to fish and aquatic invertebrates. Do not contaminate water when disposing
of equipment, washwater, or rinsate. See Directions for Use for additional precautions and
requirements."
For indoor products packaged in containers equal to or greater than 5 gallons or 50 Ibs add
the following statement:
"Do not discharge effluent containing this product into lakes, streams, ponds, estuaries, oceans, or
other waters unless in accordance with the requirements of a National Pollution Discharge
Elimination System (NPDES) permit and the permitting authority has been notified in writing prior
to discharge. Do not discharge effluent containing this product to sewer systems without previously
notifying the local sewage treatment plant authority. For guidance contact your State Water Board
or Regional Office of the EPA."
Precautionary
Statements under
Environmental Hazards
Restricted-Entry Interval
for WPS products as
required by Supplement
Three of PR Notice 93-7
"Do not enter or allow worker entry into treated areas during the restricted entry interval (REI) of
12 hours."
Directions for Use,
Agricultural Use
Requirements Box
Early Entry Personal
Protective Equipment for
Products subject to WPS as
required by Supplement
"PPE required for early entry to treated areas that is permitted under the Worker Protection
Standard and that involves contact with anything that has been treated, such as soil or water, is:
- coveralls,
- chemical-resistant gloves made of any waterproof material, and
Directions for Use,
Agricultural Use
Requirements Box
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Description
PBO Required Labeling Language
Placement on Label
Three of PR Notice 93-7
- shoes plus socks."
Entry Restrictions
for products with non-WPS
uses on the label
Note: This excludes
products labeled for use
when people are permitted
to be present (e.g. wide-area
mosquito adulticide
applications, metered
release devices, and pet
applications)
Entry Restriction for products applied as a spray (does not apply to products applied directly
to domestic animals):
"Do not enter or allow others to enter until sprays have dried."
Entry Restriction for products applied dry:
"Do not enter or allow others to enter until dusts have settled."
Entry Restriction for products applied as a space spray or as a fog::
"Do not enter or allow others to enter until vapors, mists, and aerosols have dispersed, and the
treated area has been thoroughly ventilated."
If no WPS uses on the
product label, place the
appropriate statement
in the Directions for
Use Under General
Precautions and
Restrictions. If the
product also contains
WPS uses, then create a
Non-Agricultural Use
Requirements box as
directed in PR Notice
93-7 and place the
appropriate statement
inside that box.
Entry Restrictions for
products labeled solely for
use when people are present
(e.g. wide-area mosquito
adulticide applications,
metered release devices,
and applications to pets)
Note to Registrants: No entry restrictions are required. See below under Use Restrictions for
further requirements.
Entry Restrictions for
products labeled for use
when people are present
(e.g. wide-area mosquito
adulticide applications,
metered release devices,
and applications to pets)
and for use on other sites as
a directed or space spray.
Products labeled for use as a directed spray (does not apply to products applied directly to
domestic animals):
"Except when (insert application method or site that allows people to be present), do not enter or
allow others to enter until sprays have dried."
Products labeled for use as a space spray:
"Except when (insert application method or site that allows people to be present), do not enter or
allow others to enter until vapors, mists, and aerosols have dispersed, and the treated area has been
thoroughly ventilated."
If no WPS uses on the
product label, place the
appropriate statement
in the Directions for
Use Under General
Precautions and
Restrictions. If the
product also contains
WPS uses, then create a
Non-Agricultural Use
Requirements box as
directed in PR Notice
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Description
PBO Required Labeling Language
Placement on Label
Note to Registrant: An example is as follows: Except when applying in a metered release system,
do not enter or allow others to enter until sprays have dried.
93-7 and place the
appropriate statement
inside that box.
General Application
Restrictions for products
with WPS or non-WPS uses
on the label
Note: This excludes
products that contain any
directions for uses when
people are permitted to be
present in the treated area
(e.g. . wide-area mosquito
adulticide applications,
metered release devices,
and applications to pets)
"Do not apply this product in a way that will contact workers or other persons, either directly or
through drift."
"Only protected handlers may be in the area during application."
Place in the Direction
for Use.
General Application
Restrictions for products
with WPS and non-WPS
uses on the label AND
contain directions for uses
when people are permitted
to be present in the treated
area (e.g. . wide-area
mosquito adulticide
applications, metered
release devices, and
applications to pets)
"Except when" (insert application method or site that allows people to be present) "do not apply this
product in a way that will contact workers or other persons, either directly or through drift."
"Except when" (insert application method or site that allows people to be present) "only protected
handlers may be in the area during application."
Place in the Direction
for Use.
General Application
Restrictions for products
Note to Registrants: No entry restrictions are required.
further requirements.
See below under Use Restrictions for
Place in the Direction
for Use.
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Description
PBO Required Labeling Language
Placement on Label
labeled for use solely when
people are permitted to be
present in the treated area
(e.g. wide-area mosquito
adulticide applications,
metered-release devices,
and applications to pets)
Other Application
Restrictions
Note to Registrants: Delete any reference to tolerance exemptions on labels.
