US Environmental Protection Agency 

Office of Pesticide Programs 

Reregistration Eligibility Decision 

for Ethylene Oxide 

March 31, 2008
United States Prevention, Pesticides EPA 738-R-08-003 

Environmental Protection and Toxic Substances March 2008 

Agency (7508P) 

Reregistration 

Eligibility Decision for 

Ethylene Oxide 

Table of Contents 

Ethylene Oxide Reregistration Eligibility Decision Team ................................................................5 

Glossary of Terms and Abbreviations ...............................................................................................6 

Abstract ..............................................................................................................................................8 

I. Introduction ...................................................................................................................................9 

II. Chemical Overview......................................................................................................................11 

A. Chemical Identity...................................................................................................................11 

B. Regulatory History .................................................................................................................12 

C. Use and Usage Profile ............................................................................................................14 

III. ETO Occupational Risk Assessments.........................................................................................16 

A. Medical Use (Hospitals and Contract Sterilization Facilities)...............................................17 

B. Musical Instrument Use .........................................................................................................18 

C. Library and Museum Artifact Use .........................................................................................18

D. Cosmetics Use........................................................................................................................18 

E. Spice Use ................................................................................................................................18 

F. Beekeeping Use ......................................................................................................................19 

IV. Risk Management and Reregistration Decisions........................................................................21 

A. Determination of Reregistration Eligibility ...........................................................................21 

B. Public Comments and Responses...........................................................................................21

C. Food Quality Protection Act Findings ...................................................................................22 

1. “Risk Cup” Determination................................................................................................22 

2. Determination of Safety to United States Population .......................................................22 

3. Endocrine Disruptor Effects .............................................................................................23 

4. Cumulative Risks ..............................................................................................................23 

D. Regulatory Rationale..............................................................................................................23 

1. Occupational Risk Management and Mitigation ..............................................................24 

2. Use-Specific Analyses ......................................................................................................25 

a. Medical Use (Hospital and Contract Sterilization Facilities) .....................................26 

b. Musical Instrument Use ..............................................................................................32 

c. Library and Museum Artifact Use ..............................................................................34 

 d. Cosmetics Use.............................................................................................................36 

 e. Spice Use.....................................................................................................................38 

 f. Beekeeping Use ...........................................................................................................43 

V. What Registrants Need to Do.......................................................................................................47 

A. Manufacturing-Use Products .................................................................................................47 

1. Additional Generic Data Requirements ............................................................................47 

2. Labeling for Manufacturing-Use Products .......................................................................48 

B. End-Use Products...................................................................................................................48 

1. Additional Product-Specific Data Requirements..............................................................48 

2. Labeling for End-Use Products.........................................................................................48 

VI. References...................................................................................................................................55 

Page 3 of 68 
Appendices 

Appendix A. ETO Uses and Use-Patterns Eligible for Reregistration .............................................58 

Appendix B. Table of Generic Data Requirements and Studies Used to Make the ETO 

Appendix F. EPA’s Batching of ETO Products for Meeting Data Requirements for 

Reregistration Decision......................................................................................................................59 

Appendix C. Technical Documents to Support the ETO RED.........................................................61 

Appendix D. Generic Data Call-In (GDCI) ......................................................................................62 

Appendix E. Product-Specific Data Call-In (PDCI).........................................................................63 

Reregistration.....................................................................................................................................64 

Appendix G. List of Available Related Documents and Electronically Available Forms ...............65

List of Tables 

Table 1. Summary of Toxicological Doses and Endpoints for Occupational Exposure to ETO......17 

Table 2. Summary of Non-Cancer and Cancer Risk Estimates for ETO Uses.................................20 

Table 3. Data Requirement for the Reregistration of ETO ...............................................................47 

Table 4. Summary of Labeling Changes for ETO ............................................................................49 

Page 4 of 68 
Ethylene Oxide Reregistration Eligibility Decision Team 

EPA Office of Pesticide Programs: 

