Docket Number EPA-HQ-OPP-2010-0498

www.regulations.gov

Piperonyl Butoxide

Summary Document

Registration Review: Initial Docket

December 2010

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TABLE OF CONTENTS

 

I. Preliminary Work Plan (PWP) 4

II. Fact Sheet 12

This Preliminary Work Plan and Fact Sheet summarize the Environmental Protection Agency’s 

current position based on the following documents:

1. EFED Registration Review Problem Formulation for Piperonyl Butoxide, December 13,

2010.

2. Piperonyl Butoxide Human Health Risk Scoping Document in Support of Registration 

Review, September 15, 2010.

3. Piperonyl Butoxide: Review of Human Incidents, August 19, 2010.

4. Piperonyl Butoxide Screening Level Usage Analysis (SLUA), March 05, 2010.

5. Appendix A: Uses of Piperonyl Butoxide Eligible for Reregistration, September 23, 

2010.

6. BEAD Chemical Profile for Registration Review: Piperonyl Butoxide, December 17, 

2010.

All supporting documents for the registration review of piperonyl butoxide are located in docket 

EPA-HQ-OPP-2010-0498 at www.regulations.gov. 
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I. PRELIMINARY WORK PLAN – Piperonyl Butoxide

Introduction

The Food Quality Protection Act (FQPA) of 1996 mandated a registration review program. All 

pesticides distributed or sold in the United States (U.S.) generally must be registered by the 

Environmental Protection Agency (EPA or the Agency), based on scientific data showing that 

they will not cause unreasonable risks to human health or the environment when used as directed 

on product labeling. The registration review program is intended to make sure that, as the ability 

to assess risk evolves and as policies and practices change, all registered pesticides continue to 

meet the statutory standard of no unreasonable adverse effects to human health or the 

environment. Changes in science, public policy, and pesticide use practices will occur over time. 

Through the registration review program, the Agency periodically reevaluates pesticides to make 

sure that as change occurs, products in the marketplace can be used safely. Information on this 

program is provided at: http://www.epa.gov/oppsrrd1/registration_review/ . 

The Agency is implementing the registration review program pursuant to Section 3(g) of the 

Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA), and will review each registered 

pesticide every 15 years to determine whether it continues to meet the FIFRA standard for 

registration. The Agency will consider benefits information and data as required by FIFRA. The 

public phase of registration review begins when the initial docket is opened for each case. The 

docket is the Agency’s opportunity to state what it knows about the pesticide and what additional 

risk analyses and data or information it believes are needed to make a registration review 

decision. After reviewing and responding to comments and data received in the docket during 

this initial comment period, the Agency will develop and commit to a final work plan and 

schedule for the registration review of piperonyl butoxide.

Piperonyl butoxide (PBO) is a pesticide active ingredient that acts as a synergist, enhancing the 

pesticidal properties of other chemicals. It is registered for use in combination with insecticide 

and acaricide active ingredients, such as pyrethrins, synthetic pyrethroids and organophosphates,

in a variety of agricultural and non-agricultural sites. Registered residential uses include insect 

control inside and outside of the home, as well as direct applications to pets. Formulations and 

application methods are diverse. PBO was first registered in the United States in the 1950s. The 

Reregistration Eligibility Decision for PBO was issued in 2006.

Anticipated Risk Assessment and Data Needs

The Agency anticipates requiring data considered necessary to conduct a comprehensive 

ecological risk assessment, including an endangered species risk assessment, and to update and 

revise the human health risk assessment for all uses of PBO. Below is a summary of the issues 

relevant to the registration review of PBO and the data the Agency anticipates requiring. 
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Ecological Risk:

The most recent ecological risk assessment for PBO was conducted in 2005 in support of 

the 2006 Reregistration Eligibility Decision (RED).

Exposure to PBO from agricultural use will take place mainly in soil, sediment, and 

surface water, and from consumption of plants and other food items onto which it is 

sprayed. It may also reach the aquatic environment and may pass through wastewater 

treatment plants where it may be included in wastewater discharge.

