Docket Number EPA-HQ-OPP-2013-0244 

www.regulations.gov 

Ethylene Oxide Preliminary Work Plan 

Registration Review: Initial Docket 

Case Number 2275 

Approved by: 

September 2013 

s Lewis 

Acting Director 

Antimicrobials Division 

Date: ____;, 1_.../_2-....;;;; 3_ _/ L.._o· _ .....;; 13;....._ ___ _ 

f> ~Jn Richard P. Keigwin, Jr. 

Director 

Pesticide Re-evaluation Division 

Pagel of61 
Page 2 of 61

Ethylene Oxide Registration Review Team 

Human Health & Environmental Effects

Antimicrobials Division

Donna Randall 

Srinivas Gowda 

Najm Shamim 

Siroos Mostaghimi 

Tim McMahon 

Timothy Leighton 

William Hazel 

Environmental Fate and Effects Division

Ed Odenkirchen 

Sujatha Sankula 

He Zhong 

Stephen Carey 

Health Effects Division

Ray Kent 

Angela Howard 

Sue Hummel 

Ivan Nieves 

Jessica Kidwell 

Biological and Economic Analysis Division

John Faulkner 

Sepehr Haddad 

Elizabeth Hill 

Leonard Yourman 

Risk Management

Seiichi Murasaki 

Susan Bartow 

Lance Wormell 

Cathryn Britton 

Office of General Counsel

Philip Ross 

 
Page 3 of 61

Table of Contents 

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

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

1.2 Case Overview ................................................................................................................. 6

1.3 Chemical Identification and Properties ............................................................................ 6

1.4 Use and Usage Profile ...................................................................................................... 9

1.4.1 Registrations ............................................................................................................. 9

1.4.2 Summary of Registered Uses .................................................................................... 9

1.4.3 Usage Information .................................................................................................. 11

1.5 Regulatory History ......................................................................................................... 12

1.5.1 Recent/Pending Regulatory Actions ....................................................................... 13

1.5.2 Tolerance Information ............................................................................................ 13

1.6 Incidents ......................................................................................................................... 14

1.6.1 Human Health ......................................................................................................... 14

1.6.2 Ecological ............................................................................................................... 14

2 Anticipated Data Needs ........................................................................................................ 14

3 Human Health Risk Assessment ........................................................................................... 16

3.1 Existing Toxicological Endpoints .................................................................................. 17

3.2 Dietary Exposure ............................................................................................................ 19

3.2.1 Dietary (Food - Conventional Uses) ....................................................................... 19

3.2.2 Dietary (Food - Antimicrobial Uses) ...................................................................... 20

3.2.3 Dietary (Drinking Water) ........................................................................................ 20

3.2.4 Residue Chemistry (Conventional and Antimicrobial Uses) .................................. 20

3.3 Occupational and Residential Exposures ....................................................................... 20

3.3.1 Occupational Exposure ........................................................................................... 20

3.3.2 Residential Exposures ............................................................................................. 23

3.4 Aggregate and Cumulative Exposure and Risk .............................................................. 24

3.4.1 Aggregate Exposures and Risk ............................................................................... 24

3.4.2 Cumulative Exposure and Risk ............................................................................... 25

4 Ecological Risk Assessment ................................................................................................. 25

4.1 Environmental Fate Assessment .................................................................................... 26

4.1.1 Clean Water Act ...................................................................................................... 26

4.2 Conceptual Models for Environmental Exposure Pathways .......................................... 26

4.3 Ecological Effects Assessment ....................................................................................... 27

4.3.1 Mechanism of Action .............................................................................................. 27

4.3.2 Measures of Effect (Ecotoxicology Endpoints) ...................................................... 27

4.4 Exposure Analysis Plan .................................................................................................. 29

4.4.1 Wildlife Exposure Estimates ................................................................................... 29

4.5 Effects Analysis Plan ..................................................................................................... 31

5 Endocrine Disruptor Screening Program (EDSP) ................................................................. 31

6 Guidance for Commenters .................................................................................................... 32

6.1 Preliminary Work Plan ................................................................................................... 32

6.1.1 Trade Irritants .......................................................................................................... 33

6.1.2 Water Quality .......................................................................................................... 33

6.1.3 Environmental Justice ............................................................................................. 33

6.1.4 Structure Activity Relationships ............................................................................. 33
Page 4 of 61

6.1.5 Additional Information ........................................................................................... 34

7 Next Steps ............................................................................................................................. 35

8 References ............................................................................................................................. 36

Appendix A Toxicology Profile ............................................................................................... 38

Appendix B Environmental Fate ............................................................................................. 42

Appendix C Ecotoxicology Profile .......................................................................................... 46

Appendix D Product Chemistry ............................................................................................... 52

Appendix E Modeling Input Based on ETO Release Scenarios for Spices and Herbs ........... 54

Appendix F Output Example of AERSCREEN Estimated Environmental Concentration 

(EEC) for ETO Release Scenario 2 .............................................................................................. 57

List of Tables 

Table 1 – Summary of Anticipated Risk Assessments and Data Needs: ETO ............................... 6

Table 2 – Anticipated Registration Review Schedule .................................................................... 6

Table 3 – Chemical Identification of ETO ..................................................................................... 7

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

Products........................................................................................................................................... 8

Table 5 – Summary of ETO Registered Uses ................................................................................. 9

Table 6. Maximum Rates for Registered Agricultural Uses of ETO ............................................ 11

Table 7 – Studies Anticipated as Needed for the Registration Review of ETO ........................... 15

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

Use in Past Human Risk Assessments .......................................................................................... 17

Table 9 – Summary of Medical Facility SIC Codes ..................................................................... 21

Table 10 – ETO Air Concentrations from IMIS for All Medical SIC Codes ............................... 22

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

(1988 to 2007) ............................................................................................................................... 22

Table 12 – ETO Air Concentrations for Contract Sterilization Facilities .................................... 23

Table 13 – Selected Ecological Effects Endpoints for Risk Assessment of ETO ........................ 28

Table 14. AERSCREEN Modeling Scenarios and Data Summary .............................................. 30

Table 15 – ETO – Acute Toxicity ................................................................................................. 38

Table 16 – ETO – Subchronic, Chronic Toxicity Studies ............................................................ 38

Table 17. Environmental Fate Properties of ETO ........................................................................ 42

Table 18. Effects Data on ETO ..................................................................................................... 48

Table 19. ECOSAR v1.11 Results for ETO ................................................................................. 48

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

(Degradate of ETO). ..................................................................................................................... 49

List of Figures 

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

Terrestrial Organisms.................................................................................................................... 27

Figure 2. Proposed ETO air exposure scenario for the risk assessment. ...................................... 31

 
Page 5 of 61

1 Introduction 

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

Agency”) Preliminary Work Plan (PWP) for ethylene oxide (ETO). The PWP 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. 

