Page 2 of 69

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

Meghan Radtke 

He Zhong

Stephen Carey

Gabe Rothman 

Health Effects Division

Ray Kent

Angela Howard

Sue Hummel

Ivan Nieves

Jessica Kidwell

Thurston Morton 

Jeffrey Dawson 

Biological and Economic Analysis Division

Sepehr Haddad

Michelle Ranville

Leonard Yourman

Risk Management

Donna Kamarei

Susan Bartow

Rose Kyprianou

Cathryn Britton

Sandra O’Neill

Office of General Counsel

Philip Ross
Page 3 of 69

Table of Contents

1 Introduction............................................................................................................................. 5

1.1 Statutory and Regulatory Authority ................................................................................. 5

1.2 Updates to the Workplan.................................................................................................. 6

1.3 Case Overview ................................................................................................................. 7

1.4 Chemical Identification and Properties............................................................................ 7

1.5 Use and Usage Profile .................................................................................................... 10

1.5.1 Registrations ........................................................................................................... 10

1.5.2 Summary of Registered Uses.................................................................................. 10

1.5.3 Usage Information .................................................................................................. 12

1.6 Regulatory History ......................................................................................................... 13

1.6.1 Recent/Pending Regulatory Actions....................................................................... 14

1.6.2 Tolerance Information ............................................................................................ 14

1.7 Incidents......................................................................................................................... 15

1.7.1 Human Health ......................................................................................................... 15

1.7.2 Ecological ............................................................................................................... 15

2 Anticipated Data Needs ........................................................................................................ 15

3 Human Health Risk Assessment........................................................................................... 17

3.1 Existing Toxicological Endpoints.................................................................................. 18

3.2 Dietary Exposure............................................................................................................ 20

3.2.1 Dietary (Food - Conventional Uses)....................................................................... 20

3.2.2 Dietary (Food - Antimicrobial Uses)...................................................................... 21

3.2.3 Dietary (Drinking Water)........................................................................................ 21

3.2.4 Residue Chemistry (Conventional and Antimicrobial Uses).................................. 21

3.3 Occupational and Residential Exposures....................................................................... 21

3.3.1 Occupational Exposure ........................................................................................... 21

3.3.2 Residential Exposures............................................................................................. 24

3.4 Aggregate and Cumulative Exposure and Risk.............................................................. 25

3.4.1 Aggregate Exposures and Risk ............................................................................... 25

3.4.2 Cumulative Exposure and Risk............................................................................... 26

4 Ecological Risk Assessment ................................................................................................. 26

4.1 Environmental Fate Assessment .................................................................................... 27

4.1.1 Clean Water Act...................................................................................................... 27

4.2 Conceptual Models for Environmental Exposure Pathways.......................................... 27

4.3 Ecological Effects Assessment....................................................................................... 28

4.3.1 Mechanism of Action.............................................................................................. 28

4.3.2 Measures of Effect (Ecotoxicology Endpoints)...................................................... 28

4.4 Exposure Analysis Plan.................................................................................................. 30

4.4.1 Wildlife Exposure Estimates................................................................................... 30

4.5 Effects Analysis Plan ..................................................................................................... 32

5 Endocrine Disruptor Screening Program (EDSP)................................................................. 33

6 Next Steps............................................................................................................................. 33

7 References............................................................................................................................. 34
Page 4 of 69

Appendix A Toxicology Profile............................................................................................... 36

Appendix B Environmental Fate ............................................................................................. 40

Appendix C Ecotoxicology Profile.......................................................................................... 44

Appendix D Product Chemistry............................................................................................... 50

Appendix E Modeling Input Based on ETO Release Scenarios for Spices and Herbs........... 52

Appendix F Output Example of AERSCREEN Estimated Environmental Concentration 

(EEC) for ETO Release Scenario 2 .............................................................................................. 55

Appendix G Comments Received Concerning the Preliminary Work Plan............................ 60

List of Tables

Table 1 – Summary of Anticipated Risk Assessments and Data Needs: ETO............................... 7

Table 2 – Anticipated Registration Review Schedule .................................................................... 7

Table 3 – Chemical Identification of ETO ..................................................................................... 8

Table 4 – Physical/Chemical, Fate and Transport Properties of ETO and Major Reaction 

Products........................................................................................................................................... 9

Table 5 – Summary of ETO Registered Uses............................................................................... 10

Table 6 – Maximum Rates for Registered Agricultural Uses of ETO.......................................... 12

Table 7 – Studies Anticipated as Needed for the Registration Review of ETO........................... 16

Table 8 – Summary of Toxicological Doses and Endpoints for ETO, ECH, and EG Selected for 

Use in Past Human Risk Assessments.......................................................................................... 18

Table 9 – Summary of Medical Facility SIC Codes..................................................................... 22

Table 10 – ETO Air Concentrations from IMIS for All Medical SIC Codes............................... 23

Table 11 – ETO Air Concentrations (ppm) from IMIS for All Available Medical SIC Codes 

(1988 to 2007)............................................................................................................................... 23

Table 12 – ETO Air Concentrations for Contract Sterilization Facilities .................................... 24

Table 13 – Selected Ecological Effects Endpoints for Risk Assessment of ETO ........................ 29

Table 14 – AERSCREEN Modeling Scenarios and Data Summary ............................................ 31

Table 15 – ETO – Acute Toxicity................................................................................................. 36

Table 16 – ETO – Subchronic, Chronic Toxicity Studies............................................................ 36

Table 17 – Environmental Fate Properties of ETO ...................................................................... 40

Table 18 – Effects Data on ETO................................................................................................... 46

Table 19 – ECOSAR v1.11 Results for ETO ............................................................................... 46

Table 20 – Summary of the Most Sensitive Endpoints from Aquatic Toxicity Studies for EG 

(Degradate of ETO). ..................................................................................................................... 47

List of Figures

Figure 1 – Conceptual Model for Ecological Exposure and Effects of ETO to Aquatic and 

Terrestrial Organisms.................................................................................................................... 28

Figure 2 – Proposed ETO air exposure scenario for the risk assessment. .................................... 32
Page 5 of 69

1 Introduction

This document is the United States Environmental Protection Agency’s (USEPA, EPA or “the 

Agency”) Final Work Plan (FWP) for ethylene oxide (ETO). The FWP document explains what 

EPA’s Office of Pesticide Programs (OPP) knows about ETO, highlighting anticipated data and 

assessment needs, identifying the types of information that would be especially useful to the 

Agency in conducting the review, and providing an anticipated timeline for completing ETO’s

review.

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

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

docket, to inform the public of what it knows about 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.

1.1 Statutory and Regulatory Authority

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

pesticides distributed or sold in the United States generally must be registered by the USEPA 

based on scientific data showing that they will not cause unreasonable risks to human health or 

the environment when used as directed on product labeling. The registration review program is 

intended to make sure that, as the ability to assess risk evolves and as policies and practices 

change, all registered pesticides continue to meet the statutory standard of no unreasonable 

adverse effects to human health or the environment. Changes in science, public policy, and 

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

Agency periodically reevaluates pesticides to make sure that as change occurs, products in the 

marketplace can be used safely. Information on this program is provided at 

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

The Agency is implementing the registration review program pursuant to Section 3(g) of the 

Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) and will review each registered 

pesticide every 15 years to determine whether it continues to meet the FIFRA standard for 

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

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

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

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

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

The ETO Preliminary Work Plan (PWP) was published on September 25, 2013 and the 60-day 

comment period ended on November 25, 2013. 

Public comments received concerning the PWP and documents associated with this registration 

review can be viewed at http://www.regulations.gov in docket EPA-HQ-OPP-2013-0244. Below 

is a summary of the issues relevant to this registration review case.
Page 6 of 69

1.2 Updates to the Workplan

Since the publication of the PWP, the Agency has made the following updates: 

 Corrected the timeline in Table 2, the anticipated registration review table.

 Updated Section 6, Next Steps.

 Added Appendix G, which includes the Agency’s response to comments submitted about 

the PWP.

The Agency received 12 submissions from 10 commenters during the public comment period on 

the initial docket. See Appendix G for the Agency’s responses to these comments.

Comments received did not result in a modification to the anticipated data needs in the ETO

PWP. This document makes final the work plan for the ETO registration review process.

Additionally, after the comment period closed, the Agency received additional information from 

The Ethylene Oxide Sterilization Association, Inc. that will be considered in the risk assessment 

phase of registration review. This additional information can be found in the docket for the ETO 

case.
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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 Registration Review Schedule

Anticipated Activity Target Date*Completion Date

Phase 1: Opening the Docket 

Open Docket and 60-Day Comment Period for Preliminary Work Plan 2013-09 2013-09-25

Close Public Comment Period 2013-11 2013-11-25

Phase 2: Case Development 

Issue Final Work Plan 2014-03 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).

1.3 Case Overview

The docket for the ETO Case (Case 2275) has been established at http://www.regulations.gov in 

docket number EPA-HQ-OPP-2013-0244.

1.4 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 reactive, and flammable gas at room temperature and 

ambient pressure.
Page 8 of 69

Table 3 – Chemical Identification 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* Name Oxirane

Classification

Epoxide

Oxirane

Cyclic ether

PC Code 042301

CAS Number 75-21-8

Molecular Formula C2H4O

H2COCH2

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 environmental 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). Table 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 natural 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 presence 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 inert ingredient in pesticide formulations.
Page 9 of 69

Table 4 – Physical/Chemical, Fate and Transport Properties of ETO and Major Reaction 

Products

Common name Ethylene Oxide

(ETO)

Ethylene

chlorohydrin (ECH)

Ethylene

bromohydrin (EBH)

Ethylene Glycol

(EG)

Chemical structure

C

H2

C

H2

HO OH

Molecular Formula C2H4O C2H5ClO C2H5BrO C2H6O2

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 (oC)

-111.6 -89 -80 -12.9

Boiling point,

oC 10.4 130 150 (EPISuite v4.10) 195

Density or specific 

gravity, grams/liter 

(g/L) at 25 oC

1.80 1.2015-1.2025 1.494 at 20 oC 1.1155

Water solubility, at 

20°C Not available Not available Not available Not available

Vapor pressure 1255 mm Hg at 25o C

(EPI Suite, v4.10)

7.18 mm Hg at 25 oC

(EPISuite v4.10)

2.06 mm Hg at 25 oC

(EPI Suite, v 4.10)

0.0609 mm Hg at 25 

oC

(EPISuite 4.10)

Henry’s Law Constant 

at 25 oC (atmm3

/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 Kow) at 25 oC

-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 moleculeNot applicable, nonconjugated moleculeNot applicable, nonconjugated moleculeNot 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

H2C CH2

C

H2

C

H2

HO Cl

C

H2

C

H2

HO Br
Page 10 of 69

1.5 Use and Usage Profile

1.5.1 Registrations

As of March 27, 2014, there were 23 registered Section 3 products and 1 Section 24(c) 

containing ETO. ETO is formulated and marketed as a pressurized gas or liquid. The end use 

formulations are all gas mixtures of ETO and other gases (e.g., carbon dioxide) in varying 

concentrations.

