Docket Number EPA-HQ-OPP-2013-0244 www.regulations.gov



## Ethylene Oxide Preliminary Work Plan

Registration Review: Initial Docket Case Number 2275

Approved 

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## September 2013

s Lewis Acting Director Antimicrobials Division

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# f>**~J n**  Richard P. Keigwin, Jr. Director Pesticide Re-evaluation Division

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### of61Page 2 of 61 Ethylene Oxide Registration Review Team

Human Health & Environmental Effects

Antimicrobials Division Donna Randall Srinivas Gowda Najm Shamim Siroos Mostaghimi Tim McMahon Timothy Leighton William Hazel

Environmental Fate and Effects Division Ed Odenkirchen Sujatha Sankula He Zhong Stephen Carey

Health Effects Division Ray Kent Angela Howard Sue Hummel Ivan Nieves Jessica Kidwell

Biological and Economic Analysis Division John Faulkner Sepehr Haddad Elizabeth Hill Leonard Yourman

Risk Management Seiichi Murasaki Susan Bartow Lance Wormell Cathryn Britton

Office of General Counsel Philip RossPage 3 of 61 

### Table of Contents
1 Introduction .................................................................................................................. ........... 5 1.1 Statutory and Regulatory Authority ................................................................................. 5 1.2 Case Overview ................................................................................................................. 6 1.3 Chemical Identification and Properties ............................................................................ 6 1.4 Use and Usage Profile ...................................................................................................... 9 1.4.1 Registrations ............................................................................................................. 9 1.4.2 Summary of Regist ered Uses .................................................................................... 9 1.4.3 Usage Information .................................................................................................. 11 1.5 Regulatory History ......................................................................................................... 12 1.5.1 Recent/Pending Regulatory Actions ....................................................................... 13 1.5.2 Tolerance Information ............................................................................................ 13 1.6 Incidents ..................................................................................................................... .... 14 1.6.1 Human Health ......................................................................................................... 14 1.6.2 Ecological ............................................................................................................... 14 2 Anticipated Data Needs ........................................................................................................ 14 3 Human Health Risk Assessment ........................................................................................... 16 3.1 Existing Toxicological Endpoints .................................................................................. 17 3.2 Dietary Exposure ............................................................................................................ 1 9 3.2.1 Dietary (Food - Conventional Uses) ....................................................................... 19 3.2.2 Dietary (Food - Antimicrobial Uses) ...................................................................... 20 3.2.3 Dietary (Drinking Water) ........................................................................................ 20 3.2.4 Residue Chemistry (Conventional and Antimicrobial Uses) .................................. 20 3.3 Occupational and Residential Exposures ....................................................................... 20 3.3.1 Occupational Exposure ........................................................................................... 20 3.3.2 Residential Exposures ............................................................................................. 23 3.4 Aggregate and Cumulative Exposure and Risk .............................................................. 24 3.4.1 Aggregate Exposures and Risk ............................................................................... 24 3.4.2 Cumulative Exposure and Risk ............................................................................... 25 4 Ecological Risk Assessment ................................................................................................. 25 4.1 Environmental Fate Assessment .................................................................................... 26 4.1.1 Clean Water Act ...................................................................................................... 26 4.2 Conceptual Models for Envir onmental Exposure Pathways .......................................... 26 4.3 Ecological Effects Assessment ....................................................................................... 27 4.3.1 Mechanism of Action .............................................................................................. 27 4.3.2 Measures of Effect (Ecotoxicology Endpoints) ...................................................... 27 4.4 Exposure Analysis Plan .................................................................................................. 29 4.4.1 Wildlife Exposure Estimates ................................................................................... 29 4.5 Effects Analysis Plan ..................................................................................................... 31 5 Endocrine Disruptor Screen ing Program (EDSP) ................................................................. 31 6 Guidance for Commenters .................................................................................................... 32 6.1 Preliminary Work Plan ................................................................................................... 32 6.1.1 Trade Irritants .......................................................................................................... 33 6.1.2 Water Quality .......................................................................................................... 33 6.1.3 Environmental Justice ............................................................................................. 33 6.1.4 Structure Activity Relationships ............................................................................. 33Page 4 of 61 6.1.5 Additional Information ........................................................................................... 34 7 Next Steps .................................................................................................................... ......... 35 8 References .................................................................................................................... ......... 36

Appendix A Toxicology Profile ............................................................................................... 38 Appendix B Environmental Fate ............................................................................................. 42 Appendix C Ecotoxicology Profile .......................................................................................... 46 Appendix D Product Chemistry ............................................................................................... 52 Appendix E Modeling Input Based on ETO Release Scenarios for Spices and Herbs ........... 54 Appendix F Output Example of AERSCREEN Estim ated Environmental Concentration (EEC) for ETO Release Scenario 2 .............................................................................................. 57

List of Tables Table 1 – Summary of Anticipated Risk Assessments and Data Needs: ETO ............................... 6 Table 2 – Anticipated Regist ration Review Schedule .................................................................... 6 Table 3 – Chemical Identification of ETO ..................................................................................... 7 Table 4 – Physical/Chemical, Fate and Transport Propertie s of ETO and Major Reaction Products....................................................................................................................... .................... 8 Table 5 – Summary of ETO Registered Uses ................................................................................. 9 Table 6. Maximum Rates for Registered Agricultural Uses of ETO ............................................ 11 Table 7 – Studies Anticipated as Needed for the Registration Review of ETO ........................... 15 Table 8 – Summary of Toxicological Doses and Endpoints for ETO, ECH, and EG Selected for Use in Past Human Ri sk Assessments .......................................................................................... 1 7 Table 9 – Summary of Medica l Facility SIC Codes ..................................................................... 21 Table 10 – ETO Air Concentrations from IMIS for All Medical SIC Codes ............................... 22 Table 11 – ETO Air Concentrations (ppm) from IMIS for All Available Medical SIC Codes (1988 to 2007) ................................................................................................................ ............... 22 Table 12 – ETO Air Concentrations for C ontract Sterilizatio n Facilities .................................... 23 Table 13 – Selected Ecological Effects E ndpoints for Risk Assessment of ETO ........................ 28 Table 14. AERSCREEN Modeling Scenarios and Data Summary .............................................. 30 Table 15 – ETO – Acute Toxicity ............................................................................................... .. 38 Table 16 – ETO – Subchronic, Ch ronic Toxicity Studies ............................................................ 38 Table 17. Environmental Fate Properties of ETO ........................................................................ 42 Table 18. Effects Data on ETO ................................................................................................. .... 48 Table 19. ECOSAR v1.11 Results for ETO ................................................................................. 48 Table 20. Summary of the Most Sensitive Endpoint s from Aquatic Toxicity Studies for EG (Degradate of ETO). ........................................................................................................... .......... 49

List of Figures Figure 1 – Conceptual Model for Ecological E xposure and Effects of ETO to Aquatic and Terrestrial Organisms.......................................................................................................... .......... 27 Figure 2. Proposed ETO air exposure scenario for the risk assessment. ...................................... 31Page 5 of 61 

## 1 Introduction

This document is the United States Environmen tal Protection Agency’s (USEPA, EPA or “the Agency”) Preliminary Work Plan (PWP) for et hylene oxide (ETO). The PWP document explains what EPA's Office of Pesticide Programs (OPP ) knows about ETO, highligh ting anticipated data and assessment needs, identifying th e types of information that would be especially useful to the Agency in conducting the review, and providing an anticipated timeline for completing ETO’s review. The registration review process was designed to include a publi c participation component to solicit input from interested stak eholders. The Agency intends, by sharing this information in the docket, to inform the public of what it knows ab out ETO and what types of new data or other information would be helpful for the Agency to receive as it moves toward a decision on ETO. The Agency encourages all interested stakeholde rs to review the PWP and to provide comments and additional information that will help th e Agency’s decision-making process for this chemical. 

## 1.1 Statutory and Regu latory Authority
The Food Quality Protection Act (FQPA) of 1996 mandated a regi stration review program. All pesticides distributed or sold in the United St ates generally must be registered by the USEPA based on scientific data showing that they will not cause unreasonable risk s to human health or the environment when used as directed on produc t labeling. The registra tion 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 environm ent. Changes in scien ce, 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. Inform ation on this program is provided at http://www.epa.gov/oppsrr d1/registration_review/

. The Agency is implementing the registration revi ew 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 th e FIFRA standard for registration. The regulations governing registra tion 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 registrati on review decision. After reviewing and responding to comments and data received in the docke t during this initial comment period, the Agency will develop and commit to a Final Work Plan (FWP) and anticipated schedule for the ETO Case. Documents associated with this regi stration review can be viewed at http://www.regulations.gov in docket EPA-HQ-OPP-2013-0244. Below is a summ ary of the issues relevant to this registration review case.Page 6 of 61 Table 1 – Summary of Anticipated Risk Assessments and Data Needs: ETO

Risk Assessment Assessment Necessary to Support Registration Review Date of Most Recent Assessment Type of Assessment Required Data Anticipated as Needed (See Table 7 for more detail) Dietary (food /drinking water) No (see 3.2) 2008 None None

Occupational Handler Yes 2008 Updated Toxicity Exposure Air monitoring

Residential Handler No (see 3.3.2) 2008 None None

Residental Post Application – Inhalation (bystander) Yes 2007 Updated Special acute inhalation toxicity study Aggregate & Cumulative No (see 3.4) 2008 None None

Tolerance Review Yes 2006 Updated None

Ecological Yes 2011 Section 18 Updated Ecotoxicity and air monitoring data
N/A = Not applicable Table 2 – Anticipated Regi stration Review Schedule Anticipated Activity Target Date* Completion Date Phase 1: Openin g the Docket Open Docket and 60-Day Comment Period for Preliminary Work Plan 2013-09 2013-09 Close Public Comment Period 2013-11 Phase 2: Case Development Issue Final Work Plan 2014-03 Issue Data Call-In (DCI) 2015-03 Receive Data to be Considered in Risk Assessment 2019-03 Open 30-Day Public Comment Period for Preliminary Risk Assessment(s) 2020-09 Close Public Comment Period 2020-10 Phase 3: Registration Review Decision and Implementation Open 60-Day Public Comment Period for Proposed Decision 2021-03 Close Public Comment Period 2021-05 Issue Final Decision 2021-09 Begin Post-Decision Follow-up 2021 Total (years) 8 *The anticipated schedule will be revised as necessary (e.g., need arising under the Endocrine Disruptor Screening Program with respect to the active ingredients in this case). 

## 1.2 Case Overview
The docket for the ETO Case (Cas e 2275) has been established at http://www.regulations.gov in docket number EPA-HQ-OPP-2013-0244. 

## 1.3 Chemical Identification and Properties
Table 3 presents the active ingredient to be assessed in Case 2275, ETO (PC Code 042301). ETO in its natural state is a colorless, highly reac tive, and flammable gas at room temperature and ambient pressure.Page 7 of 61 Table 3 – Chemical Id entification of ETO

Common Name Ethylene Oxide (ETO)

Chemical Name Oxirane Dihydrooxirene Dimethylene oxide Diethylene oxide Ethene oxide Oxacyclopropane Epoxyethane, 1,2- Epoxyethane Oxidoethane
IUPAC/CAS* Na me Oxirane

Classification Epoxide Oxirane Cyclic ether
PC Code 042301
CAS Number 75-21-8

Molecular Formula C 2 H 4 O H 2 COCH 2 Molecular Weight 44.052601 grams/mole (g/mole)

Molecular Structure:

*CAS: Chemical Abstracts Service; IUPAC: International Union of Pure and Applied Chemistry The ETO product chemistry and fate information (source: MRIDs 41531002, 42458502, 42466702, 42811401, 43053201, and EPI Suite v4.1) relevant to conducting a risk assessment is summarized in Table 4. Details of the environmen tal fate properties are discussed in Appendix B and product chemistry information in Appendix E. Three reaction products identified in open literature include ethylene bromohydrin (EBH), ethylene chlorohydrin (ECH), and ethylene glycol (EG) (USEPA 2008). Tabl e 4 also presents the chemical identification and chemical properties of these degradates. The halogenated reaction products, EBH and ECH, have been shown to result from fumigation of foods with ETO due to interaction with natu ral bromides and chlorides present in the food items. Residues of EBH and ECH are found in spices . At high sterilization concentrations, ETO reacts with moisture to form EG and, in the pr esence of sugars, glycol derivatives. Therefore, EBH, ECH, and EG were the chemicals of concern for dietary (oral) exposure and were assessed in the 2006 tolerance reassessment. Until 1991, EG was a registered a.i. for use as an air sanitizer/deodorizer, and is still an iner t ingredient in pesticide formulations.Page 8 of 61 Table 4 – Physical/Chemical, Fate and Tran sport Properties of ETO and Major Reaction Products

Common name Ethylene Oxide (ETO) Ethylene chlorohydrin (ECH) Ethylene bromohydrin (EBH) Ethylene Glycol (EG)

Chemical structure C H 2 C H 2 O H OH

Molecular Formula C 2 H 4 O C 2 H 5 ClO C 2 H 5 BrO C 2 H 6 O 2 Molecular Weight, grams/mole 44.053 80.514 124.965 62.068
IUPAC name Oxirane 2-chloroethanol 2-bromoethanol Ethane-1,2-diol CAS name Oxirane 2-chloroethanol 2-bromoethanol Ethylene glycol CAS # 75-21-8 107-07-3 540-51-2 107-21-1 PC Code 042301 600502 NA 042203, 800009 Melting point, degrees Celsius ( o C) -111.6 -89 -80 -12.9 Boiling point, o C 10.4 130 150 (EPISuite v4.10) 195 Density or specific gravity, grams/liter (g/L) at 25 o C 1.80 1.2015-1.2025 1.494 at 20 o C 1.1155

Water solubility, at 20°C Not available Not available Not available Not available

Vapor pressure 1255 mm Hg at 25 o C (EPI Suite, v4.10) 7.18 mm Hg at 25 o C (EPISuite v4.10) 2.06 mm Hg at 25 o C (EPI Suite, v 4.10) 0.0609 mm Hg at 25

o C (EPISuite 4.10) Henry’s Law Constant at 25 o C (atmm 3 /mole) 1.48E-04 (Conway et al 1983) 7.61E-07 (EPISuite v4.10) 4.12E-07 (EPISuite v4.10) 1.31E-07 (EPISuite v4.10)
Dissociation constant, pKa NA NA NA NA Soil Adsorption Coefficient (Koc), L/kg 4.662 (EPISuite v4.10) 3.39 (EPISuite v4.10) 4.374 (EPISuite v4.10) 0.2239 (EPISuite v4.10)
Sludge Adsorption, % removal 1.65 (EPISuite v4.10) 1.76 (EPISuite v4.10) 1.76 (EPISuite v4.10) 1.75 (EPISuite v4.10) Log Octanol/water partition coefficient (Log K ow ) at 25 o C -0.30 ( EPISuite v 4.10) 0.112 ( EPI Suite, V4.10) 0.23 ( EPISuite v4.10) -1.20 (EPISuite v 4.10)

Bioaccumulation Factor, L/kg-ww Not available Not available Not available Not available
UV/VIS absorption spectrum Not applicable, nonconjugated molecule Not applicable, nonconjugated molecule Not applicable, nonconjugated molecule Not applicable, nonconjugated molecule
Half-life in air (days) 39 (EPISuite v4.10) Not available Not available Not available
Activated Sludge Biodegradation, % removal Not available Not available Not available Not available

CAS = Chemical Abstracts Service; IUPAC = International Union of Pure and Applied Chemistry; NA = not applicable; UV = ultraviolet light; VIS = visible light O C H 2 CH 2 C H 2 C H 2 O H Cl

C H 2 C H 2 O H BrPage 9 of 61 

## 1.4 Use and Usage Profile

1.4.1 Registrations As of September 10, 2013, there were 24 registered products containing ETO . ETO is formulated and marketed as a pressurized gas or liquid. The end use formulations ar e all gas mixtures of ETO and other gases (e.g., carbon dioxi de) in varying concentrations.


### 1.4.2 Summary of Registered Uses Table 5 presents a summary of the registered uses of ETO that will be assessed in this registration review.

1.4.2.1 Agricultural Uses ETO is a commodity fumigant/sterilant regist ered for use to reduce microbials on whole and ground spices or other seasoning materials ( 40 CFR §180), and to fumigate beekeeping equipment (e.g., wooden ware, boxes and frames) in North Carolina. Sterilization/fumigation with ETO must be performed only in vacuum or gas tight chambers designed for use with ETO. It is applied by commercial applic ators only; there are no residentia l uses of ETO. It is used in vacuum chambers at full strength (100%) for he rbs and spices. The maximu m application rate is 500mg/L (or 31.22 lb a.i./1000 ft 3 ) in a sealed chamber (Table 6).

1.4.2.2 Non-Agricultural (Antimicrobial) Uses The registered antimicrobial uses of ETO incl ude the fumigation/sterilization of medical or laboratory equipment, pharmaceuticals, and aseptic packaging (21CFR §201); or to reduce the microbial load on cosmetics; and to sterilize ar tifacts, archival material, library objects, and musical instruments (40 CFR §180). Table 5 – Summary of ETO Registered Uses
EPA Registration

Number %ai Form Registration Type Use Site

7182-1 100 Pressurized
gas EP Medical/lab items; pharmaceuticals; p ackaging; spices; seasonings; artifacts, archival ma terial, library objects

36736-8 100 Pressurized
gas Technical Medical/lab items; pharmaceuticals; p ackaging; spices; seasonings; artifacts, archival ma terial, library objects

58779-5 100 Pressurized
gas Technical Medical/lab items; pharmaceuticals

67470-6 100 Pressurized
gas Technical Medical/lab items; pharmaceutical s; packaging; spices; cosmetics

67470-7 100 Pressurized
gas Technical Medical/lab items; pharmaceutical s; packaging; spices; cosmetics
36736-2 100 Liquid Technical Industrial and/or medical uses

73711-5 100 Pressurized
gas EP Surgical instruments; hospital instruments; oral and inhalation equipment; diagnostic instruments/equipment; hospital critical rubber/plastic items; hypodermic needles/syringes; veterinary hospital instruments

89514-1 100 Pressurized
gas EP Medical/lab items; pharmaceuticals; p ackaging; spices; seasonings; artifacts, archival ma terial, library objects

69340-8 98.06 Pressurized
gas EP Surgical instruments; hospital instruments; oral and inhalation equipment; diagnostic instruments/equipment; hospital critical rubber/plastic items; hypodermic needles/syringes; veterinary hospital instrumentsPage 10 of 61 EPA Registration

Number %ai Form Registration Type Use Site

69340-2 97 Pressurized
gas EP Surgical instruments; heat labile materials; oral and inhalation equipment; diagnostic instruments/equipment; hospital critical rubber/plastic items; hospital materials; first aid equipment; human face gear; contact lens

69340-7 97 Pressurized
gas EP Surgical instruments; hospital instruments; sterilizers; veterinary hospital instruments

69340-4 96 Pressurized
gas EP Surgical instruments; surgical prosthetic parts; hospital instruments; oral and inhalation equipment; diagnostic instruments/equipment; hospital critical rubber/plastic items; hospital materials; surgical dressings; hypodermic needles/syringes; veterinary hospital instruments

69340-6 96 Pressurized
gas EP Surgical instruments; hospital instruments; oral and inhalation equipment; diagnostic instruments/equipment; hospital critical rubber/plastic items; hypodermic needles/syringes; veterinary hospital instruments

69340-5 90 Pressurized
gas EP Surgical instruments; hospital instruments; oral and inhalation equipment; diagnostic instruments/equipment; hospital critical rubber/plastic items; hypodermic needles/syringes; veterinary hospital instruments

69340-1 89.4 Pressurized
gas EP Surgical instruments; hospital instruments; hospital critical equipment; heat labile materials; oral and inhalation equipment; diagnostic instruments/equipment; hospital critical rubber/plastic items; hospital materials; first aid equipment; veterinary hospital premises; veterinary hospital instruments; veterinary hospital critical equipment; human face gear; contact lens

36736-3 80 Pressurized
gas EP Medical/lab items; pharmaceuticals; p ackaging; spices; seasonings; artifacts, archival ma terial, library objects

36736-5 20 Pressurized
gas EP Medical/lab items; pharmaceuticals; p ackaging; spices; seasonings; artifacts, archival ma terial, library objects

36736-6 12 Pressurized
gas EP Medical/lab items; pharmaceuticals; p ackaging; spices; seasonings; artifacts, archival ma terial, library objects

67470-10 10.4 Pressurized
gas EP Hospital instruments; laboratory instruments; pharmaceutical equipment; pharmaceutical materials

36736-4 10 Pressurized
gas EP Medical/lab items; pharmaceuticals; p ackaging; spices; seasonings; artifacts, archival ma terial, library objects

67470-9 10 Pressurized
gas EP Medical/lab items; pharmaceuticals; packaging; cosmetics

67470-8 8.6 Pressurized
gas EP Medical/lab items; pharmaceuticals; packaging; cosmetics

36736-7 8.5 Pressurized
gas EP Medical/lab items; pharmaceuticals; p ackaging; spices; seasonings; artifacts, archival ma terial, library objects

NC950002 8.5 Pressurized
gas EP Bee keeping equipmentPage 11 of 61 Table 6. Maximum Rates for Registered Agricultural Uses of ETO

Use Method of Application Single Maximum Application Rate Application Conditions EPA Reg No.