The Agency has not conducted an ecological risk assessment that supports a complete 

endangered species determination for PBO. The ecological risk assessment planned 

during registration review will allow the Agency to determine whether PBO’s use has 

―no effect‖ or ―may affect‖ federally listed threatened or endangered species (listed 

species) or their designated critical habitats. When an assessment concludes that a 

pesticide’s use ―may affect‖ a listed species or its designated critical habitat, the Agency 

will consult with the U.S. Fish and Wildlife Service (FWS) and/or National Marine 

Fisheries Service (NMFS) (the Services), as appropriate.

A number of ecological data gaps were identified in the 2006 RED and are listed in the 

Existing Data Call-in section of this document.

Synergism studies examining the effects of Typical End Use Products containing PBO 

were required in the RED DCI. Additional synergism data is anticipated in registration 

review to examine the effects of PBO when co-applied with other pesticide active 

ingredients.

The Agency anticipates needing the following data in order to conduct a complete 

ecological risk assessment, including an endangered species assessment for PBO:

Environmental fate data gaps

o Guideline No. 835.1230 – Adsorption/Desorption (batch equilibrium)

o Guideline No. 835.4100 – Aerobic soil metabolism

o Guideline No. 835.4300 – Aerobic aquatic metabolism

o Guideline No. 835.4400 – Anaerobic aquatic metabolism

o Guideline No. 835.6100 – Analytical method for residues in soil and sediment

o Guideline No. 835.6200 – Analytical method for residues in water

o Guideline No. 875.2100 – Dislodgeable foliar residue (modified, total foliar 

dissipation data are required) 

Ecological toxicity data gaps

Data Gaps for Studies Testing Typical End Use Product (TEP)

o Guideline No. 850.3020 – Honey bee acute contact toxicity
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o Guideline No. 850.4100 - Terrestrial plant toxicity, Tier II (seeding emergence)1

o Guideline No. 850.4150 - Terrestrial plant toxicity, Tier II (vegetative vigor)1

Studies Triggered by PBO’s Use as a Synergist

o Guideline No. 850.1010 – Acute Freshwater Invertebrate Study

o Guideline No. 850.1075 – Acute Freshwater Fish Study

Data Gaps for Studies Testing Technical Grade Active Ingredient (TGAI)

o Guideline No. 850.1400 – Fish early life stage (estuarine/marine)

o Guideline No. 850.2100 – Avian acute oral toxicity (passerine species)

o Guideline No. 850.4400 – Aquatic vascular plant growth – Lemna spp. Tier II

2

o Guideline No. 850.5400 – Aquatic non-vascular plant growth Tier II

2

The Agency anticipates requiring the following data to use as an input to the Exposure and Fate 

Assessment Screening Tool’s (E-FAST) down-the-drain module to assess the amount of PBO

that would degrade during treatment, remain in biosolids, or remain in waste water. 

o Non-Guideline – Publicly-owned Treatment Works (POTWs) Effluent Monitoring 

and POTW Treatability Study

Please refer to the December 13, 2010 ―EFED Registration Review Problem Formulation 

for Piperonyl Butoxide,‖ for a more detailed discussion of the anticipated ecological risk 

assessment and data needs.

Human Health Risk:

The most recent human health risk assessment was conducted in 2006 in support of the 

2006 Reregistration Eligibility Decision.

The dietary exposure assessment (including food and water) may be updated to reflect 

current methodologies. 

The residential and occupational exposure assessments are adequate, but may be updated 

to reflect current standard operating procedures.

The aggregate risk assessment is adequate, but may be updated to incorporate any 

changes to the dietary and/or residential exposure assessments. 

A 2009 PBO Data Call-in required a number of residential and occupational exposure

and residue chemistry studies, which the Agency expects to receive in 2011. These 

studies will be considered in the PBO registration review risk assessment.

 

1 Tier II data requirements depend on the results of the Tier I study, which were included in the 2009 Data Call-in.

2 Registrants may opt to conduct a Tier I study, with the understanding that any adverse effects (even if <25%) will 

necessitate a Tier II study.
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Acute and subchronic neurotoxicity and immunotoxicity studies are required under 40 

CFR Part 158 as a part of the new data requirements for registration of a conventional 

pesticide. In the absence of required studies, EPA may use a database uncertainty factor 

of up to 10X. Once all of the newly required toxicity data have been received and 

subsequently reviewed, points of departure and safety factors may be reexamined and a 

new risk assessment may be conducted. 

