2

preliminary ecological risk hypothesis and analysis plan for evaluating and characterizing 

risk to non-target species in support of the registration of PBO.

Many of the environmental fate properties of PBO are known. Based on the 

available data, it appears that PBO has a moderate tendency to move from soil to surface 

water, but little tendency to leach to ground water, except in coarse-textured soils. In 

water, it is slowly metabolized (or rapidly when photolysis occurs) to PBO-alcohol, PBOaldehyde and PBO-acid. In sediment it tends to be stable. It has the potential to 

bioaccumulate in terrestrial food chains but little potential to partition from water to air. 

Exposure should take place mainly in soil and surface water, and from consumption of 

plants and other food items. Uncertainty exists, however, in the rate at which PBO 

dissipates on foliage.

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

estuarine invertebrates, on an acute basis. Gaps in chronic fish and invertebrate toxicity 

data and aquatic plant toxicity data, along with PBO‟s persistence in water, produce 

considerable uncertainties in chronic risk to aquatic organisms. These uncertainties 

extend to taxa at risk from toxicity of PBO and its major degradates (PBO-alcohol, PBOaldehyde and PBO-acid) in sediments. Toxicity of PBO‟s major degradates is largely 

unknown in both aquatic and terrestrial environments.

PBO is practically non-toxic to terrestrial animals on an acute basis, although 

some uncertainty exists because no toxicity data are available for passerine bird species. 

Since passerines may be more sensitive than mallards or quail, this is an uncertainty. 

Risk to terrestrial invertebrates is also uncertain. Incident reports confirm that exposure 

routes exist in which use of products that contain PBO may cause mortality to terrestrial 

invertebrates. However, the Agency can not attribute incidents to PBO alone since, as a

synergist, it is not intended for use alone, but is always applied with another insecticide

or acaricide. However, the incident data do show that PBO in conjunction with other 

insecticides has the potential to adversely affect aquatic species and beneficial insects.

PBO is used as a synergist with other pesticides; therefore, invertebrate toxicity 

data using a typical end-use product is needed to adequately characterize risk to terrestrial 

invertebrates. Similarly, typical end-use product toxicity data is also needed for 

terrestrial plants to reduce uncertainty and adequately assess risk.

A significant uncertainty for PBO is the nature of the synergistic interactions with 

other pesticides with which it is mixed and may co-occur in the environment. In order to 

evaluate the nature of this synergy, data on the synergistic interaction of each group of 

pesticides for which it is intended for co-application is needed to complete a thorough 

assessment. This will require the development and review of a large body of data. The 

Agency recognizes that this data set is extensive and is willing to consider options for a 

reduced data set that evaluates the nature of PBO synergy with a limited number of 

compounds, and allows bridging to these more extensive synergy studies from reduced 

data sets for other chemicals. Because the registered uses may result in significant 

exposure to water bodies, this data set will be required for fish and invertebrates to 

address the uncertainties associated with PBO‟s synergistic interactions with other 

pesticides. Section 7.8 and Section 9 provide details regarding the data being requested 

as part of this problem formulation.
Environmental Fate and

Ecological Risk Assessment

Problem Formulation

in Support of Registration Review

for Piperonyl Butoxide

O

O

H3C

O

O

O

H3C

 

December 13, 2010

Environmental Fate and Effects Division

Office of Pesticide Programs

US Environmental Protection Agency
2

Prepared by:

Ibrahim Abdel-Saheb, Ph.D. Environmental Scientist

Donna Judkins, Ph.D., Biologist

Secondary Revision:

Keith Sappington, Senior Scientist

José L. Meléndez, Chemist

Brian Anderson, Chief

Jean Holmes, DVM, MPH, Risk Assessment Program Leader

Environmental Risk Branch II
3

Table of Contents

1. Purpose.................................................................................................................... 4

2. Problem Formulation .............................................................................................. 4

2.1. Nature of Regulatory Action.................................................................................... 4

2.2. Previous Risk Assessments, Scientific Advisory Panels and Background.............. 5

3. Stressor Source and Distribution ............................................................................ 8

3.1. Overview of Pesticide Usage................................................................................... 9

3.2. Environmental Fate and Transport ........................................................................ 12

3.3. Monitoring Data..................................................................................................... 15

3.4. Open Literature Information.................................................................................. 15

4. Receptors............................................................................................................... 15

4.1. Aquatic and Terrestrial Effects.............................................................................. 16

4.2. Incident Database Review ..................................................................................... 23

4.3. Ecosystems Potentially at Risk .............................................................................. 24

5. Assessment Endpoints .......................................................................................... 24

6. Conceptual Model.................................................................................................. 26

6.1. Risk Hypothesis................................................................................................... 26

6.2. Conceptual Diagram ............................................................................................ 27

7. Analysis Plan ......................................................................................................... 31

7.1. Stressors of Concern .............................................................................................. 32

7.2. Measures of Exposure............................................................................................ 32

7.3. Measures of Effect................................................................................................. 34

7.4. Integration of Exposure and Effects ...................................................................... 35

7.5. Endangered Species Assessments.......................................................................... 35

7.6. Drinking Water Assessment .................................................................................. 36

7.7. Endocrine Disruptor Screening Program............................................................... 37

7.8. Preliminary Identification of Data Gaps................................................................ 37

8. References............................................................................................................. 48

9. PRD data request justification tables.................................................................... 50
4

1. Purpose

The purpose of this problem formulation is to provide the foundation for the ecological 

risk assessment being conducted for the registered uses of piperonyl butoxide, PBO, CAS 

Number 51-03-6. Piperonyl butoxide (PBO) is a pesticide active ingredient that acts as a 

synergist. Synergists are chemicals that enhance the pesticidal properties of other 

chemicals. This problem formulation articulates the purpose and objectives of the risk 

assessment, evaluates the nature of the problem, and provides a plan for analyzing the 

data and characterizing the risk (EPA, 1998). Additionally, this problem formulation is 

intended to identify data gaps, uncertainties and potential assumptions needed to address 

those uncertainties in characterizing the ecological risk associated with the registered 

uses of PBO. PBO is used in combination with a wide variety of insecticides in ratios 

ranging from 3:1 to 20:1 by weight. It is usually formulated with natural pyrethrins or 

synthetic pyrethroids and is an ingredient in many registered pest control products. It has 

numerous and varied commercial and residential applications, is available in a broad 

range of formulations, and is applied by wide variety of application methods. 

Commercial 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. Additional information on PBO 

uses is included in Section 3. 

2. Problem Formulation

2.1. Nature of Regulatory Action

This document serves asthe Environmental Fate and Effects Division‟s (EFED) Problem 

Formulation for the Registration Review of PBO. Previous risk assessments were 

completed for the uses of the chemical, which serve as the basis for this assessment.

The Food Quality Protection Act of 1996 mandated the Environmental Protection 

Agency (EPA or the Agency) to implement a new program, i.e., registration review 

(http://www.epa.gov/oppsrrd1/registration_review/). All pesticides distributed or sold in 

the United States generally must be registered by the EPA. The decision to register a 

pesticide is based on the consideration of scientific data and other factors showing that it 

will not cause unreasonable risks to human health, workers, or the environment when 

used as directed on product labeling. The registration review program is intended to 

ensure 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 and the environment. Changes in science, public policy, and 

pesticide use practices will occur over time. Through the new registration review 

program, the Agency periodically reevaluates pesticides to make sure that as change 

occurs, products in the marketplace can be used safely. 

As part of the implementation of the new Registration Review program pursuant to 

Section 3(g) of the Federal Insecticide, Fungicide and Rodenticide Act (FIFRA), the 
5

Agency is beginning its evaluation to determine whether PBO continues to meet the 

FIFRA standard for registration. This problem formulation for the environmental fate and 

ecological risk assessment chapter in support of the registration review is intended for the 

initial docket opening the public phase of the review process.

2.2. Previous Risk Assessments, Scientific Advisory Panels and Background

Previous Assessments

The most recent risk assessments and other pertinent documents available in the docket 

which serve as the basis for this problem formulation include the following:

Reregistration Eligibility Document, RED1.(D310030)

Revised Piperonyl Butoxide RED (USEPA, 2006a

2

).

Response to Comments on Piperonyl Butoxide Risk Assessment (D334539), 

2007 

2009 Scientific Advisory Panel (SAP) on the Evaluation of the Common 

Mechanism of Action of Pyrethroid Pesticides (EPA-HQ-OPP-2008-04893)

EFED Response to Data Waivers for Piperonyl Butoxide RED (D334539), 

2010

In the 2006 revised RED, levels of concern (LOCs) were exceeded for the following from 

most of the agricultural uses of Piperonyl Butoxide (PBO):

acute risk to amphibians, freshwater invertebrates and freshwater fish;

chronic risk to freshwater invertebrates and freshwater fish; and

chronic risk to birds and mammals.

Additionally, for listed species, LOCs were exceeded for:

freshwater invertebrates, and amphibians from the mosquito control use; and

mammals, birds, amphibians, freshwater invertebrates, and freshwater fish from most 

agricultural uses.

Risk could not be assessed, due to lack of data, for:

chronic risk to estuarine fish and invertebrates;

risk to freshwater fish reproduction; or

risk to non-target terrestrial plants.

The following data gaps were identified in 2006:

132-1 Total Foliar Residues;

72-4 Life-cycle estuarine invertebrate using shrimp;

72-5 Full Life Cycle Fish (freshwater); and

122-1 Tier I Terrestrial Plant Study. 

 

1

http://www.regulations.gov/search/Regs/home.html#documentDetail?R=09000064800b2cf8.

2

http://www.epa.gov/oppsrrd1/reregistration/REDs/piperonyl_red.pdf.

3

http://www.epa.gov/scipoly/sap/meetings/2009/061609meeting.html.
6

In the January 5, 2007 response to comments from the RED (D334539), EPA clarified 

that PBO had not been categorized as an endocrine disruptor, but would be screened for 

endocrine disruption potential. In November, 2009, PBO was among a group of 

chemicals for which test orders were issued for Tier I Endochrine Disruptor screening.

OPP presented a “Proposed Common Mechanism Grouping for the Pyrethrins and 

Synthetic Pyrethroids to a FIFRA SAP in June 2009. OPP proposed two subgroups based 

on Type I or Type II effects related to sodium current tails and neurobehaviorial impact. 

Information on the SAP follows; further information is also available in the docket (with 

non-copyright material available at http://www.regulations.gov) under EPA-HQ-OPP2008-0489.

1999 Scientific Advisory Panel4

A FIFRA Scientific Advisory Panel (SAP) in 1999 examined the sediment toxicity and 

fate of synthetic pyrethroids. In response to a question regarding whether sediment 

toxicity data on one pyrethroid (cypermethrin) could be used to predict sediment toxicity 

to all pyrethroids, the panel generally supported the method of using data from a few 

pyrethroids to extrapolate information on toxicity to other pyrethroids. The panel 

recommended testing cypermethrin, bifenthrin (relatively non-toxic to freshwater aquatic 

organisms, very insoluble in water, large bioconcentration factor) and possibly tefluthrin 

(highly toxic to freshwater aquatic organisms, stable in water, intermediate solubility in 

water to cypermethrin and bifenthrin). Although this agreement was made in 1999, the 

new CFR Part 158 requirements include sediment toxicity tests and these studies are 

considered particularly important for ecological risk assessment of all synthetic 

pyrethroids.

While the biota-sediment-accumulation-factor is a widely accepted method of assessment 

of bioaccumulation in sediment organisms, the Panel indicated that the bioconcentration 

data for Daphnia and Hyalella should be sufficient to predict bioconcentration of 

pyrethroids. Finally, the Panel indicated that use of a solid phase microextraction 

(SPME) method to determine the dissolved concentration in water could be used to 

account for sorption of pyrethroids to organic carbon and colloids present in the water 

column in the measurement of bioconcentration factors.

In 2003 and in response to the comments from the SAP on pyrethroids, EFED requested 

the following studies on the pyrethroids cyfluthrin, cypermethrin, esfenvalerate and 

bifenthrin (Rexrode & Meléndez, memorandum dated 12/22/03):

850.1735: Acute Sediment (freshwater)

- Test organism: Hyalella azteca and Chironomus dilutus.

- Duration: 10 days, endpoint is survival.

 

4

http://www.epa.gov/scipoly/sap/meetings/1999/022399_mtg.htm.
7

EPA/600/R01/020: Chronic Estuarine/Marine Sediment Testing

- 28 day test on Leptocheirus plumulosus.

- Percentage of neonates that survive as adults.

- Growth rate.

- Reproduction (#eggs/ female, etc.).

- Behavior.

A chronic 65-day freshwater test was also requested only for cypermethrin.

EPA/600/R-991064: Chronic Freshwater Sediment Testing

- 65 day test on Chironomus dilutus.

- Survival.

- Growth rate.

- Reproduction (# eggs/ female, time to oviposition, proportion of females 

ovipositing, % hatch).

2009 Scientific Advisory Panel

OPP presented a “Proposed Common Mechanism Grouping for the Pyrethrins and 

Synthetic Pyrethroids to a FIFRA SAP in June 2009. OPP proposed two subgroups based 

on Type I or Type II effects related to sodium current tails and neurobehavioral impact, 

with esfenvalerate and fenpropathrin showing symptoms of both types. The panel 

indicated that substances with mixed characteristics could be included in both groups.5 

2010 Response to Data Waiver Requests

In EFED‟s May 20, 2010 (D375969, D375962, D375972), Response to Data Waivers for 

Piperonyl Butoxice RED Case No. 2525 (EPA 738-06-005), EFED denied data waivers 

for:

Guideline 850.1350, Mysid (Mysidopsis bahia) Chronic Life-cycle Study;

Guideline 850.1500, Fish Life-cycle Toxicity Study; and

Guideline 850.1000, Test method EPA/600/099/064 from Office of Water, and 

OECD 218 and 219 – Chronic Toxicity Sediment Testing to Freshwater 

Invertebrates and Chronic Toxicity Sediment Testing to Estuarine Invertebrates in 

the Sediment Environment.

Open Literature Information

Papers in the open literature indicate concern over pyrethroids‟ toxicity towards benthic 

and other non-target aquatic organisms. Open literature will also be evaluated for 

information on PBO toxicity and prelevance in the environment.

Aquatic Life Criteria and Aquatic Life Benchmarks

The Clean Water Act requires the Agency to publish water quality criteria that accurately 

reflect the latest scientific knowledge on the kind and extent of all identifiable effects on 

health and welfare which might be expected from the presence of pollutants in any body 

of water, including ground water. While these recommended criteria do not, in 

 

5

See Page 18 of the SAP meeting minutes, http://www.epa.gov/scipoly/sap/meetings/2009/061609meeting.html.
8

themselves, impose any requirements, states and authorized tribes can use them to 

develop water quality standards. An Aquatic Life Ambient Water Quality Criteria 

document has not been published for PBO (refer to url: 

http://www.epa.gov/waterscience/criteria/).

Based on toxicity values revised by the EPA, the OPP publishes aquatic life benchmarks 

for freshwater species, based on the most sensitive species from the most recent risk 

assessments. For PBO, no aquatic life benchmarks have been published (see url: 

http://www.epa.gov/oppefed1/ecorisk_ders/aquatic_life_benchmark.htm#benchmarks).

Impaired Water Bodies

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_grou

p_id=885. 

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_gr

oup_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 this pesticide. 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: 

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.

3. Stressor Source and Distribution

Piperonyl butoxide is a pesticide active ingredient that acts as a synergist. Synergists are 

chemicals that enhance the pesticidal properties of other chemicals. Piperonyl butoxide 

is intended for use in combination with a wide variety of insecticides and acaricides in 

ratios ranging from 3:1 to 20:1 by weight. It is primarily mixed with natural pyrethrins 

and synthetic pyrethroids. 

As a synergist, it inhibits the mixed function oxidase system of insects and reduces the 

oxidative breakdown of other pesticides. 

A summary of physicochemical properties of PBO is included in Table 1.
9

Table 1. Summary of physicochemical properties of PBO.

PARAMETER VALUE(S) (units) SOURCE

CAS Chemical Name 5-[[2-(2-butoxyethoxy)ethoxy]methyl]-6-propyl-1,3-

benzodioxole Factsheet: 

http://www.alanwood.net/pe

sticides/index_cn_frame.ht

ml

Chemical Formula C19H30O5

IUPAC Chemical Name

5-[2-(2-butoxyethoxy)ethoxymethyl]-6-propyl-1,3-

benzodioxole or 2-(2-butoxyethoxy)ethyl 6-

propylpiperonyl ether 

PC Code 067501 OPP Databases

Chemical Structure 

(from chemical’s data 

sheet)

CAS Reg. No. 51-03-6

Factsheet: 

http://www.alanwood.net/pe

sticides/index_cn_frame.ht

ml

Molecular Weight 338.45 g/mol 2002 Farm Chemicals 

Handbook

Melting Point Liquid at 25C

FOOTPRINT Pesticide 

Properties Database @

http://sitem.herts.ac.uk/a

eru/footprint/en/

Water Solubility 14.34 μg/mL at 25 °C

RD Memorandum, 

12/31/90 (cited under 

D207185) 

Solvent Solubility

Completely miscible (95% solution) in acetone, 

methanol, petroleum distillate, petroleum ether, 

methylene chloride, and isooctane 

MRID 43288601

(D207185)

Vapor Pressure (25oC) 5 x 10-13 mmHg @ 25C (extrapolated from data at 

higher temperature)

MRID 43288601

(D207185)

Henry’s Law Constant

1.6 x 10-14 atm-m

3

/mol

(calculated as VP/solubility)

FOOTPRINT Pesticide 

Properties Database @

http://sitem.herts.ac.uk/a

eru/footprint/en/

Octanol-Water Partition 

Coefficient (20oC)

(log KOW)

4.75

FOOTPRINT Pesticide 

Properties Database @

http://sitem.herts.ac.uk

/aeru/footprint/en/

Major degradates of concern are PBO-alcohol, PBO-aldehyde, and PBO-acid.

3.1. Overview of Pesticide Usage

Piperonyl butoxide (PBO) currently has 70 tolerances (40 CFR 180.127) in/on various 

crop and livestock food commodities. Residentially, it is used to control insects inside 

the home and outside on gardens, lawns and ornamentals, patios, and other outdoor 
10

structures, and is directly applied to pets. Comprehensive information on use patterns 

and formulations is provided in the Piperonyl Butoxide Master Label which was 

submitted to the EPA by the Piperonyl Butoxide Task Force II. The risk assessments for 

piperonyl butoxide are based solely on the Master Label, since it only lists the uses that 

the Task Force II are supporting. See Table 2 for a summary of uses and Appendix A for 

a comprehensive list of uses that will be assessed for Registration Review.

Table 2. PBO Registered Crop Groups and PRZM Scenarios to Represent Them

Crop Group PRZM Scenario

1: Root and Tuber Vegetables (39 crops)

2: Leaves of Root and Tuber Vegetables (18 crops)

ID potato, ME potato, FL carrot, 

CA sugarbeet, MN sugarbeet

4: Leafy Vegetables (Except Brassica Vegetables) (31) CA lettuce

5: Brassica (cole) Leafy Vegetables (16 crops) FL cabbage

6: Legume Vegetables (succulent or dried) (43 crops)

7: Foliage of Legume Vegetables (7 crops)

MI beans, OR snapbeans

8: Fruiting Vegetables (except Cucurbits) (10crops) FL peppers, FL tomato, CA tomato, 

PA tomato

9: Cucurbit Vegetables (17 crops) FL cucumber

10: Citrus Fruits (14 crops) CA citrus, FL citrus

13: Berries (9 crops) OR berries

Miscellaneous (3 crops) MS cotton, TX cotton, NC cotton

FL turf, PA turf

FL strawberries, CA grapes

Note: Number in parentheses after Crop Group name is number of crops listed on Master Label for that 

group.

Screening level estimate of piperonyl butoxide usage performed by EPA‟s Biological and 

Economical Analysis Division (BEAD) indicates that 5,000 to 10,000 pounds of 

piperonyl butoxide are used annually in the U.S. for application to agricultural crops, 

with highest usage on potatoes (30% of treated crops) and other uses at 5% or less. An 

estimated 100,000 to 200,000 pounds are used annually for non-crop uses. 

Some agricultural usage information was obtained from the USDA Regional IPM Centers 

website www.ipmcenters.org/datasources/nass/output/NASS.cfm. A copy of the data 

table is given in Appendix A. The USDA website reports the use of PBO in some years 

between 1990 and 2001 in the following states and crops: eggplant (NJ), tomatoes (NJ, 

MI), and fall potatoes (MI, NY, PA, ME, WI). In California, use was reported on head 

and “other” lettuce, spinach, cauliflower, and celery. The quantitative reliability of the 

data could not be assessed; however, the following information was given.
11

In California, PBO was used on 1 to 3% of cauliflower (1994) and celery (1994, 1996) 

acres, on 3 to 25% of combined head/other lettuce (even years 1992-2000), and 13 to 

24% of fresh-market spinach acres (1992, 1994, 1996).

In New Jersey, PBO was used on eggplant (25 to 26% of acres in 1992, 1994), and on 21 

to 25% of fresh-market tomato acres (1992, 1994). In Michigan, PBO was used on 28% 

of tomato acres in 1992.

Potatoes appear to be the most widespread agricultural use of PBO. The use of PBO on 

fall potatoes in Maine was 4 to 7% of acres (1993-4); 45 to 70% of acres in Michigan 

(1992-4); 22 to 41 % of acres in New York (1992-4); 1 to 75% of acres in Pennsylvania 

(1992-5, 1998); and 17 to 33% of acres in Wisconsin (1995, 1997-9, 2001).

The highest reported use rates for PBO were in New Jersey on eggplant (average 4.4 to 

5.1 applications totaling 2.4 to 2.89 lb/acre/year) and on tomatoes (average 3.5 to 5.3 

applications totaling 1.89 to 2.47 lb/acre/year). The highest use reported on potatoes was 

in New York (1994), with an average 2.8 applications totaling 2.24 lb/acre/year. In 

California lettuce, the highest reported use rate was 0.58 lb/acre/year from 1 to 2 

applications.

Piperonyl butoxide can be applied with aerial or ground equipment. There are many other 

use sites for PBO, as shown in the Stressor Source and Distribution section. 

Based on private market pesticide usage data from 1998-2008, the annual total 

agricultural usage averaged approximately 97,000 pounds active ingredient for almost 

664,000 million acres of all crops (EPA proprietary data, 1998-2008). There was no 

PBO use on alfalfa, except in 2003 (almost 4,500 lbs.), no use on lemons from 1998-03, 

almost 2,000 lbs. in 04 and started to decline from then on, use on lettuce peaked in 05 

(almost 4,000 lbs.) and went down to 341 lbs. in 2008, usage on potatoes peaked in 04 

(almost 8,500 lbs.) and went down to zero in following years, sorghum/milo was treated 

only in 2000 (almost 8,000 lbs.), use on strawberries was mainly in 2000 (almost 4,000 

lbs.), and almost went down to zero there after, sweet corn was treated by piperonylbutoxide in 2000 only (almost 4,000 lbs.), and winter wheat was mainly treated in 2007 

(almost 38,000 lbs.). 

During the same time period,1998-2008, the largest markets in terms of total pounds of 

active ingredient applied were: winter wheat (39%), potatoes (13%), milo sorghum (8%), 

lettuce (6%), alfalfa, strawberries, & lemons (5%, each), and sweet corn (4%) (GfK 

Kynectec, 1998-2008, Figure 1). 
12

Figure 1. Estimated Use of PBO

Piperonyl-Butoxide Largest Crop Markets

40%

8% 13%

6%

5%

5%

5%

4%

14%

Wheat, Winter

Potatoes

Sorghum (Milo)

Lettuce

Alfalfa

Straw berries

Lemons

Sw eet Corn

Other

3.2. Environmental Fate and Transport

A summary of environmental fate/ transport properties from Subdivision N guideline 

studies for PBO is presented in Table 3. Aquatic modeling inputs will be generated 

using data included in Table 3 using the most current guideance on input selection.

Table 3. Summary of environmental fate and transport properties of PBO. 

Guideline Test Value or Result Reference/ Comment

Hydrolysis Stable MRID 43595601

Aqueous Photolysis Parent half-life 8.4 hours at 

25C and pH 7

Total Toxic Residues (TTR; 

PBO-alcohol, PBO-aldehyde, 

and PBO-acid) half-life 5.7 

days

MRID 436372-01

as amended 5/17/2004

Soil Photolysis Result uncertain due to rapid 

degradation of dark control

MRID 43720801

Aerobic Soil Metabolism Parent half-life 14 days in 

sandy loam soil

TTR half-life 24 days

MRID 43806401

as amended 5/17/2004

Anaerobic Aquatic 

Metabolism

Stable for 181days in flooded 

sandy loam soil-water system 

at 25C

MRID 43836501

Aerobic Aquatic 

Metabolism

Parent half-life 75 days

TTR half-life 133 days

MRID 43803401

as amended 5/17/2004
13

Guideline Test Value or Result Reference/ Comment

Adsorption-Desorption 

(Batch Equilibrium)

Adsorption Koc range 399 -

830 mL/g

Desorption Koc range 390 -

1152 mL/g

MRID 43673801

43673802

Adsorption-Desorption 

(Column Leaching)

Unaged soil Column: Parent 

PBO leached only in sand 

soil

43673801

43673802

Hydroxyl Radical 

Reaction half-life

0.1 day (estimated by EPISuite)

Accumulation in Fish 

Tissue

260x, 91x, and 380x for 

whole fish, edible tissue, and 

nonedible tissue (MRIDs 

42404401 and 42538803)

MRID 42404401

42538803

Taken together, these data indicate that PBO will have a moderate tendency to move 

from soil to surface water, and little tendency to leach to ground water except in coarsetextured soils. 

Degradation and Metabolism

In water bodies, PBO will be slowly metabolized (75-day half-life), or in shallow, clear 

waters, rapdily degraded by photolysis to PBO-alcohol, PBO-aldehyde, and PBO-acid 

(see Appendix B for structures). PBO reaching anaerobic sediments will tend to be 

stable and available for desorption to the water column.

Soil Sorption and Mobility/Field Dissipation

In soil, PBO metabolism appears to be relatively quick (parent half-life 14 days in one 

soil tested). PBO-acid is the main degradate formed in soil (17% at 30 days). While 

parent PBO is not expected to leach, except in coarse soil, PBO-acid is expected to be 

more soluble (2000 ppm or more) and, therefore, more mobile and subject to leaching.

Bioaccumulation

A flow-through fish bioaccumulation study in bluegill sunfish produced bioaccumulation 

factors of 260x, 91x, and 380x for whole fish, edible tissue, and nonedible tissue, 

respectively (MRIDs 42404401 and 42538803). These data suggest that bioaccumulation 

in fish is not a primary concern.

Transport

PBO will have very little tendency to partition from water to the atmosphere. If present 

in the air as a vapor or spray drift, it is expected to react rapidly with hydroxyl radicals. 

The major degradates PBO-alcohol, PBO-aldehyde, and PBO-acid are expected to have

less tendency to partition from water to air, due to their much higher expected solubility 

in water.
14

Exposure to PBO from agricultural use will therefore 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.

Uncertainties

Several areas of uncertainty exist at this time for assessing PBO, including:

The dissipation rate for foliar residues is uncertain.

Field dissipation rates are uncertain.

Aerobic metabolism in soil, and both aerobic and anaerobic metabolism in water.

Absorption/desorption potential.

Aquatic exposure is not currently quantifiable for the exposure route involving PBO 

or major degradates (PBO-alcohol, PBO-aldehyde, and PBO-acid) passing through 

municipal wastewater treatment plants and being discharged into an aquatic receiving 

stream.

Comparative toxicity of degradates is not well known. Assuming that degradates and 

parent are equally toxic may over- or under-estimate toxicity.

Field incidents reported under section 6(a)(2) indicate that PBO with pyrethrin or 

pyrethroid insecticides may cause plant mortality. Since this is an area of great 

uncertainty due to lack of data, Tier I terrestrial plant studies are needed to decrease 

this uncertainty.

Since passerine birds may be more sensitive to pesticides than mallards or quail, this 

is considered an uncertainty.

Incident reports confirm that exposure routes exist in which products containing PBO 

may cause mortality to terrestrial invertebrates. Data is unavailable to quantify 

effects of a typical end-use product on terrestrial invertebrates.

Gaps in chronic fish and aquatic invertebrate toxicy data and aquatic plant toxicity 

data, along with PBO‟s persistence in water, produce considerable uncertainties in 

chronic risk to aquatic organisms, from both water column and sediment exposure. 

A significant uncertainty for PBO is the nature of the synergistic interactions with 

other pesticides with which it is mixed, and may co-occur in the environment. In 

order to evaluate the nature of this synergy, data on the synergistic interaction of each 

of these pesticides is needed to complete an accurate risk assessment. Because the 

registered uses may result in significant exposure to water bodies this data will be 

required for fish and invertebrates to address the uncertainties associated with PBO‟s 

synergistic interactions with other pesticide (see section 9 for details).

Labels under which PBO is currently sold do not always specify the pesticides or 

mixing ratios, leaving the mixtures virtually undefinable. This labeling issue results 

in significant uncertainty and should be addressed in registration review. 