Indoor Food: Processed herbs, spices and dried vegetables Sterilization chamber / Fumigation Chamber <500 mg/L (a.i.) (<8hrs) &

<500 mg/L (a.i.) (<16hrs) Evacuate the gas from the chamber using a sequence of not less than 1) 21 steam washes, 5.0 PSIA at 115oF and 2) 16 steam washes, 5.0 PSIA at 120oF 36736-2 (100% ai), 36736-3 (80% ai & 20% CO 2 ), 36736-4 (10% ai & 90% CO 2 ), 36736-5 (20% ai & 80% CO 2 ), 36736-6 (12% ai & 88% dischlorodifluormethane), 36736-7 (8.5% ai & 91.5% CO 2 ), 36736-8 (100% ai) & 67470-6 (100% ai)



### 1.4.3 Usage Information According to the Biological and Economic Analysis Division (BEAD) (USEPA 2013a), agricultural uses for ETO include processed herbs and spices (except basil), and processed vegetables (dried/dehydrated). Sterilization or fumigation with ETO must be performed in vacuum chambers with outside venting designed for use with ETO. The Agency estimated about 8.2 million pounds of ETO were used annually in the U.S. for commercial fumigation or sterilization of medical and laboratory items or equipment and about 800,000 pounds of ETO (approximately 10%) are used annually for fumiga tion of herbs and spices (USEPA 2008). ETO treated spices account for 40-85% of spices consumed in the U.S. (ASTA, 2005). The use for vegetable processing comprises less than 1% of the total annual usage. At the time of the 2008 RED, approximately 1,900 hospitals had in-house ETO sterilization chambers. Hospitals tend to have small self -contained units for ETO sterilization. Bulk sterilization occurs at contract sterilization facili ties that handle multiple pallet sterilizations. The scope of materials potentially ster ilized within these types of c ontract sterilization facilities is assumed to include medical devices (representin g the majority of use), musical instruments, library and museum artifacts, and cosmetic ingr edients. There were approximately 30 contract sterilization facilities in the Un ited States; 21 of thos e facilities represented 90 percent of the contract medical device ster ilization capacity in the Un ited States. In addition, many manufacturers of medical devices used ETO in-house to sterilize th eir products. ETO’s pesticidal use to reduce microbial loads on cosmetics is minimal (less than 1 percent of total ETO pesticidal use). At the time of the 2008 RED, there were approximat ely 9 contract steriliza tion facilities in the United States that treat both medi cal devices and spices and 6 cont ract sterilization facilities in the United States that only treat spices; each facili ty had 2 to 3 workers that are actively involved in the ETO treatment process in some capacity. The beekeeping use of ETO currently is limited to a state-managed facility in North Carolina. The North Carolina Department of Agricultu re and Consumer Affairs (NCDA&CS) uses 2 vacuum tight chambers designed for use with ETO. Both chambers are located outdoors. Approximately a half dozen employees in NC currently are involved with the ETO use for sterilization/fumigation of beekeeping equipment.Page 12 of 61 

## 1.5 Regulatory History
ETO was first registered as a pesticide in 1966. It has been us ed to treat food products since 1957. ETO is a FIFRA List B 1 reregistration pesticide thr ough the FIFRA amendments of 1988. ETO entered EPA’s Special Review proce ss in 1978 based on concern for potential developmental toxicity, mutageni city, and neurotoxic effects in workers. A Position Document 1 (PD1) was published in the Federal Register of January 27, 1978, to annou nce the initiation of the Special Review. In the early 1980s, the carcinogenicity of ETO became of concern and was added to the Special Review. On August 3, 2005, EPA opened the public docket with the preliminary risk assessments for ETO. The Agen cy completed its Reregistration Eligibility Decision (RED) for ETO in 2008 and addressed the major risks identified at that time due to occupational exposure, which included the workers who are exposed while th ey work to sterilize medical instruments and spices. A voluntary requ est to terminate the use of ETO on basil was published in the Federal Register of October, 2008 and the cancelation order followed on May 20, 2009 2

. EPA’s Office of Research and Development (ORD), National Center for Environmental Assessment (NCEA) is re-evaluating the carcinogenic potential of ETO as pa rt of the Integrated Risk Information System (IRIS) program review . The Special Review is still open, pending the outcome of this review. The timeline and projec ted dates for this re-assessment are posted at: http://cfpub.epa.gov/ncea/iristrac/index.cfm?f useaction=viewChemical.showChemical&sw_id=1 004

. The Occupational Safety and Health Administra tion (OSHA) regulates wo rker exposure to ETO. In 1984, OSHA reduced the permissible exposure limit (PEL) from 50 ppm to 1 ppm. In 1988, OSHA established a short-term exposure limit (S TEL) of 5 ppm for exposures up to 15 minutes. In 1996, EPA required pesticide product label improvements to standardize precautionary statements, specify items to be treated with ETO, and require all user s to adopt OSHA’s risk reduction measures. The EPA’s Office of Air and Radiation (OAR ) promulgated ETO emission standards for sterilization facilities on December 6, 1994. The rule regulate s major commercial sterilization facilities and area sources requiring the appl ication of Maximum Achievable Control Technology (MACT) and/or Generally Availa ble Control Technology (GACT). OAR assessed risks from residual ETO emissions after the app lication of MACT standards to determine if further control was warranted. After conducting th is review, OAR determined that no additional control requirements were warranted. OAR issued a final decision for ETO emissions standards for sterilization facilities on April 7, 2006 (available at http://www.epa.go v/fedrgstr/EPATOX/2006/April/Day-07/t3314.htm ). More recently, OAR analyzed ETO emissions from hospital sterilizers. OAR issued a final ru le for hospital emissions on December 28, 2007 (available at http://www.epa.gov/fedrgstr/EPA-A IR/2007/December/Day-28/a25233.htm ). The final rule required that all hospi tals that do not cont rol their emissions of ETO reduce emissions by sterilizing full loads of equi pment to the extent possible.

1 http://www.epa.gov/oppsrrd1/registration_review/
2 http://www.regulations.gov/#!document Detail;D=EPA-HQ-OPP-2008-0722-0001 and http://www.regulations.gov/#!documen tDetail;D=EPA-HQ-OPP-2008-0722-0025Page 13 of 61 The Food and Drug Administration (FDA) is an im portant federal partner in ETO regulation. For ETO’s medical uses, FDA reviews the efficacy of ETO in the sterilization of a wide variety of medical devices and approves ETO sterilizers for medical use. Ster ilization methods available in the United States for the steril ization of medical devices and regulated by FDA fall into two categories. The first category incl udes sterilization methods used in health care facilities to resterilize devices designed for reuse in patient care. The second general cat egory of sterilization subject to FDA regulation is the sterilization of manufactured medical devices (Murphy, 2006). For ETO’s spice uses, FDA is responsible for ensuring that food, incl uding spices, is not adulterated or misbranded. FDA samples importe d spice shipments as well as domestic spice commodities for the presence of pathogens. FDA detains spice shipments when pathogens are found. When a spice shipment is detained, a reconditioning proposal can be submitted by the responsible firm to FDA. ETO is often us ed to recondition the shipment. After the reconditioning, the shipment is tested again to veri fy that the contaminant load has been reduced. Also, as part of ensuring that foods are not a dulterated, FDA is responsible for the enforcement of pesticide tole rances in foods. The Federal Food, Drug, and Cosmetic Act (FFDCA) prohibits the marketing of adulterated or misbranded cosmetics in interstate commerce and vests FDA with authority in this area. In addition, under the authority of the Fair Packaging and Labeli ng Act (FPLA), FDA requires an ingredient declaration for finished cosmetic products. ETO and its reac tion products (EBH, ECH, and EG) are not considered cosm etic ingredients. They are not listed in the International Cosmetic Ingredient Dictionary, the primary source of cosmetic ingredient nomenclature. FDA also regulates finished cosm etic products after they are in commercial distribution and have entered interstate commerce. During the manuf acturing of cosmetics, ETO is used as an ethoxylating agent for the synthesis of ethoxylated su rfactants that are used in cosmetic products. FDA monitors cosmetic products for levels of 1,4-dioxane, a reaction product of ETO formed during the ethoxylation process. There is a pote ntial for residual ETO to be present in ethoxylated surfactants and cosmetic products containing these ingred ients. In addition, there are many cosmetic ingredients that ar e derivatives of EG. Any unreac ted EG present in a cosmetic ingredient, may also be present in a finished cosmetic product (Havery, 2008).


### 1.5.1 Recent/Pending Regulatory Actions A DCI was issued in November 2007, in conjun ction with the 2006 TRED, requiring submission of UV/visible absorption data for ETO (Guideline 830.7050), as well as a prenatal developmental toxicity study (870.3700), and a reproduction and fertility effects study (870.3800) for the reaction product ECH. Waivers we re granted for the UV/visible absorption and prenatal developmental toxicity studies. The reproduction and fertility effects study was submitted to the Agency in 2012 and currently is being reviewed.


### 1.5.2 Tolerance Information

The EPA Tolerance Reassessmen t Decision (TRED) for ETO was issued July 24, 2006. The TRED is available in the public docket EP A-HQ-OPP-2005-0203 located in the Federal Docket Management System (FDMS) at http://www.regulations.gov . Tolerances for ETO and ECH are established under 40 CFR 180.151 for herbs and spices, dried vegetable, and walnuts 3

.

3 Tolerances for ETO and ECH were added for licorice roots, tops of peppermint and spearmint, and sesame seed in September 2009. ( http://www.regulations.gov/#!documen tDetail;D=EPA-HQ-OPP-2008-0834-0036 )Page 14 of 61 Tolerances for ETO on basil were removed follo wing the use being voluntarily cancelled by the registrant. The tolerance expression for ETO w ill be reviewed during registration review to ensure that it appropriately cove rs the metabolites and degradates of ETO and that it specifies the residues to be measured for each commodity. 

## 1.6 Incidents

1.6.1 Human Health

The evaluation of incidents related to human exposure to ETO was discussed in a separate memorandum from the Health Effects Di vision dated May 8, 2013 (D411127). For this evaluation, both OPP Incident Data System (ID S) and the Centers for Disease Control and Prevention/National Institute for Occupational Sa fety and Health (CDC/ NIOSH) and Sentinel Event Notification System for Occupational Risk-Pesticides (SENSOR) databases were consulted for pesticide incident data on th e active ingredient ETO (PC Code: 042301). The purpose of the database search is to identify potential patterns in the frequency and severity of the health effects attributed to ETO exposure. From the IDE database, one incident was repor ted from January 2008 to February 2013. This reported incident involved a worker who attribut ed his acute promyeloctyic leukemia to ETO in his capacity as a worker at a st erilization facility. In the aggreg ate IDS database, which reports human incidents of a minor nature, from Janua ry 1, 2008 to February 19, 2013 there were three reported incidents involving ETO. These incident s were classified as minor in severity.

The SENSOR-Pesticides database identified nine cases, stemming from five events involving ETO from 1998-2009. All cases/events involve d a single active ingredient. One case was classified as moderate in severity and eight cases were classified as low in severity. Eight of the nine cases were work related; seven of nine cases were exposures in a hospital.


### 1.6.2 Ecological There are no reported incidents for ETO in the ecological incident (EII S) or Avian Monitoring System (AIMS) databases, as well as no reports of aggregate incidents for the time period from 2005 to 2013. The absence of reported incidents s hould not be construed as the absence of incidents. Incident reports for non-target organisms typica lly provide information only on mortality events and plant damage. Sublethal e ffects in organisms such as abnormal behavior, reduced growth and/or impaire d reproduction are rarely report ed, except for some phytotoxic effects in terrestrial plants. EPA's changes in th e registrant reporting re quirements for incidents in 1998 may also account for a reduced number of reported incidents. Re gistrants are now only required to submit detailed information on ’major’ fish, wildlife, and plant incidents. Minor fish, wildlife, and plant incidents, as well as all other non-target in cidents, are generally reported aggregately and are not included in EIIS. In addition, there have been changes in state monitoring efforts due to a lack of resources. 

## 2 Anticipated Data Needs

Table 7 presents a summary of the data anticipate d as being needed to su pport this registration review.Docket Number EPA-HQ-OPP-2013-0244www.regulations.govPage15of61Table 7 – Studies Anticipated as Neededfor the Registration Review of ETOGLNStudy NameTestSubstanceTime Frame(Measured inmonths from DCIReceipt)RiskAssessment(s)Data WillSupportUse Site(s)TriggeringAnticipated DataRequirementApplicable Exposure ScenarioStudies Anticipated to be Required through the Registration Review DCISpecialStudyAcute inhalation toxicitystudy4ETO 24Occupational andbystanderinhalationAll worker/bystander acute inhalation exposures870.4300Chronictoxicity/carcinogenicitystudyECH 48Occupational andResidentialAll chronic dietary exposure to ECH875.1400Inhalation exposure studyfor applicatorsETO 12 Occupational All applicator inhalation exposure875.1700 Product use information ETO 12 All All All875.2500Post-application inhalationexposure studyETO 12Post-application(site specific)All emissions from specific facilitiesSpecialstudyMonitoring data onfumigated commodities4ETO 24 Occupational Allemission from treated commodities/materials andthe potential for occupational exposure due tothose emissions in the channels of trade afterfumigation activities are completeSpecialStudyAmbient Air MonitoringStudyETO 36 Residential Allambient air concentrations for communities inproximity to treated facilitiesSpecialStudyAvian Acute InhalationToxicity Study4,5ETO 24 Ecological Allinhalation of air emissions by non-target wildlifeSpecialStudyHoneybee Acute VaporExposure Toxicity Study4ETO 24 Ecological All850.4150Vegetative Vigor6,7, GasChamber Exposure StudyETO 24 Ecological All contact with air emissions by non-target plants4A protocol is expected to be required to besubmitted for review prior to conduct of the study.5An acute avian inhalation study using the Northern bobwhite quailspecies is expected to be necessary to satisfy the toxicityprofile for ETO.6Data from five dicot species of atleast three families (excluding soybean (Glycine max) which has already been tested), andfour dicot species of at least twofamilies, one species of which is corn (Zea mays) are expected to be required. Additionally of the ten species tested, at least one species should be a root crop(either a monocot such as onion or dicot such as carrot, table beet or sugar beet).7Studies should be modified to accommodateexposure to a volatile substance by using environmental chambers that maintain the air concentrationsof the gas, see850.4230.Docket Number EPA-HQ-OPP-2013-0244 www.regulations.gov

Page 16 of 61 

## 3 Human Health Risk Assessment

In 2008, the EPA’s Office of Pesticide Progr ams (OPP) published a human health risk assessment in support of the RED for ETO ( http://www.epa.gov/oppsrrd1/REDs/ethylene-oxidered.pdf ). The Agency’s OPP anticipates conducting a human health risk assessment for ETO as part of the registration review. This will include both a non-cancer and cancer risk assessment. Non-cancer endpoints for ETO and th e reaction products of ETO have been previously selected and published by the Agency in the ETO RED. In the 2008 RED, it was recommended that a range of rodent unit risk estimates from 2.22 E-02 (mg/m 3 ) -1 to 2.67 E-03 (mg/m 3 ) -1 based on lung adenomas/carcinomas in male B6C3F1 mice at the high end and brain tumors in male F344 rats at the low end be considered for carcinogeni city risk assessment purposes. Since publication of the RED, the carcinogenic pot ential of ETO is being re-evalu ated by the National Center for Environmental Assessment’s IRIS program. Th e time line and projected dates for this reassessment are posted at: http://cfpub.epa.gov/ncea/iristrac/index.cfm?f useaction=viewChemical.showChemical&sw_id=1 004

. When this re-assessment is finalized, any modi fication to the carcinogenic potency estimate for ETO will be used by OPP in conducting the ca rcinogenicity risk assessment for ETO. For ETO, the Health Effects Division’s H azard and Science Policy Council (HASPOC) identified the need for a special acute inha lation toxicity study for ETO and additional information on the chronic toxicity and carci nogenicity of the ETO reaction product ECH. A special acute inhalation toxicity study is needed for ETO because as part of the risk assessment for ETO, the Agency will need to conduct an acute worker and acute bystander assessment. This special study has shown to be useful in fumiga nt risk assessment because it often provides the most sensitive acute endpoint for risk assessmen t. Inhalation studies with ETO have shown that the nasal cavity is a ta rget organ for ETO. Therefore, ther e is a reasonable likelihood that a special acute inhalation toxicity study would identify an endpoint that would be protective of acute effects in workers and bystanders exposed to ETO. This special acute inhalation toxicity study s hould include the evalua tion of the following: histopathology of the respiratory tract, includi ng incidence and severity at multiple tested concentrations; GSH measurements (i.e., nose) ; pharmacokinetics/tissue dosimetry including time course; and sublethal portal of entry effects (i.e., within the respirat ory tract) along with information on dose response, incidence, and se verity. The protocol fo r this special acute inhalation study should be submitted for Agen cy review, prior to study initiation.