In addition add the following restrictions depending on the registered product uses and formulation:
Wettable powder formulations:
"Do not apply this product as a dust."
"Do not apply in forestry areas."
Dust formulations:
"Aerial applications are prohibited."
"Applications with power duster equipment is prohibited, except when making applications to
agricultural commodities."
Products labeled for use as a space spray:
"Do not remain in treated area. Exit area immediately and remain outside the treated area until
aerosols, vapors, and/or mists have dispersed."
Products labeled for spray applications to plants:
"Do not wet plants to point of runoff or drip."
Products labeled for spray applications to articles:
"Do not wet articles to point of runoff or drip."
"Do not use treated article until spray has dried."
Directions for Use
under General
Precautions and
Restrictions and/or
Application
Instructions
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Description
PBO Required Labeling Language
Placement on Label
Products labeled for applications to clothing articles:
"Dry clean treated clothes before wearing."
Products labeled for dip applications:
"Do not use treated article before it is dry."
Products labeled for crack and crevice, surface or space spray, fogging or dust applications
indoors:
"Remove or cover exposed food and drinking water before application."
"Remove or cover dishes, utensils, food processing equipment, and food preparation surfaces, or
wash them before use."
Products labeled for applications to non-residential indoor sites:
"Do not use in aircraft cabins except in compliance with PR Notice 96-3."
"When used in dairy barns or facilities: Close milk bulk tank lids to prevent contamination from
spray and from dead or falling insects. Remove or cover milking utensils before application. Wash
teats of animals before milking."
Products labeled for use in food handling and processing facilities:
"Do not make space spray applications when facility is in operation."
"During space spray applications, cover or remove food."
"During space spray applications, cover food processing surfaces or clean after treatment with a
suitable detergent and rinse with potable water before use."
Rate Related Application
Restrictions
(Note: The maximum
application rate and
maximum seasonal rates
specified in this table must
be listed as pounds or
gallons of formulated
Food Crops Grown Outdoors or in Greenhouses in Agricultural Settings
Maximum application rates:
Field and orchard- 0.5 Ibs ai/acre or 0.012 Ib ai 71000 square feet
Hydroponically grown crops - 1.0 ppm ai in water
Greenhouse space sprays - 0.0014 Ibs ai/1000 cubic feet
Greenhouse surface spray - 0.012 Ibs per 1000 square feet or 0.5 Ibs ai per acre
Use restrictions:
Directions for Use
under General
Precautions and
Restrictions and/or
Application
Instructions
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Description
PBO Required Labeling Language
Placement on Label
product per acre/square
ft/ppm/cubic feet etc., not
just as pounds active
ingredient)
"Do not apply more than 10 times per season."
"Do not reapply within 3 days except under extreme pest pressure."
"In case of extreme pest pressure do not reapply within 24 hours."
"Do not apply to cotton within 14 days of seed harvest." (For labels with cotton only)
Forestry
Maximum application rate:
1.25 Ib ai per acre
Sod farms
Maximum application rate:
1 Ib ai per acre
Rice Fields
"A 10 day water hold is required for all pyrethrins applications when rice fields are flooded."
Greenhouse Grown Ornamental, Flowering and Foliage Plants:
Maximum application rates:
Surface applications - 0.036 Ibs ai/1000 square feet (or 1.5 Ib ai/acre)
Space sprays (including space, total release, and fogger applications) - 0.0042 Ibs ai/1000
cubic feet
Use restrictions:
"Do not apply more than 1 time per day."
Post-harvest Application to Vegetables (Potato, Tomato, Pea, Sweet Potato), Fruits (Apple,
Blackberry, Blueberry, Boysenberry, Cherry, Crabapple, Currant, Dewberry, Fig,
Gooseberry, Grape, Guava, Loganberry, Mango, Muskmelon, Orange, Peach, Pear,
Pineapple, Plum, Raspberry) Nuts (Almonds, Walnuts)and Other Commodities (Copra and
Peanut
Page 92 of 111
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Description
PBO Required Labeling Language
Placement on Label
Maximum application rates:
Surface applications - 0.10 Ib ai/ 1000 square feet
Surface application to fruits or tomatoes in baskets or hampers - 1.6 x 10-6 Ibs ai/ Ib of fruit
(or 1.6 ppm)
Space spray to fruits, vegetables, copra - 0.001 Ibs ai/1000 cubic feet
Dip or spray - 0.004 Ibs ai/ gallon
Use restrictions:
"Do not apply more than 1 time per day."
"Do not reapply within 7 days."
"Do not apply more than 10 times to sweet potatoes."
