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### Macleaya Extract – Table of Contents

I. Introduction ............................................................................................................... ...........3

A. General Background ....................................................................................................4

II. Scientific Assessments .................................................................................................... ....4

A. Human Health Assessment..........................................................................................5

B. Environmental Assessment .........................................................................................5

C. Endangered Species Assessment .................................................................................5

D. Use and Usage Information .........................................................................................6

E. Endocrine Disruptor Screening Program ..................................................................6

III. Proposed Interim Regist ration Review Decision ............................................................7

IV. Next Steps and Timeline ................................................................................................... 73 I. Introduction

This document is the Environmental Prot ection Agency’s (EPA or the Agency) Proposed Interim Registration Review Decision for macleaya extract and is being issued pursuant to 40 CFR sections 155.56 and 155.58. A registration review decision is the Agency’s determination whether a pesticide meets, or does not meet, the standard for registration in the Federal Insecticide, Fungicide, and R odenticide Act (FIFRA). The Agency may issue, when it determines it to be appropriate, a proposed interim registration review decision before completing a registration review. Among other thi ngs, the proposed interim registration review decision may (1) require new risk mitigation measures; (2) impose interim risk mitigation measures; (3) identify data or information required to complete the review; and (4) include schedules for submitting the required data, c onducting new risk assessments or revising preliminary assessments, and completing the re gistration review. For further information on macleaya extract, additional documents can be found in EPA’s public docket (EPA-HQ-OPP2011-0172) at www.regulations.gov

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FIFRA, as amended by the Food Quality Pr otection Act (FQPA) of 1996, mandated the continuous review of existing pest icides. All pesticides distributed or sold in the United States generally must be registered by the EPA based on sc ientific data showing that they will not cause

unreasonable risks to human health or to the environment when used as directed on product labeling. The registration review program is intended to make sure that, as the ability to assess and reduce risk evolves and as polic ies and practices change, all regi stered pesticides continue to meet the statutory standard of no unreasonable a dverse effects. Changes in science, public policy, and pesticide use practices will occur over time. Through the registration review program, the Agency periodically reevaluates pes ticides to make sure that as these changes occur, products in the marketplace can continue to be used safely. Information on this program is provided as www.epa.gov/oppsrrd1/registration_review/

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In 2006, the Agency implemented the regist ration review program pursuant to FIFRA section 3(g) and will review each registered pesticide every 15 years to determine whether it

continues to meet the FIFR A standard for registration.

Pursuant to 40 CFR Section 155.50, EPA forma lly initiated registration review for macleaya extract (case 7024). Th e following highlights significan t events that have occurred during the registration revi ew of macleaya extract:

 March 30, 2011 – Publication of the Macleaya Extract Summary Document for a 60-day public comment period. The Summary Document included the preliminary work plan (PWP) and was accompanied by the scoping document and problem formulation.

 August 17, 2011 - Final Work Plan (FWP) for macleaya extract was signed -- two public comments were received during the 60-day comment period for the Macleaya Extract Summary Document . However, the comments did not affect the risk assessments to be performed, or the projected registration re view timeline and thus, the FWP did not modify the Summary Document

.4  A Data Call-In (DCI) was issued in June 2012 for a number of human toxicity studies. The required studies were subsequently waived by the Hazard and Science Policy Council (HASPOC) in 2013 based on the Weight of Evidence (WOE) approach considering the following: 1) the limited exposure profile of macleaya extract; 2) there are no registered food uses of macleaya extr act at this time; 3) no exposure to macleaya extract is expected through dri nking water; 4) the use of an oral point of departure (POD) results in dermal margins of exposure (MOEs) that do not exceed the Agency’s level of concern (LOC) (MOEs >300 are below the Ag ency’s LOC) for highest occupational exposures (i.e., MOEs are greater than 3,600 and 440 for handlers and post-application workers, respectively); 5) the use of an oral POD results in inhalation MOEs that do not exceed the Agency’s level of concern for wo rkers (MOE greater than 13,000); and 6) the low vapor pressure and physical chemical pr operties of sanguinarine, a major component of macleaya extract. EPA completed the hum an health risk assessment for macleaya extract using available data and data from surrogate chemicals, sanguinaria extract and sanguinarine chloride. The preliminary human health and ecological risk assessments are

now available in the docket for this registration review along with this Proposed Interim Registration Review Decision and a public comment period for the three documents has

been initiated.