Studies are being requested to address each of these uncertainties. In the absence of data, 

risk will be presumed to exceed concern levels and effectiveness of potential mitigation 

options may not be possible. 
15

3.3. Monitoring Data 

The USGS NAWQA and the USEPA "Pesticides in Ground Water Database a 

compilation of Monitoring Studies: 1971 -1991 "databases were searched, and no 

monitoring data on the concentration of Piperonyl butoxide in surface water or 

groundwater were found at the present time. Piperonyl butoxide was not included in the 

The USGS NAWQA (1991-2001) list of analytes. However, the Agency is aware of 

limited monitoring data that demonstrates environmental co-occurrence of PBO and 

pyrethroids can occur, though the spatial and temporal extent to which this occurs is not 

clear (Weston et al, 2006; Amweg et al, 2006)."

3.4. Open Literature Information

The open literature contains many valuable studies on the toxicity of PBO and its 

influence on the toxicity of other pesticides; see the revised RED (2006a) for a review of 

PBO‟s synergistic and antagonistic effects to other pesticides. The presence of PBO in a 

water body was found to either increase or decrease the toxicity of a mixture of 

insecticides, depending on which ones were present. PBO increased the toxicity of 

pyrethroids/pyrethrins, decreased the toxicity of OP insecticides that require metabolic 

activation, and had no effect on OP insecticides that did not require activation. A 

literature search will be conducted using the Ecotox database, and relevant open literature 

will be evaluated when the risk assessment is completed.

4. Receptors

Consistent with the process described in the Overview Document6, the risk assessment 

for PBO will rely on a surrogate species approach. Toxicological data generated from 

surrogate test species, that are intended to be representative of broad taxonomic groups, 

are used to extrapolate to potential effects on a variety of species (receptors) included 

under these taxonomic groupings. 

Acute and chronic toxicity data from studies submitted by pesticide registrants along with 

the available open literature are used to evaluate the potential direct and indirect effects 

of PBO on aquatic and terrestrial receptors. Toxicity studies for the technical grade 

active ingredient (TGAI) and the typical end-use product (TEP) will all be considered in 

the ecological risk assessment. Open literature studies are identified using EPA‟s 

ECOTOX database7that employs a literature search engine for locating chemical toxicity 

data for aquatic life, terrestrial plants, and wildlife. Research papers accepted into the 

ECOTOX database are screened using standard procedures to ensure consistent, high 

quality information; these studies will be considered during the „Analysis‟ phase of risk 

assessment process. The Ecological Incident Information System (EIIS, version 2.18) 

that tracks incident reports submitted to EPA and the Avian Monitoring Information 

 

6Overview of the Ecological Risk Assessment Process in the Office of Pesticide Programs. Office of Prevention, 

Pesticides, and Toxic Substances. Office of Pesticide Programs. Washington, D.C. January 23, 2004. 

7

http://www.epa.gov/ecotox

8

http://www.epa.gov/oppefed1/general/databasesdescription.htm
16

System (AIMS9) will be used to identify supportive, line of evidence information on 

exposure of aquatic and terrestrial receptors. Data from all of these sources can also 

provide insight into the direct and indirect effects of PBO on biotic communities from 

loss of species that are sensitive to the chemical and from changes in structure and 

functional characteristics of the affected communities.

4.1. Aquatic and Terrestrial Effects

Effects on Aquatic Organisms 

Acute aquatic toxicity data are available for PBO; however, chronic toxicity data are 

incomplete, lacking a fish life cycle study, estuarine/marine chronic studies, sediment 

toxicity studies, as well as aquatic plant studies. Table 4 provides a summary of the most 

sensitive data from taxonomic groups and the surrogate species used to characterize 

potential acute and chronic aquatic effects of PBO. A list of all submitted studies to date 

is found in Appendix C.

Table 4. Aquatic toxicity profile for PBO

Taxon Exposure 

Duration

Guideline

Most 

Sensitive 

Species 

Tested

Toxicity 

Value

Acute 

Toxicity 

Category1

Classification

Data Gap

Yes/No MRID

Freshwater 

Fish

Acute 850.1075

Rainbow trout 

Oncorhynchus 

mykiss

LC50= 1.9 

mg/L

using 

TGAI, no 

data for 

TEP, 

synergistic 

data

Moderately 

Toxic

Acceptable

--

No

Yes for 

TEP, 

degradates 

and

synergistic 

data

42540303

--

Chronic

850.1400

850.1500

Fathead 

minnow 

Pimephales 

promelas

NOAEC = 

0.04 mg 

a.i./L

LOAEC = 

0.11 mg 

a.i./L

2

Missing 

Data for 

Fish LC3

test

NA

ELS3test, 

Acceptable

Unfulfilled 

DCI5for LC

test, waiver 

request 

denied (DP 

375972)

Yes6

for LC 

study

43300301

--

Estuarine/ 

Marine Fish

Acute 850.1075

Sheepshead 

minnow 

Cyprinodon 

variegatus

LC50= 

3.94 mg 

a.i./L

Moderately 

Toxic Acceptable No 42540304

Chronic 850.1400 --

7 No Data -- -- Yes6

--

Freshwater 

Invertebrates Acute 850.1010

Waterflea 

Daphnia 

magna

LC50= 

0.51 mg 

a.i./L using 

TGAI, no 

data for 

TEP

synergistic 

data, 

Highly 

Toxic

Acceptable

--

No

Yes, for 

TEP,

synergistic 

data, 

42540301

--

 

9 American Bird Conservency database, http://www.abcbirds.org/.
17

Taxon Exposure 

Duration

Guideline

Most 

Sensitive 

Species 

Tested

Toxicity 

Value

Acute 

Toxicity 

Category1

Classification

Data Gap

Yes/No MRID

Chronic

850.1300 Waterflea D. 

magna

NOAEC = 

0.03 mg

a.i./L

LOAEC = 

0.047 mg

a.i./L8

NA Acceptable No 43311301

SS850.1000 Invertebrate 

Sediment Test

No Data --

Unfulfilled 

DCI, waiver 

request 

denied (DP 

375969)

Yes6--

Estuarine/ 

Marine 

Invertebrates

Acute

Mysid shrimp 

Mysidopsis 

bahia

Eastern 

Oyster

Crassostrea 

virginica

LC50 = 

0.49 mg 

a.i./L

LC50 = 

0.23 mg 

a.i./L

Highly 

Toxic

Acceptable

Supplemental, 

Qualitative

No

43901801

42540305

Chronic

850.1350 -- No Data --

Unfulfilled 

DCI, waiver 

request 

denied (DP 

375962)

Yes6--

SS850.1000 Invertebrate 

Sediment Test

No Data --

Unfulfilled 

DCI, waiver 

request 

denied (DP 

375969)

Yes6--

Amphibians Acute No 

Guideline

Western 

chorus frog 

tadpole 

Pseudacris 

triseriata

LC50 = 

0.210 mg 

a.i./L

Highly 

Toxic Supplemental No 40098001

Nonvascular 

plant

Tier I and 

Tier II9 850.5400 -- No Data --

Unfulfilled 

DCI

Yes6 for 

TEP --

Vascular 

plant

Tier I and 

Tier II9 850.4400 -- No Data --

Unfulfilled 

DCI Yes6

--

1Categories of acute toxicity for aquatic organisms based on LC50 (mg/L): < 0.1 very highly toxic; 0.1-1 highly toxic; >1-10 moderately 

toxic; >10-100 slightly toxic; >100 practically nontoxic.

2 Based on embryo survival at hatch, and length and weight of larvae.

3 ELS = early life-stage.

4 DCI = data call-in

5 LC = life cycle.

6 DCIs have been issued for these studies but data has not been submitted; therefore, a data gap still exists.

7 Missing Data.

8 Based on reproductive effects.

9

If exceed 50% effect in Tier I, also need Tier II. 

A significant uncertainty for PBO is the nature of the synergistic interactions with other 

pesticides with which it is mixed, and may co-occur in the environment. In order to 

evaluate the nature of this synergy, data on the synergistic interaction of each group of 

pesticides for which it is intended for co-application is needed to complete a risk 
18

assessment. This will require the development and review of a large body of data. The 

Agency recognizes that this data set is extensive and is willing to consider options for a 

reduced data set that evaluates the nature of PBO synergy with a limited number of 

compounds, and allows bridging to these more extensive synergy studies from reduced 

data sets for other chemicals. Some submitted studies exist that look at the toxicity of a 

single PBO + pyrethrins product (60% PBO and 6% pyrethrins) on both freshwater and 

estuarine/marine inverts & fish (Table 27b on page 64 of the pyrethrins RED, USEPA, 

2006b).

Freshwater Fish and Aquatic-Phase Amphibians

PBO is moderately toxic to freshwater fish and aquatic-phase amphibians on an acute 

basis (LC50 = 1.9 ppm, MRID 42540303). A no-observed adverse effect concentration 

(NOAEC) of 0.04 ppm was estimated from a chronic early life stage study with fathead 

minnows in which embryo survival at hatch, and length and weight of larvae, were 

observed at the lowest-observed adverse effect concentration (LOAEC) of 0.11 ppm

(MRID 43300301). Because PBO can be directly applied to water, EPA needs toxicity 

data on the typical end-use product (TEP) and major degradates (which have similar 

structures and, therefore, are expected to have similar toxicological properties) to 

characterize the risks to fish and aquatic-phase amphibians. The data set described 

above to address uncertainties associated with PBO‟s synergistic interactions with other 

pesticides would satisfy the TEP requirement (see Section 9). 

PBO and its major degradates are persistent, mobile and may pass through wastewater 

treatment processes. Since the expected peak EECs (58 to 160 ppb, for aerial application 

to lettuce, cabbage, citrus, cucumber, pepper, strawberry, potato, tomato, beans, 

sugarbeets and cotton, 2005 RED eco chapter10) exceed 0.1 of the NOAEC from the 

early-life stage study of 40 ug/L (40ppb*0.1 = 4 ppb, MRID 42540304), a fish life-cycle 

test is required. This requirement is based on PBO use in a variety of products applied 

directly to water and used in agriculture. This study was requested as part of the RED and 

remains unfulfilled. 

Freshwater Invertebrates 

PBO is moderately (daphnid LC50 = 12.0 ppm) toxic to freshwater invertebrates, on an 

acute basis. An NOAEC of 0.030 ppm was determined from a chronic life cycle study 

where Daphnia magna exhibited reproduction affects at the LOAEC (0.047 ppm). 

Because PBO can be directly applied to water, EPA needs toxicity data on the TEP to 

characterize the risks to invertebrates. The data set described above to address 

uncertainties associated with PBO‟s synergistic interactions with other pesticides would 

satisfy the TEP requirement. 

 

10 Piperonyl Butoxide: Environmental Risk Assessment, Revised September, 2005. D139408.
19

Estuarine/Marine Fish 

PBO is moderately toxic (LC50 = 3.94 ppm) to estuarine/marine fish based on observed 

effects to sheepshead minnow from acute exposure to PBO. There are no chronic data 

available for estuarine fish. An early life-stage study on sheepshead minnows is also 

required due to the potential for direct application of PBO to saltwater. 

Estuarine/Marine Invertebrates 

PBO is highly toxic to estuarine invertebrates (LC50 = 0.49 ppm for mysid, MRID 

43901801 and 0.23 ppm for oysters, MRID 42540305). Chronic toxicity data are 

required per 40 CFR Part 158.630 due to the potential for direct application of PBO to the 

estuarine/marine environment, acute toxicity value that is <1 ppm (0.23 for the oyster), 

and the expected peak EECs (58 to 160 ppb, for aerial application to lettuce, cabbage, 

citrus, cucumber, pepper, strawberry, potato, tomato, beans, sugarbeets and cotton, 2005 

RED eco chapter11) exceed 0.01 of the acute toxicity values (this would be 4.9 ppb for 

mysid and 2.3 ppb for oysters). There are no chronic data available for estuarine/marine 

invertebrates. Chronic studies were requested in the RED, but no data have been 

submitted to date. Therefore, this guideline requirement remains unfulfilled. 

Whole Sediment Survival, Growth, and Reproduction Studies 

The 1999 SAP4called for sediment toxicity testing for pyrethroids (see Section 1.0 for 

more details); afterward, the new CFR Part 158 requirements included sediment toxicity 

tests. These studies are considered particularly important for ecological risk assessment 

of all synthetic pyrethroids and synergists such as PBO. 

The new data requirements include chronic sediment toxicity studies for freshwater and 

marine organisms. According to 40 CFR Part 158, the following conditions can trigger 

the need for chronic sediment toxicity studies:

A. If the half-life of the pesticide in the sediment is ≥ 10 days in either the 

aerobic soil or aquatic metabolism studies, and

B. If any of the following conditions exist:

1. The soil partition coefficient (Kd) is ≥ 50.

2. The log KOW is ≥ 3.

3. The KOC is ≥ 1000, and, 

C. If the estimated environmental concentration (EEC) in sediment is > 0.1 of 

the acute LC50/EC50 values.

PBO and its major degradates are persistent, mobile and may pass through wastewater 

treatment processes. PBO has a half-life of 14d in aerobic soil and 75d in aerobic water 

(MRIDs 43806401 and 43803401 both as amended 5/17/2004), a log Kow of 4.75 and 

Koc of up to1152 (MRID 43673802, also see Table 3). Expected peak EECs (58 to 160 

ppb, for aerial application to lettuce, cabbage, citrus, cucumber, pepper, strawberry, 

potato, tomato, beans, sugarbeets and cotton, 2005 RED eco chapter12) exceed 0.1 of the 

acute LC/EC50 (490*0.1 = 49 ppb for M. bahia, MRID 43901801). The criteria are, 

 

11 Piperonyl Butoxide: Environmental Risk Assessment, Revised September, 2005. D139408.

12 Piperonyl Butoxide: Environmental Risk Assessment, Revised September, 2005. D139408.
20

therefore, met for requiring chronic sediment toxicity studies. The required studies

include whole sediment survival, growth, and reproduction studies with Chironomus 

tentans, Leptocheirus plumulosus, and Hyalella azteca (USEPA, 2000). Test protocols 

should be submitted before beginning the study. This is a data gap. In the absence of 

data, EPA will have to presume risk to sediment dwelling freshwater and marine 

organism.

Amphibians 

PBO is highly toxic to aquatic-phase amphibians on an acute basis (LC50 = 0.21 ppm). 

No approved guidelines for amphibian acute toxicity testing exist at this time. Available 

data will be used to assess the risk to amphibians; often fish are used as a surrogate for 

aquatic-phase amphibians, and birds are typically used as a surrogate for terrestrial-phase 

amphibians and reptiles..

Aquatic Plants

No data are available to evaluate PBO risk to aquatic plants. Aquatic plant studie 

were requested as part of the RED; however, no studies have been submitted to date. 

Therefore, this guideline requirement remains unfulfilled.

Effects on Terrestrial Organisms

Laboratory and field toxicity studies are available for characterization of the effects of 

PBO to birds (also surrogate for terrestrial-phase amphibians and reptiles) and mammals. 

For terrestrial invertebrates data is available for toxicity of TGAI, but not TEP. No plant 

data is available. Table 5 provides a summary of the most sensitive species tested for 

each terrestrial taxonomic group; see Appendix C for a complete list of submitted studies 

to date. 

Table 5. Terrestrial toxicity profile for PBO

Taxon Exposure 

Duration

Most 

Sensitive 

Species 

Tested

Guidelin

e

Toxicity 

Value

Acute 

Toxicity 

Category

Classification

Data 

Gap

Yes/

No

MRID

Mammals

Acute

Rat

Rattus 

norvegicus 850.2400

LD50 = 

4570 mg 

ai/kg bw

Practically 

Non-toxic -- No 41969001

Chronic Rat

R. norvegicus

850.2400

NOAEC = 

1000 ppm 

(89 

mg/Kg/d)

LOAEC = 

5000 ppm 

(469 

mg/Kg/d) 1

NA -- No 00161118
21

Taxon Exposure 

Duration

Most 

Sensitive 

Species 

Tested

Guidelin

e

Toxicity 

Value

Acute 

Toxicity 

Category

Classification

Data 

Gap

Yes/

No

MRID

Birds

Acute Oral

Bobwhite 

quail 

Colinus 

virginianus

Passerine

850.2100

LD50= 

>2250 mg

ai/Kg bw

No Data

Practically 

Non-toxic

Acceptable

--

2

No

Yes

41969008

--

Sub-acute 

Dietary

Bobwhite 

quail 

Colinus 

virginianus

and 

Mallard duck 

Anas 

platyrhynchos

850.2200

LD50= 

>5620 mg 

ai/kg 

NOAEC = 

1000 mg 

ai/kg3

Practically 

Non-toxic

Acceptable

Acceptable

No

41969006

41969007

Chronic

Reproduction

Bobwhite 

quail 

Colinus 

virginianus

and 

Mallard duck

Anas 

platyrhynchos

850.2300

NOAEC = 

300 mg 

ai/kg

LOAEC = 

1500 mg 

ai/kg4

NOAEC = 

300 mg 

ai/kg

LOAEC = 

1200 mg 

ai/kg5

NA Acceptable No 43876301

Terrestrial 

Invertebrates

Acute

Honey Bee

Apis mellifera

with TGAI

with TEP6

850.3020

LD50= >25

μg a.i./bee, 

NOAEC = 

25 μg

a.i./bee7

No Data

Practically 

Non-toxic

Acceptable

--

No

Yes

41969009

--

Terrestrial 

Plants

Tier I and 

Tier II8

Seedling 

Emergence 

and 

Vegetative 

Vigor using 

TEP

850.4100

850.4150

No Data --

Unfulfil

led DCI Yes9

--

1 Based on decreased weight gain in both adults and pups.

2 All pesticides with exposure routes that include consumption by passerine species must be using guideline 850.2100; this 

is a new data requirement.

3 Based on mortality and toxicosis.

4,5 Based on number of viable embryos, eggs laid, eggs per female and other parameters tested, including eggshell thickness.

6 TEP = typical end-use product.

7 Based on mortality.

8

If exceed 25% effect in Tier I test, also need Tier II.

9A DCI has been submitted for these data but no data has been submitted to date; therefore, the data gap remains.

Acute toxicity to terrestrial animals is categorized using the classification system shown 

in Table 6 (U.S. EPA, 2004). Toxicity categories for terrestrial plants have not been 

defined.
22

Table 6. Categories of Acute Toxicity for Avian and Mammalian Studies

Toxicity Category Oral LD50 Dietary LC50

Very highly toxic < 10 mg/kg < 50 ppm

Highly toxic 10 - 50 mg/kg 50 - 500 ppm

Moderately toxic 51 - 500 mg/kg 501 - 1000 ppm

Slightly toxic 501 - 2000 mg/kg 1001 - 5000 ppm

Practically non-toxic > 2000 mg/kg > 5000 ppm

Mammals, Birds, Terrestrial-Phase Amphibians and Reptiles

PBO is categorized as practically non-toxic toxic to birds, mammals, terrestrial-phase 

amphibians and reptiles, based on mammal and bird acute oral tests (LD50 = 4570 and 

>2250 mg a.i./Kg, respectively; MRIDs 41969001 and 41969008). Acceptable acute 

avian oral toxicity data are not currently available for a passerine species, which is now 

required under the 40 CFR Part 158 (CFR 40 2008) data requirements for conventional 

pesticides. This guideline requirement is a data gap.

Sub-acute and chronic studies, available for birds show PBO to be practically non-toxic 

via the dietary route on an acute basis (both quail and mallard LC50 = >5620 ppm; 

MRIDs 41969006 and 41969007); however, PBO reduced the number of viable embryos, 

eggs laid, eggs per female and other parameters tested, including eggshell thickness

(mallard NOAEC = 300 ppm; MRID 43876301) at 1200 ppm. Studies conducted on 

laboratory rats were substituted in lieu of wild mammal testing prior to the RED. In 

a rat developmental study (MRID 00161118) the NOAEC was 89 mg/kg/day (1000 

ppm) based on decreased body weight gain in both adults and pups. 

Terrestrial Invertebrates

Terrestrial invertebrate toxicity data are required to quantitatively assess the potential 

impacts on this group of organisms. Data are needed from the honey bee acute contact 

study due to wide spread use and possible drift to off site vegetation in bloom. A 

honey bee acute contact study (GLN 850.3020; MRID 41969009) shows PBO to be 

practically non-toxic to honey bees (LD50 >25 μg/bee). For honeybees, a pesticide is 

considered highly toxic if the LD50 is <2 μg a.i./bee, moderately toxic if 2-11 μg a.i./bee

and practically non-toxic if >11μg a.i./bee. Since PBO acts as a synergist, the effects 

of a typical end-use product may be much greater. Therefore, studies using the TEP 

are required and are considered a data gap. Without TEP data, EPA would presume 

that risk to terrestrial invertebrates exceeds LOCs. 

Terrestrial Plants (Guideline 850.4100 and 850.4150) using the TEP

Toxicity data for terrestrial plants are not available. Based on the 40 CFR Part 158 data 

requirements, Tier I level non-target terrestrial plant data are required for pesticides with 

a terrestrial, forestry, or residential outdoor use patterns. Therefore, this data gap must be 

filled and non-target terrestrial plant data are required. In the absence of Tier I data, 

EFED will use data available from the open literature or will presume risk to terrestrial 

monocots and dicots (and to organisms that depend on them for survival, growth, or 
23

reproduction) if no data are available. Results from Tier I tests may necessitate the 

performance of a Tier II test. If a tested terrestrial species exhibits a 25 percent or greater 

detrimental effect in a Tier I study, a Tier II study is required. If the registrant chooses to 

only submit a Tier II study, a Tier I study will not be required.

The TEP tested should be a representative end-use product. The proposed rule 

establishing use of the TEP for vegetative vigor and seedling emergence studies states, 

“The TEP that contains the highest percentage of active ingredient, and/or is the most 

commonly used, would be required” (FR Vol. 70 No. 47; March 11, 2005; 12289). 

4.2. Incident Database Review 

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

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

(AIMS), for more information, see Receptors section, above. Reported ecological 

incidents associated with the use of PBO are summarized in Table 7. 

Table 7. Summary of Reported Incidents Involving PBO

Taxon

Number of Incidents Involving PBO

Registered 

Use/Misuse, 

(Undetermined)

Likelihood, 

Highly 

Probable

Likelihood, 

Possible

Likelihood, Not 

Likely

Terrestrial 

Vertebrates 0/0 (1) -0- 1 -0-

Terrestrial 

Invertebrates 1/0 (2) -0- 3 -0-

Terrestrial 

Plants 5/0 (2) -0- 7 -0-

Aquatic 

Animals 1/1 (1) -0- 3 -0-

Fourteen incidents were found, two additional beyond those described in the RED; both 

occurred in 2005. In Florida (I016728-007), 12 to 24 butterflies were killed probably by 

spray drift from mosquito control using Biomist 31 + 66 ULV. In North Dakota 

(I016634-001) the death of 4 Koi carp was possibly (but unlikely) linked to use of Anvil 

10+10 ULV. In both of these incidents, proper use was not determined. 

In the incidents reviewed in the RED, as well as the two new incidents, EFED could not 

attribute any of the incidents to PBO alone since, as an insecticide synergist, it is never 

used alone but always with another insecticide. 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 pyrethrin with PBO. Therefore, the incidents do show that PBO in 
24

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

ecosystems and beneficial insect populations. 

4.3. Ecosystems Potentially at Risk 

PBO may be applied on a variety of food crops, including (but not limited to) tuber and 

bulb vegetables, leafy vegetables, legumes, fruits, cucurbits, nuts, cereals, herbs, spices 

and miscellaneous commodities. In addition, it may be used in numerous animal food 

uses including forage, fodder, straw, cereals, grass, hay, ornamentals, foliage and lawn 

plants, and non-growing crop uses such as food and feed storage areas and postharvest 

application. It is applied to animals and their housing, both indoor (including down-thedrain uses such as shampoos) and outdoor, including corrals and other handling areas, 

rights-of-way, fallow lands, pastures, rangelands, irrigation systems and flooded areas 

(for mosquito abatement). It is also used in human food prep and eating areas, and on 

transportation equipment, including airplanes, boats, buses, boxcars and various 

transportation containers. Thus, the ecosystems at risk may be extensive in scope, and as 

a result it may not be possible to identify specific ecosystems during the development of 

a baseline risk assessment. In general terms, terrestrial ecosystems potentially at risk due 

to the use of PBO, could include the treated field and areas immediately adjacent to the 

treated field that may receive drift or runoff. Areas adjacent to the treated field could 

include cultivated fields, fencerows and hedgerows, meadows, fallow fields or 

grasslands, woodlands, riparian habitats and other uncultivated areas. Due to the 

persistence of PBO, it is expected to drift and/or runoff due to application to food crops, 

resulting in possible exposure to aquatic ecosystems. Aquatic ecosystems potentially at 

risk due to the use of PBO include water bodies adjacent to, or down stream from, the 

treated field and might include impounded bodies such as ponds, lakes and reservoirs, or 

flowing waterways such as streams or rivers. For uses in coastal areas, aquatic habitat 

also includes marine ecosystems, including estuaries. For mosquito abatement, it may be 

directly applied to waterbodies during flooding or for irrigation. Since it is used in 

shampoos and other animal products, it may go down the drain and reach wastewater 

treatment plants.

5. Assessment Endpoints

Assessment endpoints are defined as “explicit expressions of the actual environmental 

value that is to be protected.” Defining an assessment endpoint involves two steps: 1) 

identifying the valued attributes of the environment that are considered to be at risk; and 

2) operationally defining the assessment endpoint in terms of an ecological entity (i.e., a 

community of fish, aquatic-phase amphibians and aquatic invertebrates) and its attributes 

(i.e., survival and reproduction). Therefore, selection of the assessment endpoints is 

based on valued entities (i.e., ecological receptors), the ecosystems potentially at risk, the 

migration pathways of pesticides, and the routes by which ecological receptors are 

exposed to pesticide-related contamination. The selection of clearly defined assessment 

endpoints is important because they provide direction and boundaries in the risk 

assessment for addressing risk management issues of concern. Changes to assessment 

endpoints are typically estimated from the available toxicity studies, which are used as 
25

the measures of effects to characterize potential ecological risks associated with exposure 

to a pesticide, such as PBO.

In its ecological risk assessments, the Agency does not routinely include an evaluation of 

mixtures of active ingredients, either those mixtures of multiple active ingredients in 

product formulations or those in the applicator‟s tank. In the case of the product 

formulations of active ingredients (that is, a registered product containing more than one 

active ingredient), each active ingredient is subject to an individual risk assessment for 

regulatory decision regarding the active ingredient on a particular use site. If effects data 

are available for a formulated product containing more than one active ingredient, the 

data may be used qualitatively or quantitatively in accordance with the Agency‟s 

Overview Document and the Services‟ Evaluation Memorandum (USEPA, 2004; 

Williams and Hogarth, 2004). 

In this case available toxicity data for environmental mixtures of PBO with other 

pesticides will be presented as part of the ecological risk assessment. Because PBO is a 

pesticide synergist, it is only used in combination with other pesticides to enhance their 

effectiveness (toxicity) to target organisms. Therefore, assessing potential ecological 

risks of PBO requires evaluating potential exposure and toxicity of the active ingredient 

(PBO alone) and evaluating the enhanced toxicity of other pesticides with which it is 

simultaneously applied. Data are being requested as part of this problem formulation to 

allow for an assessment of the enhanced toxicity to aquatic organisms resulting form 

enhanced toxicity of pesticides from co-exposure to PBO. 

To estimate exposure concentrations, the ecological risk assessment considers 

applications at maximum rates. If multiple applications are allowed, the maximum 

amount per application and minimum interval between applications are used – provided 

that maximum total annual application amounts are also included in this configuration. 

Several EFED exposure models (e.g., PRZM-EXAMS, T-REX) are used to estimate 

likely high-end exposure to PBO. The most sensitive toxicity endpoints are used from 

surrogate test species to estimate treatment-related direct effects on acute mortality and 

chronic reproductive, growth and survival assessment endpoints. Toxicity tests are 

intended to determine effects of pesticide exposure on birds, mammals, fish, amphibians, 

terrestrial and aquatic invertebrates, and plants. These tests include short-term acute, 

sub-acute, and reproduction studies and are typically arranged in a hierarchical or tiered 

system that progresses from basic laboratory tests to applied field studies. The toxicity 

studies are used to evaluate the potential of a pesticide to cause adverse effects, to 

determine whether further testing is required, and to determine the need for precautionary 

label statements to minimize the potential adverse effects to non-target animals and 

plants.
26

6. Conceptual Model

For a chemical to pose an ecological risk, it must reach ecological receptors in 

biologically significant concentrations. An exposure pathway is the means by which a 

pesticide moves in the environment from a source to an ecological receptor. For an 

ecological exposure pathway to be complete, it must have a source, a release mechanism, 

an environmental transport medium, a point of exposure for ecological receptors, and a 

feasible route of exposure.

A conceptual model provides a written description and visual representation of the 

predicted relationships between bifenthrin, potential routes of exposure, and the predicted 

effects for the assessment endpoint. A conceptual model consists of two major 

components: risk hypothesis and a conceptual diagram (USEPA, 1998).

6.1. Risk Hypothesis

Risk hypotheses are specific assumptions about potential adverse effects (i.e., changes in 

assessment endpoints) and may be based on theory and logic, empirical data, 

mathematical models, or probability models (USEPA 1998). For this assessment, the risk 

is stressor-initiated, where the stressor is the release of PBO into the environment. The 

following risk hypotheses are presumed for this screening-level assessment:

PBO, along with its three major degradates (PBO-alcohol, PBO-aldehyde and 

PBO-acid), when used in accordance with registered labels, will likely lead to offsite movement of the compound via runoff, spray drift, and eroded soil leading to 

exposure of nontarget plants and animals. Based on information on the 

environmental fate, mode of action, direct toxicity and potential indirect effects, 

EFED assumes that registered uses of PBO have the potential to cause reduced 

survival, growth, and reproduction to non-target terrestrial and aquatic animals 

and plants. In addition, PBO enhances the toxicity of other pesticides, which may 

result in increased risk to fish, aquatic invertebrates, and benthic invertebrates. 