1.5.2 Summary of Registered Uses

Table 5 presents a summary of the registered uses of ETO that will be assessed in this 

registration review.

1.5.2.1 Agricultural Uses

ETO is a commodity fumigant/sterilant registered 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 applicators only; there are no residential uses of ETO. It is used in 

vacuum chambers at full strength (100%) for herbs and spices. The maximum application rate is 

500mg/L (or 31.22 lb a.i./1000 ft3) in a sealed chamber (Table 6).

1.5.2.2 Non-Agricultural (Antimicrobial) Uses

The registered antimicrobial uses of ETO include 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 artifacts, 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; packaging; spices; seasonings; 

artifacts, archival material, library objects

36736-8 100 Pressurized 

gas

Technical Medical/lab items; pharmaceuticals; packaging; spices; seasonings; 

artifacts, archival material, library objects

58779-5 100 Pressurized 

gas

Technical Medical/lab items; pharmaceuticals

67470-6 100 Pressurized 

gas

Technical Medical/lab items; pharmaceuticals; packaging; spices; cosmetics

67470-7 100 Pressurized 

gas

Technical Medical/lab items; pharmaceuticals; 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; packaging; spices; seasonings; 

artifacts, archival material, library objects
Page 11 of 69

EPA 

Registration

Number

%ai Form Registration 

Type Use Site

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 instruments

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; packaging; spices; seasonings; 

artifacts, archival material, library objects

36736-5 20 Pressurized 

gas

EP Medical/lab items; pharmaceuticals; packaging; spices; seasonings; 

artifacts, archival material, library objects

36736-6 12 Pressurized 

gas

EP Medical/lab items; pharmaceuticals; packaging; spices; seasonings; 

artifacts, archival material, 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; packaging; spices; seasonings; 

artifacts, archival material, 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; packaging; spices; seasonings; 

artifacts, archival material, library objects

NC070004 8.5 Pressurized 

gas

EP Bee keeping equipment
Page 12 of 69

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% CO2), 36736-4 (10% ai & 90% CO2), 

36736-5 (20% ai & 80% CO2), 36736-6 

(12% ai & 88% dischlorodifluormethane), 

36736-7 (8.5% ai & 91.5% CO2), 36736-8 

(100% ai) & 67470-6 (100% ai)

1.5.3 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 fumigation 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 facilities that handle multiple pallet sterilizations. The 

scope of materials potentially sterilized within these types of contract sterilization facilities is 

assumed to include medical devices (representing the majority of use), musical instruments, 

library and museum artifacts, and cosmetic ingredients. There were approximately 30 contract 

sterilization facilities in the United States; 21 of those facilities represented 90 percent of the 

contract medical device sterilization capacity in the United States. In addition, many 

manufacturers of medical devices used ETO in-house to sterilize their 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 approximately 9 contract sterilization facilities in the 

United States that treat both medical devices and spices and 6 contract sterilization facilities in 

the United States that only treat spices; each facility 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 Agriculture 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 13 of 69

1.6 Regulatory History

ETO was first registered as a pesticide in 1966. It has been used to treat food products since 

1957. ETO is a FIFRA List B1reregistration pesticide through the FIFRA amendments of 1988. 

ETO entered EPA’s Special Review process in 1978 based on concern for potential 

developmental toxicity, mutagenicity, and neurotoxic effects in workers. A Position Document 1 

(PD1) was published in the Federal Register of January 27, 1978, to announce 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 Agency 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 they work to sterilize 

medical instruments and spices. A voluntary request 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, 20092.

EPA’s Office of Research and Development (ORD), National Center for Environmental 

Assessment (NCEA) is re-evaluating the carcinogenic potential of ETO as part of the Integrated 

Risk Information System (IRIS) program review. The Special Review is still open, pending the 

outcome of the IRIS review. The timeline and projected dates for this re-assessment are posted 

at: 

http://cfpub.epa.gov/ncea/iristrac/index.cfm?fuseaction=viewChemical.showChemical&sw_id=1

004.

The Occupational Safety and Health Administration (OSHA) regulates worker 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 (STEL) 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 users 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 regulates major commercial sterilization 

facilities and area sources requiring the application of Maximum Achievable Control 

Technology (MACT) and/or Generally Available Control Technology (GACT). OAR assessed 

risks from residual ETO emissions after the application of MACT standards to determine if 

further control was warranted. After conducting this 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.gov/fedrgstr/EPATOX/2006/April/Day-07/t3314.htm). More recently, OAR analyzed ETO emissions from 

hospital sterilizers. OAR issued a final rule for hospital emissions on December 28, 2007 

(available at http://www.epa.gov/fedrgstr/EPA-AIR/2007/December/Day-28/a25233.htm). The 

final rule required that all hospitals that do not control their emissions of ETO reduce emissions 

by sterilizing full loads of equipment to the extent possible.

 

1 http://www.epa.gov/oppsrrd1/registration_review/

2 http://www.regulations.gov/#!documentDetail;D=EPA-HQ-OPP-2008-0722-0001 and 

http://www.regulations.gov/#!documentDetail;D=EPA-HQ-OPP-2008-0722-0025
Page 14 of 69

The Food and Drug Administration (FDA) is an important 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. Sterilization methods available in 

the United States for the sterilization of medical devices and regulated by FDA fall into two 

categories. The first category includes sterilization methods used in health care facilities to 

resterilize devices designed for reuse in patient care. The second general category 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, including spices, is not 

adulterated or misbranded. FDA samples imported 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 used to recondition the shipment. After the 

reconditioning, the shipment is tested again to verify that the contaminant load has been reduced.

Also, as part of ensuring that foods are not adulterated, FDA is responsible for the enforcement 

of pesticide tolerances 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 Labeling Act (FPLA), FDA requires an 

ingredient declaration for finished cosmetic products. ETO and its reaction products (EBH, ECH, 

and EG) are not considered cosmetic ingredients. They are not listed in the International 

Cosmetic Ingredient Dictionary, the primary source of cosmetic ingredient nomenclature.

FDA also regulates finished cosmetic products after they are in commercial distribution and have 

entered interstate commerce. During the manufacturing of cosmetics, ETO is used as an 

ethoxylating agent for the synthesis of ethoxylated surfactants 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 potential for residual ETO to be present in 

ethoxylated surfactants and cosmetic products containing these ingredients. In addition, there are 

many cosmetic ingredients that are derivatives of EG. Any unreacted EG present in a cosmetic 

ingredient, may also be present in a finished cosmetic product (Havery, 2008).

1.6.1 Recent/Pending Regulatory Actions

A DCI was issued in November 2007, in conjunction 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 were 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.

1.6.2 Tolerance Information

The EPA Tolerance Reassessment Decision (TRED) for ETO was issued July 24, 2006. The 

TRED is available in the public docket EPA-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 walnuts3. 

 

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/#!documentDetail;D=EPA-HQ-OPP-2008-0834-0036)
Page 15 of 69

Tolerances for ETO on basil were removed following the use being voluntarily cancelled by the 

registrant. The tolerance expression for ETO will be reviewed during registration review to 

ensure that it appropriately covers the metabolites and degradates of ETO and that it specifies the 

residues to be measured for each commodity.

1.7 Incidents

1.7.1 Human Health 

The evaluation of incidents related to human exposure to ETO was discussed in a separate 

memorandum from the Health Effects Division dated May 8, 2013 (D411127). For this 

evaluation, both OPP Incident Data System (IDS) and the Centers for Disease Control and 

Prevention/National Institute for Occupational Safety and Health (CDC/ NIOSH) and Sentinel 

Event Notification System for Occupational Risk-Pesticides (SENSOR) databases were 

consulted for pesticide incident data on the 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 reported from January 2008 to February 2013. This 

reported incident involved a worker who attributed his acute promyeloctyic leukemia to ETO in 

his capacity as a worker at a sterilization facility. In the aggregate IDS database, which reports 

human incidents of a minor nature, from January 1, 2008 to February 19, 2013 there were three

reported incidents involving ETO. These incidents 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 involved 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.

1.7.2 Ecological

There are no reported incidents for ETO in the ecological incident (EIIS) 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 should not be construed as the absence of 

incidents. Incident reports for non-target organisms typically provide information only on 

mortality events and plant damage. Sublethal effects in organisms such as abnormal behavior, 

reduced growth and/or impaired reproduction are rarely reported, except for some phytotoxic 

effects in terrestrial plants. EPA's changes in the registrant reporting requirements for incidents 

in 1998 may also account for a reduced number of reported incidents. Registrants 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 incidents, 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 anticipated as being needed to support this registration 

review.
Docket Number EPA-HQ-OPP-2013-0244

www.regulations.gov

Table 7 – Studies Anticipated as Needed for the Registration Review of ETO

GLN Study Name Test 

Substance

Time Frame 

(Measured in 

months from DCI 

Receipt)

Risk 

Assessment(s) 

Data Will 

Support

Use Site(s) 

Triggering 

Anticipated Data 

Requirement

Applicable Exposure Scenario

Studies Anticipated to be Required through the Registration Review DCI

Special 

Study

Acute inhalation toxicity 

study4 ETO 24

Occupational and 

bystander 

inhalation 

All worker/bystander acute inhalation exposures

870.4300

Chronic 

toxicity/carcinogenicity

study

ECH 48 Occupational and 

Residential

Post-harvest 

fumigant use on food 

commodities 

chronic dietary exposure to ECH

875.1400 Inhalation exposure study 

for applicators ETO 12 Occupational All applicator inhalation exposure

875.1700 Product use information ETO 12 All All All

875.2500 Post-application inhalation 

exposure study ETO 12 Post-application(site specific) All emissions from specific facilities

Special 

study

Monitoring data on 

fumigated commodities44

ETO 24 Occupational All uses except for 

medical items

emission from treated commodities/materials and 

the potential for occupational exposure due to 

those emissions in the channels of trade after 

fumigation activities are complete

Special 

Study

Ambient Air Monitoring 

Study ETO 36 Residential All ambient air concentrations for communities in proximity to treated facilities

Special 

Study

Avian Acute Inhalation 

Toxicity Study4,5 ETO 24 Ecological All

inhalation of air emissions by non-target wildlife Special 

Study

Honeybee Acute Vapor 

Exposure Toxicity Study4 ETO 24 Ecological All

850.4150 Vegetative Vigor6,7

, Gas 

Chamber Exposure Study ETO 24 Ecological All contact with air emissions by non-target plants

 

4 A protocol is expected to be required to be submitted for review prior to conduct of the study.

5 An acute avian inhalation study using the Northern bobwhite quail species is expected to be necessary to satisfy the toxicity profile for ETO.