Special Review and Reregistration Division 

Susan Bartow 

Richard Dumas 

Robert McNally 

Anne Overstreet 

Health Effects Division 

Matthew Crowley 

Rebecca Daiss 

William Dykstra (in memory of) 

Ray Kent 

Jerry Stokes 

Environmental Fate and Effects Division 

Edward Odenkirchen 

Biological and Economic Analysis Division 

David Donaldson 

Arnet Jones 

Tim Kiely 

Raphael Prieto 

Leonard Yourman 

Antimicrobial Division 

Dennis Edwards 

Mark Hartman 

Diane Isbell 

Timothy Leighton 

Cassi Walls 

EPA Office of General Council: 

Robert Perlis 

Phil Ross 

Page 5 of 68 
Glossary of Terms and Abbreviations 

ai 

ARC 

ASTA 

BQA 

CAS 

CDC 

CFR 

CFSAN 

CSF 

DCI 

DNT 

EBH 

ECH 

EDSP 

EDSTAC 

EG 

EOSA 

EPA 

ETO 

EUP 

FDA 

FDA/BVM 

FDMS 

FIFRA 

FFDCA 

FQPA 

FPLA 

FR 

GACT 

GAP 

GLN 

GMP 

HACPP 

HEC 

IARC 

IMIS 

IRIS 

LOC 

LOAEL 

MACT 

μg/g 

μg/L 

mg/kg/day 

mg/L 

Active Ingredient 

ARC Specialty Products, Balchem Corporation 

American Spice Trade Association 

Baltimore Quality Assurance 

Chemical Abstracts Service 

Centers for Disease Control and Prevention 

Code of Federal Regulations 

FDA Center for Food Safety and Applied Nutrition 

Confidential Statement of Formulation 

Data Call-In 

Developmental Neurotoxicity 

Ethylene Bromohydrin 

Ethylene Chlorohydrin 

Endocrine Disruptor Screening Program 

Endocrine Disruptor Screening and Testing Advisory Committee 

Ethylene Glycol 

Ethylene Oxide Sterilization Association 

Environmental Protection Agency 

Ethylene Oxide 

End-Use Product 

Food and Drug Administration 

Food and Drug Administration Bureau of Veterinary Medicine 

Federal Docket Management System 

Federal Insecticide, Fungicide, and Rodenticide Act 

Federal Food, Drug, and Cosmetic Act 

Food Quality Protection Act 

Fair Packaging and Labeling Act 

Federal Register 

Generally Available Control Technology 

Good Agricultural Practices 

Guideline Number 

Good Manufacturing Practices 

Hazard Analysis and Critical Control Point 

Human Equivalent Concentration 

International Agency for Research on Cancer 

Integrated Management Information System 

Integrated Risk Information System 

Level of Concern 

Lowest Observed Adverse Effect Level 

Maximum Achievable Control Technology 

Micrograms Per Gram 

Micrograms Per Liter 

Milligram Per Kilogram Per Day 

Milligram Per Liter 

Page 6 of 68 
mg/m Milligram Per Meter 

MOE Margin of Exposure 

MRID Master Record Identification Number. EPA's system for recording and 

tracking studies submitted. 

