Docket Number EPA

- HQ

- OPP

- 2010

- 0498

www.regulations.gov



## Piperonyl Butoxide Final Work Plan Registration Review

May 20113

Introduction

This is the Environmental Protection Agency’s (EPA’s) Final Work Plan for the registration review

of piperonyl butoxide . This work plan includes the expected registration review timeline. The work plan also addresses public comments received concerning the Preliminary Work Plan in the Summary Document , which was posted in the piperonyl butoxide registration review docket ( EPA

HQ

- OPP

- 2010

- 0 498 ), and any other comments concerning the initial docket postings. The Summary Document provided information on what EPA knows about the pesticide and what additional risk analyses and data or information the Agency believes are neede d to make a registration review decision.

The Agency is implementing the registration review program pursuant to Section 3(g) of the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA), and will review each registered pesticide every 15 years to d etermine whether it continues to meet the FIFRA standard for registration. Changes in science, public policy, and pesticide use practices will occur over time. The registration review program is intended to make sure that, as the ability to assess risk e volves and as policies and practices change, all registered pesticides continue to meet the statutory standard. The public phase of registration review begins when the initial docket is opened for each case. Information on this program is provided at: http://www.epa.gov/oppsrrd1/registration_review/

.

Piperonyl butoxide (PBO) is a pesticide active ingredient that acts as a synergist, enhancing the pesticidal properties of other chemicals. It is registered for use in combination with insecticide and acaricide active ingredients, such as pyrethrins, synthetic pyrethroid s and organophosphate s, in a variety of agricultural and non

- agricultural sites. Registered residential uses include insect co ntrol inside and outside of the home, as well as direct applications to pets. Formulations and application methods are diverse. PBO was first registered in the United States in the 1950s. The Reregistration Eligibility Decision (RED) for PBO was issued in 2006.

Comments Received on Preliminary Work Plan

Multiple comments were received during the 60

- day public comment period on the planned ecological assessment and human health scoping document discussed in the Preliminary Work Plan

. H owever, these com ments do not alter the Agency’s Preliminary Work Plan for the registration

review of PBO

. For further discussion on these comments please see the Summary of Comments and Agency Responses section of this document. In the Preliminary Work Plan , EPA also solicited comments on three specific topics: environmental justice, water body impairment, and trade irritants. No comments or information were received during the comment period concerning environmental justice or trade irritants, however, the Agency di d receive comments on potential impaired water bodies in Californi a (CA) attributed to PBO’s synergistic effect on other pesticides

.

Anticipated Risk Assessment and Data Needs The Agency anticipates requiring data considered necessary to conduct a com prehensive ecological risk assessment, including an endangered species risk assessment, and to update and revise the4

human health risk assessment for all uses of PBO

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

Ecological Risk:

Exposure to PBO from agricultural use will take place mainly in soil, sediment, and surface water, and from consumption of plants and other food items onto which it is sprayed. It may

also reach the aquatic environment and may pass through wastewater treatment plants where it may be included in wastewater discharge.

The Agency has not conducted an ecological risk assessment that supports a complete endangered species determination for PBO. The ecolo gical risk assessment planned during registration review will allow the Agency to determine whether PBO ’s use has “no effect” or “may affect” federally listed threatened or endangered species (listed species) or their designated critical habitats. When an assessment concludes that a pesticide’s use “may affect” a listed species or its designated critical habitat, the Agency will consult with the U.S.

Fish and Wildlife Service ( FWS ) and/or National Marine Fisheries Service (NMFS) (the Services), as appropriate.

A 2009 PBO Da ta Call

- in required a number of studies that will be considered in the PBO registration review ecological risk assessment.

Synergism studies examining the toxicity of t ypical e nd

- use p roducts containing PBO were required in the RED data call

- in ( DCI ) . Additional synergism data is anticipated in registration review to examine the effects of PBO when co

- applied with other pesticide active ingredients.

The Agency anticipates needing the following data in order to conduct a complet e ecological risk assessment, including an endangered species assessment for PBO :

Environmental fate data gaps

o G uideline No. 835.1230

– Adsorption/Desorption (batch equilibrium)

o G uideline No. 835.4100

– Aerobic soil metabolism

o G uideline No. 835.4 3 00

– Aerobic aquatic metab o lism

o G uideline No. 835.4 4 00

– A na erobic aquatic metab o lism

o Guideline No. 835.6100

– Analytical method for residues in soil and sediment

o Guideline No. 835.6200

– Analytical method for residues in water

o G uideline No. 875.2100

– Di slodgeable foliar residue (modified, total foliar dissipation data are required)5