The Agency will re-evaluate the tolerance expression for PBO during registration 

review to ensure it appropriately covers the metabolites and degradates of PBO and that 

it specifies the residues to be measured for each commodity.

A number of human health data gaps were identified in the 2006 RED and are listed in 

the Existing Data Call-in section of this document.

The Agency anticipates requiring the following data in order to conduct a complete 

human health risk assessment for PBO:

o Guideline No. 870.6200 – Acute and subchronic neurotoxicity

o Guideline No. 870.7800 – Immunotoxicity study

o Guideline No. 860.1900 – Field accumulation study in rotational crops3

Please refer to the September 15, 2010 ―Piperonyl Butoxide Human Health Risk Scoping 

Document in Support of Registration Review‖ available in the docket, for a detailed discussion of 

the anticipated human health risk assessment and data needs.

Endocrine Disruptor Screening Program

As required under FFDCA section 408(p), EPA has developed the Endocrine Disruptor 

Screening Program (EDSP) to determine whether certain substances (including pesticide active 

and other ingredients) may have an effect in humans or wildlife similar to an effect produced by 

a “naturally occurring estrogen, or other such endocrine effects as the Administrator may 

designate.” The EDSP employs a two-tiered approach to making the statutorily required 

determinations. Tier 1 consists of a battery of 11 screening assays to identify the potential of a 

chemical substance to interact with the estrogen, androgen, and or thyroid (E, A, or T) hormonal 

systems. Chemicals that go through Tier 1 screening and are found to have the potential to 

interact with E, A, or T hormonal systems will proceed to the next stage of the EDSP where EPA 

will determine which, if any, of the Tier 2 tests are necessary based on the available data. Tier 2 

testing is designed to identify any adverse endocrine related effects caused by the substance, and 

establish a quantitative relationship between the dose and the E, A, or T effect.

 

3 This study may be waived depending on the results of the confined accumulation in rotational crops study 

(Guideline 860.1850), which was included in RED Data Call-in.
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Between October 2009 and February 2010, EPA issued test orders/data call-ins for the first 

group of 67 chemicals, which contains 58 pesticide active ingredients and 9 inert ingredients. 

This list of chemicals was selected based on the potential for human exposure through pathways 

such as food and water, residential activity, and certain post-application agricultural scenarios. 

This list should not be construed as a list of known or likely endocrine disruptors.

PBO is among the group of 58 pesticide active ingredients on the initial list to be screened under 

the EDSP. For information on the status of the orders issued under the EDSP for each chemical, 

please visit our website at http://www.epa.gov/endo/ and click on the "Status of EDSP 

Orders/DCIs" in the Highlights Box. Additional information on the EDSP, including the policies 

and procedures, the list of 67 chemicals, the test guidelines and the Tier 1 screening battery, can 

also be found at this website.

Timeline

 

The Agency has created the following estimated timeline for the completion of the piperonyl 

butoxide registration review.

Registration Review for Piperonyl Butoxide – Projected Registration Review Timeline

Activities Estimated Date

Opening the docket

Open Docket and Public Comment Period 2010 – December

Close Public Comment 2011 – February

Case Development

Final Work Plan 2011 – May

Issue DCI 2012 – Jan. – March

Data Submission 2014 – Jan. - March

Open Public Comment Period for Preliminary Risk Assessments 2015 – July – Sept.

Close Public Comment Period 2015 – Oct. – Dec.

Registration Review Decision

Open Public Comment Period for Proposed Registration Review 

Decision

2016 – Jan. – March

Close Public Comment Period 2016 – Apr.- June

Registration Review Decision and Begin Post-Decision Follow-up 2016

Total (years) 6

Guidance for Commenters

The public is invited to comment on EPA’s preliminary registration review work plan and 

rationales. The Agency will carefully consider all comments, as well as any additional 
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information or data provided in a timely manner, prior to issuing a final work plan for the 

piperonyl butoxide case.

Trade Irritants

Through the registration review process, the Agency intends to solicit information on trade 

irritants and, to the extent feasible, take steps toward facilitating irritant resolution. Growers and 

other stakeholders are asked to comment on any trade irritant issues resulting from lack of 

Maximum Residue Limits (MRLs) or disparities between U.S. tolerances and MRLs in key 

export markets, providing as much specificity as possible regarding the nature of the concern.