The Agency encourages all interested stakeholders to review the PWP and to provide comments 

and additional information that will help the Agency’s decision-making process for this 

chemical. 

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. After 

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

comment period, the Agency will develop and commit to a Final Work Plan (FWP) and 

anticipated schedule for the ETO Case. 

Documents associated with this 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 61

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

Risk Assessment 

Assessment Necessary to 

Support Registration 

Review 

Date of Most 

Recent 

Assessment 

Type of 

Assessment 

Required 

Data Anticipated 

as Needed 

(See Table 7 for 

more detail) 

Dietary (food /drinking 

water) No (see 3.2) 2008 None None 

Occupational Handler Yes 2008 Updated 

Toxicity 

Exposure 

Air monitoring 

Residential Handler No (see 3.3.2) 2008 None None 

Residental Post 

Application – Inhalation 

(bystander) 

Yes 2007 Updated 

Special acute 

inhalation toxicity 

study 

Aggregate & Cumulative No (see 3.4) 2008 None None 

Tolerance Review Yes 2006 Updated None 

Ecological Yes 2011 Section 18 Updated Ecotoxicity and air 

monitoring data 

N/A = Not applicable 

Table 2 – Anticipated 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 

Close Public Comment Period 2013-11 

Phase 2: Case Development 

Issue Final Work Plan 2014-03 

Issue Data Call-In (DCI) 2015-03 

Receive Data to be Considered in Risk Assessment 2019-03 

Open 30-Day Public Comment Period for Preliminary Risk Assessment(s) 2020-09 

Close Public Comment Period 2020-10 

Phase 3: Registration Review Decision and Implementation 

Open 60-Day Public Comment Period for Proposed Decision 2021-03 

Close Public Comment Period 2021-05 

Issue Final Decision 2021-09 

Begin Post-Decision Follow-up 2021 

Total (years) 8 

*The anticipated schedule will be revised as necessary (e.g., need arising under the Endocrine Disruptor Screening Program with

respect to the active ingredients in this case).

1.2 Case Overview 

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

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

1.3 Chemical Identification and Properties 

Table 3 presents the active ingredient to be assessed in Case 2275, ETO (PC Code 042301). ETO 

in its natural state is a colorless, highly reactive, and flammable gas at room temperature and 

ambient pressure. 
Page 7 of 61

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 8 of 61

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 (o

C) -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 o

C 

1.80 1.2015-1.2025 1.494 at 20 o

C 1.1155 

Water solubility, at 

20°C Not available Not available Not available Not available 

Vapor pressure 1255 mm Hg at 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 

o

C 

(EPISuite 4.10) 

Henry’s Law Constant 

at 25 o

C (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 o

C 

-0.30 

( EPISuite v 4.10) 

 0.112 

 ( EPI Suite, V4.10) 

0.23 

 ( EPISuite v4.10) 

-1.20 

(EPISuite v 4.10) 

Bioaccumulation 

Factor, L/kg-ww Not available Not available Not available Not available 

UV/VIS absorption 

spectrum 

Not applicable, nonconjugated molecule Not applicable, nonconjugated molecule Not applicable, nonconjugated molecule Not applicable, nonconjugated molecule 

Half-life in air (days) 39 

(EPISuite v4.10) Not available Not available Not available

Activated Sludge 

Biodegradation, % 

removal 

Not available Not available Not available Not available 

CAS = Chemical Abstracts Service; IUPAC = International Union of Pure and Applied Chemistry; NA = not applicable; UV = 

ultraviolet light; VIS = visible light 

O

H2C CH2 C

H2

C

H2

HO Cl

C

H2

C

H2

HO Br
Page 9 of 61

1.4 Use and Usage Profile 

1.4.1 Registrations 

As of September 10, 2013, there were 24 registered products containing ETO. ETO is formulated 

and marketed as a pressurized gas or liquid. The end use formulations are all gas mixtures of 

ETO and other gases (e.g., carbon dioxide) in varying concentrations. 

1.4.2 Summary of Registered Uses 

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

registration review. 

1.4.2.1 Agricultural Uses 

ETO is a commodity fumigant/sterilant 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). 

1.4.2.2 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 

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 
Page 10 of 61

EPA 

Registration 

Number

%ai Form Registration 

Type Use Site

69340-2 97 Pressurized 

gas 

EP 

Surgical instruments; heat labile materials; oral and inhalation 

equipment; diagnostic instruments/equipment; hospital critical 

rubber/plastic items; hospital materials; first aid equipment; human 

face gear; contact lens 

69340-7 97 Pressurized 

gas 

EP Surgical instruments; hospital instruments; sterilizers; veterinary 

hospital instruments 

69340-4 96 Pressurized 

gas 

EP 

Surgical instruments; surgical prosthetic parts; hospital instruments; 

oral and inhalation equipment; diagnostic instruments/equipment; 

hospital critical rubber/plastic items; hospital materials; surgical 

dressings; hypodermic needles/syringes; veterinary hospital 

instruments 

69340-6 96 Pressurized 

gas 

EP 

Surgical instruments; hospital instruments; oral and inhalation 

equipment; diagnostic instruments/equipment; hospital critical 

rubber/plastic items; hypodermic needles/syringes; veterinary 

hospital instruments 

69340-5 90 Pressurized 

gas 

EP 

Surgical instruments; hospital instruments; oral and inhalation 

equipment; diagnostic instruments/equipment; hospital critical 

rubber/plastic items; hypodermic needles/syringes; veterinary 

hospital instruments 

69340-1 89.4 Pressurized 

gas 

EP 

Surgical instruments; hospital instruments; hospital critical 

equipment; heat labile materials; oral and inhalation equipment; 

diagnostic instruments/equipment; hospital critical rubber/plastic 

items; hospital materials; first aid equipment; veterinary hospital 

premises; veterinary hospital instruments; veterinary hospital 

critical equipment; human face gear; contact lens 

36736-3 80 Pressurized 

gas 

EP Medical/lab items; pharmaceuticals; 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 