6 Data from five dicot species of at least three families (excluding soybean (Glycine max) which has already been tested), and four dicot species of at least two 

families, 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).

7 Studies should be modified to accommodate exposure to a volatile substance by using environmental chambers that maintain the air concentrations of the gas, see 

850.4230.
Docket Number EPA-HQ-OPP-2013-0244

www.regulations.gov

3 Human Health Risk Assessment

In 2008, the EPA’s Office of Pesticide Programs (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 the 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/m3)

-1

to 2.67 E-03 (mg/m3)

-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 carcinogenicity risk assessment purposes. Since publication 

of the RED, the carcinogenic potential of ETO is being re-evaluated by the National Center for 

Environmental Assessment’s IRIS program. The time line and projected dates for this reassessment are posted at:

http://cfpub.epa.gov/ncea/iristrac/index.cfm?fuseaction=viewChemical.showChemical&sw_id=1

004.

When this re-assessment is finalized, any modification to the carcinogenic potency estimate for 

ETO will be used by OPP in conducting the carcinogenicity risk assessment for ETO. 

For ETO, the Health Effects Division’s Hazard and Science Policy Council (HASPOC) 

identified the need for a special acute inhalation toxicity study for ETO and additional 

information on the chronic toxicity and carcinogenicity 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 fumigant risk assessment because it often provides the 

most sensitive acute endpoint for risk assessment. Inhalation studies with ETO have shown that 

the nasal cavity is a target organ for ETO. Therefore, there 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 should include the evaluation of the following: 

histopathology of the respiratory tract, including 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 respiratory tract) along with 

information on dose response, incidence, and severity. The protocol for this special acute 

inhalation study should be submitted for Agency review, prior to study initiation.

The HASPOC also concluded that an immunotoxicity study (as required in both the 158 

conventional pesticide test rule and the 158 antimicrobial pesticide test rule) would not be 

needed for ETO. This decision was made on the basis of several factors, including: (1) The 

toxicology databases for ETO and ECH do not reveal any evidence of treatment related effects 

on the immune system. The overall weight of evidence (WOE) suggests that ETO does not 

directly target the immune system; (2) Dietary risk assessments were not conducted for ETO 

since residues are unlikely to be found in sterilized spices available for consumption; (3) Dietary 

risk assessments for the reaction product ECH are based on the most sensitive endpoints from 

studies conducted with the subject chemicals; (4) The dietary risk assessment indicates that for 

all supported commodities, the acute dietary exposure estimates for ECH indicate no risks of 

concern for the general population or other population subgroups. The chronic dietary exposure 
Page 18 of 69

estimates for both ECH and EG indicate no risks of concern for the general population or other 

population subgroups; (5) Points of Departure (POD) for the most sensitive endpoints 

(neurotoxicity) seen in the most sensitive species (mouse) from a route-specific study (i.e., 

inhalation study) are used for assessing risks from 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 used for assessing risks from longterm inhalation exposures to ETO.

The Agency also anticipates requiring additional information on the chronic toxicity and 

carcinogenicity of ECH. When considering whether the chronic toxicity and/or carcinogenicity 

studies were needed for ECH, the HASPOC used a weight of evidence (WOE) approach

including: (1) the current use pattern which results in dietary exposure to ECH at up to 940 ppm 

as a residue on food commodities (ECH is not found in drinking water); (2) the lack of feeding 

studies in rodents (mice and rats) that could provide a POD or an endpoint of concern for 

assessing risk from chronic dietary 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/carcinogenicity study and/or the 

carcinogenicity study in mice may be conducted to fill this need. However, if there are additional 

exposure, pharmacokinetic, or other data/information which could be used to better understand 

the exposure or toxicological profile of ECH, the registrant is encouraged 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 studies that are expected to be 

required for registration review will be considered in establishing the 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 and 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 19 of 69

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 control 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 effects 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) and 

IntermediateTerm

(1 - 6 months)

NOAEL= 7.5 

ppm (13.5 mg/m3)

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/m3) based on 

neurological effects (altered gait and decreased motor 

activity) and absolute and relative organ weight 

changes

Inhalation 

Long-Term

(> 6 months)

NOAEL= 7.5

ppm (13.5 mg/m3)

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/m3) 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 carcinogenicity in animals and humans. The Agency is 

currently determining the carcinogenicity classification of ETO. 

Unit Risk Factor (CDHS) based on mononuclear leukemia in female rats and analysis by 

linearized multistage model = 8.8x10-5 per μg/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 μg/m3 or 1.6 per ppm

UF = uncertainty factor, FQPA SF = FQPA safety factor, NOAEL = no observed adverse effect level, LOAEL = lowest observed 

adverse effect level, PAD = population adjusted dose (a = acute, c = chronic) RfD = reference dose, MOE = margin of exposure, 

LOC = level of concern, N/A = Not Applicable, HDT = highest does tested, CDHS = California Department of Health Services
Page 20 of 69

3.2 Dietary Exposure 

In the tolerance reassessment conducted for ETO in 2006, study data from spice sterilization 

indicated that ETO levels declined rapidly after sterilization, but 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, including those listed, the acute dietary exposure 

estimates for ECH were below the Agency’s level of concern. The acute dietary exposure (food 

only) utilized 96% of the aPAD for the highest exposed population subgroup, children 1-2 years 

of age. It was based on a refined 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 seed, 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 Dietary 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 reaction 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 model 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 population 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 existing registrations.
Page 21 of 69

3.2.2 Dietary (Food - Antimicrobial Uses)

There is no anticipated dietary exposure in food from the non-agricultural (antimicrobial) uses of 

ETO (see 1.5.2.2). A dietary assessment 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 uses of ETO. Therefore, 

residue chemistry data or assessment of risk associated with drinking water is not expected to be 

needed.

3.2.4 Residue Chemistry (Conventional and Antimicrobial Uses)

ETO residues disappear rapidly after 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 sterilization concentrations, ETO reacts with moisture to 

form EG and, in the presence of sugars, glycol derivatives. 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 fumigation, as no livestock 

feedstuffs are treated (see 1.5.2.1).

The qualitative nature of ETO residues in plants is adequately understood. The residues of 

potential concern in plants are ECH and EG because 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 spice sterilization study indicate that it disappears 

rapidly after sterilization. ECH is a reaction product from sterilization of herbs, spices and 

walnuts. ECH is not removed by out-gassing.

The residue chemistry database for ETO is adequate 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 assessment of ETO occupational exposures (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 worker exposure for the sterilization process for the 

spice industry and the beekeeping equipment were substantially similar. No worker exposure 
Page 22 of 69

frequency data was submitted to the Agency regarding ETO spice sterilization activities; 

therefore, it was assumed that exposure frequency 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 (Crowley, 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 requiring data regarding potential 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-application 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 operators, etc.). Potential exposures due to offgassing will also be assessed for workers conducting post-application activities near treatment 

operations.

3.3.1.2 Antimicrobial Uses

Antimicrobial use sites of ETO include medical devices, musical instruments, library and 

museum artifacts, and cosmetic ingredients. Two sources of observational information were used 

to assess the medical device sterilization in the 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 the ETO Sterilization Association, Inc (MRID 

47331801, DP348868) was used as the basis for the contract sterilization facility treatments. The 

scope of materials potentially sterilized within the contract sterilization facilities includes 

medical devices (representing the majority of use), musical instruments, library and museum 

artifacts, and cosmetic ingredients.

The 2008 RED assessment of the medical facility treatments 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 Standard. The 2008 RED assessment of the medical 

facilities was based on the Standard Industrial Classification (SIC) codes and facility descriptions 

provided in Table 9. The summaries of the air concentrations associated with the medical 

industries listed in Table 9 are provided in Table 10 and Table 11 below. 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 the air samples were not exclusively obtained from 

one particular area in the medical facility (e.g., sterilization chamber) rather they were taken 

from every area that the person entered during his/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 apparatus
Page 23 of 69

SIC Code Description

3842

Orthopedic, 

Prosthetic, and 

Surgical Appliances 

and Supplies

Establishments primarily engaged in manufacturing orthopedic, prosthetic, and 

surgical appliances and supplies, arch supports and other foot appliances; fracture 

appliances, elastic hosiery, abdominal supporters, 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 having the degree of M.D. and engaged in 

the practice of general or specialized 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 providing 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 providing general medical and surgical 

services and other hospital services.

8063 Psychiatric Hospitals Establishments primarily engaged in providing diagnostic medical services and 

inpatient treatment for the mentally ill.

8069 Specialty Hospitals, 

Except Psychiatric

Establishments primarily engaged in providing diagnostic services, treatment, and 

other hospital services for specialized categories of patients, except mental. 

8099

Health and Allied 

Services, Not 

Elsewhere Classified

Establishments primarily engaged in providing health and allied services, not 

elsewhere classified. 

Table 10 illustrates the reduction in air concentrations based 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 concentrations for all medical 

SIC codes as well as a delineation of air concentrations by individual SIC codes.

Table 10 – ETO Air Concentrations from IMIS for All Medical SIC Codes

Statistic 1979 to 1987 (ppm) 1988 to 2007 (ppm)

Arithmetic mean ± std 2.44 ± 24 0.49 ± 2

50th %tile 0.029 0.026

75th %tile 0.17 0.21

90th %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 years 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 24 of 69

The 2008 RED assessment of the contract sterilization facilities was based on the ETO

Sterilization Association, Inc., submission (MRID 47331801, DP348868). Their submission 

(2008) is a summary of existing ETO observational air concentration data obtained from 21 

contract sterilization facilities. At the time of the submission, the 21 facilities represented 90 

percent of the contract sterilization 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 exposure to workers not wearing respirators (i.e., 

workers working in areas of the facility not in the aeration/unloading 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 for 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

50th %tile 0.10 0.13

75th %tile 0.27 0.21

90th %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 mitigation measures to further reduce the potential 

exposure and risks to workers. The upcoming registration review assessment should be based on 

the air concentrations post-mitigation. The reassessment 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 post-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 anticipated to be required for ETO:

875.1400 – applicator inhalation data

875.1700 – product use data

3.3.2 Residential Exposures

There are no residential handler (applicator) uses for ETO.

3.3.2.1 Conventional Uses

There is a potential for bystander exposures which 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 residential risk assessment for ETO which estimated cancer as 
Page 25 of 69

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, according to the RED, the 

Agency concluded that potential cancer and non-cancer risks did not indicate any further 

regulatory action was necessary at the time for residential inhalation exposure. As a supplement 

to the 2005 OAR analysis and any future refinements of their analysis, bystander exposures will

be reassessed, for registration review and as per other fumigants, using computer modeling (e.g.,

PERFUM).