PBO, along with its three major degradates (PBO-alcohol, PBO-aldehyde and 

PBO-acid), when used indoors, in accordance with current labels, may result in 

off-site movement of the compound via wash-off into surface waters via drains 

and treatment plants, leading to exposure of nontarget aquatic plants and 

animals. This potential exposure pathway may result in adverse effects upon the 

survival, growth, and/or reproduction of non-target aquatic animals and plants.

The conceptual model is a generic graphic depiction of the risk hypothesis. It includes 

the potential pesticide or stressor (PBO), the source of the pesticide and/or transport

pathways, exposure media, exposure point, biological receptor types, and attribute 

changes.
27

6.2. Conceptual Diagram

The conceptual site model is a generic graphic depiction of the risk hypothesis, and 

assumes that the insecticide synergist, PBO, having multiple outdoor agricultural and 

non-agricultural uses, is capable of affecting aquatic and terrestrial animals provided that 

environmental concentrations are sufficiently elevated as a result of proposed label uses. 

Based on an examination of the physicochemical properties of PBO, the fate and 

disposition in the environment, and mode of application, a conceptual model was 

developed that represents the possible relationships between the stressors, ecological 

receptors, and the assessment endpoints. Through a preliminary iterative process of 

examining available data, the conceptual model (i.e., the representation of the risk 

hypothesis) may be refined to reflect the likely exposure pathways and the organisms that 

are most relevant and applicable to this assessment (see Figure 2 and Figure 3, below). 

They include the total toxic residues (TTR) from the pesticide synergist, or stressor

(PBO), along with its major degradates, PBO-alcohol, PBO-aldehyde, and PBO-acid, the 

sources and/ or transport pathways, exposure media and exposure points, biological 

receptor types and attribute changes.

In order for a chemical to pose an ecological risk, it must reach ecological receptors in 

biologically significant concentrations. An exposure pathway is the means by which a 

pesticide moves in the environment from a source to an ecological receptor. For an 

ecological exposure pathway to be complete, it must have a source, a release mechanism, 

an environmental transport medium, a point of exposure for ecological receptors, and a 

feasible route of exposure. In addition, the potential mechanisms of degradation/ 

transformation (i.e., which degradation/ transformation products may form in the 

environment, in which media, and how much) must be understood, especially if for the 

chemical, its metabolites/ transformation products are of greater toxicological concern 

than the parent compound. In this case, the TTR is examined. The assessment of 

ecological exposure pathways, therefore, includes an examination of the source and 

potential migration pathways for constituents, and the determination of potential 

exposure routes.

Under the possible uses of PBO, the sources and mechanisms of release of the compound 

are from ground or aerial spray or ULV applications (note that this conceptual model 

considers agricultural applications as well as certain non-agricultural applications). 

Surface runoff from the areas of application is assumed to depend on factors such as 

topography, irrigation, and rainfall events. Direct deposition may result in contamination 

of food items that may be consumed by terrestrial organisms. Spray drift results in 

contaminated adjacent areas, including bodies of water. As mentioned in Section 3.2, 

above, PBO will have a moderate tendency to move from soil to surface water, and little 

tendency to leach to ground water except in coarse-textured soils. Due to the low 

potential for volatilization, atmospheric transport of PBO or its major degradates (PBOalcohol, PBO-aldehyde, and PBO-acid) is unlikely. It is noted that PBO TTR is quite 

stable in the environment with an aquatic aerobic half-life of 133 days (though only 5.7 

days when exposed to photolytic conditions).
28

For aquatic receptors, the major point of exposure is through direct contact with the water 

column, sediment, and pore water (gill/ integument) contaminated with spray drift (from 

spray application) and/or runoff from treated areas. Indirect effects to aquatic organisms 

(fish, aquatic-phase amphibians and aquatic invertebrates) can also occur through impact 

to various food chains. The representative aquatic receptors are certain freshwater and 

estuarine/ marine fish, invertebrates, and, in certain cases, aquatic plants. The major 

point of exposure for terrestrial animals is consumption of food contaminated with 

residues such as grass, foliage, and small insects. For plants, the point of exposure is 

direct contact or root uptake. The representative terrestrial receptors are mammals, birds 

and terrestrial plants. The attribute changes used to assess risk to terrestrial receptors 

depend on the type of test (e.g., reduced survival, growth, or reproduction for animals and 

seedling emergence and vegetative vigor for plants). It should be noted, that these 

species do not cover all the possible species in the animal and plant kingdoms; certain 

taxa are considered as surrogates for other taxa. For example, fish may be considered 

surrogates for aquatic phase amphibians.

This conceptual model also shows details about biomagnification for a chemical (see 

piscivorous birds and mammals in (Figure 2). However, bioconcentration of PBO is not 

a primary concern. 

PBO shows a fairly high solubility and a high KOW. These properties suggest that the 

chemical can partition with sediments, and with organic matter suspended in the water 

bodies, to some degree, but also remain in solution to a significant degree. In water 

column, it will be slowly metabolized (75-day half-life), or in shallow, clear waters, 

rapdily degraded by photolysis to PBO-alcohol, PBO-aldehyde, and PBO-acid. PBO 

TTRs may concentrate in the sediments, where they could persist. Such sediments could 

serve as repositories of the chemical(s) for extended periods of time and could potentially 

be toxic to sediment dwelling organisms, affecting the food chain. These issues will also 

be assessed in the risk assessment for PBO.

As mentioned in Section 3, PBO will have very little tendency to partition from water to 

the atmosphere since it would react rapidly with hydroyl radicals. PBO-alcohol, PBOaldehyde, and PBO-acid would have even less tendency to partition to air due to their 

much higher solubility in water. Therefore, exposure to PBO TTRs from agricultural use 

should take place mainly in soil and surface water, and from consumption of plants and 

other food items onto which PBO is sprayed.

This risk assessment will also evaluate the potential for PBO TTRs to go down the drain 

with some use patterns, such as animal shampoos. Due to its high solubility and stability 

this pathway will also be explored, see Figure 4.
29

Figure 2. Conceptual model depicting stressors, exposure pathways, and potential 

effects to aquatic organisms from the use of PBO on agricultural and certain nonagricultural sites. Dotted lines indicate exposure pathways that have a low 

likelihood of contributing to ecological risk.

**Route of exposure includes only ingestion of fish and aquatic inverts.

Stressor

Source

Receptors

Attribute

Change

PBO (and degradates) applied to agricultural or non-agricultural use site

Spray drift

Aquatic animals

Invertebrates 

Vertebrates

**Piscivorous mammals 

 and birds 

Individual organisms

Reduced survival

Reduced growth

Reduced reproduction

Food chain

Reduction in algae and 

 vascular plants

Reduction in prey

Modification of PCEs 

 related to prey

availability

Habitat integrity

Reduction in primary

productivity

Reduced cover

Community change

Modification of PCEs 

related to habitat

Surface water/

Sediment

Runoff

Aquatic Animals

Invertebrates

Vertebrates

Exposure

Media

Uptake/gills

or integument

Ingestion Ingestion

Atmospheric 

transport

Wet/dry deposition

Soil Leaching to

Groundwater

Uptake/gills

or integument

Aquatic Plants

Non-vascular

Vascular

Uptake/cell, 

roots, leaves Riparian plants

terrestrial 

exposure 

pathways; see 

Figure 6.1b
30

Figure 3. Conceptual model depicting stressors, exposure pathways, and potential 

effects to terrestrial organisms from the use of PBO on agricultural and certain nonagricultural sites. Dotted lines indicate exposure pathways that have a low 

likelihood of contributing to ecological risk. 

The conceptual model for potential risks of PBO to aquatic organisms for various indoor 

uses of the chemical that could potentially end up in a domestic wastewater “drain” is 

depicted in Figure 4. The stressor is the chemical of concern, PBO TTRs. It is noted 

that the transport pathway is wastewater flow, the exposure media is the treatment facility 

that discharges into a surface water body of water (where it may undergo dilution), and 

the exposure point or route, receptor and attribute changes for aquatic organisms are 

similar to the conceptual model for agricultural applications.

Stressor

Source

Attribute

Change

PBO (and degradates) applied to agricultural or non-agricultural terrestrial 

use site

Direct

application Spray drift

Terrestrial 

vertebrates

Terrestrial 

invertebrates

Individual 

organisms

Reduced survival

Reduced growth

Reduced reproduction

Food chain

Reduction in prey and food

Modification of PCEs 

 related to prey availability

Habitat integrity

Reduction in primary productivity

Reduced cover

Community change

Modification of PCEs related

 to habitat

Terrestrial plants

grasses/ forbs, fruit, seeds 

(trees, shrubs)

Runoff

Terrestrial 

vertebrates 

Exposure Media 

& Receptors Soil

Ingestion

Ingestion

Ingestion

Dermal uptake/Ingestion

Atmospheric 

transport

Root uptake/contact

Wet/dry deposition

Ingestion

Leaching to

Groundwater

Irrigation 

water
31

Figure 4. Conceptual model for potential risks of PBO to aquatic organisms for 

various indoor uses of the chemical that could potentially end up in the “drain”

7. Analysis Plan 

In registration review, pesticide ecological risk assessments will follow the Agency‟s 

Guidelines for Ecological Risk Assessment, will be in compliance with the paper titled 

“Overview of the Ecological Risk Assessment Process in the Office of Pesticide 

Programs, U.S. Environmental Protection Agency” (USEPA, 2004), and will be done in 

accordance with Section 7 of the Endangered Species Act.

Previously completed screening level risk assessments and exceedances of Agency levels 

of concern indicate a need to further examine and refine risk. Analysis of potential 

indirect effects on listed species is also required. This analysis plan will be revisited and 

may be revised depending upon the data available in the open literature and the 

information submitted by the public in response to the opening of the Registration 

Review docket.

Stressor PBO Applications that Could Potentially End Up “Down-the-drain”

Source/

Transport

Pathways

Wastewater flow

Source/

Exposure

Media

Treatment Facility 

Discharges into Surface 

Waters

Exposure

Route

Gill/

Integument 

Uptake

Receptors

Attribute

Changes

Aquatic 

Invertebrates,

Vertebrates

Individual 

Vertebrates and 

Invertebrates

Reduced survival 

or reproduction

Plant Population

Reduced 

population 

growth

Aquatic 

Plants

Uptake/ 

Adsorption
32

Use information will be retrieved from registration labels and used as inputs for 

estimating exposure concentrations from the various use scenarios. PBO‟s use patterns 

suggest potential risk concerns to aquatic and terrestrial organisms. The range of 

potential exposure to PBO to non-target terrestrial organisms can vary on application 

method (aerial or ground), application rate, and use pattern. 

7.1. Stressors of Concern

The focus of this assessment is on the total toxic residues (TTR), which include parent 

material, PBO, plus major degradates: PBO-alcohol, PBO-aldehyde and PBO-acid. 

Available toxicity data on pesticide mixtures (products containing multiple active 

ingredients) and environmental mixtures of PBO with other pesticides (those mixtures 

occurring in the environment following application), will be presented as part of the 

ecological risk assessment. PBO may be applied in tank mixtures with other products 

approved for use on registered crops. It is expected that the toxic effect of PBO, in 

combination with other pesticides used in the environment, is likely to be a function of 

many factors including, but not necessarily limited to: (1) the exposed species, (2) the cocontaminants in the mixture, (3) the ratio of PBO and co-contaminant concentrations, (4) 

differences in the pattern and duration of exposure among contaminants, and (5) the 

differential effects of other physical/ chemical characteristics of the receiving waters (e.g.

organic matter present in sediment and suspended water). Quantitatively predicting the 

combined effects of all these variables on mixture toxicity to any given taxa with 

confidence is beyond the capabilities of the available data and methodologies. However, 

a qualitative discussion of implications of the available pesticide mixture effects data on 

the confidence of risk assessment conclusions will be addressed as part of the uncertainty 

analysis.

7.2. Measures of Exposure

In order to estimate risks of PBO exposures in aquatic and terrestrial environments, all 

exposure modeling and resulting risk conclusions will be made based on maximum 

application rates for the current use patterns. Measures of exposure are based on aquatic 

and terrestrial models that predict estimated environmental concentrations of PBO using 

maximum labeled application rates and methods, as well as any mitigation measures 

specifically indicated on the label. The models used to predict aquatic EECs are the 

Pesticide Root Zone Model coupled with the Exposure Analysis Model System 

(PRZM/EXAMS). Also, to estimate exposure related to releases of PBO from domestic 

wastewater treatment plants, the Exposure and Fate Assessment Screening Tool‟s (EFAST2) down-the-drain module will be used. The model used to predict terrestrial 

exposure is T-REX. The model used to derive EECs relevant to terrestrial and wetland 

plants is TerrPlant. The potential for bioaccumulation for the chemical is assessed using 

the KABAM model, as well the results from bioconcentration in fish studies (the 

bioconcentration factors). These models are parameterized using relevant reviewed 

registrant-submitted environmental fate and transport data.
33

PRZM (v.3.12.2, May 2005) and EXAMS (v.2.98.4.6, April 2005) are screening 

simulation models coupled with the input shell PE5.pl (August, 2007) to generate daily 

exposures and 1-in-10 year EECs of PBO, that may occur from spray drift and runoff to 

surface water bodies adjacent to application sites. PRZM simulates pesticide 

application, movement and transformation on an agricultural field and the resultant 

pesticide loadings to a receiving water body via runoff, erosion and spray drift. The 

EXAMS model simulates the fate of the pesticide and resulting concentrations in the 

water body. The standard scenario used for ecological pesticide assessments assumes 

application to a 10-hectare agricultural field that drains into an adjacent 1-hectare water 

body that is 2 meters deep (20,000 m3volume) with no outlet. PRZM/ EXAMS is used 

to estimate screening-level exposure of aquatic organisms to PBO and its transformation 

products. The measure of exposure for aquatic species is the 1-in-10 year return peak or 

rolling mean concentration. The 1-in-10 year peak is used for estimating acute exposures 

of direct effects to aquatic organisms. The 1-in-10-year 60-day mean is used for assessing 

chronic exposure to fish and aquatic-phase amphibians. The 1-in-10-year 21-day mean is 

used for assessing aquatic invertebrate chronic exposure.

Given the aquatic toxicity of PBO and its likelihood to occur in sediment, the Agency 

will also consider the potential exposures resulting from benthic/ sediment concentrations 

(EECs). Pore water concentrations are commonly used to predict toxicity of non-ionic 

substances in sediments and characterize exposure to organisms that spend time in or 

near sediments (Di Toro et al. 1991). PRZM/ EXAMS estimates 1-in-10-year peak and 

21-day mean EECs for pore water.

To estimate exposure related to releases of PBO to domestic wastewater treatment, the 

Agency will rely on the Office of Pollution Prevention and Toxics (OPPT) model, 

Exposure and Fate Assessment Screening Tool (E-FAST, version 2.0, 2007, or EFAST2). 

From this model, the Agency used the “Down-the-Drain” module, which is designed for 

releases to domestic wastewater treatment. It is suitable for all the sources of PBO that 

could potentially be exposed through a “down-the-drain” scenario. The model provides 

screening level estimate concentrations of chemicals in surface water that may result 

from household uses and the disposal of consumer products into wastewater using a few 

simple input parameters (production volume and fraction of the chemical removed during 

wastewater treatment). Additionally, the Agency will evaluate any available treatability 

data to help characterize risk from PBO or degradates that might pass through water 

treatment plants.

Exposure estimates for terrestrial animals assumed to be in the target area are derived 

using the T-REX model (version 1.3.1, 12/07/2006). For pesticides such as PBO, which 

can be applied as a dust, this includes the amount of pesticide per square foot, used in 

LD50 per square foot risk assessment calculations. EECs for terrestrial plants inhabiting 

dry and wetland areas are derived using TerrPlant (version 1.2.2, 12/26/2006). This 

model uses estimates of pesticides in runoff and in spray drift (assumed to be 0% for 

granulars) to calculate EECs. EECs are based upon solubility, application rate and 

minimum incorporation depth.
34

As indicated in Table 3.1 and its associated text in Section 3, PBO appears to have some 

potential to bioaccumulate in aquatic and terrestrial organisms; however, available 

bioconcentration studies in fish do not suggest that bioconcentration is a primary concern 

in fish, although PBO‟s bioconcentration potential in invertebrates has not been 

evaluated... The potential for bioaccumulation of PBO will be further examined in the 

risk assessment. Bioaccumulation will be assessed using the results from 

bioaccumulation in fish studies, as well as the KABAM model (KOW (based) Aquatic 

BioAccumulation Model, version 1.0, 2009), adjusting for biotransformation rates. 

KABAM is used to estimate potential bioaccumulation of hydrophobic organic pesticides 

in freshwater aquatic ecosystems and risks to mammals and birds consuming aquatic 

organisms which have bioaccumulated these pesticides.

To better determine availability of PBO and its major degradates, more information is 

needed on aerobic soil metabolism, aerobic and anaerobic aquatic metabolism and 

absorption/desorption. To determine availability and exposure to terrestrial organisms 

that feed on plants, foliar dissipation data are needed. See Section 9 for additional 

details.

7.3. Measures of Effect

Ecological effects data are used as measures of direct and indirect effects to biological 

receptors. Data are typically obtained from registrant-submitted studies or from literature 

studies identified by ECOTOX. The ECOTOX database provides more ecological effects 

data in an attempt to bridge existing data gaps. ECOTOX is a source for locating single 

chemical toxicity data and potential chemical mixture toxicity data for aquatic life, 

terrestrial plants, and wildlife. ECOTOX was created and is maintained by the USEPA, 

Office of Research and Development, and the National Health and Environmental Effects 

Research Laboratory's Mid-Continent Ecology Division.

The acute measures of effect used for animals in this assessment are the LD50, LC50 and 

EC50. LD stands for "Lethal Dose", and LD50 is the amount of a material, given all at 

once, that is estimated to cause the death of 50% of the test organisms. LC stands for 

“Lethal Concentration” and LC50 is the concentration of a chemical that is estimated to 

kill 50% of the test organisms. EC stands for “Effective Concentration” and the EC50 is 

the concentration of a chemical that is estimated to produce a specific effect in 50% of 

the test organisms. Endpoints for chronic measures of exposure for listed and non-listed 

animals are the NOAEL and NOAEC. NOAEL stands for “No Observed-AdverseEffect-Level” and refers to the highest tested dose of a substance that has been reported 

to have no harmful (adverse) effects on test organisms. The NOAEC (i.e., “NoObserved-Adverse-Effect-Concentration”) is the highest test concentration at which none 

of the observed effects were statistically different from the control. For non-listed plants, 

only acute exposures are assessed (i.e., EC25 for terrestrial plants and EC50 for aquatic 

plants); for listed plants either the NOAEC or EC05 is used.

Information on the potential effects of PBO on non-target animals is also collected from 

the Ecological Incident Information System (EIIS). The EIIS is a database containing 
35

adverse effect (typically mortality) reports on non-target organisms where such effects 

have been associated with the use of pesticides. Information on incidents involving avian 

species is also provided through the Avian Monitoring Information System (AIMS), 

which is maintained by the American Bird Conservancy. 

Where available, sub-lethal effects observed in both registrant-submitted and open 

literature studies will be evaluated qualitatively. Such effects may include behavioral 

changes (e.g., lethargy and changes in coloration). Quantitative assessments of risks, 

though, are limited to those endpoints that can be directly linked to the Agency‟s 

assessment endpoints of impaired survival, growth and reproduction.

The assessment of risk for direct effects to non-target organisms makes the assumption 

that the toxicity of PBO to birds is similar to terrestrial-phase amphibians and reptiles. 

The same assumption is made for fish and aquatic-phase amphibians.

Several toxicity studies are needed to better assess the potential risk of PBO exposure to 

non-target organisms, including passerine acute oral toxicity, honey bee acute contact 

toxicity (from a typical end-use product, TEP), fish full life cycle toxicity, fish and 

invertebrate chronic toxicity to saltwater species, sediment toxicity (both freshwater and 

saltwater), aquatic and terrestrial plant toxicity data (using TEP), and a data set to address 

the acute synergistic affects of PBO with other pesticides to freshwater fish and 

invertebrates

7.4. Integration of Exposure and Effects

Risk characterization is the integration of exposure and ecological effects characterization 

to determine the potential ecological risk from the use of pesticides and the likelihood of 

direct and indirect effects to non-target organisms in aquatic and terrestrial habitats. The 

exposure and toxicity effects data are integrated in order to evaluate the risks of adverse 

ecological effects on non-target species. For the assessment of risks, the risk quotient 

(RQ) method is used to compare exposure and measured toxicity values. EECs are 

divided by acute and chronic toxicity values. The resulting RQs are then compared to the 

Agency‟s Levels of Concern (LOCs) (USEPA 2004). These criteria will be used to 

indicate when PBO‟s uses, as directed on the label, have the potential to cause adverse 

direct or indirect effects to non-target organisms. In addition, incident data from the EIIS 

will be considered as part of the risk characterization.

7.5. Endangered Species Assessments

Consistent with the Agency‟s responsibility under the Endangered Species Act (ESA), 

the Agency will evaluate risks to Federally-listed threatened and/or endangered (listed) 

species from registered uses of PBO. This assessment will be conducted in accordance 

with the Overview Document (USEPA 2004), provisions of the ESA, and the Services‟ 

Endangered Species Consultation Handbook (USFWS/NMFS, 2004).
36

The assessment of effects associated with the registration of PBO is based on an action 

area. The action area is considered to be the area directly or indirectly affected by the 

federal action, as indicated by the exceedance of Agency Levels of Concern (LOCs) used 

to evaluate direct or indirect effects. The Agency‟s approach to defining the action area 

under the provisions of the Overview Document (USEPA 2004) considers the results of 

the risk assessment process to establish boundaries for that action area with the 

understanding that exposures below the Agency‟s defined LOCs constitute a no-effect 

threshold. For the purposes of this assessment, attention will be focused on the footprint 

of the action (i.e., the area where PBO application occurs), plus all areas where offsite 

transport may result in potential exposure that exceeds the Agency‟s LOCs. Specific 

measures of ecological effect that define the action area for listed species include any 

direct and indirect effects and/ or potential modification of its critical habitat, including 

reduction in survival, growth, and reproduction as well as the full suite of sub-lethal 

effects available in the effects literature. Therefore, the action area extends to a point 

where environmental exposures are below any measured lethal or sub-lethal effect 

threshold for any biological entity at the whole organism, organ, tissue, and/ or cellular 

level of organization. In situations where it is not possible to determine the threshold for 

an observed effect, the action area is not spatially limited and is assumed to be the entire 

United States.

Probit Analysis

Analysis of raw data from the aquatic acute toxicity studies for PBO will be used to 

estimate probabilities of effects to aquatic and terrestrial animals. Slope estimates along 

with 95% conficence intervals will be used. When slope data is unavailable, a default 

slope of 4.5 is used with confidenct intervals of 2 and 9 (Urban and Cook, 1986).

7.6. Drinking Water Assessment

At the time of the risk assessment, a water assessment will be done considering the 

following:

* New data has been submitted to the agency.

* Changes in the label uses and rates.

* Any mitigation that has been proposed in the previous assessments.

* New models has been developed that used for drinking water assessment.

A drinking water assessment will be conducted to support future human health risk 

assessments of PBO should it be required. The drinking water assessment will 

incorporate model estimates of PBO in surface and ground waters. Concentrations in 

surface waters will be estimated using FQPA Index Reservoir Screening Tool (FIRST, 

v.1.1.1, 12/18/07) (or subsequently using PRZM/ EXAMS, with the Index Reservoir - see 

description above, if refinements are required). Ground water estimates of concentrations 

will be estimated using the Screening Concentration in Ground Water (SCI-GROW) 

model (v.2.3, July 2003). The drinking water assessment will also include a summary of 

available surface and ground water monitoring data.
37

Drinking water exposure of PBO to avian and mammalian species will be screened to 

determine if this is a potential pathway of concern. The Screening Imbibition Program 

(SIP v.1.0, Released June 15, 2010) will be used to calculate an upper bound estimate of 

exposure using PBO‟s solubility, the most sensitive acute and chronic avian toxicity 

endpoints, and the most sensitive acute and chronic mammalian toxicity endpoints. 

7.7. 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, 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 dose-response 

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

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 postapplication agricultural scenarios. This list should not be construed as a list of known or 

likely endocrine disruptors. PBO was included in the list and test orders were issued in 

November, 2009.

For further information on the status of the EDSP, the policies and procedures, the list of 

67 chemicals, the test guidelines and the Tier 1 screening battery, please visit our 

website: http://www.epa.gov/endo/.

7.8. Preliminary Identification of Data Gaps

The Agency does foresee requiring additional fate and ecological effects studies prior to 

conducting the planned assessments. Data gaps, uncertainties and potential paths forward 

for the assessment of PBO are described below.
38

Fate

After evaluation of the available data for PBO, the fate data gaps for registration review 

consist of the following. These studies have not been previously requested:

Guideline Number: 835.4100, Aerobic Soil Metabolism

Guideline Number: 835.4300, Aerobic Aquatic Metabolism

Guideline Number: 835.4400, Anaerobic Aquatic Metabolism

Guideline Number: 835.1230, Adsorption/Desorption

Guideline Number: 835.6100, Analytical Method for Residues in Soil and 

Sediment

Guideline Number: 835.6200, Analytical Method for Residues in Water

Guideline Number: 875.2100 Dislodgable Foliar Residues (modified for total 

foliar residue) – protocol needs to be submitted prior to study initiation

Effects

After evaluation of the available data for PBO, the effects data gaps for registration 

review are listed below, most have already been requested in previous data call-ins:

Previously requested studies:

Guideline Number: 850.1075, Study Title: Fish Acute Toxicity Test with 

TEP (typical end-use product). TEP studies are required for pesticides that 

may be directly applied to water. 

Guideline Number: 850.1010, Study Title: Aquatic Invertebrate Acute 

Toxicity Test, Freshwater Daphnid with TEP. TEP studies are required for 

pesticides that may be directly applied to water. 

Guideline Number: 850.1350, Study Title: Aquatic Invertebrate Life Cycle 

Toxicity (estuarine/marine) with TGAI (technical grade active ingredient).

Guideline Number: 850.1500, Full Life Cycle Fish Test (freshwater) with 

TGAI.

Guideline Number: Non-guideline (at time of submission, current Guideline 

Numbers 850.1760; 850.1770; 850.1780), Sediment Toxicity with TEP

(freshwater and saltwater).Guideline Number: 850.4100, Seedling Emergence 

Tier I study to determine the EC25 and NOAEC using TEP. 

Guideline Number: 850.4150, Vegetative Vigor Tier I study to determine the 

EC25 and NOAEC using TEP. 

New Data Requirements not Previously Requested:

Guideline Numbers: 835.6100, Study Title: Analytical Method (and Associated 

Independent Laboratory Validation) for Residues in Soil and Sediment

Guideline Number 835.6200: Study Title: Analytical Method (and Associated 

Independent Laboratory Validation) for Residues in Water

Guideline Number: 850.2100, Study Title: Acute Avian Oral Toxicity Test 

using a Passerine species with TGAI. 

Guideline Number: 850.3020, Honey Bee Acute Contact Toxicity using TEP.

Guideline Number: 850.1075, Study Title: Fish Acute Toxicity Test with 

major degradates. 
39

Guideline Number: 850.1075, Study Title: Fish Acute Toxicity Test, data 

addressing the synergistic interaction of pesticides and PBO. These studies 

are expected to be modified guideline studies, and protocols need to be 

submitted prior to study initiation. This requirement was included in the 

RED; however, the RED specified that synergism data were only required for 

TEPs. Data are currently being requested to address synergism with all 

pesticide active ingredients (and other chemicals with similar modes of action) 

with which PBO is recommended for co-application. 

Guideline Number: 850.1010, Study Title: Aquatic Invertebrate Acute 

Toxicity Test, Freshwater Daphnid, data addressing the synergistic interaction 

of pesticides and PBO. These studies are expected to be modified guideline 

studies, and protocols need to be submitted prior to study initiation. This 

requirement was included in the RED; however, the RED specified that 

synergism data were only required for TEPs. Data are currently being 

requested to address synergism with all pesticide active ingredients (and other 

chemicals with similar modes of action) with which PBO is recommended for 

co-application. 

Guideline Number: 850.1400, Fish Early Life-Stage Test (estuarine/marine) 

with TGAI.

Guideline Number: 850.4400, Aquatic Plant Tier I study using Lemna spp. to 

determine EC50 and NOAEC using TGAI.

Guideline Number: 850.5400, Aquatic Plant Tier I Algal toxicity study to 

determine EC50 and NOAEC using TGAI.

For registration review, the following studies are being requested to fulfill data gaps:

Guideline Number: 835.4100

Study Title: Aerobic Soil Metabolism

As per OCSPP Harmonized Test Guidelines; Aerobic and anaerobic studies with one soil 

type are generally sufficient for the evaluation of transformation pathways. Rates of 

transformation should be determined in at least three additional soils. At this time, EPA 

has only one acceptable study done with one soil.

Guideline Number: 835.4300

Study Title: Aerobic Aquatic Metabolism

As per OCSPP Harmonized Test Guidelines; At least two sediments and their associated 

waters are used for both the aerobic and the anaerobic studies respectively. EPA has only 

one upgradable to acceptable study done with one sediment.

Guideline Number: 835.4400

Study Title: Anaerobic Aquatic Metabolism 

As per OCSPP Harmonized Test Guidelines; At least two sediments and their associated 

waters are used for both the aerobic and the anaerobic studies respectively. EPA has only 

one supplemental study done with one sediment.