Additional information about m acleaya extract, including this Proposed Interim Registration Review Decision and the following supporting documents can be found in EPA’s public docket, EPA-HQ-OPP-2011-0172, accessed at www.regulations.gov

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 Macleaya Extract: Preliminary Risk Asse ssment for Registration Review. June 12,

2014.

 Registration Review: Preliminary Ecol ogical Risk Assessment and Endangered Species Effects Determination fo r Macleaya Extract. June 11, 2014.

A. General Background

Macleaya extract is a plant extract of Macleaya cordata , and is registered for use only in enclosed commercial greenhouses, as an ornament al plant fungicide for the control of foliar fungal diseases. There are no registered food uses of macleaya extract. The only end use formulation of macleaya extract is a soluble/concen trate liquid. It is applied as a foliar spray by backpack or high pressure sprayer and has no residential uses. Macleaya extract was first registered in 2002 and therefore wa s not subject to reregistration.

II. Scientific Assessments

A summary of the Agency’s human health risk assessment a nd ecological risk

assessment, Macleaya Extract: Preliminary Risk A ssessment for Registration Review (June 12, 2014) and Registration Review: Pr eliminary Ecological Risk Assessment and Endangered Species Effects Determination for Macleaya Extract (June 11, 2014) , is presented below. For the actual assessments, see the macleaya extrac t public docket (EPA-HQ-OPP-2011-0172) accessed

at www.regulations.gov

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Hazard Characterization

The toxicological database is considered ade quate for characterizing hazard and assessing risk from macleaya extract. A poi nt of departure (POD) was iden tified for occupational exposure only.

Dietary Exposure Assessment
There are no registered food/feed uses and existing use patterns are not expected to contaminate surface or ground water; thus, a di etary exposure assessment was not conducted.

Food Tolerances

There are no U.S. tolerances established for macleaya extract because macleaya extract is not registered for any food/feed uses.

Residential and O ccupational Exposure

Macleaya extract has no register ed residential uses; residentia l exposures are, therefore, not expected. The only end use fo rmulation of macleaya extract is a liquid concentrate and it is applied as a foliar spray by backpack or hi gh pressure sprayer in enclosed commercial greenhouses. Although exposure may occur during occupational handling and post-application activities, a screening level assessment based on maximum application rates and baseline attire

indicated no risk of concern vi a dermal and inhalation routes of exposure. Furthermore, the current label requires all handlers to wear personal protective equipment (i.e., chemical-resistant gloves in addition to baseline attire ) and includes a restri cted entry interval of 12 hours, which is considered to be adequately protective. Theref ore, EPA concludes that risk from occupational exposure to macleaya extract will not be of concern. ( Macleaya Extract: Preliminary Risk Assessment for Registration Review, June 12, 2014)

B. Environmental Assessment

The Agency previously concluded in a 1999 review that the enclosed commercial greenhouse use for macleaya extract does not provide a feasible route of e xposure to non-target organisms, and therefore would not result in any significant exposure or risk to non-target organisms. As the use pattern has not changed since the previous review in 1999, the Agency concluded that a quantitative ecological ri sk assessment and a drinking water exposure assessment were not necessary for the regi stration review of macleaya extract.

C. Endangered Species Assessment

There is no reasonable expecta tion for registered use of m acleaya extract in enclosed commercial greenhouses to cause dir ect or indirect adverse effect s to threatened and endangered species. No adverse modification of critical habita t is expected from the use of macleaya extract. Based on the indoor-only use pattern for macleaya extract and the lack of a complete exposure pathway, EPA has made a “no effects” determ ination under the Endange red Species Act (ESA) for all listed species as well as a “no habitat modification” de termination for all designated

critical habitats for the current ly registered use of macleaya ex tract. The Agency has therefore

concluded that consultation with the Fish and Wildlife Service and the National Marine Fisheries6 Service under ESA section 7(a)(2) is not re quired. EPA anticipates conducting no further analysis of potential risks to endangered or threatened species, unless data or information are obtained during the Registration Review process that would indicate such an assessment would be needed to inform the Agency’s decision. ( Registration Review: Prelim inary Ecological Risk Assessment and Endangered Species Effects Determ ination for Macleaya Extract, June 11,

2014 )

D. Use and Usage Information

Use of macleaya extract was not reported in the National Agricultural Statistics Service (NASS) nursery and floriculture usage su rveys conducted in 2002, 2004, or 2007. In addition, usage was not reported in the 2006-2008 California Department of Pesticide Regulation pesticide usage reports. Macleaya extract wa s not reported in these surveys indicating that the usage of this chemical is likely to be low.

