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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 Registration Review Decision ............................................................7 

IV. Next Steps and Timeline ...................................................................................................7 
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I. Introduction 

This document is the Environmental Protection 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 Rodenticide 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 things, 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, conducting new risk assessments or revising 

preliminary assessments, and completing the registration 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. 

 FIFRA, as amended by the Food Quality Protection Act (FQPA) of 1996, mandated the 

continuous review of existing pesticides. All pesticides distributed or sold in the United States 

generally must be registered by the EPA based on scientific 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 policies and practices change, all registered pesticides continue to 

meet the statutory standard of no unreasonable adverse effects. Changes in science, public 

policy, and pesticide use practices will occur over time. Through the registration review 

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

In 2006, the Agency implemented the registration 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 FIFRA standard for registration. 

Pursuant to 40 CFR Section 155.50, EPA formally initiated registration review for 

macleaya extract (case 7024). The following highlights significant events that have occurred 

during the registration review 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 review timeline and thus, the FWP did not 

modify the Summary Document. 
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 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 extract at this time; 3) no exposure to macleaya 

extract is expected through drinking 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 Agency’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 workers (MOE greater than 13,000); and 6) the 

low vapor pressure and physical chemical properties of sanguinarine, a major component 

of macleaya extract. EPA completed the human 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 macleaya 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. 

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

2014. 

 Registration Review: Preliminary Ecological Risk Assessment and Endangered 

Species Effects Determination for 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 ornamental 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/concentrate 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 was not subject to reregistration. 

II. Scientific Assessments

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

assessment, Macleaya Extract: Preliminary Risk Assessment for Registration Review (June 12, 

2014) and Registration Review: Preliminary Ecological Risk Assessment and Endangered 

Species Effects Determination for Macleaya Extract (June 11, 2014), is presented below. For the 

actual assessments, see the macleaya extract public docket (EPA-HQ-OPP-2011-0172) accessed 

at www.regulations.gov. 
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A. Human Health Assessment 

 Hazard Characterization 

The toxicological database is considered adequate for characterizing hazard and assessing 

risk from macleaya extract. A point of departure (POD) was identified 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 dietary 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 Occupational Exposure 

Macleaya extract has no registered residential uses; residential exposures are, therefore, 

not expected. The only end use formulation of macleaya extract is a liquid concentrate and it is 

applied as a foliar spray by backpack or high 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 via 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 restricted entry interval of 12 hours, which is 

considered to be adequately protective. Therefore, 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 exposure 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 risk assessment and a drinking water exposure 

assessment were not necessary for the registration review of macleaya extract. 

C. Endangered Species Assessment 

There is no reasonable expectation for registered use of macleaya extract in enclosed 

commercial greenhouses to cause direct or indirect adverse effects to threatened and endangered 

species. No adverse modification of critical habitat 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” determination under the Endangered Species Act (ESA) 

for all listed species as well as a “no habitat modification” determination for all designated 

critical habitats for the currently registered use of macleaya extract. The Agency has therefore 

concluded that consultation with the Fish and Wildlife Service and the National Marine Fisheries 
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Service under ESA section 7(a)(2) is not required. 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: Preliminary Ecological Risk 

Assessment and Endangered Species Effects Determination 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 surveys 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 was not reported in these surveys indicating that the usage of this 

chemical is likely to be low. 

Macleaya extract can be used in organic production of greenhouse ornamentals1

. 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 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.” Under FFDCA section 408(p), the 

Agency must screen all pesticide chemicals. 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 list nor is it proposed on the second list of 

chemicals to be screened under the EDSP. Accordingly, as part of registration review, EPA will 

issue future EDSP orders/data call-ins for registration 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 for screening, the test guidelines and the Tier 1 

screening battery, please visit our website: http://www.epa.gov/endo/.

 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. 
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III. Proposed Interim Registration Review Decision

Per the macleaya extract Preliminary Work Plan, EPA has completed a human health and 

an ecological risk assessment, as part of registration review. The Agency is, therefore, issuing a 

Proposed Interim Registration Review Decision 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 preliminary risk assessments in the fall 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 review of macleaya extract were revised and the 

Agency now anticipates issuing an Interim Registration 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 registrations or their labeling are needed 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 significant exposure or risk to non-target 

organisms. As such, EPA concludes “no effect” for 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 that leads the Agency to change its decision, 

EPA may issue an Interim Registration Review 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 final decision on the macleaya extract registration 

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