NC950002 8.5 Pressurized 

gas EP Bee keeping equipment 
Page 11 of 61

Table 6. Maximum Rates for Registered Agricultural Uses of ETO 

Use Method of 

Application 

Single 

Maximum 

Application 

Rate 

Application 

Conditions EPA Reg No.

Indoor Food: 

Processed 

herbs, spices 

and dried 

vegetables 

Sterilization 

chamber / 

Fumigation 

Chamber

<500 mg/L 

(a.i.) (<8hrs) & 

<500 mg/L 

(a.i.) (<16hrs) 

Evacuate the gas from 

the chamber using a 

sequence of not less than 

1) 21 steam washes, 5.0 

PSIA at 115oF and 2) 16 

steam washes, 5.0 PSIA 

at 120oF

36736-2 (100% ai), 36736-3 (80% ai & 

20% 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) 

1.4.3 Usage Information 

According to the Biological and Economic Analysis Division (BEAD) (USEPA 2013a), 

agricultural uses for ETO include processed herbs and spices (except basil), and processed 

vegetables (dried/dehydrated). Sterilization or fumigation with ETO must be performed in 

vacuum chambers with outside venting designed for use with ETO. The Agency estimated about 

8.2 million pounds of ETO were used annually in the U.S. for commercial fumigation or 

sterilization of medical and laboratory items or equipment and about 800,000 pounds of ETO 

(approximately 10%) are used annually for 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 12 of 61

1.5 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 B1 reregistration 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 this 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 13 of 61

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). 

1.5.1 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. 

1.5.2 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 14 of 61

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. 

1.6 Incidents 

1.6.1 Human Health 

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

memorandum from the Health Effects 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.

1.6.2 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 

Page 15 of 61

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 S

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 

870.4300 

Chronic toxicity/carcinogenicity study 

ECH 48 Occupational and Residential All chronic dietary exposur

875.1400 Inhalation exposure study for applicators ETO 12 Occupational All applicator inhalation ex875.1700 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 Special study 

Monitoring data on fumigated commodities4 ETO 24 Occupational All 

emission from treated cthe potential for occupathose emissions in the cfumigation activities ar

Special Study 

Ambient Air Monitoring Study ETO 36 Residential All ambient air concentratio

proximity to treated fac

Special Study 

Avian Acute Inhalation Toxicity Study 4,5 ETO 24 Ecological All inhalation of air emissio

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 emissio4 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 E6 Data from five dicot species of at least three families (excluding soybean (Glycine max) which has already been tested), and four dicot s

families, one species of which is corn (Zea mays) are expected to be required. Additionally of the ten species tested, at least one species 

(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 con

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

www.regulations.gov 

Page 16 of 61

3 Human Health Risk Assessment 

In 2008, the EPA’s Office of Pesticide 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 17 of 61

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

population subgroups; (5) Points of Departures (PODs) for the most sensitive endpoints 

(neurotoxicity) seen in the most sensitive 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 carcinogencity 

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 18 of 61

Exposure 

Scenario

Dose Used in 

Risk Assessment, 

UF 

Special FQPA 

SF* and Level of 

Concern for 

Risk Assessment

Study and Toxicological Effects

Chronic 

Dietary 

(All 

populations) 

NOAEL= 45

mg/kg/day 

UF = 1000

Chronic RfD = 

0.045 mg/kg/day 

FQPA SF = 1X

cPAD = 

chronic RfD

 FQPA SF 

= 0.045 

mg/kg/day 

Subchronic Toxicity Study – Albino Rats (Courtney 

et al., 1982). 

LOAEL: 67.5 mg/kg/day 

Decreased mean body weight in males (↓34%), poor 

survival, i.e., 32% in males and 24% in females as 

compared to 100% in 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 19 of 61

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 20 of 61

3.2.2 Dietary (Food - Antimicrobial Uses) 

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

ETO (see 1.4.2.2). 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 1.4.2.1). 

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 21 of 61

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 22 of 61

SIC Code Description 

3842 

Orthopedic, 

Prosthetic, and 

Surgical Appliances 

and Supplies 

Establishments primarily engaged in manufacturing orthopedic, prosthetic, and 

surgical appliances and supplies, arch 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 23 of 61

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 24 of 61

well as acute and chronic non-cancer risk to bystanders (EPA/OAR, Mark Morris, 2005; 

http://www.epa.gov/ttnatw01/eo/eo_rra.pdf ). Based on the results, 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 25 of 61

chemicals of concern for dietary exposure while ETO is the compound of concern for residential 

exposure).

3.4.2 Cumulative Exposure and Risk 

Section 408(b)(2)(D)(v) of FFDCA requires that, when considering whether to establish, modify, 

or revoke a tolerance, the Agency consider “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 26 of 61

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 o

C, 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 auotocatalyzes into methane, ethane, hydrogen, and carbon dioxide (MRID 

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

waters. Based on the chemical and physical 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 risk concerns from ETO use scenario are likely through the inhalation pathway. 

4.1.1 Clean Water Act 

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

section 303(d) of the Clean Water Act8. In addition, no Total Maximum Daily Loads (TMDL) 

have been developed for ETO9

. 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. 