The HASPOC also concluded that an immunot oxicity study (as required in both the 158 conventional pesticide test rule and the 158 anti microbial pesticide test rule) would not be needed for ETO. This decision was made on the ba sis of several factors, including: (1) The toxicology databases for ETO and ECH do not rev eal any evidence of trea tment related effects on the immune system. The overall weight of evidence (WOE) suggests that ETO does not directly target the immune sy stem; (2) Dietary risk assessments were not conducted for ETO since residues are unlikely to be found in sterilized spices availa ble for consumption; (3) Dietary risk assessments for the reaction product ECH are based on the most sensitive endpoints from studies conducted with the subjec t chemicals; (4) The dietary risk assessment indicates that for all supported commodities, the acute dietary expo sure estimates for ECH indicate no risks of concern for the general population or other popu lation subgroups. The ch ronic dietary exposurePage 17 of 61 estimates for both ECH and EG indicate no risks of concern for the general population or other population subgroups; (5) Points of Departures (PODs) for the most sensitive endpoints (neurotoxicity) seen in the most sensitive sp ecies (mouse) from a route-specific study (i.e., inhalation study) are used for assessing risks fr om short-and intermediate term inhalation exposures to ETO; (6) A POD for the most sensitive endpoints in the most sensitive population (offspring) seen in a route-specific ( i.e., inhalation) study is usedfor assessing risks from longterm inhalation exposures to ETO. The Agency also anticipates requiring additi onal information on the chronic toxicity and carcinogenicity of ECH. When considering whethe r the chronic toxicity and/or carcinogencity studies were needed for ECH, the HASPOC us ed a weight of evidence (WOE) approach including: (1) the current use pa ttern which results in dietary exposure to ECH at up to 940 ppm as a residue on food commodities (E CH is not found in drinking water); (2) the lack of feeding studies in rodents (mice and ra ts) that could provide a POD or an endpoint of concern for assessing risk from chronic dietar y exposures as well as asses the carcinogenic potential of ECH; and (3) the lack of confidence in the available long-term study (Johnson et al , 1967) which tested low levels of ECH in drinking water in an inadequate number of animals.

The HASPOC concludes that data to inform the potential for chronic toxicity and/or carcinogenicity are needed for ECH at this time. The rat chronic/carcinoge nicity study and/or the carcinogenicity study in mice may be conducted to fill this need. Ho wever, if there are additional exposure, pharmacokinetic, or ot her data/information which could be used to better understand the exposure or toxicological profile of ECH, th e registrant is encour aged to discuss this information with the Agency. 

## 3.1 Existing Toxicological Endpoints
Toxicological endpoints were selected for ETO, ECH, and EG as part of the 2008 RED. The existing endpoints are shown below in Table 8. All available information including existing guidelines toxicology studies, valid scientific literature, and the st udies that are expected to be required for registration review will be considered in establishing th e endpoints to be used in the registration review risk assessment. A detailed description of the toxicity studies is provided in Appendix A . Table 8 – Summary of Toxicological Doses a nd Endpoints for ETO, ECH, and EG Selected for Use in Past Human Risk Assessments Exposure Scenario Dose Used in Risk Assessment, UF Special FQPA SF* and Level of Concern for Risk Assessment Study and Toxicological Effects

ECH Acute Dietary (General populations) Dose for Risk Assessment = 100 mg/kg/day UF = 1000 Acute RfD = 0.1 mg/kg/day FQPA SF = 1X aPAD = acute RfD FQPA SF

= 0.10 mg/kg/day Developmental Toxicity Study – CD-1 Mice (Courtney et al ., 1982) At 150 mg/kg/day, 75% mortality of maternal animals observed after 2-4 treatments (days) of dosing. Note: The study NOAEL/LOAELfor this endpoint is different from the overall study NOAEL/LOAEL.Page 18 of 61 Exposure Scenario Dose Used in Risk Assessment, UF Special FQPA SF* and Level of Concern for Risk Assessment Study and Toxicological Effects

Chronic Dietary (All populations) NOAEL= 45 mg/kg/day UF = 1000 Chronic RfD = 0.045 mg/kg/day FQPA SF = 1X cPAD = chronic RfD FQPA SF

= 0.045 mg/kg/day Subchronic Toxicity Study – Albino Rats (Courtney et al ., 1982). LOAEL: 67.5 mg/kg/day Decreased mean body weight in males ( ↓ 34%), poor survival, i.e., 32% in males and 24% in females as compared to 100% in co ntrol males and 96% in control females, labored breathing and gross effects such as dark liver and lungs and hemorrhagic gastro intestinal tissues and adrenal and pituitary glands. Histopathological eff ects include subacute myocarditis, colloid depletion in thyroid, thyroid congestion, fatty liver and congestive pulmonary changes. EG Chronic Dietary (All populations) NOAEL= 40 mg/kg/day UF = 100 Chronic RfD = 0.4 mg/kg/day FQPA SF = 1X cPAD = chronic RfD FQPA SF

= 0.4 mg/kg/day Chronic Oral Toxicity in Rats (DePass et al ., 1986b). Increased oxalate crystals in urine of both sexes and possible fatty liver changes in females at 200 mg/kg/day. At the HDT, 100% mortality by 12 months, decreased body weight, changes in clinical chemistry and hematological parameters, organ weight changes, and chronic nephritis in males and mild fatty changes in the liver of females. ETO Inhalation Short-Term (1 - 30 days) andIntermediateTerm (1 - 6 months) NOAEL= 7.5 ppm (13.5 mg/m 3 ) Inhalation Absorption Rate = N/A Residential MOE =N/A

Occupational MOE = 30 Subchronic Inhalation Toxicity Study in Mice (Snellings et al ., 1984a) LOAEL = 37.5 ppm (68 mg/m 3 ) based on neurological effects (altere d gait and decreased motor activity) and absolute and relative organ weight changes Inhalation Long-Term (> 6 months) NOAEL= 7.5 ppm (13.5 mg/m 3 ) Inhalation Absorption Rate = N/A Residential MOE =N/A

Occupational MOE = 30 Two Generation Reproduction Study, Inhalation Exposure, Rats (MRID 42788101) Systemic LOAEL = 25 ppm (45 mg/m 3 ) based on decreased mean body weight gains in F0 males and females and F1 males during premating period. Reproductive LOAEL = 25 ppm based on increased postimplantation loss (two-fold) and decreased live pups per litter in F0 generation were observed. Offspring LOAEL = 25 ppm based on decreased mean pup body weight gain in both F0 and F1 generations. Cancer (Inhalation) Studies indicate positive evidence for carcinogeni city in animals and humans. The Agency is currently determining the carcinoge nicity classification of ETO. Unit Risk Factor (CDHS) based on mononuclear leukemia in female rats and analysis by linearized multistage model = 8.8x10 -5 per μ g/m3 or 0.16 per ppm Unit Risk Factor (ORD, Pending Review) based on lympho hematopoietic cancer in humans and analyzed by linear regression = 9.0 x 10 -4 per μ g/m3 or 1.6 per ppm UF = uncertainty factor, FQPA SF = FQPA safety factor, NOAEL = no observed adverse effect level, LOAE L = lowest observed adverse effect level, PAD = population adjusted dose (a = acute, c = chroni c) RfD = reference dose, MOE = margin of exposure, LOC = level of concern, N/A = Not Applicable, HDT = highest does tested, CDHS = California Department of Health ServicesPage 19 of 61 

## 3.2 Dietary Exposure

In the tolerance reasse ssment conducted for ETO in 2006, st udy data from spice sterilization indicated that ETO levels declin ed rapidly after sterilization, bu t persistent levels of ECH and EG remained. Therefore, endpoints were selected to assess risks associated with dietary exposure to these reaction products. The assessment in the 2006 TRED indicated no risks of concern for acute or chronic dietary exposure to ECH or EG.


### 3.2.1 Dietary (Food - Conventional Uses) The most recent dietary exposure and risk assessment (B. Daiss, 6/30/09, DP316651) was performed as an addendum to the June 21, 2006 assessment (conducted for the TRED) of dietary risk from exposures to ECH resulting from use of ETO as a food fumigant using an improved fumigation process (B. Daiss, DP316677). This addendum revised the dietary exposure assessment to include the following commodities: licorice, roots; peppermint, tops, dried; sesame, seed; spearmint, tops, dried. Based on the revised dietary analysis, inclusion of the four listed commodities did not significantly affect the dietary risk assessment. This assessment concluded that for all supported commodities, in cluding those listed, the acute dietary exposure estimates for ECH were below the Agency’s leve l of concern. The acute dietary exposure (food only) utilized 96% of the aPAD for the highe st exposed population subgroup, children 1-2 years of age. It was based on a refi ned acute dietary risk assessment of exposure to ECH conducted using the Dietary Exposure Evaluation Model (DEEM-FCID  , Version 2.03) which uses food consumption data from the USDA’s Continuing Surveys of Food Intakes by Individuals (CSFII) from 1994-1996 and 1998. Residue data for this assessment was provided in 2001 ETO spice sterilization study submitted by the American Spice Trade Association (ASTA) (MRID 46635201). The entire distribution of fumigated commodity residues was used for the acute assessment. Since specific residue data are not available for the four additional commodities added to the analysis (licorice roots, peppermint tops, sesame s eed, and spearmint tops), existing data for spice commodities were assumed to be representative of those commodities. Maximum percent crop treated (sterilized) was used for the acute assessment. Refined chronic dietary risk assessments were conducted using the Diet ary Exposure Evaluation Model (DEEM-FCID  , Version 2.03), and the Lifeline Model Version 2.0 which use food consumption data from the USDA’s Continuing Surveys of Food Intakes by Individuals (CSFII) from 1994-1996 and 1998. Residue data obtained from an ETO spice sterilization study were used for the chronic assessments. Average residues and average percent crop sterilized were used for the chronic assessment. Only the ETO react ion products, ECH and EG, were included in the dietary assessment for ETO treated commodities products. The chronic dietary exposure estimates for both ECH and EG were below The Agency’s level of concern. For ECH, the DEEM and Lifeline mode l chronic dietary exposure estimates for the highest exposed population subgroup , children 1-2 years of age, were both 38% of the chronic population adjusted dose (cPAD) for treated commodities. For EG, the DEEM and Lifeline model chronic dietary exposure estimates for the highest exposed popul ation subgroup, children 1-2 years of age, were 19% and 12% of the cPAD respectively for treated commodities. The dietary exposure database is adequate to support the exis ting registrations.Page 20 of 61 

### 3.2.2 Dietary (Food - Antimicrobial Uses) There is no anticipated dietary e xposure in food from the non-agricu ltural (antimicrobial) uses of ETO (see 1.4.2.2). A dietary assessmen t will not be needed for the exposures resulting from antimicrobial uses of ETO.


### 3.2.3 Dietary (Drinking Water) Based on the chemical and physical properties (see 4.1 and Appendix B ), there is no drinking water exposure to ETO residues expected from the currently registered us es of ETO. Therefore, residue chemistry data or assessme nt of risk associated with dri nking water is not expected to be needed.


### 3.2.4 Residue Chemistry (Conventional and Antimicrobial Uses) ETO residues disappear rapidly afte r sterilization and are unlikely to be found in spices and other food commodities by the time they are available for consumption. ECH and EBH have been shown to result from fumigation of foods with ETO due to reaction with natural chlorides and bromides present in the crop. At high sterilizat ion concentrations, ETO reacts with moisture to form EG and, in the presence of sugars, glycol de rivatives. Spice sterilization study data indicate persistent high levels of the reaction products ECH and EG in treated spices and herbs and walnuts. EBH residues are also found in treated commodities but are minimal relative to ECH. No residues are expected in livestock commodities as a result of ETO fumig ation, as no livestock feedstuffs are treated (see 1.4.2.1). The qualitative nature of ETO residues in plan ts is adequately unders tood. The residues of potential concern in plants are ECH and EG becau se of the high levels of these reaction products present in treated spices and herbs and walnuts. ETO is not considered a residue of concern for dietary exposure because data from an ETO spi ce sterilization study indicate that it disappears rapidly after sterilization. ECH is a reaction pr oduct from sterilization of herbs, spices and walnuts. ECH is not removed by out-gassing. The residue chemistry database for ETO is adequa te for registration review (see Appendix B and Appendix D ). 

## 3.3 Occupational and Residential Exposures

3.3.1 Occupational Exposure

3.3.1.1 Conventional Uses In the 2008 RED, conventional uses for ETO include sterilization in the spice industry and for beekeeping equipment in North Carolina. Inhalation exposure was identified as the route of most concern. While there may be potential for dermal exposure to residues of ETO reaction products, ECH and EG, during post-sterilization activities; the Agency concluded that handling of the actual treated materials is limited, and therefore, dermal exposure is negligible.

In the most recent assessme nt of ETO occupational expos ures (Crowley, M., 3/24/2008, D347717), inhalation exposure was assessed using observational monitoring data submitted by the American Spice Trade Association (ASTA) where two workers at two different facilities were monitored for 10 days. Inhalation exposures were assessed for short-, intermediate-, and long-term durations and it was assumed that work er exposure for the sterilization process for the spice industry and the beekeeping equipment were substantially similar. No worker exposurePage 21 of 61 frequency data was submitted to the Agency regarding ETO spice sterilization activities; therefore, it was assumed that exposure fr equency was 240 days per year. For activities associated with sterilizing beekeeping equipment, it was indicated that ETO can be used approximately 40 times per year (Cro wley, M., D347717, 3/24/08; electronic mail correspondence from Dan Hopkins, NC Dept. of Agriculture to Susan Bartow, EPA/OPP/SRRD; 2/7/2008).

The results of the 2008 risk assessment indicate that in some circumstances ETO exposures could occur at levels which are of concern to the Agency; however, this conclusion is based on very limited information. EPA anticipates requiri ng data regarding poten tial worker exposure associated with commodity fumigation as detailed in sections 3.3.1.3 and 3.3.2.3 below. Further consideration may be given to post-appl ication exposures pending future evaluation of the air monitoring data submitted. As part of registration review, tasks near fumigation facilities/operations need to be defined to properly assess risks to workers performing postapplication activities (i.e., aerators, fork-lift ope rators, etc.). Potential exposures due to offgassing will also be assessed for workers conduc ting post-application activ ities near treatment operations.

3.3.1.2 Antimicrobial Uses

Antimicrobial use sites of ETO include medical devices, musical inst ruments, library and museum artifacts, and cosmetic ingredients. Two sources of observational information were used to assess the medical device sterilization in th e 2008 RED. Information obtained from OSHA’s Integrated Management Information System (IMIS) was used as the basis for the medical facility treatments (DP339831) and a submission by th e ETO Sterilization Association, Inc (MRID 47331801, DP348868) was used as the basis for the contra ct sterilization facility treatments. The scope of materials potentially st erilized within the contract st erilization facilities includes medical devices (representing th e majority of use), musical instruments, library and museum artifacts, and cosmetic ingredients. The 2008 RED assessment of the medical facility tr eatments using the IMIS data base covered the years from 1979 to 1987 and from 1988 to 2007 (DP339831). The delineation by years was necessary to reflect the 1988 OSHA Standa rd. The 2008 RED assessment of the medical facilities was based on the Standard Industrial Classifica tion (SIC) codes and f acility descriptions provided in Table 9. The summaries of the air concentrations associated with the medical industries listed in Table 9 are pr ovided in Table 10 and Table 11 be low. The data used in these analyses were restricted to 8-hr time weighted averages (TWA) from personal air samplers from the observational data. It should be noted that th e air samples were not ex clusively obtained from one particular area in the medi cal facility (e.g., sterilization ch amber) rather they were taken from every area that the person entered during hi s/her 8-hour work day and averaged over time to obtain an 8-hr TWA. Table 9 – Summary of Medical Facility SIC Codes
SIC Code Description

3841 Surgical, Medical Instruments and Apparatus Establishments primarily engaged in manufacturing medical, surgical, ophthalmic, and veterinary instruments and apparatusPage 22 of 61 SIC Code Description

3842 Orthopedic, Prosthetic, and Surgical Appliances and Supplies Establishments primarily engaged in manufacturing orthopedic, prosthetic, and surgical appliances and supplies, arch su pports and other foot appliances; fracture appliances, elastic hosiery, abdominal su pporters, braces, and trusses; bandages; surgical gauze and dressings; sutures; adhesive tapes and medicated plasters; and personal safety appliances and equipment.

6324 Hospital and Medical Service Plans Establishments primarily engaged in providing hospital, medical, and other health services to subscribers or members in accordance with prearranged agreements or service plans.

8011 Offices and Clinics of Doctors of

Medicine Establishments of licensed practitioners havi ng the degree of M.D. and engaged in the practice of general or specia lized medicine and surgery.

8043 Offices and Clinics of Podiatrists Establishments of licensed practitioners having the degree of D.P. and engaged in the practice of podiatry.

8051 Skilled Nursing Care Facilities Establishments primarily engaged in prov iding inpatient nursing and rehabilitative services to patients who require continuous health care, but not hospital services.

8062 General Medical and Surgical Hospitals Establishments primarily engaged in pr oviding general medical and surgical services and other hospital services.
8063 Psychiatric Hospitals Establishments primarily engaged in prov iding diagnostic medical services and inpatient treatment for the mentally ill.

8069 Specialty Hospitals, Except Psychiatric Establishments primarily engaged in prov iding diagnostic services, treatment, and other hospital services for specialized cat egories of patients, except mental.

8099 Health and Allied Services, Not Elsewhere Classified Establishments primarily engaged in pr oviding health and allied services, not elsewhere classified.

Table 10 illustrates the reduction in air concentrations base d on the 1988 OSHA Standard. Only the air concentrations from 1988 to 2007 were used in the assessment for the 2008 RED to reflect the current practices as of 2008. Table 11 provides the air concentr ations for all medical SIC codes as well as a delineation of air concentrations by in dividual SIC codes.
Table 10 – ETO Air Concentrations fr om IMIS for All Medical SIC Codes Statistic 1979 to 1987 (ppm) 1988 to 2007 (ppm) Arithmetic mean ± std 2.44 ± 24 0.49 ± 2 50 th %tile 0.029 0.026 75 th %tile 0.17 0.21 90 th %tile 0.83 0.83 Maximum 312 22 Number of observations 171 343 Note: 1⁄2 Level of Detection (LOD) (where LOD = 52.2 ppb for y ears prior to 1984 and 3 ppb for years 1984+) was used for all non-detects Table 11 – ETO Air Concentrations (ppm) from IMIS for All Available Medical SIC Codes (1988 to 2007)

SIC Code All codes 3841 3842 6324 8011 8043 8051 8062 8063* 8069 8099 Arithmetic mean 0.49 0.43 0.65 0.22 0.20 0.0015 0.57 0.42 NA 0.09 2.02 Std 2.0 0.46 1.91 0.39 0.20 0.0 0.98 2.13 NA 0.20 4.85 50%tile 0.026 0.37 0.16 0.0015 0.20 0.0015 0.0015 0.0015 NA 0.03 0.05 75%tile 0.21 0.52 0.50 0.34 0.20 0.0015 0.85 0.09 NA 0.07 0.51 90%tile 0.83 1.09 1.18 0.54 0.20 0.0015 1.36 0.65 NA 0.17 5.69

Min 0.0015 0.0015 0.0015 0.0015 0.20 0.0015 0.0015 0.0015 NA 0.0015 0.02
Max 22.0 1.7 13.8 0.67 0.20 0.0015 1.7 22.0 NA 0.83 13.0 Number of observations 343 18 76 3 1 2 3 216 NA 17 7 *No samples were collected after 1988 for SIC Code 8063.Page 23 of 61 The 2008 RED assessment of the contract ster ilization facilities was based on the ETO Sterilization Association, Inc., subm ission (MRID 47331801, DP348868). Their submission (2008) is a summary of existi ng ETO observational air concen tration data obtained from 21 contract sterilization f acilities. At the time of the submi ssion, the 21 facilities represented 90 percent of the contract steriliza tion facility capacity in the United States. ETO air concentrations were retrieved from worker activity log sheets as well as the facility records of the air concentrations. The results of the inhalation exposure to workers that were used in the 2008 RED assessment are reported in Table 12. The average inhalation expos ure to workers not wear ing respirators (i.e., workers working in areas of the facility not in the aeration/unloadi ng rooms) is 0.30 ± 0.57 ppm (n=271). For the workers involved in the aeration process, hence wearing respirators for some portion of the work shift, the average inhalation exposure is 0.15 ± 0.10 ppm (n=294) (adjusted for respirator use if appropriate). For a more detailed description of the sampling methodology the reader is referred to DP 348868.