Environmental Justice

EPA seeks to achieve environmental justice, the fair treatment and meaningful involvement of all 

people, regardless of race, color, national origin, or income, in the development, implementation, 

and enforcement of environmental laws, regulations, and policies. To help address potential 

environmental justice issues, the Agency seeks information on any groups or segments of the 

population who, as a result of their location, cultural practices, or other factors, may have 

atypical, unusually high exposure to PBO compared to the general population. Please comment 

if you are aware of any sub-populations that may have atypical, unusually high exposure, 

compared to the general population.

Water Quality

PBO is not identified as a cause of impairment for any water bodies listed as impaired under 

section 303(d) of the Clean Water Act, based on information provided at 

http://iaspub.epa.gov/tmdl_waters10/attains_nation_cy.cause_detail_303d?p_cause_group_id=88

5. However, the pyrethroids as a group have been identified as a cause for impairment for three 

water bodies in Central Valley, CA: Del Puerto Creek, Ingram Creek Site (confluence with 

Hospital Creek to Hwy 33 crossing) and second Ingram Creek Site (confluence with San Joaquin 

River to confluence with Hospital Creek). This may be relevant to the PBO registration review 

case since PBO is commonly used in combination with pyrethroids.

Nonetheless, no Total Maximum Daily Load (TMDL) criteria have been developed for PBO, 

based on information provided at 

http://iaspub.epa.gov/tmdl_waters10/attains_nation.tmdl_pollutant_detail?p_pollutant_group_id

=885&p_pollutant_group_name=PESTICIDES. More information on impaired water bodies and 

TMDLs can be found at http://www.epa.gov/owow/tmdl/. The Agency invites submission of 

water quality data for these pesticides. To the extent possible, data should conform to the quality 

standards in Appendix A of the OPP Standard Operating Procedure: Inclusion of Impaired 

Water Body and Other Water Quality Data in OPP’s Registration Review Risk Assessment and 

Management Process (see: 
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http://www.epa.gov/oppsrrd1/registration_review/water_quality_sop.htm) in order to ensure they 

can be used quantitatively or qualitatively in pesticide risk assessments.

Other Information

Stakeholders are also specifically asked to provide information and data that will assist the 

Agency in refining risk assessments, including any species-specific ecological effects 

determinations for PBO. The Agency is interested in receiving the following information:

1. For non-agricultural uses, information on target pests, efficacy of PBO and its technically 

feasible alternatives (e.g., MGK-264), and treatment costs.

2. Confirmation of the major target pests for which PBO is used in agricultural production.

3. For the major target pests in agricultural uses, comparative efficacy of PBO versus other 

synergists.

4. Recent resistance reports for PBO in populations of important target pests.

5. For agricultural uses, worker activities that occur in treated fields at the typical time of 

PBO applications.

6. Comparative costs of PBO versus other synergists in crops identified as major usage 

sites.

7. Confirmation on the following label information.

a. sites of application

b. formulations

c. application methods and equipment

d. maximum application rates

e. frequency of application, application intervals, and maximum number of 

applications per season and per year

f. geographic limitations on use

8. Use or potential use distribution (e.g. geographical distribution of relevant uses).

9. Use history.

10. Median and 90th percentile reported use rates (lb/A, lb 1K sq.ft) from usage data –

national, state and county.

11. Application timing (date of first application and application intervals) by use – national, 

state, and county.

12. Usage/use information for non-agricultural uses. 

13. Directly acquired county-level usage data (not derived from state level data).

a. maximum reported use rate (lb/cc) from usage data – county

b. median and 90th percentile number of applications – county

c. total pounds per year – county

d. the year the pesticide was last used in the county/sub-county area

e. the years in which the pesticide was applied in the county/sub-county area

14. Typical application interval (days).

15. State or local use restrictions.
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16. Ecological incidents (non-target plant damage and avian, fish, reptilian, amphibian, 

mammalian mortalities, and bee or beneficial insect mortalities) not already reported to 

the Agency.

