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Table of Contents

Contents

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

II. Scientific Assessments............................................................................................................ 5

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

Hazard Characterization.......................................................................................................... 5

Dietary Exposure Assessment................................................................................................. 5

Residential and Occupational Exposure ................................................................................. 5

Aggregate Risks...................................................................................................................... 5

Food Tolerances...................................................................................................................... 5

Human Incidents..................................................................................................................... 5

B. Environmental Assessment ................................................................................................... 6

Environmental Fate, Exposure, and Risk................................................................................ 6

Endangered Species Assessment ............................................................................................ 6

Ecological Incidents................................................................................................................ 6

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

III. Proposed Interim Registration Review Decision................................................................. 8

IV. Next Steps and Timeline...................................................................................................... 8
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I. Introduction

This document is the Environmental Protection Agency’s (EPA or the Agency) Proposed Interim 

Registration Review Decision for piperalin 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 require new 

risk mitigation measures, impose interim risk mitigation measures, identify data or information 

required to complete the review, and include schedules for submitting the required data, 

conducting the new risk assessment and completing the registration review. For further 

information on piperalin, additional documents can be found in EPA’s public docket (EPA-HQOPP-2009-0483) 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.

The first pesticide product containing piperalin was registered in 1964 for use to treat powdery 

mildew fungal infections of ornamental plants in greenhouses. Currently, piperalin is registered 

exclusively for use to control powdery mildew on ornamental plants, shrubs, vines, and trees 

grown in commercial greenhouses and other similar enclosed structures with nonporous 

coverings. There are no registered outdoor or residential uses. The Reregistration Eligibility 

Decision document (RED) for piperalin was completed in 1994. 

Pursuant to 40 CFR section 155.50, EPA formally initiated registration review for piperalin (case 

3114) in 2009. The following highlights significant events that have occurred during the 

registration review of piperalin:

 September, 2009 - Publication of Piperalin 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.
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 March, 2010 - Final Work Plan (FWP) for Piperalin was issued -- no public comments 

were received during the 60-day comment period for the Piperalin PWP; thus, the FWP 

did not modify the PWP.

 September, 2010 – Generic Data Call-In (GDCI) for Piperalin issued, requiring a number 

of human health toxicity studies. Because of the low toxicity of piperalin, after additional 

analysis all studies were waived. 

 March, 2014 – The Agency published the Preliminary Ecological Risk Assessment for the 

Registration Review of Piperalin and the Registration Review Preliminary Human Health 

Risk Assessment for Piperalin for a 60-day public comment period. One comment in 

support of EPA’s No Effects determination was received from the Center for Biological 

Diversity during the comment period.

 September, 2014 – The Agency is now publishing the Piperalin Proposed Interim 

Registration Review Decision, dated September 24, 2014 in docket number EPA-HQOPP-2009-0483 for a 60-day public comment period.

Additional information on piperalin can be found in EPA’s public docket, EPA-HQ-OPP2009-0483, accessed at www.regulations.gov.
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II. Scientific Assessments

A. Human Health Assessment

A summary of the Agency’s human health risk assessment is presented below. The Agency used 

the HED scoping document, its supporting documents, and the most updated Agency science 

policies and risk assessment methodologies to prepare a qualitative risk assessment in support of 

the registration review of piperalin. The most recent human health risk assessment was 

conducted in March, 2014. For a detailed discussion, see the Piperalin: Qualitative Preliminary 

Risk Assessment for Registration Review, published in March, 2014 in the public docket EPAHQ-OPP-2009-0483, which can be accessed on http://www.regulations.gov/. 

Hazard Characterization 

The toxicology database is limited but sufficient for assessing risks from piperalin. No 

toxicological endpoints of concern have been identified for risk assessment based on its low 

toxicity, limited exposure scenarios, and the low percentage active ingredient in the product. 

Acute toxicity studies range from toxicity category III or IV. 

Dietary Exposure Assessment

Based on the use pattern, dietary exposure from food and drinking water is unlikely to occur.

Therefore, no dietary assessment is needed.

Residential and Occupational Exposure

Based on the registered uses, there are no residential exposures for piperalin; therefore, a 

residential exposure assessment is not needed.

A screening level occupational handler and post-application risk assessment indicated all risk via 

the dermal and inhalation routes of exposure were below the level of concern.

Aggregate Risks

The potential for residential exposure is low because the registered uses are limited to 

commercial greenhouses and/or other confined structures. Therefore, aggregate exposure 

assessments were not needed.

Food Tolerances 

There are no food uses for piperalin and there are no tolerances or exemptions from tolerances 

for piperalin.

Human Incidents

A review of the Main and Aggregate Incident Data System (IDS) in February 2014 for the time 

period from January 1, 2009 to February 11, 2014 indicates that there are no reported human

incidents associated with the use of piperalin. A review of the National Institute of Occupational 
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Safety and Health Sentinel Event Notification System for Occupational Risks (NIOSH 

SENSOR-Pesticides), for the time period from 1998 to 2010, indicates that there was one 

incident in which the product Pipron® was associated with a low-severity, work-related 

occurrence of pruritis (itchy skin) in California in 2001. These incident data indicate that the risk 

posed to human health by piperalin is minimal and there does not appear to be a concern at this 

time that would warrant further investigation.