TMDL established for glycol (daily max) = 125 mg/L and for thirty average it is 190.0 mg/L. It 

is to be noted that these TMDL are not because of ETO use as a pesticide. More information on 

impaired water bodies and TMDLs can be found at EPA’s website10. 

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, see Section 

6.1.5 for information the Agency is seeking. However, under ambient conditions ETO scrubbed 

from vented air to water is expected, with a half-life of <1 h, to volatilize along the way to a 

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 

 

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

9

http://iaspub.epa.gov/tmdl_waters10/attains_nation.tmdl_pollutant_detail?p_pollutant_group_id=885&p_pollutant_

group_name=PESTICIDES

10 http://www.epa.gov/owow/tmdl/
Page 27 of 61

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

organisms are assumed to occupy areas immediately adjacent to treatment sites and aquatic nontarget 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 to terrestrial animals is via inhalation of the gas and to terrestrial 

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

Figure 1 – Conceptual Model for Ecological 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 PCEsrelated

to prey availability

Habitat integrity

Reduction in primary productivity

Reduced cover

Community change

Modification of PCEsrelated to

habitat

Terrestrial Animals

Birds(Reptiles, Amphibians)

Mammals, Beneficial Insects

Inhalation

Key

Mostlikely

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)

SurfaceWater

Sediment

AquaticOrganisms

Invertebrates

Vertebrates

Algae, Plants

WWTP

microorganisms

Uptake or

sorption Uptakeby gills  or integument or

sorption by cells

Population

Respiration

inhibition

Contact

Terrestrial Plants

VegetativeVigor
Page 28 of 61

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-listed2

 IC50 >0.86 mg/L 47921703 Acceptable4, 5

Listed3 NOAEC > 0.86 

Aquatic vascular Duckweed (Lemna 

gibba) 

Non-listed2

 IC50 > 0.87 mg/L 47921702 Acceptable4, 5

Listed3 NOAEC > 0.87 mg/L 
Page 29 of 61

Receptor Group Surrogate Species Risk 

Scenario Toxicity Endpoint Reference (MRID) 

Aquatic Rooted 

Macrophytes Seedling Emergence Non-listed No data available, not a data gap as exposure pathway is 

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 30 of 61

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/m3

 according the current 

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

with 10,000ft3 spaces 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, exposures 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 31 of 61

Figure 2. Proposed ETO air exposure scenario for the risk assessment. 

ETO concentrations in air will be modeled or monitored using the maximum labeled application 

rates and numbers of 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 pesticides11. 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. 

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 

 

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 32 of 61

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 2008 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. 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 

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

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

an EDSP FFDCA section 408(p) determination. 

6 Guidance for Commenters 

6.1 Preliminary Work Plan 

The public is invited to comment on EPA’s Preliminary Work Plan and rationale. The Agency 

will carefully consider all comments as well as any additional information or data provided in a 

timely manner prior to issuing a final work plan for the ETO registration review case. 

 

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

chemicals. 

13 http://www.epa.gov/endo/
Page 33 of 61

6.1.1 Trade Irritants 

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

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

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

modify tolerance levels to do so, when possible. Stakeholders are asked to comment on any 

trade irritant issues resulting from lack of MRLs or disparities between U.S. tolerances and 

MRLs in key export markets, providing as much specificity as possible regarding the nature of 

the concern. 

6.1.2 Water Quality 

The Agency invites submission of water quality data for this pesticide, see 4.1.1. To the 

extent possible, data should conform to the quality standards in Appendix A of the OPP 

Standard Operating Procedure: Inclusion of Impaired Water Body and Other Water Quality 

Data in OPP’s Registration Review Risk Assessment and Management Process14 in order to 

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

6.1.3 Environmental Justice 

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

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

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

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

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

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

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

compared to the general population.

6.1.4 Structure Activity Relationships 

EPA must rely upon information of appropriate quality and reliability for each decision made by 

the Agency. In the OPP, the evaluation process for a pesticide chemical traditionally begins with 

the applicant’s submission of a set of studies conducted with the specific pesticide chemical of 

interest. The use of the results of such testing (measured data) is a logical, scientifically rigorous 

process that identifies the physical, chemical, and environmental fate properties of the pesticide, 

as well as the dose and endpoints at which an adverse effect can occur in various animal species. 

Today, there is significant interest in alternative techniques, i.e., techniques other than data 

generation that could significantly inform the Agency’s decision-making process. Recently, OPP 

has made increasing use of structure activity relationship (SAR) as part of its regulatory 

decision-making process. In the SAR process, a chemical's molecular structure is compared to 

that of other chemicals for which data are available. These structural similarities are then used to 

make predictive judgments about a chemical’s physical, chemical, and biological properties. 

Thus, the chemical’s physical, chemical, and biological properties are a function of (or directly 

related to) the chemical’s molecular structure. Quantitative SAR is referred to as QSAR. To 

develop a QSAR, a selected set of measured data on a single physical, chemical, or biological 

property is used to derive a model (an equation) to predict the value of that property. 

 

14 http://www.epa.gov/oppsrrd1/registration_review/water_quality_sop.htm
Page 34 of 61

Since SAR assessments and QSAR modeling are another set of tools that are available to Agency 

scientists, OPP has begun a process shift that envisions shifting from the current study-by-study 

approach to an approach in which the use of predicted data, generated using validated models, is 

considered along with information from open literature and studies specifically generated under 

Part 161 requirements. All relevant information would be considered as part of a weight-of-theevidence evaluation. 

At this time, EPA believes that for certain endpoints, especially physical/chemical and fate 

properties, that SAR and QSAR might be effectively utilized to fulfill these data requirements 

for many antimicrobial pesticide chemicals. When considering biological properties, at this time, 

EPA believes that SAR and QSAR can be most effectively utilized in the evaluation of 

chemicals that exhibit lower toxicity for human health and/or ecotoxicity parameters. This is 

appropriate because the risk assessment for lower toxicity chemicals can be stream-lined, i.e., a 

screening-level assessment procedure rather than multiple tiers of assessments with progressively 

more data requirements. 