17. Monitoring data, including existing or ongoing Publically Owned Treatment Works 

(POTWs) effluent monitoring data for the pyrethroids be submitted to the Agency. These 

data may be relevant to the PBO registration review case since PBO is commonly used in 

combination with pyrethroids.

Next Steps

After the 60-day comment period closes, the Agency will consider and respond to any comments 

received in a timely manner. The Agency expects to issue a Final Work Plan in May of 2011 for 

PBO.
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II. FACT SHEET

Background Information

Piperonyl butoxide case number: 2525.

Piperonyl butoxide PC Code: 067501; CAS # 51-03-6.

Piperonyl butoxide was first registered in the 1950s.

The Reregistration Eligibility Decision for piperonyl butoxide was issued in June 2006. 

The RED and its supporting risk assessments are available in docket EPA-HQ-OPP2005-0042 at www.regulations.gov. 

Technical registrants: Bayer Environmental Science, Endura S.P.A., McLaughlin 

Gormley King Co., Prentiss Inc., Pyranha Inc., S.C. Johnson & Son Inc., Takasago 

International Corp., Valent Biosciences Corp., Whitmire Micro-Gen Research 

Laboratories Inc.

Active registrations as of May 2010:

o 814 Section 3 registrations

o 10 Section 24(c) registrations (Special Local Need)

Pesticide Re-evaluation Division Contact: Jose Gayoso (gayoso.jose@epa.gov).

Registration Division Contact: Richard Gebken (gebken.richard@epa.gov).

Use and Usage Information

For additional details, please refer to ―Piperonyl Butoxide Screening Level Usage Analysis, 

March 05, 2010,‖ ―Appendix A: Uses of Piperonyl Butoxide Eligible for Reregistration, 

September 23, 2010,‖ and ―BEAD Chemical Profile for Registration Review: Piperonyl 

Butoxide, December 17, 2010,‖ available in the piperonyl butoxide docket.

From 1998-2008, PBO annual total agricultural usage averaged approximately 9,000 lbs 

active ingredient (a.i.) for almost 60,000 acres of all crops.

The states with the most agricultural usage in terms of pounds a.i. applied include 

Oklahoma, California, Wisconsin, Arkansas, Iowa, Alabama, and Texas.

Uses include pre- and post-harvest application to food and non-food agricultural crops, 

applications in food and non-food handling commercial and agricultural structures and 

outdoor premises, housing for veterinary and farm animals, and direct application to 

veterinary and farm animals.

Residential uses include insect control both inside the home and outside on gardens, 

lawns and ornamentals, patios, and other outdoor structures, and direct application to 

pets.

In agricultural settings, common formulations used include liquid, wettable powder, and 

microencapsulate (since these are formulations that are used in combination with 

synthetic pyrethroids). In non-agricultural settings (e.g., residential and food-handling 

establishments), commonly used formulations include ready-to-use solutions, liquids, and 

aerosols.

Application methods include aerosol cans, mist blowers, metered aerosol units, aerial 

application, truck-mounted ultra low volume (ULV) equipment, hand held sprayers, 
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thermal fogging equipment, conventional dusting equipment (e.g., shaker cans), and 

irrigation systems.

Non-agricultural PBO usage data are limited.

PBO usage trends (in both agricultural and non-agricultural sites) probably reflect those 

of several synthetic pyrethroids with which it is co-formulated. Synthetic pyrethroids are 

typically used to control a variety of caterpillars, aphids, beetles, and 

grasshoppers/crickets.

Recent and Pending Actions

There are no recent or pending actions for PBO.

Ecological Risk Assessment Status

The following are key findings from the most recent ecological risk assessments regarding the 

environmental fate, ecological effects and risks of PBO. Please refer to the December 13, 2010 

―EFED Registration Review Problem Formulation for Piperonyl Butoxide,‖ located in the 

docket, for a detailed discussion.

The most recent ecological risk assessment on PBO was conducted in 2005 in support of 

the 2006 PBO RED.

Environmental Fate:

PBO degrades rapidly (8.4-hour half-life) in the environment by photolysis in water, and 

is metabolized by soil microorganisms (half-life 14 days in one experiment). 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. 

Little volatilization from soil or water is expected; however, PBO may enter the 

atmosphere as an aerosol as a result of spraying. 

