Docket Number EPA

- HQ

- OPP

- 2010

- 0498

www.regulations.gov



## Piperonyl Butoxide

Summary Document Registration Review: Initial Docket

December 20103 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. Pipero nyl 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 B utoxide, December 1 7

, 2010

.

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

EPA

- HQ

- OPP

- 2010

- 0498 at www.regulations.gov.4

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 S tates (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 healt h 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 marketp lace 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. T he 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 insec ticide

and acaricide active ingredients, such as pyrethrins, synthetic pyrethroid s and organophosphate s, in a variety of agricultura l and non

- agricultural sites. Re gistered re sidential 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 end angered species risk assessment

, and to update and

revise the human health risk assessment for all uses of PBO

. Below is a s ummary of the issues relevant to the registration review of PBO and the data the Agency anticipates requiring

.5

Ecological Risk:

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

the 2006 Reregistration Eligibility D ecision (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 reg istration 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, th e 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 w ere 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 ass essment for PBO :

Environmental fate data gaps

o G uideline No. 835.1230

– A dsorption/ D esorption ( batch equilibrium )

o G uideline No. 835.4100

– Aerobic soil metabolism

o G uideline No. 835.4 3 00

– Aerobic aquatic metab o lism

o G uideline No. 835.4 4 00

– A na erobic aquat ic metab o lism

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 G uideline No. 875.2100

– Dislodgeable foliar residue (modified, total foliar dissipation data are r equired)

Ecological toxicity data gaps

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

o G uideline No. 850. 302 0

– Honey bee acute contact toxicity6

o G uideline No. 850.4100

- Terrestrial plant toxicity, Tier II (seeding emergence) 1

o G uideline No. 850.4150

- Terrestrial plant toxicity, Tier II (vegetative vigor) 1

Studies Triggered by PBO’s Use as a Synergist

o G uideline No. 850. 1010

– Acute Freshwater Invertebrate Study

o G uideline No. 850. 1075

– Acute Freshwater Fish Study

Data Gaps for Studies Tes ting Technical Grade Active Ingredient ( TGAI )

o G uideline No. 850. 1400

– Fish early life stage ( estuarine/marine )

o G uideline No. 850.2100

– Avian acute oral toxicity (passerine species )

o G uideline No. 850.4400

– Aquatic vascular plant growth

– Lemna spp. Tier I I 2

o G uideline No. 850. 5 400

– Aquatic non

- vascular plant growth T ier I I 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

- G uideline

– 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 Reregis tration Eligibility Decision.

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

The residential and occupational exposure assessment s 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

a nd 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 req uirements 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.7

Acute and s ubchronic neurotoxicity and immunotoxicity studies are required under 40

CFR Part 158 a s 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 subsequent ly 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 a nd 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 req uiring 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

– F ield accumulation study in r otational crops 3

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 n eeds.

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. T ier 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 end ocrine related effects caused by the substance, and establish a quantitative relationship between the dose and the E, A, or T effect.

3 This stud y 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.8

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

PBO is a mong 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 und er 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

a nd 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 201 1

– February Case Development

Final Work Plan 2011

– May

Issue DCI 201 2

– Jan

. – March

Data Submission 201 4

– 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

D ecision 2016

– Jan.

– March

Close Public C omment P eriod 2016

– Apr.

- June Registration Review D ecision and Begin P ost

- D ecision F ollow

- up 2016 Total ( years ) 6

Guidance for Commenters

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

rationale s . The Agency will carefully consider all comments, as well as any additional9

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 st akeholders 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 c oncern.

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 environme ntal 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 atypi cal, 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://ia spub.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 (con fluence 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 pyr ethroids.

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 submissi on of water quality data for the s e pesticide s . 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:10

http://www.epa.gov/oppsrrd1/registration_re view/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 refi ning 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, c omparative efficacy of PBO versus other synergists.

4. Recen t r esistance reports for PBO in populations of important target pests.

5. For agricultural uses, w orker 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 ma jor 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 a nd 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 90 th percentile reported use rates (lb/A, lb 1K sq.ft) from usage data

– national, state and county.

11. Appl ication 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 90 th 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/s ub

- county area
14. Typical application interval (days).

15. State or local use restrictions.11

16. Ecological inciden ts (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 P ublically O wned T reatment W orks (POTWs) effluent monitoring data for the pyrethroids be submitted to the Agenc y. These data may be relevant to the PBO registration review case since PBO is com monly used in combination with pyrethroids.

Next Steps

After the 6 0

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

re ceive d in a timely manner . The Agency expects to issue a Final Work Plan in May o f 2011 for

PBO

.12

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 2 006.

The RED and its supporting risk assessments are available in docket EPA

- HQ

- OPP

2005

- 0042 at www.regulations.gov

. T echnical registrant s: Bayer Environmental Science, Endura S.P.A., McLaughlin Gormley King C o., Prentiss Inc., Pyranha Inc., S.C. Johnson & Son Inc., Takasago International Corp., Valent Biosciences Corp., Whitmire Micro

- Gen Research

Laboratories Inc. Active registrations a s 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 C ontact: Richard Gebken ( gebken.richard @epa.gov )

.

Use and Usage Information For additional details, please ref er 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 1 7 , 2010

, ‖ available in the piperonyl butoxide docket.

