2

Propylene Oxide (PPO) Preliminary Work Plan – Table of Contents

Overview 4

Anticipated Data Needs 5

Statutory and Regulatory Authority 7

Chemical Facts 7

Use and Usage Information 8

Recent Actions 9

Anticipated Risk Assessments for Registration Review 10

Timeline 12

Next Steps 12

Appendix – Additional Areas Considered in the PPO Registration Review 13

References:

This Preliminary Work Plan summarizes the Environmental Protection Agency's current position 

based on the following documents:

1. Registration Review: Preliminary Problem Formulation for Environmental Fate and 

Ecological Risk, Endangered Species, and Drinking Water Assessments for Propylene 

Oxide (PPO). Stephen Carey, He Zhong. August 8, 2013.

2. Propylene Oxide. Human Health Assessment Scoping Document in Support of Registration 

Review. Thurston Morton, Angela Howard, Susan V. Hummel, Ivan Nieves. September 5, 

2013.

3. Propylene Oxide: Review of Human Incidents. Elizabeth Evans, Shana Recore. April 17, 

2013.

4. BEAD Chemical Profile for Registration Review: Propylene oxide (042501). Leonard 

Yourman, Sepehr Haddad, John Faulkner. May 23, 2012. 

5. PRD Label Data Report: Food/Feed & Non-Food/Non-Feed Uses Considered in 

Registration Review Work Planning. January 15, 2013.
3

These and other supporting documents for the Propylene Oxide (PPO) registration review case 

may be found in the docket EPA-HQ-OPP-2013-0156 at http://www.regulations.gov.
4

OVERVIEW

The docket for propylene oxide (PPO) is now open, initiating the first public comment period for

this registration review (docket number EPA-HQ-OPP-2013-0156). Propylene oxide is 

registered for use as an insecticidal fumigant on several foods such as processed spices, dried 

garlic and onion, cocoa (beans and powder), in-shell and processed nutmeats (except peanuts), 

figs, raisins, and prunes. Nonfood uses include those on cosmetics, non-edible gums, ores, 

packaging, pigments, pharmaceutical materials, and discarded nut shells prior to disposal. In 

addition, there is a label claim that PPO aids in the control of microbiological spoilage and it is 

used as a sterilant on food and nonfood products for this purpose. This Preliminary Work Plan 

(PWP) document explains what EPA's Office of Pesticide Programs knows about PPO, 

highlighting anticipated data and assessment needs, identifying the types of information that 

would be especially useful to the Agency in conducting the review, and providing an anticipated 

timeline for completing the registration review for PPO.

The registration review process was designed to include a public participation component to 

solicit input from interested stakeholders. The Agency intends, by sharing this information in the 

docket, to inform the public of what it knows about PPO and what types of new data or other 

information would be helpful for the Agency to receive as it moves toward a decision on PPO. 

The Agency encourages all interested stakeholders to review the PWP and Appendix and to 

provide comments and additional information that will help the Agency’s decision-making 

process for this chemical. In addition to general areas on which persons may wish to comment, 

there are some areas identified in the PWP and Appendix about which the Agency specifically 

seeks comments and information. Interested stakeholders could include: environmental nonprofit or interest groups; pesticide manufacturers; agricultural labor or commodity groups; 

commercial, institutional, residential, and other users of pesticides; or the public at large.

The Preliminary Work Plan begins by listing the anticipated data needs for PPO. Next, it 

discusses the statutory and regulatory authority for registration review. Then the document 

provides chemical facts, use and usage information, recent actions, the anticipated risk 

assessments, and a projected registration review timeline for PPO. Finally, the Appendix to this 

document includes identification and discussion of some areas that are considered generally in 

registration review along with some additional chemical case-specific information.
5

ANTICIPATED DATA NEEDS

Table 1 below summarizes anticipated data needs for PPO. For additional discussion of the 

anticipated data needs, see the Propylene Oxide Human Health Assessment Scoping Document in 

Support of Registration Review and Registration Review: Preliminary Problem Formulation for 

Environmental Fate and Ecological Risk, Endangered Species, and Drinking Water Assessments 

for Propylene Oxide (PPO).