There is sufficient information to complete such analyses for ETO. However, in the event that 

the available information suggests that there may be bystander risks of concern, a more refined 

analysis would be possible if additional data were available. Types of information that could be 

used to refine the bystander assessment include: information on treatment conditions such as 

volumes treated, concentration/time schedules used, release height, and air exchange rates. In 

summary, to the extent that the available data show potential for bystander exposure, updated 

residential assessments will be conducted during registration review. Additionally, the OAR 

bystander assessment and any refinements to this analysis will be considered 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 commercial sterilization sources. Based on a qualitative 

screening-level risk assessment 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 additional 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 releases resulting from commercial sterilization 

sources relied on EPA’s Office of Air and Radiation (OAR) residual risk assessment conducted 

in 2005 for ETO (DP338729) as cited in section 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 with meteorological data, and (2) U.S. Bureau of Census 

population data for 2000 and the census block level. The HEM-Screen's dispersion model is a 

Gaussian model. OAR estimated ambient concentration at census blocks at varying distances 

from ETO commercial sterilization sources. For details of the assessment 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 anticipated to be required for ETO:

875.2500 – Post application bystander inhalation exposure data

Special Study - Monitoring data on fumigated commodities

3.4 Aggregate and Cumulative 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 there is not a common chemical exposure for 

residential and dietary exposure scenarios (i.e., the reaction products ECH and EG are the 
Page 26 of 69

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 “available information” concerning the cumulative 

effects of a particular pesticide'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 the purposes of this tolerance reassessment action, therefore, EPA has 

not assumed that ETO has a common mechanism of toxicity with other substances. For 

information regarding EPA’s efforts to determine which chemicals have a common mechanism 

of toxicity and to evaluate the cumulative effects of such chemicals, see the policy statements 

released by EPA’s OPP concerning common mechanism determinations and procedures for 

cumulating effects from substances found to have 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 involving substances of a gaseous, highly volatile liquid or highly 

reactive solid do not typically 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 has not required submission of environmental fate or effects data.

Therefore, the information that is currently available 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 exposures of concern to the 

environment based on an assumption that exposures 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 fumigation and monitoring data from use facilities 

demonstrating releases of ETO, a more quantitative assessment of risks will be conducted during 

registration review. The ecological risk assessment planned during registration review will allow 

the Agency to determine potential risks to organisms 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 habitats. When an assessment concludes that a 

pesticide’s use 'may affect' a listed species or its designated critical habitat, the Agency will 

consult with the U.S. Fish and Wildlife Service and/or National Marine Fisheries Services (the 

Services), as appropriate.
Page 27 of 69

4.1 Environmental Fate Assessment

ETO is a gas in its natural state, and is used primarily as a fumigant. 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 soluble (1000 g/L at 25 oC, EPI Suite version 

4.10) but also has a high tendency to volatilize from water (half-life <1 hour, Conway, 1983; 

vapor pressure 1255 millimeters of mercury, EPISuite v4.10). Additionally ETO is not stable in 

aqueous medium (fresh water and sea water) under aerobic conditions and in water the 

concentration of ETO would be further reduced due to hydrolytic degradation. The likely 

hydrolytic degradates are: EG, ECH, and possibly EBH. A study by Gomer, and Noyes (1950), 

showed that ETO autocatalyzes into methane, ethane, hydrogen, and carbon dioxide (MRID 

49126104). Since ETO is biodegradable and volatile, it is not likely to be present in ground 

water. Based on the chemical and physical properties, ETO is unlikely to accumulate in soils or 

sediments and it will volatilize as water evaporates, 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 potential for risk concerns from ETO use is most 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 deicing is carried out on planes by using glycol. The 

TMDL established a daily maximum for glycol of 125 mg/L and for a thirty-day average it is 

190.0 mg/L. These TMDL are not associated with 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 Environmental Exposure Pathways

Based on the summary of registered uses of ETO presented in Table 5, physical/chemical 

properties and environmental fate data presented in Table 4 and Appendix B, the Agency has 

developed a conceptual exposure model diagram for terrestrial and aquatic organisms to ETO.

Under ambient environmental conditions, ETO released 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 employed in some facilities. More information is 

needed to identify if this is a method used to remove ETO from air before venting. However, 

under ambient conditions ETO scrubbed from vented air to water is expected, with a half-life of 

<1 h, to volatilize along the way to a Waste Water Treatment Plant (WWTP). Chemicals that are 

released down-the-drain can typically take from a few to several hours to reach wastewater 

treatment plant intakes following their discharge and from several hours to roughly a day 

following their 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 available for runoff or leaching, it will not be considered for aquatic exposure 

 

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

9http://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 28 of 69

(USEPA 2013b). For the purposes of this risk assessment, terrestrial non-target organisms are 

assumed to occupy areas immediately adjacent to treatment sites and aquatic non-target 

organisms are assumed to occupy water bodies immediately adjacent to treatment sites. For a 

gaseous pesticide released from a treatment chamber, the terrestrial exposure pathways 

considered most likely to occur are those to terrestrial animals via inhalation of the gas and to 

terrestrial plants via contact of the gas to the external layer of plant tissues.

Figure 1 – Conceptual Model for Ecological Exposure 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 universal poison for protoplasm. It causes clotting of 

proteins, deactivation of enzymes 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, federal laboratory data, or from the public literature are tabulated in 

Appendix C along with the data requirements 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 Vigor
Page 29 of 69

These selected endpoints will be updated during 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 are 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, risk 

would 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 are not expected to reach the 

receptors due to the rapid decline 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

LD50 = 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 minnow1

(Pimephales promelas)

Acute 96-h LC50 = 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 EC50 = 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 LC50 = 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 concentrations 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-listed2IC50 >0.86 mg/L 47921703 Acceptable4, 5

Listed3 NOAEC > 0.86

Aquatic vascular Duckweed (Lemna 

gibba)

Non-listed2IC50 > 0.87 mg/L 47921702 Acceptable4, 5

Listed3 NOAEC > 0.87 mg/L
Page 30 of 69

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 

Listed not likely.

Terrestrial Plants Vegetative vigor

Non-listed IC50 > 252 mg a.i./m3 47921701 

Acceptable

Data gap for nine species. Listed NOAEC = 252 mg a.i./m 7

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 (IC50) 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 substance by using environmental chambers 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./m3

4.4 Exposure Analysis Plan

4.4.1 Wildlife Exposure Estimates

Available OPP models will be used to determine 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 exposure will only be the parent compound, ETO. Three 

reaction products were identified based on the open literature data as EBH, ECH, and EG 

(USEPA 2008). There is not any evidence that the residues of these reaction products exist in 

terrestrial or aquatic environment 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 sterilization near the treatment facility (USEPA 2013b, 

http://www.epa.gov/scram001/dispersion_screening.htm). The model estimates the "worst-case" 

of 1-hour concentrations for a single source, without the need for hourly meteorological data.
Page 31 of 69

AERSCREEN is intended to produce concentration estimates that are equal to or greater than the 

estimates produced by other refined air dispersion model with a fully developed set of 

meteorological and terrain data, but the degree of conservatism may vary depending on the 

application. The maximum concentration in the first hour is 0.687 g/m3according the current 

label at 31.22 lb/1000 ft3 (500 mg/L) with 16 steam washes on an estimated treatment facility 

with 10,000ft3spaces based on the second release scenario. The detailed modeling information 

can be found in Appendices E and F.

In order to address the risk hypothesis, the potential for adverse effects on the environment will 

be assessed by estimated air concentration adjacent to the treatment facility 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 integrated to assess risk. This will be accomplished 

using a risk quotient (ratio of exposure concentration to effects concentration) approach.

Although risk is often defined as the likelihood and 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 either the level of concern or actual calculated risk quotient 

value.

The aquatic exposure pathways considered is unlikely to occur to aquatic organisms. In the worst 

case scenario, ETO is introduced to surface water during precipitation events where the gas 

dissolves in the precipitation. However, exposure to ETO is expected to be limited by its rapid 

evaporation from water bodies with a one-hour dissipation half life (see 4.1 and Appendix B ).

Table 14 – AERSCREEN Modeling Scenarios and Data Summary

Maximum 

1-Hr Conc 

(μg/m3)

Scaled 3-Hr 

Conc (μg/m3)

Scaled 8-Hr 

Conc (μg/m3)

Scaled 24-Hr 

Conc (μg/m3)

Scaled Annual 

Conc (μg/m3)

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+05
Page 32 of 69

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 applications, the minimum application intervals, 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 estimated by a Tier-I screening model, AERSCREEN 

(http://www.epa.gov/scram001/dispersion_screening.htm). The Tier-I model will produce 

estimates of "worst-case" 1-hour concentrations for a single source, without 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 may be refined by the Tier II Probabilistic 

Exposure and Risk Model for Fumigants (PERFUM). PERFUM is capable of producing a 

distribution of air EECs from a range of different meteorological conditions.

This analysis plan may be revisited and revised depending upon a full review of the data 

available in the open literature and the information 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 searched during the risk assessment phase of ETO and 

the data reviewed following the Agency’s policy 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 and/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 Laboratory's Mid-Continent Ecology Division.

 

11http://www.epa.gov/pesticides/science/efed/policy_guidance/team_authors/endangered_species_reregistration_wor

kgroup/esa_evaluation_open_literature.htm

Treatment

Chamber

Release Vent or Stack
Page 33 of 69

5 Endocrine Disruptor Screening Program (EDSP)

As required by FIFRA and FFDCA, EPA reviews numerous studies to assess potential adverse 

outcomes from exposure to chemicals. Collectively, these studies include acute, subchronic and 

chronic toxicity, including assessments of carcinogenicity, neurotoxicity, developmental, 

reproductive, and general or systemic toxicity. These studies include endpoints which may be 

susceptible to endocrine influence, including effects on endocrine target organ histopathology, 

organ weights, estrus cyclicity, sexual maturation, fertility, pregnancy rates, reproductive loss, 

and sex ratios in offspring. For ecological hazard assessments, EPA evaluates acute tests and 

chronic studies that assess growth, developmental and reproductive effects in different 

taxonomic groups. As part of its reregistration 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 FFDCA section 408(p), ETO is subject to the

endocrine screening part of the Endocrine Disruptor Screening Program (EDSP).