Post-harvest Applications to Stored Grain and Seed (Barley, Beans, Lima Beans, Birdseed,
Buckwheat, Cocoa beans, Corn, Cottonseed, Flax, Grain sorghum, Oats, Field Peas, Rice,
Rye, Wheat)
Products must be formulated to deliver no more than this maximum rate when used according
to directions:
Surface applications - 0.50 Ibs ai/1000 square feet
Direct application to bulk grain and seed - 1.0 Ib ai/1000 bushels grain
Maximum application rates:
Barley - 0.033 oz ai per cwt
Beans - 0.027 oz ai per cwt
Lima beans - 0.029 oz ai per cwt
Birdseed - 0.032 oz ai per cwt
Buckwheat - 0.033 oz ai per cwt
Cocoa beans - 0.037 oz ai per cwt
Corn - 0.029 oz ai per cwt
Cottonseed - 0.057 oz ai per cwt
Flax - 0.029 oz ai per cwt
Grain sorghum - 0.029 oz ai per cwt
Oats - 0.050 oz ai per cwt
Field peas - 0.027 oz ai per cwt
Page 93 of 111
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Description
PBO Required Labeling Language
Placement on Label
Rice - 0.036 oz ai per cwt
Rye - 0.029 oz ai per cwt
Wheat (club, common, durham) - 0.027 oz ai per cwt
What (emmer, spelt) - 0.040 oz ai per cwt)
Use restrictions:
"Do not reapply within 30 days."
Food Stored in Bags
Products must be formulated to deliver no more than this maximum rate when used according
to directions:
Space sprays may be made to the surfaces of bags of stored food products at the rate of 0.025
Ibs ai/1000 cubic foot.
Use restrictions:
"Direct application to food contact surfaces is prohibited."
Direct Application to Non-domestic Animals/Livestock
Use restrictions:
"Do not apply more than 1 time per day."
"Do not apply microencapsulated product to lactating or food animals."
Indoor Agricultural Premises and Commercial Animal Housing and Equipment (when
animals are NOT present)
Products must be formulated to deliver no more than this maximum rate when used according
to directions:
Surface applications - 0.56 Ibs ai/1000 square feet
Crack/crevice or spot surface - 0.56 Ibs ai/1000 square feet
Space sprays when non-domestic animals are absent- 0.025 Ibs ai/1000 cubic feet (Rate
changed from 0.033 Ibs)
Metered release device space sprays - 0.05 Ibs ai/1000 cubic feet/day
Page 94 of 111
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Description
PBO Required Labeling Language
Placement on Label
Use Restrictions:
"Do not apply more than 1 time per day."
Indoor Agricultural Premises and Commercial Animal Housing and Equipment (when
animals are present)
Products must be formulated to deliver no more than this maximum rate when used according
to directions:
Space sprays when non-domestic animals are present - 0.008 Ib ai/1000 cubic feet/day
Indoor Food Handling/Processing Facilities
Products must be formulated to deliver no more than this maximum rate when used according
to directions:
Surface applications - 0.56 Ibs ai/1000 square feet
Crack/crevice or spot surface -0.56 Ibs ai/1000 square feet
Space sprays- 0.025 Ibs ai/1000 cubic feeta
Metered release device space sprays - 0.05 Ibs ai/1000 cubic feet/day
Use Restrictions:
"Do not apply more than 1 time per day."
In addition, these label statements should be deleted from all products registered for food
handling and processing facilities:
"Except in Federally inspected meat and poultry plants, food processing operations may
continue when the product is applied as a general surface spray with care and in accordance
with the directions and precautions on the label, at a maximum rate of 0.11 pounds of
piperonyl butoxide per 1000 square feet."
"Except in Federally inspected meat and poultry plants, food processing operations may
continue when the product is applied as a crack and crevice treatment with care and in
accordance with the directions and precautions on the label, at a maximum rate of 0.56 pounds
of piperonyl butoxide per 1000 square feet."
Page 95 of 111
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Description
PBO Required Labeling Language
Placement on Label
Residential Dwellings and Commercial, Institutional Indoor Sites
Products must be formulated to deliver no more than this maximum rate when used according
to directions:
Surface applications - 0.56 Ibs ai/1000 square feet
Crack/crevice or spot surface - 0.56 Ibs ai/1000 square feet
Space sprays- 0.025 Ibs ai/1000 cubic feet
Metered release device space sprays - 0.05 Ibs ai/1000 cubic feet/day
Outdoor Agriculture Premises
Products must be formulated to deliver no more than this maximum rate when used according
to directions:
Surface applications - 0.020 Ibs ai/1000 square feet (or 1.0 Ibs ai/acre)
Crack/crevice or spot surface (including applications for fire ant applications or turf diagnostic
aid) - 0.56 Ibs ai/1000 square feetb
User Restrictions:
"Do not apply more than 1 time per day."
General Outdoor Sites (including Non-Agricultural rights-of-way,
Commercial/Institutional/Industrial Premises and Outdoor Eating Establishments)
Products must be formulated to deliver no more than this maximum rate when used according
to directions:
Surface applications - 0.075 Ibs ai/1000 square feet
Crack/crevice or spot surface - 0.56 Ibs ai/1000 square feet
User Restrictions:
"Do not apply more than 1 time per day."