Guideline Number: 835.1230
40

Study Title: Adorption-Desorption (Batch Equilibrium)

As per OCSPP Harmonized Test Guidelines; At least two soils should be used. EPA has 

only one acceptable study done with one soil.

Guideline Number: 875.2100 (modified)

Study Title: Dislodgable Foliar Residues (modified for total foliar residue) –

protocol needs to be submitted prior to study initiation. The risk assessments showed a 

potential for chronic risk to mammals and birds from PBO using the default half-life of 

35 days. A measured foliar dissipation rate, if shorter than 35 days, might remove the 

presumption of risk.

Guideline Number: 835.6100

Study Title: Analytical Method (and Associated Independent Laboratory 

Validation) for Residues in Soil and Sediment

Environmental chemistry methods in soil or sediment have not been submitted in support 

of submitted terrestrial or aquatic field dissipation studies of piperonyl butoxide (PBO). 

An independently validated environmental chemistry method in soil (and in sediment if 

procedures for sediment differ from those for soil) is necessary to evaluate the results of 

submitted terrestrial field dissipation studies and to provide outside agencies an analytical 

method with which to monitor for PBO residues in soil and aquatic sediment. In the 

absence of an independently validated environmental chemistry method in soil and 

sediment, submitted terrestrial field dissipation studies are not acceptable and entities 

outside the Agency may lack a chemical-specific method for analyses in soil and 

sediment. An independently validated environmental chemistry method will be used to 

evaluate submitted terrestrial field dissipation studies in which it is used and will be made 

available for enforcement and monitoring purposes at the federal, state, and local levels.

Guideline Number: 835.6200

Study Title: Analytical Method (and Associated Independent Laboratory 

Validation) for Residues in Water

Environmental chemistry methods in water have not been submitted in support of 

submitted aquatic field dissipation studies. An independently validated environmental 

chemistry method in water is necessary to evaluate the results of submitted aquatic field 

dissipation studies and to provide outside agencies an analytical method with which to 

monitor for PBO residues in water. In the absence of an independently validated 

environmental chemistry method in water, submitted aquatic field dissipation studies are 

not acceptable and entities outside the Agency may lack chemical-specific methods for 

analyses in water. An independently validated environmental chemistry method will be 

used to evaluate submitted aquatic field dissipation studies in which it is used and will be 

made available for enforcement and monitoring purposes at the federal, state, and local 

levels.

Guideline Number: 850.1075

Study Title: Fish Acute Toxicity Test (freshwater) with TEP and major degradates.

No acceptable acute studies for PBO TEP have been submitted for fish. Since PBO can 

be directly applied to water, EPA needs data on the formulated product. Without 
41

toxicity data on the range of TEPs produced, the Agency woud have to presume acute 

toxicity to listed and non-listed fish and aquatic-phase amphibians, but would not be able 

to quantify the risk.

Guideline Number: 850.1075

Study Title: Fish Acute Toxicity Test, data addressing synergistic affect of PBO with 

each pesticide with which it may be simultaneously applied.

No acceptable acute studies have been submitted for fish which address the synergistic 

affect of PBO with other pesticides. Due to fate charactersistics and registered uses of 

PBO there may be significant exposure in water bodies. PBO is a pesticide synergist. 

Therefore, it is used in combination with other pesticides to enhance their effectiveness 

(toxicity) to target organisms. Assessing potential ecological risks of PBO requires 

evaluating potential exposure and toxicity of the active ingredient (PBO alone) and 

evaluating the enhanced toxicity of other pesticides with which it is simultaneously 

applied. Given the number of chemicals with which PBO may be simultaneously 

applied, designing a study that examines the range of synergistic effects is difficult. A 

comprehensive evaluation of potential synergistic effects of PBO and all chemicals with 

which it may be simultaneously applied will require the development and review of a 

large body of data. The Agency is interested in obtaining data on (or bridging data to) 

pesticide active ingredients (in addition to other chemicals with similar modes of action) 

that are co-applied (or expected to be co-applied) with PBO for its synergistic properties 

including those that are formulated with PBO and those that are otherwise recommended 

for mixing with PBO prior to application. The Agency recognizes that this data set is 

extensive and is willing to consider options for a reduced data set that evaluates the 

nature of PBO synergy with a limited number of compounds, and allows bridging to 

these more extensive synergy studies from reduced data sets for other chemicals. The 

goal of obtaining this set of data is to determine the potential range of magnitudes of 

synergistic effects for pesticide active ingredients that are co-applied with PBO for the 

purpose of enhancing efficacy due to synergism. Protocols need to be submitted to the 

Agency prior to study initiation. Without this data set, the Agency would have to presume 

acute toxicity to listed and non-listed invertebrates, but would not be able to quantify the 

risk.

Guideline Number: 850.1010 

Study Title: Aquatic Invertebrate Acute Toxicity Test, Freshwater Daphnid, with 

TEP

No acceptable acute studies for PBO TEP have been submitted for aquatic invertebrates. 

Since PBO can be directly applied to water, EPA needs data on the formulated product. 

Without toxicity data on the range of TEPs produced, the Agency woud have to presume 

acute toxicity to listed and non-listed fish, but would not be able to quantify the risk. A 

formulated product that is applied directly to water needs to be the subject of the study.

Guideline Number: 850.1010 or 850.1035

Study Title: Aquatic Invertebrate Acute Toxicity Test, Freshwater Daphnid, data 

addressing synergistic affect of PBO with each pesticide with which it is 

simultaneously applied.
42

No acceptable acute studies have been submitted for invertebtatesd which address the 

synergistic affect of PBO with other pesticides. Due to the fate charactersistics and the 

registered uses of PBO there may be significant exposure to water bodies. PBO can act 

as a synergist to other pesticides. In order to evaluate the nature of this synergy, data on 

the synergistic interaction of each pesticide is needed to complete an an accurate risk 

assessment. This will require the development and review of a large body of data. The 

Agency is interested in obtaining data on (or bridging data to) pesticide active ingredients 

(in addition to other chemicals with similar modes of action) that are co-applied with 

PBO for its synergistic properties including those that are formulated with PBO and those 

that are otherwise recommended for mixing with PBO prior to application. The Agency 

recognizes that this data set is extensive and is willing to consider options for a reduced 

data set that evaluates the nature of PBO synergy with a limited number of compounds, 

and allows bridging to these more extensive synergy studies from reduced data sets for 

other chemicals. The goal of obtaining this set of data is to determine the potential 

range of magnitudes of synergistic effects for pesticide active ingredients that are coapplied with PBO for the purpose of enhancing efficacy due to synergism. Without this 

data set, the Agency would have to presume acute toxicity to listed and non-listed 

invertebrates, but would not be able to quantify the risk.

Guideline Number: 850.1350 

Study Title: Aquatic Invertebrate Life Cycle Toxicity (Saltwater) with TGAI

No acceptable chronic studies for PBO have been submitted for estuarine/marine 

invertebrates. The acute toxicity of PBO to estuarine/marine invertebrates and 

environmental fate properties indicate the potential for chronic exposure and effects to 

animals in this taxon, per 40 CFR Part 158 data requirements. The persistence of PBO in 

water is expected to substantially exceed the 4-d half life criterion (75 d for parent, 133 d 

for total toxic residues, Table 3). Chronic toxicity data are required per 40 CFR Part 

158.630 due to the potential for direct application of PBO to the estuarine/marine 

environment, acute toxicity value that is <1 ppm (0.23 for the oyster), and the expected 

peak EECs (58 to 160 ppb, for aerial application to lettuce, cabbage, citrus, cucumber, 

pepper, strawberry, potato, tomato, beans, sugarbeets and cotton, 2005 RED eco 

chapter13) exceed 0.01 of the acute toxicity values (this would be 4.9 ppb for mysid and 

2.3 ppb for oysters). Without this study, the Agency would have to presume chronic risk 

to listed and non-listed estuarine/marine invertebrates, but would not be able to quantify 

the risk.

Guideline Number: 850-1400

Study Title: Fish Early Life Stage (Saltwater) with TGAI

No acceptable chronic studies for PBO have been submitted for marine fish. The acute 

toxicity of PBO to estuarine/marine fish and environmental fate properties indicate the 

potential for chronic exposure and effects to animals in this taxon, per 40 CFR Part 158 

data requirements. Chronic toxicity data are required per 40 CFR Part 158.630 due to the 

potential for direct application of PBO to the estuarine/marine environment, acute 

toxicity value that is <1 ppm (0.23 for the oyster), and the expected peak EECs (58 to 

 

13 Piperonyl Butoxide: Environmental Risk Assessment, Revised September, 2005. D139408.
43

160 ppb, for aerial application to lettuce, cabbage, citrus, cucumber, pepper, strawberry, 

potato, tomato, beans, sugarbeets and cotton, 2005 RED eco chapter14) exceed 0.01 of the 

acute toxicity values (this would be 39.4 ppb for sheepshead minnows to 2.3 ppb for 

oysters, MRIDs 42540304 and 42540305). Without this study, the Agency would have to 

presume chronic risk to listed and non-listed estuarine/marine fish, but would not be able 

to quantify the risk.

Guideline Number: 850.1500 

Study Title: Full Life Cycle Fish Test (Freshwater) with TGAI.

PBO and its major degradates are persistent, mobile and may pass through wastewater 

treatment processes. PBO may also be applied directly to both freshwater and 

estuarine/marine environments. Since the expected peak EECs (58 to 160 ppb, for aerial 

application to lettuce, cabbage, citrus, cucumber, pepper, strawberry, potato, tomato, 

beans, sugarbeets and cotton, 2005 RED eco chapter17) exceed 0.1 of the early life stage 

study, a fish life-cycle test is required. This DCI remains unfulfilled. Without this study, 

the Agency would have to presume chronic risk to listed and non-listed fish and aquaticphase amphibians, but would not be able to quantify the risk.

Guideline Number: 850.1760; 850.1770; 850.1780 - Study Title: Whole sediment: 

chronic invertebrates freshwater and marine

For PBO, available information indicates that benthic organisms may be exposed via runoff or spray drift applications used in agricultural, forest, and residential settings, as well 

as direct applications to water. The panel 1999 SAP panel called for sediment toxicity 

testing for pyrethroids (see Section 1.0 for more details); afterward, the new CFR Part 

158 requirements included sediment toxicity tests. The new data requirements include 

chronic sediment toxicity studies for freshwater and marine organisms. The criteria are

met for requiring chronic sediment toxicity studies for PBO due to its half-life of 14d in 

aerobic soil and 75d in aerobic water (MRIDs 43806401 and 43803401 both as amended 

5/17/2004), log Kow of 4.75 and Koc of up to1152 (MRID 43673802) and expected peak 

EECs (58 to 160 ppb, for aerial application to lettuce, cabbage, citrus, cucumber, pepper, 

strawberry, potato, tomato, beans, sugarbeets and cotton, 2005 RED eco chapter17) which 

exceed 0.1 of the acute LC/EC50 (490*0.1 = 49 ppb for M. bahia, MRID 43901801). 

For sediment studies, tests on Hyalella azteca, Chironomus dilutus, and Leptocheirus 

plumulosus are requested. Although both are freshwater species, Hyalella and 

Chironomus differ substantially in their ecological niche (i.e., epibenthic vs. infaunal 

species). Furthermore, Hyalella and Chironomus differ significantly in their physiology 

and life history, with Chironomus being the only sediment test species undergoing 

metamorphosis and emergence from an aquatic to a terrestrial life stage. There is also 

evidence suggesting Hyalella is among the more sensitive invertebrates to some 

pyrethroids based on water column tests (Anderson et al. 2006, Maund et al., 2002). PBO 

has the potential to enter estuarine/marine water bodies based on current usuage patterns 

that include coastal areas. Therefore, testing is required for Leptocheirus plumulosus, an 

estuarine/marine sediment-dwelling invertebrate species.

 

14 Piperonyl Butoxide: Environmental Risk Assessment, Revised September, 2005. D139408.
44

Guideline Number: 850.4400

Study Title: Aquatic Vascular Plant Growth-Lemna spp. Tier I/II with TGAI

No acceptable studies for PBO have been submitted for vascular aquatic plants. The 

Agency has finalized its update to the data requirements in 40 CFR Part 158. In these 

updated data requirements, which were promulgated on October 26, 2007, vascular plant 

testing is required for pesticides such as PBO with outdoor uses. Tier I testing is 

required, followed by Tier II if required by Tier I results as specified in Tier I guidelines.

Guideline Number: 850.5400

Study Title: Algal Toxicity test, Tier I/II with TGAI

No toxicity data are currently available to assess the risk of PBO to aquatic nonvascular 

plants. Since PBO has outdoor uses, Tier I/II aquatic nonvascular plant studies are 

required. These phytotoxicity data are needed to evaluate the level of pesticide exposure 

to non-target aquatic plants and to assess the impact of pesticides on endangered and 

threatened plants. Tier I testing is required, followed by Tier II if required by Tier I 

results as specified in Tier I guidelines.

Guideline Number: 850.3020

Study Title: Honey Bee Acute Contact Toxicity using TEP 

Terrestrial invertebrate toxicity data are required to quantitatively assess the potential 

impacts on this group of organisms. Data are needed from the honey bee acute contact 

study due to wide spread use and possible drift to off site vegetation in bloom. 

Available data (MRID 41969009) show PBO to be moderately toxic to practically 

non-toxic to honey bees (LD50 >25 μg/bee). Since PBO acts as a synergist 

insecticide, the effects of a typical end-use product may be much greater. 

Guideline Number: 850-2100

Study Title: Passerine Acute Avian Oral 

Although an acute avian oral study was received for both the Mallard duck and Bobwhite 

quail, the Agency updated its data requirements in 40 CFR Part 158 (October 26, 2007) 

to include an acute oral toxicity study for both a passerine species and either a waterfowl 

or an upland game species. Prior to starting toxicity testing, a protocol will need to be 

provided for review. Many passerine species utilize agricultural fields, forests, residential 

areas and surrounding areas, and, therefore, have the potential to be exposed to pesticides 

used in agricultural, forest, and residential settings. It is likely that, for most pesticide use 

patterns, passerines are more likely to be exposed to pesticides than upland game species 

and waterfowl. Passerines are smaller in size and generally have faster metabolisms than 

the waterfowl and upland game bird species traditionally used in avian toxicity tests 

which could impact their sensitivity to chemicals.

Guideline Numbers: 850.4100 and 850.4150

Study Title: Vegetative vigor and Seedling emergence, Tier I/II with TEP

No acceptable toxicity data are currently available to assess the risk of PBO to non-target 

terrestrial plants. Since PBO has outdoor uses, vegetative vigor and seedling emergence 

studies are required. These phytotoxicity data are needed to evaluate the level of 
45

pesticide exposure to non-target terrestrial and aquatic plants and to assess the impact of 

pesticides on endangered and threatened plants. Results from Tier I tests very often 

necessitate the performance of a Tier II test. If a tested terrestrial species exhibits a 25 

percent or greater detrimental effect in a Tier I study, a Tier II study is required. If the 

registrant chooses to only submit a Tier II study, a Tier I study will not be required.

Guidance on Testing with Typical end-use products (TEP) 

According to the Part 158 data requirements, testing on the typical end-use product may 

be required for aquatic toxicity tests when any of the following conditions exist: 

1. The end-use product will be introduced directly into the aquatic environment.

2. The maximum expected environmental concentration or estimated 

environmental concentration in the aquatic environment is greater than or equal to 

one-half the LC50 or EC50 of the TGAI.

3. An ingredient in the end-use formulation other than the active ingredient is 

expected to enhance the toxicity of the active ingredient or cause toxicity to 

aquatic organisms.

A Typical End-Use Product is defined in the Pesticide Assessment Guidelines 

Subdivision J Hazard Evaluation: Nontarget plants on Part 120-2(1) on Page 18 as “a 

pesticide product that is representative of a major formulation category (e.g., emulsifiable 

concentrate, granular product, wettable powder) and pesticide group (e.g., herbicide, 

fungicide, insecticide etc.) and contains the active ingredient of the applicant‟s product.” 

(Holst and Ellwanger, 1982).

Page 5 of the Pesticide Assessment Guidelines Subdivision J Hazard Evaluation: 

Nontarget plants provide additional information on what TEP data should be tested for 

toxicity testing in the following excerpt.

“The Agency seeks to avoid imposing a burden of duplicative testing on 

applicants for registration. Therefore, where 40 CFR Part 158 specifies that the 

test substance should be a representative end-use product, testing may be 

performed using the formulation in question (end-use product being registered) or 

similar, yet representative, end-use product. It is not necessary to repeat the test 

using other similar products.” (Holst and Ellwanger, 1982).

When TEP data are requested, data should be submitted for the different formulations, 

e.g., wettable powder, emulsifiable concentrate, granular, along with a rationale as to why 

the TEP is representative of other similar end-use products. Acute aquatic toxicity studies 

conducted with the Typical End-Use Product (TEP) may be used to assess effects as a 

result of exposure to spray drift only and reflect potential effects from a brief exposure to 

the formulation. Therefore, appropriate TEPs should be selected from formulations that 

are registered for agricultural uses, not residential.

Additional Programs:

Study Title: Endocrine Disruptor Screening Program
46

PBO is part of the Endocrine Disruptor Screening Program; certain data has been 

required for the chemical under the program (DCI on 11/19/09; 90-day response by 

02/27/10). Please, refer to the website: http://www.epa.gov/endo/. 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 dose-response relationship 

between the dose and the E, A, or T effect.

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 postapplication 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. The Agency will review the EDSP Tier 1 data and any “other 

scientifically relevant information” submitted in response to test orders. Based on this 

review the Agency will determine the need for additional testing. For further information 

on the status of the EDSP, the policies and procedures, the list of 67 chemicals, the test 

guidelines and the Tier 1 screening battery, please visit our website: 

http://www.epa.gov/endo/ .

Study Title: POTW Effluent Monitoring and POTW Treatability Study

PBO is part of an effort to determine amounts of pyrethroids making it through 

publically-owned treatment works (POTWs). The Agency is requiring bench scale 

treatability studies for pyrethroids, to assess amounts that would degrade during 

treatment, remain in biosolids, or remain in waste water.

Other Information Needs

There is specific information that will assist the Agency in refining the ecological risk 

assessment, including any species-specific effects determinations. The Agency is very 

much interested in obtaining the following information:

1. confirmation on the following label information
47

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

applications per season

b. geographic limitations on use

2. names of chemicals that are co-applied with PBO for its synergistic properties 

including those that are formulated with PBO and those that are otherwise 

recommended for mixing with PBO prior to application.

3. use or potential use distribution (e.g., acreage and geographical distribution of 

relevant crops)

4. use history

5. median and 90th percentile reported use rates (lbs. a.i./acre) from usage data –

national, state, and county

6. application timing (date of first application and application intervals) by crop –

national, state, and county

7. sub-county crop location data

8. usage/use information for non-agricultural uses (e.g., forestry, residential, rightsof-way)

9. directly acquired county-level usage data (not derived from state level data)

a. maximum reported use rate (lbs. a.i./acre) from usage data – county

b. percent crop treated – county

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

d. total pounds per year – county

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

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

10. typical interval (days)

11. state or local use restrictions

12. ecological incidents (non-target plant damage and avian, fish, reptilian, amphibian 

and mammalian mortalities) not already reported to the Agency

13. monitoring data 

The analysis plan will be revisited and may be revised depending upon the data available 

in the open literature and the information submitted by the public in response to the 

opening of the Registration review docket.
48

8. References

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Piperonyl Butoxide on Permethrin Toxicity in the Amphipod Hyalella azteca. 

Environmental Toxicology and Chemistry, Vol. 25, No. 7, pp. 1817–1825.

Anderson et al. 2006, Barile, F. A. 2004. Clinical Toxicology: Principles and 

Mechanisms. Boca Raton, FL: CRC Press .

Barile, F. A. 2004. Clinical Toxicology: Principles and Mechanisms. Boca Raton, FL: 

CRC Press.,

DiToro, D. M., Zarba, C. S., Hansen, D. J., Berry, W. J., Schwartz, R. C., Cowan, C. E., 

et al. 1991. Technical basis for establishing sediment quality criteria for nonionic 

organic chemicals using equilibrium partitioning. Environmental Toxicology and 

Chemistry, 10, 1541-1586.

Farm Chemicals Handbook 2002: Global Guide to Crop Protection. Meister Publishing 

Company. ISBN13: 9781892829054. ISBN10: 1892829053

Gibly, R. L., & Sullivan Jr., J. B. 2001. Chapter 103. Pyrethrins. In J. B. Sullivan Jr. & G. 

R. Krieger (Eds.), Clinical Principles of Environmental Health. Philadelphia, PA: 

Lippincott Williams & Wilkins. 

Hodgson, E., & Smart, R. C. (Eds.). 2001. Introduction to Biochemcial Toxicology (Third 

ed.). New York: Wiley-Interscience.

Holst, R. W., & Ellwanger, T. C. 1982. Pesticide Assessment Guidelines. Subdivision J. 

Hazard Evaluation: Nontarget Plants. EPA-540/09-82-020. October 1982. 

Office of Pesticide Programs. Office of Pesticides and Toxic Substances. United 

States Environmental Protection Agency. 

Lewis, R. A. 1998. Lewis' Dictionary of Toxicology. In R. A. Lewis (Ed.). Boca Raton: 

Lewis Publishers.S.J. Maund, M.J. Hamer, M.C. Lane, E. Farrelly, J.H. Rapley, 

U.M. Goggin and W.E. Gentle, Partitioning, bioavailability, and toxicity of the 

pyrethroid insecticide Cypermethrin in sediments, Environ. Toxicol. Chem. 21 (1) 

(2002), pp. 9–15

Morton, T. 2004. Piperonyl Butoxide: Revised Anticipated Residues and Acute probabilistic 

and Chronic Dietary Exposure Assessment for the Reregistration Eligibility Decision. 

D310032; November 23, 2004.

Urban, J.D., and Cook, N.J. (1986) Ecological Risk Assessment: Standard Evaluation 

Procedures. Report No. EPA 540/9-85-001. US Environmental Protection 

Agency, Hazard Evaluation Division, Washington, D.C. Available from NTIS 

(National Technical Information Service), Springfield, Virginia 22161, as PB 86-

247-657. 

USEPA. 1998. Guidelines for Ecological Risk Assessment. United States Environmental 

Protection Agency (USEPA). Risk Assessment Forum. Office of Research and 

Development. Available at 

http://cfpub.epa.gov/ncea/cfm/recordisplay.cfm?deid=12460 (Accessed June 19, 

2009).

USEPA. 2000. Prediciton of sediment toxicity using consensus-based freshwater 

sediment quality guidelines. EPA 905/R-00/007.

USEPA. 2003. Technical basis for the derivation of equilibrium partitioning sediment 

benchmarks (ESBs) for the protection of benthic organisms: Nonionic organics 
49

(draft). Office of Research and Development. United States Environmnetal 

Protection Agency. 

USEPA, 2004. Overview of the Ecological Risk Assessment Process in the Office of 

Pesticide Programs, US Environmental Protection Agency. Endangered and 

Threatened Species Effects Determinations. Jan. 23, 2004.

USEPA, 2006a. Reregistration Eligibility Decision for Piperonyl Butoxide (PBO). 

United States Environmental Protection Agency (USEPA). Prevention, Prsticides 

and Toxic Substances. EPA 738-R-06-005. June 2006. Available at 

http://www.epa.gov/oppsrrd1/reregistration/REDs/piperonyl_red.pdf.

USEPA, 2006b. Revised Pyrethrins RED Chapter After Additional 60-Day Comment

Period, Phase 5. United States Environmental Protection Agency (USEPA). 

Prevention, Pesticides and Toxic Substances. June 2006.

USFWS/NMFS/NOAA.2004. 50 CFR Part 402. Joint Counterpart Endangered Species 

Act Section 7 Consultation Regulations; Final Rule. Federal Register Volume 69. 

Number 20.Pages 47731-47762. August 5, 2004

Weston, D.P., E.L. Amweg, A. Mekebri, R.S. Ogle and M.J. Lydy. 2006. Aquatic 

Effects of Aerial Spraying for Mosquito Control over an Urban Area. Environ. 

Sci. Technol. 40, 5817-5822.

Williams, S., & Hogarth, W. 2004. Letter providing an evaluation by the U.S. Fish and 

Wildlife Service and National Marine Fisheries Service of an approach to 

assessing the ecological risks of pesticide products. Memorandum From to S. 

Hazen. January 26, 2004. United States Fish and Wildlife Service (USFWS) and 

National Marine Fisheries Service (NMFS). 
50

9. PRD data request justification tables 

The following proposed Data Call-in tables include rationales for requiring the data 

requested in this problem formulation, explanations of the utility of the data, and 

explanations for how the data might impact risk assessment, following the format 

provided by the Pesticide Registration Division.

Guideline Number: 835.4100

Study Title: Aerobic Soil Metabolism

Rationale for Requiring the Data

The Agency has a limited understanding of how PBO behaves in soil once applied. Depending on how 

quickly, to what extent, and to which transformation products the compound degrades, PBO may or may 

not pose potential exposure concern. Only one acceptable study (using one soil only) has been reviewed 

by the agency at this time (MRID# 43806401). This is a major deficiency and hinders our ability to 

determine 1) the pattern of PBO decline, 2) the patterns of formation and decline of the degradates, and 3) 

an aerobic soil half life. The aerobic soil metabolism half-life is a key input parameter in modeling 

drinking water as well as for ecological risk assessment.

Practical Utility of the Data

How will the data be used?

Additional aerobic soil metabolism data will facilitate a better understanding of the fate of PBO residues

in soil. If data indicate that degradation in aerobic soil occurs rapidly and produces nontoxic 

transformation products, then the Agency could potentially determine that PBO residues of concern do 

not persist in soil under aerobic conditions. If data indicate that degradation is not appreciable in soil or 

that the transformation products are of similar or higher toxicity than the parent compound, then the 

Agency could conclude that PBO residues of concern persist in soil under some aerobic conditions.

How could the data change the Agency’s decision or impact the Agency’s future decision-making? 

In the absence of the required data, PBO will be conservatively assumed to degrade in aerobic soils at a 

rate three times slower than the submitted data indicate. If the required data indicate that PBO in aerobic 

soils is rapidly biodegraded to nontoxic transformation products, then risk assessment conclusions and 

associated labeled use precautions and/or restrictions could be made less restrictive.

Guideline Number: 835.4300

Study Title: Aerobic Aquatic Metabolism

Rationale for Requiring the Data

The Agency has a limited understanding of how PBO behaves in aerobic aquatic environments once 

applied. The agency has only one upgradable to acceptable study using one sediment (MRID# 

43836501). Depending on how quickly, to what extent, and to which transformation products the 

compound degrades, PBO may or may not pose potential exposure concern in water. As per OCSPP 

Harmonized Test Guidelines; At least two sediments and their associated waters are used for the aerobic 

aquatic metabolism study; aerobic surface water systems is not well understood, the Agency is requiring 

data.

Practical Utility of the Data

How will the data be used?

Aerobic aquatic metabolism data will facilitate a better understanding of the fate of PBO residues in 

water. If data indicate that degradation in aerobic conditions occurs rapidly in aquatic systems and 

produces nontoxic transformation products, then the Agency could potentially determine that PBO 

residues of concern do not persist in these systems. If data indicate that degradation is not appreciable in 

aquatic systems or that the transformation products are of similar or higher toxicity than the parent 
51

compound, then the Agency could conclude that PBO residues of concern persist in surficial aquatic 

systems under aerobic conditions. 

How could the data change the Agency’s decision or impact the Agency’s future decision-making? 

In the absence of the requested data, PBO will be assumed stable to biodegradation in aerobic, surficial

aquatic environments. If the required data indicate that PBO in aerobic surficial aquatic environments is 

rapidly biodegraded to nontoxic degradation products, then risk assessment conclusions and associated 

labeled use precautions and/or restrictions could be made less restrictive.

Guideline Number: 835.4400

Study Title: Anaerobic Aquatic Metabolism

Rationale for Requiring the Data

The Agency has a limited understanding of how PBO behaves in anaerobic aquatic environments once 

applied. The agency has only one supplemental study using one sediment (MRID# 43836501). 

Depending on how quickly, to what extent, and to which transformation products the compound 

degrades, PBO may or may not pose potential exposure concern in water. As per OCSPP Harmonized 

Test Guidelines; At least two sediments and their associated waters are used for the anaerobic aquatic 

metabolism study; anaerobic surface water systems is not well understood, the Agency is requiring data.

Practical Utility of the Data

How will the data be used?

Anaerobic aquatic metabolism data will facilitate a better understanding of the fate of PBO residues in 

water. If data indicate that degradation in anaerobic conditions occurs rapidly in aquatic systems and 

produces nontoxic transformation products, then the Agency could potentially determine that PBO 

residues of concern do not persist in these systems. If data indicate that degradation is not appreciable in 

aquatic systems or that the transformation products are of similar or higher toxicity than the parent 

compound, then the Agency could conclude that PBO residues of concern persist in surficial aquatic 

systems under anaerobic conditions. 

How could the data change the Agency’s decision or impact the Agency’s future decision-making? 

In the absence of the requested data, PBO will be assumed stable to biodegradation in anaerobic, surficial

aquatic environments. If the required data indicate that PBO in anaerobic surficial aquatic environments 

is rapidly biodegraded to nontoxic degradation products, then risk assessment conclusions and associated 

labeled use precautions and/or restrictions could be made less restrictive.