MUP Manufacturing-Use Product 

NCDA&CS North Carolina Department of Agriculture and Consumer Affairs 

NIH National Institute of Health 

NOAEL No Observed Adverse Effect Level 

OAR EPA Office of Air and Radiation 

OPP EPA Office of Pesticide Programs 

OPPTS EPA Office of Prevention, Pesticides, and Toxic Substances 

ORD EPA Office of Research and Development 

OSHA Occupational Safety and Health Administration 

PD Pharmacodynamic 

PEL Permissible Exposure Limit 

PK Pharmacokinetic 

ppb Parts Per Billion 

PPE Personal Protective Equipment 

ppm Parts Per Million 

PPO Propylene Oxide 

PVC Polyvinyl Chloride 

RED Reregistration Eligibility Decision 

RfC Reference Concentration 

RfD Reference Dose 

RGDR Regional Gas Dose Ratio 

RQ Risk Quotient 

SAP Science Advisory Panel 

SCBA Self Contained Breathing Apparatus 

SF Safety Factor 

SLN Special Local Needs 

STEL Short-term Exposure Limit 

TGAI Technical Grade Active Ingredient 

TRED Tolerance Reassessment Decision 

UF Uncertainty Factor 

URF Unit Risk Factor 

USDA United States Department of Agriculture 

USDA-ARS United States Department of Agriculture-Agricultural Research Service 

VHP Vaporized Hydrogen Peroxide 

WPS Worker Protection Standard 

Page 7 of 68 
Abstract 

This document presents the Environmental Protection Agency’s (EPA’s or the Agency’s) 

decision regarding the reregistration eligibility of the registered uses of the active ingredient 

ethylene oxide (ETO). The Agency has revised its occupational risk assessments for ETO which 

incorporate worker exposure monitoring from medical and spice contract sterilization facilities. 

The Agency has determined that the benefits of ETO use outweigh the occupational risks 

associated with its use provided that the risk mitigation measures outlined in this document are 

adopted and label amendments are made to reflect these measures. The Agency has therefore 

determined that products containing the active ingredient ETO are eligible for reregistration 

provided that the risk mitigation measures outlined in this document are adopted and label 

amendments are made to reflect these measures. 

EPA has identified potential human health risks of concern associated with the current 

registered uses of ETO from occupational exposure. To reduce these exposures and to address 

current risks of concern, the Agency, in agreement with the technical registrants of ETO, will 

implement label restrictions (single chamber technology for hospitals, and respirator use for 

beekeeping use in North Carolina) for application of ETO to address occupational exposure 

concerns. The Agency is also specifying that employee safety and awareness training occur for 

all employees (including office staff) in contract sterilization facilities to ensure that all 

employees are aware of the risks associated with ambient levels of ETO from sterilization 

processes. In addition, the Agency encourages additional aeration of contract sterilization 

facilities as a Best Management Practice. For contract sterilization facilities, future monitoring 

efforts should include the entire facility (including monitoring and documenting air 

concentrations in office space, loading and unloading areas, break areas, etc.) to have accurate 

information regarding exposure of employees that are not wearing respirators as part of their 

daily routine on account of the nature of their work. 

Page 8 of 68 
I. Introduction 

The Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) was amended in 1988 

to accelerate the reregistration of products with active ingredients registered prior to November 

1, 1984. The amended Act calls for the development and submission of data to support the 

reregistration of an active ingredient, as well as a review of all data submitted to the 

Environmental Protection Agency (hereafter referred to as EPA or the Agency). Reregistration 

involves a thorough review of the scientific database underlying a pesticide’s registration. The 

purpose of the Agency’s review is to reassess the potential hazards arising from the currently 

registered uses of a pesticide, to determine the need for additional data on health and 

environmental effects, and to determine whether or not the pesticide meets the “no unreasonable 

adverse effects” standard of FIFRA. 

On August 3, 1996, the Food Quality Protection Act (FQPA) was signed into law. This 

Act amended FIFRA and the Federal Food, Drug, and Cosmetic Act (FFDCA) to require 

reassessment of all existing tolerances for pesticides in food. EPA decided that, for those 

chemicals that have tolerances and are undergoing reregistration, tolerance reassessment would 

be accomplished through the reregistration process. Under FQPA, in reassessing these 

tolerances, the Agency must consider, among other things, aggregate risks from nonoccupational sources of pesticide exposure, whether there is increased susceptibility among 

infants and children, and the cumulative effects of pesticides that have a common mechanism of 

toxicity. FQPA requires EPA to consider available information concerning the cumulative 

effects of a particular pesticide's residues and "other substances that have a common mechanism 

of toxicity" when considering whether to establish, modify, or revoke a tolerance. Potential 

cumulative effects of chemicals with a common mechanism of toxicity are considered because 

low-level exposure to multiple chemicals causing a common toxic effect by a common 

mechanism could lead to the same adverse health effect as would a higher level of exposure to 

any one of these individual chemicals. 