Outdoor Ornamental and Lawns
Maximum application rates:
Page 96 of 111
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Description
PBO Required Labeling Language
Placement on Label
Surface applications - 0.020 Ibs ai/1000 square feet (or 1.0 Ibs ai/acre)
Crack/crevice or spot surface (including applications for fire ant applications or turf diagnostic
aid) - 0.56 Ibs ai/1000 square feet
User Restrictions:
"Do not apply more than 1 time per day."
Manholes
Products must be formulated to deliver no more than this maximum rate when used according
to directions:
Surface applications to manholes - 0.04 Ibs ai per manhole over a length of 200 feet
User Restrictions:
"Do not apply more than 1 time per day."
Pet Care
Use restrictions:
"Do not apply to pets less than 12 weeks old."
"Consult a veterinarian before applying this product on medicated, debilitated, aged, pregnant,
or nursing animals."
"Sensitivities may occur after using any pesticide product for pets. If signs of sensitivity occur
bathe your pet with mild soap and rinse with large amounts of water. If signs continue,
consult a veterinarian immediately."
Registrant Note: Follow instructions in PR Notice 96-6, Pet Pesticide Product Label
Statements, for including reapplication restrictions on the end-use product label.
Pet Premise Treatment
Products must be formulated to deliver no more than this maximum rate when used according
to directions:
Surface - 0.56 Ib per 1000 square feet
Crack and crevice - 0.56 Ibs per 1000 square feet
Page 97 of 111
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Description
I*BU Kequirea L:
Space spray - 0.033 Ibs per 1000 square feet
PBO Required Labeling Language
Placement on Label
Application Restrictions for
products used in Metered
Release Devices
Note to Registrants: Delete nurseries, day care centers, and nursing homes as registered use sites
on all product labels.
Add the following statements:
"Do not use in nurseries or rooms where infants, ill, or aged persons are confined."
"Do not place metering device directly over or within 8 feet of exposed food, dishes, utensils, food
processing equipment, and food handling or preparation."
"Do not install within 3 feet of air vents."
"Carefully follow directions for the dispenser unit when installing the dispenser and replacing cans
or conducting maintenance."
Directions for Use
under General
Precautions and
Restrictions and/or
Application
Instructions
Use-Specific Application
Restrictions for all liquid
and wettable powder labels
(Outdoor residential misting
system requirement)
(Note: The maximum
allowable application rate
and maximum allowable
seasonal rate must be listed
as pounds or gallons of
formulated product per acre,
not just as pounds active
ingredient per acre.)
Outdoor Residential Misting Systems
Products not intended for use in outdoor residential misting systems must contain the
following statement:
"Not for use in outdoor residential misting systems."
Products intended for use in outdoor residential misting systems must contain the following
statements:
"Directions for use in outdoor residential misting systems:"
"When using this product installers and service technicians must comply with the license,
certification, or registration requirements of the state(s), tribe(s), or local authority(ies) where they
are installed."
"If the system works on an automatic timer, set the timing for application when people, pets, and
food are unlikely to be present."
Directions for Use
under General
Precautions and
Restrictions and/or
Application
Instructions
Page 98 of 111
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Description
PBO Required Labeling Language
Placement on Label
"If the system works when a person operates a remote activation device, then application of this
pesticide when people, pets, and food are present is prohibited."
"Do not use in an evaporative cooling system."
"Direct nozzles to spray towards the target area and away from swimming pools, water bodies, or
eating and cooking areas."
"If used in a system with a reservoir tank for the end use dilution, the system reservoir tank must be
locked. Securely attach the end use pesticide label and a dilution statement to the system reservoir
tank in a weather protected area or plastic sleeve. The dilution statement must be phrased as
follows: this container holds parts {product name] to parts water"
"If used in a direct injection system, the pesticide container must be locked. Securely attach the end
use label to the pesticide container in a weather protected area or plastic sleeve." (These
instructions not applicable to wettable powder products).
"This product must only be used in systems that have been calibrated to apply no more than the
maximum application rate of [insert product application rate that is equal to 0.00058 Ibs piperonyl
butoxide per 1000 cubic feet per day].
Note to registrant: Also express this application rate as pounds or gallons of end-use product
formulation.
Use-Specific Application
Restrictions for products
labels for Wide Area
Mosquito Adulticide
Application by ground or
air.
(Note: The maximum
allowable application rate
and maximum allowable
seasonal rate must be listed
as pounds or gallons of
"For use by federal, state, tribal, or local government officials responsible for public health or
vector control, or by persons certified in the appropriate category or otherwise authorized by the
state or tribal lead pesticide regulatory agency to perform adult mosquito control applications, or by
persons under their direct supervision."
The maximum application rate for wide area mosquito adulticide applications is 0.025 Ibs ai/acre.