B. Environmental Assessment

A summary of the Agency’s environmental risk assessment for piperalin is presented below. For 

detailed discussions of all aspects of the environmental risk assessment, see the Registration 

Review: Preliminary Ecological Risk Assessment and Endangered Species Effects Determination 

for Piperalin published on March 4, 2014 in the public docket EPA-HQ-OPP-2009-0483, which 

can be accessed on http://www.regulations.gov/. 

Environmental Fate, Exposure, and Risk

The single registered use of piperalin is for ornamental (non-food) crops in an enclosed, indoor 

greenhouse environment with an impermeable roof, and as such, there is a lack of a complete 

exposure pathway from the use site to non-target terrestrial and aquatic organisms. 

In addition to an incomplete exposure pathway based on the use pattern, piperalin has a low total 

usage amount nationally and a relatively limited geographic use. Therefore, EPA has determined 

that a full ecological risk assessment for piperalin is not necessary based on de minimis exposure.

The expectation of no exposure, and therefore no risk, to non-target organisms in this assessment 

is based on the presumption that piperalin use is limited to indoors, as is specified on the label. 

Endangered Species Assessment

There is no reasonable expectation for any registered use of piperalin to cause direct or indirect

adverse effects to threatened and endangered species. No adverse modification of critical habitat 

is expected from the use of piperalin. This is because piperalin is registered for use solely in

commercial greenhouses and other similar enclosed structures with nonporous coverings. EPA 

has made a “no effect” determination under the Endangered Species Act (ESA) for all listed 

species and designated critical habitat for such species and has therefore concluded that 

consultation with the Fish and Wildlife Service and the National Marine Fisheries Service under 

ESA section 7(a)(2) is not required.

Ecological Incidents

A review of the Ecological Incident Information System (EIIS) maintained by the Agency’s 

Office of Pesticide Programs (OPP) in January 2014 indicates that there are no reported 

ecological incidents associated with the use of piperalin. A review of OPP’s Incident Data 

System (IDS) in February 2014 indicates that there was one incident in which the product 

Pipron® was associated with minor damage to plants. A search of the American Bird 

Conservancy’s Avian Incident Monitoring System (AIMS) Database in January 2014 did not 
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indicate any reported incidents in birds involving the use of piperalin. In general, an absence of 

reported incidents cannot be construed as the absence of incidents though. 

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, subchronic 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 endocrine 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 for piperalin, EPA reviewed 

these data and selected the most sensitive endpoints for relevant risk assessment scenarios from 

the existing hazard database. However, as required by FFDCA section 408(p), piperalin is

subject to the endocrine screening part of the Endocrine Disruptor Screening Program (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 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. 

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. A second list of 

chemicals identified for EDSP screening was published on June 14, 20131 and includes some 

pesticides scheduled for Registration Review and chemicals found in water. For further 

information on the status of the EDSP, the policies and procedures, the lists of chemicals, future 

lists, the test guidelines and the Tier 1 screening battery, please visit our website.i2 

In the interim, EPA is making no human health or environmental safety findings associated with 

the EDSP screening of piperalin. Before completing this Registration Review, the Agency will 

make an EDSP FFDCA section 408(p) determination.

 

1 See http://www.regulations.gov/#!documentDetail;D=EPA-HQ-OPPT-2009-0477-0074 for the final second list of 

chemicals.

2 http://www.epa.gov/endo/
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III. Proposed Interim Registration Review Decision

In accordance with 40 CFR Sections 155.56 and 155.58, the Agency is issuing this proposed 

interim registration review decision document. EPA’s proposed Interim Registration Review 

Decision determination for piperalin is that (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. In addition, 

EPA does not expect piperalin to have direct or indirect adverse effects to non-listed and listed 

species or to adversely modify any designated critical habitat for such species and has made a 

“no effect” determination under the Endangered Species Act (ESA) for all listed species and 

designated critical habitat for such species. This proposed interim decision does not cover the 

EDSP component of the piperalin registration review case. 

In the Registration Review: Preliminary Ecological Risk Assessment and Endangered Species 

Effects Determination for Piperalin, additional label language was suggested to clarify the 

intended use directions for the piperalin product, Pipron. There was some uncertainty about the 

potential for runoff from contaminated potting soil or water discharged from a greenhouse that 

could produce runoff capable of entering any irrigation or drainage ditch, canal, or other body of 

water. After receiving additional use information from the piperalin registrants and confirming 

the information with EPA’s Biological and Economic Analysis Division, EPA believes that 

given the current use patterns of piperalin and the low national usage, risk of exposure from 

water discharge or potential runoff from contaminated potting soil is low. Piperalin is applied to 

the upper surface of leaves, so little residue is expected to be contained within the potting soil or 

other growing media. Runoff from greenhouses is not likely to reach surface waters, as piperalin 

binds tightly to soil. Over ninety percent of piperalin is applied in California; many California 

greenhouses employ a variety of good management practices aimed at minimizing the impact of 

water discharge from greenhouses, such as run-off water quality monitoring, collection and 

recycling, and improved irrigation methods.3 Therefore, EPA is not proposing to require any 

additional labeling changes for products containing piperalin.

IV. Next Steps and Timeline

A. Interim Registration Review Decision

A Federal Register Notice will announce the availability of this Proposed Interim Registration 

Review Decision for piperalin 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 piperalin (case 3478). However, a final decision for piperalin may be issued without 

having previously issued an interim decision. A final decision on the piperalin registration 

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

3 Nurseries Surveyed in Southern California Adopt Best Practices for Water Quality. Mangiafico, Salvatore S. 

California Agriculture. January, 2010.