Guideline Number: 835.1230

Study Title: Adsorption/Desorption

Rationale for Requiring the Data

The Agency has a limited understanding of PBO behaves in the environment once applied. Depending on 

the mobility of the compound in the environment, PBO may or may not be transported to surface water 

and/or ground water bodies used by organisms in the environment and/or by humans for drinking water. 

Unaged soil column data are available from one acceptable study (MRID# 43673801). As per OCSPP 

Harmonized Test Guidelines; At least two soils should be used to fulfill this guideline requirment. Because 

PBO mobility in the environment is not well understood, the Agency is requiring additional batch 

equilibrium data.

Practical Utility of the Data

How will the data be used?

Batch equilibrium data at concentrations resulting from labeled application rates will facilitate a better 

understanding of PBO mobility in the environment. If data confirm that the compound has low mobility at 

these concentrations, then the Agency could potentially determine that PBO would not likely contribute to 
52

environmental exposure. If data indicate that the compound is mobile at concentrations resulting from 

labeled application rates, then the Agency could not necessarily conclude that environmental exposure is 

negligible and further study and/or restrictions would be required. 

How could the data impact the Agency’s future decision-making? 

In the absence of the required data, data from the open literature based on high concentrations will be used 

for ecological risk and drinking water exposure assessment. If the required data indicate that PBO is 

mobile in the environment at concentrations resulting from labeled application rates, then environmental 

exposure may be of concern and additional use precautions and/or restrictions may be necessary.

Guideline Number: 875.2100

Study Title: Dislodgable Foliar Residues (modified for total foliar residue) – protocol to be 

submitted prior to study initiation

Rationale for Requiring the Data

The Agency has a limited understanding of PBO behaves in the environment once applied. This includes 

foliar residues and foliar dissipation half-lives for PBO and its three major degradates, PBO-alcohol, PBOaldehyde and PBO-acid. Previous risk assessment shows a potential for chronic risk to mammals and 

birds from PBO using the default half-life of 35 days. 

Practical Utility of the Data

How will the data be used? Foliar dissipation rate data will be used to estimate the risk to terrestrial 

animals feeding on plants that have been exposed to PBO and its degradates through registered use.

How could the data impact the Agency’s future decision-making? 

Without this information, the Agency will assume a default 35-d dissipation rate, possibly overestimating 

or underestimating risk.

Guideline Number: 835.6100

Study Title: Analytical Method (and Associated Independent Laboratory Validation) for Residues 

in Soil and Sediment

Rationale for Requiring the Data

Independently validated analytical methods for residues in soil, water, sediment, and plant material 

(environmental chemistry methods) submitted by the registrant are used to evaluate analyses described in 

submitted environmental fate and ecological effects studies. Submitted analytical methods are also used 

by various Federal, State, Tribal, and local agencies to detect and monitor residues that are or are 

suspected to be in environmental compartments due to outdoor uses and accidental releases. Independent 

laboratory validations for submitted analytical methods are necessary to confirm that the methods are 

functional and to confirm the levels of detection and quantitation reported in registrant-prepared 

validations.

Environmental chemistry methods in soil or sediment have not been submitted in support of submitted 

terrestrial or aquatic field dissipation studies of piperonyl butoxide (PBO). An independently validated 

environmental chemistry method in soil (and in sediment if procedures for sediment differ from those for 

soil) is necessary to evaluate the results of submitted terrestrial field dissipation studies and to provide

outside agencies an analytical method with which to monitor for PBO residues in soil and aquatic 

sediment.

The submitted environmental chemistry method should include as analytes PBO and its major 

transformation products identified in laboratory environmental fate studies, which currently include PBOalcohol, PBO-aldehyde, and PBO-acid. The level of quantitation (LOQ) should be below concentrations 
53

that result in potential risks to benthos (i.e., should be less than the lowest toxicological level of concern 

with respect to benthos for PBO alone and for PBO plus the most toxic chemical with which it is coapplied). This LOQ will likely depend on the lowest toxicological level of concern for the most toxic coapplied chemical and the ratio of PBO to this chemical at which PBO is most synergistic with it. 

Therefore, development of this environmental chemistry method should pend the results of the called-in 

data in order to include as analytes all major transformation products identified in the submitted and 

called-in environmental fate studies and to include levels of quantitation below toxicological levels of 

concern determined in the submitted and called-in ecotoxicity studies, including the called-in synergism 

studies.

Practical Utility of the Data

How will the data be used?

In the absence of an independently validated environmental chemistry method in soil and sediment, 

submitted terrestrial field dissipation studies are not acceptable and entities outside the Agency may lack 

a chemical-specific method for analyses in soil and sediment. An independently validated environmental 

chemistry method will be used to evaluate submitted terrestrial field dissipation studies in which it is used

and will be made available for enforcement and monitoring purposes at the federal, state, and local levels.

How could the data change the Agency’s decision or impact the Agency’s future decision-making? 

Risk assessment conclusions could be altered if they are not supported by either study data or 

environmental monitoring detections that are based on independently validated environmental chemistry 

methods. Furthermore, while not directly related to Agency decision-making, independently validated 

environmental chemistry methods are necessary to ensure the safety of those in proximity to releases of 

PBO and co-applied chemicals in the environment.

Guideline Number: 835.6200

Study Title: Analytical Method (and Associated Independent Laboratory Validation) for Residues 

in Water

Rationale for Requiring the Data

Independently validated analytical methods for residues in soil, water, sediment, and plant material 

(environmental chemistry methods) submitted by the registrant are used to evaluate analyses described in 

submitted environmental fate and ecological effects studies. Submitted analytical methods are also used 

by various Federal, State, Tribal, and local agencies to detect and monitor residues that are or are 

suspected to be in environmental compartments due to outdoor uses and accidental releases. Independent 

laboratory validations for submitted analytical methods are necessary to confirm that the methods are 

functional and to confirm the levels of detection and quantitation reported in registrant-prepared 

validations.

Use of piperonyl butoxide (PBO) may impact surface water quality due to drift of residues and to runoff 

of rain water carrying dissolved residues and residues adsorbed to suspended sediment. PBO residues 

have a high potential for reaching surface water via runoff for several weeks after application. Therefore, 

outside agencies may request analytical methods with which to monitor for PBO residues in water.

Environmental chemistry methods in water have not been submitted in support of submitted aquatic field 

dissipation studies. An independently validated environmental chemistry method in water is necessary to 

evaluate the results of submitted aquatic field dissipation studies and to provide outside agencies an 

analytical method with which to monitor for PBO residues in water.

The submitted environmental chemistry method should include as analytes PBO and its major 

transformation products identified in laboratory environmental fate studies, which currently include PBOalcohol, PBO-aldehyde, and PBO-acid. The level of quantitation (LOQ) should be below concentrations 
54

that result in potential risks to aquatic organisms (i.e., should be less than the lowest toxicological level of 

concern with respect to aquatic organisms for PBO alone and for PBO plus the most toxic chemical with 

which it is co-applied). This LOQ will likely depend on the lowest toxicological level of concern for the 

most toxic co-applied chemical and the ratio of PBO to this chemical at which PBO is most synergistic

with it. Therefore, development of this environmental chemistry method should pend the results of the 

called-in data in order to include as analytes all major transformation products identified in the submitted 

and called-in environmental fate studies and to include levels of quantitation below toxicological levels of 

concern determined in the submitted and called-in ecotoxicity studies, including the called-in synergism 

studies.

Practical Utility of the Data

How will the data be used?

In the absence of an independently validated environmental chemistry method in water, submitted aquatic 

field dissipation studies are not acceptable and entities outside the Agency may lack chemical-specific 

methods for analyses in water. An independently validated environmental chemistry method will be used 

to evaluate submitted aquatic field dissipation studies in which it is used and will be made available for 

enforcement and monitoring purposes at the federal, state, and local levels.

How could the data change the Agency’s decision or impact the Agency’s future decision-making? 

Risk assessment conclusions could be altered if they are not supported by either study data or 

environmental monitoring detections that are based on independently validated environmental chemistry 

methods. Furthermore, while not directly related to Agency decision-making, independently validated 

environmental chemistry methods are necessary to ensure the safety of those in proximity to releases of 

PBO and co-applied chemicals in the environment.

Guideline Number: 850.1075

Study Title: Fish Acute Toxicity Test, Freshwater TEP 

Rationale for Requiring the Data

PBO may be applied directly to water. Therefore, testing of a TEP applied to water is required to 

evaluate the potential effects of the ingredients within the TEP on fish. 

Without toxicity data on the range of TEPs produced, the Agency would presume acute risk to 

listed and non-listed fish exceeds LOCs, but would not be able to quantify the risk and would not 

be able to evaluate efficacy of mitigations.

Practical Utility of the Data

How will the data be used? Toxicity data with at least one TEP and a bridging strategy to others 

would allow the Agency to further analyze potential acute effects. The effects data would be used 

to determine the likelihood that acute risks can potentially impact aquatic communities, either by 

direct effects on fish or by indirect effects by reducing their food sources. By refining the 

assessment, the Agency would be able to determine whether the mitigation imposed as part of the 

registration review process was appropriate due to toxicity concerns with PBO use.

How could the data impact the Agency’s future decision-making? If future endangered species 

risk assessments are performed without these data, the Agency would have to assume that PBO 

products "may affect" endangered fish directly (and endangered species from other taxa 

indirectly), and use of PBO products might need to be restricted in areas where endangered species 

could be exposed. The lack of these data will limit the flexibility the Agency and registrants have 

in coming into compliance with the Endangered Species Act and could result in use restrictions for 

PBO products which are unnecessarily severe.
55

Guideline Number: 850.1075

Study Title: Fish Acute Toxicity Test, Freshwater using PBO-alcohol

Rationale for Requiring the Data

PBO may be applied directly to water. Since PBO-alcohol has a similar structure, it is expected to 

have similar piscicidal properties. Without toxicity data on degradates, the Agency will 

assess risks using a strategy of total toxic residues.

Practical Utility of the Data

How will the data be used? Toxicity data on major degradates would allow the Agency to 

further analyze potential acute effects. The effects data would be used to determine the likelihood 

that acute risks can potentially impact aquatic communities, either by direct effects on fish or by 

indirect effects by reducing their food sources. By refining the assessment, the Agency would be 

able to determine whether any mitigation imposed as part of the registration review process is 

appropriate due to toxicity concerns with PBO use.

How could the data impact the Agency’s future decision-making? If future endangered species 

risk assessments are performed without these data, the Agency would have to assume that PBOalcohol is at least as toxic as PBO or that PBO products "may affect" endangered fish directly (and 

endangered species from other taxa indirectly), and use of PBO products might need to be 

restricted in areas where endangered species could be exposed. The lack of these data will limit 

the flexibility the Agency and registrants have in coming into compliance with the Endangered 

Species Act and could result in use restrictions for PBO products which are unnecessarily severe.

Guideline Number: 850.1075

Study Title: Fish Acute Toxicity Test, Freshwater using PBO-aldehyde

Rationale for Requiring the Data

PBO may be applied directly to water. Since PBO-aldehyde has a similar structure, it is expected 

to have similar piscicidal properties. Without toxicity data on degradates, the Agency will 

assess risks using a strategy of total toxic residues.

Practical Utility of the Data

How will the data be used? Toxicity data on major degradates would allow the Agency to 

further analyze potential acute effects. The effects data would be used to determine the likelihood 

that acute risks can potentially impact aquatic communities, either by direct effects on fish or by 

indirect effects by reducing their food sources. By refining the assessment, the Agency would be 

able to determine whether any mitigation imposed as part of the registration review process is 

appropriate due to toxicity concerns with PBO use.

How could the data impact the Agency’s future decision-making? If future endangered species 

risk assessments are performed without these data, the Agency would have to assume that PBOaldehyde is at least as toxic as PBO or that PBO products "may affect" endangered fish directly 

(and endangered species from other taxa indirectly), and use of PBO products might need to be 

restricted in areas where endangered species could be exposed. The lack of these data will limit 

the flexibility the Agency and registrants have in coming into compliance with the Endangered 

Species Act and could result in use restrictions for PBO products which are unnecessarily severe.

Guideline Number: 850.1075

Study Title: Fish Acute Toxicity Test, Freshwater using PBO-acid
56

Rationale for Requiring the Data

PBO may be applied directly to water. Since PBO-acid has a similar structure, it is expected to 

have similar piscicidal properties. Without toxicity data on degradates, the Agency will 

assess risks using a strategy of total toxic residues.

Practical Utility of the Data

How will the data be used? Toxicity data on major degradates would allow the Agency to 

further analyze potential acute effects. The effects data would be used to determine the likelihood 

that acute risks can potentially impact aquatic communities, either by direct effects on fish or by 

indirect effects by reducing their food sources. By refining the assessment, the Agency would be 

able to determine whether any mitigation imposed as part of the registration review process is 

appropriate due to toxicity concerns with PBO use.

How could the data impact the Agency’s future decision-making? If future endangered species 

risk assessments are performed without these data, the Agency would have to assume that PBOacid is at least as toxic as PBO or that PBO products "may affect" endangered fish directly (and 

endangered species from other taxa indirectly), and use of PBO products might need to be 

restricted in areas where endangered species could be exposed. The lack of these data will limit 

the flexibility the Agency and registrants have in coming into compliance with the Endangered 

Species Act and could result in use restrictions for PBO products which are unnecessarily severe.
57

Guideline Number: 850.1075

Study Title: Fish Acute Toxicity Test, Freshwater (Modified Guideline Study designed to 

evaluate synergism)

Rationale for Requiring the Data

PBO and its major degradates are persistent, mobile and may pass through wastewater treatment 

processes. It may also be applied directly to water. PBO is a pesticide synergist. Therefore, it is 

used in combination with other pesticides to enhance their effectiveness (toxicity) to target 

organisms. Assessing potential ecological risks of PBO requires evaluating potential exposure and 

toxicity of the active ingredient (PBO alone) and evaluating the enhanced toxicity of other 

pesticides with which it is simultaneously applied. Given the number of chemicals with which 

PBO may be simultaneously applied, designing a study that examines the range of synergistic 

effects is difficult. A comprehensive evaluation of potential synergistic effects of PBO and all 

chemicals with which it may be simultaneously applied will require the development and review 

of a large body of data. The Agency recognizes that this data set is extensive and is willing to 

consider options for a reduced data set that evaluates the nature of PBO synergy with a limited 

number of compounds, and allows bridging to these more extensive synergy studies from reduced 

data sets for other chemicals. The goal of obtaining this set of data is to determine the 

potential range of magnitudes of synergistic effects for pesticide active ingredients that are 

co-applied with PBO for the purpose of enhancing efficacy due to synergism. The 

Agency is interested in obtaining data on (or bridging data to) pesticide active ingredients 

(in addition to other chemicals with similar modes of action) that are co-applied with PBO 

for its synergistic properties including those that are formulated with PBO and those that 

are otherwise recommended for mixing with PBO prior to application. 

Protocols need to be submitted to the Agency prior to study initiation.

Without toxicity data on the range of TEPs produced, the Agency would presume acute risk to 

listed and non-listed fish and aquatic-phase amphibians exceeds LOCs, but would not be able to 

quantify the risk and would not be able to evaluate efficacy of mitigations.

Practical Utility of the Data

How will the data be used? Toxicity data with at least one TEP and a bridging strategy to others

would allow the Agency to further analyze potential acute effects. The effects data would be used 

to determine the likelihood that acute risks can potentially impact aquatic communities, either by 

direct effects on fish and aquatic-phase amphibians or by indirect effects by reducing their food 

sources. By refining the assessment, the Agency would be able to determine whether the 

mitigation imposed as part of the registration review process was appropriate due to toxicity 

concerns with PBO use.

How could the data impact the Agency’s future decision-making? If future endangered species 

risk assessments are performed without these data, the Agency would have to assume that PBO 

products "may affect" endangered fish and aquatic-phase amphibians directly (and endangered 

species from other taxa indirectly), and use of PBO products might need to be restricted in areas 

where endangered species could be exposed. The lack of these data will limit the flexibility the 

Agency and registrants have in coming into compliance with the Endangered Species Act and 

could result in use restrictions for PBO products which are unnecessarily severe.
58

Guideline Number: 850.1400

Study Title: Fish Early Life Stage (Saltwater)

Rationale for Requiring the Data

The acute toxicity of PBO to estuarine/marine fish and environmental fate properties indicate the potential for 

chronic exposure and effects to animals in this taxon, per 40 CFR Part 158 data requirements (October 26, 

2007). For example, the acute LC50 for oysters (0.23 mg a.i./L) is below 1.0 mg/L and the estimated peak EECs 

(58-160 ppb for aerieal applications to several crops) exceed 0.01 of the acute toxicity value for sheepshead 

(39.4 ppb), both criteria specified in 40 CFR Part 158 for conditionally requiring this study. Furthermore, the 

persistence of PBO in water is expected to substantially exceed the 4-d half life criterion specified in 40 CFR 

Part 158.

Practical Utility of the Data

How will the data be used? 

The estuarine/ marine fish early life stage study would allow the Agency to analyze chronic effects, including 

effects on reproductive success and growth, to saltwater species. The effects data would be used to determine 

the likelihood that the chronic risks can potentially impact aquatic communities, either by direct effects on fish 

or by indirect effects by reducing their food sources. By refining the assessment, the Agency would be able to 

determine whether the mitigation imposed as part of the registration review process was appropriate due to 

toxicity concerns with PBO.

How could the data impact the Agency’s future decision-making?

If future endangered species risk assessments are performed without these data, the Agency would have to 

assume that PBO "may affect" endangered estuarine/ marine fish directly (and endangered species from other 

taxa indirectly), and use of PBO might need to be restricted in areas where endangered species could be exposed. 

The lack of these data will limit the flexibility the Agency and registrants have in coming into compliance with 

the Endangered Species Act and could result in use restrictions for PBO which are unnecessarily severe.

Guideline Number: 850.1500

Study Title: Fish Full Life-cycle Test (Freshwater)

Rationale for Requiring the Data

The acute toxicity of PBO to fish and environmental fate properties indicate the potential for chronic exposure 

and effects to animals in this taxon, per 40 CFR Part 158 data requirements (October 26, 2007). Expected EECs 

exceed the early life stage NOAEC of 40 ug/L for a number of uses. A life-cycle study is triggered if expected 

environmental concentrations exceed 1/10th the early-life stage NOAEC. Based on the early life stage study in 

freshwater fish, Furthermore, the persistence of PBO in water is expected to substantially exceed the 4-d half life 

criterion specified in 40 CFR Part 158.

The preferred test species would be the rainbow trout since acute data are available on this species. If another 

species is chosen, for which EPA does not have acute data, acute data will also be needed on that species.

Practical Utility of the Data

How will the data be used? 

The full life-cycle study would allow the Agency to analyze chronic effects, including effects on reproductive 

success and growth. The effects data would be used to determine the likelihood that the chronic risks can 

potentially impact aquatic communities, either by direct effects on fish and aquatic-phase amphibians or by 

indirect effects by reducing their food sources. By refining the assessment, the Agency would be able to 

determine whether the mitigation imposed as part of the registration review process was appropriate due to 

toxicity concerns with PBO.
59

How could the data impact the Agency’s future decision-making?

If future endangered species risk assessments are performed without these data, the Agency would have to 

assume that PBO "may affect" endangered fish and aquatic-phase amphibians directly (and endangered species 

from other taxa indirectly), and use of PBO might need to be restricted in areas where endangered species could 

be exposed. The lack of these data will limit the flexibility the Agency and registrants have in coming into 

compliance with the Endangered Species Act and could result in use restrictions for PBO which are 

unnecessarily severe.

Guideline Numbers: 850.1770

Study Title: Chronic whole sediment: Freshwater Hylella

Rationale for Requiring the Data

Available information indicates that benthic organisms may be exposed via run-off or spray drift 

applications used in agricultural, forest, and residential settings, or by direct application to water. 

Chronic sediment toxicity tests are required to satisfy the Agency‟s updated data requirements for 

outdoor uses in 40 CFR Part 158 (October 26, 2007). Specifically, PBO has a half-life of 14d in 

aerobic soil and 75d in aerobic water (MRIDs 43806401 and 43803401 both as amended

5/17/2004), a log Kow of 4.75 and Koc of up to1152 (MRID 43673802) and expected peak EECs 

(58 to 160 ppb, for aerial application to lettuce, cabbage, citrus, cucumber, pepper, strawberry, 

potato, tomato, beans, sugarbeets and cotton, 2005 RED eco chapter15) which exceed 0.1 of the 

acute LC/EC50 (490*0.1 = 49 ppb for M. bahia, MRID 43901801). 

The criteria are, therefore, met for requiring chronic sediment toxicity studies. 

Finally, the potential for persistent exposure from PBO in sediment is also indicated by open 

literature studies on pyrethroids (Weston et al. 2005, Amweg et al. 2006 and Ding et al. 2009). 

For sediment studies involving pyrethroids, chronic tests on Hyalella azteca, Chironomus tentans, 

and Leptocheirus plumulosus are requested. Although both Hyalella and Chironomus are both 

freshwater species, they differ substantially in their ecological niche (i.e., epibenthic vs. infaunal), 

physiology, and potential sensitivities to pyrethroid exposure. PBO has the potential to enter 

estuarine/marine water bodies based on current usuage patterns that include coastal areas. 

Therefore, testing is required for Leptocheirus plumulosus, an estuarine/marine sediment-dwelling 

invertebrate species.

Practical Utility of the Data

How will the data be used? 

Data from sediment toxicity studies will be used to estimate potential risks to benthic organisms 

associated with uses of PBO. The data will reduce uncertainties associated with the current risk 

assessment for benthic species and will improve our understanding of the potential effects of 

PBO.

How could the data impact the Agency’s future decision-making?

Acceptable data for benthic organisms will reduce the uncertainty from previous assessments. 

Since potential risk was found for adverse effects to other aquatic organisms, acceptable data for 

benthic organisms will reduce the uncertainty from the previous assessment. If the data indicate 

that registered PBO usage may pose a risk of adverse effects to non-target benthic organisms 

above the Agency Level of Concern, the Agency may explore decision options to mitigate this 

risk. The lack of these data will limit the flexibility the Agency and registrants have in coming 

into compliance with the Endangered Species Act, and could result in use restrictions for PBO 

which may otherwise be avoided, or which are unnecessarily severe.

 

15 Piperonyl Butoxide: Environmental Risk Assessment, Revised September, 2005. D139408.
60

Guideline Numbers: 850.1760

Study Title: Chronic whole sediment: Freshwater chironimid 

Rationale for Requiring the Data

Available information indicates that benthic organisms may be exposed via run-off or spray drift 

applications used in agricultural, forest, and residential settings, or by direct application to water. 

Chronic sediment toxicity tests are required to satisfy the Agency‟s updated data requirements for 

outdoor uses in 40 CFR Part 158 (October 26, 2007). Specifically, PBO has a half-life of 14d in 

aerobic soil and 75d in aerobic water (MRIDs 43806401 and 43803401 both as amended 

5/17/2004), a log Kow of 4.75 and Koc of up to1152 (MRID 43673802, also see Table 3). 

Estimated EECs can exceed 0.1 of the acute toxicity LC/EC50 for mysids (see Freshwater Fish

section above). The criteria are, therefore, met for requiring chronic sediment toxicity studies. 

Finally, the potential for persistent exposure from PBO in sediment is also indicated by open 

literature studies on pyrethroids (Weston et al. 2005, Amweg et al. 2006 and Ding et al. 2009). 

For sediment studies involving pyrethroids, chronic tests on Hyalella azteca, Chironomus tentans, 

and Leptocheirus plumulosus are requested. Although both Hyalella and Chironomus are both 

freshwater species, they differ substantially in their ecological niche (i.e., epibenthic vs. infaunal), 

physiology, and potential sensitivities to pyrethroid exposure. PBO has the potential to enter 

estuarine/marine water bodies based on current usuage patterns that include coastal areas. 

Therefore, testing is required for Leptocheirus plumulosus, an estuarine/marine sediment-dwelling 

invertebrate species.

In addition, depending on the results of the fish and invertebrate special studies designed to 

evaluate synergism, the study design of this sediment toxicity study may need to be modified to 

address synergistic effects of pesticides applied simultaneously with PBO. 

Practical Utility of the Data

How will the data be used? 

Data from sediment toxicity studies will be used to estimate potential risks to benthic organisms 

associated with uses of PBO. The data will reduce uncertainties associated with the current risk 

assessment for benthic species and will improve our understanding of the potential effects of 

PBO.

How could the data impact the Agency’s future decision-making?

Acceptable data for benthic organisms will reduce the uncertainty from previous assessments. 

Since potential risk was found for adverse effects to other aquatic organisms, acceptable data for 

benthic organisms will reduce the uncertainty from the previous assessment If the data indicate 

that registered PBO usage may pose a risk of adverse effects to non-target benthic organisms 

above the Agency Level of Concern, the Agency may explore decision options to mitigate this 

risk. The lack of these data will limit the flexibility the Agency and registrants have in coming 

into compliance with the Endangered Species Act, and could result in use restrictions for PBO 

which may otherwise be avoided, or which are unnecessarily severe.
61

Guideline Numbers: 850.1780

Study Title: Chronic whole sediment: Marine invertebrates 

Rationale for Requiring the Data

Available information indicates that benthic organisms may be exposed via run-off or spray drift 

applications used in agricultural, forest, and residential settings, or by direct application to water. 

Chronic sediment toxicity tests are required to satisfy the Agency‟s updated data requirements for 

outdoor uses in 40 CFR Part 158 (October 26, 2007). Specifically, PBO has a half-life of 14d in 

aerobic soil and 75d in aerobic water (MRIDs 43806401 and 43803401 both as amended 

5/17/2004), a log Kow of 4.75 and Koc of up to1152 (MRID 43673802, also see Table 3). 

Estimated EECs can exceed 0.1 of the acute toxicity LC/EC50 for mysids (see Freshwater Fish

section above). The criteria are, therefore, met for requiring chronic sediment toxicity studies. 

Finally, the potential for persistent exposure from PBO in sediment is also indicated by open 

literature studies on pyrethroids (Weston et al. 2005, Amweg et al. 2006 and Ding et al. 2009). 

For sediment studies involving pyrethroids, chronic tests on Hyalella azteca, Chironomus tentans, 

and Leptocheirus plumulosus are requested. Although both Hyalella and Chironomus are both 

freshwater species, they differ substantially in their ecological niche (i.e., epibenthic vs. infaunal), 

physiology, and potential sensitivities to pyrethroid exposure. PBO has the potential to enter 

estuarine/marine water bodies based on current usuage patterns that include coastal areas. 

Therefore, testing is required for Leptocheirus plumulosus, an estuarine/marine sediment-dwelling 

invertebrate species.

Practical Utility of the Data

How will the data be used? 

Data from sediment toxicity studies will be used to estimate potential risks to benthic organisms 

associated with uses of PBO. The data will reduce uncertainties associated with the current risk 

assessment for benthic species and improve our understanding of the potential effects of PBO.

How could the data impact the Agency’s future decision-making?

Acceptable data for benthic organisms will reduce the uncertainty from previous assessments. 

Since potential risk was found for adverse effects to other aquatic organisms, acceptable data for 

benthic organisms will reduce the uncertainty from the previous assessment If the data indicate 

that registered PBO usage may pose a risk of adverse effects to non-target benthic organisms 

above the Agency Level of Concern, the Agency may explore decision options to mitigate this 

risk. The lack of these data will limit the flexibility the Agency and registrants have in coming 

into compliance with the Endangered Species Act, and could result in use restrictions for PBO 

which may otherwise be avoided, or which are unnecessarily severe.
62

Guideline Number: 850.1010 

Study Title: Aquatic Invertebrate Acute Toxicity Test, Freshwater Daphnids, TEP 

Rationale for Requiring the Data

PBO may be applied directly to water. Therefore, testing of a TEP applied to water is required to 

evaluate the potential effects of the ingredients within the TEP on fish. 

Without toxicity data on the range of TEPs produced, the Agency would presume acute risk to 

listed and non-listed fish exceeds LOCs, but would not be able to quantify the risk and would not 

be able to evaluate efficacy of mitigations.

Practical Utility of the Data

How will the data be used? Toxicity data with at least one TEP and a bridging strategy to others 

would allow the Agency to further analyze potential acute effects. The effects data would be used 

to determine the likelihood that acute risks can potentially impact aquatic communities, either by 

direct effects on fish or by indirect effects by reducing their food sources. By refining the 

assessment, the Agency would be able to determine whether the mitigation imposed as part of the 

registration review process was appropriate due to toxicity concerns with PBO use.

How could the data impact the Agency’s future decision-making? If future endangered species 

risk assessments are performed without these data, the Agency would have to assume that PBO 

products "may affect" endangered fish directly (and endangered species from other taxa 

indirectly), and use of PBO products might need to be restricted in areas where endangered species 

could be exposed. The lack of these data will limit the flexibility the Agency and registrants have 

in coming into compliance with the Endangered Species Act and could result in use restrictions for 

PBO products which are unnecessarily severe.
63

Guideline Number: 850.1010

Study Title: Aquatic Invertebrate Acute Toxicity Test, Freshwater Daphnids (modified 

guideline study to evaluate synergism)

Rationale for Requiring the Data

PBO and its major degradates are persistent, mobile and may pass through wastewater treatment 

processes. PBO is a pesticide synergist. Therefore, it is used in combination with other 

pesticides to enhance their effectiveness (toxicity) to target organisms. Assessing potential 

ecological risks of PBO requires evaluating potential exposure and toxicity of the active ingredient 

(PBO alone) and evaluating the enhanced toxicity of other pesticides with which it is 

simultaneously applied. Given the number of chemicals with which PBO may be simultaneously 

applied, designing a study that examines the range of synergistic effects is difficult. A 

comprehensive evaluation of potential synergistic effects of PBO and all chemical with which it 

may be simultaneously applied will require the development and review of a large body of data. 