When targeting Aedes Taeirorhynchus and other difficult species applications may be made up to
0.08 Ibs ai/acre.
"Do not apply more than 2.0 Ibs ai/acre/year in any treated area More frequent treatments may be
made to prevent or control a threat to public and/or animal health determined by a state, tribal, or
local health or vector control agency on the basis of documented evidence of disease causing agents
Directions for Use
under General
Precautions and
Restrictions and/or
Application
Instructions
Page 99 of 111
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Description
PBO Required Labeling Language
Placement on Label
formulated product per acre,
not just as pounds active
ingredient per acre.)
in vector mosquitoes or the occurrence of mosquito-borne disease in animal or human populations,
or if specifically approved by the state or tribe during a natural disaster recovery effort."
Spray Drift Label Language
for all products labeled for
outdoor applications to
agricultural use sites
"SPRAY DRIFT MANAGEMENT for AGRICULTURE CROPS"
"Avoiding spray drift at the application site is the responsibility of the applicator and the grower.
The interactions of many equipment and weather-related factors determine the potential for spray
drift. The applicator and the grower are responsible for considering all these factors when making
decisions."
"Do not apply at wind speeds greater than 10 mph at the application site."
"Do not make any type of application into temperature inversions."
"Apply as a medium or coarser spray (ASABE standard 572)."
"Additional requirements for aerial applications:"
"Do not release spray at a height greater than 10 feet above the ground or crop canopy."
"The boom length must not exceed 75% of the wingspan or 90% of the rotor blade diameter."
"Aerial applicators must consider flight speed and nozzle orientation in determining droplet size."
"When applications are made with a cross-wind, the swath will be displaced downwind. The
applicator must compensate for this displacement at the downwind edge of the application area by
adjusting the path of the aircraft upwind."
"Additional requirements for ground applications:"
"Do not release spray at a height greater than 4 feet above the ground or crop canopy."
"Additional requirements for airblast applications:"
"Direct sprays into the canopy."
Directions for Use
under General
Precautions and
Restrictions
Page 100 of 111
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Description
PBO Required Labeling Language
"Turn off outward pointing nozzles at row ends and when spraying outer rows
Placement on Label
Spray Drift Label Language
for ALL Products Intended
for ULV Mosquito
Abatement Programs
"SPRAY DRIFT MANAGEMENT for WIDE AREA MOSQUITO ABATEMENT"
"A variety of factors including weather conditions (e.g., wind direction, wind speed, temperature,
relative humidity) and method of application (e.g., ground, aerial, airblast, chemigation) can
influence pesticide drift. The applicator must evaluate all factors and make appropriate adjustments
when applying this product."
WIND SPEED:
"Apply only when wind speed is greater than or equal to 1 mph."
Directions for Use
under General
Precautions and
Restrictions
Spray Drift Label Language
For End-Use Products
Applied with Ground-Based
Mechanical Application
Equipment for ULV
Mosquito Abatement
Programs
"Ground-based wide area mosquito abatement application:
Spray equipment must be adjusted so that the volume median diameter is less than 30 microns (Dv
0.5 < 30 um) and that 90% of the spray is contained in droplets smaller than 50 microns (Dv 0.9 <
50 um). Directions from the equipment manufacturer or vendor, pesticide registrant or a test
facility using a laxer-based measurement instrument must be used to adjust equipment to produce
acceptable droplet size spectra. Application equipment must be tested at least annually to confirm
that pressure at the nozzle and nozzle flow rate(s) are properly calibrated."
Directions for Use
under General
Precautions and
Restrictions
Spray Drift Label Language
for Products Applied as an
Aerial Spray for ULV
Mosquito Abatement
Programs
"Aerial wide area mosquito abatement application:
Spray equipment must be adjusted so that the volume median diameter produced is less than 60
microns (Dv 0.5 < 60 um) and that 90% of the spray is contained in droplets smaller than 80
microns (Dv 0.9 < 80 um). The effects of flight speed, and for non-rotary nozzles, nozzle angle on
the droplet size spectrum must be considered. Directions from the equipment manufacturer or
vendor, pesticide registrant or a test facility using a wind tunnel and laser-based measurement
instrument must be used to adjust equipment to produce acceptable droplet size spectra.
Application equipment must be tested at least annually to confirm that pressure at the nozzle and
nozzle flow rate(s) are properly calibrated."
RELEASE HEIGHT:
Directions for Use
under General
Precautions and
Restrictions
Page 101 of 111
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Description
PBO Required Labeling Language
Placement on Label
Fixed wing:
"Apply using a nozzle height of no less than 100 feet above the ground or canopy.
Rotary wing:
"Apply using a nozzle height of no less than 75 feet above the ground or canopy."
Products Primarily Used by Consumers/Homeowners
Entry Restrictions
for products except those
products that contain any
directions for uses when
people are permitted to be
present in the treated area
(e.g.. applications to pets)
Entry Restriction for products applied as a spray except for sprays applied directly to
domestic animals:
"Do not allow adults, children, or pets to enter the treated area until sprays have dried."