Table 12 – ETO Air Concentrations fo r Contract Sterilization Facilities

Statistic Individual Sampling Badge Results for Workers in Areas Needing No Respirator (ppm) Workers involved in aeration process (i.e

. , only workers who wore respirators) (ppm) Arithmetic mean ± std 0.30 ± 0.57 0.15 ± 0.10 50 th %tile 0.10 0.13 75 th %tile 0.27 0.21 90 th %tile 0.63 0.27 Maximum 5.30 0.52 Number of observations 271 294 Note: 1⁄2 LOD to the full LOD was used for all non-detects. The 2008 RED process resulted in additional mitiga tion measures to further reduce the potential exposure and risks to workers. The upcoming regi stration review assessment should be based on the air concentrations post-mitigation. The reassessm ent of the air concentrations in both medical facilities and contract sterilization facilities would be better refined by the submission of the most current OSHA data (available at http://www.osha.gov/opengov/healthsamples.html ). Postmitigation contract facility observational monitoring data would also help refine the upcoming registration review assessment. In lieu of pos t-mitigation air concentration data, the above estimates from the 2008 assessment for the RED would be used in the reassessment.

3.3.1.3 Occupational Data Anticipated as Needed The following data are anticipat ed to be required for ETO: 875.1400 – applicator inhalation data 875.1700 – product use data


### 3.3.2 Residential Exposures

There are no residential handl er (applicator) uses for ETO.

3.3.2.1 Conventional Uses There is a potential for bystander exposures wh ich can occur from emissions during treatment and aeration of commodities associated with ETO. In 2005, the EPA’s Office of Air and Radiation (OAR) conducted a resi dential risk assessment for ETO which estimated cancer asPage 24 of 61 well as acute and chronic non-cancer risk to bystanders (EPA/OAR, Mark Morris, 2005; http://www.epa.gov/ttnatw01/eo/eo_rra.pdf ). Based on the results, a ccording to the RED, the Agency concluded that potenti al cancer and non-cancer risks did not indicate any further regulatory action was necessary at the time for re sidential inhalation exposure. As a supplement to the 2005 OAR analysis and any future refinement s of their analysis, bystander exposures will be reassessed, for registration review and as pe r other fumigants, using computer modeling (e.g., PERFUM). There is sufficient information to complete such analyses for ETO. Howeve r, in the event that the available information suggests that there ma y be bystander risks of concern, a more refined analysis would be possible if addi tional data were available. Type s of information that could be used to refine the bystander assessment include : information on treatment conditions such as volumes treated, concentration/tim e schedules used, release height , and air exchange rates. In summary, to the extent that the available data show potential for bysta nder exposure, updated residential assessments will be conducted dur ing registration review. Additionally, the OAR bystander assessment and any refinements to this an alysis will be consid ered as appropriate.

3.3.2.2 Antimicrobial Uses Potential residential exposure may result from the use of ETO as a sterilant for musical wind instruments, and from releases from commerc ial sterilization sources . Based on a qualitative screening-level risk assessmen t conducted in the 2008 RED, residues from the use of ETO for the sterilization of musical wind instrument are not likely to result in adverse health effects to musicians (D. Smegal, D309124, 2/15/05). No additiona l information is available to contradict this qualitative screening assessment, thus the Agency is not anticipating quantifying this scenario during registration review. The 2008 residential/bystander assessment of rel eases resulting from commercial sterilization sources relied on EPA’s Office of Air and Radiation (OAR) re sidual risk assessment conducted in 2005 for ETO (DP338729) as cited in sec tion 3.3.2.1. The ambient air assessment was based on the EPA Human Exposure - Screen (HEM-Screen ). The HEM-Screen model contained (1) an atmospheric dispersion model w ith meteorological data, and (2) U.S. Bureau of Census population data for 2000 and the census block leve l. The HEM-Screen's dispersion model is a Gaussian model. OAR estimated ambient concentr ation at census blocks at varying distances from ETO commercial sterilization sources. For details of the assessm ent the reader is referred to DP338729. An updated residential assessment will be conducted during registration review.

3.3.2.3 Residential Data Anticipated as Needed The following data are anticipat ed to be required for ETO: 875.2500 – Post application bystand er inhalation exposure data Special Study - Monitoring data on fumigated commodities 

## 3.4 Aggregate and Cumulati ve Exposure and Risk

3.4.1 Aggregate Exposures and Risk As noted in the 2008 RED for ETO, “An aggregate assessment of risk is not required because drinking water exposures are not expected and ther e is not a common chemical exposure for residential and dietary exposure scenarios (i .e., the reaction products ECH and EG are thePage 25 of 61 chemicals of concern for dietary exposure while ETO is the compound of concern for residential exposure).


### 3.4.2 Cumulative Exposure and Risk Section 408(b)(2)(D)(v) of FFDCA requires that, when considering whether to establish, modify, or revoke a tolerance, the Agency consider “a vailable information” concerning the cumulative effects of a particular pesticid e's residues and “other substances that have a common mechanism of toxicity.” EPA does not have, at this time, available data to determine whether ETO has a common mechanism of toxicity with other substances . Unlike other pesticides for which EPA has followed a cumulative risk approach based on a common mechanism of toxicity, EPA has not made a common mechanism of toxicity finding as to ETO and any other substances and, ETO does not appear to produce a toxic metabolite produced by other substances which have tolerances in the U. S. For th e purposes of this tolerance rea ssessment action, therefore, EPA has not assumed that ETO has a common mechanis m of toxicity with other substances. For information regarding EPA’s efforts to determ ine which chemicals have a common mechanism of toxicity and to evaluate th e cumulative effects of such chem icals, see the policy statements released by EPA’s OPP concerning common mech anism determinations and procedures for cumulating effects from substances found to ha ve a common mechanism on EPA’s website at http://www.epa.gov/fedrgstr/EPA_PEST/2002/January/Day_16/

. 

## 4 Ecological Risk Assessment

In accordance with EPA regulations (40 CFR Sections 158.630, 660, and 1300), indoor conventional pesticides involvi ng substances of a gaseous, hi ghly volatile liquid or highly reactive solid do not typica lly require submission of environmental fate data, or data on effects to non-target terrestrial wildlife, aquatic organisms, or plants. Similarly for the antimicrobial sterilization use, the Agency ha s not required submission of envir onmental fate or effects data. Therefore, the information that is currently avai lable on the fate and effects of ETO is based on public literature and fate and effect models. The Agency has not conducted a quantitative ecological risk assessment for the ETO uses. Previous assessments have presumed indoor uses would not result in exposur es of concern to the environment based on an assumption that exposure s to non-target wildlife, aquatic organisms, and plants from such labeled indoor uses of a gaseous substance are negligible. However, considering the production volume used for fumiga tion and monitoring data from use facilities demonstrating releases of ETO, a more quantitati ve assessment of risks will be conducted during registration review. The ecological risk assessmen t planned during registration review will allow the Agency to determine potential risks to orga nisms exposed to ETO transported from treatment sites into the environment. The risk assessment also will allow the Agency to determine whether uses of ETO have 'no effect' or 'may affect' federally listed threatened or endangered species (listed species) or their designated critical ha bitats. 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 Services (the Services), as appropriate.Page 26 of 61 

## 4.1 Environmental Fate Assessment
ETO is a gas in its natural state, and is used primarily as a fumiga nt. For this use, ETO enters the environment primarily when gases are vented during aeration. ETO released to the air is expected to be persistent. ETO is highly water sol uble (1000 g/L at 25 o C, EPI Suite version 4.10) but also has a high tendenc y to volatilize from water (hal f-life <1 hour, Conway, 1983; vapor pressure 1255 millimeters of mercury, EPISu ite v4.10). Additionally ETO is not stable in aqueous medium (fresh water and sea water) under aerobic conditi ons and in water the concentration of ETO would be further reduced due to hydrol ytic degradation. The likely hydrolytic degradates are: EG, ECH, and po ssibly EBH. A study by Gomer, and Noyes (1950), showed that ETO auotocataly zes into methane, ethane, hydr ogen, and carbon dioxide (MRID 49126104). Since ETO is biodegradable and volatile, it is not likely to be present in ground waters. Based on the chemical and physical properti es, ETO is unlikely to accumulate in soils or sediments and it will volatilize as water evapor ates, leach through the soil, or be removed by runoff during rainstorms. Also, ETO has a low Log Kow (-0.30, EPISuite v4.10) and is not likely to bioaccumulate.

The risk concerns from ETO use scenario are likely through the inhalation pathway.


### 4.1.1 Clean Water Act ETO is not identified as a cause of impairment for any water bodies listed as impaired under section 303(d) of the Clean Water Act 8 . In addition, no Total Maximum Daily Loads (TMDL) have been developed for ETO 9

. EG was identified as contributing to the impairment of the Creek near Iowa International Airport, where the de icing is carried out on planes by using glycol. TMDL established for glycol (dai ly max) = 125 mg/L and for thir ty average it is 190.0 mg/L. It is to be noted that these TMDL are not because of ETO use as a pesticide. More information on impaired water bodies and TMDLs can be found at EPA’s website 10

. 

## 4.2 Conceptual Models for Enviro nmental Exposure Pathways
Based on the summary of regist ered uses of ETO presented in Table 5, physical/chemical properties and environmental fate data presented in Table 4 a nd Appendix B, the Agency has developed a conceptual exposure model diagram for terrestrial and aquatic organisms to ETO. Under ambient environmental conditions, ETO releas ed to air is expected to be persistent resulting in potential inhalation exposure of terrestrial wildlife. There is some indication that scrubbing of ETO from air using water is employe d in some facilities. More information is needed to identify if th is is a method used to remove ETO from air before venting, see Section 6.1.5 for information the Agency is seeking. However, under ambient conditions ETO scrubbed from vented air to water is expected, with a half-life of <1 h, to vol atilize along the way to a WWTP. Chemicals that are releas ed down-the-drain can typically take from a few to several hours to reach wastewater treatment plant inta kes following their discharge and from several hours to roughly a day following th eir discharge down-the-drain to subsequently be discharged from wastewater treatment plants to surface water. Since uses of ETO are not expected to have a significant component that is av ailable for runoff or leaching, it will not be considered for

8 http://iaspub.epa.gov/tmdl_waters10/attains_nation_cy.cause_detail_303d?p_cause_group_id=885
9 http://iaspub.epa.gov/tmdl_waters10/attains_nation.tmdl _pollutant_detail?p_pollutant_group_id=885&p_pollutant_ group_name=PESTICIDES
10 http://www.epa.gov/owow/tmdl/Page 27 of 61 aquatic exposure (USEPA 2013b). For the purposes of this risk assessment, terrestrial non-target organisms are assumed to occupy areas immediatel y adjacent to treatment sites and aquatic nontarget organisms are assumed to occupy water bo dies immediately adjacent to treatment sites. For a gaseous pesticide released from a treatme nt chamber, the terrestrial exposure pathways considered most likely to occur to terrestrial animals is via inhala tion of the gas and to terrestrial plants is via contact of the gas to its external layer of plant tissues.

Figure 1 – Conceptual Model for Ecological Ex posure and Effects of ETO to Aquatic and Terrestrial Organisms 

## 4.3 Ecological Effects Assessment

4.3.1 Mechanism of Action ETO is a strong alkylating agent that is a univer sal poison for protoplasm. It causes clotting of proteins, deactivation of enzyme s and other biologically important components of a living organism (WHO, 2003).


### 4.3.2 Measures of Effect (Ecotoxicology Endpoints) Ecotoxicity endpoint data are used as measures of effects to aquatic and terrestrial organisms. All available ecotoxicity endpoints in the Agency’s files from ETO studies submitted by registrants or other interested parties, fede ral laboratory data, or from the pub lic literature are tabulated in Appendix C along with the data re quirements and data gaps. Where models could be used to estimate values for missing endpoints, the models and results are also described in Appendix C. The most sensitive values for each receptor group are used for the risk assessment (Table 13).

Stressor

Source/ Exposure Media

Receptors and Exposure Routes

Attribute Change(s) Individual organisms Reduced survival (emergence*) Reduced growth Reduced reproduction** Food chain Reduction in prey Modification of PCEs related
to prey availability Habitat integrity Reduction in primary productivity Reduced cover Community change Modification of PCEs related to habitat Terrestrial Animals Birds (Reptiles, Amphibians) Mammals, Beneficial Insects Inhalation

Key Most likely

exposure pathway contributing to risk Low likelihood of contributing to risk Fumigation/Sterilization at Facilities

Venting to Outside Air Scrubbed to Water

Waste Water Treatment Plant (WWTP)

Surface Water

Sediment

Aquatic Organisms Invertebrates Vertebrates Algae, Plants WWTP microorganisms Uptake or sorption Uptake by gills or integument or sorption by cells

Population Respiration inhibition Contact

Terrestrial Plants Vegetative VigorPage 28 of 61 These selected endpoints will be updated duri ng the risk assessment phase based on any additional submitted data or data found in the public literature. Table 13 – Selected Ecological Effects Endpoints for Risk Assessment of ETO

Receptor Group Surrogate Species Risk Scenario Toxicity Endpoint Reference (MRID)

Birds 6 Northern bobwhite Acute Oral No data. Data are not expected to be required since significant concentrations ar e not expected to reach the receptors via the oral and dietary routes (ETO is a gas, and the exposure pathway most likely to occur to birds is via inhalation).

Acute Inhalation Data gap (Special Study): An acute avian inhalation study using the Northern bobwhite quail species is necessary to satisfy the toxicity profile for ETO. Without data, riskwould be presumed for birds, reptiles, and terrestrialphase amphibians, including listed species.

Subacute Dietary No data. Data are not expected to be required because significant concentrations ar e not expected to reach the receptors due to the rapid dec line of air concentrations of the gas which results in low potential for chronic exposure and residues are not expected to accumulate or persist in food items. Chronic

Mammals Laboratory mice Acute Inhalation LD 50 = 1.5 mg/kg-bw (820 ppm) IPCS, 2003

Laboratory rat Chronic Inhalation NOAEL = 10 ppm (0.18 mg/mL) 8 42788101

Freshwater fish 1 Fathead minnow 1 ( Pimephales promelas ) Acute 96-h LC 50 = 84 mg a.i./L Conway et al., 1983, Supplemental

Chronic No data available, not an anticipated data gap as this is expected to be a negligible exposure pathway.

Freshwater invertebrates Waterflea ( Daphnia
magna ) Acute 48-h EC 50 = 137 mg a.i./L Conway et al., 1983, Supplemental

Chronic No data available, not an anticipated data gap as this is expected to be a negligible exposure pathway. Freshwater benthic invertebrates -- Subchronic or Chronic Data not anticipated to be required: Not expected to be associated with sediment

Estuarine/marine fish Striped mullet ( Mugil cephalus ) Acute 96-h LC 50 = 89 mg ai/L Crews et al, 1974 Supplemental 4

Chronic No data available, not an anticipated data gap as this is expected to be a negligible exposure pathway.

Estuarine/marine invertebrates Eastern oyster (shell deposition/embryo larval) Acute No data, but data are not anticipated to be required because significant concentrat ions are not expected to reach the receptors due to the rapid decline of water concentrations of the gas which results in low potential for chronic exposure nor is it expected to be in the sediment. Mysid Acute Chronic Estuarine/marine benthic invertebrates -- Subchronic or Chronic

Aquatic Nonvascular plants Freshwater green alga Pseudokirchneriella subcapitata Non-listed 2 IC 50 >0.86 mg/L 47921703 Acceptable 4, 5
Listed 3 NOAEC > 0.86
Aquatic vascular Duckweed ( Lemna gibba ) Non-listed 2 IC 50 > 0.87 mg/L 47921702 Acceptable 4, 5 Listed 3 NOAEC > 0.87 mg/LPage 29 of 61 Receptor Group Surrogate Species Risk Scenario Toxicity Endpoint Reference (MRID)
Aquatic Rooted Macrophytes Seedling Emergence Non-listed No data available, not a data gap as exposure pathway is not likely. Listed

Terrestrial Plants Vegetative vigor Non-listed IC 50 > 252 mg a.i./m 3 47921701 Acceptable Data gap for nine species. 7 Listed NOAEC = 252 mg a.i./m 3

Beneficial insects Honey bee Acute
contact No data, not an anticipated data gap since significant concentrations are not expected to reach the receptors via the oral and contact routes since the greatest exposure pathway to honeybees is via inhalation because ETO is a
gas. Acute oral

Acute vapor-phase Data gap, Special Study: a honeybee acute vapor-phase exposure toxicity study is necessary to satisfy the toxicity profile for ETO. Without data, risk would be presumed for beneficial insects, including listed species.

1 Freshwater fish may be surrogates for aquatic-phase amphibians.
2 For aquatic plants, the guideline standard half maximal inhibitory concentration (IC 50 ) value is used for assessing risk to non-target, non-listed species.
3 For aquatic plants, the guideline standard NOAEC value is used for assessing risk to non-target, listed species.
4 The studies were modified to accommodate a volatile substa nce by using environmental ch ambers that maintain the air concentrations of the gas.
5 PPO data.
6 Birds represent surrogates for terrestrial-phase amphibians and reptiles.
7 Only one species out of a battery of ten has been tested, the data for the remaining nine species is a data gap. The study was modified to accommodate a volatile substance by using environmental chambers that maintained the air concentrations of the gas.
8 1 ppm = 1.83 mg a.i./m 3 

## 4.4 Exposure Analysis Plan

4.4.1 Wildlife Exposure Estimates

Available OPP models will be used to determ ine the estimated environmental concentration (EECs) in the aquatic environment. Resulting exposure estimates will be compared to the toxicity endpoints to determine if levels of concern are exceeded for each receptor group.

Stressors of Concern The stressors of concern for ecological exposur e will only be the parent compound, ETO. Three reaction products were identified based on the op en literature data as EBH, ECH, and EG (USEPA 2008). There is not any evidence that th e residues of these r eaction products exist in terrestrial or aquatic environmen t following fumigant application.

Antimicrobial Uses Monitoring data collected from around facilities for assessment of human health risk will be used to evaluate exposure and risk. Spice and Herb AERSCREEN, an air screening model, was used for preliminary estimation of the fumigant concentration after the st erilization near the treat ment facility (USEPA 2013b, http://www.epa.gov/scram 001/dispersion_screening.htm ). The model estimates the "worst-case" of 1-hour concentrations for a single source, w ithout the need for hourly meteorological data.Page 30 of 61 AERSCREEN is intended to produce concentration es timates that are equal to or greater than the estimates produced by other refined air disper sion model with a fully developed set of meteorological and terrain data, but the degr ee of conservatism may vary depending on the application. The maximum concentra tion in the first hour is 0.687 g/m 3 according the current label at 31.22 lb/1000 ft 3 (500 mg/L) with 16 steam washes on an estimated treatment facility with 10,000ft 3 spaces based on the second release scen ario. The detailed modeling information can be found in Appendices E and F. In order to address the risk hypot hesis, the potential for adverse effects on the environment will be assessed by estimated air concentration adjace nt to the treatment f acility through modeling or monitoring (Fig. 1) (USEPA 2013b). The use of ETO fumigant and quantity of air emission, and ecological effects will be characterized and integr ated to assess risk. This will be accomplished using a risk quotient (ratio of exposure concen tration to effects con centration) approach. Although risk is often defined as the likelihood a nd magnitude of adverse ecological effects, the risk quotient-based approach does not provide a quantitative estimate of likelihood or magnitude of an adverse effect. However, as outlined in the Overview Document (USEPA, 2004), the likelihood of effects to individual organisms from particular uses of ETO will be estimated using the probit dose-response slope and ei ther the level of concern or actual calculated risk quotient value. The aquatic exposure pathways considered is unlike ly to occur to aquatic organisms. In the worst case scenario, ETO is introduced to surface water during precip itation events where the gas dissolves in the precipitation, exposures to ETO is expected to be limited by its rapid evaporation from water bodies with a one-hour dissipa tion half life (see 4.1 and Appendix B ). Table 14. AERSCREEN Modeling S cenarios and Data Summary
Maximum 1-Hr Conc (μg/m 3 ) Scaled 3-Hr Conc (μg/m 3 ) Scaled 8-Hr Conc (μg/m 3 ) Scaled 24-Hr Conc (μg/m 3 ) Scaled Annual Conc (μg/m 3 )

Scenario 1: assume 21 air exchanges per hour 0.6766E+06 0.6766E+06 0.6090E+06 0.4060E+06 0.6766E+05

Scenario 2: assume 16 air exchanges per hour 0.6871E+06 0.6871E+06 0.6184E+06 0.4123E+06 0.6871E+05Page 31 of 61 Figure 2. Proposed ETO air exposure scenario for the risk assessment.