The Agency recognizes that this data set is extensive and is willing to consider options for a 

reduced data set that evaluates the nature of PBO synergy with a limited number of compounds, 

and allows bridging to these more extensive synergy studies from reduced data sets for other 

chemicals. The goal of obtaining this set of data is to determine the potential range of 

magnitudes of synergistic effects for pesticide active ingredients that are co-applied with 

PBO for the purpose of enhancing efficacy due to synergism. The Agency is interested in 

obtaining data on (or bridging data to) pesticide active ingredients (in addition to other 

chemicals with similar modes of action) that are co-applied with PBO for its synergistic 

properties including those that are formulated with PBO and those that are otherwise 

recommended for mixing with PBO prior to application. 

Protocols need to be submitted to the Agency prior to study initiation.

Without toxicity data on the range of TEPs produced, the Agency woud have to presume acute 

toxicity to listed and non-listed fish and aquatic-phase amphibians, but would not be able to 

quantify the risk or effectiveness of potential mitigations.

Practical Utility of the Data

How will the data be used? Toxicity data with at least one TEP and a bridging strategy to others

would allow the Agency to further analyze potential acute effects. The effects data would be used 

to determine the likelihood that acute risks can potentially impact aquatic communities, either by 

direct effects on fish and aquatic-phase amphibians or by indirect effects by reducing their food 

sources. By refining the assessment, the Agency would be able to determine whether the 

mitigation imposed as part of the registration review process was appropriate due to toxicity 

concerns with PBO use.

How could the data impact the Agency’s future decision-making? If future endangered species 

risk assessments are performed without these data, the Agency would have to assume that PBO 

products "may affect" endangered fish and aquatic-phase amphibians directly (and endangered 

species from other taxa indirectly), and use of PBO products might need to be restricted in areas 

where endangered species could be exposed. The lack of these data will limit the flexibility the 

Agency and registrants have in coming into compliance with the Endangered Species Act and 

could result in use restrictions for PBO products which are unnecessarily severe.
64

Guideline Number: 850.1350

Study Title: Aquatic Invertebrate Life-cycle Toxicity (Saltwater)

Rationale for Requiring the Data

PBO and its major degradates are persistent, mobile and may pass through wastewater treatment 

processes. Chronic toxicity data are required per 40 CFR Part 158.630 due to the potential for 

direct application of PBO to the estuarine/marine environment, acute toxicity value that is <1 ppm 

(0.23 for the oyster), and the expected peak EECs (58 to 160 ppb, for aerial application to lettuce, 

cabbage, citrus, cucumber, pepper, strawberry, potato, tomato, beans, sugarbeets and cotton, 2005 

RED eco chapter16) exceed 0.01 of the acute toxicity values (this would be 4.9 ppb for mysid and 

2.3 ppb for oysters). This requirement is based on PBO use in a variety of products applied 

directly to water and used in agriculture. 

Practical Utility of the Data

How will the data be used? The full life-cycle study would allow the Agency to further analyze 

potential chronic effects. The effects data would be used to determine the likelihood that the 

chronic risks can potentially impact aquatic communities, either by direct effects on fish or by 

indirect effects by reducing their food sources. By refining the assessment, the Agency would be 

able to determine whether the mitigation imposed as part of the registration review process was 

appropriate due to toxicity concerns with PBO.

How could the data impact the Agency’s future decision-making? If future endangered species 

risk assessments are performed without these data, the Agency would have to assume that PBO 

"may affect" endangered fish directly (and endangered species from other taxa indirectly), and use 

of PBO might need to be restricted in areas where endangered species could be exposed. The lack 

of these data will limit the flexibility the Agency and registrants have in coming into compliance 

with the Endangered Species Act and could result in use restrictions for PBO which are 

unnecessarily severe.

Guideline Number: 850.4400

Study Title: Aquatic Vascular Plant Growth - Tiers I/II

Rationale for Requiring the Data

No acceptable studies for PBO have been submitted for vascular aquatic plants. The Agency has 

finalized its update to the data requirements in 40 CFR Part 158. In these updated data 

requirements, which were promulgated on October 26, 2007, vascular plant testing is required 

for pesticides such as PBO with outdoor uses. Tier I testing is required, followed by Tier II if 

required by Tier I results as specified in Tier I guidelines.

Practical Utility of the Data

How will the data be used?

Data from aquatic plant toxicity studies will be used to estimate potential risks to plants 

associated with uses of PBO. The data will reduce uncertainties associated with the current risk 

assessment for aquatic plants and will improve our understanding of the potential effects on 

vascular aquatic plants. 

How could the data change the Agency’s decision, or impact the Agency’s future decisionmaking? 

Because plants form the basis of most habitats and significantly contribute to overall 

environmental quality, a solid understanding of the potential risks to aquatic plants is essential 

for sound environmental management. Without plant growth data for PBO, the Agency cannot 

 

16 Piperonyl Butoxide: Environmental Risk Assessment, Revised September, 2005. D139408.
65

determine the levels of PBO that result in effects to vascular aquatic plants. If the data indicates 

that registered PBO usage may pose a risk of adverse effects to non-target aquatic vascular 

plants above the Agency Level of Concern, the Agency may explore decision options to mitigate 

this risk. 

If future endangered species risk assessments are performed without these data, the Agency 

would have to assume that PBO "may affect" endangered plants and use of PBO might need to 

be restricted in areas where endangered species could be exposed. The lack of these data will 

limit the flexibility the Agency and registrants have in coming into compliance with the 

Endangered Species Act and could result in use restrictions for PBO that may be unnecessarily 

severe.

Guideline Number: 850.5400

Study Title: Algal toxicity test, Tier I/II 

Rationale for Requiring the Data

No toxicity data are currently available to assess the risk of PBO to aquatic nonvascular plants. 

Since PBO has residential outdoor uses, Tier I/II aquatic nonvascular plant studies are required. 

These phytotoxicity data are needed to evaluate the level of pesticide exposure to non-target 

aquatic plants and to assess the impact of pesticides on endangered and threatened plants. The 

Agency updated its data requirements in 40 CFR Part 158 (October 26, 2007) to include plant 

studies. Tier I testing is required, followed by Tier II if required by Tier I results as specified in 

Tier I guidelines.

Practical Utility of the Data

How will the data be used? 

Data from Tier I/II nonvascular aquatic plant toxicity studies will be used to estimate potential 

risks to plants associated with uses of PBO. The data will reduce uncertainties associated with the 

current risk assessment for nonvascular aquatic plants and will improve our understanding of the 

potential effects of PBO. 

How could the data impact the Agency’s future decision-making?

Because plants form the basis of most habitats and significantly contribute to overall 

environmental quality, a solid understanding of the potential risks to nonvascular aquatic plants is 

essential for sound environmental management. Without plant growth data for PBO, the Agency 

cannot determine the levels that result in effects to aquatic plants. If the data indicates that 

registered usage may pose a risk of adverse effects to non-target aquatic nonvascular plants above 

the Agency Level of Concern, the Agency may explore decision options to mitigate this risk. The 

lack of these data will limit the flexibility the Agency and registrants have in coming into 

compliance with the Endangered Species Act, and could result in use restrictions for PBO which 

may otherwise be avoided, or which are unnecessarily severe.

Guideline Number: 850.3020 

Study Title: Honey Bee Acute Contact Toxicity Test using TEP

Rationale for Requiring the Data

Terrestrial invertebrate toxicity data are required to quantitatively assess the potential impacts on 

this group of organisms. Data are needed from the honey bee acute contact study due to wide 

spread use and possible drift to off site vegetation in bloom. Available data (MRID 

41969009) show PBO to be moderately toxic to practically non-toxic to honey bees (LD50

>25 μg/bee). Since PBO acts as a synergist insecticide, the effects of a typical end-use 

product (TEP) may be much greater. 
66

Practical Utility of the Data

How will the data be used? The honeybee study using TEP would allow the Agency to analyze 

pollinators and other non-target terrestrial insects. The effects data would be used to determine the 

likelihood that the risks can potentially impact terrestrial invertebrate communities. By refining 

the assessment, the Agency would be able to determine whether the mitigation imposed as part of 

the registration review process was appropriate due to toxicity concerns with PBO.

How could the data impact the Agency’s future decision-making? If future endangered species 

risk assessments are performed without these data, the Agency would have to assume that PBO 

TEPs "may affect" endangered terrestrial insects directly (and endangered species from other taxa 

indirectly), and use of PBO might need to be restricted in areas where endangered species could be 

exposed. The lack of these data will limit the flexibility the Agency and registrants have in 

coming into compliance with the Endangered Species Act and could result in use restrictions for 

PBO which are unnecessarily severe.

Guideline Numbers: 850.4100 and 850.4150

Study Title: Vegetative vigor and Seedling emergence with TEP, Tier I/Tier II

Rationale for Requiring the Data

No acceptable toxicity data are currently available to assess the risk of PBO to terrestrial plants. 

The Agency updated its data requirements in 40 CFR Part 158 (October 26, 2007) to include 

plant studies.

Since PBO has residential outdoor uses, vegetative vigor and seedling emergence studies using 

TEP are required. These phytotoxicity data are needed to evaluate the level of pesticide 

exposure to non-target terrestrial and aquatic plants and to assess the impact of pesticides on 

endangered and threatened plants. Tier I testing is required, followed by Tier II if required by 

Tier I results as specified in Tier I guidelines.

Practical Utility of the Data

How will the data be used? 

Data from terrestrial plant toxicity studies will be used to estimate potential risks to plants 

associated with uses of PBO. The data will reduce uncertainties associated with the current risk 

assessment for terrestrial plants and will improve our understanding of the potential effects of 

PBO on plants. 

How could the data impact the Agency’s future decision-making?

Because plants form the basis of most habitats and significantly contribute to overall 

environmental quality, a solid understanding of the potential risks to terrestrial plants is essential 

for sound environmental management. Without acceptable plant growth data for PBO, the 

Agency cannot determine the levels of PBO that result in effects to terrestrial plants. If the data 

indicates that registered PBO usage may pose a risk of adverse effects to non-target terrestrial 

plants plants above the Agency Level of Concern, the Agency may explore decision options to 

mitigate this risk. The lack of these data will limit the flexibility the Agency and registrants 

have in coming into compliance with the Endangered Species Act, and could result in use 

restrictions for PBO which may otherwise be avoided, or which are unnecessarily severe.
67

Guideline Number: 850.2100 

Study Title: Avian Acute Oral Toxicity Test

Rationale for Requiring the Data

Acceptable acute avian oral toxicity data were not submitted for a passerine species exposed to 

PBO, which is now required under the 40 CFR Part 158 (CFR 40 2008) data requirements for 

conventional pesticides. The revised Part 158 data requirements specify that acute avian oral 

toxicity data be submitted for either one waterfowl or one upland game species and one passerine 

species. The available acute oral toxicity data for mallard ducks and bobwhite quails, when 

compared to estimated environmental concentrations, indicate that levels of concern are not 

exceeded for birds on an acute basis. Many passerine species utilizing forests, residential areas and 

surrounding areas, have the potential to be exposed to pesticides used in agricultural, forest, and 

residential settings. It is likely that, for most pesticide use patterns, passerines are more likely to 

be exposed to pesticides than upland game species and waterfowl. Because passerine species have 

higher metabolic rates due to their smaller sizes than either waterfowl or upland game bird species 

and because they may utilize different metabolic pathways, they may be more or less sensitive to 

PBO. In order to properly characterize risk to passerines, an avian oral toxicity test is required for 

passerine birds. A passerine study protocol must be submitted for review by the Agency prior to 

initiation of the study.

Practical Utility of the Data

How will the data be used?

Acute avian oral toxicity data for passerine species will be used to refine the screening-level risk 

assessment by determining whether there are differences in avian species sensitivity to PBO

between currently tested passerine and upland game and/or waterfowl species that are beyond the 

simple allometric predictions currently employed in the absence of such passerine data. The 

current extrapolation method may be under- or over-estimating risks to passerines.

How could the data impact the Agency’s future decision-making?

If future risk assessments, including listed species assessments, are performed without these data, 

the Agency would have to assume that PBO “may affect” listed birds directly (and listed species 

from other taxa indirectly), and use of PBO and its formulated products may need to be restricted 

in areas where listed species could be exposed. The lack of these data will limit the flexibility the 

Agency and registrants have in complying with the Endangered Species Act and could result in 

restrictions for PBO use that might prove to be unnecessary given data to address this area of 

uncertainty.

Guideline Number: None

Study Title: POTW Effluent Monitoring and POTW Treatability Study

Rationale for Requiring the Data

POTW Effluent Monitoring – Request any existing or ongoing POTW effluent monitoring data 

for the pyrethroids be submitted to the Agency.

POTW Treatability Study – In addition, the Agency is requiring a bench scale study of waste 

water treatment, to assess amounts that would degrade during treatment, remain in the waste 

water, or partition to biosolids.

Practical Utility of the Data

How will the data be used? 

These data would be used to inform removal percentages by waste water treatment, which is an 

input to the Exposure and Fate Assessment Screening Tool‟s (E-FAST) down-the-drain module.
68

Guideline Number: None

Study Title: POTW Effluent Monitoring and POTW Treatability Study

How could the data impact the Agency’s future decision-making?

Without these data, the Agency will have to make assumptions regarding the level of removal of 

PBO (e.g., results of modeling from the EPIWEB v.4.0 may be used). Since the assumptions are 

likely to be crude and conservative. The lack of these data will limit the flexibility the Agency 

and registrants have in coming into compliance with the Endangered Species Act, and could 

result in use restrictions for PBO which may otherwise be avoided, or which are unnecessarily 

severe.
69

Appendix A: Uses of Piperonyl Butoxide Eligible for Reregistration

Updated 9/23/10

A-1: Food/Feed Uses

Appendix A-1: Food/Feed Uses of Piperonyl Butoxide Subject to Reregistration.

Site

Application Type

Max. Single 

Application 

Rate, ai

Max. No. of 

Applications 

Per Season

PHI 

(Days) Use Directions and Limitations 

AGRICULTURAL

Preharvest Application to Field, Orchard, and Greenhouse Food Crops 

Crop Group 1: Root and Tuber Vegetables [including Arracacha; Arrowroot; Artichoke, Chinese; Artichoke, Jerusalem; Beet, 

garden, Beet, sugar; Burdock, edible; Canna edible; Carrot; Cassava; Celeriac; Chayote; Chervil, turnip-rooted; Chicory; Chufa; 

Dandelion; Dasheen; Ginger; Ginseng; Horseradish; Leren; Parsley, turnip-rooted; Parsnip; Potato; Radish; Radish, Oriental; 

Rutabaga; Salsify; Salsify, black; Salsify, Spanish; Skirret; Sweet Potato; Tanier; Taro; Turmeric; Turnip; Yam bean; and Yam, 

true]

Application to outdoor growing 

crops

0.5 lb/A 10 0

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 harvest until spray has dried.

Aerial applications: do not apply less than 2 

gal. of diluted solution/A to field crops or less 

than 10 gal. of diluted solution/A to orchard 

crops.

Do not wet plants to point of runoff or drip.

Application to hydroponically grown 

crops

1.0 ppm in 

water 10 0

Surface application to greenhouse 

grown crop

0.012 

lb/1,000 sq. ft 

or

0.5 lb/A

10 0

Space application to greenhouse 

grown crop

0.0014 

lb/1,000 cu. ft 10 0

Crop Group 2: Leaves of Root and Tuber Vegetables [including Beet, garden; Beet, sugar; Burdock, edible; Carrot; Cassava; 

Chervil, turnip-rooted; Chicory; Dasheen; Parsnip; Radish; Radish, Oriental; Rutabaga; Salsify, black; Tanier; Taro; Turnip; and 

Yam, true]

Application to outdoor growing 

crops

0.5 lb/A 10 0 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 harvest until spray has dried.

Aerial applications: do not apply less than 2 

gal. of diluted solution/A to field crops or less 

than 10 gal. of diluted solution/A to orchard 

crops.

Do not wet plants to point of runoff or drip.

Application to hydroponically grown 

crops

1.0 ppm in 

water 10 0

Surface application to greenhouse 

grown crop

0.012 

lb/1,000 sq. ft 

or

0.5 lb/A

10 0

Space application to greenhouse 

grown crop

0.0014 

lb/1,000 cu. ft 10 0

Crop Group 3: Bulb Vegetables [including Garlic; Garlic, great headed; Leek; Onion, dry bulb; Onion, green; Onion, potato; 

Onion, tree; Onion, welsh; and Shallot]

Application to outdoor growing 

crops

0.5 lb/A 10 0 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 harvest until spray has dried.

Aerial applications: do not apply less than 2 

gal. of diluted solution/A to field crops or less 

than 10 gal. of diluted solution/A to orchard 

crops.

Do not wet plants to point of runoff or drip.

Application to hydroponically grown 

crops

1.0 ppm in 

water 10 0

Surface application to greenhouse 

grown crop

0.012 

lb/1,000 sq. ft 

or

0.50 lb/A

10 0

Space application to greenhouse 

grown crop

0.0014 

lb/1,000 cu. ft 10 0
70

Appendix A-1: Food/Feed Uses of Piperonyl Butoxide Subject to Reregistration.

Site

Application Type

Max. Single 

Application 

Rate, ai

Max. No. of 

Applications 

Per Season

PHI 

(Days) Use Directions and Limitations 

Crop Group 4: Leafy Vegetables (Except Brassica Vegetables) [including Amaranth, leafy; Arugula; Cardoon; Celery; 

Celery, Chinese; Celtuce; Chervil; Chrysanthemum, edible-leaved; Chrysanthemum, garland; Corn salad; Cress, garden; Cress, 

upland; Dandelion; Dock; Endive; Fennel, Florence; Kale, sea; Lettuce, head; Lettuce, leaf; Orach; Parsley; Purslane, garden;

Purslane, winter; Radicchio; Rhubarb; Spinach; Spinach, Chinese; Spinach, New Zealand; Spinach, vine; Swiss chard; and 

Tampala] 

Application to outdoor growing 

crops

0.5 lb/A 10 0 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 harvest until spray has dried.

Aerial applications: do not apply less than 2 

gal. of diluted solution/A to field crops or less 

than 10 gal. of diluted solution/A to orchard 

crops.

Do not wet plants to point of runoff or drip.

Application to hydroponically grown 

crops

1.0 ppm in 

water 10 0

Surface application to greenhouse 

grown crop

0.012 

lb/1,000 sq. ft 

or

0.50 lb/A

10 0

Space application to greenhouse 

grown crop

0.0014 

lb/1,000 cu. ft 10 0

Crop Group 5: Brassica (Cole) Leafy Vegetables [including Broccoli; Broccoli, Chinese; Broccoli raab; Brussels sprouts; 

Cabbage; Cabbage, Chinese, Bok choy; Cabbage, Chinese, mustard; Cabbage, Chinese, napa; Cauliflower; Collards; Kale; 

Kohlrabi; Mustard greens; Mustard spinach; and Rape greens] 

Application to outdoor growing 

crops

0.5 lb/A 10 0 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 harvest until spray has dried.

Aerial applications: do not apply less than 2 

gal. of diluted solution/A to field crops or less 

than 10 gal. of diluted solution/A to orchard 

crops.

Do not wet plants to point of runoff or drip.

Application to hydroponically grown 

crops

1.0 ppm in 

water 10 0

Surface application to greenhouse 

grown crop

0.012 

lb/1,000 sq. ft 

or

0.5 lb/A

10 0

Space application to greenhouse 

grown crop

0.0014 

lb/1,000 cu. ft 10 0

Crop Group 6: Legume Vegetables (Succulent or Dried) [including Bean (adzuki, broad, dry, kidney, lablab, lima, moth, 

mung, navy, pink, pinto, rice, runner, snap, tepary, urd, wax, yardlong); Catjang; Chickpea; Cowpea; Guar; Gum, edible; 

Jackbean; Lentil; Lupin, grain; Pea (blackeyed, crowder, dry, dwarf, edible-pod, English, field, garden, green, pigeon, snow, 

southern, succulent, sugar snap); Soybean; and Swordbean] 

Application to outdoor growing 

crops

0.5 lb/A 10 0

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 harvest until spray has dried.

Aerial applications: do not apply less than 2 

gal. of diluted solution/A to field crops or less 

than 10 gal. of diluted solution/A to orchard 

crops.

For rice, a 10 day water hold is required for all 

applications when rice fields are flooded.

Do not wet plants to point of runoff or drip.

Application to hydroponically grown 

crops

1.0 ppm in 

water 10 0

Surface application to greenhouse 

grown crop

0.012 

lb/1,000 sq. ft 

or

0.5 lb/A

10 0

Space application to greenhouse 

grown crop

0.0014 

lb/1,000 cu. ft 10 0

Crop Group 7: Foliage of Legume Vegetables [including Bean (dry, lima, snap); cowpea; Lupin, grain; Pea (field and pigeon); 

Soybean]

Application to outdoor growing 

crops

0.5 lb/A 10 0

Do not reapply within 3 days except under 

extreme pest pressure.

In case of extreme pest pressure, do not reapply 

within 24 hours.

Application to hydroponically grown 

crops

1.0 ppm in 

water 10 0
71

Appendix A-1: Food/Feed Uses of Piperonyl Butoxide Subject to Reregistration.

Site

Application Type

Max. Single 

Application 

Rate, ai

Max. No. of 

Applications 

Per Season

PHI 

(Days) Use Directions and Limitations 

Surface application to greenhouse 

grown crop

0.012 

lb/1,000 sq. ft 

or

0.5 lb/A

10 0

Do not harvest until spray has dried.

Aerial applications: do not apply less than 2 

gal. of diluted solution/A to field crops or less 

than 10 gal. of diluted solution/A to orchard 

crops.

Do not wet plants to point of runoff or drip. Space application to greenhouse 

grown crop

0.0014 

lb/1,000 cu. ft 10 0

Crop Group 8: Fruiting Vegetables (Except Cucurbits) [including Chili; Eggplant; Groundcherry; Pepino; Pepper (bell, 

nonbell, nonbell sweet); Tomatillo; Tomato]

Application to outdoor growing 

crops

0.5 lb/A 10 0 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 harvest until spray has dried.

Aerial applications: do not apply less than 2 

gal. of diluted solution/A to field crops or less 

than 10 gal. of diluted solution/A to orchard 

crops.

Do not wet plants to point of runoff or drip.

Application to hydroponically grown 

crops

1.0 ppm in 

water 10 0

Surface application to greenhouse 

grown crop

0.012 

lb/1,000 sq. ft 

or

0.5 lb/A

10 0

Space application to greenhouse 

grown crop

0.0014 

lb/1,000 cu. ft 10 0

Crop Group 9: Cucurbit Vegetables [including Balsam apple; Balsam pear; Cantaloupe; Chayote; Cucumber; Cucumber, 

Chinese; Gherkin, West Indian; Gourd, edible; Melon; Melon, citron; Muskmelon; Pumpkin; Squash; Squash, summer; Squash, 

winter; Watermelon; Waxgourd, Chinese]

Application to outdoor growing 

crops

0.5 lb/A 10 0 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 harvest until spray has dried.

Aerial applications: do not apply less than 2 

gal. of diluted solution/A to field crops or less 

than 10 gal. of diluted solution/A to orchard 

crops.

Do not wet plants to point of runoff or drip.

Application to hydroponically grown 

crops

1.0 ppm in 

water 10 0

Surface application to greenhouse 

grown crop

0.012 

lb/1,000 sq. ft 

or

0.5 lb/A

10 0

Space application to greenhouse 

grown crop

0.0014 

lb/1,000 cu. ft 10 0

Crop Group 10: Citrus Fruits (Citrus spp., Fortunella spp.) [including Calamondin; Citron, citrus; Citrus; Citrus hybrids; 

Grapefruit; Kumquat; Lemon; Lime; Mandarin, satsuma; Orange, sour; Orange, sweet; Pummelo; Tangelo; Tangerine]

Application to outdoor growing 

crops

0.5 lb/A 10 0 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 harvest until spray has dried.

Aerial applications: do not apply less than 2 

gal. of diluted solution/A to field crops or less 

than 10 gal. of diluted solution/A to orchard 

crops.

Do not wet plants to point of runoff or drip.

Application to hydroponically grown 

crops

1.0 ppm in 

water

10 0

Surface application to greenhouse 

grown crop

0.012 

lb/1,000 sq. ft 

or

0.50 lb/A

10 0

Space application to greenhouse 

grown crop

0.0014 

lb/1,000 cu. ft 10 0

Crop Group 11: Pome Fruits [including Apple; Crabapple; Loquat; Mayhaw; Pear; Oriental Pear; and Quince]

Application to outdoor growing 

crops

0.5 lb/A 10 0

Do not reapply within 3 days except under 

extreme pest pressure.

In case of extreme pest pressure, do not reapply 

within 24 hours.

Application to hydroponically grown 

crops

1.0 ppm in 

water 10 0
72

Appendix A-1: Food/Feed Uses of Piperonyl Butoxide Subject to Reregistration.

Site

Application Type

Max. Single 

Application 

Rate, ai

Max. No. of 

Applications 

Per Season

PHI 

(Days) Use Directions and Limitations 

Surface application to greenhouse 

grown crop

0.012 

lb/1,000 sq. ft 

or

0.5 lb/A

10 0

Do not harvest until spray has dried.

Aerial applications: do not apply less than 2 

gal. of diluted solution/A to field crops or less 

than 10 gal. of diluted solution/A to orchard 

crops.

Do not wet plants to point of runoff or drip. Space application to greenhouse 

grown crop

0.0014 

lb/1,000 cu. ft 10 0

Crop Group 12: Stone Fruits [including Apricot; Cherry, sweet; Cherry, tart; Nectarine; Peach; Plum; Plum, chickasaw; Plum, 

damson; Plum, Japanese; and Plum, prune]

Application to outdoor growing 

crops

0.5 lb/A 10 0 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 harvest until spray has dried.

Aerial applications: do not apply less than 2 

gal. of diluted solution/A to field crops or less 

than 10 gal. of diluted solution/A to orchard 

crops.

Do not wet plants to point of runoff or drip.

Application to hydroponically grown 

crops

1.0 ppm in 

water 10 0

Surface application to greenhouse 

grown crop

0.012 

lb/1,000 sq. ft 

or

0.5 lb/A

10 0

Space application to greenhouse 

grown crop

0.0014 

lb/1,000 cu. ft 10 0

Crop Group 13: Berries [including Blackberry, Blueberry; Currant; Elderberry; Gooseberry; Huckleberry; Loganberry; and 

Raspberry (black and red)]

Application to outdoor growing 

crops

0.5 lb/A 10 0 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 harvest until spray has dried.

Aerial applications: do not apply less than 2 

gal. of diluted solution/A to field crops or less 

than 10 gal. of diluted solution/A to orchard 

crops.

Do not wet plants to point of runoff or drip.

Application to hydroponically grown 

crops

1.0 ppm in 

water 10 0

Surface application to greenhouse 

grown crop

0.012 

lb/1,000 sq. ft 

or

0.5 lb/A

10 0

Space application to greenhouse 

grown crop

0.0014 

lb/1,000 cu. ft 10 0

Crop Group 14: Tree Nuts [including Almond; Beech nut; Brazil nut; Butternut; Cashew; Chestnut; Chinquapin; Filbert; 

Hickory nut; Macadamia nut; Pecan; Pistachio; Walnut, black; and Walnut, English]

Application to outdoor growing 

crops

0.5 lb/A 10 0 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 harvest until spray has dried.

Aerial applications: do not apply less than 2 

gal. of diluted solution/A to field crops or less 

than 10 gal. of diluted solution/A to orchard 

crops.

Do not wet plants to point of runoff or drip.

Application to hydroponically grown 

crops

1.0 ppm in 

water 10 0

Surface application to greenhouse 

grown crop

0.012 

lb/1,000 sq. ft 

or

0.50 lb/A

10 0

Space application to greenhouse 

grown crop

0.0014 

lb/1,000 cu. ft 10 0

Crop Group 15: Cereal Grains [including Barley; Buckwheat; Corn (field, pod, pop, and sweet); Millet; Millet, pearl; Millet, 

proso; Oat; Rice; Rice, wild; Rye; Sorghum, grain; Teosinte; Triticale; Wheat; Wheat, vavilovi; Wheat, wild einkorn; and Wheat, 

wild emmer]

Application to outdoor growing 

crops

0.5 lb/A 10 0

Do not reapply within 3 days except under 

extreme pest pressure.

In case of extreme pest pressure, do not reapply 

within 24 hours.

Application to hydroponically grown 

crops

1.0 ppm in 

water 10 0
73

Appendix A-1: Food/Feed Uses of Piperonyl Butoxide Subject to Reregistration.

Site

Application Type

Max. Single 

Application 

Rate, ai

Max. No. of 

Applications 

Per Season

PHI 

(Days) Use Directions and Limitations 

Surface application to greenhouse 

grown crop

0.012 

lb/1,000 sq. ft 

or

0.50 lb/A

10 0

Do not harvest until spray has dried.

Aerial applications: do not apply less than 2 

gal. of diluted solution/A to field crops or less 

than 10 gal. of diluted solution/A to orchard 

crops.

For rice, a 10 day water hold is required for all 

applications when rice fields are flooded.

Do not wet plants to point of runoff or drip.