Entry Restriction for products applied dry:
"Do not allow adults, children, or pets to enter the treated area until dusts have settled."
Entry Restriction for products applied as a space spray or as a fog:
"Do not allow adults, children, or pets to enter until vapors, mists, and aerosols have dispersed, and
the treated area has been thoroughly ventilated."
Directions for use
under General
Precautions and
Restrictions
Entry Restrictions for
products products that only
contain directions for uses
when people are permitted
to be present (e.g. pet
applications)
Note to Registrants: No entry restrictions are required. See below under Use Restrictions for
further requirements.
Directions for use
under General
Precautions and
Restrictions
Entry Restrictions for
products that contain
directions for uses when
people are permitted to be
present in the treated area
Products labeled for use as a surface spray (does not apply to products applied directly to
domestic animals):
"Except when applying directly to pets, do not allow adults, children, or pets to enter until sprays
have dried."
Directions for use
under General
Precautions and
Restrictions
Page 102 of 111
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Description
PBO Required Labeling Language
Placement on Label
(e.g. applications to pets)
AND for use on other sites
as a surface spray.
General Application
Restrictions for all products
except those that contain
any directions for uses
when people are permitted
to be present in the treated
area (e.g. . applications to
pets)
"Do not apply this product in a way that will contact adults, children, or pets, either directly or
through drift."
Place in the Direction
for Use
General Application
Restrictions for products
that only contain directions
for uses when people are
permitted to be present (e.g.
pet applications)
Note to Registrants: No entry restrictions are required. See below under Use Restrictions for
further requirements.
Place in the Direction
for Use
General Application
Restrictions for products
that contain directions for
uses when people are
permitted to be present in
the treated area (e.g.
applications to pets) AND
for use on other sites as a
surface spray.
"Except when applying directly to pets, do not apply this product in a way that will contact adults,
children, or pets, either directly or through drift."
Place in the Direction
for Use
Environmental Hazards for
Residential Products
(Note: Products used on
domestic animals like flea
collars and ear tags,
generally do not require an
Environmental Hazards
"ENVIRONMENTAL HAZARDS"
"This product is toxic to aquatic organisms, including fish and invertebrates. Do not contaminate
water when disposing of equipment, washwater, or rinsate. See Directions for Use for additional
precautions and requirements."
Note to Registrants: For products with outdoor uses include the following statement.
Precautionary
Statements under
Environmental Hazards
Page 103 of 111
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Description
PBO Required Labeling Language
Placement on Label
statement.
In addition, products
containing the statement:
"For indoor use only," may
also omit the environmental
hazards statement.)
"Do not apply directly to or near water. Drift and run-off may be hazardous to fish in water
adjacent to treated areas."
Homeowner User Safety
Recommendations
Statements
"User Safety Recommendations
Users should wash hands with plenty of soap and water before eating, drinking, chewing gum, using
tobacco, or using the toilet.
Users should remove clothing immediately if pesticide gets inside. Then wash thoroughly and put
on clean clothing."
Precautionary
Statements under:
Hazards to Humans and
Domestic Animals
immediately following
Engineering Controls
(Must be placed in a
box.)
Other Application
Restrictions
Note to Registrants: Delete any reference to tolerance exemptions on labels.
In addition add the following restrictions depending on the registered product uses and formulation:
Wettable powder formulations:
"Do not apply this product as a dust."
"Do not apply in forestry areas."
Dust formulations:
"Aerial applications are prohibited."
"Applications with power duster equipment is prohibited, except when making applications to
agricultural commodities."
Products labeled for use as a space spray:
"Do not remain in treated area. Exit area immediately and remain outside the treated area until
aerosols, vapors, and/or mists have dispersed."
Products labeled for spray applications to plants:
Directions for Use
under General
Precautions and
Restrictions and/or
Application
Instructions
Page 104 of 111
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Description
PBO Required Labeling Language
Placement on Label
"Do not wet plants to point of runoff or drip."
Products labeled for spray applications to articles:
"Do not wet articles to point of runoff or drip."
"Do not use treated article until spray has dried."
Products labeled for applications to clothing articles:
"Dry clean treated clothes before wearing."
Products labeled for dip applications:
"Do not use treated article before it is dry."
Products labeled for crack and crevice, surface or space spray, fogging or dust applications
indoors:
"Remove or cover exposed food and drinking water before application."
"Remove or cover dishes, utensils, food processing equipment, and food preparation surfaces, or
wash them before use."
Products labeled for applications to non-residential indoor sites:
"Do not use in aircraft cabins except in compliance with PR Notice 96-3."
"When used in dairy barns or facilities: Close milk bulk tank lids to prevent contamination from
spray and from dead or falling insects. Remove or cover milking utensils before application. Wash
teats of animals before milking."
