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 Assessment s for Registration Review 10

Time line 12

Next Steps 12

Appendix

– Additional Areas Considered in the PPO Registration Review 13

References:

This Preliminary Work Plan summarize s 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 Chem ical 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 o xide (P PO) 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 proc essed nutmeats (except peanuts), figs, raisins, and prunes. N onfood uses include those on cosmetic s
, non

- edible gums, ores, packaging, pigments, pharmaceutical materials, and discarded nut shells prior to disposal. In

add ition, 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 EP A'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 com pleting 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, b y 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 Appen dix about which the Agency specifically

seeks comments and information. Interested stakeholders could include: environmental non

profit or interest groups; pesticide manufacturers; agricultural labor or commodity groups; commercial, institutional, reside ntial, 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 r egistration r eview. 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 consider ed generally in

r egistration r eview 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 Propylen e 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

Number 1 Study Title 1 Test Material Estimated

Timeframe

(Months from receipt of DCI)

Anticipate d Data Needs for the Parent PPO

Non

Guideline Avian acute i nhalation toxicity TGAI 24

Non

Guideline Honeybee acute vapor e xposure toxicity TGAI 24

Non

Guideline Terrestrial p lant t oxicity TEP 12

875.1400 Inhalation indoor exposure TEP 24

875.1700 Product use i nformation TEP 12

875.2500 Inhalation e xposure study 2 TEP 24

Non

Guideline Acute inhalation t oxicity study

- rodent T GAI 24

Non

Guideline M onitoring data on fumigated commodities TEP 24

Non

Guideline Ambient air monitoring TEP 36

Anticipated Data Needs f or Propylene C hlorohydrin (PCH), Reaction Product

870.6200 Acute n euro toxicity

- rat Reaction Product 12

870.3700 Prenatal d evelopmental toxicity

– rat and rabbit Reaction Product 24
Outstanding Data Requirements from GDCI

- 042501

- 26627 3

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 A vailability” 77 FR 38282, June 27, 2012. http://www.regulations.gov/#!documentDetail;D=EPA

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2 This study is needed to assess post

- application ex posures 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 stil l 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

Number 1 Study Title 1 Test Material Estimated

Timeframe

(Months from receipt of DCI)

860.1650 Submittal of analytical reference s tandards PAI , residue of

concern Du e August

2008 TGAI = technical grade active ingredient; TEP = typical end

- use product7 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 cau se 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 p esticides 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 Age ncy periodically reevaluates pesticides to make sure that as change occurs, products in the marketplace can be used safely. Informatio n 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

. T he 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 i n the docket during this initial comment period, the Agency will develop a F inal W ork P lan (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 Insect icid al fumigant and sterilant

Chemical class Alcohol/Ether ( Epoxide )

R eregistration Eligibility Decision (R E D) 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 a s a chemical intermediate in the production of other compounds, including polyurethane polyols, propylene glycols, gl y col 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

- 31 94

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 contro l 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 chamber s. 8% PPO is used i n non

- sealed structures including trailers, containers, rail cars, t arped materials and tents

. A gricultural commodities include : processed spices, dried garlic and onion, cocoa (beans and powder), in

- shell and proces sed nutmeats (except peanuts). The 8% PPO product is also used on figs, dried plums (prunes), and raisins

. N on

- agricultural commodities include : cosmetic articles, non

- edible gums, ores, packaging, pigments, pharmaceutical mater ials, and discarded nut shells prior to disposal

. Summary of Usage The California Depa rtment 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 proprie tary data is available on

usage . However, as stated in the 2006 RED, an estimated 64.8 million pounds of commodities were annually treate d 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 products 5 (1 technical and 2 end

- use products)

Restricted Use Yes

Guidance for Commente rs: Additi onal areas of use and usage related information requested for this registration r eview , and of particular interest to EPA, are described below.

• There are un certainties 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, type s 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 dimensio n s and number/ relative locations of stacks/ vents that serve as the release points during aeration operations. Without further infor mation, EPA expects to use conservative assumptions to approximate these parameters in order to conduct a quantitative risk

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

PPO product labels

.

• C onfirmation 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

.