Table 1: Anticipated Data Needs for the Propylene Oxide (PPO) Registration Review

Guideline 

Number1 Study Title1

Test Material

Estimated 

Timeframe

(Months from 

receipt of DCI)

Anticipated Data Needs for the Parent PPO

NonGuideline Avian acute inhalation toxicity TGAI 24

NonGuideline Honeybee acute vapor exposure toxicity TGAI 24

NonGuideline Terrestrial plant toxicity TEP 12

875.1400 Inhalation indoor exposure TEP 24

875.1700 Product use information TEP 12

875.2500 Inhalation exposure study2 TEP 24

NonGuideline Acute inhalation toxicity study - rodent TGAI 24

NonGuideline Monitoring data on fumigated commodities TEP 24

NonGuideline Ambient air monitoring TEP 36

Anticipated Data Needs for Propylene Chlorohydrin (PCH), Reaction Product

870.6200 Acute neurotoxicity - rat Reaction Product 12

870.3700 Prenatal developmental toxicity – rat and rabbit Reaction Product 24

Outstanding Data Requirements from GDCI-042501-266273

 1 On June 27, 2012, EPA announced certain revisions in harmonized guideline series 850 – Ecological Effects Tests 

– including renumbering and other designations or changes for some guideline studies. See “Final Test Guidelines; 

OCSPP 850 Series; Notice of Availability” 77 FR 38282, June 27, 2012. 

http://www.regulations.gov/#!documentDetail;D=EPA-HQ-OPPT-2009-0154-0028

2 This study is needed to assess post-application exposures for workers within and near structural fumigation 

facilities/operations or who work with treated commodities/materials.

3 The studies listed in this section were previously required through a generic data call-in issued in August 2006 and 

are still outstanding. These studies will not be included in the anticipated Registration Review DCI because they 

are already required through the earlier DCI. The Agency is working with the registrant to follow up on the 

overdue study. 
6

Table 1: Anticipated Data Needs for the Propylene Oxide (PPO) Registration Review

Guideline 

Number1 Study Title1

Test Material

Estimated 

Timeframe

(Months from 

receipt of DCI)

860.1650 Submittal of analytical reference standards PAI, residue of 

concern

Due August 

2008

TGAI = technical grade active ingredient; TEP = typical end-use product
7

STATUTORY AND REGULATORY AUTHORITY

The Food Quality Protection Act (FQPA) of 1996 mandated a registration review program. All 

pesticides distributed or sold in the United States (U.S.) generally must be registered by the 

Environmental Protection Agency (EPA or the Agency), based on scientific data showing that 

they will not cause unreasonable risks to human health or the environment when used as directed 

on product labeling. The registration review program is intended to make sure 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 or the 

environment. 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 change occurs, products in the marketplace can be used safely. Information on this 

program is provided on EPA’s website.

4

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 determine whether it continues to meet the FIFRA standard for 

registration. The regulations governing registration review begin at 40 CFR 155.40. The 

Agency will consider benefits information and data as required by FIFRA. The public phase of 

registration review begins when the initial docket is opened for each case. The docket is the 

Agency’s opportunity to state what it knows about the pesticide and what additional risk analyses 

and data or information it believes are needed to make a registration review decision. After 

reviewing and responding to comments and data received in the docket during this initial 

comment period, the Agency will develop a Final Work Plan (FWP) and anticipated schedule for 

the registration review of PPO.

CHEMICAL FACTS

Table 2 provides a summary of the chemical facts for PPO.

Table 2: Chemical Facts for PPO

PC code 042501

Case Number 2560

CAS Number 75-76-9

Year first registered 1982 

Pesticide Type Insecticidal fumigant and sterilant 

Chemical class Alcohol/Ether (Epoxide)

Reregistration Eligibility 

Decision (RED)

July 2006, amended September 2008 and June 2009

Tolerance Reassessment 

Eligibility Decision 

(TRED)

Not Applicable 

Cumulative group Not Applicable. PPO has not been identified as a member of a 

cumulative group that shares a common mechanism of toxicity. 

 4 http://www.epa.gov/oppsrrd1/registration_review/
8

Table 2: Chemical Facts for PPO

40 CFR Citation Tolerances for PPO are established in 40 CFR §180.491.

Dual-use There is a label claim that PPO aids in the control of microbial 

spoilage and it is used for this purpose. The assessment of the food 

use of PPO as an insecticidal fumigant will cover the antimicrobial 

use.

Non-pesticidal uses PPO is used primarily as a chemical intermediate in the production 

of other compounds, including polyurethane polyols, propylene 

glycols, glycol ethers, di- and tri-propylene glycols, and 

miscellaneous compounds; as well as for preparation of lubricants, 

surfactants, and oil emulsifiers. 