Use-Specific Application
Restrictions
For products with directions
for residential uses
Requirement for Liquid Formulations (except for Ready to Use) with outdoor uses:
"Do not apply directly to or near water, storm drains, or drainage ditches. Do not apply when
windy. To prevent product run-off, do not over water the treated area(s) or apply when heavy rain
is expected. Rinse applicator over lawn or garden area only."
Directions for Use
under General
Precautions and
Restrictions and/or
Application
Instructions
Page 105 of 111
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Description
Residential Use restriction
(Note: The maximum
allowable application rate
and maximum allowable
seasonal rate must be listed
as pounds or gallons of
formulated product per acre
or per square feet or per
cubic feet, not just as
pounds active ingredient per
unit area.)
PBO Required Labeling Language
Requirement for Ready to Use Liquid or Dust Formulations with outdoor uses:
"Do not apply directly to or near water, storm drains, or drainage ditches. Do not apply when
windy. To prevent product run-off, do not over water the treated area(s) or apply prior to heavy
rainfall."
Home Garden or Home Greenhouse Applications
Maximum application rates:
Garden and orchard- 0.5 Ibs ai/acre or 0.012 Ib ai 71000 square feet
Hydroponically grown crops - 1.0 ppm ai in water
Greenhouse space sprays - 0.0014 Ibs ai/1000 cubic feet
Greenhouse surface spray - 0.012 Ibs per 1000 square feet or 0.5 Ibs ai per acre
Use restrictions:
"Do not apply more than 10 times per season."
"Do not reapply within 3 days except under extreme pest pressure."
"In case of extreme pest pressure do not reapply within 24 hours."
"Do not apply to cotton within 14 days of seed harvest." (For labels with cotton only)
Residential Dwellings - Indoors
Products must be formulated to deliver no more than this maximum rate when used according
to directions:
Surface applications - 0.56 Ibs ai/1000 square feet
Crack/crevice or spot surface - 0.56 Ibs ai/1000 square feet b
Space sprays- 0.025 Ibs ai/1000 cubic feet a
General Outdoor Sites
Products must be formulated to deliver no more than this maximum rate when used according
to directions:
Surface applications - 0.075 Ibs ai/1000 square feet
Crack/crevice or spot surface - 0.56 Ibs ai/1000 square feet b
Placement on Label
Directions for Use
under General
Precautions and
Restrictions and/or
Application
Instructions
Page 106 of 111
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Description
PBO Required Labeling Language
Placement on Label
User Restrictions:
"Do not apply more than 1 time per day."
Outdoor Ornamental and Lawns
Maximum application rates:
Surface applications - 0.020 Ibs ai/1000 square feet (or 1.0 Ibs ai/acre)
spot treatment (including applications for fire ant applications or turf diagnostic aid) - 0.56 Ibs
ai/1000 square feetb
User Restrictions:
"Do not apply more than 1 time per day."
Pet Care
Use restrictions:
"Do not apply to pets less than 12 weeks old."
"Consult a veterinarian before sing this product on medicated, debilitated, aged, pregnant, or
nursing animals."
"Sensitivities may occur after using any pesticide product for pets. If signs of sensitivity occur
bathe your pet with mild soap and rinse with large amounts of water. If signs continue,
consult a veterinarian immediately."
Dusts
Use Restrictions:
"Only apply as a spot treatment to areas no greater than 3 feet by 3 feet per room."
Use-Specific Application
Restrictions for all liquid
and wettable powder labels
(Outdoor residential misting
Outdoor Residential Misting Systems
Products not intended for use in outdoor residential misting systems must contain the
following statement:
Directions for Use
under General
Precautions and
Restrictions and/or
Application
Page 107 of 111
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Description
PBO Required Labeling Language
Placement on Label
system requirement)
(Note: The maximum
allowable application rate
and maximum allowable
seasonal rate must be listed
as pounds or gallons of
formulated product per acre,
not just as pounds active
ingredient per acre.)
"Not for use in outdoor residential misting systems."
Products intended for use in outdoor residential misting systems must contain the following
statements:
"Directions for use in outdoor residential misting systems:"
"When using this product installers and service technicians must comply with the license,
certification, or registration requirements of the state(s), tribe(s), or local authority(ies) where they
are installed."
"If the system works on an automatic timer, set the timing for application when people, pets, and
food are unlikely to be present."
"If the system works when a person operates a remote activation device, then application of this
pesticide when people, pets, and food are present is prohibited."
"Do not use in an evaporative cooling system."
"Direct nozzles to spray towards the target area and away from swimming pools, water bodies, or
eating and cooking areas."
"If used in a system with a reservoir tank for the end use dilution, the system reservoir tank must be
locked. Securely attach the end use pesticide label and a dilution statement to the system reservoir
tank in a weather protected area or plastic sleeve. The dilution statement must be phrased as
follows: this container holds parts \product name] to parts water"
"If used in a direct injection system, the pesticide container must be locked. Securely attach the end
use label to the pesticide container in a weather protected area or plastic sleeve." (These
instructions not applicable to wettable powder products).