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. For the purposes of this reregistration eligibility decision, 

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 Office of Pesticide Programs 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/pesticides/cumulative/. 

EPA completed the tolerance reassessment for ETO in 2006. This evaluation considered 

the aggregate risk from exposure to ETO and its reaction products through food and drinking 

water and any potential residential or bystander exposure. The Agency concluded in its 2006 

Tolerance Reassessment Decision (TRED) for ETO that risks from aggregate exposure to ETO 

are not of concern. Therefore, the tolerances for ETO and its reaction product ethylene 

chlorohydrin (ECH) were reassessed as safe after risk mitigation options were adopted. The 

Page 9 of 68 
TRED is available in the public docket EPA-HQ-OPP-2005-0203 located on-line in the Federal 

Docket Management System (FDMS) at <http://www.regulations.gov>. 

This document addresses the remaining potential risks to workers and as such completes 

the Agency’s Reregistration Eligibility Decision (RED) for ETO. Risks summarized in this 

document are for ETO only because ETO is the chemical of concern for occupational exposure 

(not the ETO reaction products). 

On August 3, 2005, EPA opened the public docket with the preliminary risk assessments 

for ETO. Public comment was taken and the risk assessments were revised during phases 3 and 

4 of the Public Participation process. The risk assessments were revised to incorporate public 

comment and new data, and released again on February 22, 2006, for public comment during 

Phase 5 of the Public Participation process. The TRED was issued July 24, 2006. Based on 

public comment and incorporation of new information, a second Phase 5 public comment was 

opened on May 30, 2007. 

This document presents EPA’s revised occupational risk assessments which incorporate 

newly available worker exposure monitoring data from medical and spice contract sterilization 

facilities and the reregistration eligibility decision for ETO. This document consists of six 

sections. Section I contains the regulatory framework for reregistration. Section II provides a 

description of the chemical and a profile of the use and usage of the chemical. Section III 

provides an overview of the revised occupational risk assessments. Section IV presents the 

Agency's risk management and reregistration eligibility decisions and rationale. Section V 

outlines specific label changes and language necessary to implement the risk mitigation measures 

outlined in Section IV. Section VI, the References, provides the sources cited in this document. 

The appendices provide related information and supporting documents. The preliminary and 

revised risk assessments for ETO are available in the public docket EPA-HQ-OPP-2005-0203 

located on-line in the Federal Docket Management System (FDMS) at 

<http://www.regulations.gov>. 

Page 10 of 68 
II. Chemical Overview 

A. Chemical Identity 

Chemical Structure: C H

O 2 CH2

Molecular Formula: C2H4O 

Common Name: Ethylene Oxide 

CAS Name: Oxirane 

CAS Registry Number: 75-21-8 

OPP Chemical Code: 042301 

Case Number: 2275 

Honeywell Corporation and ARC Specialty Products of Balchem Technical Registrants: Corporation 

ETO has three reaction products— ethylene bromohydrin (EBH), ethylene chlorohydrin 

(ECH), and ethylene glycol (EG). 

OH Br

Ethylene Bromohydrin 

Chemical Structure: C C 

H2 H2 

OH Cl 

H

Ethylene Chlorohydrin 

Chemical Structure: C C 

2 H2 

Ethylene Glycol 

OH OH

Chemical Structure: C C

H2 H2 

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, these reaction products (EBH, 

Page 11 of 68 
ECH, and EG) were the chemicals of concern for dietary (oral) exposure and were assessed in 

the 2006 TRED. In the TRED, the Agency determined that dietary risk resulting from exposure 

to ETO and its reaction products is below the Agency’s level of concern after risk mitigation 

options were adopted. 

ETO is the compound of concern for residential non-dietary bystander (inhalation) 

exposure (i.e., the reaction products mentioned in the previous paragraph do not form during 

inhalation exposure to bystanders). EPA’s Office of Air and Radiation (OAR) conducted a 

residential risk assessment which estimated cancer as well as acute and chronic non-cancer risk 

to bystanders (USEPA, 2005). The Agency concluded that potential cancer and non-cancer risks 

do not indicate any further regulatory action is necessary at this time for residential inhalation 

exposure. 