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

.

• M edian and 90 th percentile reported use rates (lbs ai/ A ) from usage data

– national, state, and county

.

• Usage/use information for non

- agricultural uses

.

• S tate or local use re strictions

.

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

market

.

RECENT ACTIONS

The RED was signed in July 2006 6 , and was amended in September 2008 7 and June 2009 8 . The product reregistration process , which starts after completion of a RED, is complete for PPO. A ll

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

( http://oaspub.epa.gov/pestlabl/ppls.home ).

6 http://www.regulations.gov/#!documentDetail;D=EPA

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- 2005

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- 0044

7 http://www.regulations.gov/#!documentDetail;D=EPA

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- 2005

- 0253

- 0070 ; http://www.regulations.gov/#!documentDetail;D=EPA

- HQ

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- 0253

- 007510 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 f or 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 registrati ons in October 2006 (71 FR 61463)

, and t he 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

. T he most recent ecological and environmental fate risk assessment was completed in June 2006 for the RED . Findings and con clusions from

these risk assessments are summarized in the Propylene Oxide Human Health Assessment Scoping Document in Support of Registration Review a nd the Registration Review: Preliminary Problem Formulation for Environmental Fate and Ecological Risk, E ndangered Species, and Drinking Water Assessments for Propylene Oxide (PPO ).

During registration review, t he Agency anticipates the need to conduct a comprehensive ecological risk assessment, including an endangered species assessment, for all uses of PP O

. For human health, EPA anticipates the need to conduct revised dietary, residential

, aggregate, and occupational risk assessment s 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 assessment s
, as well as any changes to the standard operating

p rocedures or default exposure assumptions

.

T able 4 below summarizes the anticipated registration review r isk 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

Eco logical 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 Th ere 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

- 007711 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 c onsumption

information

, and utilization of the newest version of

DEEM

- FCID

. Drinking water N PPO is unlikely to have detectable residue s 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 T asks for workers near fumigat ion

facilities /operations n eed 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 treat ment 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 E valuates the combined risk from dietary and residential exposures. Aggregate risk asse ssments may be required during registration r eview 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 fo r PPO see

p a g e 10 of the Scoping Document and Propylene Oxide: Review of Human Incidents

.

Guidance for Commente rs: Additional ecological i nformation r equested for this registration r eview , and of particular interest to EPA, is described below.

• Ec ological incidents (non

- target plant damage and avian, fish, reptilian, amphibian and mammalian mortalities) not already reported to the Agency

.

• Water quality m onitoring data (see Appendix for further details)

.

TIMELINE

EPA has created the following esti mated timeline for the completion of the PPO registration

review in Table 5 below

.

Table 5: Projected PPO Registration Review Timeline

Activities Estimated Dat e 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

6 0

- day Public Comment Period for Draft Risk

Assessments 9 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 20 20

Total (years) 7

NEXT STEPS

After the 6 0

- 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 perio d

of at least 30 calendar days for draft risk assessments; see 40 CFR Part 155.53(c). For conventional pesticides, t he Agency plans to provide a 60 calendar day public comment period generally for draft risk assessment s

.13 

### Appendix

– Additional Areas Considered in the PPO Registration Review

PUBLIC COMMENTS AND FEEDBACK :

Guidan ce for C ommenters: The areas below highlight topics of special interest to the Agency where your comments, data submissions, or reference to sou rces of additional information c ould 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 r esidue limits (MRL s ) 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 market s, 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, n o Total Maximum Daily Load s (TMDL s ) 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 Process 13 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 popula tion 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 h igh exposure compared to the general population.

10 http://iaspub.epa.gov/tmdl_waters10/attains_nation_cy.cause_detail_303d?p_cause_group_id=885

11 http://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.htm14 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

t he 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 l isted 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 FFD CA, 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, reproduct ive, 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 rat es, 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 regi stration 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 “n aturally 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

chemical s, which contains 58 pesticide active ingredients and 9 inert ingredients. A second list of chemicals identified for EDSP screening was published on June 14, 2013 14 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 list s 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 envi ronmental 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 R eview Board review of certain research involving intentional exposure of human subjects.

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