Ecological toxicity data gaps

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

o G uideline No. 850. 302 0

– Honey bee acute contact toxicity

o G uideline No. 850.4100

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

o G uideline No. 850.4150

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

Studies Triggered by PBO’s Use as a Synergist

o G uideline No. 850. 1010

– Acute Freshwater Invertebrate Study

o G uideline No. 850. 1075

– Acute Freshwater Fish Study

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

o G uideline No. 850. 1400

– Fish early life stage (estuarine/marine)

o G uideline No. 850.2100

– Avi an acute oral toxicity (passerine species )

o G uideline No. 850.4400

– Aquatic vascular plant growth

– Lemna spp. Tier II 2

o G uideline No. 850. 5 400

– Aquatic non

- vascular plant growth T ier II 2

The Agency anticipates requiring the following data to use as an input to the Exposure and Fate Assessment Screening Tool’s ( E

- FAST) down

- the

- drain module to assess the amount of PBO that would degrade during treatment, remain in biosolids, or remain in waste water.

o Non

- G uideline

– Publicly

- owned Treatment Works (POTWs) Effluent Monitoring and POTW Treatability Study

Please refer to the December 13 , 2010 “ EFED Registration Review Problem Formulation for Piperonyl Butoxide

, ” for a more detailed discussion of the anticipated ecological risk

assessment and data nee ds.

Human Health Risk:

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

A 2009 PBO Da ta Call

- in required a number of studies that will be considered in the PBO registration review human health risk assessment.

The residential and occupational exposure assessments are adequate, but may be updated to reflect current standard operating procedures.

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

- in.

2 Registrants may opt to conduct a Tier I study, with the understanding that any adverse effects (even if <25%) will necessitate a Tier II study.6

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

the diet ary and/or residential exposure assessments.

Acute and s ubchronic neurotoxicity and immunotoxicity studies are required under 40 CFR Part 158 as a part of the new data requirements for registration of a conventional pesticide

. In the absence of required studies, EPA may use a database uncertainty factor of up to 10X. Once all of the newly required toxicity data have been received and subsequently reviewed, points of departure and safety factors may be reexamined and a new risk as sessment may be

conducted.

The Agency will re

- evaluate the tolerance expression for PBO during registration review to ensure it appropriately covers the metabolites and degradates of PBO and that it specifies

the residues to be measured for each commodi ty.

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

health risk assessment for PBO:

o Guideline No. 870.6200

– Acute and subchronic neurotoxicity

o Guideline No. 870.7800

– Immunotoxicity study

o Guideline No. 860.1900

– Field accumulation study in rotational crops

Please refer to the September 15, 2010 “ Piperonyl Butoxide Human Health Risk Scoping Document in Support of Registration Review ” available in the docket, for a detailed discussion of the anticipated

human health risk assessment and data needs.

Endocrine Disruptor Screening Program

As required by FIFRA and FFDCA, EPA reviews numerous studies to assess potential adverse outcomes from exposure to chemicals. Collectively, these studies include acute, s ubchronic and chronic toxicity, including assessments of carcinogenicity, neurotoxicity, developmental, reproductive, and general or systemic toxicity. These studies include endpoints which may be susceptible to endocrine influence, including effects on en docrine target organ histopathology, organ weights, estrus cyclicity, sexual maturation, fertility, pregnancy rates, reproductive loss, and sex ratios in offspring. For ecological hazard assessments, EPA evaluates acute tests and chronic studies that assess growth, developmental and reproductive effects in different taxonomic groups. As part of its most recent registration decision

, EPA reviewed these data and select ed the most sensitive endpoints for relevant risk assessment scenarios from the existing hazard database. However, as required by FFDCA section 408(p ), piperonyl butoxide is subject to the endocrine screening part of the Endocrine Disruptor Screening Prog ram (EDSP).

EPA has developed the 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 endo crine effects as the Administrator may designate.”7

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 de termine 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.

Under FFDCA section 408(p), the Agency must screen all pesticide chemicals. 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

. Piperonyl butoxide is

included on that list and h ave been issued an order to conduct the Tier 1 testing. Once all required Tier 1 and Tier 2 data have been received and reviewed, the endpoints and safety factors used for risk assessment purposes will be examined and a new risk assessment performed if neces sary. For further information on the status of the EDSP, the policies and procedures, the list of 67 chemicals, future lists, the test guidelines and the Tier 1 screening battery, please visit our website: http://ww w.epa.gov/endo/

.

Timeline

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

butoxide registration review. One year has been added to the projected timeline in cluded the Preliminary Work Plan. In the Prelimina ry Work Plan, the time frame between issuing the DCI and data submission was projected to be two years. However, one of the anticipated data requirements, f

ield accumulation study in rotational crops (Guideline No. 860.1900)

, is actually a three year stud y

.