If stakeholders believe that submission of predicted data can fulfill one of the data needs for the 

ETO Case, then the Agency invites submission of this information. The submitter would be 

expected to supply a rationale describing the utility of the information and provide 

documentation on the scientific validity of the information. The determination that the predicted 

data fulfills the data requirement would be at the sole discretion of the Agency. Pre-submission 

consultation with the Agency is encouraged. 

6.1.5 Additional Information 

Stakeholders are also specifically asked to provide available information and data that will assist 

the Agency in refining its risk assessments, including any species-specific ecological effects 

determinations. The Agency is interested in receiving the following information: 

1. Confirmation on the following label information: 

A. Sites of application 

B. Formulations 

C. Application methods and equipment 

D. Maximum application rates 

E. Frequency of application, application intervals and maximum number of 

applications 

F. Geographic limitations on use 

2. Use or potential use distribution 

3. Use history 

4. Usage/use information for non-agricultural uses (e.g., materials preservation) 

5. Typical application interval 

6. State or local use restrictions 

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

mammalian mortalities) not already reported to the Agency 

8. Monitoring data 

9. Availability of scrubber technology for ETO, prevalence of use, and efficiency 
Page 35 of 61

7 Next Steps 

After the 60-day comment period closes in November 2013, the Agency will review and respond 

to any comments received in a timely manner, and then issue a Final Work Plan for the Ethylene 

Oxide Case. 
Page 36 of 61

8 References 

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

reregistration risk assessment of 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 37 of 61

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 38 of 61

Appendix A Toxicology Profile 

The following tables summarize the toxicity of ETO and ECH. The tables include both the acute 

toxicity profile and the profile 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 39 of 61

Study/Species MRID or 

Publication Doses Results/Classification 

Two-Generation 

Reproduction Study, 

Rats 

42788101 Doses 

(inhalation): 0, 

10, 33, 100 

ppm 

6h/day, 

5d/week 

Parental NOAEL: 10 ppm 

Parental LOAEL: 33 ppm 

Decreased body weight and/or weight gain in F0 and F1 males during 

premating 

Reproductive NOAEL: 10 ppm 

Reproductive LOAEL: 33 ppm 

Increased post implantation loss in F0 generation 

Offspring NOAEL: 10 ppm 

Offspring LOAEL: 33 ppm 

Decreased mean body weight and 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 40 of 61

Study/Species MRID or 

Publication Doses Results/Classification 

Combined Chronic Carcinogenicity 

Chronic 

Carcinogenicity 

Study, Rats 

2 years 

Snellings et al. 

(1984b) 

Garman et al. 

(1985), Garman 

and Snellings, 

(1986) 

Doses 

(inhalation): 

0, 10, 33, 100 

ppm 

(6h/day, 

5d/week) 

Systemic NOAEL: 10 ppm 

Systemic LOAEL: 33 ppm 

Decreased survival and body weight 

Type of cancer incidence-0, 10, 33, 100 ppm: mononuclear cell 

leukemia-13/97, 9/51, 12/39, 9/30 (m), 11/116, 11/54, 14/48, 15/26 (f); 

peritoneal mesothelioma- 2/97, 2/51, 4/39, 4/30 (m), brain 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 41 of 61

Study/Species MRID or 

Publication Doses Results/Classification 

Mutation/Genotoxicity 

 IPCS, 2003 - Positive evidence for mutation in bacteria, eukaryotic somatic and germ 

cells; Increased chromosomal aberrations, sister chromatid exchange 

and unscheduled DNA synthesis in mammalian cells,, Induction of 

dominant lethal mutations and heritable translocations in mice. In 

humans, increased chromosomal aberrations in peripheral blood 

leukocytes of workers exposed to ETO. 

Human Studies 

 Steenland et al. 

2003 

- Breast cancer incidence studied in a cohort of 7576 women. Breast 

cancer reported in 319 subjects. The 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 42 of 61

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 43 of 61

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 auotocatalyzes into methane, ethane, 

hydrogen, carbondioxide (MRID# 49126104). 

Hydrolysis 

ETO degradation in water through ionic reactions and hydrolysis appear to be comparatively 

slow in the environment. 

In 1999, Gangolli reported a 12-14 day hydrolytic half life for ETO in fresh water, with 9-11 day 

hydrolytic half-life in seawater. Thus this study indicates that under biotic conditions, ETO 

hydrolyzes, and is not considered as 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 44 of 61

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 45 of 61

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 46 of 61

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 47 of 61

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 

species15 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. 

 

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

max), and four dicot species of at least two families, one species of which is corn (Zea mays). Additionally of the 

ten species tested, at least one species should be a root crop (either a monocot such as onion or dicot such as carrot, 

table beet or sugar beet). 
Page 48 of 61

Table 18. Effects Data on ETO 

Data 

Requirement 

Test Species, Test 

Type Value 

Submitted Studies 

(MRID or 

Citation) 

Study Classifications/ 

Toxicity 

Classification 

Freshwater fish, 

acute toxicity 

Fathead minnow 

(Pimephales 

promelas), static, 

nominal 

96-h 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. 2

Toxicity categories have not been assigned for aquatic plants.

Table 19. ECOSAR v1.11 Results for ETO 

Organism Endpoints 

Fish, Freshwater generic 96-h 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 49 of 61

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 50 of 61

Jacobson, K.H., Hackley, E.B., & Feinsilver, L. (1956) The toxicity of inhaled ethylene oxide 

and Ethylene oxide vapors. Arch. ind. Health, 13: 237-244. 

United States Environmental Protection Agency (USEPA). 1985. Health assessment document 

for ethylene oxide, Washington DC, US 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 

-------------------------------------- 
Page 51 of 61

ECOSAR v1.1 Class-specific Estimations 

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

Epoxides, mono 

 Predicted 

ECOSAR Class Organism Duration End Pt mg/L (ppm) 

=========================== ================== ======== ====== ========== 

Epoxides, mono : Fish 96-hr LC50 57.672 

Epoxides, mono : Fish 14-day LC50 31.003 

Epoxides, mono : Daphnid 48-hr LC50 277.857 

Epoxides, mono : Green Algae 96-hr EC50 501.535 

Epoxides, mono : Fish ChV 0.015 

Epoxides, mono : Daphnid ChV 27.803 ! 