ETO concentrations in air will be modeled or monitored using the maximum labeled application rates and numbers of applicati ons, the minimum application inte rvals, and application methods that have the greatest potential for off-site transport.

ETO Concentration in Air near the Treatment Facility ETO concentrations in air will be initially es timated by a Tier-I screening model, AERSCREEN (http://www.epa.gov/scram001/dispersion_screen ing.htm). The Tier-I model will produce estimates of "worst-case" 1-hour concentrations for a single source, withou t the need for hourly meteorological data. AERSCREEN is intended to produce concentration estimates that are equal to or greater than the estimates produced by more refined models, but the degree of conservatism will vary depending on the application. Air EECs ma y be refined by the Tier II Probabilistic Exposure and Risk Model for Fumigants (PER FUM). PERFUM is capable of producing a distribution of air EECs from a range of different meteorological conditions. This analysis plan may be revisited and re vised depending upon a full review of the data available in the open literature and the inform ation submitted by the public in response to the opening of the registration review docket. 

## 4.5 Effects Analysis Plan
Additional open literature studies will be identified through EPA’s ECOTOXicology (ECOTOX) database. The ECOTOX database will be search ed during the risk asse ssment phase of ETO and the data reviewed following the Agency’s polic y for reviewing public literature for use in assessing risks from pesticides 11 . Those ecotoxicity values found in the public literature to be more sensitive than those currently in Table 13 a nd/or which satisfy an existing data gap(s) will be used during the risk assessment phase of ETO to update Table 13. ECOTOX was created and is maintained by the USEPA, Office of Research and Development, and the National Health and Environmental Effects Research Labora tory's Mid-Continent Ecology Division. 

## 5 Endocrine Disruptor Screening Program (EDSP)

As required by FIFRA and FFDCA, EPA reviews num erous studies to asse ss potential adverse outcomes from exposure to chemicals. Collectiv ely, these studies includ e acute, subchronic and

11 http://www.epa.gov/pesticides/science/efed/policy_guidan ce/team_authors/endangered_s pecies_reregistration_wor kgroup/esa_evaluation_open_literature.htm Treatment Chamber Release Vent or StackPage 32 of 61 chronic toxicity, including asse ssments of carcinogenicity, ne urotoxicity, developmental, reproductive, and general or systemic toxicity. These studies include e ndpoints which may be susceptible to endocrine influe nce, including effects on endocri ne target organ histopathology, organ weights, estrus cyclicity, sexual maturatio n, fertility, pregnancy rates, reproductive loss, and sex ratios in offspring. For ecological hazard assessments, EPA evaluates acute tests and chronic studies that assess gr owth, developmental and reprod uctive effects in different taxonomic groups. As part of its 2008 reregistra tion decision for ETO, EPA reviewed these data and selected the most sensitive endpoints for relevant risk assessment scenarios from the existing hazard database. However, as required by FFD CA section 408(p), ETO is subject to the endocrine screening part of the Endocrine Disruptor Screenin g Program (EDSP). EPA has developed the EDSP to determine whet her 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 ot her such endocrine effect s as the Administrator may designate.” The EDSP employs a two-tiered approach to making th e 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 estrog en, androgen, or thyroid (E, A, or T) hormonal systems. Chemicals that go th rough Tier 1 screening and are found to have the potential to interact with E, A, or T hormonal systems will proceed to the next stag e of the EDSP where EPA will determine which, if any, of th e Tier 2 tests are necessary base d on the available data. Tier 2 testing is designed to identify a ny adverse endocrine-related eff ects 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 scre en all pesticide chemicals. Between October 2009 and February 2010, EPA issued test orders/dat a call-ins for the firs t group of 67 chemicals, which contains 58 pesticide active ingredients and 9 inert ingredient s. A second list of chemicals identified for EDSP screening was published on June 14, 2013 12 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 screeni ng battery, please visit our website. 13
In the interim, EPA is making no human health or environmental safety findings associated with the EDSP screening of ETO. Before completing th is Registration Review, the Agency will make an EDSP FFDCA section 408(p) determination. 

## 6 Guidance for Commenters

6.1 Preliminary Work Plan
The public is invited to comment on EPA’s Preliminary Work Plan and rationale. The Agency will carefully consider all comments as well as any additional information or data provided in a timely manner prior to issuing a final work pl an for the ETO registration review case.

12 See http://www.regulations.gov/#!documentDetail;D=EPA-HQ-OPPT-2009-0477-0074 for the final second list of chemicals.
13 http://www.epa.gov/endo/Page 33 of 61 

### 6.1.1 Trade Irritants Through the registration review process, the Ag ency intends to solicit information on trade irritants and, to the extent feas ible, 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. Stakeholders are asked to comment on any trade irritant issues resulting fr om lack of MRLs or disparities between U.S. tolerances and MRLs in key export markets, providing as much specificity as possible re garding the nature of the concern.


### 6.1.2 Water Quality
The Agency invites submissi on of water quality data for this pesticide, see 4.1.1. To the extent possible, data should conform to the quality standards in Appendix A of the OPP Standard Operating Procedure: Inclusi on of Impaired Water Body and Other Water Quality Data in OPP’s Registration Review Ri sk Assessment and Management Process 14 in order to ensure they can be used quantitatively or qualitatively in pesticide risk assessments.


### 6.1.3 Environmental Justice

EPA seeks to achieve environmenta l justice, the fair tr eatment and meaningful involvement of all people, regardless of race, color, national origi n, or income, in the deve lopment, implementation, and enforcement of environmental laws, regulati ons, 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 thei r location, cultural practices, or other factors, may have atypical, unusually high exposure to ETO compared to th e general population. Please comment if you are aware of any sub-populations that may have atypical, unusually high exposure compared to the general population.


### 6.1.4 Structure Activity Relationships EPA must rely upon information of appropriate qual ity and reliability for each decision made by the Agency. In the OPP, the evaluation process for a pesticide chemical trad itionally begins with the applicant’s submission of a set of studies con ducted with the specific pesticide chemical of interest. The use of the results of such testing (meas ured data) is a logical, scientifically rigorous process that identifies the physical , chemical, and environmental fate properties of the pesticide, as well as the dose and endpoints at which an adverse effect can occu r in various animal species. Today, there is significant interest in alternat ive techniques, i.e., tech niques other than data generation that could significantly inform the Agency’s decision-making process. Recently, OPP has made increasing use of stru cture activity relationship (SAR ) as part of its regulatory decision-making process. In the SAR process, a ch emical's molecular structure is compared to that of other chemicals for which data are availabl e. These structural similarities are then used to make predictive judgments about a chemical’s physical, chemical, and biological properties. Thus, the chemical’s physical, chemical, and biol ogical properties are a f unction of (or directly related to) the chemical’s molecular structure. Quantitative SAR is referred to as QSAR. To develop a QSAR, a selected set of measured da ta on a single physical, chemical, or biological property is used to derive a model (an equatio n) to predict the valu e of that property.

14 http://www.epa.gov/oppsrrd1/registration_review/water_quality_sop.htmPage 34 of 61 Since SAR assessments and QSAR modeling are anothe r set of tools that are available to Agency scientists, OPP has begun a proce ss shift that envisions shifting from the current study-by-study approach to an approach in which the use of pr edicted data, generated us ing validated models, is considered along with information from open litera ture and studies specifically generated under Part 161 requirements. All relevant information w ould be considered as pa rt of a weight-of-theevidence evaluation. At this time, EPA believes that for certain e ndpoints, especially physi cal/chemical and fate properties, that SAR and QSAR might be effect ively utilized to fulfill these data requirements for many antimicrobial pesticide chemicals. When considering biological prope rties, at this time, EPA believes that SAR and QSAR can be most effectively utilized in the evaluation of chemicals that exhibit lower toxicity for human health and/or ecotoxicity parameters. This is appropriate because the risk assessment for lower toxicity chemicals can be stream-lined, i.e., a screening-level assessment procedure rather than multiple tiers of assessments with progressively more data requirements. If stakeholders believe that submission of predic ted data can fulfill one of the data needs for the ETO Case, then the Agency invites submission of this information. The submitter would be expected to supply a rationale describing th e utility of the information and provide documentation on the scientific va lidity of the information. The de termination that the predicted data fulfills the data requirement would be at the sole discretion of the Agency. Pre-submission consultation with the Agency is encouraged.


### 6.1.5 Additional Information Stakeholders are also specifically asked to provid e available information a nd data that will assist the Agency in refining its risk assessments, including any species-spec ific ecological effects determinations. The Agency is interested in receiving the following information:

1. Confirmation on the following label information: A. Sites of application B. Formulations C. Application methods and equipment D. Maximum application rates E. Frequency of application, applicatio n intervals and maximum number of applications F. Geographic limitations on use 2. Use or potential use distribution 3. Use history 4. Usage/use information for non-agricultura l uses (e.g., material s preservation) 5. Typical application interval 6. State or local use restrictions 7. Ecological incidents (non-target plant damage and avian, fish, reptilian, amphibian and mammalian mortalities) not alr eady reported to the Agency 8. Monitoring data 9. Availability of scrubber technology for ETO , prevalence of use, and efficiencyPage 35 of 61 

## 7 Next Steps

After the 60-day comment period closes in N ovember 2013, the Agency will review and respond to any comments received in a timely manner, a nd then issue a Final Work Plan for the Ethylene Oxide Case.Page 36 of 61 

## 8 References

ASTA (American Spice Trade Association). 2005. Public comments to Phase 3 of the reregistration risk assessment of et hylene oxide. Docket ID: OPP-2005-0203-0032/0034. http://www.regulations.gov/#!docum entDetail;D=EPA-HQ-OPP-2005-0203-0034 ATSDR (Agency for Toxic Substances and Dise ase Registry) 1990, Toxicological Profile for Enthylene Oxide, a report by ATSDR, U.S. Public Health Service. pp122 Bogyo, D.A., Lande, S.S., Meylan, W.M., Howar d, P.H. and Santodonato J. 1980. Investigation of Selected Potential Environmental Contam inants: Epoxides. A final report submitted to USEPA Office of Toxic Substa nces, Contract No. 68-01-3920. 216 pp. Conway, R.A., Waggy, G.T., Spiegel, M.H. and Berglund, R.L. (1983) Environmental fate and effects of ethylene oxide. Environ. Sci. Technol., 17,107-112. Cupitt, L.T. 1980. Fate of toxic and hazardous mate rials in the environment, Research Triangle Park, North Carolina, USEPA, Environmental Sciences Laboratory, Office of Research and Development (US EPA 600/3-80-084, PB 80-221948). Gangolli, S, 1999: The Dictionary of Substances a nd their effects, 2nd ed., The Royal Society of Chemistry. GDCh, BUA: The German Chemical Society-A dvisory Committee on Ex isting Chemicals of Environmental Relevance, 1995: Ethene Oxide BUA Report No. 141S, Hezl Verlag, Stuttgart. Gennari, M, Negre, M and Ambrosoli, R, 1987: Effects of ETO on Soil and Microbial Content and Some Soil Chemical Characteri stics. Plant and Soil, 102:197-200. Gomer, R, and Noyes, A. 1950. Photochemical Studies, XLII: ETO. J. Amer. Chem. Soc
., 72:101-108 (MRID 49126104). Hansch, C, and Leo A. 1979. Substituent constant s for correlation analysis in chemistry and biology. New York, NY: John Wiley & Sons, Inc., 176. Hazardous Substance Data Bank (HSDB), 1988: National Library of Medicine, National Toxicological Information Program, Bethesda, MD. Hellman, T.M. & Small, F.H. (1974) Char acterization of the odor properties of 101 petrochemicals using sensory methods. J. Air Pollut. Control Assoc., 24: 979-982. Howard Philips, 1989: Handbook of Environmenta l Fate and Exposure Data for Organic Chemicals, Lewis Publishers , Inc., Chelsea, MI, USA. IPCS. 2003. International Programme on Chemical Safety. Concise International Chemical Assessment Document 54. (http://www.inchem.org/documents/cicad s/cicads/cicad54.htm) (Accessed 2/27/2013). Jacobson, K.H., Hackley, E.B., & Feinsilver, L. (1956) The toxicity of inhaled ethylene oxide and Ethylene oxide vapors. Arch. ind. Health, 13: 237-244. Joshi, SB, Dodge, MC, and Bufalani, JJ. 1982. 2. Reactivities of Selected Organic Compounds and Contamination Effects. Atmospheric Environment , 16: 1301-1310: (MRID 49126101). Lyman, WJ, Reehl, WF, and Rosenblatt, DH, 1982: Handbook of Chemical Property Estimation Methods, Chapter 15, McGraw-Hill, NY (quoted from US NLM, HSDB, 2003). Public Health Risk Evaluation Database (PHRED), 1988, US EPA, Washington, DC. USEPA. 1985. Health assessment document for ethylene oxide, Washington DC, US Environmental Protection Ag ency (EPA 600/8-84/009F). USEPA. 2001. EFED RED Chapter for Ethylene Oxide DP279672. 2ppPage 37 of 61 USEPA. 2002. ECOTOX User Guide: ECOT OXicology Database System. Version 3.0. Available: http://www.epa.gov/ecotox/ USEPA. 2004. Overview of the Ecological Risk Assessment Process in th e Office of Pesticide Programs, U.S. Environmental Protection Ag ency. Endangered and Threatened Species Effects Determinations. Office of Prevention, Pe sticides and Toxic Substances, Office of Pesticide Programs, Washi ngton, D.C. January 23, 2004. USEPA. 2008. Review of Calculat ed Ethylene Oxide Exposures for Ethylene Oxide Sterilization Plant Workers (MRID 47331801) Submitted in Support of the Occupational Exposure Assessment of the Antimicrobial Uses of Ethylene Oxide for the Reregistration Eligibility Decision (RED). DP 348868. USEPA. 2008. Reregistration Eligibility Decision for ETO, 2008. Online at http://www.epa.gov/oppsrrd1/ REDs/ethylene-oxide-red.pdf USEPA. Ecological Structure Activity Re lationships (ECOSAR). 2011. Version 1.10, http://www.epa.gov/oppt/newchems/tools/21ecosar.htm

. USEPA. 2013a. BEAD Chemical Profile for Re gistration Review: Ethylene oxide (042301). 5pp. USEPA. 2013b. Guidance for Conducting Fumigant Exposure Assessment in Ecological Risk Assessment. Interim Divisional Guidance, EFED. 118pp. WHO. 1985. Environmental Health Criteria 55: Ethylene oxide, Geneva, Switzerland, World Health Organization, 79 pp. WHO. 2003. Concise International Chemical Assessment Document 54. Ethylene oxide, Geneva, Switzerland, World Health Organization, 63 pp.Page 38 of 61 

# Appendix A Toxicology Profile

The following tables summarize the toxicity of ETO and ECH. The tables include both the acute toxicity profile and the profile afte r repeated dosing for both chemicals. Table 15 – ETO – Acute Toxicity Study/ Species MRID or Publication Results Classification

870.1100 Acute Oral Rats Mice

Guinea pigs IPCS, 2003 IPCS, 2003

IPCS, 2003 LD 50 = 330 mg/kg (m) LD 50 = 365 mg/kg (m) LD 50 = 280 mg/kg (f) LD 50 = 270 mg/kg (m&f) Category II Category II

Category II 870.1200 Acute Dermal, Rabbits No Study Identified N/A N/A 870.1300 Acute Inhalation, Rats Acute Inhalation, Rats Acute Inhalation, Mice Acute Inhalation, Dogs 42046601 42429201 IPCS, 2003 IPCS, 2003 4h-LC 50 = 1741 ppm (3.1 mg/L) (m&f) 1h-LC 50 =5029 ppm (9.2 mg/L) (m&f) 4h-LC 50 = 820 ppm (1.5 mg/L) 4h-LC 50 = 983 ppm (1.8 mg/L) Category IV Category IV Category III Category III 870.2400 Primary Eye Irritation, Rabbits No Study identified

870.2500 Primary Skin Irritation, Rabbits No Study Identified

870.2600 Dermal Sensitization, Human case study 40087801 Sensitization possible

870.6200 Acute Neurotoxicity 44256402 Doses: 0, 100, 300, 500 ppm NOAEL:100 ppm LOAEL: 300 ppm Drooping eyelids/half-closed eyes, low arousal, no response to approach Acceptable/Guideline

LD 50 = lethal dose, 50% Table 16 – ETO – Subchronic, Chronic Toxicity Studies

Study/Species MRID or Publication Doses Results/Classification
Developmental/Reproduction Toxicity Developmental Toxicity Rats 42797702 Doses (inhalation): 0, 50, 125, 225
ppm (6h/day, GD 6- 15) Maternal NOAEL: 50 ppm Maternal LOAEL: 125 ppm Decreased body weight gain on GDs 6-15 and GDs 0-21 Developmental NOAEL: 50 ppm Developmental LOAEL: 125 ppm Decreased fetal weight, increased litter incidence of delayed ossification in phalanges, metatarsals, metacarpals and sternebrae #4-6 Acceptable/Guideline Developmental Toxicity, Rabbits 41874102 Doses (inhalation) : 0, 150 ppm GD7-19, GD1- 19 7h/day Maternal and Developmental NOAEL: 150 ppm Maternal and Developmental LOAEL: Not Established

Unacceptable/Guideline No dose response effect s were determinedPage 39 of 61 Study/Species MRID or Publication Doses Results/Classification

Two-Generation Reproduction Study, Rats 42788101 Doses (inhalation): 0, 10, 33, 100
ppm 6h/day, 5d/week Parental NOAEL: 10 ppm Parental LOAEL: 33 ppm Decreased body weight and/or weight gain in F0 and F1 males during premating Reproductive NOAEL: 10 ppm Reproductive LOAEL: 33 ppm Increased post implantation loss in F0 generation Offspring NOAEL: 10 ppm Offspring LOAEL: 33 ppm Decreased mean body weight and we ight gain of F1pups on PND 7 and PND 21 Acceptable/Guideline Subchronic Toxicity Subchronic Neurotoxicity, Rats, 13 weeks