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 PBO from agricultural use will take place mainly in soil and surface water, 

and from consumption of plants and other food items onto which it is sprayed. It may 

also reach the aquatic environment by passing through wastewater treatment plants and 

being discharged.

Ecological Effects:

PBO is moderately toxic to fish and freshwater invertebrates, and highly toxic to 

estuarine invertebrates, on an acute basis.
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PBO is practically non-toxic to terrestrial birds, mammals, and insects.

Levels of concern (LOCs) were exceeded for the following as a result of the agricultural 

uses of PBO:

o Acute risk to amphibians, estuarine/marine invertebrates, freshwater invertebrates and 

freshwater fish

o Chronic risk to freshwater invertebrates and freshwater fish

LOCs were exceeded for acute risk to freshwater invertebrates, estuarine/marine 

invertebrates, and amphibians as a result of the mosquito control use of PBO.

Endangered species LOCs were exceeded for acute risk to freshwater invertebrates, 

estuarine/marine invertebrates, and amphibians as a result of spray drift caused by aerial 

applications.

Endangered species LOCs were exceeded for acute risk to amphibians as a result of 

ground application spray drift.

LOCs were exceeded for chronic risk to birds and mammals for applications using the 

maximum rate of 0.5 lbs ai/acre.

Mitigation measures to address these risks, such as reducing rates and setting maximum 

seasonal applications, were required in the 2006 PBO RED.

Human Health Risk Assessment Status

The following are key findings from the human health risk assessments conducted for PBO

registered uses. Please refer to the September 15, 2010 ―Piperonyl Butoxide Human Health Risk 

Scoping Document in Support of Registration Review,‖ located in the docket, for a detailed 

discussion of the human health risk assessment status.

Human Studies:

Past PBO risk assessments rely in part on data from studies in which adult human 

subjects were intentionally exposed to a pesticide to determine their dermal and 

inhalation exposure. Many such studies, involving exposure to many different pesticides, 

comprise generic pesticide exposure databases such as the Pesticide Handlers Exposure 

Database (PHED), the Agricultural Reentry Task Force (ARTF) Database and the 

Outdoor Residential Exposure Task Force (ORETF) Database. EPA has reviewed all the 

studies supporting these multi-pesticide generic exposure databases, and has found no 

clear and convincing evidence that the conduct of any of them was either fundamentally 

unethical or significantly deficient relative to the ethical standards prevailing at the time 

the research was conducted. All applicable requirements of EPA’s Rule for the 

Protection of Human Subjects of Research (40 CFR Part 26) have been satisfied, and 

there is no regulatory barrier to continued reliance on these studies.
15

Hazard Characterization:

PBO has a low acute toxicity by oral, inhalation and dermal routes (Toxicity Category 

IV). It is minimally irritating to eyes and skin and is negative for dermal sensitization 

effects. In a subchronic inhalation toxicity study, mild hyperplasia and metaplasia were 

noticed in the respiratory tract of rats.

The major target organ for PBO-induced toxicity is the liver. Subchronic and chronic 

studies in rats, mice and dogs showed PBO treatment caused clinical and 

histopathological effects in the liver.

PBO is classified as a Group C -possible human carcinogen based primarily on 

statistically significant increases in hepatocellular tumors in both sexes of the CD-1

mouse (adenomas, carcinomas and combined adenomas/carcinomas in males and 

adenomas in females).

No developmental effects were noted in guideline studies using rats and rabbits. 

Neurotoxic effects of PBO were not evident from the clinical signs reported in 

developmental, reproductive and chronic studies submitted to the Agency.

Although PBO was reported to inhibit microsomal enzymes in mammalian systems, it 

was shown to exhibit biphasic effects, i.e., initial inhibition followed by stimulation of 

microsomal enzymes upon continued exposure. Evidence from the published literature 

indicated that PBO does not effectively act as a pyrethroid synergist in mammals, 

including humans. 

Toxicity points of departure (PODs) were selected for oral and inhalation exposure 

pathways for the risk assessment conducted for the 2006 RED. No dose or endpoints 

were selected for dermal exposure because no systemic effects were observed at the limit 

dose in the 21-day dermal toxicity study in rabbits.