Space application to greenhouse 

grown crop

0.0014 

lb/1,000 cu. ft 10 0

Crop Group 16: Forage, Fodder, and Straw of Cereal Grains [including Barley; Corn (field, pod, pop, and sweet); Millet; 

Millet, pearl; Millet, proso; Oat; Rice; Rice, wild; Rye; Sorghum (forage and grain); Teosinte; Triticale; Wheat; Wheat, vavilovi; 

Wheat, wild einkorn; and Wheat, wild emmer]

Application to outdoor growing 

crops

0.5 lb/A 10 0

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 harvest until spray has dried.

Aerial applications: do not apply less than 2 

gal. of diluted solution/A to field crops or less

than 10 gal. of diluted solution/A to orchard 

crops.

For rice, a 10 day water hold is required for all 

applications when rice fields are flooded.

Do not wet plants to point of runoff or drip.

Application to hydroponically grown 

crops

1.0 ppm in 

water 10 0

Surface application to greenhouse 

grown crop

0.012 

lb/1,000 sq. ft 

or

0.50 lb/A

10 0

Space application to greenhouse 

grown crop

0.0014 

lb/1,000 cu. ft 10 0

Crop Group 17: Grass Forage, Fodder, and Hay [including Alkali sacaton; Alkaligrass; Arizona cottontop; Bahiagrass; 

Beachgrass; Bentgrass; Bentgrass, spike; Bermudagrass; Blowoutgrass; Bluegrass; Bluegrass, silky; Bluestem australian; 

Bluestem, big; Bluestem, Caucasian; Bluestem, Diaz; Bluestem, little; Bluestem, sand; Bluestem, silver; Bluestem, south African; 

Bluestem, yellow; Bristlegrass, plains; Bromegrass; Broomsedge; Buffalograss; Buffelgrass; Canarygrass, annual; Canarygrass, 

reed; Caribgrass; Carpetgrass; Carpetgrass, broadleaf; Centipedegrass; Cordgrass, marsh hay; Crabgrass; Curly mesquite; 

Dallisgrass; Dropseed, pine; Dropseed, sand; Dropseed, tall; Fescue; Fingergrass, feather; Foxtail, creeping; Foxtail, meadow; 

Gamagrass, eastern; Grass; Grass, galleta; Grass, gama; Grass, muhly; Grass, pasture; Grass, St. Augustine; Grass, wildrye; 

Grass, zoysia; Hairgrass tufted; Hardinggrass; Indiangrass; Junegrass; Limpograss; Lovegrass; Maidencane; Mannagrass; Millet,

foxtail; Millet, Japanese; Molassesgrass; Napiergrass; Needlegrass; Oat, sand; Oat, slender; Oat, wild; Oatgrass; Oatgrass, tall; 

Oniongrass; Orchardgrass; Pangolagrass; Panicgrass; Paspalum; Polargrass; Quackgrass; Redtop; Reedgrass; Rhodesgrass; 

Rhodesgrass, multiflower false; Ricegrass, indian; Ryegrass, Italian; Ryegrass, perennial; Sandreed, prairie; Sixweeks threeawn; 

Sloughgrass; Smilograss; Sorghum, forage; Spikeoat; Sprangletop, green; Squirreltail; Sudangrass; Sunolgrass; Tanglehead; 

Timothy; Timothy, alpine; Trisetum, spike; Vaseygrass; Veldtgrass, perennial; Velvetgrass; Wheatgrass; Wheatgrass, bluebunch;

Wheatgrass, crested; Wheatgrass, fairway; Wheatgrass, intermediate; Wheatgrass, pubescent; Wheatgrass, Siberian; Wheatgrass, 

slender; Wheatgrass, streambank; Wheatgrass, tall; Wheatgrass, thickspike; Wheatgrass, western; and Windmillgrass, hooded]

Application to outdoor growing 

crops

0.5 lb/A 10 0

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 harvest until spray has dried.

Aerial applications: do not apply less than 2 

gal. of diluted solution/A to field crops or less 

than 10 gal. of diluted solution/A to orchard 

crops.

For rice, a 10 day water hold is required for all 

applications when rice fields are flooded.

Do not wet plants to point of runoff or drip.

Application to hydroponically grown 

crops

1.0 ppm in 

water 10 0

Surface application to greenhouse 

grown crop

0.012 

lb/1,000 sq. ft 

or

0.50 lb/A

10 0

Space application to greenhouse 

grown crop

0.0014 

lb/1,000 cu. ft 10 0

Crop Group 18: Nongrass Animal Feeds (Forage, Hay, Straw, and Hay) [including Alfalfa; Arrowleaf balsamroot; 

Burclover; Clover; Clover, alsike; Clover, alyce; Clover, arrowleaf; Clover, ball; Clover, berseem; Clover, bigflower; Clover, 

crimson; Clover, hop; Clover, lappa; Clover, persian; Clover, red; Clover, rose; Clover, seaside; Clover, strawberry; Clover, 

striate; Clover, sub; Clover, sweet; Clover, true; Clover, white; Clover, whitetip; Crownvetch; Kudzu; Lespedeza; Lupine; 

Lupine, forage; Lupine, sweet; Mustard; Sainfoin; Trefoil; Velvetbean; Vetch; and Vetch, milk]
74

Appendix A-1: Food/Feed Uses of Piperonyl Butoxide Subject to Reregistration.

Site

Application Type

Max. Single 

Application 

Rate, ai

Max. No. of 

Applications 

Per Season

PHI 

(Days) Use Directions and Limitations 

Application to outdoor growing 

crops

0.5 lb/A 10 0 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 harvest until spray has dried.

Aerial applications: do not apply less than 2 

gal. of diluted solution/A to field crops or less 

than 10 gal. of diluted solution/A to orchard 

crops.

Do not wet plants to point of runoff or drip.

Application to hydroponically grown 

crops

1.0 ppm in 

water 10 0

Surface application to greenhouse 

grown crop

0.012 

lb/1,000 sq. ft 

or

0.5 lb/A

10 0

Space application to greenhouse 

grown crop

0.0014 

lb/1,000 cu. ft 10 0

Crop Group 19: Herbs and Spices [Including Allspice; Angelica; Anise; Anise hyssop (mint); Anise, star; Annatto; Balm; 

Basil; Borage; Burnet; Camomile; Caper; Caraway; Caraway, black; Cardamom; Cardamon amomum; Cassia; Catnip; Celery, 

seed; Chervil; Chive; Chive, Chinese; Cinnamon; Clary; Clove; Coriander; Costmary; Cilantro (False coriander); Cumin; Curry; 

Dill; Dillweed; Fennel; Fennel, florence; Fenugreek; Grains of paradise; Horehound; Juniper berry; Lavender; Lemongrass; 

Lovage; Mace; Marigold, pot; Marjoram (Oregano); Mustard; Nasturtium; Nutmeg; Parsley; Pennyroyal; Pepper, black; Pepper, 

white; Poppy; Rosemary; Rue; Saffron; Sage; Savory, summer; Savory, winter; Sweet bay; Tansy; Tarragon; Thyme; Vanilla; 

Wintergreen; Woodruff; and Wormwood]

Application to outdoor growing 

crops

0.5 lb/A 10 0 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 harvest until spray has dried.

Aerial applications: do not apply less than 2 

gal. of diluted solution/A to field crops or less 

than 10 gal. of diluted solution/A to orchard 

crops.

Do not wet plants to point of runoff or drip.

Application to hydroponically grown 

crops

1.0 ppm in 

water 10 0

Surface application to greenhouse 

grown crop

0.012 

lb/1,000 sq. ft 

or

0.5 lb/A

10 0

Space application to greenhouse 

grown crop

0.0014 

lb/1,000 cu. ft 10 0

Miscellaneous Fruit, Subtropical/Tropical [including Acerola; Atemoya, Avocado; Banana; Carob bean; Cherimoya; Date; 

Durian; Feijoa; Fig; Guava; Kiwifruit; Lychee; Mango; Papaya; Passionfruit; Persimmon; Pineapple; Pomegranate; Rambutan; 

and Starfruit (Carambola) ]

Application to outdoor growing 

crops

0.5 lb/A 10 0 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 harvest until spray has dried.

Aerial applications: do not apply less than 2 

gal. of diluted solution/A to field crops or less 

than 10 gal. of diluted solution/A to orchard 

crops.

Do not wet plants to point of runoff or drip.

Application to hydroponically grown 

crops

1.0 ppm in 

water 10 0

Surface application to greenhouse 

grown crop

0.012 

lb/1,000 sq. ft 

or

0.5 lb/A

10 0

Space application to greenhouse 

grown crop

0.0014 

lb/1,000 cu. ft 10 0

Vegetable, Oriental [including Artichoke, Chinese; Balsam pear (bitter melon); Bean, mung; Bean, yardlong; Broccoli, Chinese; 

Cabbage, Chinese, bok choy; Cabbage, Chinese, mustard; Cabbage, Chinese, napa; Coriander (Cilantro); Dasheen; Ginger; 

Ginseng; Melon, citron; Radish, oriental; Spinach, Chinese; and Waxgourd, Chinese] 

Note: Individual crops listed above belong to various crop groups previously listed.

Application to outdoor growing 

crops

0.5 lb/A 10 0 Do not reapply within 3 days except under 

extreme pest pressure.

In case of extreme pest pressure, do not reapply 

within 24 hours.

Application to hydroponically grown 

crops

1.0 ppm in 

water 10 0
75

Appendix A-1: Food/Feed Uses of Piperonyl Butoxide Subject to Reregistration.

Site

Application Type

Max. Single 

Application 

Rate, ai

Max. No. of 

Applications 

Per Season

PHI 

(Days) Use Directions and Limitations 

Surface application to greenhouse 

grown crop

0.012 

lb/1,000 sq. ft 

or

0.5 lb/A

10 0

Do not harvest until spray has dried.

Aerial applications: do not apply less than 2 

gal. of diluted solution/A to field crops or less 

than 10 gal. of diluted solution/A to orchard 

crops.

Do not wet plants to point of runoff or drip. Space application to greenhouse 

grown crop

0.0014 

lb/1,000 cu. ft 10 0

Miscellaneous Commodities: Asparagus; Coffee; Cotton; Cranberry; Grape; Jojoba; Okra; Safflower; Strawberry; Sugarcane; 

Sunflower; and Tea

Application to outdoor growing 

crops

0.5 lb/A 10

14 

(cotton 

seed)

0 (all 

other 

crops)

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 harvest until spray has dried.

Aerial applications: do not apply less than 2 

gal. of diluted solution/A to field crops or less 

than 10 gal. of diluted solution/A to orchard 

crops.

Do not wet plants to point of runoff or drip 

For labels with cotton: Do not apply to cotton 

within 14 days of seed harvest.

.

Application to hydroponically grown 

crops

1.0 ppm in 

water 10 0

Surface application to greenhouse 

grown crop

0.012 

lb/1,000 sq. ft 

or

0.5 lb/A

10 0

Space application to greenhouse 

grown crop

0.0014 

lb/1,000 cu. ft 10 0

RESIDENTIAL

Preharvest Application to Garden Crops (see Agricultural; Preharvest Application to Field, Orchard, and Greenhouse Crops)

Application to outdoor growing crops

0.012 

lb/1,000 sq. ft 

or

0.50 lb/A

10 0

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 more than 1 time per day.

Do not harvest until spray has dried.

Do not wet foliage to point of runoff or drip. 

Application to hydroponically grown 

crops

1.0 ppm in 

water 10 0

NON-FOOD CROPS 

(Residential and Non-Residential)

Non-food Crops in Greenhouse: Ornamental, Flowering and Foliage Plants

Surface applications

0.036 

lbs/1,000 sq.ft

or

1.5 lb/A

NA NA

Do not apply more than 1 time per day.

Do not wet foliage to point of runoff or drip. 

Space spray

0.0042 

lbs/1,000 cu. 

ft.

NA NA

Non-food Crops Grown Outside: Ornamentals, Flowering and Foliage Plants, and Lawns 

Surface applications (including fire 

ants and turf diagnostic aid)

0.02 lbs/1,000 

sq ft

or

1.0 lbs/A

NA NA Do not apply more than 1 time per day.

Do not wet plants to point or runoff or drip. 
76

A-2: Non-Growing Crop Uses

Appendix A-2: Non-Growing Crop Uses of Piperonyl Butoxide Subject to Reregistration.

Site

Application Type

Max. Single 

Application 

Rate, ai Use Directions and Limitations 

Postharvest Application to Vegetables, Fruit, and Nuts 

Food/Feed Storage Areas -Full: Postharvest Application to Apple, Blackberry, Blueberry, Boysenberry, Cherry, Crabapple, 

Currant, Dewberry, Fig, Gooseberry, Grape, Guava, Loganberry, Mango, Muskmelon, Orange, Peach, Pear, Pea, Pineapple, 

Plum, Potato, Raspberry, or Tomato in baskets, on trucks, in processing plants, in hampers, or in temporary storage areas 

(including raw stock stacked in yards)

Copra (processed) in baskets, on trucks, in processing plants, in hampers, or in temporary storage areas (including raw stock

stacked in the yard)

Postharvest application to Almonds, Peanuts, and Walnuts (English/black) in bulk 

Surface - General 0.1 lb/1,000 sq. 

ft 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. Surface - Direct application to fruits 

or tomatoes in baskets or hampers

1.6 x 10-6lb/ lb 

of fruit or 

vegetable (1.6 

ppm)

Dip or spray 0.004 lbs ai/ 

gallon

Space - Fruits, vegetables, and copra .

0.01 lb/1,000 

cu. Ft

Postharvest Direct Application to Bulk Grain and Seed 

Barley, Beans, Lima Beans, Birdseed, Buckwheat, Cocoa beans, Corn, Cottonseed, Flax, Grain sorghum, Oats, Pea (field), Rice, 

Rye, Wheat (club, common, durham), Wheat (emmer, spelt)

Bulk Grain and Seed 1.0 lb/1,000 

bushels grain

Do not reapply within 30 days.

See below for rate in ounces Piperonyl Butoxide per 100 lb grain or 

seed.

- Barley 0.033 oz/cwt

Do not reapply within 30 days.

- Beans 0.027 oz/cwt

- Beans, lima 0.029 oz/cwt

- Birdseed 0.032 oz/cwt

- Buckwheat 0.033 oz/cwt

- Cocoa beans 0.037 oz/cwt

- Corn 0.029 oz/cwt

- Cottonseed 0.057 oz/cwt

- Flax 0.029 oz/cwt

- Grain sorghum 0.029 oz/cwt

- Oats 0.050 oz/cwt

- Pea (field) 0.027 oz/cwt

- Rice 0.036 oz/cwt

- Rye 0.029 oz/cwt

- Wheat: club, common, durham 0.027 oz/cwt

- Wheat: emmer, spelt 0.040 oz/cwt

Direct Application to Animals
77

Appendix A-2: Non-Growing Crop Uses of Piperonyl Butoxide Subject to Reregistration.

Site

Application Type

Max. Single 

Application 

Rate, ai Use Directions and Limitations 

Cattle (Beef/Range/Feeder and Dairy); Hogs/Pig/Swine; Goats (Meat and Dairy); Kids; Sheep; Lamb; Rabbits; Game Animals 

(including Beefalo, Buffalo, Deer, Exotics such as European red deer, Llamas, Moose, Elk); Livestock (including Donkeys, 

Horses, Ponies, Mules); and Poultry

Direct application to livestock and 

poultry - Dust 10.0%

Do not apply more than 1 time per day.

Do not apply microencapsulated products to lactating or food animals.

Direct application to livestock –

Liquid Solution 0.35 lb/gal

Direct application to livestock -

Towelette 2.0%

Direct application to livestock - Spoton or Pour-on

10.0%

Direct application to poultry – Liquid 

Solution 0.1%

Application to Agricultural Premises and Equipment - Indoor

Greenhouses (empty)

Agricultural/Farm Structures/Buildings and Equipment: Animal houses; Calf hutches; Calving pens and parlors; Dairies; Dairy 

farms; Goat houses; Livestock housing structures; Loafing sheds; Poultry houses; Poultry operations; Rabbit houses; Rabbit 

hutches; Stables; Swine houses.

Barns/Barnyards/Auction Barns: Barns (Beef, Cattle, Dairy, Horse, Hog, and Livestock)

Dairy Farm Milking Stalls/Parlors: Milk houses; Milking parlors

Dairy Farm Milk Storage Rooms/Houses/Sheds: Milk rooms

Dairy Farm Milk Handling Facilities/Equipment: Milk handling equipment

Dairy Farm Milking Equipment: Milking equipment

Seed Houses/Stores/Storage Areas/Warehouses: Stored seed warehouses; Seed warehouse bins; Granaries; Seed storage sites; 

Seed bins; Stable bins; Stored seed warehouses

Silos and Mushroom houses 

IMPORTANT NOTE: The following rates allow animals to be present during application. 

Surface – General 0.56 lb ai/

1,000 sq. ft Remove or cover exposed food and water before application.

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.

Do not apply more than 1 time per day.

Space – General

0.0033 lb ai/

1,000 cu. 

ft/application

And

0.008 lbs 

ai/1000 cu. 

ft./day 
78

Appendix A-2: Non-Growing Crop Uses of Piperonyl Butoxide Subject to Reregistration.

Site

Application Type

Max. Single 

Application 

Rate, ai Use Directions and Limitations 

Space - Metered release 0.008 lbs 

ai/1000 cubic 

feet/day

Not for use in Residential areas. 

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 

feeds, dishes, milking utensils, and feed handling or preparation areas.

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.

Remove or cover exposed food and water before application.

Commercial Animal Housing

Animal areas and quarters; Animal shelters; Catteries; Dog runs; Kennels; Pet grooming shops; Pet stores; Research animal 

quarters; Zoos. (Animals are not present during application)

Surface - General 0.56 lb/

1,000 sq. ft

Do not apply more than 1 time per day.

Remove or cover exposed food and water before application.

Surface - Crack and crevice or spot 0.56 lb/

1,000 sq. ft

Space - General 0.025 lb/

1,000 cu. ft

Space - Metered release 0.008 lbs 

ai/1000 cubic 

feet/day

Not for use in Residential areas. Does this include non-commercial 

barns & stables?

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 

feeds, dishes, milking utensils, and feed handling or preparation areas.

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.

Remove or cover exposed food and water before application.

Outdoor Agricultural Premises 

Empty Uncultivated Agricultural Areas: Corrals; Dairy areas; Farms; Goat holding areas; Hog operations; Rights-of-way; Sheep 

holding areas.

Empty Cattle Feedlots: Beef cattle operations; Feedlots; Holding lots; Livestock lots; Swine lots and yards.

Surface - General 0.02 lb/

1,000 sq. ft

Do not apply more than 1 time per day.

Surface - Crack and crevice or 

spot

0.56 lb/

1,000 sq. ft

INDOOR

Residential - Indoor
79

Appendix A-2: Non-Growing Crop Uses of Piperonyl Butoxide Subject to Reregistration.

Site

Application Type

Max. Single 

Application 

Rate, ai Use Directions and Limitations 

Household/Domestic Dwellings: Apartments; Cabins; Campers; Condominiums; Dwellings; Homes; Mobile homes; Recreational 

vehicles; Residences; Public housing; Sheds; Toolsheds; Townhouses.

Household/Domestic Dwelling Contents: Beds (cracks, crevices, framework); Bedding; Bookcases; Box springs; Boxes; 

Cabinets; Carpet; Cooking equipment; Cut Flowers; Drawers; Dressers; Draperies; Dryers; Equipment; Fabrics; Flowering plants; 

Foliage plants; Formica; Furniture; Furniture bases; Furniture legs; Glass; Light fixtures; Linoleum; Machinery; Mattresses; 

Picture frames; Plastic fabric bags; Refrigerator; Rugs; Shelves; Shrubs; Sofas and Chairs; Sofa and Chair surfaces; Soffits; 

Stainless steel; Storage drawers; Stored items; Stoves; Tables; Tiles; Trees; Upholstered furniture; Upholstery; Vinyl tile;

Washers.

Household/Domestic Dwellings Indoor Food Handling Areas (food covered): Cupboards; Kitchens; Sinks; Underneath sinks; 

Food areas.

Household/Domestic Dwellings Indoor Nonfood Handling Areas: Attics; Basements; Bedrooms; Closets; Closed porches; Crawl 

spaces; Dining rooms; Garages; Pantries; Porches; Solariums; Storage areas; Sun porches; Utility rooms; Bathrooms.

Household Domestic Dwellings Indoor Premises: Baseboards; Closed void areas; Cracks and crevices; Dark corners; Doorframes; 

Door jambs; Doors; Door sills; Drains; Equipment voids; False ceilings; Floors; Foundations; Moldings; Moist places; Niches; 

Pipes; Screens; Soffits; Tunnels and cavities in wood; Walls; Windows; Window frames; Window sills; Weep holes; Woodwork; 

Voids in attics, walls, ceilings, and equipment.

Electrical Supplies/Equipment: Meter boxes; Electrical equipment; Electrical fittings.

Human Clothing (Insect and Mold/Mildew Control): Clothing; Clothing (outerwear); Clothing (in storage); Woolens. 

Garbage cans and Garbage/trash compactors.

Surface - General 0.56 lb/

1,000 sq. ft

Remove or cover exposed food and water before application.

Remove or cover dishes, utensils, food processing equipment, and food 

preparation surfaces, or wash them thoroughly before use.

Do not apply more than 1 time per day.

For articles: 

- Do not wet articles to point of runoff or drip.

- Do not use treated article until spray has dried.

Surface - Crack and crevice or spot 0.56 lb/

1,000 sq. ft

Space – General

NOTE: Deleted the Space- Metered 

Release application from the row 

below.

0.025 lb/

1,000 cu. ft

Space - Metered release

0.05 lbs 

ai/1000 cubic 

feet/day

Not for use in Residential areas.

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 

feeds, dishes, milking utensils, and feed handling or preparation areas.

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.

Remove or cover exposed food and water before application.

Commercial/Industrial/Institutional Establishments - Indoor

Apartments; Auditoriums; Buildings; Churches; Commercial buildings; Correctional facilities; Communications centers; 

Courthouses; Day care centers; Dormitories; Drugstores; Elevators; Equipment voids; Factories; Fake ceilings; Florists; Food 

service storage and preparation areas; Gas stations; Hotels; Industrial buildings; Industrial installations; Institutions; 

Interiorscapes; Jails; Kitchens; Laboratories; Laundry areas; Lavatories; Libraries; Locker rooms; Lathhouses; Missions; Motels; 

Movie Theatres; Museums; Non-food areas of commercial buildings; Non-residential buildings; Offices and office buildings; 

Other commercial, industrial, and governmental sites; Parking garages; Prisons; Public buildings; Resorts; Schools; Shadehouses; 

Sheds; Stores; Textile mills & warehouses; Theaters; Universities; Utilities/utility rooms; Health care facilities; Hospices;

Hospitals; Nursing homes; Veterinary clinics.
80

Appendix A-2: Non-Growing Crop Uses of Piperonyl Butoxide Subject to Reregistration.

Site

Application Type

Max. Single 

Application 

Rate, ai Use Directions and Limitations 

Surface – General 0.56 lb ai/

1,000 sq. ft

Remove or cover exposed food and water before application.

Remove or cover dishes, utensils, food processing equipment, and food 

preparation surfaces, or wash them thoroughly before use.

Do not apply more than 1 time per day.

Surface - Crack and crevice or spot 0.56 lb/

1,000 sq. ft

Space – General 0.033 lb/

1,000 cu. ft

Space - Metered release

0.05 lbs 

ai/1000 cubic 

feet/day

Not for use in Residential areas.

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 

feeds, dishes, milking utensils, and feed handling or preparation areas.

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.

Remove or cover exposed food and water before application.

Eating Establishments -Indoor

Eating Establishments (Food Contact) [Equipment/Utensils; Food Handling Areas; Food Serving Areas]: Cafeterias; Restaurants; 

Mess halls

Surface – General 0.56 lb ai/

1,000 sq. ft

UNITS?

Remove or cover exposed food and water before application.

Remove or cover dishes, utensils, food processing equipment, and food 

preparation surfaces, or wash them thoroughly before use.

Do not apply more than 1 time per day.

Surface - Crack and crevice or spot 0.56 lb/

1,000 sq. ft

Remove or cover exposed food and water before application.

Remove or cover dishes, utensils, food processing equipment, and food 

preparation surfaces, or wash them thoroughly before use.

Do not apply more than 1 time per day.

Space - General 0.033 lb/

1,000 cu. ft

Do not make space spray applications when facility is in operation.

During space spray operations, cover or remove food.

During space spray operations, cover food processing surfaces or clean 

after treatment and before use.

Do not apply more than 1 time per day.

Space - Metered release

0.05 lbs 

ai/1000 cubic 

feet/day

Not for use in Residential areas.

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 

feeds, dishes, milking utensils, and feed handling or preparation areas.

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.

Remove or cover exposed food and water before application.

Food Handling and Processing Establishments - Indoor
81

Appendix A-2: Non-Growing Crop Uses of Piperonyl Butoxide Subject to Reregistration.

Site

Application Type

Max. Single 

Application 

Rate, ai Use Directions and Limitations 

Food Handling and Processing Plant Premises and Equipment (Food Contact): Bakeries; Bottling plants; Beverage plants; 

Canneries; Conveying Equipment; Dried fruit processing plants; Feed areas of commercial buildings; Food areas of commercial 

buildings; Food processing plants; Fruit packing sheds; Mushroom processing plants; Peanut processing plants; Processing areas 

of dried food products; Tobacco processing plants; Wineries

Meat Processing Plant Premises and Equipment (Food Contact): Conveying equipment; Edible product areas of official 

establishments operating under the meat; poultry; shell egg grading and egg products inspection operations; Meat packing plants; 

Poultry processing plants; Rabbit processing plants; USDA inspected meat and poultry plants

Dairies/Cheese Processing Plant Premises and Equipment (Food Contact): Dairies

Egg Processing Plants

Tobacco Processing Plants

Feed Mills/Feed Processing Plants: Conveying equipment; Feed processing and handling sites; Flour mills; Grain mills; Mills; 

Milling operations; Roll housing and hoppers; Stored grain mills; Rice mills

Feed/Food Treatment - Storage/Processing/Handling Equipment: Conveying equipment; Grain handling equipment

Surface - General–

0.56 lb ai/

1,000 sq. ft

Do not make space spray applications when facility is in operation.

Remove or cover exposed food and water before application.

Remove or cover dishes, utensils, food processing equipment, and food 

preparation surfaces, or wash them thoroughly before use.

Do not apply more than 1 time per day. 

Surface - Crack and crevice or spot 0.56 lb/

1,000 sq. ft

Do not make space spray applications when facility is in operation.

Remove or cover exposed food and water before application.

Remove or cover dishes, utensils, food processing equipment, and food 

preparation surfaces, or wash them thoroughly before use.

Do not apply more than 1 time per day.

Space - General 0.033 lb ai/

1,000 cu. ft

Do not make space spray applications when facility is in operation.

During space spray operations, cover or remove food.

During space spray operations, cover food processing surfaces or clean 

after treatment and before use.

Do not apply more than 1 time per day.

Space - Metered release

0.05 lbs 

ai/1000 cubic 

feet/day

Not for use in Residential areas.

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 

feeds, dishes, milking utensils, and feed handling or preparation areas.

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.

Remove or cover exposed food and water before application.

Retail and Storage - Indoor

Commercial Storage/Warehouses Premises: Brandy storage warehouses; Dried fruit warehouses; Elevators; Food storage areas; 

Freight containers; Peanut storage warehouses; Spirit storage; Storage areas; Storage areas of dried food products; Stored seed 

warehouses; Warehouses; Wine storage warehouses; Tobacco warehouses

Food Stores/Markets/Supermarkets Premises and Equipment: Food marketing - storage- distribution; Grocery and convenience 

stores; Stores; Supermarkets; Conveying equipment; Freight containers; Stored product areas

Food/Feed Storage Areas-Full: Stored product areas.
82

Appendix A-2: Non-Growing Crop Uses of Piperonyl Butoxide Subject to Reregistration.

Site

Application Type

Max. Single 

Application 

Rate, ai Use Directions and Limitations 

Surface - General 0.56 lb/

1,000 sq. ft

Remove or cover exposed food and water before application.

Remove or cover dishes, utensils, food processing equipment, and food 

preparation surfaces, or wash them thoroughly before use.

Do not apply more than 1 time per day.

Surface - Crack and crevice or spot 0.56 lb/

1,000 sq. ft

Remove or cover exposed food and water before application.

Remove or cover dishes, utensils, food processing equipment, and food 

preparation surfaces, or wash them thoroughly before use.

Do not apply more than 1 time per day.

Space - General 0.033 lb/

1,000 cu. ft

Do not make space spray applications when facility is in operation.

During space spray operations, cover or remove food.

During space spray operations, cover food processing surfaces or clean 

after treatment and before use.

Do not apply more than 1 time per day.

Space - Metered release

0.05 lbs 

ai/1000 cubic 

feet/day

Not for use in Residential areas.

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 

feeds, dishes, milking utensils, and feed handling or preparation areas.

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.

Remove or cover exposed food and water before application.

Transportation - Indoor

Commercial Transportation Facilities: Airplanes; Boats; Box cars; Buses; Cabins and holds of aircraft; Commercial 

transportation centers; Freight containers; Ocean fright containers; Pallets; Passenger rail cars; Railroad cars; Recreational 

vehicles; Ships & ships‟ holds; Trains; Trucks; Trailers; Truck trailers; Livestock hauling equipment; Horse trailers.

Commercial Transportation Facilities – Empty: Grain transportation containers (truck beds; planes; box cars; cargo ship holds); 

Pallets.

Commercial Shipping Containers- Empty: Grain transportation containers (truck beds; planes; box cars; cargo ship holds); 

Pallets.