EPA has developed the EDSP to determine whether certain substances (including pesticide 

active and other ingredients) may have an effect in humans or wildlife similar to an effect 

produced by a “naturally occurring estrogen, or other such endocrine effects as the Administrator 

may designate.” The EDSP employs a two-tiered approach to making the statutorily required 

determinations. Tier 1 consists of a battery of 11 screening assays to identify the potential of a 

chemical substance to interact with the estrogen, androgen, or thyroid (E, A, or T) hormonal 

systems. Chemicals that go through Tier 1 screening and are found to have the potential to 

interact with E, A, or T hormonal systems will proceed to the next stage of the EDSP where EPA 

will determine which, if any, of the Tier 2 tests are necessary based on the available data. Tier 2 

testing is designed to identify any adverse endocrine-related effects caused by the substance, and 

establish a dose-response relationship between the dose and the E, A, or T effect. 

Under FFDCA section 408(p), the agency must screen all pesticide chemicals. Between October 

2009 and February 2010, EPA issued test orders/data call-ins for the first group of 67 chemicals, 

which contains 58 pesticide active ingredients and 9 inert ingredients. A second list of chemicals 

identified for EDSP screening was published on June 14, 201312 and includes some pesticides 

scheduled for registration review and chemicals found in water. Neither of these lists should be 

construed as a list of known or likely endocrine disruptors.

For further information on the status of the EDSP, the policies and procedures, the lists of 

chemicals, future lists, the test guidelines and the Tier 1 screening battery, please visit our 

website.13

6 Next Steps

A DCI will be developed regarding the data needs listed under the “Risk Assessments and

Anticipated Data Needs” section of this document. The Agency expects to issue the DCI by

March 2015.

 

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 34 of 69

7 References 

ASTA (American Spice Trade Association). 2005. Public comments to Phase 3 of the 

reregistration risk assessment of ethylene oxide. Docket ID: OPP-2005-0203-0032/0034. 

http://www.regulations.gov/#!documentDetail;D=EPA-HQ-OPP-2005-0203-0034

ATSDR (Agency for Toxic Substances and Disease 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., Howard, P.H. and Santodonato J. 1980. Investigation 

of Selected Potential Environmental Contaminants: Epoxides. A final report submitted 

to USEPA Office of Toxic Substances, 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 materials 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 and their effects, 2nd ed., The Royal Society of 

Chemistry.

GDCh, BUA: The German Chemical Society-Advisory Committee on Existing 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 Characteristics. 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 constants 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) Characterization of the odor properties of 101 

petrochemicals using sensory methods. J. Air Pollut. Control Assoc., 24: 979-982.

Howard Philips, 1989: Handbook of Environmental 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/cicads/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 Agency (EPA 600/8-84/009F).

USEPA. 2001. EFED RED Chapter for Ethylene Oxide DP279672. 2pp
Page 35 of 69

USEPA. 2002. ECOTOX User Guide: ECOTOXicology Database System. Version 3.0. 

Available: http://www.epa.gov/ecotox/

USEPA. 2004. Overview of the Ecological Risk Assessment Process in the Office of Pesticide 

Programs, U.S. Environmental Protection Agency. Endangered and Threatened Species 

Effects Determinations. Office of Prevention, Pesticides and Toxic Substances, Office of 

Pesticide Programs, Washington, D.C. January 23, 2004.

USEPA. 2008. Review of Calculated 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 Relationships (ECOSAR). 2011. Version 1.10, 

http://www.epa.gov/oppt/newchems/tools/21ecosar.htm.

USEPA. 2013a. BEAD Chemical Profile for Registration 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 36 of 69

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 after 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

LD50 = 330 mg/kg (m)

LD50 = 365 mg/kg (m)

LD50 = 280 mg/kg (f)

LD50 = 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-LC50 = 1741 ppm (3.1 mg/L) (m&f) 

1h-LC50 =5029 ppm (9.2 mg/L) (m&f) 

4h-LC50 = 820 ppm (1.5 mg/L)

4h-LC50 = 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

LD50 = 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 effects were determined
Page 37 of 69

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 weight 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 cerebral cortex at 200 ppm (1 male), 

mononuclear cell leukemia (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 righting reflex and organ weight 

changes.

Acceptable/Non-Guideline

Chronic Toxicity

870.4100

Chronic 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 conduction 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, inadequate hematological and clinical 

parameters etc..); small number of animals tested (only 2 animals were 

sacrificed after 2 years of exposure).

Acceptable/Non-Guideline Study
Page 38 of 69

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 tumors 

which 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: mononuclear cell 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 hematological 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 hematopoietic 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 amount of inhaled ETO is found 

distributed in liver, kidneys and lungs with small amounts in spleen, 

testes and brain. In rats, greater 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 acid, formic acid and carbon dioxide. 

This is predominant in larger species 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 glutathione conjugates; Small amounts (10%) 

are eliminated as carbon dioxide and negligible amounts (1%) are 

eliminated via lungs as the parent compound
Page 39 of 69

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 standardized 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 categories, 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 excess 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 cancers in males (p=0.02). The odds ratios with 15 

year lag for hematopoietic cancer mortality 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 tumors (non-Hodgkin’s lymphoma, 

myeloma, lymphocytic leukemia). Although 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 40 of 69

Appendix B Environmental Fate

Environmental Fate and Transport Properties of ETO

The primary mode of transport of ETO for both the 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 use category for conventional pesticides and 

historically an indoor use pattern for antimicrobials and is a gaseous 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

Mobility

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 atmosphere will occur rapidly via oxidation by hydroxyl 

radicals. The atmospheric residence time of ETO was calculated to be 5.8 days based on the 

theoretical rate constant for 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 photolytic reactivity of five oxygen containing 

hydrocarbons, ETO being one of them, in smog chambers specially made for the study.

Irradiation was provided through fluorescent lamps consisting of 22 black lights, and 7 sunlamps 

kept around the smog chamber. Initial concentration of ETO was 4 ppm, and the residual 

concentration of ETO was monitored 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 supplemental because not all raw data is available for 

independent review. The information is useable in a risk assessment.
Page 41 of 69

Gomer and Noyes, 1950 (MRID 49126104) investigated the direct impact of sunlight on the 

photodecomposition and characterization 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 were: methane, ethane, hydrogen and carbon monoxide, 

and minor quantities of formaldehyde and acetaldehyde. 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 degraded by direct sunlight in the atmosphere 

(GDCh BUA, 1995).

Water and Sediment

Evaporation from water is expected to be a significant ETO removal process. Conway et al. 

(1983) found a half-life of <1 h for ETO evaporation from water. ETO degradation in water 

through ionic reactions and hydrolysis 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 perturbation is not a required condition 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-ethanediol and 23% forms 2-chloroethanol with a half-life of 9 days 

(Conway et al., 1983). The results indicate that the half lives in these three media are quite 

similar to each other (9 to 14 days), which likely means that presence of biota is not a condition 

for the degradation of ETO. This study is classified as supplemental because not all raw data is 

available for independent review. The information is useable in a risk assessment and no 

additional volatilization data is required.

A study by Gomer, and Noyes (1950), showed that ETO autocatalyzes 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 persistent in biotic conditions (MRID 49126105).

Conway et al., 1983 (MRID 49126102) conducted a hydrolysis study with ETO in three different 

media sources: distilled water, natural fresh water, 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 known quantity of ETO was 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 distilled water it was measured to 

be about 12 days. Chemical degradates in these media included ethylene glycol (or simply 
Page 42 of 69

glycol), chlorohydrin, and in sea water bromohydrin. The study is a non-guideline study and was 

published as a research paper. This study is classified as supplemental because not all raw data is 

available for independent review. The information is useable in a risk assessment and no 

additional hydrolysis data are 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 logarithm of the octanol/water partition coefficient (Kow) 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 theoretical oxygen after 5 and 20 days, respectively 

(Bridié et al., 1979; Conway et al., 1983).

Soil

The log Koc value of ETO is 0.325 which indicates a highly 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, 14th 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 cannot 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 assessment and no additional activated sludge 

biodegradation data are expected to be required.

Bioaccumulation

The log Kow of ETO (-0.30) is very small, and thus it is not likely to bioaccumulate in aquatic 

organisms. There are no published reports of measured bioconcentration in any aquatic 

organisms. A bioconcentration factor can be estimated using the log Kow:

Log BCF = (0.76)(log Kow) - 0.23

With a log Kow 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, particularly 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 photoionization detector (PID) 

for detection (Bond and Dumas 1982; Collins and Barker 1983). A method for the determination 
Page 43 of 69

of ETO in water and soil samples by partition infrared spectrophotometry has been reported 

(APHA 1985; Environment Canada 1985). 

References Appendix B

Conway, RA, Waggy, GT, Spiegel, 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 and their effects, 2nd ed., The Royal Society of 

Chemistry.

GDCh, BUA: The German Chemical Society-Advisory Committee on Existing 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 Characteristics. 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 Environmental 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 Federal 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 2-79
Page 44 of 69

Appendix C Ecotoxicology Profile

Toxicity of ETO to Terrestrial Receptors

Mammals

There is acute oral information for three mammalian species: laboratory rats, mice, and guinea 

pigs. Selected endpoints for these species are provided in the Appendix A Toxicology Profile for 

human health. The median lethal dose (LD50) ranges from 270 mg/kg-bw for guinea pigs (male 

and female, combined) to 365 mg/kg-bw for male rats (IPCS, 2003). These results categorize 

ETO as moderately toxic to mammalian wildlife on an acute oral basis.

There is acute inhalation data for three mammalian species: laboratory rats, mice, and dogs.

Selected endpoints for these species are provided in the Appendix A Toxicology Profile for 

human health (MRIDs 42046601 and 42429201; IPCS, 2003). The four hour median lethal 

concentration (4-h LC50) 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 LC50 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 observed adverse effect concentration (NOAEC) from the study is 

10 ppm (0.018 mg/L).

Birds

There is no ETO acute or chronic toxicity data for birds. Inhalation data for birds are anticipated 

as needed to determine risk from ETO use patterns. 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 study 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 released to the atmosphere after aeration of the 

treatment chamber, the terrestrial animal exposure route considered most likely to occur is 

through inhalation of the gas. Therefore, the Agency expects to require a non-guideline 

inhalation study with birds instead of the oral and dietary studies. Since this 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, the acute risk to birds exposed to 

ETO cannot be precluded and will be presumed.