Since there were adequate developmental studies in rats and rabbits, an adequate multigeneration study in rats and no residual uncertainties that indicated the need for retaining 

an additional factor, the FQPA factor was reduced to 1x. An uncertainty factor of 100x 

was applied to endpoints selected for oral exposure (10x for interspecies extrapolation, 

10x for intraspecies variation). An uncertainty factor of 300 was applied to short- and 

intermediate-term inhalation endpoints (conventional uncertainty factor of 100x plus an 

additional 3x for the lack of a No Observed Adverse Effect Level (NOAEL) and use of a 

Lowest Observed Adverse Effect Level (LOAEL)). An uncertainty factor of 1000 was 

applied to long-term inhalation endpoints due to use of a subchronic study to assess 

chronic exposures.

Dietary Risk:
16

Acute and chronic dietary (food only) assessments showed no risks of concern for the 

general U.S. population and all population subgroups. Acute dietary risk did not exceed 

the Agency’s level of concern for the general US population at 6% of the Acute 

Population Adjusted Dose (aPAD). The risk estimate for the most highly exposed 

subpopulation, children 1-2, was below the Agency’s level of concern at 20% of the 

aPAD. The chronic dietary risk was below the Agency’s level of concern; risk 

estimates are 11% Chronic Population Adjusted Dose (cPAD) for the general U.S. 

population, and 32% of the cPAD for children 1-2 years old, the most exposed 

subpopulation. 

Residential Risk:

Residential scenarios assessed include short and intermediate-term exposures of handlers 

(mixers, loaders, applicators, etc.) that occur during application of PBO and short-term 

post-application exposure from activities in treated areas. The results of the residential 

assessment indicated that most residential handler and post-application exposure 

scenarios were not of concern. The two quantitative post-application exposure scenarios 

that presented potential risks of concern were applications from indoor metered release 

devices and applications from outdoor residential misting systems. In addition, based on 

a qualitative analysis, the broadcast dust applications to carpets scenario was identified as 

posing potential risks of concern. A quantitative assessment of application of dust with 

shaker can, bulb duster, and power duster was not conducted due to lack of dust-specific 

or adequate surrogate data on inhalation exposure associated with this activity. 

Mitigation measures, including limiting use of metered release devices, reducing rate for 

misting systems, and prohibiting application with specific dusting equipment, were 

required in the RED to address the risks identified above.

Aggregate Risk:

Acute and chronic aggregate exposure assessments for PBO showed no risks of concern 

(i.e., model-based estimates for allowable concentrations in surface water and 

groundwater were below the calculated drinking water levels of concern for each 

scenario). 

The short-term aggregate risk assessment integrates the assessments conducted for 

dietary, drinking water and residential exposure. The toxicity endpoints selected for the 

dietary, drinking water, and incidental oral routes of exposure were aggregated because 

of the common toxicity endpoints (decreased body weight gain) via these routes. The 

short-term aggregate exposure assessment for PBO showed no risks of concern.

Occupational Risk:

Thirty-four occupational exposure scenarios were assessed for agricultural, forestry, 

professional pest control operator, and mosquito control applications of PBO. The eight 

scenarios that indicated potential risk concerns were mixing and loading wettable 

powders, indoor fogging application using handheld foggers, application of dust 

formulations with power duster equipment, mixing and loading liquids for aerial forestry 
17

applications, application of indoor crack and crevice treatment with a low pressure 

handwand, greenhouse applications with high pressure handwand equipment, application 

of indoor space sprays, and exposure to metered release systems used in dairy barns and 

other structures. Mitigation measures, including reducing rates, prohibiting certain 

application methods, and requiring additional Personal Protective Equipment, were 

required in the RED to address the risks identified above. 

Cumulative Risk:

At this time, EPA does not have available data to determine whether PBO has a common 

mechanism of toxicity with other substances. EPA has not made a common mechanism 

of toxicity finding for PBO and any other substances and, PBO does not appear to 

produce a toxic metabolite produced by other substances which have tolerances in the 

United States. Therefore, EPA has not assumed that PBO has a common mechanism of 

toxicity with other substances. 