Trunks of Automobiles, Taxis, Limousines. 

Surface - General 0.56 lb/

1,000 sq. ft

Do not use in aircraft cabins except in compliance with PR Notice 96-3.

Do not apply more than 1 time per day. Surface - Crack and crevice or spot 2.2 lb/1,000 sq. ft

Space - General 0.033 lb/

1,000 cu. ft
83

Appendix A-2: Non-Growing Crop Uses of Piperonyl Butoxide Subject to Reregistration.

Site

Application Type

Max. Single 

Application 

Rate, ai Use Directions and Limitations 

Space - Metered release

0.05 lbs 

ai/1000 cubic 

feet/day

Not for use in Residential areas.

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 

feeds, dishes, milking utensils, and feed handling or preparation areas.

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.

Remove or cover exposed food and water before application.

Pet Care

Birds: Amazon parrots; Budgies; Canaries; Cockatiels; Finches; Love birds; Macaws; Ostrich; Parakeets; Parrots.

Cats (including kittens), Dogs (including puppies), Monkeys, Ferrets, Rabbits. 

Chimpanzees; Chinchillas; Horses; Llamas; Lemurs; Minks; Ponies; Pot bellied pigs.

Rodents: Gerbils; Guinea pigs; Hamsters; Mice; Rats.

Shampoos 3.0% a.i. 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.

 

Sprays

0.1% a.i.

Spot-on or Pour-on 10.0% a.i.

Dust 10.0% a.i.

Towelettes 2.0% a.i.

Pet Premise Treatment

Pet Living/Sleeping Quarters: Areas of floors & floor coverings where pets may be present; areas where female insects may crawl 

to lay eggs, and similar hiding places; Dog houses and other sleeping quarters; Dog runs; Pet bedding and premises; Pet premises; 

Pet resting areas; Kennels.

Surface

0.56 lb per 

1000 square 

feet

For dusts: Only apply as a spot treatment to areas no greater than 3 feet 

by 3 feet per room.

Crack and crevice 0.56 lbs ai per 

1000 square 

feet

Space Spray

0.033 lbs per 

1000 square 

feet

OUTDOOR

Residential Sites - Outdoor
84

Appendix A-2: Non-Growing Crop Uses of Piperonyl Butoxide Subject to Reregistration.

Site

Application Type

Max. Single 

Application 

Rate, ai Use Directions and Limitations 

Ant hills; Ant nests; Ant trails; Backyards; Doors; Driveways; Entranceways; Mud dauber, wasp, and yellow jacket nests; Outside 

surfaces of buildings; Patio furniture; Picnic areas; Residential areas; Screens; Siding; Spigots; Storage areas; Tree holes; Under 

eaves; Under siding; Wall voids; Windows.

Nonagricultural Outdoor Buildings/Structures: Atriums; Carports; Decks; Fences; Gazebos; Lanais; Porches; Sheds; Tree houses;

Tunnels and cavities in wood; Verandas; Tents.

Fencerows; Hedgerows; Nonagricultural Rights-of-way; Paths; Patios; Paved Areas: Private Roads; Sidewalks; Garbage bins; 

Dumpsters; Meter boxes; Electrical equipment; Electrical fittings; Manure; Compost piles.

Surface – General 0.075 lb ai/

1,000 sq. ft Do not apply more than 1 time per day.

Surface Remove or cover exposed food and drinking water before application. - Crack and crevice or spot 0.56 lb ai/

1,000 sq. ft

General Outdoor Sites including Non-Agricultural rights-of-way, Commercial/Institutional/Industrial Premises and 

Equipment, Outdoor Eating Establishments, and Utensils

Ant hills; Ant nests; Ant trails; Backyards; Doors; Driveways; Entranceways; Mud dauber, wasp, and yellow jacket nests; Outside 

surfaces of buildings; Patio furniture; Picnic areas; Residential areas; Screens; Siding; Spigots; Storage areas; Tree holes; Under 

eaves; Under siding; Wall voids; Windows.

Nonagricultural Outdoor Buildings/Structures: Atriums; Carports; Decks; Fences; Gazebos; Lanais; Porches; Sheds; Tree houses;

Tunnels and cavities in wood; Verandas; Tents.

Fencerows; Hedgerows; Nonagricultural Rights-of-way; Paths; Patios; Paved Areas: Private Roads; Sidewalks; Garbage bins; 

Dumpsters; Meter boxes; Electrical equipment; Electrical fittings; Manure; Compost piles.

Surface – General 0.075 lb ai/

1,000 sq. ft Do not apply more than 1 time per day.

Surface Remove or cover exposed food and drinking water before application. - Crack and crevice or spot 0.56 lb ai/

1,000 sq. ft

Outdoor Eating Establishments 

Eating Establishments Equipment/Utensils, Food Handling Areas, Food Serving Areas, Non-Food Areas of outdoor eating 

establishments and drive-in restaurants

Surface applications 

0.075 lbs 

ai/1000 square 

feet

Remove or cover exposed food and water before application.

Remove or cover dishes, utensils, food processing equipment, and food 

preparation surfaces, or wash them thoroughly before use.

Crack/crevice or spot surface Do not apply more than 1 time per day.

0.56 lbs 

ai/1000 square 

feet

Mosquito Abatement - Adulticide

Agricultural Crops/Soils: Groups of Agricultural Crops Which Cross Established Crop Groupings (Croplands);

Agricultural Uncultivated Areas: Fallow lands, Pastures, and Rangelands; 

Intermittently Flooded Areas/Water;

Irrigation Systems
85

Appendix A-2: Non-Growing Crop Uses of Piperonyl Butoxide Subject to Reregistration.

Site

Application Type

Max. Single 

Application 

Rate, ai Use Directions and Limitations 

Thermal fog

Non-thermal fog

ULV

0.025 lb/A

Do not apply more than 0.2 lbs ai/acre/year in any treated area.

Apply only when wind speed is greater than or equal to 1 mph.

For ground applications: Spray equipment must be adjusted so that the 

volume median diameter is less than 30 microns (Dv 0.5 < 30 μm) and 

that 90% of the spray is contained in droplets smaller than 50 microns 

(Dv 0.9 < 50 μm).

For aerial applications: Spray equipment must be adjusted so that the 

volume median diameter produced is less than 60 microns (Dv 0.5 < 60 

μm) and that 90% of the spray is contained in droplets smaller than 80 

microns (Dv 0.9 < 80 μm). 

Apply using a nozzle height of no less than 100 feet above the ground or 

canopy for aerial applications with fixed wing equipment. 

Apply using a nozzle height of no less than 75 feet above the ground or 

canopy for aerial applications with rotary wing equipment.

0.08 lb/A

Do not apply more than 0.2 lbs ai/acre/year in any treated area.

Apply only when wind speed is greater than or equal to 1 mph.

For ground applications: Spray equipment must be adjusted so that the 

volume median diameter is less than 30 microns (Dv 0.5 < 30 μm) and 

that 90% of the spray is contained in droplets smaller than 50 microns 

(Dv 0.9 < 50 μm).

For aerial applications: Spray equipment must be adjusted so that the 

volume median diameter produced is less than 60 microns (Dv 0.5 < 60 

μm) and that 90% of the spray is contained in droplets smaller than 80 

microns (Dv 0.9 < 80 μm). 

Apply using a nozzle height of no less than 100 feet above the ground or 

canopy for aerial applications with fixed wing equipment. 

Apply using a nozzle height of no less than 75 feet above the ground or 

canopy for aerial applications with rotary wing equipment.

Manholes

Surface

0.04 

lbs/manhole 

over a 200 foot 

length

Do not apply more than 1 time per day. 
86

Appendix B: PBO Major Degradate Structures

O

O

O

O

O

Piperonyl butoxide

O

O

OH

PBO -alcohol

hydroxymethyl dihydrosafrol

M DPB-alcohol

3,4-methylene-6-propylbenzyl alcohol

O

O

O

PBO -aldehyde

dihydrosafrol aldehyde

M DPB-aldehyde

3,4-methylene-6-propylbenzaldehyde

O

O

O

OH

PBO -acid

M DPB-acid

3,4-methylene-6-propylbenzoic acid

Piperonyl Butoxide Degradation: Pathw ay 1

Side-Chain Cleavage and O xidation

C O2
87

O

O

O

O

O

Piperonyl butoxide

O

O

OH

PBO -alcohol

hydroxymethyl dihydrosafrol

M DPB-alcohol

3,4-methylene-6-propylbenzyl alcohol

O

O

O

PBO -aldehyde

dihydrosafrol aldehyde

M DPB-aldehyde

3,4-methylene-6-propylbenzaldehyde

O

O

O

OH

PBO -acid

M DPB-acid

3,4-methylene-6-propylbenzoic acid

Piperonyl Butoxide Degradation: Pathw ay 1

Side-Chain Cleavage and O xidation

C O2
88

Appendix C: Submitted Effects Studies for Piperonyl Butoxide

71-1 Avian Single Dose Oral Toxicity

MRID Citation Reference

41969008 Campbell, S.; Lynn, S.; Smith, G. (1991) An Acute Oral Toxicity Study With 

Piperonyl Butoxide in the Northern Bobwhite Quail: Lab Project Number: 306-

103. Unpublished study prepared by Wil- dlife International Ltd. 35 p. 

71-2 Avian Dietary Toxicity

MRID Citation Reference

00031369 or 

00055509

IBT study

Fletcher, D. (1974) Report to McLaughlin Gormley King Company: 8- Day 

Dietary LC50 Study with X-2840-74 in Mallard Ducklings: IBT No. 651-05280. 

(Unpublished study received Dec 17, 1975 under 1021-88; prepared by 

Industrial Bio-Test Laboratories, Inc., submitted by McLaughlin, Gormley, King 

Co., Minneapolis, Minn.; CDL:221996-N) 

00072879 or 

00073000

Fink, R. (1975) Final Report: Eight-Day Dietary LCI50^--Mallard Duck: Project 

No. 104-112. (Unpublished study received Sep 18, 1980 under 279-482; 

prepared by Truslow Farms, Inc., submitted by FMC Corp., Philadelphia, Pa.; 

CDL:243249-E) 

Aldrin + Pipronyl Butoxide + Pyrethrins

00072999 Fink, R. (1975) Final Report: Eight-Day Dietary LCI50^--Bobwhite Quail: 

Project No. 104-111. (Unpublished study received Jan 19, 1977 under 4816-

428; prepared by Truslow Farms, Inc., sub- mitted by Fairfield American Corp., 

Medina, N.Y.; CDL:227641-B) 

Aldrin + Pipronyl Butoxide + Pyrethrins

41969006 Grimes, J.; Lynn, S.; Smith, G. (1991) A Dietary LC50 Study With Piperonyl 

Butoxide in the Northern Bobwhite Quail: Lab Project Number: 306-101. 

Unpublished study prepared by Wildlife Intern- ational Ltd. 58 p. 

41969007 Grimes, J.; Lynn, S.; Smith, G. (1991) A Dietary LC50 Study With Piperonyl 

Butoxide in the Mallard: Lab Project Number: 306-102. Unpublished study 

prepared by Wildlife International Ltd. 57 p. 

00031373 Taylor, R.E. (1967) To Determine the Toxicity of Sample on Tropical Fish, 

Parakeets and Canaries. (Unpublished study received Dec 17, 1975 under 

1021-88; prepared by Harris Laboratories, Inc., submitted by McLaughlin, 

Gormley, King Co., Minneapolis, Minn.; CDL:221996-R) 

Aldrin + Pipronyl Butoxide + Pyrethrins

71-4 Avian Reproduction

MRID Citation Reference

43876301 Rodgers, M. (1995) Piperonyl Butoxide: Effects on Reproduction in Bobwhite 

Quail After Dietary Administration: Lab Project Number: PBT/2: PBT 2/950167. 
89

Unpublished study prepared by Huntingdon Research Centre, Ltd. 258 p. 

43876302 Rodgers, M. (1995) Piperonyl Butoxide: Effects on Reproduction in the Mallard 

Duck After Dietary Administration: Lab Project Number: PBT/3: PBT 3/950168. 

Unpublished study prepared by Huntingdon Research Centre, Ltd. 225 p. 

72-1 Acute Toxicity to Freshwater Fish

MRID Citation Reference

00084069 Lewallen, L.L. (1973) Letter sent to Joseph B. Moore dated Dec 3, 1973 ?Data 

on the toxicity of pyrethrim and dimethrin on the mosquito fish~Gambusia 

affinis~?|. (California, Health and Wel- fare Agency, Dept. of Health, Vector 

Control Section; unpub- lished study; CDL:221987-AN) 

00107544 Taylor, R. (1967) To Determine the Toxicity of Sample ?Pyrocide Intermediate 

6440| on Tropical Fish, Parakeets and Canaries. (Unpublished study received 

Sep 19, 1969 under 2915-14; pre- pared by Harris Laboratories, Inc., submitted 

by Fuller Brush Co., Great Bend, KS; CDL:006959-A) Aldrin + Pipronyl 

Butoxide + Pyrethrins

00111966 Cope, O. (1965) Letter sent to J. Moore dated Mar 16, 1965 ?Tox- icity figures 

for McLaughlin Gormley King compound no. F-1755 against bluegill and 

rainbow trout|. (U.S. Fish and Wildlife Service, Fish-Pesticide Research 

Laboratory; unpublished study; CDL:005246-A) 

40991204 McAllister, W. (1984) Resmethrin: Acute Toxicology of Scourge to Rainbow 

Trout (Salmo gairdneri) (432-667): Laboratory ID: 31370. Unpublished study 

prepared by Analytical Bio-Chemistry Labora- tories, Inc. 58 p. Scourge MF = 

46% PB + 18 % R

40991205 Bills, T.; Marking, L.; Dawson, V. (1985) Acute Toxicity of Pipe- ronyl Butoxide 

to Selected Species of Fish. Unpublished study prepared by US Fish & Wildlife 

Service. 158 p. Check Mayer and Ellersieck

41153301 McAllister, W. (1984) Resmethrin: Acute Toxicity of Scourge to Bluegill Sunfish 

(Lepomis macrochirus): Laboratory ID No. 31371: ABC Protocol No. 7601. 

Unpublished study prepared by Analytical Bio-Chemistry Laboratories, Inc. 58 

p.

42540302 Holmes, C.; Smith, G. (1992) A 96-hour Flow-through Acute Toxicity Test with 

Piperonyl Butoxide in the Bluegill (Lepomis macrochirus): Amended Final 

Report: Lab Project Number: 306A-101. Unpublished study prepared by 

Wildlife International Ltd. 195 p. 

42540303 Holmes, C.; Smith, G. (1992) A 96-hour Flow-through Acute Toxicity Test with 

Piperonyl Butoxide in the Rainbow Trout (Oncorhynchus mykiss): Amended 

Final Report: Lab Project Number: 306A-106: PWR3. Unpublished study 

prepared by Wildlife International Ltd. 191 p. 

43082302 Machado, M. (1994) Pyrenone Crop Spray (Sample Ref. 13650): A FlowThrough Acute Toxicity Test with Bluegill Sunfish (Lepomis macrochirus): Final 

Report: Lab Report Number 93/11/5008. Unpublished study prepared by 

Springborn Laboratories, Inc. 66 p. 

00031373 Taylor, R.E. (1967) To Determine the Toxicity of Sample on Tropical Fish,
90

Parakeets and Canaries. (Unpublished study received Dec 17, 1975 under 

1021-88; prepared by Harris Laboratories, Inc., submitted by McLaughlin, 

Gormley, King Co., Minneapolis, Minn.; CDL:221996-R) 

40094602 Johnson, W.; Finley, M. (1980) Handbook of Acute Toxicity of Chemicals to 

Fish and Aquatic Invertebrates: Resource Publi- cation 137. US Fish and 

Wildlife Service, Washington, D.C. 106 p.

40098001 Mayer, F.; Ellersieck, M. (1986) Manual of Acute Toxicity: Inter- pretation and 

Data Base for 410 Chemicals and 66 Species of Freshwater Animals. US Fish 

& Wildlife Service, Resource Pub- lication 160. 579 p.

72-2 Acute Toxicity to Freshwater Invertebrates

MRID Citation Reference

40991208 McAllister, W. (1984) Resmethrin: Acute Toxicology of Scourge to (Daphnia 

magna) (432-667): Laboratory ID: #31372. Unpublished study prepared by 

Analytical Bio-Chemistry Laboratories, Inc. 35 p.

40991209 Forbis, A. (1986) Acute Toxicity of Piperonyl Butoxide Technical to Daphnia 

magna: Laboratory ID: 34490. Unpublished study prepared by Analytical BioChemistry Laboratories, Inc. 43 p. 

42540301 Holmes, C.; Smith, G. (1992) A 48-hour Flow-through Acute Toxicity Test with 

Piperonyl Butoxide in Daphnids (Daphnia magna): Amended Final Report: Lab 

Project Number: 306A-105A. Unpublished study prepared by Wildlife 

International Ltd. 208 p. 

43858301 Ward, G. (1995) Scourge: Acute Toxicity to the Water Flea, Daphnia magna, 

Under Flow-Through Test Conditions: Lab Project Number: F602: J9308003D. 

Unpublished study prepared by Toxikon Environmental Sciences. 87 p. 

TN 870 USEPA Beltsville Animal Biology Lab study with Daphnia magna.

72-3 Acute Toxicity to Estuarine/Marine Organisms

MRID Citation Reference

00109941 Heitmuller, T. (1975) Acute Toxicity of Pyrenone to Pink Shrimp (Penaeus 

duorarum) and Fiddler Crabs (Uca pugilator). (Unpub- lished study received 

Sep 17, 1975 under 4816-178; prepared by Bionomics, EG & G, Inc., 

submitted by Fairfield American Corp., Medina, NY; CDL:165023-C) 

40991211 Ward, G. (1986) Acute Toxicity of Piperonyl Butoxide Technical to the Embryos 

and Larvae of the Eastern Oyster (Crassostrea vir- ginica): (432-209): 

Laboratory ID: D-EC86.2/PBT-OE. Unpublished study prepared by 

Environmental Science & Engineering, Inc. 28 p. 

40991213 Ward, G. (1984) Resmethrin: Acute Toxicity of Scourge to Pink Shrimp 

(Penaeus duorarum) and Sheepshead Minnow (Cyprinodon variegatus): (432-

667): Laboratory ID: #BP-84-3-19. Unpublished study prepared by Springborn 

Bionomics, Inc. 28 p. 
91

40991216 Surprenant, D. (1986) Resmethrin: Acute Toxicity of SBP-1382, 40 MF to 

Embryos-Larvae of the Quahog Clam (Mercenaria mercenaria): (432-596): 

Laboratory ID: # BW-86-12-2214. Unpublished study prepared by Springborn 

Bionomics, Inc. 33 p.

40991219 Ward, G. (1986) Acute Toxicity of Piperonyl Butoxide Technical to the Pink 

Shrimp (Penaeus duorarum): (432-209): Laboratory ID: D-ECBI.2/PS-PBT. 

Unpublished study prepared by Environmental Science & Engineering, Inc. 29 

p. 

40991220 Ward, G. (1986) Acute Toxicity of Piperonyl Butoxide Technical to the 

Sheepshead Minnow (Cyprinodon variegatus): (432-209): Lab- oratory ID: DECBI.2/SHM-PBT. Unpublished study prepared by Environmental Science & 

Engineering, Inc. 31 p. 

42540304 Holmes, C.; Smith, G. (1992) A 96-hour Flow-through Acute Toxicity Test with 

Piperonyl Butoxide in Sheepshead Minnow (Cyprinodon variegatus): Amended 

Final Report: Lab Project Number: 306A-108A: PWR3. Unpublished study 

prepared by Wildlife International Ltd. 207 p. 

42540305 Holmes, C.; Smith, G. (1992) A 96-hour Shell Deposition Test with Piperonyl 

Butoxide in the Eastern Oyster (Crassostrea virginica): Amended Final Report: 

Lab Project Number: 306A-110A: DBR31. Unpublished study prepared by 

Wildlife International Ltd. 208 p. 

42540306 Holmes, C.; Smith, G. (1992) A 96-hour Flow-through Acute Toxicity Test with 

Piperonyl Butoxide in Mysid Shrimp (Mysidopsis bahia): Amended Final 

Report: Lab Project Number: 306A-109: PWR3. Unpublished study prepared 

by Wildlife International Ltd. 206 p. 

43858302 Ward, G. (1995) Scourge: Acute Effect on New Shell Growth of the Eastern 

Oyster, Crassostrea virginica: Lab Project Number: J9308003F. Unpublished 

study prepared by Toxikon Environmental Sciences. 94 p. 

43901801 Roberts, C.; Swigert, J. (1995) Piperonyl Butoxide: A 96-Hour Flow Through 

Acute Toxicity Test with the Saltwater Mysid (Mysidopsis bahia): Final Report: 

Lab Project Number: SDR20: 306A-111A. Unpublished study prepared by 

Wildlife International Ltd. 46 p. 

00084053 Frederick, J.J. (1974) Toxicities of Some Mosquito Adulticides to Non-target 

Marine Organisms. (Monroe County (Florida), Mosquito Control District; 

CDL:221987-Q) 

72-4 Fish Early Life Stage/Aquatic Invertebrate Life Cycle 

Study

MRID Citation Reference

00031368 Rausina, G. (1974) Report to McLaughlin Gormley King Company: Four- Day 

Static Fish Toxicity Studies with X-2840-74 in Rainbow Trout and Bluegills: IBT 

No. 621-05281. (Unpublished study received Dec 17, 1975 under 1021-88; 

prepared by Industrial Bio-Test Laboratories, Inc., submitted by McLaughlin, 

Gormley, King Co., Minneapolis, Minn.; CDL:221996-M) Aldrin + Pipronyl 

Butoxide + Pyrethrins
92

00042583 Bentley, R.E. (1975) Acute Toxicity of Pyrenone O.T. 75-7.5 to Bluegill 

(?~Lepomis macrochirus~?) and Rainbow Trout (?~Salmo ?~gairdneri~?): 

NCT 589:61. (Unpublished study received Sep 18, 1980 under 279-482; 

prepared by Bionomics, EG&G, submitted by FMC Corp., Philadelphia, Pa.; 

CDL:243249-D) 

40991224 Bills, T.; Marking, L.; Dawson, V. (1986) Chronic Toxicity of Piperonyl Butoxide 

to Developing Rainbow Trout (Salmo gairdneri). Unpublished compilation 

prepared by US Dept. of the Interior, National Fishing Research Laboratory. 

142 p. 

41081901 McAliister, W. (1986) Early Life Stage Toxicity of ?Carbon|-Pipero- nyl Butoxide 

to Fathead Minnows (Pimephales promelas) in a Flow- through System: Final 

Report # 34562. Unpublished study pre- pared by Analytical Bio-Chemistry 

Laboratories, Inc. 38 p. 

42335902 or 

42538802

Holmes, C.; Smith, G. (1992) A Flow-through Life-Cycle Toxicity Test with 

Piperonyl Butoxide in Daphnids (Daphnia magna): Final Report: Lab Project 

Number: 306A-104. Unpublished study prepared by Wildlife International Ltd. 

224 p. 

43300301 Machado, M. (1994) Piperonyl Butoxide Technical Task Force Blend PB200-

The Toxicity to Fathead Minnow (Pimephales promelas) During an Early Lifestage Exposure: Amended Final Report: Lab Project Number: 94-5-5264: 

13513.0194.6102.120: 90/FIFRA/72-4/FM-ELS. Unpublished study prepared 

by Springborn Labs, Inc. 86 p. 

43311301 Putt, A. (1994) Piperonyl Butoxide Technical Task Force Blend PB200-The 

Chronic Toxicity to Daphnia magna under Flow-Through Conditions: Lab 

Project Number: 94-5-5270: 13513.0194.6101.130. Unpublished study 

prepared by Springborn Labs., Inc. 105 p. 

47860901 Cathcart, C. (2009) Waiver Request - Regarding Requirement for Mysid 

Chronic Toxicity Study for Piperonyl Butoxide. Unpublished study prepared by 

Piperonyl Butoxide Task Force II. 4 p.

72-5 Aquatic Field study

40695801 Sjogren, R. (1986) Results of Scourge and Resmethrin 40 MF Field Applications 

against Rainbow Trout in Aquaculture Ponds in Central Minnesota, September 

1986: Laboratory Project ID: LG402. Unpublished study prepared by Mosquito 

Control Technology in cooperation with Penick Bio UCLAF. 67 p. 

40695802 Pierce, R. (1986) Acute Toxicity of Scourge on Select Estuarine Organisms 

during Field Applications. Unpublished study prepared by Mote Marine 

Laboratory in cooperation with Louisiana State University. 21 p. 

141-1 Honey bee acute contact

MRID Citation Reference

41969009 Lynn, S.; Hoxter, K. (1991) An Acute Contact Toxicity Study With Piperonyl 

Butoxide with the Honey Bee: Lab Project Number: 306- 104. Unpublished study 
93

prepared by Wildlife International Ltd. 31 p. 

00140615 Johansen, C.; Eves, J. (1971) Bee Research Investigations, 1971: ?Sevin & 

Others|. (Unpublished study received Feb 3, 1972 under 1021-1026; prepared by 

Washington State Univ., Dept. of Ento- mology, submitted by McLaughlin 

Gormley King Co., Minneapolis, MN; CDL:005289-A) 

141-2 Honey bee residue on foliage

MRID Citation Reference

44501701 Hoxter, K.; Palmer, S.; Krueger, H. (1998) Scourge Insecticide: A Foliage 

Residue Toxicity Study with the Honey Bee: Lab Project Number: 312-111: 

CO97W500. Unpublished study prepared by Wildlife International Ltd. 28 p. 

47431601 Sindermann, A.; Porch, J.; Krueger, H. (2008) Multicide Fogging Concentrate 

2798: A Foliage Residue Toxicity Study with the Honeybee: Final Report. Project 

Number: 163/123, 163/080107/BFR/SUB16. Unpublished study prepared by 

Wildlife International Ltd. 37 p.

Piperonyl butoxide + Phenothrin + Prallethrin mixture

142-3 Simulated or Actual Field Testing

MRID Citation Reference

00107568 Schuyler, K.; Massing, R. (1973?) Observations on Ground ULV Appli- cations of 

Synergized Pyrethrins on Non-target Insects and Mosquitoes in Centre County, 

Pennsylvania. (Pennsylvania, Dept. of Environmental Resources, Bureau of 

Community Environmental Control; unpublished study; CDL:018069-B) 

850.4100 Terrestrial plant toxicity, Tier 1 (seeding 

emergence)

MRID Citation Reference

47431602 Porch, J.; Krueger, H. (2008) Multicide Fogging Concentrate 2798: A Toxicity 

Test to Determine the Effects of the Test Substance on Seedling Emergence of 

Ten Species of Plants: Final Report. Project Number: 163/124. Unpublished 

study prepared by Wildlife International Ltd. 58 p. Piperonyl butoxide + 

Phenothrin + Prallethrin mixture

850.4150 Terrestrial plant toxicity, Tier 1 (vegetative vigor)

MRID Citation Reference

47431603 Porch, J.; Krueger, H. (2008) Multicide Fogging Concentrate 2798: A Toxicity 

Test to Determine the Effects of the Test Substance on Vegetative Vigor of Ten 

Species of Plants: Final Report. Project Number: 163/125. Unpublished study 
94

prepared by Wildlife International Ltd. 79 p. Piperonyl butoxide + Phenothrin + 

Prallethrin mixture

Non Guideline Selections

00011488 Frederick, J.J. (1974?) Toxicities of some mosquito adulticides to non-target 

organisms. Pages 56-59,~In~Report of 45th Annual Meeting; 1974. Florida AntiMosquito Association. (Also ~?In~unpublished submission received Feb 8, 1977 

under 20954-1; submitted by Zoecon Corp., Palo Alto, Calif.; CDL:231486-AM) 

00042368

00042913

00110077

McLaughlin, Gormley, King Company, Incorporated (19??) Toxicity of Piperonyl 

butoxide to Warm-Blooded Animals. (Unpublished study received Nov 19, 1964 

under unknown admin. no.; CDL:104177-A) 

00081019 Baker, G.J. (1963) The dual synergist system of piperonyl butoxide and MGK 

264. Pyrethrum Post 7(1):16-18. (Also~In~unpublished submission received Jan 

5, 1966 under 6H1946; submitted by McLaughlin, Gormley, King Co., 

Minneapolis, Minn.; CDL:221620-H) 

00107551 Pimentel, D. (1971) Ecological Effects of Pesticides on Non-target Species. By 

Cornell Univ., Dept. of Entomology and Limnology. (S.l.): Executive Office of the 

President, Office of Science and Technology. (Pages 66-67 only; available from: 

Superintend- ent of Documents, U.S. Government Printing Office, Washington, 

DC 20402; stock no. 4106-0029; published study; CDL:005501-B) 

00122493 Verece, R.; Malone, J. (1970) Inhalation and Dermal Toxicity of 

Bioallethrin/Piperonyl Butoxide and Pybuthrin Aerosol Formula- tions to Canaries 

and Budgerigars: Report Series B No. 82-70. (Unpublished study received Sep 

22, 1972 under 1021-1217; sub- mitted by McLaughlin Gormley King Co., 

Minneapolis, MN; CDL: 051098-G) 

42335901 Holmes, C.M. and G.J. Smith (1992) Determination of the Stability of Piperonyl 

Butoxide in Fresh and Salt Water. Project No. 306A-103. Prepared by Wildlife 

International Ltd., Eastern, MD. Submitted by Piperonyl Butoxide Task Force II, 

Washington, DC (EPA MRID No. 42335901)