Subchronic Neurotoxicity, Rats, 4 weeks 44359401

44256401 Doses (inhalation): 0, 25, 50, 100, 200 ppm

Doses (inhalation): 0, 100, 300, 400, 500 ppm NOAEL: 100 ppm LOAEL: 200 ppm Decreased body weight gain in both sexes and decreased hindlimb grip strength in females Note: Cancer incidence in all treated groups during 13 weeks recovery period. Malignant glioma in cerebra l cortex at 200 ppm (1 male), mononuclear cell leukemi a (1 male at 100 ppm), hemangiosarcoma of skin (1 male at 25 ppm) and basal cell carcinoma of the skin (1 female at 50 ppm; 1 female at 200 ppm) 5/sex/dose evaluated Acceptable/Guideline NOAEL: 100 ppm LOAEL: 300 ppm Decreased body weight, body weight gain, hindlimb grip strength Range Finding Study Subchronic (14 weeks) B6C3F1 Mice NTP (1987) Doses (inhalation): 0, 50, 100, 200, 400, 800
ppm NOAEL: 50 ppm LOAEL: 100 ppm Renal tubular degeneration Acceptable/Non-Guideline

Subchronic (10 weeks) B6C3F1 Mice Snellings et al
., 1984 Doses (inhalation): 0, 10, 50, 100, 250 ppm NOAEL 50 ppm LOAEL 100 ppm Neurological effects such as altered gait, decreased locomotor activity and abnormal ri ghting reflex and organ weight changes. Acceptable/Non-Guideline Chronic Toxicity 870.4100Chronic ToxicityMonkeys 2 years MRID 42159401, Setzer et al ., 1996 and IPCS, 2003 Doses (inhalation): 0, 50, 100
ppm 6-7h/day, 5d/wk, 24 months, 12 males/
treatment NOAEL: Not Established LOAEL: 50 ppm Eye lesions, demyelination of the sciatic nerve, axonal dystrophy in the nucleus gracilis, decreased sperm counts and motility abnormalities; Decreased mean conductio n velocity at 100 ppm Deficiencies: Age of animals unknown; inadequate dose groups, Incomplete study details with regard to study examination, individual gross or histological data, inadeq uate hematological and clinical parameters etc..); small number of animals tested (only 2 animals were sacrificed after 2 years of exposure). Acceptable/Non-Guideline StudyPage 40 of 61 Study/Species MRID or Publication Doses Results/Classification

Combined Chronic Carcinogenicity Chronic Carcinogenicity Study, Rats 2 years Snellings et al

. (1984b) Garman et al

. (1985), Garman and Snellings, (1986) Doses (inhalation): 0, 10, 33, 100
ppm (6h/day, 5d/week) Systemic NOAEL: 10 ppm Systemic LOAEL: 33 ppm Decreased survival and body weight Type of cancer incidence-0, 10, 33, 100 ppm: mononuclear cell leukemia-13/97, 9/51, 12/39, 9/30 (m), 11/116, 11/54, 14/48, 15/26 (f); peritoneal mesothelioma- 2/97, 2/51, 4/39, 4/30 (m), brain tumorswhich include glioma, malignant reticuloses and granular cell tumors1/181, 1/92, 5/85, 7/87 (m), 1/188, 1/94, 3/92, 4/80 (f) Acceptable/Non-Guideline Study Chronic Carcinogenicity Study, Male Rats Lynch et al (1984) Doses (inhalation): 0, 50, 100 ppm (males only) (7h/day, 5d/week) Systemic NOAEL: Not Established Systemic LOAEL: 50 ppm Decreased body weight gain, organ weights and non-neoplastic lesions in adrenal cortex, spleen and respiratory tract) Type of cancer incidence-0, 50 , 100 ppm: mononuclearcell leukemia24/77, 38/79, 30/76; peritoneal mesothelioma- 3/78, 9/79, 21/79; mixed cell brain glioma-0/76, 2/77, 5/79 Note: No interim clinical and hema tological parameters measurements; inadequate clinical parameter measurements at the termination (NIOSH study) Acceptable/Non-Guideline Study 870.4300 Combined Chronic Toxicity/Carcinogeni city Mice NTP (1987) Doses (inhalation): 0, 50, 100
ppm (6h/day, 5d/week) Systemic NOAEL: 100 ppm Systemic LOAEL: Not Established (Type of cancer incidence, control, 50, 100 ppm): alveolar/bronchiolar carcinoma-6/50, 10/50, 16/50 (m), 0/49, 1/48, 7/49 (f); harderian gland papillary cystadenoma-1/43, 9/44, 8/42 (m), 1/46, 6/46, 8/47 (f); malignant lymphoma of hematopoieti c system-9/49, 6/48, 22/49 (f); uterine adenocarcinoma-0/49, 1/ 47, 5/49 (f), mammary gland adenocarcinoma or adenosquamous carcinoma-1/49, 8/48, 6/49 (f) Acceptable/Non-Guideline Subchronic Dermal Toxicity 21-Day Dermal Toxicity (Rats) No Study identified - -
Dermal Absorption No Study identified - -

Metabolism Rat Metabolism IPCS, 2003 - Absorption: Very soluble in blood; rapid absorption in several species; limited by the concentration in air and ventilation rate Distribution: In mice greater am ount of inhaled ETO is found distributed in liver, kidneys and l ungs with small amounts in spleen, testes and brain. In rats, greate r amount of inhaled ETO is found in urinary bladder, liver, packed blood cells, adrenal glands and lower levels in fat Metabolism: Two pathways are identified. 1) ETO is found hydrolyzed to EG and subsequently to oxalic ac id, formic acid and carbon dioxide. This is predominant in larger sp ecies such as rabbits and dogs 2) Conjugation with glutathione. This step is predominant in rats and mice. Excretion: In rats and mice 40-80% of the inhaled dose is eliminated in urine within 48 hours Large amount of the administered ETO are eliminated in the urine as glutat hione conjugates; Small amounts (10%) are eliminated as carbon dioxide and negligible amounts (1%) are eliminated via lungs as the parent compoundPage 41 of 61 Study/Species MRID or Publication Doses Results/Classification

Mutation/Genotoxicity IPCS, 2003 - Positive evidence for mutation in bacteria, eukaryotic somatic and germ cells; Increased chromosomal aberrations, sister chromatid exchange and unscheduled DNA synthesis in mammalian cells,, Induction of dominant lethal mutations and heritable translocations in mice. In humans, increased chromosomal aberrations in peripheral blood leukocytes of workers exposed to ETO. Human Studies Steenland et al

. 2003 - Breast cancer incidence studied in a cohort of 7576 women. Breast cancer reported in 319 subjects. The st andardized incidence ratio (SIR) for incident breast cancer in the whole cohort was below the US population. Trend analysis in SIRs, using Poisson regression was positive with increasing exposure (p=0.002). The odds ratios with 15 year lag for cumulative exposure ca tegories, 0 (lagged out), <647, 647- 2026, 2026-4919, 4919-14620, >14620 ppm-days were 1.00, 1.06, 0.99, 1.24, 1.42, and 1. 87, respectively. Steenland et al

. 2004 - In the mortality analysis of a 1998 follow-up study of a large cohort of 18235 men and women, 2852 deaths present. The mortality analysis of the overall cohort indicates no exce ss risk for hematopoietic cancers combined or of non-Hodgkin’s lymphoma. However, internal exposure response analyses conducted using a 15 year lag found positive trends for hematopoietic cancer s in males (p=0.02). The odds ratios with 15 year lag for hematopoietic cancer mo rtality in males were 1.00, 1.23, 2.52, 3.13, and 3.42 for 0 (lagged out), >0-1199, 1200-3679, 3680- 13499, >13500 ppm-days, respectively . The trend in hematopoietic cancer was driven by lymphoid tu mors (non-Hodgkin’s lymphoma, myeloma, lymphocytic leukemia). A lthough there is no excess overall risk for breast cancer, internal exposure analyses found positive trend for breast cancer using the log of cumulative exposures with a 20 year lag (p=0.01). The odds ratios with 20 year lag for breast cancer mortality correspond to 1.00, 1.76, 1. 77, 1.97, and 3.13 for cumulative exposure categories, 0 (lagged out), >0-646, 647-2779, 2780-12321, >12322 ppm-days, respectively.Page 42 of 61 

# Appendix B Environmental Fate

Environmental Fate and Transport Properties of ETO The primary mode of transport of ETO for both th e antimicrobial and conventional uses is via air emissions into the atmosphere. ETO enters the environment mainly through vented gases during use. Because ETO uses fall under the indoor us e category for conventional pesticides and historically an indoor use patter n for antimicrobials and is a ga seous substance, submission of environmental fate data has not been required (40 CFR Sections158.630, 660, and 1300). Table 17. Environmental Fate Properties of ETO Parameter Value Reference Hydrolysis (t 1⁄2 @ 25oC, pH 7) 13.8 days Bogyo et al., 1980 Aqueous Photolysis (t 1⁄2) N/A Atmospheric Oxidation (t 1⁄2 @ 25 oC, 12-hr day) 38.16 days EPI V4.10 Soil Photolysis (t 1⁄2) N/A Aerobic Soil Metabolism (t 1⁄2) N/A Anaerobic Aquatic Metabolism (t 1⁄2) N/A Aerobic Aquatic Metabolism (t 1⁄2) N/A BCF Estimates 3.162 L/Kg wet-wt EPI V4.10
M

obilit y Koc 4.662 (mL/g) EPI V4.10 Field Dissipation Terrestrial Field Dissipation (t 1⁄2) N/A Volatilization (t 1⁄2 from Model River) 3.30 (hrs) EPI V4.10 Volatilization (t 1⁄2 from Model Lake) 91.68 (hrs) EPI V4.10

Air The major removal of ETO from the atmosphe re will occur rapidly via oxidation by hydroxyl radicals. The atmospheric residence time of ET O was calculated to be 5.8 days based on the theoretical rate constant fo r this reaction (Cupitt, 1980). However, experimental data have shown the residence time to be 100 - 215 days, depending on the hydroxyl radical concentration and the ambient temperature (US EPA, 1985). Because of its high solubility in water (1000 g/L), ETO levels in air can also be reduced via washout by rain (Conway et al., 1983). The photochemical reactivity of ETO ozone-forming ability is low (Joshi et al., 1982). Joshi et al. 1982 (MRID 49126101) determined the photolyt ic reactivity of five oxygen containing hydrocarbons, ETO being one of them, in sm og chambers specially made for the study. Irradiation was provided through fl uorescent lamps consisting of 22 black lights, and 7 sunlamps kept around the smog chamber. Initial concentrat ion of ETO was 4 ppm, and the residual concentration of ETO was monitore d by using Porapak Q columns at 100 o C. The photooxidation of ETO is slow in the atmosphere; its half life was measured to be 53 hours. This is a non-guideline study. It is classified as suppl emental because not all raw data is available for independent review. The information is useable in a risk assessment.Page 43 of 61 Gomer and Noyes, 1950 (MRID 49126104) investigated the direct impact of sunlight on the photodecomposition and characteriza tion of photochemical degradates of ultra pure ETO in the presence or absence of some reactants. The photochemical degradates of ETO with direct sunlight in the absence of any reactants we re: methane, ethane, hydrogen and carbon monoxide, and minor quantities of formaldehyde and acetald ehyde. The duration of the formation of the photodegradates was not determined. The study is a non-guideline study. It is classified as supplemental. A German Study concluded that ETO is not degr aded by direct sunlight in the atmosphere (GDCh BUA, 1995).

Water and Sediment Evaporation from water is expected to be a si gnificant ETO removal process. Conway et al. (1983) found a half-life of <1 h for ETO evaporation from wate r. ETO degradation in water through ionic reactions and hydrolys is appear to be comparatively slow in the environment. Volatilization from Water or Water Desorption Conway et al. 1983 (MRID 49126102) studied the volatilization of ETO from water under no wind and under a 5 meter/second wind conditions. The study showed that with no wind, the volatilization half life of ETO is 0.72 hours and that under a wind flow of 5 meters/second the half life is 0.88 hours in neutral conditions. The results under perturbed and non-perturbed conditions indicate that pe rturbation is not a required condi tion for volatilization. ETO is broken down in fresh water to form 1,2-ethanediol with a half-life of 14 days at 25 °C. In 3% saline water, 77% ETO forms 1,2-ethanedi ol and 23% forms 2-chloroethano l with a half-life of 9 days (Conway et al., 1983). The results indicate that th e half lives in these three media are quite similar to each other (9 to 14 days), which likel y means that presence of biota is not a condition for the degradation of ETO. This study is classifi ed as supplemental because not all raw data is available for independent review. The informa tion is useable in a risk assessment and no additional volatilizati on data is required. A study by Gomer, and Noyes (1950), showed that ETO auotocatalyzes into methane, ethane, hydrogen, carbondioxide (MRID# 49126104). Hydrolysis ETO degradation in water through ionic reactions and hydrolysis appear to be comparatively slow in the environment. In 1999, Gangolli reported a 12-14 day hydrolytic half life for ETO in fresh water, with 9-11 day hydrolytic half-life in seawater. Thus this study indicates that under biotic conditions, ETO hydrolyzes, and is not considered as pers istent in biotic conditions (MRID 49126105). Conway et al., 1983 (MRID 49126102) conducted a hydrol ysis study with ETO in three different media sources: distilled water, natural fresh wate r, and salt water. Natural fresh water samples were made from the water collected from Kanawha River (South Carolina). Salt water was created by adding sodium chloride at 0%, 1% , and 3%, mixing dipotassium hydrogen phosphate, and sodium dihydrogen phosphate, and then a kn own quantity of ETO wa s dissolved in the solution. Hydrolysis half life in natural water was determined to be 14 days; in salt water it was about 9 days (in the presence of 3% sodium chloride); and in di stilled water it was measured to be about 12 days. Chemical degradates in th ese media included ethylene glycol (or simplyPage 44 of 61 glycol), chlorohydrin, and in sea water bromohy drin. The study is a non-guideline study and was published as a research paper. This study is classified as supplemen tal because not all raw data is available for independent review. The informa tion is useable in a risk assessment and no additional hydrolysis data ar e expected to be required. Virtanen (1963) reported that ETO ’s half-life is 309 days at 0 °C, and the reaction is acid- and base-catalyzed. Bogyo et al., ( 1980) reported that ETO hydrolyzes under neutral conditions with a half life of 13.8 days at 25°C. Octanol-Water Partition Coefficient ETO is a very polar chemical with a logarith m of the octanol/water partition coefficient (K ow ) of -0.30 (EPI Suite, version 4.10) Biotic Metabolism - Aquatic Microorganisms were found to degrade ETO very slowly with biological oxygen demand varying from between 3-5% and 52% of the theo retical oxygen after 5 and 20 days, respectively (Bridié et al., 1979; Conway et al., 1983).

Soil The log K oc value of ETO is 0.325 which indicates a hi ghly mobility through soil. Thus if ETO has not degraded while migrating through soils, it might contaminate ground water. Fate and Transport in WWTP Conway et al., 1983 (MRID 49126102) conducted a biodegradation study using an American Public Health Association method as outlines in the Standard Methods for the Examination of Water and Wastewater Method (APHA, 14 th Edition, Washington, DC). The results showed that ETO was degraded 5% by day 5, 22% by day 10 , and by day 20, it had degraded by 52%. This study indicates that ETO is degradable, but canno t be classified as ready biodegradable. This study is classified as supplemental because not all raw data is available for independent review. The information is useable in a risk a ssessment and no additional activated sludge biodegradation data are e xpected to be required.

Bioaccumulation The log Kow of ETO (-0.30) is very small, and t hus it is not likely to bioaccumulate in aquatic organisms. There are no published reports of measured bioconcent ration in any aquatic organisms. A bioconcentration factor can be estimated using the log Kow: Log BCF = (0.76)(log K ow) - 0.23 With a log K ow of -0.45, then the log BCF is 0.167 , which indicates that the likelihood bioaccumulation of ETO into aquatic organism is low. Analytical Method(s) ETO in environmental samples is most commonly determined after derivatization to stable, volatile halogenated species, pa rticularly 2-bromoethanol followed by GC/ECD (Cummins et al. 1987), or by GC/MS (Farmer et al. 1986). ETO in air samples can be directly analyzed by a portable gas chromatograph using clean air as a carrier gas and a photoion ization detector (PID) for detection (Bond and Dumas 1982; Collins and Ba rker 1983). A method for the determinationPage 45 of 61 of ETO in water and soil samples by partition in frared spectrophotometry has been reported (APHA 1985; Environment Canada 1985). References Appendix B Conway, RA, Waggy, GT, Spiege l, MH, and Berglund, RL. 1983. Environmental Fate and Effects of Ethylene Oxide. Environmental Sci. Technol. , 17(2): 107-112 (MRID 49126102). Gangolli, S, 1999: The Dictionary of Substances a nd their effects, 2nd ed., The Royal Society of Chemistry. GDCh, BUA: The German Chemical Society-A dvisory Committee on Ex isting Chemicals of Environmental Relevance, 1995: Ethene Oxide BUA Report No. 141S, Hezl Verlag, Stuttgart. Gennari, M, Negre, M and Ambrosoli, R, 1987: Effects of ETO on Soil and Microbial Content and Some Soil Chemical Characteri stics. Plant and Soil, 102, pp 197-200. Gomer, R, and Noyes, A. 1950. Photochemical Studies, XLII: ETO. J. Amer. Chem. Soc
., 72:101-108 (MRID 49126104). Hazardous Substance Data Bank (HSDB), 1988: National Library of Medicine, National Toxicological Information Program, Bethesda, MD. Howard Philips, 1989: Handbook of Environmenta l Fate and Exposure Data for Organic Chemicals, Lewis Publishers , Inc., Chelsea, MI, USA. Joshi, SB, Dodge, MC, and Bufalani, JJ. 1982. 2. Reactivities of Selected Organic Compounds and Contamination Effects. Atmospheric Environment , 16: 1301-1310: (MRID 49126101). Lyman, WJ, Reehl, WF, and Rosenblatt, DH, 1982: Handbook of Chemical Property Estimation Methods, Chapter 15, McGraw-Hill, NY (quoted from US NLM, HSDB, 2003). Public Health Risk Evaluation Database (PHRED), 1988, US EPA, Washington, DC. USEPA, 1982b: US EPA Fede ral Register, # 47, 26992-27008 USEPA, 1988: US EPA, Part V, Federal Register; # 53: 38642-38654 WHO, 1985: Environmental Health criteria 55: Ethylene oxide, Geneva, Switzerland, pp 2-79Page 46 of 61 

# Appendix C Ecotoxicology Profile

Toxicity of ETO to Terrestrial Receptors

Mammals

There is acute oral information for three mamm alian species: laboratory rats, mice, and guinea pigs. Selected endpoints for these species are pr ovided in the Appendix A Toxicology Profile for human health. The median lethal dose (LD 50 ) ranges from 270 mg/kg-bw for guinea pigs (male and female, combined) to 365 mg/kg-bw for ma le rats (IPCS, 2003). These results categorize ETO as moderately toxic to mammalian wildlife on an acute oral basis.

There is acute inhalation da ta for three mammalian species: laboratory rats, mice, and dogs. Selected endpoints for these species are provi ded in the Appendix A Toxicology Profile for human health (MRIDs 42046601 and 42429201; IPCS , 2003). The four hour median lethal concentration (4-h LC 50 ) values range from 820 ppm (1.5 mg /L) for mice (males and females, combined) to 1741 ppm (3.1 mg/L) for rats (male and femal, combined); the 1-hr LC 50 value available for rats (males and females, combined) is 5029 ppm (9.2 mg/L). There is also an inhalation exposure, two- generation rat study (MRID 42788101). The parental, reproductive and offspring no obser ved adverse effect concentrat ion (NOAEC) from the study is 10 ppm (0.018 mg/L).