"This product must only be used in systems that have been calibrated to apply no more than the
maximum application rate of [insert product application rate that is equal to 0.00058 Ibs piperonyl
butoxide per 1000 cubic feet per day].
Instructions
Page 108 of 111
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Description
PBO Required Labeling Language
Note to registrant:
formulation.
Also express this application rate as pounds or gallons of end-use product
Placement on Label
1 PPE that is established on the basis of Acute Toxicity of the end-use product must be compared to the active ingredient PPE in this document. The more protective PPE
must be placed in the product labeling. For guidance on which PPE is considered more protective, see PR Notice 93-7.
Page 109 of 111
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Appendix: Technical Support Documents
Additional documentation in support of this RED is maintained in the OPP
docket, located in room S-4400, One Potomac Yard (South Building), 2777 S. Crystal
Drive, Arlington, VA 22202. It is open Monday through Friday, excluding legal holidays,
from 8:30 am to 4 pm.
All documents, in hard copy form, may be viewed in the OPP docket room or
downloaded or viewed via the Internet at the following site: http://www.regulations.gov
These documents include:
HED Documents:
Piperonyl Butoxide HED Revised Risk Assessment for Reregi strati on Eligibility
Document (RED). Daiss, B.; D326576; February 21, 2006.
Piperonyl Butoxide: Addendum to Occupational and Residential Exposure Assessment.
Daiss, B.; D327790; July 5, 2006.
Revised Occupational and Residential Exposure Assessment and Recommendation for
the Reregi strati on Eligibility Decision (RED) for Piperonyl Butoxide. Daiss, B.;
D318743; September 8, 2005.
Occupational and Residential Exposure Assessment for the Use of Piperonyl Butoxide in
Residential Outdoor Automatic Mister Systems. Crowley, M., D315334; August 30.
2005.
Piperonyl Butoxide: Risk-Based Application Rate for Residential Outdoor Automatic
Mister Systems. Crowley, M.; D325918; July 5, 2006.
Piperonyl Butoxide: Toxicology Chapter for the RED. Ramasamy, S.; D296885; TXR
0052707; September 23, 2004.
Piperonyl Butoxide: Revised Anticipated Residues and Acute probabilistic and Chronic
Dietary Exposure Assessment for the Reregi strati on Eligibility Decision. Morton, T.;
D310032; November 23, 2004.
Piperonyl Butoxide-First Report of the Hazard Identification Assessment Review
Committee. Ramasamy, S.; TXR 0052600; June 8, 2004.
Piperonyl Butoxide RED - Reregi strati on Eligibility Decision. Revised Product and
Residue Chemistry Considerations. Morton, T.; D310030; November 23, 2004.
Piperonyl Butoxide: Revised Metabolism Assessment Review Committee Report.
Morton, T, and Ramasamy, S.; D321269; September 1, 2005.
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Review of Pyrethrins Incident Reports - Second Revisions. Blondell, J.; D320300;
August 16, 2005.
Review of Piperonyl butoxide Incident Reports. Blondell, J.; D302030; May 10, 2004.
HED Response to Comments Documents:
Piperonyl Butoxide: Response to Public Comments on the HED Risk Assessment for
Piperonyl Butoxide RED Chapter. Daiss, B.; D324670; January 31, 2006.
Piperonyl Butoxide: Response to Phase 3 Comments - Toxicity Document. Ramasamy,
S.;D310025; September 14, 2005.
Piperonyl Butoxide: Response to Public Comments on the HED Risk Assessment for
Piperonyl Butoxide RED Chapter. Daiss, B.; D321496; September 9, 2005.
Piperonyl Butoxide (PBO), Pyrethrins and MGK-264: Health Effects Division's
response to the Registrant's concerns for using metaplasia seen in the larynx in
subchronic inhalation studies as an endpoint for inhalation risk assessment. Ramasamy,
S., et al.; D319913, D319914, andD320298; September 8, 2005.
EFED Documents:
Piperonyl Butoxide: EFED's Response to Public Comments and our Revised Ecological
Risk Assessment. Davy, M., and Eckel, W.; D296889 and D296881; September 6, 2005.
Tier 1 Drinking Water Assessment for Piperonyl Butoxide (Terrestrial Agriculture).
Eckel, W.; D286223, D286227, D286228, D286229; May 17, 2004.
EFED Response to Comments Documents:
Response to Comments of Phase 5 Period About Water Quality, and Other Issues on the
Revised Draft EFED RED Chapters for Pyrethrins, PBO and MGK-264. Davy, M., et al.:
D324663, D324664, D324667, D324662, D324671, and D324673; January 30, 2006.
EFED Response to Error-Only Review: Ecological Risk Assessment For Piperonyl
Butoxide. Eckel, W.; D296879; February 24, 2005.
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