Registration Review for Piperonyl Butoxide

– Projected Registration Review Timeline

Activities Estimated Date Opening the docket Open Docket and Public Comment Period 2010

– December

Close Public Comment 2011

– February Case Development

Final Work Plan 2011

– May

Issue DCI 2012

– Jan.

– March

Data Submission 201 5

– Jan.

- March Open Public Comment Period for Preliminary Risk Assessments 2016

– July

– Sept.

Close Public Comment Period 2016

– Oct.

– Dec. Registration Review Decision8

Open Public Comment Period for Proposed Registration Review

D ecision 2017

– Jan.

– March

Close Public C omment P eriod 2017

– Apr.

- June Registration Review D ecision and Begin P ost

- D ecision F ollow

- up 201 7 Total ( years ) 7

Summary of Comments and Agency Responses

The piperonyl butoxide registration review docket was open for a 60

- day comment period beginning

on December 22 , 2010. The comments received did not result in a change to the Agency’s Preliminary Work Plan for PBO

.

The Piperonyl Butoxide Ta sk Force II , a group composed of the PBO technical registrants,

commented on the human health risk assessment work plan. They requested a description of changes made within the last 5 years to EPA’s risk assessment methodologies, and asked the Agency

to p rovide a list of the data requirements specified in the RED DCI which remain outstanding. The

Task Force submitted multiple comments on the e cological data requirements and requested

information on the ecological risk assessment approach for other active ingredients co

- applied with

PBO. Clarification has been provided in the response to comments documents.

The California Regional Water Quality Control Board and the California Stormwater Quality Association provided comments in support of the additional data the Agency is seeking to assess the risks from the synergism of PBO. They cited a study that suggests PBO spray drift contributed to the synergism of pyrethroids already present in C alifornia waterways. The Agency made note of the

comments

.

The Physicians Committee for Responsible Medicine commented on potential alternative methods for conducting some of the anticipated toxicity studies. T he Agency responded that the studies

propos ed would be considered during registration review

.

The public comments and the two Agency response document s
, “ Piperonyl Butoxide: Response to Comments on the Human Health Assessment Scopi ng Document in Support of Registration Review ,”

dated April 14, 20 11 , and “ EFED Response to Public Comments on Registration Review Problem Formulation for Piperonyl Butoxide

, ” dated May 5, 2011, are available in docket EPA

- HQ

- OPP

2010

- 0684

.

Next Steps

The A gency plans to issue a Data Call

- in for PBO in 2011 . The information received in response to this DCI will be used to conduct the planned human health, ecological risk, and endangered species

assessment s for PBO

.9

Summary of Data Needs for the registration review of PBO

Guideline

Number Data Requirement Test

Material Estimated

Timeframe (Months)

835.1230 Adsorption/Desorption (batch equilibrium) TGAI 12

835.4100 Aerobic soil metabolism TGAI 24

835.4300 Aerobic aquatic metabolism TGAI 24

835.4400 Anaerobic aquatic metabolism TGAI 24

835.6100 Analytical method and Independent Laboratory

Validation for residues in soil and sediment TGAI 24

835.6200 Analytical method and Independent Laboratory

Validation for residues in water TGAI 24

850.1010 Acute Freshwater Invertebrate Study TEP 24

850.1075 Acute Freshwater Fish Study TEP 24

850.1400 Fish early life stage (estuarine/marine) TGAI 12

850.2100 Avian acute oral toxicity (passerine species) TGAI 12

850.3020 Honey bee acute contact toxicity TEP 12

850.4100 Terrestrial plant toxicity, Tier II (seeding

emergence) 1 TEP 12

850.4150 Terrestrial plant toxicity, Tier II (vegetative vigor) 1 TEP 12

850.4400 Aquatic vascular plant growth

– Lemna spp. Tier II 2 TGAI 12

850.5400 Aquatic non

- vascular plant growth Tier II 2 TGAI 12

860.1900 Field accumulation study in rotational crops 3 TGAI 36

870.6200 Acute and subchronic neurotoxicity TGAI 12

870.7800 Immunotoxicity TGAI 12

875.2100 Dislodgeable foliar residue (modified, total foliar

dissipation data are required) TGAI 12

Non

- GDLN POTW Effluent Monitoring TGAI 12

Non

- GDLN POTW Treatability Study TGAI 12

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

- in.

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

3 This study may be waived depending on the results of the confined accumulation in rotational crops study (Guideline 860.1850), which was included in RED Data Call

- in.