Beneficial Insects

ETO has fumigant uses that may result in exposure 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 insects are expected (as observed in other terrestrial 

invertebrate studies), the Agency expects to require a non-guideline vapor-phase exposure 

toxicity study with bees to assess whether the effects seen in bees are similar to those observed in 
Page 45 of 69

other terrestrial invertebrates. Since this vapor-phase exposure study is a non-guideline study, a 

study protocol that calculates a vapor-phase exposure LD50 for adult bees would need to be 

submitted for review by the Agency prior to initiation of the study. Until an acute vapor-phase 

exposure endpoint to evaluate the toxicity 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 exposure to terrestrial plants. Typically, the Agency 

requires seedling emergence and vegetative vigor studies to assess the effects to terrestrial plants 

exposed to a pesticide as a result of surface water runoff or/and off-site spray drift, respectively; 

however, because ETO will be released from treatment chambers as a gas, the terrestrial plant 

exposure pathway considered most likely to occur 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 vegetative vigor data with actively growing plants 

to assess the effects of ETO when the gas penetrates the plants. The Agency uses a battery of ten 

species14 representing at least six different families to evaluate potential effects to all flora. There 

is one vegetative vigor study with a dicot species (soybean) exposed to ETO as a gas (MRID 

47921701). At the highest exposure concentration of 252 mg ai/m3, no effects to vegetative vigor 

were observed (i.e., IC25 >252 mg ai/m3, NOAEC >252 mg ai/m3). 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 Table 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 duration of the test due to volatilization, hydrolysis to EG, and 

biodegradation. ECOSAR version 1.10 was used to estimate aquatic toxicity results for the green 

algae, and acute and chronic results for a generic freshwater fish and a freshwater daphnia (see 

the following ECOSAR version 1.10 results page). ETO is a member of the mono epoxides 

group, which was used in ECOSAR version 1.10 to model toxicity results. There is a footnote in 

the ECOSAR version 1.10 results output that empirical ETO data, a fish 96-h LC50 value and a 

48-h EC50 value for a daphnid (Conaway et al., 1983), are included in the structure activity 

model for the mono epoxides group. Current guideline 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 significant 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.

 

14 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 should be a root crop (either a monocot such as onion or dicot such as carrot, 

table beet or sugar beet).
Page 46 of 69

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 LC50 = 85 mg 

a.i./L

Conway et al., 

1983

Supplemental/

Slightly toxic

Freshwater 

invertebrate

acute toxicity

Waterflea (Daphnia 

magna), static, nominal

48-h EC50 = 137 mg 

a.i./L Conway et al, 1983 Supplemental/Practically non-toxic

Estuarine/Marine 

fish

Acute toxicity

Striped mullet (Mugil 

cephalus)

96-h LC50 = 89 mg 

a.i./L Crews et al., 1974 Supplemental/Slightly oxic

Acute toxicity Brine shrimp1

Artemia sp.

EC50 = 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)

IC50 >0.87 mg/L

NOAEC > 0.87 47921702 Acceptable/--

2

Aquatic plant 

growth:

Tier I algae

Freshwater green alga 

(Pseudokirchneriella 

subcapitata), static

IC50 >0.86 mg/L

NOAEC > 0.86 47921703 Acceptable/--

2

1 Brine shrimp, which are found in specialized habitat, are not used as a surrogate for estuarine/marine species.

2Toxicity categories have not been assigned for aquatic plants.

Table 19 – ECOSAR v1.11 Results for ETO

Organism Endpoints

Fish, Freshwater generic 96-h LC50 = 57.7 mg/L ChV = 0.015 mg/L

Daphnia, Freshwater Invertebrate, 

generic 48-h EC50 = 278 mg/L ChV = 27.8 mg/L

Green algae, generic 96-h IC50 = 501 mg/L ChV = 168 mg/L

ChV = geometric mean of the NOEC and LOEC, also referred to as the MATC

Effects of ETO on Soil Microbes

Gennari et al. 1987 (MRID 49126103) investigated the 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, actinomycetes, aerobic and anaerobic nitrogen fixers, 

ammonifiers, nitrifying, denitrifying, proteeolytic, ammololytic, pectinolytic, aerobic and 

anaerobic cellulolytic.

The exposure with ETO was carried out for four hours and eight hours. The study was conducted 

by taking 10% ETO in a chamber containing carbon dioxide (CO2) atmosphere (3375 mm Hg 

pressure), where 65% relative humidity was maintained and temperature was kept at 40 oC. After 

3 days, desorption process was carried out. Microbial analysis on the 4 hour-treated soil did not 

show any degree of sterilization; however, 8 hour treated soil showed complete elimination of all 

microorganisms. Slight changes in soil characteristics were observed for the ETO-treated soil.

These changes were: a slight increase in pH, an increase in organic matter, and an increase in 
Page 47 of 69

available phase iron (Fe) and manganese (Mn). These metals were extractable by ethylene 

diamine tetraacetate (EDTA) analysis. A slight decrease in cation exchange capacity and total 

nitrogen (N) content was also observed with ETO-treated soil. This study indicated a strong 

pesticidal effect of ETO on the soil microorganisms. The study is a non-guideline study. It is 

classified as supplemental and useable for characterizing 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 Endpoints from Aquatic Toxicity Studies for 

EG (Degradate of ETO).

Receptor 

Group

Surrogate

Species

Risk

Scenario

Toxicity

Endpoint

Reference

(MRID)

Freshwater fish1

Fathead minnow1

(Pimephales 

promelas)

Acute 96-h LC50 > 100,000 mg a.i./L Conway et al., 

1983

Freshwater 

invertebrates

Waterflea (Daphnia 

magna)

Acute 48-h EC50 >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 ethylene oxide. Docket ID: OPP-2005-0203-0032/0034. 

http://www.regulations.gov/#!documentDetail;D=EPA-HQ-OPP-2005-0203-0034

ATSDR (Agency for Toxic Substances and Disease 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., Howard, P.H. and Santodonato J. 1980. Investigation 

of Selected Potential Environmental Contaminants: Epoxides. A final report submitted 

to USEPA Office of Toxic Substances, 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 materials 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 Characteristics Plant ands Soil, 102:197-200.

Hansch, C, and Leo A. 1979. Substituent constants for correlation analysis in chemistry and 

biology. New York, NY: John Wiley & Sons, Inc., 176.

Hellman, T.M. & Small, F.H. (1974) Characterization 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/cicads/cicads/cicad54.htm) (Accessed 2/27/2013).
Page 48 of 69

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 Environmental 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 the Office of Pesticide 

Programs, U.S. Environmental Protection Agency. Endangered and Threatened Species 

Effects Determinations. Office of Prevention, Pesticides and Toxic Substances, Office of 

Pesticide Programs, Washington, 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 Relationships (ECOSAR). 2011. Version 1.10, 

http://www.epa.gov/oppt/newchems/tools/21ecosar.htm.

USEPA. 2013a. BEAD Chemical Profile for Registration 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, Geneva, 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

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

ECOSAR v1.1 Class-specific Estimations

--------------------------------------
Page 49 of 69

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 50 of 69

Appendix D Product Chemistry

The ETO product chemistry information is summarized in Table D1 (source: MRIDs 41531002, 

42458502, 42466702, 42811401, 43053201, and EPI Suite v4.1). 

Table D1 – 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/cm3 

0.882 g/cm3 at 25 °C

0.8697 g/ml 20 °C
Page 51 of 69

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 (noctanol/water) Log Kow− 0.30 (Log P)

830.7840 Solubility in water Infinitely soluble.

830.7860 Solubility in organic solvents Readily soluble in water, ethanol, diethyl ether, acetone, 

benzene and many organic solvents.

830.7950 Vapor pressure 1255 mm Hg at 25°C
Page 52 of 69

Appendix E Modeling Input Based on ETO 

Release Scenarios for Spices and Herbs

ETO is used to treat spices, dried vegetables, and seasonings in fumigation chambers. Labels 

specify maximum application rates, or indoor concentrations of ETO, which are maintained over 

periods of time for treatments inside the chambers. Fumigation chambers have a maximum size 

of 10,000 cubic feet.

15 Labels all require mechanical, or forced, aeration following a treatment of 

the commodities. Mechanical aeration releases the fumigant outdoors from the treatment 

chamber through a stack or vent. Product labels particularly specify that ETO is to be evacuated 

from chambers through the use of steam scavenging techniques, and specifies the number of 

washes that are to be applied during aeration. Labels also specify the temperature of the steam 

which renders the aeration as a buoyant release. ETO labels specify the following mechanical 

release parameters given the following maximum application rates:

First Release Scenario

 Maximum Application Rate (per chamber) = 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 chamber) = 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 location. The labels do not specify a maximum amount 

of simultaneous fumigation chamber treatments.

AERSCREEN Description

The Agency’s recommended screening dispersion model for the near field, the American 

Meteorological Society/EPA Regulatory Screening Model (AERSCREEN), will be used to 

generate screening EECs for the various 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 conditions (light winds and stagnant conditions) 

and downwash16 parameters are assumed to calculate peak air EECs, representing one-hour 

average concentrations. Documentation on the AERSCREEN model is available at 

http://www.epa.gov/scram001/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 downwind from the building at ground level.

 

15 Fumigation chambers are assumed to possess similar size to railcars. Citation: 

http://www.csx.com/index.cfm/customers/equipment/railroad-equipment/

16 Downwash is defined as the downward flow often observed on the leeside of buildings induced by wake 

turbulence. Pollutants released from buildings can often become embedded in downwash flows and wake cavities.
Page 53 of 69

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 described above will be modeled to capture all 

possible combinations of release parameters. Either 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 described above. Each modeled 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 modeling captures the upper-bound air 

exposure from release scenarios consolidated above from information on the ETO product label.

Table E1. AESCREEN input parameter values capturing 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.3chamber released in one-hour 

period1

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 (f3/min.) 3,500 2,667

Scenario 1:

Based on 21 steam washes specified on label –

assume 21 air exchanges per hour for hourly 

release3

Scenario 2:

Based on 16 steam washes specified on label –

assume 16 air exchanges per hour for hourly 
Page 54 of 69

Input Parameter Option/Value Notes

Scenario 1 Scenario 2

release3

Urban or Rural? R (Rural) Conservative default

Minimum Distance to Ambient 

Air (ft.) 3.3 Conservative default

NO2 Chemistry 1 (No chemistry/pollutant 

is not NO2)

Tracer gas NOx 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 Default - 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 base 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 source4

Bowen Ratio 3.0 Bare surface assumed around source4

Surface Roughness Length (m) 0.001 Bare surface assumed around source4

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 Assessment 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 55 of 69

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 TEMPORAL
Page 56 of 69

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: 3.00
Page 57 of 69

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

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

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 58 of 69

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 59 of 69

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.

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

********************** AERSCREEN MAXIMUM IMPACT SUMMARY *********************

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

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
Page 60 of 69

Appendix G Comments Received 

Concerning the Preliminary Work Plan

On September 25, 2013, EPA opened a 60-day public comment period on the preliminary work 

plan (PWP) for the registration review of ethylene oxide. The comment period ended on 

November 25, 2013. During the public comment period the Agency received 12 submissions

from 10 commenters. Table 1 below lists the submitters. 