Pesticide Re-evaluation 

Division, Chemical 

Review Manager

Garland Waleko, waleko.garland@epa.gov, 703-308-8049

Antimicrobials Division Seiichi Murasaki, murasaki.seiichi@epa.gov, 703-347-0163

Registration Division, 

Product Manager

Shaja Joyner, joyner.shaja@epa.gov, 703-308-3194

USE AND USAGE INFORMATION

Table 3 summarizes the use and usage information for PPO. Please see the BEAD Chemical 

Profile for Registration Review: Propylene oxide (042501) in the registration review docket for 

more details.

Table 3: PPO Use and Usage Information

Summary of Use PPO is an insecticidal fumigant with food and non-food uses, 

targeting beetles, moths, and grain borers. There is also a label 

claim that PPO aids in the control of microbial spoilage, and it is 

used as a sterilant on food and non-food products for this purpose 

against mold, bacteria, fungi, and microbes.

Use Sites 100% PPO is used in sealed vacuum chambers.

8% PPO is used in non-sealed structures including trailers, 

containers, rail cars, tarped materials and tents. 

Agricultural commodities include: processed spices, dried garlic 

and onion, cocoa (beans and powder), in-shell and processed 

nutmeats (except peanuts). The 8% PPO product is also used on 

figs, dried plums (prunes), and raisins.

Non-agricultural commodities include: cosmetic articles, non-edible 

gums, ores, packaging, pigments, pharmaceutical materials, and 

discarded nut shells prior to disposal.

Summary of Usage The California Department of Pesticide Regulation (CDPR) 

reported that a total of 300,000 lb of PPO was used in California in 

2010. No private market research or proprietary data is available on 

usage. However, as stated in the 2006 RED, an estimated 64.8 

million pounds of commodities were annually treated with PPO, 
9

Table 3: PPO Use and Usage Information

primarily on nutmeats (1.8% commodity treated) and spices (1% of 

commodity treated). 

Formulation Type(s) Pressurized gas

Application Method(s) Applied indoors or outdoors as a gas in vacuum sealed chambers, or 

in unsealed chambers or other structures such as atmospheric 

chambers, tents, tarped product, rail cars and shipping containers. 

Technical Registrant(s) Aberco, Inc. 

No. of Registrations 3 Section 3 products5 (1 technical and 2 end-use products)

Restricted Use Yes 

Guidance for Commenters: Additional areas of use and usage related information

requested for this registration review, and of particular interest to EPA, are described below.

• There are uncertainties regarding PPO usage, treatment facilities, and treatment 

conditions, including: maximum number of treatment chambers, frequency of treatment, 

volumes treated, concentration/time schedules used, air exchange rates, types of emision 

control device, release height, and historical emissions data. In addition, there is a lack of 

information on the building/structure type used for the fumigation, such as dimensions

and number/relative locations of stacks/vents that serve as the release points during 

aeration operations. Without further information, EPA expects to use conservative 

assumptions to approximate these parameters in order to conduct a quantitative risk 

assessment. However, the Agency will work with registrants to clarify information on 

PPO product labels.

• Confirmation of the following label information: sites of application; formulations;

application methods and equipment; maximum application rates; frequency of 

application, application intervals, and maximum number of applications per season; and 

geographic limitations on use.

• Use distribution (e.g., geographical distribution of relevant use sites).

• Median and 90th percentile reported use rates (lbs ai/A) from usage data – national, state, 

and county.

• Usage/use information for non-agricultural uses.

• State or local use restrictions.

• Foreign technical registrants not listed above who supply technical PPO to the US 

market.

RECENT ACTIONS

The RED was signed in July 20066

, and was amended in September 20087 and June 20098. The 

product reregistration process, which starts after completion of a RED, is complete for PPO. All 

 5 Section 3 product labels can be obtained from the Pesticide Product Label System (PPLS) website 

(http://oaspub.epa.gov/pestlabl/ppls.home). 6 http://www.regulations.gov/#!documentDetail;D=EPA-HQ-OPP-2005-0253-0044 7 http://www.regulations.gov/#!documentDetail;D=EPA-HQ-OPP-2005-0253-0070; 

http://www.regulations.gov/#!documentDetail;D=EPA-HQ-OPP-2005-0253-0075
10

labels have been updated to reflect the mitigation outlined in the RED, which is available in the 

docket at EPA-HQ-OPP-2005-0253. 

No new uses have been registered since the RED was issued. Tolerances for pine nuts were

added in May 2012 (77 FR 28493) as a technical correction and to cover already registered uses 

on raw nuts. In 2007, tolerances were established for figs, prunes, and raisins (72 FR 49646). 