Macleaya extract can be used in or ganic production of greenhouse ornamentals 1 . There

are no known resistance concerns for the macleaya extract end use product. Please see the BEAD Chemical Profile for Registration Review: Macleaya Extract in the registration review docket for

more details.

E. Endocrine Disruptor Screening Program

EPA has developed the Endocrine Disruptor Screening Program to determine whether certain substances (including pesticide active an d 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 Admi nistrator may designate.” Under FFDCA section 408(p), the Agency must screen all pesticide chemical s. Between October 2009 and November 2010, EPA

issued test orders/data call-ins for the first group of 67 chemicals and published a second list of chemicals proposed for order issuance in the future. Macleaya extract was not among the group of 58 pesticide active ingredients on the initial li st nor is it proposed on the second list of

chemicals to be screened under the EDSP. Accord ingly, as part of registration review, EPA will issue future EDSP orders/data call-ins for regi stration review chemicals, including macleaya

extract. For further information on the status of the EDSP, the policies and procedures, the list of 67 chemicals, future chemical lists proposed fo r screening, the test gui delines and the Tier 1 screening battery, plea se visit our website: http://www.epa.gov/endo/

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In the interim, EPA is making no human health or environmental safety findings associated with the EDSP screening of macleaya extract. Before completing this Registration Review, the Agency will make an EDSP FFDCA section 408(p) determination.

1 Copping, L.G. and Duke, S.O. 2007. Natural products that have been used commercially as crop protection agents. Pest Management Science 63:524-554.7 III. Proposed Interim Registration Review Decision

Per the macleaya extract Preliminary Work Pl an, EPA has completed a human health and an ecological risk assessment, as part of regist ration review. The Agency is, therefore, issuing a Proposed Interim Registration Review Decisi on pursuant to 40 CFR Sections 155.56 and 155.58. The registration review timeline in the Macleaya Extract Final Work Plan projected that the Agency would issue the prelimin ary risk assessments in the fa ll of 2015 and issue the proposed registration review decision in the spring of 2016. However, since EPA waived the data requirements that were initially anticipated for use in the human health risk assessment, the Agency was able to complete qualitative human health and ecological risk assessments earlier than projected. Also, since the preliminary human health and ecological risk assessments indicate no risks of concern, the Agency has decided to instead issue for public comment this Proposed Interim Registration Review Decision concurrently with the preliminary risk assessments. The anticipated timeframes for the registration revi ew of macleaya extract were revised and the Agency now anticipates issuing an Interim Registrati on Review Decision in late 2014.

In accordance with 40 CFR Sections 155.56 and 155.58, the Agency is issuing this Proposed Interim Registration Review Decision document. Except for the EDSP component of the macleaya extract registration review case, the Agency has made the following Proposed Interim Registration Review Decision: (1) no additional data are required at this time; and (2) no changes to the affected registra tions or their labeling are need ed at this time. EPA has not identified any risks of concern to human health. EPA has determined that use of macleaya extract in commercial greenhouses should not result in any si gnificant exposure or risk to non-target organisms. As such, EPA concludes “no effect” fo r listed species and no adverse modification of designated critical habitat for all currently registered uses of macleaya extract.

IV. Next Steps and Timeline

A Federal Register Notice will announce the availability of this Proposed Interim Registration Review Decision for macleaya extract and the preliminary risk assessments and allow a 60-day comment period. If there are no significant comments or additional information submitted to the docket during the comment period th at leads the Agency to change its decision, EPA may issue an Interim Registration Revi ew Decision for macleaya extract (case 7024). However, a final decision for macleaya extract may be issued without having previously issued an Interim Registration Review Decision. A fina l decision on the macleaya extract registration

review case will occur after an FFDCA secti on 408(p) EDSP determination has been made.