Table 1. Submitters of Comments on the “Ethylene Oxide Preliminary Workplan”

3M Health Care (2 submissions)

American Farm Bureau Federation (AFBF)

ARC Specialty Products, Balchem Corporation (ARC)

McDermott Will & Emery – on behalf of the American Spice Trade Association (ASTA)

Minor Crop Farmer Alliance (MCFA)

Physicians Committee for Responsible Medicine

Sterigenics International, LLC (Sterigenics) (2 submissions)

STERIS Corporation

The Ethylene Oxide Sterilization Association, Inc. (EOSA)

University of Florida

This appendix is divided into three sections. Section I includes general comments to the PWP. 

Section II offers all comments related to the human health assessment. Section III offers all 

comments related to the environmental fate and effects assessment. 
Page 61 of 69

I. General Comments 

(Agency response to comments 1-4 is below comment 4)

1. Usage Information

EOSA, ARC, ASTA: The usage information on page 11 of the PWP may no longer be 

accurate. EOSA requests the opportunity to review these industry data and provide 

current reliable usage information. Due to the time and resources necessary to compile 

these data, they will not be available for the November 25, 2013, comment period 

deadline. ETO has been used for sterilization and fumigation purposes for decades. 

Approximately 98% of the total pounds of ETO sold for pesticidal purposes are used for 

the sterilization of medical devices by contract sterilizers and medical device 

manufacturers. The number of hospitals performing in-house sterilization has declined 

since the 2008 Reregistration Eligibility Decision (RED), and will continue to decline 

substantially. The industry now estimates that less than 1% of the total pounds of ETO 

used for pesticide purposes will be used in hospitals or other medical facilities. 

Additionally, the use for spice treatment has also declined since the 2008 RED. The 

industry now estimates that less than 1% of total pounds of ETO sold for pesticidal 

purposes are used for fumigation of herbs and spices. 

Therefore, the typical usage of ETO is by large contract sterilization companies or 

medical device manufacturers. All of these companies comply with EPA’s National 

Emission Standards for Hazardous Air Pollutants (NESHAP) for Commercial 

Sterilization Facilities (Subpart O of 40 C.F.R. Part 63). This ETO usage is different than 

the typical agricultural field pesticide use, as the process is performed in vacuum 

chambers. The extent of its use is different from what was published in the 2008 RED.

2. Use or Potential Use Distribution 

EOSA: Products containing ETO are currently being used at over 80 contract 

sterilization facilities, medical device manufacturing facilities, and spice treatment 

facilities in 31 states and Puerto Rico. According to the 2008 RED, there are 

approximately 1,900 hospitals and other medical facilities in nearly all states where 

treatment with ETO takes place. EOSA believes, however, the number of hospital 

facilities has significantly decreased since the 2008 RED was released. Additional time 

will be required to obtain current information.

3. Typical Application Interval 

EOSA: There are no “typical” application intervals for medical device sterilization. Spice 

treatment parameters are specified on the label. 

4. Confirmation of Label Information 

EOSA & ARC: The PWP requests additional information and confirmation on label 

information. The following comments provide additional label information regarding 

sites of application; formulations; application methods and equipment; maximum 

application rates; frequency of application, application intervals, and maximum number 

of applications; and geographic limitations on use.
Page 62 of 69

Application sites: ETO may be used only to sterilize medical or laboratory items, 

pharmaceuticals, and aseptic packaging (21 C.F.R. § 201.1(d)(5)) or to reduce microbial 

load on cosmetics, whole and ground spices, or other seasoning materials (40 C.F.R. § 

180.151), and artifacts, archival materials, or library objects. The use of ETO is only 

approved for industrial and hospital use. 

Formulations: Currently, there are 23 active Federal Insecticide, Fungicide, and 

Rodenticide Act (FIFRA) registrations for products containing ETO as the active 

ingredient. Of those products, eight contain 100% ETO. The remaining 15 products 

contain ETO in various percentages from 8.5% up to 98.06%; all are blended with inert 

ingredients, not other actives. 

Application methods and equipment: ETO may only be used in vacuum or gas-tight 

chambers.

Maximum application rates: For sterilization of medical devices, the concentration of 

ETO is determined by the process used to validate the sterilization cycle in accordance 

with FDA requirements. For the treatment of spices and other seasoning materials, the 

method described on the label specifies a maximum ETO concentration of 500 mg/L. 

Frequency of application, application intervals, and maximum number of applications:

ETO treatment facilities typically operate seven days per week, however, application 

intervals and the number of applications vary from site to site depending on the products 

needing to be treated. The maximum number of treatments for medical device 

sterilization is controlled by FDA requirements. 

Geographic limitations on use: Products containing ETO are registered in all 50 states 

and Puerto Rico. EOSA is not aware of any geographic limitations on use in the United 

States. EPA-registered products containing ETO are also shipped to other countries.

Response to 1-4: The Agency thanks the submitters for these comments and welcomes 

the submission of any additional data commenters have on hand related to use, usage, 

application details, and/or benefits of ethylene oxide. The Agency is lacking current 

information regarding the uses for spice (e.g., rates, spice types, etc.) including the 

availability, efficacy, and use patterns of alternatives. Similarly, the Agency does not 

have the latest information on any alternatives that overlap ETO efficacy for medical 

devices, especially those that might be available for hospital use sites. During the 

registration review of ETO, additional use and usage information and details about 

alternatives may be needed.

5. AFBF: AFBF has been actively engaged for years as a member of the agency’s Pesticide 

Policy Dialogue Committee (PPDC) and values its membership on that committee. At the 

same time, AFBF has longstanding policy, adopted by our national membership, that 

reflects the views of our agricultural producers on how EPA should utilize its authority in 

regulating agricultural chemicals. AFBF strongly recommends that EPA: 

 Base its implementation of FIFRA on credible scientific information; 

 Test pesticides based on realistic levels of exposure or consumption; 

 Consider the risks and benefits when determining whether to cancel or restrict 

pesticides or chemicals used in agricultural production; and 
Page 63 of 69

 Consider actual use data in the risk assessment process and not make decisions 

based on worst-case assumptions.

Response: The Agency thanks AFB for its comment on the registration review process.

The Agency uses the best available data in making its decisions, which may include

actual use and usage information, field studies, monitoring data, modeling, and 

information from incidents. The Agency considered both the risks and benefits of the 

fumigants during the reregistration process, and those decisions were issued in 2008.

During registration review of the fumigants, the Agency is looking at what has changed 

since the last assessments, how significant these changes are, if there is a need for any 

new information or studies to conduct updated risk assessments, and if the Agency’s 

regulatory position is likely to change as a result of any new information.

6. ASTA: McDermott, Will & Emery submitted comments on behalf of the ASTA, 

emphasizing the importance of ETO for the prevention of pests and microbial 

contaminants in spices; expressing concern regarding the potential impact of data 

requirements on the continued availability of ETO for this use; and stating the intention 

of ASTA to be involved in the registration review process, including a suggestion to have 

a focus meeting to identify issues that will be considered in the review and to confirm use 

practices.

Response: The Agency thanks ASTA for their comment on the spice uses of ETO. EPA 

hosted a focus meeting on January 29, 2014 with the ETO registrants and stakeholders to 

discuss comments submitted by the stakeholders pertaining to the ETO Preliminary Work 

Plan (PWP). The stakeholders presented an overview on ETO usage and industrial and

hospital ETO sterilization (typical ETO sterilization processes, emission controls and 

worker exposure control measures). Participants also discussed anticipated data needs 

and areas where the risk assessment could be refined with data from ETO stakeholders.

A summary of the meeting and presentation materials will be available in the docket at 

EPA-HQ-OPP-2013-0244. Additional focus meetings will be held during the registration 

review process as needed.

7. University of Florida: University of Florida is concerned about further increases in 

regulatory costs’, or the loss of chemical fumigants’, impact on the fruit and vegetable 

industries of Florida and other support industries. A summary of some UF fumigant 

research was provided.

Response: This comment pertains to the fumigants used for pre-plant soil treatment, not 

ETO. The comment was placed in the relevant soil fumigant dockets and is addressed in 

those dockets.

8. MCFA: The MCFA is anticipating the need to move forward with interim changes to 

the most current product labels to address problems that users are experiencing.
Page 64 of 69

Response: The Agency is committed to discussing progress on post-RED label 

implementation for the fumigants whenever questions or issues arise. Please contact the 

active ingredient chemical review manager in the Pesticide Re-evaluation Division or the 

Antimicrobials Division who will consult with the fumigant review team on the 

appropriate path forward for any issues with labeling specified by the RED. For other 

label changes, please contact the appropriate Product Manager in the Antimicrobials 

Division.

9. MCFA: The MCFA would appreciate periodic updates regarding the progress being 

made, and any information needs that could be supplied by its members.

Response: The Agency appreciates the offer for assistance with information, and will 

keep this in mind moving forward in the registration review process.

II. Human Health Comments 

1. Acute inhalation toxicity study

EOSA & Sterigenics: EOSA requests clarification and detail regarding the acute 

inhalation toxicity study (special study). EPA notes that this might be an update to the 

2008 occupational handler risk assessment (Table 1). It is not clear whether EPA is 

requesting an update to the 2008 study or if review and subsequent determination by the 

industry that the study accurately reflects current worker exposure will be sufficient. A 

complete new study, as indicated in Table 7, does not appear to be necessary. 

Additionally, we believe the worker exposure scenario assessment would be the “worst 

case” and the industry’s segregation, control of visitors, and area monitoring is sufficient 

to maintain the safety of “bystanders.” 

3M: The concern for bystander exposure through inhalation is acknowledged. 

Nevertheless, there are questions surrounding the endpoints and study design for the 

proposed study that would benefit from a face-to-face discussion to resolve. Acute 

inhalation toxicity studies are typically conducted after 4 hour or 8 hour exposure. 

However, the changes may be so subtle that requested pathological endpoints may not 

provide any meaningful information given the short exposure. The requested 

pharmacokinetic/tissue dosimetry data may require a different dosing regimen as well. A 

more detailed outline of study objectives would be appropriate. As noted by EPA in 

Table 8 of the Preliminary Work Plan, short-term inhalation toxicity data (1-30 days) 

already exists.

PCRM: It appears that data is available for the acute inhalation study: 

Ethylene oxide was tested on groups of rats for either 4-hour or 1-hour inhalation 

exposure, followed by 14 days of observation. Groups of five Sprague-Dawley rats/sex 

were exposed, and clinical signs and mortality were recorded. Clinical signs noted

included irregular breathing, absence of certain reflexes, and tremors. Rats that died had 

moderate to severe pulmonary congestion. The calculated LC50 values, reported as ppm 

by volume (with 95% confidence limits), were as follows. 4-hour LC50 values were 1972 
Page 65 of 69

(1887 to 2061) ppm for males; 1537 (1391 to 1698) ppm for females; 1741 (1655 to 

1831) ppm for the combined sexes. The 1-hour LC50 values were 5748 (5276 to 6262) 

ppm for males; 4439 (4034 to 4884) ppm for females; 5029 (4634 to 5459) ppm for the 

combined sexes. 