The use on edible gums was deleted on registrations in October 2006 (71 FR 61463), and the use 

on birdseed was voluntarily canceled in September 2006.

ANTICIPATED RISK ASSESSMENTS FOR REGISTRATION REVIEW

The most recent comprehensive human health risk assessment for PPO was completed in June

2006 in preparation for the RED, and an updated dietary exposure analysis was completed in 

October 2011 to address tolerances on pine nuts. The most recent ecological and environmental 

fate risk assessment was completed in June 2006 for the RED. Findings and conclusions from 

these risk assessments are summarized in the Propylene Oxide Human Health Assessment 

Scoping Document in Support of Registration Review and the Registration Review: Preliminary 

Problem Formulation for Environmental Fate and Ecological Risk, Endangered Species, and 

Drinking Water Assessments for Propylene Oxide (PPO). 

During registration review, the Agency anticipates the need to conduct a comprehensive

ecological risk assessment, including an endangered species assessment, for all uses of PPO. For 

human health, EPA anticipates the need to conduct revised dietary, residential, aggregate, and 

occupational risk assessments during registration review. If toxicological endpoints or points of 

departure are revised based on the data that are anticipated to be required for registration review, 

they will be considered in the new assessments, as well as any changes to the standard operating 

procedures or default exposure assumptions.

Table 4 below summarizes the anticipated registration review risk assessments based on the 

EFED Problem Formulation and HED Scoping Document.

Table 4: Anticipated Risk Assessments for the PPO Registration Review

Type of Risk Assessment Conduct? Notes

Ecological and Environmental Fate

Comprehensive ecological 

(species to be assessed 

include terrestrial organisms) 

including endangered species

Y Only the parent PPO will be assessed. There is no 

evidence that degradates will form substantially in air 

for terrestrial non-target exposure. Aquatic non-target 

exposure will not be assessed because of PPO’s 

volatility and short retention time in water. 

Incidents Will check for 

updates

There are no reported incidents. For a discussion of 

reported ecological incidents for PPO, see page 13 of 

the Problem Formulation.

Human Health

Dietary

 8 http://www.regulations.gov/#!documentDetail;D=EPA-HQ-OPP-2005-0253-0077
11

Food Y A new dietary exposure risk assessment may be 

required during Registration Review to incorporate 

potential changes to the PPO and PCH toxicological 

points of departure (PODs), updated consumption 

information, and utilization of the newest version of 

DEEM-FCID.

Drinking water N PPO is unlikely to have detectable residues for both 

parent and degradates in surface water and ground 

water.

Occupational

Handlers (mixers, loaders, 

applicators)

Y A new occupational handler risk reassessment may be 

completed during registration review to incorporate

the most recent exposure data, Agency policies, or if 

toxicological reevaluation of PPO results in changes 

to endpoints. 

Post-application Y Tasks for workers near fumigation

facilities/operations need to be defined in order to 

assess post-application activities. Potential exposures 

due to off-gassing will also be assessed for workers 

conducting post-application activities near treatment 

operations.

Residential

Handlers N There are no residential uses of PPO.

Post-application N There are no residential uses of PPO.

Bystander Y Additional or revised residential bystander risk 

assessments may be necessary based on the most 

recent exposure data, Agency policies, or if the 

toxicological reevaluation results in changes to the 

endpoints. Additional use information requested 

above under the Use and Usage Information –

Guidance for Commenters section would refine this 

analysis. 

Other

Aggregate Y Evaluates the combined risk from dietary and 

residential exposures. Aggregate risk assessments 

may be required during registration review because 

residential bystander exposure may be assessed. 

Cumulative N EPA has not made a common mechanism of toxicity 

finding as to PPO and any other substance, and has

also not assumed that PPO has a common mechanism 

of toxicity with other substances.

Tolerances Y The tolerance expression for propylene oxide will be 

reviewed during registration review to ensure that it 

appropriately covers metabolites and degradates and 

that it specifies the residues to be measured for each 

commodity; modifications will be made as needed.
12

Incidents Will check for 

updates

No cases involving PPO were identified. For a 

discussion of reported human incidents for PPO see 

page 10 of the Scoping Document and Propylene 

Oxide: Review of Human Incidents.

Guidance for Commenters: Additional ecological information requested for this 

registration review, and of particular interest to EPA, is described below.

• Ecological incidents (non-target plant damage and avian, fish, reptilian, amphibian and 

mammalian mortalities) not already reported to the Agency.