Fr om 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, C alifornia, 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 struct ures and outdoor premises, housing for veterinary and farm animals, and direct application to veterinary and farm animals.

Residential uses include insect control bot h 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

- agricultur al 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

- mou nted ultra low volume (ULV) equipment, hand held sprayers,13

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

- ag ricultural 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 Action s
There are no recent or pending action s 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 th e December 13 , 2010

― EFED Registration Review Problem Formulation for Piperonyl Butoxide

, ‖ located in the

do cket, for a detailed discussion.

The most r ecent ecological risk asses sment on PBO was conducted in 200 5 in support of

the 2006 PBO RED

.

Environme ntal 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 estimate d 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 plant s 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 E

ffects : PBO is moderately toxic to fish and freshwater invertebrates, and highly t oxic to estuarine invertebrates, on an acute basis.14

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, e stuarine/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 res ult 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 application s

.

Endangered species LOCs wer e 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 risk s , such a s reducing rates and setting maximum seasonal applications, were required in the 2006 PBO RED.

Human Health Risk Assessment Status

T he following are key findings from the human health risk assessments conducted for PBO registered uses

. Please refer to th e 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 p art 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 dat abases such as the Pesticide Ha ndlers 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. A ll appl icable requirements of EPA’s Rule for the Protection of Human Subjects of Research (40 CFR Part 26) have been satisfied , and

t here is no regulatory barrier to continued reliance on these studies

.15

Hazard Characterization :
PBO has a low acute toxicity by or al, 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 respirat ory 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

- possi ble 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 no ted 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 enzym es 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

indicate d that PBO does not effectively act as a pyre throid 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 becaus e 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 multi

generation study in rats and no residual uncertainties that indica te d the need for retaining

a n additional factor, the FQPA factor was reduced to 1 x

. An uncertainty factor of 100x was applied to endpoints selected for oral exposure (10x for interspecies extrapolation, 10x for intraspecies variation). An uncertainty fac tor of 300 was applied to short

- and

intermediate

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

additional 3 x for the lack of a No Observed Adverse Effect Level ( NOAEL ) and use of a Lowest Observed Adverse Effect Level ( LOAEL) ) . An uncertainty fac tor of 1000 was applied to long

- term inhalation endpoints due to use of a subchronic study to assess chronic exposures.

Di etary Risk :16

Acute and chronic dietary (food only) assessments showed no risks of concern for the general U.S. p opulation and all population subgroups. Acute dietary risk d id 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, childre n 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 ch ildren 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 indicate d that most residential handler and post

- application exposure

scenarios were not of concern. The t wo quantitative post

- application exposure scenario s that presented potential risks of concern were applications from indo or 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 a pplication of dust with shaker can, bulb duster, and power duster was not conducted d ue to lack of dust

- specific or adequate surrogate data on inhalation exposure associate d 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 ea ch 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 wer e 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 asse ssed 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 f oggers, application of dust formulations with power duster equipment, mixing and loading liquids for aerial forestry17

applications, application of indoor crack and crevice treatment with a low pressure handwand, greenhouse applications with high pressure ha ndwand 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 Person al 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

U nited States . Therefore, EPA has not assumed that PBO has a common m echanism of toxicity with other substances.

Incident s

Ecological:

A n 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 in cidents 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 a nd 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

.

Fo r 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 w ere 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 pyrethrin s with PBO. Therefore , the incidents do show that PBO in conjunction with an insecticide has the potential to cause adverse ef fects 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 for18

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 analysi s 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. In formation 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 ga ps 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 ass essments for the registration review of PBO

. The following data have been required:

o G uideline No. 830.7050 UV/Visible absorption

o G uideline No. 840.1100 Spray droplet size spectrum

o G uideline No. 840.1200 Spray drift field deposition

o G uideline No. 850.1010 F reshwater invertebrate acute toxicity

o G uideline No. 850.1075 Freshwater and marine f ish acute toxicity

o G uideline No. 850.1350 Mysid chronic toxicity

o G uideline No. 850.1500 Fish full life cycle toxicity

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

o G uideline No. 850.4150 Te rrestrial plant toxicity, Tier I (vegetative vigor)

o G uideline No. 860.1380 Storage stability data

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

o G uideline No. 860.1520 Processed food /feed (for apple, barley, coconut, field corn, fig, flax, oat, peanut, pineapple, plum, rice, rye, sorghum, and wheat)

o G uideline No. 860.1850 Confined accumulation in rotational crops

o G uideline No. 875.1300 Inhalation exposure

— outdoor (ORETF)

o G uideline No. 875.1400 Inhalation exposure

— indoor (metered release devices)

o G uideline No. 875.1400 Inhalation exposure

- indoor

- ULV fogger

o G uideline No. 875.1700 Product use information (outdoor residential misting systems)

o G uideline No. 875.2300 Indoor surface resi due dissipation

o G uideline No. 875.2500 Inhalation exposure (fogging)19

o G uideline No. 875.2500 Inhalation exposure

- post application (outdoor residential misting systems)

o Non

- guideline Chr onic freshwater sediment toxicity

o Non

- guideline Chronic estuarine s ediment toxicity

L abels

Active Section 3 l abels for PBO can be obtained from the Pesticide Product Label System (PPLS) website: http://oaspub.epa.gov/pestlabl/ppls.home

.