Birds There is no ETO acute or chronic toxicity data fo r birds. Inhalation data for birds are anticipated as needed to determine risk from ETO use pattern s. ETO has fumigant uses that may result in exposure to birds. The acute effects to birds exposed to ETO are unknown. Avian acute inhalation toxicity data were not submitted for birds exposed to ETO; however, the study anticipated to be required is a non-guideline st udy under the 40 CFR Part 158 data requirements. Typically, the Agency asks for avian acute oral and dietary studies with an upland game bird, a passerine bird and a waterfowl to assess the acute effects to birds via the oral and dietary routes; however, because ETO is a gas, which is releas ed to the atmosphere after aeration of the treatment chamber, the terrestrial animal expos ure route considered most likely to occur is through inhalation of the gas. Therefore, th e Agency expects to require a non-guideline inhalation study with birds instead of the oral and dietary studies. Since th is inhalation study is a non-guideline study, a study protocol would need to be submitted for review by the Agency prior to test initiation. The preferred bird species is the Northern bobwhite quail. Until an acute inhalation endpoint to evaluate acute risk to birds is available, th e acute risk to birds exposed to ETO cannot be precluded and will be presumed.

Beneficial Insects ETO has fumigant uses that may result in e xposure to honeybees. The toxicity of ETO to honeybees is unknown. Honeybee acute vapor-phase exposure toxicity data were not submitted for beneficial insects exposed to ETO; however , the study anticipated to be required is a nonguideline study under the 40 CFR Part 158 data requirements. ETO is an insecticide which is formulated to kill insects, some effects to inse cts are expected (as observed in other terrestrial invertebrate studies), the Agen cy expects to require a non-gu ideline vapor-phase exposure toxicity study with bees to assess whether the effects seen in bees are similar to those observed inPage 47 of 61 other terrestrial invertebrates. Since this vapor-phase expos ure study is a non-guideline study, a study protocol that calculate s a vapor-phase exposure LD 50 for adult bees would need to be submitted for review by the Agency prior to in itiation of the study. Until an acute vapor-phase exposure endpoint to evaluate the to xicity to honeybees is available, the acute risk to beneficial insects exposed to ETO cannot be precluded and will be presumed.

Terrestrial Plants ETO has fumigant uses that may result in exposur e to terrestrial plants. Typically, the Agency requires seedling emergence and vegetative vigor studi es to assess the effects to terrestrial plants exposed to a pesticide as a result of surface wate r runoff or/and off-site spray drift, respectively; however, because ETO will be released from treatme nt chambers as a gas, the terrestrial plant exposure pathway considered most likely to occu r is through contact of the external layer of plant tissues as a result of spray drift. Instead of needing both seedling emergence and vegetative vigor studies, the Agency only expects to need ve getative vigor data with actively growing plants to assess the effects of ETO when the gas penetrat es the plants. The Agency uses a battery of ten species 15 representing at least six different families to evaluate potential effects to all flora. There is one vegetative vigor study with a dicot speci es (soybean) exposed to ETO as a gas (MRID 47921701). At the highest exposure concentration of 252 mg ai/m 3 , no effects to vegetative vigor were observed (i.e., IC 25 >252 mg ai/m 3 , NOAEC > 252 mg ai/m 3 ). The Agency expects to require vegetative vigor data with ETO for the remaining nine species in the battery. 

### Toxicity of ETO to Aquatic Receptors
No aquatic toxicity data has been submitted for ETO. Conaway et al., 1983 tested ETO with several aquatic species; they are provided in Ta ble 18. These studies were conducted under static conditions and results are based on nominal, not measured exposure concentrations. Given the known fate characteristics of ETO in water, the concentration of ETO in these studies was not likely stable throughout the durati on of the test due to volatil ization, hydrolysis to EG, and biodegradation. ECOSAR version 1.10 was used to es timate aquatic toxicity results for the green algae, and acute and chronic resu lts for a generic freshwater fish and a freshwater daphnia (see the following ECOSAR version 1.10 results pa ge). ETO is a member of the mono epoxides group, which was used in ECOSAR version 1.10 to m odel toxicity results. There is a footnote in the ECOSAR version 1.10 results output th at empirical ETO data, a fish 96-h LC 50 value and a 48-h EC 50 value for a daphnid (Conaway et al ., 1983), are included in the structure activity model for the mono epoxides group. Current guid eline standards call for flow through tests and measured concentrations for such test substances to ensure stable exposure concentrations for the duration of the study (USEPA 1986). Since ETO’s vapor pressure and experimental half -life <1 hr indicates it will rapidly volatilize out of water, exposure of aquatic organisms is not considered a significa nt exposure pathway and additional aquatic toxicity data is not anticipated as being needed to conduct the risk assessment for the sterilization and spice fumigation use patterns.

15 Battery of species consists of six dicot species of at least four families, one species of which is soybean ( Glycine

max ), and four dicot species of at least two families, one species of which is corn ( Zea mays ). Additionally of the ten species tested, at least one species s hould be a root crop (either a monocot su ch as onion or dicot such as carrot, table beet or sugar beet).Page 48 of 61 Table 18. Effects Data on ETO

Data Requirement Test Species, Test Type Value Submitted Studies (MRID or Citation) Study Classifications/ Toxicity Classification

Freshwater fish, acute toxicity Fathead minnow ( Pimephales promelas ), static, nominal 96-h LC 50 = 85 mg a.i./L Conway et al., 1983 Supplemental/ Slightly toxic

Freshwater invertebrate acute toxicity Waterflea ( Daphnia
magna ), static, nominal 48-h EC 50 = 137 mg a.i./L Conway et al, 1983 Supplemental/ Practically non-toxic

Estuarine/Marine fish Acute toxicity Striped mullet ( Mugil cephalus ) 96-h LC 50 = 89 mg a.i./L Crews et al., 1974 Supplemental/ Slightly oxic

Acute toxicity Brine shrimp 1
Artemia sp. EC 50 = 490 mg a.i./L Conway et al, 1983 Supplemental/ Not surrogate for estuarine/marine Aquatic plant growth: Tier I vascular plants Duckweed ( Lemna gibba ) IC 50 >0.87 mg/L NOAEC > 0.87 47921702 Acceptable/

-- 2

Aquatic plant growth: Tier I algae Freshwater green alga ( Pseudokirchneriella subcapitata ), static IC 50 >0.86 mg/L NOAEC > 0.86 47921703 Acceptable/

-- 2

1 Brine shrimp, which are found in specialized habitat, ar e not used as a surrogate for estuarine/marine species.
2 Toxicity categories have not been assigned for aquatic plants.
Table 19. ECOSAR v1.11 Results for ETO Organism Endpoints Fish, Freshwater generic 96-h LC 50 = 57.7 mg/L ChV = 0.015 mg/L Daphnia, Freshwater Invertebrate, generic 48-h EC 50 = 278 mg/L ChV = 27.8 mg/L
Green algae, generic 96-h IC 50 = 501 mg/L ChV = 168 mg/L ChV = geometric mean of the NOEC and LO EC, also referred to as the MATC 

### Effects of ETO on Soil Microbes
Gennari et al. 1987 (MRID 49126103) investigated th e effects of ETO on soil microflora in a west German soil sample with specifications similar to the US sandy loam soil. Suspensions were prepared by adding 100 grams of soil in 100 ml of water. Effects on the following microorganisms were monitored: fungi, actinomy cetes, aerobic and anaerobic nitrogen fixers, ammonifiers, nitrifying, denitrif ying, proteeolytic, ammololyti c, pectinolytic, aerobic and anaerobic cellulolytic. The exposure with ETO was carried out for f our hours and eight hours. The study was conducted by taking 10% ETO in a chamber containing carbon dioxide (CO 2 ) atmosphere (3375 mm Hg pressure), where 65% relative humidity was ma intained and temperature was kept at 40 o C. After 3 days, desorption process was carried out. Microb ial analysis on the 4 ho ur-treated soil did not show any degree of sterilization; however, 8 hour treated soil showed comple te elimination of all microorganisms. Slight changes in soil characteri stics were observed for the ETO-treated soil. These changes were: a slight incr ease in pH, an increase in orga nic matter, and an increase inPage 49 of 61 available phase iron (Fe) and manganese (Mn). These metals were extractable by ethylene diamine tetraacetate (EDTA) analysis. A slight d ecrease in cation excha nge capacity and total nitrogen (N) content was also observed with ETO -treated soil. This study indicated a strong pesticidal effect of ETO on th e soil microorganisms. The stu dy is a non-guideline study. It is classified as supplemental and useable for charac terizing effects to soil microflora and function from exposure to ETO. 

### Aquatic Toxicity of Degradate EG

There is an acute freshwater fish and invertebrate value for EG (Table 20). Both results indicate this degradate is significantly less toxic than the parent ETO. Table 20. Summary of the Most Sensitive Endpoi nts from Aquatic Toxicity Studies for EG (Degradate of ETO). Receptor Group Surrogate Species Risk Scenario Toxicity Endpoint Reference (MRID)

Freshwater fish 1 Fathead minnow 1 ( Pimephales
p romelas ) Acute 96-h LC 50 > 100,000 mg a.i./L Conway et al., 1983

Freshwater invertebrates Waterflea ( Daphnia
magna ) Acute 48-h EC 50 >100,000 mg a.i./L Conway et al., 1983

References Appendix C ASTA (American Spice Trade Association). 2005. Public comments to Phase 3 of the reregistration risk assessment of et hylene oxide. Docket ID: OPP-2005-0203-0032/0034. http://www.regulations.gov/#!docum entDetail;D=EPA-HQ-OPP-2005-0203-0034 ATSDR (Agency for Toxic Substances and Dise ase Registry) 1990, Toxicological Profile for Enthylene Oxide, a report by ATSDR, U.S. Public Health Service. pp122 Bogyo, D.A., Lande, S.S., Meylan, W.M., Howar d, P.H. and Santodonato J. 1980. Investigation of Selected Potential Environmental Contam inants: Epoxides. A final report submitted to USEPA Office of Toxic Substa nces, Contract No. 68-01-3920. 216 pp. Conway, R.A., Waggy, G.T., Spiegel, M.H. and Berglund, R.L. (1983) Environmental fate and effects of ethylene oxide. Environ. Sci. Technol., 17,107-112. Cupitt, L.T. 1980. Fate of toxic and hazardous mate rials in the environment, Research Triangle Park, North Carolina, USEPA, Environmental Sciences Laboratory, Office of Research and Development (US EPA 600/3-80-084, PB 80-221948). Gennari, M, Negre, M, Ambrosoli, R. 1987. Effects of Ethylene Oxide on Soil Microbial Content and Some Soil Chemical Charact eristics Plant ands Soil, 102:197-200. Hansch, C, and Leo A. 1979. Substituent constant s for correlation analysis in chemistry and biology. New York, NY: John Wiley & Sons, Inc., 176. Hellman, T.M. & Small, F.H. (1974) Char acterization of the odor properties of 101 petrochemicals using sensory methods. J. Air Pollut. Control Assoc., 24: 979-982. IPCS. 2003. International Programme on Chemical Safety. Concise International Chemical Assessment Document 54. (http://www.inchem.org/documents/cicad s/cicads/cicad54.htm) (Accessed 2/27/2013).Page 50 of 61 Jacobson, K.H., Hackley, E.B., & Feinsilver, L. (1956) The toxicity of inhaled ethylene oxide and Ethylene oxide vapors. Arch. ind. Health, 13: 237-244. United States Environmental Protection Agency (USEPA). 1985. Health assessment document for ethylene oxide, Washington DC, US Envi ronmental Protection Agency (EPA 600/8- 84/009F). USEPA. 2001. EFED RED Chapter for Ethylene Oxide DP279672. 2pp USEPA. 2004. Overview of the Ecological Risk Assessment Process in th e Office of Pesticide Programs, U.S. Environmental Protection Ag ency. Endangered and Threatened Species Effects Determinations. Office of Prevention, Pesticides and Toxic Substances, Office of Pesticide Programs, Washi ngton, D.C. January 23, 2004. USEPA. 2008. Reregistration Eligibility Decision for ETO, 2008. Online at http://www.epa.gov/oppsrrd1/ REDs/ethylene-oxide-red.pdf USEPA. Ecological Structure Activity Re lationships (ECOSAR). 2011. Version 1.10, http://www.epa.gov/oppt/newchems/tools/21ecosar.htm

. USEPA. 2013a. BEAD Chemical Profile for Re gistration Review: Ethylene oxide (042301). 5pp. USEPA. 2013b. Guidance for Conducting Fumigant Exposure Assessment in Ecological Risk Assessment. Interim Divisional Guidance, EFED. 118pp. WHO. 1985. EHC 55: Ethylene oxide, Ge neva, World Health Organization, 79 pp. 

### ECOSAR Version 1.10 Results Page

SMILES : O(C1)C1 CHEM : Oxirane CAS Num: 000075-21-8 ChemID1: MOL FOR: C2 H4 O1 MOL WT : 44.05 Log Kow: -0.045 (EPISuite Kowwin v1.68 Estimate) Log Kow: (User Entered) Log Kow: -0.30 (PhysProp DB exp value - for comparison only) Melt Pt: (User Entered for Wat Sol estimate) Melt Pt: -111.70 (deg C, PhysProp DB exp value for Wat Sol est) Wat Sol: 3.067E+005 (mg/L, EPISuite WSKowwin v1.43 Estimate) Wat Sol: (User Entered) Wat Sol: 1E+006 (mg/L, PhysProp DB exp value)

-------------------------------------- Values used to Generate ECOSAR Profile

-------------------------------------- Log Kow: -0.045 (EPISuite Kowwin v1.68 Estimate) Wat Sol: 1E+006 (mg/L, PhysProp DB exp value)

------------------------------------------------ Available Measured Data from ECOSAR Training Set

------------------------------------------------

Measured CAS No Organism Duration End Pt mg/L (ppm) Ecosar Class Reference

=========== ========== ========== ====== ========== ============== =================== 000075-21-8 Daphnid 48-hr LC50 137 Epoxides, mono Conway et al., 1983 000075-21-8 Fish 96-hr LC50 84 Epoxides, mono Conway et al., 1983

--------------------------------------Page 51 of 61 ECOSAR v1.1 Class-specific Estimations

-------------------------------------- Epoxides, mono Predicted ECOSAR Class Organism Duration End Pt mg/L (ppm)

=========================== ================== ======== ====== ========== Epoxides, mono : Fish 96-hr LC50 57.672 Epoxides, mono : Fish 14-day LC50 31.003 Epoxides, mono : Daphnid 48-hr LC50 277.857 Epoxides, mono : Green Algae 96-hr EC50 501.535 Epoxides, mono : Fish ChV 0.015 Epoxides, mono : Daphnid ChV 27.803 ! Epoxides, mono : Green Algae ChV 168.525

=========================== ================== ======== ====== ========== Neutral Organic SAR : Fish 96-hr LC50 2486.310 (Baseline Toxicity) : Daphnid 48-hr LC50 892.307 : Green Algae 96-hr EC50 817.901 : Fish ChV 194.495 : Daphnid ChV 67.386 : Green Algae ChV 68.573

Note: * = asterisk designates: Chemical may not be soluble enough to measure this predicted effect. If the effect level exceeds the water solubility by 10X, typically no effects at saturation (NES) are reported.

NOTE: ! = exclamation designates: The toxicity value was estimated through application of acute-to-chronic ratios per methods outlined in the ECOSAR Methodology Document provided in the ECOSAR Help Menu.

------------------------------ Class Specific LogKow Cut-Offs

------------------------------ If the log Kow of the chemical is greater than the endpoint specific cut-offs presented below, then no effects at saturation are expected for those endpoints.

Epoxides, mono:

-------------- Maximum LogKow: 5.0 (Fish 96-h LC50, Daphnid LC50) Maximum LogKow: 6.0 (Fish 14-day) Maximum LogKow: 6.4 (EC50) Maximum LogKow: 8.0 (ChV)

Baseline Toxicity SAR Limitations:

--------------------------------- Maximum LogKow: 5.0 (Fish 96-hr LC50; Daphnid LC50) Maximum LogKow: 6.4 (Green Algae EC50) Maximum LogKow: 8.0 (ChV)Page 52 of 61 

# Appendix D Product Chemistry

The ETO product chemistry information is su mmarized in Table E1 (source: MRIDs 41531002, 42458502, 42466702, 42811401, 43053201, and EPI Suite v4.1). Table E1 – Product Chemistry of ETO
Guideline Number Physical and Chemical Properties Value

830.1550 Product identity and composition Refer to Table 3. 830.1600 Description of materials used to produce the product Confidential Business Information (CBI)

830.1620 Description of production process CBI 830.1650 Description of Formulation Process CBI 830.1670 Discussion of formulation of impurities CBI

830.1700 Preliminary analysis CBI 830.1750 Certified limits CBI 830.1650 Description of Formulation Process CBI 830.1800 Enforcement analytical method Gas chromatography (GC). 830.1900 Submittal of samples CBI 830.6302 Color ETO is a colorless gas or liquid. 830.6303 Physical State ETO is a colorless gas at 25 °C and is a mobile liquid at 0 °C. 830.6304 Odor The gas has a characteristic sweet odor of ether. 830.6313 Stability to normal and elevated temperature, metals/metal ions ETO is stable at ordinary conditions of temperature and pressure and in ordinary use, handling and storage. ETO is a reactive molecule. Its ability to chemically combine with itself and other molecules (and the necessary conditions) is reported. Protect from sunlight. Store in a well-ventilated place. 830.6314 Oxidation/Reduction:

Chemical Incompatibility: Highly reactive. It is reactive in both the liquid and vapor phases. Materials to avoid: Alcohols, alkali metals, ammonia, oxidizing agents, chemically active metals and its salts. 830.6315 Flammability-Flash point Flammable gas. It is extremely flammable and explosive, therefore, it is commonly handled and shipped as a refrigerated liquid. Flash point

− 20.0 °C

− closed cup Flash point <

− 18.0 °C – tag open cup 830.6316 Explodability It is extremely flammable and explosive; therefore, it is commonly handled and shipped as a refrigerated liquid. 830.7000 pH This requirement does not apply to ETO because it is not an acid or base. It is a gas. 830.7050 UV/Visible Absorption Not applicable.

830.7100 Viscosity 0 °C – 0.325 cP 20°C – 0.260 cP Viscosity of liquid ETO at 0 °C is about 5.5 times lower than that of water. 830.7200 Melting point: Freezing point: − 111.7 °C

− 112.778 °C 830.7220 Boiling point 10.6 °C at 760 mmHg 830.7300 Density 0.995 g/cm 3 0.882 g/cm3 at 25 °C 0.8697 g/ml 20 °CPage 53 of 61 Guideline Number Physical and Chemical Properties Value 830.7370 Dissociation Constant in water (pKa) ETO is a covalently bonded organic molecule (an alkyl epoxide) and does not dissociate. 830.7550 Partition coefficient ( n

octanol/water) Log Kow − 0.30 (Log P)

830.7840 Solubility in water Infinitely soluble.

830.7860 Solubility in organic solvents Readily soluble in water, et hanol, diethyl ether, acetone, benzene and many organic solvents. 830.7950 Vapor pressure 1255 mm Hg at 25°CPage 54 of 61 

# Appendix E Modeling Input Based on ETO Release Scenarios for Spices and Herbs

ETO is used to treat spices, dried vegetables , and seasonings in fumi gation chambers. Labels specify maximum application rates, or indoor concentrations of ETO, which are maintained over periods of time for treatments inside the chambe rs. Fumigation chambers have a maximum size of 10,000 cubic feet 16 . Labels all require mechanical, or fo rced, aeration follow ing a treatment of the commodities. Mechanical aer ation releases the fumigant outdoors from the treatment chamber through a stack or vent. Product labels part icularly specify that ETO is to be evacuated from chambers through the use of steam scave nging techniques, and specifies the number of washes that are to be applied during aeration. Labels also specif y the temperature of the steam which renders the aeration as a buoyant release. ETO labels sp ecify the following mechanical release parameters given the follo wing maximum application rates:

First Release Scenario

 Maximum Application Rate (per ch amber) = 500 mg/L = 31.22 lbs./1,000 ft. 3

 Flow Rate = 21 steam washes specified

 Chamber/Stack Temperature: 115°F

Second Release Scenario

 Maximum Application Rate (per ch amber) = 500 mg/L = 31.22 lbs./1,000 ft. 3

 Flow Rate = 16 steam washes specified

 Chamber/Stack Temperature: 120°F It is important to note that it is possible that more than one ETO treatment inside fumigation chambers can occur at a time at the same loca tion. The labels do not specify a maximum amount of simultaneous fumigation chamber treatments. AERSCREEN Description The Agency’s recommended screening dispersi on model for the near field, the American Meteorological Society/EPA Regulatory Screen ing Model (AERSCREEN), will be used to generate screening EECs for the va rious release scenarios. The Tier I analysis will consider the emission rates and release flow rates and stack parameters for the various mechanical release scenarios for ETO. Worst-case meteorological c onditions (light winds an d stagnant conditions) and downwash 17 parameters are assumed to calculat e peak air EECs, representing one-hour average concentrations. Documentation on the AERSCREEN model is available at http://www.epa.gov/scram 001/dispersion_screening.htm . A schematic of release scenarios from treatment chambers and the related conceptual model for ground-level exposure is shown in Figure E1 . For purposes of this screening analysis , all ecological receptors of concern will assumed to be present directly downw ind from the buildi ng at ground level.