Epoxides, mono : Green Algae ChV 168.525 

=========================== ================== ======== ====== ========== 

Neutral Organic SAR : Fish 96-hr LC50 2486.310 

(Baseline Toxicity) : Daphnid 48-hr LC50 892.307 

 : Green Algae 96-hr EC50 817.901 

 : Fish ChV 194.495 

 : Daphnid ChV 67.386 

 : Green Algae ChV 68.573 

 Note: * = asterisk designates: Chemical may not be soluble enough to 

 measure this predicted effect. If the effect level exceeds the 

 water solubility by 10X, typically no effects at saturation (NES) 

 are reported. 

 

 NOTE: ! = exclamation designates: The toxicity value was estimated through 

 application of acute-to-chronic ratios per methods outlined in 

 the ECOSAR Methodology Document provided in the ECOSAR Help Menu. 

 

 

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

Class Specific LogKow Cut-Offs 

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

If the log Kow of the chemical is greater than the endpoint specific cut-offs 

presented below, then no effects at saturation are expected for those endpoints. 

 

Epoxides, mono: 

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

Maximum LogKow: 5.0 (Fish 96-h LC50, Daphnid LC50) 

Maximum LogKow: 6.0 (Fish 14-day) 

Maximum LogKow: 6.4 (EC50) 

Maximum LogKow: 8.0 (ChV) 

 

Baseline Toxicity SAR Limitations: 

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

Maximum LogKow: 5.0 (Fish 96-hr LC50; Daphnid LC50) 

Maximum LogKow: 6.4 (Green Algae EC50) 

Maximum LogKow: 8.0 (ChV) 

 
Page 52 of 61

Appendix D Product Chemistry 

The ETO product chemistry information is summarized in Table E1 (source: MRIDs 41531002, 

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

Table E1 – Product Chemistry of ETO 

Guideline 

Number Physical and Chemical Properties Value 

830.1550 Product identity and composition Refer to Table 3. 

830.1600 Description of materials used to 

produce the product 

Confidential Business Information (CBI) 

830.1620 Description of production process CBI 

830.1650 Description of Formulation Process CBI 

830.1670 Discussion of formulation of 

impurities 

CBI 

830.1700 Preliminary analysis CBI 

830.1750 Certified limits CBI 

830.1650 Description of Formulation Process CBI 

830.1800 Enforcement analytical method Gas chromatography (GC). 

830.1900 Submittal of samples CBI 

830.6302 Color ETO is a colorless gas or liquid. 

830.6303 Physical State ETO is a colorless gas at 25 °C and is a mobile liquid at 0 °C. 

830.6304 Odor The gas has a characteristic sweet odor of ether. 

830.6313 Stability to normal and elevated 

temperature, metals/metal ions 

ETO is stable at ordinary conditions of temperature and 

pressure and in ordinary use, handling and storage. 

ETO is a reactive molecule. Its ability to chemically combine 

with itself and other molecules (and the necessary conditions) 

is reported. 

Protect from sunlight. Store in a well-ventilated place. 

830.6314 Oxidation/Reduction: 

Chemical Incompatibility: 

Highly reactive. It is reactive in both the liquid and vapor 

phases. 

Materials to avoid: Alcohols, alkali metals, ammonia, 

oxidizing agents, chemically active metals and its salts. 

830.6315 Flammability-Flash point Flammable gas. 

It is extremely flammable and explosive, therefore, it is 

commonly handled and shipped as a refrigerated liquid.

Flash point −20.0 °C − closed cup 

Flash point <−18.0 °C – tag open cup 

830.6316 Explodability It is extremely flammable and explosive; therefore, it is 

commonly handled and shipped as a refrigerated liquid. 

830.7000 pH This requirement does not apply to ETO because it is not an 

acid or base. It is a gas. 

830.7050 UV/Visible Absorption Not applicable. 

830.7100 Viscosity 0 °C – 0.325 cP 

20°C – 0.260 cP 

Viscosity of liquid ETO at 0 °C is about 5.5 times lower than 

that of water.

830.7200 Melting point: 

Freezing point: 

−111.7 °C 

−112.778 °C 

830.7220 Boiling point 10.6 °C at 760 mmHg 

830.7300 Density 0.995 g/cm3 

0.882 g/cm3 at 25 °C 

0.8697 g/ml 20 °C 
Page 53 of 61

Guideline 

Number Physical and Chemical Properties Value 

830.7370 Dissociation Constant in water (pKa) ETO is a covalently bonded organic molecule (an alkyl 

epoxide) and does not dissociate. 

830.7550 Partition coefficient (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 54 of 61

Appendix E Modeling Input Based on ETO 

Release Scenarios for Spices and Herbs 

ETO is used to treat spices, dried vegetables, and seasonings in 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 feet16. 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 downwash17 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. 

 

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

http://www.csx.com/index.cfm/customers/equipment/railroad-equipment/ 17 Downwash is defined as the downward flow often observed on the leeside of buildings induced by wake 

turbulence. Pollutants released from buildings can often become embedded in downwash flows and wake cavities. 
Page 55 of 61

Figure E1. Schematic illustrating fumigation releases from treatment chambers and conceptual 

model for ground-level exposure. 