Furthermore, please see our comments for Propylene Oxide, as there we provide 

information on in vitro methods, additional existing data, and structure-activity 

relationships (SAR) that may prove helpful for this endpoint. 

Response: The Agency thanks the submitters for these comments. The anticipated 

requirement of a special acute inhalation study was based on a weight of evidence (WOE) 

approach due to the lack of currently available hazard and exposure information for ETO. 

Inhalation is the primary route of exposure and there is a lack of non-lethal 

histopathology data (respiratory tract). Therefore, the special acute inhalation study 

would include respiratory tract histology, glutathione (GSH) measurements (i.e., nose) 

and kinetics/tissue dosimetry (time course) that would directly inform the acute 

occupational and residential bystander assessments. The registrant will have the option of 

submitting to the Agency and the HED Hazard and Science Policy Council (HASPOC) 

an alternative approach/method that would specifically address all of the acute inhalation 

study data requirements. 

To clarify, the special acute inhalation toxicity study is different from the standard acute 

inhalation toxicity study which measures lethality (LC50). Special acute inhalation 

studies have been required of all the commodity and soil fumigants. The parameters that 

are expected to be requested for the special acute inhalation toxicity study are not 

included as measurements in any of the current acute inhalation toxicity studies on ETO. 

The study mentioned in Table 8, as mentioned in the comment above, is a subchronic 

repeated dose inhalation study, which is different from the special acute (single exposure) 

inhalation study which is the study anticipated as being requested for ETO. Once the data 

are required, if the registrant wishes to submit a formal waiver request with all pertinent 

worker and bystander exposure information, then the HASPOC would consider this 

additional information for a weight-of-evidence determination.

2. Inhalation exposure study

EOSA: We also request additional detail on the inhalation exposure study for applicators 

(875.1400). This study appears redundant to the acute inhalation toxicity special study for 

workers/bystanders. 

The post-application (site-specific) inhalation exposure study (875.2500) and ambient air 

monitoring study (special study) appear to have similar objectives. EOSA requests 

additional information and clarification on the need for each.

3M: Inhalation exposure study for applicators EPA Guideline Number 875.1400

The exposure data for individual hospital users are kept at the hospital site as required by 

OSHA. [4] This information is difficult to obtain by 3M due to confidentiality concerns.

When the 3M Steri-VacTM Sterilizer is installed and operated per manufacturer’s

instructions, user exposure is below OSHA permissible limits.
Page 66 of 69

Sterigenics: We also request more detail on the inhalation exposure study for applicators 

(875.1700). This study seems redundant to the Special Study for the acute inhalation 

toxicity study for the worker/ bystander exposures. 

Response: These data are worker exposure data, not to be confused with the acute 

inhalation toxicity study. The inhalation exposure data are anticipated as being required 

to provide EPA with the most accurate measurements of ETO air concentrations for 

workers and ambient air (residential exposures) based on the current industry practices. 

For example, Section 3.3.1.2 of the PWP lists the air concentrations available in OSHA’s 

Integrated Management Information System (IMIS) for the medical facilities (e.g., 

hospitals). These measurements are based on air concentrations collected until 2007. 

Subsequently, the medical facilities have switched to single chambers for ETO 

sterilization. It is anticipated that the air concentrations that workers are exposed to in 

medical facilities have been reduced based on the use of single chambers. EPA 

anticipates requiring the new representative exposure data (i.e., air concentrations) to 

refine the inhalation exposures to be used in the risk assessment. EPA recommends 

searching the new version of the IMIS database and gauge its representativeness and seek 

additional information from individual hospitals as necessary. EPA/OPP will work with 

EPA/OAR to model ambient ETO concentrations in order to better define what potential 

bystander exposure data are needed. Stakeholders are encouraged to work with EPA to 

supply data to refine the ambient modeling results (e.g., effectiveness and prevalence of 

ETO scrubbers and aeration methods). The level of concern for workers and bystanders 

(residential areas/ambient) is yet undetermined and will focus on the results of the 

EPA/ORD IRIS reassessment once peer reviewed.

3. Chronic toxicity/carcinogenicity study-870.4300 

PCRM: ETO, contrary to many other chemicals and as the Agency is aware, has a large 

body of existing evidence, including in humans, as to its carcinogenicity: 

“Ethylene oxide is known to be a human carcinogen based on sufficient evidence of 

carcinogenicity from studies in humans, including epidemiological studies and studies on 

mechanisms of carcinogenesis. Ethylene oxide was first listed in the Fourth Annual 

Report on Carcinogens in 1985 as reasonably anticipated to be a human carcinogen based 

on limited evidence of carcinogenicity from studies in humans and sufficient evidence of 

carcinogenicity from studies in experimental animals. The listing was revised to known 

to be a human carcinogen in the Ninth Report on Carcinogens in 2000.” 

Furthermore, the EPA has indicated, in the documents for this docket and in previous 

guidance, that it is willing to accept information obtained using QSAR, weight-ofevidence, and other “non-testing” approaches in lieu of new in vivo data in some cases. 

We believe that ETO may be a case where these approaches can help to avoid additional 

testing. 

We refer the registrant to the OECD QSAR Toolbox, where one will find several data 

entries for the carcinogenicity endpoint for ETO. These data points include tests in rats 

and mice by both inhalation and oral route, and in rats via dosed feed. 
Page 67 of 69

Response: The information anticipated to be requested is for the ETO reaction product 

epichlorhydrin (ECH) and not ETO. The agency is aware of the database on 

carcinogenicity of ETO and the current IRIS document under review. 

4. Availability of Scrubber Technology for ETO, Prevalence of Use, and Efficiency 

EOSA: Facilities using products containing ETO are required to operate in compliance 

with the requirements of either the NESHAP for Commercial Sterilization Facilities 

(Subpart O of 40 C.F.R. Part 63) or the NESHAP for Hospital Ethylene Oxide Sterilizers 

(Subpart WWWWW of 40 C.F.R. Part 63). Many sterilization companies use acid 

scrubbers, catalytic oxidizers, absorbent systems, or a combination of these systems to 

meet the NESHAP requirements.

Response: Sources which use greater than 10 tons of ETO annually are required under 

the Clean Air Act (42 U.S.C. 7401 et seq.) to have scrubbers which reduce emissions by a 

factor of 99%. The prevalence of sites which use enough ETO to be required to use 

scrubbers is important to EPA to accurately assess and characterize ambient 

exposure/risk. It is also important to establish how the efficacy of the scrubbing systems 

is ensured by determining how compliance with the 99 percent emission reduction 

criteria is assured. It is also important to consider that the national emissions standards 

for ethylene oxide (40 CFR § 63.362 Subpart O) indicates no control is required for 

sources less than 1 ton which means more ETO could be emitted from a facility 

compared to a facility which used 10 tons of ETO and greater that were equipped with 

scrubbers. In summary, EPA needs to accurately characterize how ETO use is distributed 

amongst user facilities and to better understand surety around scrubber performance in 

order to best characterize potential emissions that could result in exposures to ambient air 

levels of ETO.

5. Monitoring data on fumigated commodities 

EOSA: EOSA also requests further clarification of the requirement for monitoring data 

on fumigated commodities (special study). FDA regulates the residual levels in sterilized 

pharmaceutical and medical device products. As it relates to the use on spices, EPA 

already possesses monitoring data. EOSA requests clarification of why the existing 

monitoring data are not sufficient.

Response: EPA is not requiring monitoring data for residues on fumigated spices and 

related commodities. The commenter is correct in stating that those data are adequate.

EPA anticipates requiring monitoring data for the off-gassing of the fumigant from the 

commodity after the fumigation process, and after the initial aeration has been completed. 

Since FDA regulates the residual levels in sterilized pharmaceutical and medical device 

products, the requirement is only anticipated for the other uses of ETO, such as those on 

spices, and musical instruments. 
Page 68 of 69

III. Environmental Fate and Effect Comments 

1. Ecological toxicity studies 

EOSA & Sterigenics: EOSA and Sterigenics request additional detail on the types of 

ecological and air monitoring data required for the avian acute inhalation toxicity (special 

study), honeybee acute vapor exposure toxicity (special study), and vegetative vigor 

(850.4150) studies. As discussed below, we believe that the ETO emissions from the 

typical ETO usage process are significantly lower than what is presented in the PWP. 

Due to the reduced quantities of ETO emissions and the rapid dilution anticipated, many 

of the studies outlined in Table 7 of the PWP, including the post-application, residential, 

and ecological risk assessments would be of limited value. EOSA believes these studies 

are unnecessary if EPA considers the emission controls from sterilization facilities.

3M: Ecological toxicity studies – Special Study for Avian and Honeybee vapor exposure 

and Vegetative Vigor (EPA Guideline Number 850.4150).

Due to the low quantities of emissions from the hospital setting, the breakdown of ETO

within the venting pipe and rapid dilution anticipated at release, this study would be of

limited value. There have been no reports of ecological incidents due to hospital 

emissions.

Response: The Agency reiterates the importance of generating the anticipated data needs 

for ecological risk assessment regardless of the emission control. The directions on 

obtaining the above toxicity studies are listed in Appendix C in ETO Preliminary Work 

Plan (Docket Number EPA-HO-OPP-2013-0244). ETO has fumigant uses that may result 

in exposure to birds, honeybees and plants. The acute effects to birds, honeybees, and 

plants exposed to ETO gas are unknown. Without the knowledge of the ETO vapor 

concentration in air and toxicity levels for birds, honeybees and plants, the Agency is 

unable to determine the ecological risk associated with ETO daily emission (or reduced 

emission as stated above) adjacent to the treatment facility. In the absence of data, the 

ecological risk to these taxa from ETO vapor exposure will be assumed because of the 

uncertainties in what levels elicit toxic responses of concern.

2. Guidance for Commenters --Water Quality

EOSA, ARC, Sterigenics: In Section 6.1.2 of the PWP, EPA requests further 

information on the water quality data for this pesticide. There are no water emissions 

from the typical ETO sterilization process. Therefore, there does not appear to be any 

need for additional water quality data associated with ETO sterilization.

Response: The Agency concurs that the water quality data will not be needed for ETO.

3. Environmental Exposure Modeling

EOSA: Prior to requiring the development of field data, it is suggested that modeling of 

the environmental exposure could be done using revised common site configurations that 

better reflect current ETO usage with the required emission controls, similar to what is 

described for spices and herbs in Appendices E and F of the PWP. 
Page 69 of 69

Response: The Agency will consider this approach at the risk assessment stage in the 

registration review process. Also see response to comment “2. Inhalation exposure 

study” starting on page 66.