Incidents

Ecological:

An incident review was made on August 31, 2010 by querying the Ecological Incident 

Information System (EIIS, version 2.1) and the Avian Monitoring Information System 

(AIMS). Fourteen incidents were found, including the addition of two incidents since the 

2006 RED; both occurred in 2005. In Florida, 12 to 24 butterflies were killed most likely

by spray drift from mosquito control using Biomist 31 + 66 ULV (active ingredients 

permethrin and PBO). In North Dakota, the death of 4 Koi carp was possibly (but 

unlikely) linked to use of Anvil 10+10 ULV (active ingredients phenothrin and PBO). In 

both of these incidents, it was unclear whether the products were used according to the 

label. 

For the incidents reviewed in the RED, as well as the two new incidents, the Agency 

could not attribute any of the incidents to PBO alone since, as an insecticide synergist, it 

is always co-formulated with another insecticide or acaricide. Seven incidents were from 

registered use of PBO, one from misuse, and six undetermined. The aquatic incident 

(flounder, flukes, shrimp and crabs) involved resmethrin with PBO; the terrestrial animal 

incidents involved permethrin with PBO (monarch butterflies and bees) and rotenone 

with PBO (swans and geese); the terrestrial plant incidents (mostly ornamental plants) 

involved permethrin or pyrethrins with PBO. Therefore, the incidents do show that PBO 

in conjunction with an insecticide has the potential to cause adverse effects to aquatic 

ecosystems and beneficial insect populations. 

Human Health:

In general, a moderately large number of incidents have been reported involving PBO. 

Although none of the incidents involved cases reported for products containing PBO

present as a single chemical only, human incident data may warrant further analysis for 
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the human health risk assessment and/or risk management of PBO. The Agency will 

continue to monitor the incident information and, if a concern is triggered, additional 

analysis will be included in the risk assessment. For details, please see the August 19, 

2010 ―Piperonyl Butoxide: Review of Human Incidents,‖ available in the docket.

Tolerances and International Harmonization

PBO tolerances can be found in 40 CFR 180.127. Information on tolerance reassessment 

can be found in the 2006 PBO RED. 

The Agency will work to harmonize tolerances/MRLs, where feasible, with Canada, 

Mexico, and the Codex Alimentarius Commission during registration review.

Existing Data Call-Ins

A DCI was issued to PBO technical registrants in May 2009 to address data gaps 

identified in the 2006 RED. These data, along with the anticipated registration review 

data requirements, will be used to develop the forthcoming human health and ecological 

risk assessments for the registration review of PBO. The following data have been 

required:

o Guideline No. 830.7050 UV/Visible absorption

o Guideline No. 840.1100 Spray droplet size spectrum

o Guideline No. 840.1200 Spray drift field deposition

o Guideline No. 850.1010 Freshwater invertebrate acute toxicity

o Guideline No. 850.1075 Freshwater and marine fish acute toxicity 

o Guideline No. 850.1350 Mysid chronic toxicity 

o Guideline No. 850.1500 Fish full life cycle toxicity

o Guideline No. 850.4100 Terrestrial plant toxicity, Tier I (seeding emergence)

o Guideline No. 850.4150 Terrestrial plant toxicity, Tier I (vegetative vigor)

o Guideline No. 860.1380 Storage stability data 

o Guideline No. 860.1500 Crop field trials (for various commodities)

o Guideline No. 860.1520 Processed food/feed (for apple, barley, coconut, field corn, 

fig, flax, oat, peanut, pineapple, plum, rice, rye, sorghum, and wheat)

o Guideline No. 860.1850 Confined accumulation in rotational crops

o Guideline No. 875.1300 Inhalation exposure—outdoor (ORETF)

o Guideline No. 875.1400 Inhalation exposure—indoor (metered release devices)

o Guideline No. 875.1400 Inhalation exposure - indoor - ULV fogger

o Guideline No. 875.1700 Product use information (outdoor residential misting 

systems)

o Guideline No. 875.2300 Indoor surface residue dissipation

o Guideline No. 875.2500 Inhalation exposure (fogging)
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o Guideline No. 875.2500 Inhalation exposure - post application (outdoor residential 

misting systems)

o Non-guideline Chronic freshwater sediment toxicity

o Non-guideline Chronic estuarine sediment toxicity

Labels

Active Section 3 labels for PBO can be obtained from the Pesticide Product Label System 

(PPLS) website: http://oaspub.epa.gov/pestlabl/ppls.home.