AERSCREEN Release Scenarios

Each release scenario from the ETO label 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.3 chamber 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 56 of 61

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 57 of 61

Appendix F Output Example of 

AERSCREEN Estimated Environmental 

Concentration (EEC) for ETO Release 

Scenario 2 

 AERSCREEN 11126 / AERMOD 1234 04/19/13 

 15:56:35 

 TITLE: ETO-16 

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

 ***************************** STACK PARAMETERS **************************** 

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

 SOURCE EMISSION RATE: 39.3372 g/s 312.200 lb/hr 

 STACK HEIGHT: 1.52 meters 5.00 feet 

 STACK INNER DIAMETER: 1.006 meters 39.60 inches 

 PLUME EXIT TEMPERATURE: 322.0 K 120.0 Deg F 

 PLUME EXIT VELOCITY: 1.584 m/s 5.20 ft/s 

 STACK AIR FLOW RATE: 2667 ACFM 

 RURAL OR URBAN: RURAL 

 INITIAL PROBE DISTANCE = 5000. meters 16404. feet 

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

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

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

 BUILDING HEIGHT: 1.5 meters 5.0 feet 

 MAX BUILDING DIMENSION: 13.6 meters 44.7 feet 

 MIN BUILDING DIMENSION: 13.6 meters 44.7 feet 

 BUILDING ORIENTATION TO NORTH: 0. degrees 

 STACK DIRECTION FROM CENTER: 0. degrees 

 STACK DISTANCE FROM CENTER: 6.8 meters 22.3 feet 

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

 ************************** FLOW SECTOR ANALYSIS *************************** 

 25 meter receptor spacing: 1. meters - 5000. meters 

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

 FLOW BUILD BUILD MAX 1-HR DIST TEMPORAL 
Page 58 of 61

 SECTOR WIDTH LENGTH XBADJ YBADJ CONC (m) PERIOD 

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

 10 15.80 15.79 -14.59 -1.18 0.2151E+06 1.0 ANN 

 20 17.48 17.47 -15.12 -2.32 0.2694E+06 1.0 ANN 

 30 18.63 18.62 -15.20 -3.40 0.3072E+06 1.0 ANN 

 40 19.21 19.21 -14.81 -4.37 0.3252E+06 1.0 ANN 

 50 19.21 19.21 -13.97 -5.21 0.2594E+06 1.0 ANN 

 60 18.62 18.63 -12.71 -5.88 0.2600E+06 1.0 ANN 

 70 17.47 17.48 -11.06 -6.39 0.2554E+06 25.0 ANN 

 80 15.79 15.80 -9.08 -6.69 0.2702E+06 25.0 ANN 

 90 13.63 13.64 -6.82 -6.80 0.2830E+06 25.0 ANN 

 100 15.79 15.80 -6.72 -6.69 0.3118E+06 25.0 ANN 

 110 17.47 17.48 -6.42 -6.39 0.3058E+06 25.0 ANN 

 120 18.62 18.63 -5.92 -5.88 0.3136E+06 25.0 ANN 

 130 19.21 19.21 -5.24 -5.21 0.3241E+06 25.0 ANN 

 140 19.21 19.21 -4.40 -4.37 0.3431E+06 25.0 ANN 

 150 18.63 18.62 -3.43 -3.40 0.3424E+06 25.0 ANN 

 160* 17.48 17.47 -2.35 -2.32 0.3483E+06 25.0 ANN 

 170 15.80 15.79 -1.20 -1.18 0.3428E+06 25.0 ANN 

 180 13.64 13.63 -0.02 0.00 0.3241E+06 25.0 ANN 

 190 15.80 15.79 -1.20 1.18 0.3428E+06 25.0 ANN 

 200 17.48 17.47 -2.35 2.32 0.3483E+06 25.0 ANN 

 210 18.63 18.62 -3.43 3.40 0.3424E+06 25.0 ANN 

 220 19.21 19.21 -4.40 4.37 0.3431E+06 25.0 ANN 

 230 19.21 19.21 -5.24 5.21 0.3241E+06 25.0 ANN 

 240 18.62 18.63 -5.92 5.88 0.3136E+06 25.0 ANN 

 250 17.47 17.48 -6.42 6.39 0.3058E+06 25.0 ANN 

 260 15.79 15.80 -6.72 6.69 0.3118E+06 25.0 ANN 

 270 13.63 13.64 -6.82 6.80 0.2830E+06 25.0 ANN 

 280 15.79 15.80 -9.08 6.69 0.2702E+06 25.0 ANN 

 290 17.47 17.48 -11.06 6.39 0.2554E+06 25.0 ANN 

 300 18.62 18.63 -12.71 5.88 0.2600E+06 1.0 ANN 

 310 19.21 19.21 -13.97 5.21 0.2594E+06 1.0 ANN 

 320 19.21 19.21 -14.81 4.37 0.3252E+06 1.0 ANN 

 330 18.63 18.62 -15.20 3.40 0.3072E+06 1.0 ANN 

 340 17.48 17.47 -15.12 2.32 0.2694E+06 1.0 ANN 

 350 15.80 15.79 -14.59 1.18 0.2151E+06 1.0 ANN 

 360 13.64 13.63 -13.61 0.00 0.1402E+06 25.0 ANN 

 * = worst case flow sector 

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

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

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

 MIN/MAX TEMPERATURE: 249.8 / 310.9 (K) 

 MINIMUM WIND SPEED: 0.5 m/s 

 ANEMOMETER HEIGHT: 10.000 meters 

 SURFACE CHARACTERISTICS INPUT: USER ENTERED 

 ALBEDO: 0.60 

 BOWEN RATIO: 3.00 
Page 59 of 61

 ROUGHNESS LENGTH: 0.001 (meters) 

 METEOROLOGY CONDITIONS USED TO PREDICT OVERALL MAXIMUM IMPACT 

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

 YR MO DY JDY HR 

 -- -- -- --- -- 

 10 06 01 1 01 

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

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

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

 HT REF TA HT 

 - - - - - - - - - - - 

 10.0 310.9 2.0 

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

 METEOROLOGY CONDITIONS USED TO PREDICT AMBIENT BOUNDARY IMPACT 

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

 YR MO DY JDY HR 

 -- -- -- --- -- 

 10 06 28 1 01 

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

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

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

 HT REF TA HT 

 - - - - - - - - - - - 

 10.0 310.9 2.0 

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

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

 ************************ AERSCREEN AUTOMATED DISTANCES ********************** 

 OVERALL MAXIMUM CONCENTRATIONS BY DISTANCE 

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

 MAXIMUM MAXIMUM 

 DIST 1-HR CONC DIST 1-HR CONC 

 (m) (ug/m3) (m) (ug/m3) 

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

 1.01 0.3252E+06 2525.00 8586. 