• Water quality monitoring data (see Appendix for further details).

TIMELINE

EPA has created the following estimated timeline for the completion of the PPO registration

review in Table 5 below.

Table 5: Projected PPO Registration Review Timeline

Activities Estimated Date

Opening the Docket

Open Docket and 60-day Public Comment Period 2013 – September 

Close Public Comment 2013 – November 

Case Development

Final Work Plan 2014 – February

Issue DCI 2014 – April - June

Data Submission 2017– April - June

60-day Public Comment Period for Draft Risk 

Assessments9

2018 – Oct. – Dec. 

Registration Review Decision

60-day Public Comment Period for Proposed 

Registration Review Decision

2019 – April - June

Registration Review Decision and Begin Post-Decision 

Follow-up

2020

Total (years) 7

NEXT STEPS

After the 60-day public comment period closes, the Agency will review and respond to any 

comments received in a timely manner and then issue a Final Work Plan for the registration 

review of PPO. 

 9 The regulations governing Registration Review generally require the Agency to provide a public comment period 

of at least 30 calendar days for draft risk assessments; see 40 CFR Part 155.53(c). For conventional pesticides, the 

Agency plans to provide a 60 calendar day public comment period generally for draft risk assessments.
13

Appendix – Additional Areas Considered in the PPO Registration Review

PUBLIC COMMENTS AND FEEDBACK:

Guidance for Commenters: The areas below highlight topics of special interest to the Agency 

where your comments, data submissions, or reference to sources of additional information could 

be of particular use.

Trade Irritants:

Through the registration review process, the Agency intends to solicit information on trade 

irritants and, to the extent feasible, take steps toward facilitating irritant resolution. The Agency 

will work to harmonize tolerances and international maximum residue limits (MRLs) and may 

modify tolerance levels to do so, when possible. Growers and other stakeholders are asked to 

comment on any trade irritant issues resulting from lack of MRLs or disparities between U.S. 

tolerances and MRLs in key export markets, providing as much specificity as possible regarding 

the nature of the concern. 

Water Quality:

PPO is not identified as a cause of impairment for any water bodies listed as impaired under 

section 303(d) of the Clean Water Act.

10 In addition, no Total Maximum Daily Loads (TMDLs) 

have been developed for PPO.

11 More information on impaired water bodies and TMDLs can be 

found at the Agency’s website.

12 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 Process13 in 

order to ensure they can be used quantitatively or qualitatively in pesticide risk assessments.

Environmental Justice:

EPA seeks to achieve environmental justice, the fair treatment and meaningful involvement of all 

people, regardless of race, color, national origin, or income, in the development, implementation, 

and enforcement of environmental laws, regulations, and policies. To help address potential 

environmental justice issues, the Agency seeks information on any groups or segments of the 

population who, as a result of their location, cultural practices, or other factors, may have 

atypical, unusually high exposure to PPO compared to the general population. Please comment 

if you are aware of any sub-populations that may have atypical, unusually high exposure 

compared to the general population.

 10 http://iaspub.epa.gov/tmdl_waters10/attains_nation_cy.cause_detail_303d?p_cause_group_id=885 11http://iaspub.epa.gov/tmdl_waters10/attains_nation.tmdl_pollutant_detail?p_pollutant_group_id=885&p_pollutant

_group_name=PESTICIDES

12 http://www.epa.gov/owow/tmdl/ 13 http://www.epa.gov/oppsrrd1/registration_review/water_quality_sop.htm
14

ENDANGERED SPECIES:

A risk assessment that supports a complete endangered species determination has not been 

conducted for PPO. The ecological risk assessment planned during registration review will allow 

the Agency to determine whether use of PPO 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 and/or National Marine 

Fisheries Service (the Services), as appropriate.

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 PPO, 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), PPO 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, 201314 and includes some 

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

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

chemicals.
15

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. 15

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

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

an EDSP FFDCA section 408(p) determination.

HUMAN STUDIES:

Chemical-specific Human Studies

Past PPO risk assessments have relied in part on an occupational human study which may have 

involved intentional exposure to PPO. In the course of registration review EPA will reconsider 

these studies, as well as any other research involving intentional exposure of human subjects to 

PPO brought to its attention. If EPA decides to rely on any of these studies, EPA will ensure that 

all applicable regulatory requirements are met, including, but not limited to, the requirements for 

EPA ethics review and Human Studies Review Board review of certain research involving 

intentional exposure of human subjects.

 15 http://www.epa.gov/endo/