16 Fumigation chambers are assumed to possess similar size to railcars. Citation: http://www.csx.com/index.cfm/custom ers/equipment/railroad-equipment/
17 Downwash is defined as the downward flow often observed on the leeside of buildings induced by wake turbulence. Pollutants released from buildings can of ten become embedded in downwash flows and wake cavities.Page 55 of 61 Figure E1. Schematic illustrating fumigation releases from treatment chambers and conceptual model for ground-level exposure.

AERSCREEN Release Scenarios

Each release scenario from the ETO label desc ribed above will be modeled to capture all possible combinations of release parameters. Ei ther release scenario may result in the upperbound air EEC at ground-level based upon individual contributions between the flow rate and temperature of the steam. Scenario 1 of the AERSCREEN evaluation represents the first aeration scenario specified on the label described above. Scenario 2 represents the second aeration scenario specified on the label desc ribed above. Each mode led release scenarios conservatively assumes that aeration is complete after one hour which results in maximized peak (one-hour average) concentrations. The input parameter values used in AERSCREEN for the screening analysis of ETO air exposure is shown in Table E1 below. The AERSCREEN modeli ng captures the upper-bound air exposure from release scenarios consolidated ab ove from information on the ETO product label.

Table E1. AESCREEN input parameter values cap turing the upper-bound combination of release scenarios identified on the ETO label.

Input Parameter Option/Value Notes Scenario 1 Scenario 2 English or Metric Units E (English) Source Type P (Point) Stack releases

Emission Rate (lbs./hr) 312.2 All mass from labeled specified application rate inside 10,000 ft. 3 chamber released in one-hour period 1
Stack or Release Height Above Ground (ft.) 5 Not specified on label Default for 10,000 ft. 3 building size based on methyl bromide assessment 2
Stack Diameter (in.) 39.6 Default for 10,000 ft. 3 building size based on methyl bromide assessment (1 meter) 2
Stack Temperature (°F) 115 120 Based on stack temperatures provided on the labels Option for Flow Rate or Flow Velocity 3 (Flow Rate ACFM)

Stack Exit Stream Flow Rate (f 3 /min.) 3,500 2,667 Scenario 1: Based on 21 steam washes specified on label –

assume 21 air exchanges per hour for hourly release 3

Scenario 2: Based on 16 steam washes specified on label –

assume 16 air exchanges per hour for hourlyPage 56 of 61 Input Parameter Option/Value Notes Scenario 1 Scenario 2 release 3 Urban or Rural? R (Rural) Conservative default Minimum Distance to Ambient Air (ft.) 3.3 Conservative default

NO 2 Chemistry 1 (No chemistry/pollutant is not NO 2 ) Tracer gas NO x emissions not modeled
Include Building Downwash? Y (Yes) Downwash is feasible downward transport mechanism for plume in release scenarios Use Pre-Existing BPIPPRM File? N (No) Downwash parameters to be input manually
Building Height (ft.) 5 Equivalent to stack height Maximum Horizontal Building Dimension (ft.) 44.72 Square chamber footprint consistent with building heights specified above Minimum Horizontal Building Dimension (ft.) 44.72 Square chamber footprint consistent with building heights specified above Maximum Building Dimension Angle to True North (degrees) 0 Conservative parameterization of building downwash – stack located on the leeward edge of the building Direction of Stack from Building Center (degrees) 0

Distance Between Stack and Building Center (ft.) 22.3

Terrain Heights? N (No) Only flat terrain considered Maximum Distance to Probe (m) 5,000 Defau lt - maximum feasible distance for screen Include Discrete Receptors N (No) Automated receptors sufficient Flagpole Receptors N (No) Ground-level concentrations assumed Source Elevation (ft.) 0 Stack ba se from ground release assumed Minimum Temperature (°F) -10 Default – typical national temperature range Maximum Temperature (°F) 100 Default – typical national temperature range Minimum Wind Speed (m/s) 0.5 Minimum in model: conservative default

Anemometer Height (ft.) 33 Typical boundary layer reference height (10 meters)
Surface Characteristics Option 1 (Single User Specified Values) Albedo 0.6 Bare surface assumed around source 4
Bowen Ratio 3.0 Bare su rface assumed around source 4 Surface Roughness Length (m) 0.001 Bare surf ace assumed around source 4

1 Scenario 1 and 2 Emission Rate (lbs./hr) = [Application Rate (lbs./ft. 3 ) x Chamber Size (ft. 3 ) /Duration of Release (hr.)]
2 Methyl bromide risk assessment citation: Dawson, J. 2008. Second Addenda to the 2006 (DP Barcode 304623)

Phase 5 Human Health Risk Assessmen t for Commodity Uses. Office of Pesticide Programs. Washington, DC. (November 26, 2008) (EPA DP Barcode 304612).
3 Flow rate (ft. 3 /min) = Air exchange rate (air exchanges/hr.) x Chamber Size (ft. 3 ) x (hours / 60 minutes)
4 Default values for bare soil assumed. Please refer to, “User’s Guide for the AERMOD Meteorological

Preprocessor (AERMET)”, (EPA, 2004) for further details.Page 57 of 61 

# Appendix F Output Example of AERSCREEN Estimated Environmental Concentration (EEC) for ETO Release Scenario 2

AERSCREEN 11126 / AERMOD 1234 04/19/13 15:56:35

TITLE: ETO-16

----------------------------------------------------------------------------- ***************************** STACK PARAMETERS ****************************

-----------------------------------------------------------------------------
SOURCE EMISSION RATE: 39.3372 g/s 312.200 lb/hr STACK HEIGHT: 1.52 meters 5.00 feet STACK INNER DIAMETER: 1.006 meters 39.60 inches PLUME EXIT TEMPERATURE: 322.0 K 120.0 Deg F PLUME EXIT VELOCITY: 1.584 m/s 5.20 ft/s STACK AIR FLOW RATE: 2667 ACFM RURAL OR URBAN: RURAL

INITIAL PROBE DISTANCE = 5000. meters 16404. feet

----------------------------------------------------------------------------- *********************** BUILDING DOWNWASH PARAMETERS **********************

-----------------------------------------------------------------------------

BUILDING HEIGHT: 1.5 meters 5.0 feet MAX BUILDING DIMENSION: 13.6 meters 44.7 feet MIN BUILDING DIMENSION: 13.6 meters 44.7 feet BUILDING ORIENTATION TO NORTH: 0. degrees STACK DIRECTION FROM CENTER: 0. degrees STACK DISTANCE FROM CENTER: 6.8 meters 22.3 feet

----------------------------------------------------------------------------- ************************** FLOW SECTOR ANALYSIS *************************** 25 meter receptor spacing: 1. meters - 5000. meters

-----------------------------------------------------------------------------

FLOW BUILD BUILD MAX 1-HR DIST TEMPORALPage 58 of 61 SECTOR WIDTH LENGTH XBADJ YBADJ CONC (m) PERIOD

----------------------------------------------------------------------------- 10 15.80 15.79 -14.59 -1.18 0.2151E+06 1.0 ANN 20 17.48 17.47 -15.12 -2.32 0.2694E+06 1.0 ANN 30 18.63 18.62 -15.20 -3.40 0.3072E+06 1.0 ANN 40 19.21 19.21 -14.81 -4.37 0.3252E+06 1.0 ANN 50 19.21 19.21 -13.97 -5.21 0.2594E+06 1.0 ANN 60 18.62 18.63 -12.71 -5.88 0.2600E+06 1.0 ANN 70 17.47 17.48 -11.06 -6.39 0.2554E+06 25.0 ANN 80 15.79 15.80 -9.08 -6.69 0.2702E+06 25.0 ANN 90 13.63 13.64 -6.82 -6.80 0.2830E+06 25.0 ANN 100 15.79 15.80 -6.72 -6.69 0.3118E+06 25.0 ANN 110 17.47 17.48 -6.42 -6.39 0.3058E+06 25.0 ANN 120 18.62 18.63 -5.92 -5.88 0.3136E+06 25.0 ANN 130 19.21 19.21 -5.24 -5.21 0.3241E+06 25.0 ANN 140 19.21 19.21 -4.40 -4.37 0.3431E+06 25.0 ANN 150 18.63 18.62 -3.43 -3.40 0.3424E+06 25.0 ANN 160* 17.48 17.47 -2.35 -2.32 0.3483E+06 25.0 ANN 170 15.80 15.79 -1.20 -1.18 0.3428E+06 25.0 ANN 180 13.64 13.63 -0.02 0.00 0.3241E+06 25.0 ANN 190 15.80 15.79 -1.20 1.18 0.3428E+06 25.0 ANN 200 17.48 17.47 -2.35 2.32 0.3483E+06 25.0 ANN 210 18.63 18.62 -3.43 3.40 0.3424E+06 25.0 ANN 220 19.21 19.21 -4.40 4.37 0.3431E+06 25.0 ANN 230 19.21 19.21 -5.24 5.21 0.3241E+06 25.0 ANN 240 18.62 18.63 -5.92 5.88 0.3136E+06 25.0 ANN 250 17.47 17.48 -6.42 6.39 0.3058E+06 25.0 ANN 260 15.79 15.80 -6.72 6.69 0.3118E+06 25.0 ANN 270 13.63 13.64 -6.82 6.80 0.2830E+06 25.0 ANN 280 15.79 15.80 -9.08 6.69 0.2702E+06 25.0 ANN 290 17.47 17.48 -11.06 6.39 0.2554E+06 25.0 ANN 300 18.62 18.63 -12.71 5.88 0.2600E+06 1.0 ANN 310 19.21 19.21 -13.97 5.21 0.2594E+06 1.0 ANN 320 19.21 19.21 -14.81 4.37 0.3252E+06 1.0 ANN 330 18.63 18.62 -15.20 3.40 0.3072E+06 1.0 ANN 340 17.48 17.47 -15.12 2.32 0.2694E+06 1.0 ANN 350 15.80 15.79 -14.59 1.18 0.2151E+06 1.0 ANN 360 13.64 13.63 -13.61 0.00 0.1402E+06 25.0 ANN * = worst case flow sector

----------------------------------------------------------------------------- *************** ******* MAKEMET METEOROLOGY PARAMETERS   ** ****** *********

-----------------------------------------------------------------------------
MIN/MAX TEMPERATURE: 249.8 / 310.9 (K)

MINIMUM WIND SPEED: 0.5 m/s

ANEMOMETER HEIGHT: 10.000 meters

SURFACE CHARACTERISTICS INPUT: USER ENTERED

ALBEDO: 0.60 BOWEN RATIO: 3.00Page 59 of 61 ROUGHNESS LENGTH: 0.001 (meters)

METEOROLOGY CONDITIONS USED TO PREDICT OVERALL MAXIMUM IMPACT

-------------------------------------------------------------

YR MO DY JDY HR

-- -- -- --- -- 10 06 01 1 01

H0 U* W* DT/DZ ZICNV ZIMCH M-O LEN Z0 BOWEN ALBEDO REF WS

- - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -4.06 0.054 -9.000 0.020 -999. 291. 3.8 0.001 3.00 0.60 2.50

HT REF TA HT

- - - - - - - - - - - 10.0 310.9 2.0

ESTIMATED FINAL PLUME HEIGHT (non-downwash): 5.3 meters

METEOROLOGY CONDITIONS USED TO PREDICT AMBIENT BOUNDARY IMPACT

--------------------------------------------------------------

YR MO DY JDY HR

-- -- -- --- -- 10 06 28 1 01

H0 U* W* DT/DZ ZICNV ZIMCH M-O LEN Z0 BOWEN ALBEDO REF WS

- - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -13.42 0.124 -9.000 0.020 -999. 101. 13.7 0.001 3.00 0.60 4.00

HT REF TA HT

- - - - - - - - - - - 10.0 310.9 2.0

ESTIMATED FINAL PLUME HEIGHT (non-downwash): 2.6 meters

----------------------------------------------------------------------------- ************************ AERSCREEN AUTOMATED DISTANCES ********************** OVERALL MAXIMUM CONCENTRATIONS BY DISTANCE

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MAXIMUM MAXIMUM DIST 1-HR CONC DIST 1-HR CONC (m) (ug/m3) (m) (ug/m3)

--------------------- --------------------- 1.01 0.3252E+06 2525.00 8586. 25.00 0.3483E+06 2550.00 8512. 50.00 0.2898E+06 2575.00 8439. 75.00 0.2450E+06 2600.00 8367. 100.00 0.2128E+06 2625.00 8296. 125.00 0.1890E+06 2650.00 8226.Page 60 of 61 150.00 0.1706E+06 2675.00 8156. 175.00 0.1550E+06 2700.00 8088. 200.00 0.1387E+06 2725.00 8020. 225.00 0.1222E+06 2750.00 7953. 250.00 0.1056E+06 2775.00 7887. 275.00 0.8956E+05 2800.00 7821. 300.00 0.7444E+05 2825.00 7757. 325.00 0.6068E+05 2850.00 7693. 350.00 0.4852E+05 2875.00 7630. 375.00 0.4011E+05 2900.00 7568. 400.00 0.3704E+05 2925.00 7506. 425.00 0.3435E+05 2950.00 7445. 450.00 0.3197E+05 2975.00 7386. 475.00 0.2986E+05 3000.00 7326. 500.00 0.2906E+05 3025.00 7268. 525.00 0.2880E+05 3050.00 7210. 550.00 0.2848E+05 3075.00 7153. 575.00 0.2812E+05 3100.00 7096. 600.00 0.2771E+05 3125.00 7041. 625.00 0.2728E+05 3150.00 6986. 650.00 0.2683E+05 3175.00 6931. 675.00 0.2637E+05 3200.00 6877. 700.00 0.2589E+05 3225.00 6824. 725.00 0.2541E+05 3250.00 6771. 750.00 0.2493E+05 3275.00 6726. 775.00 0.2445E+05 3300.00 6687. 800.00 0.2398E+05 3325.00 6649. 825.00 0.2350E+05 3350.00 6611. 850.00 0.2304E+05 3375.00 6573. 875.00 0.2258E+05 3400.00 6535. 900.00 0.2213E+05 3425.00 6498. 925.00 0.2169E+05 3450.00 6461. 950.00 0.2126E+05 3475.00 6424. 975.00 0.2083E+05 3500.00 6387. 1000.00 0.2042E+05 3525.00 6351. 1025.00 0.2002E+05 3550.00 6315. 1050.00 0.1963E+05 3575.00 6279. 1075.00 0.1924E+05 3600.00 6244. 1100.00 0.1887E+05 3625.00 6208. 1125.00 0.1851E+05 3650.00 6173. 1150.00 0.1815E+05 3675.00 6142. 1175.00 0.1781E+05 3700.00 6112. 1200.00 0.1747E+05 3725.00 6081. 1225.00 0.1715E+05 3750.00 6051. 1250.00 0.1683E+05 3775.00 6022. 1275.00 0.1652E+05 3800.00 5992. 1300.00 0.1622E+05 3825.00 5962. 1325.00 0.1593E+05 3850.00 5933. 1350.00 0.1564E+05 3875.00 5904. 1375.00 0.1537E+05 3900.00 5877. 1400.00 0.1510E+05 3925.00 5849. 1425.00 0.1484E+05 3950.00 5822. 1450.00 0.1458E+05 3975.00 5795. 1475.00 0.1433E+05 4000.00 5768. 1500.00 0.1409E+05 4025.00 5741. 1525.00 0.1387E+05 4050.00 5714.Page 61 of 61 1550.00 0.1366E+05 4075.00 5687. 1575.00 0.1346E+05 4100.00 5661. 1600.00 0.1326E+05 4125.00 5634. 1625.00 0.1307E+05 4150.00 5608. 1650.00 0.1288E+05 4175.00 5582. 1675.00 0.1269E+05 4200.00 5556. 1700.00 0.1251E+05 4225.00 5530. 1725.00 0.1233E+05 4250.00 5505. 1750.00 0.1216E+05 4275.00 5479. 1775.00 0.1199E+05 4300.00 5454. 1800.00 0.1182E+05 4325.00 5428. 1825.00 0.1166E+05 4350.00 5403. 1850.00 0.1150E+05 4375.00 5378. 1875.00 0.1135E+05 4400.00 5354. 1900.00 0.1120E+05 4425.00 5329. 1925.00 0.1105E+05 4450.00 5305. 1950.00 0.1090E+05 4475.00 5280. 1975.00 0.1076E+05 4500.00 5256. 2000.00 0.1062E+05 4525.00 5232. 2025.00 0.1048E+05 4550.00 5208. 2050.00 0.1034E+05 4575.00 5184. 2075.00 0.1021E+05 4600.00 5161. 2100.00 0.1008E+05 4625.00 5137. 2125.00 9957. 4650.00 5114. 2150.00 9833. 4675.00 5091. 2175.00 9715. 4700.00 5068. 2200.00 9628. 4725.00 5045. 2225.00 9542. 4750.00 5022. 2250.00 9458. 4775.00 4999. 2275.00 9374. 4800.00 4977. 2300.00 9291. 4825.00 4954. 2325.00 9209. 4850.00 4932. 2350.00 9128. 4875.00 4910. 2375.00 9048. 4900.00 4888. 2400.00 8968. 4925.00 4866. 2425.00 8890. 4950.00 4845. 2450.00 8813. 4975.00 4823. 2475.00 8736. 5000.00 4802. 2500.00 8661.

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MAXIMUM SCALED SCALED SCALED SCALED 1-HOUR 3-HOUR 8-HOUR 24-HOUR ANNUAL CALCULATION CONC CONC CONC CONC CONC PROCEDURE (ug/m3) (ug/m3) (ug/m3) (ug/m3) (ug/m3)

--------------- ---------- ---------- ---------- ---------- ---------- FLAT TERRAIN 0.6871E+06 0.6871E+06 0.6184E+06 0.4123E+06 0.6871E+05

DISTANCE FROM SOURCE 16.00 meters directed toward 160 degrees IMPACT AT THE AMBIENT BOUNDARY 0.3252E+06 0.3252E+06 0.2927E+06 0.1951E+06 0.3252E+05

DISTANCE FROM SOURCE 1.01 meters directed toward 40 degrees