 25.00 0.3483E+06 2550.00 8512. 

 50.00 0.2898E+06 2575.00 8439. 

 75.00 0.2450E+06 2600.00 8367. 

 100.00 0.2128E+06 2625.00 8296. 

 125.00 0.1890E+06 2650.00 8226. 
Page 60 of 61

 150.00 0.1706E+06 2675.00 8156. 

 175.00 0.1550E+06 2700.00 8088. 

 200.00 0.1387E+06 2725.00 8020. 

 225.00 0.1222E+06 2750.00 7953. 

 250.00 0.1056E+06 2775.00 7887. 

 275.00 0.8956E+05 2800.00 7821. 

 300.00 0.7444E+05 2825.00 7757. 

 325.00 0.6068E+05 2850.00 7693. 

 350.00 0.4852E+05 2875.00 7630. 

 375.00 0.4011E+05 2900.00 7568. 

 400.00 0.3704E+05 2925.00 7506. 

 425.00 0.3435E+05 2950.00 7445. 

 450.00 0.3197E+05 2975.00 7386. 

 475.00 0.2986E+05 3000.00 7326. 

 500.00 0.2906E+05 3025.00 7268. 

 525.00 0.2880E+05 3050.00 7210. 

 550.00 0.2848E+05 3075.00 7153. 

 575.00 0.2812E+05 3100.00 7096. 

 600.00 0.2771E+05 3125.00 7041. 

 625.00 0.2728E+05 3150.00 6986. 

 650.00 0.2683E+05 3175.00 6931. 

 675.00 0.2637E+05 3200.00 6877. 

 700.00 0.2589E+05 3225.00 6824. 

 725.00 0.2541E+05 3250.00 6771. 

 750.00 0.2493E+05 3275.00 6726. 

 775.00 0.2445E+05 3300.00 6687. 

 800.00 0.2398E+05 3325.00 6649. 

 825.00 0.2350E+05 3350.00 6611. 

 850.00 0.2304E+05 3375.00 6573. 

 875.00 0.2258E+05 3400.00 6535. 

 900.00 0.2213E+05 3425.00 6498. 

 925.00 0.2169E+05 3450.00 6461. 

 950.00 0.2126E+05 3475.00 6424. 

 975.00 0.2083E+05 3500.00 6387. 

 1000.00 0.2042E+05 3525.00 6351. 

 1025.00 0.2002E+05 3550.00 6315. 

 1050.00 0.1963E+05 3575.00 6279. 

 1075.00 0.1924E+05 3600.00 6244. 

 1100.00 0.1887E+05 3625.00 6208. 

 1125.00 0.1851E+05 3650.00 6173. 

 1150.00 0.1815E+05 3675.00 6142. 

 1175.00 0.1781E+05 3700.00 6112. 

 1200.00 0.1747E+05 3725.00 6081. 

 1225.00 0.1715E+05 3750.00 6051. 

 1250.00 0.1683E+05 3775.00 6022. 

 1275.00 0.1652E+05 3800.00 5992. 

 1300.00 0.1622E+05 3825.00 5962. 

 1325.00 0.1593E+05 3850.00 5933. 

 1350.00 0.1564E+05 3875.00 5904. 

 1375.00 0.1537E+05 3900.00 5877. 

 1400.00 0.1510E+05 3925.00 5849. 

 1425.00 0.1484E+05 3950.00 5822. 

 1450.00 0.1458E+05 3975.00 5795. 

 1475.00 0.1433E+05 4000.00 5768. 

 1500.00 0.1409E+05 4025.00 5741. 

 1525.00 0.1387E+05 4050.00 5714. 
Page 61 of 61

 1550.00 0.1366E+05 4075.00 5687. 

 1575.00 0.1346E+05 4100.00 5661. 

 1600.00 0.1326E+05 4125.00 5634. 

 1625.00 0.1307E+05 4150.00 5608. 

 1650.00 0.1288E+05 4175.00 5582. 

 1675.00 0.1269E+05 4200.00 5556. 

 1700.00 0.1251E+05 4225.00 5530. 

 1725.00 0.1233E+05 4250.00 5505. 

 1750.00 0.1216E+05 4275.00 5479. 

 1775.00 0.1199E+05 4300.00 5454. 

 1800.00 0.1182E+05 4325.00 5428. 

 1825.00 0.1166E+05 4350.00 5403. 

 1850.00 0.1150E+05 4375.00 5378. 

 1875.00 0.1135E+05 4400.00 5354. 

 1900.00 0.1120E+05 4425.00 5329. 

 1925.00 0.1105E+05 4450.00 5305. 

 1950.00 0.1090E+05 4475.00 5280. 

 1975.00 0.1076E+05 4500.00 5256. 

 2000.00 0.1062E+05 4525.00 5232. 

 2025.00 0.1048E+05 4550.00 5208. 

 2050.00 0.1034E+05 4575.00 5184. 

 2075.00 0.1021E+05 4600.00 5161. 

 2100.00 0.1008E+05 4625.00 5137. 

 2125.00 9957. 4650.00 5114. 

 2150.00 9833. 4675.00 5091. 

 2175.00 9715. 4700.00 5068. 

 2200.00 9628. 4725.00 5045. 

 2225.00 9542. 4750.00 5022. 

 2250.00 9458. 4775.00 4999. 

 2275.00 9374. 4800.00 4977. 

 2300.00 9291. 4825.00 4954. 

 2325.00 9209. 4850.00 4932. 

 2350.00 9128. 4875.00 4910. 

 2375.00 9048. 4900.00 4888. 

 2400.00 8968. 4925.00 4866. 

 2425.00 8890. 4950.00 4845. 

 2450.00 8813. 4975.00 4823. 

 2475.00 8736. 5000.00 4802. 

 2500.00 8661. 

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

 ********************** 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