ETO is also the compound of concern for occupational (inhalation) exposure. While 

inhalation exposure is the route of most concern, potential exists for dermal exposure to ETO, 

halohydrin and EG residues during post-sterilization activities (e.g., transportation of treated 

materials, bagging/containerizing treated spices). However, it is reasonable to assume that 

handling of the actual treated materials during post-sterilization activities is limited and dermal 

exposure is negligible. Therefore, this RED addresses risk only from ETO. 

B. Regulatory History 

ETO was first registered as a pesticide in 1966. It is a FIFRA List B reregistration 

pesticide. 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. Based on the reregistration assessments discussed in this RED and 

the supporting documentation, the Special Review of ETO will be concluded pursuant to the 

Agency’s Special Review regulations and a notice closing out the Special Review will be issued 

in the near future. 

In 1994, the International Agency for Research on Cancer (IARC) reclassified ETO as a 

known human carcinogen based on epidemiology and mutagenicity effects in humans. EPA’s 

Office of Research and Development (ORD), National Center for Environmental Assessment 

(NCEA) is in the midst of an Integrated Risk Information System (IRIS) review of ETO. NCEA 

is conducting its evaluation of the carcinogenicity of ETO based on available human 

epidemiological data. This analysis is anticipated to be finalized in September 2009. Should this 

information materially alter EPA’s understanding of ETO, the Agency will consider appropriate 

action. 

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 

Page 12 of 68 
precautionary statements, specify items to be treated with ETO, and require all users to adopt 

OSHA’s risk reduction measures. 

EPA issued a Data Call-In (DCI) Notice for ETO in 1989 requiring submission of 

product chemistry, residue chemistry, and toxicology studies. Additional DCIs were issued in 

1992 to address chemistry data deficiencies. The toxicology database has been reviewed and is 

considered complete for ETO. A DCI was issued in conjunction with the 2006 TRED requiring 

submission of toxicology studies for the reaction product ECH. 

The Agency’s Office of Air and Radiation (OAR) promulgated ETO emission standards 

for sterilization facilities on December 6, 1994. The rule regulates approximately 65 major 

commercial sterilization facilities and 35 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/EPA-TOX/2006/April/Day-07/t3314.htm>). 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/EPAAIR/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. 

The Food and Drug Administration (FDA) is an important federal partner with respect to 

ETO regulation. In the case of 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). 

With respect to ETO’s spice uses, FDA is responsible for ensuring that food, including 

spices, are 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. 

The 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 

Page 13 of 68 
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). 

ETO’s pesticidal use to reduce microbial loads on cosmetics is minimal (less than 1 

percent of total ETO pesticidal use). This RED addresses only the worker exposure from the 

pesticidal use of ETO on cosmetics. 

C. Use and Usage Profile 

Ninety percent of ETO use is for non-pesticidal industrial uses that are beyond the scope 

of FIFRA. The following is information on the currently registered pesticidal uses of ETO. 

Sections IV and V include information on those currently registered uses which are eligible for 

reregistration and Appendix A provides a detailed table of those uses which are eligible for 

reregistration. 

Type of ETO is an antimicrobial and conventional chemical. It is a biocide, 

Pesticide: fungicide, fumigant, herbicide, insecticide, rodenticide used to control the 

following pests: American foulbrood disease (Bacillus larvae), animal 

pathogenic bacteria, animal pathogenic fungi, bacteria, bacterial spores, 

Candida albicans, European foulbrood disease (Streptoccus pluton), Herpes 

simplex virus, Hew (FDA/BVM), unspecified microorganisms, 

Mycobacterium spp., Nosema apis, Pseudomonas spp., Rhinoviruses, storage 

microorganisms, stored product insects, wax moth. 

Formulations: ETO is formulated and marketed as a gas or a pressurized liquid. The end 

use formulations are all gas mixtures of ETO and inert gases (e.g., carbon 

dioxide) in varying concentrations. 

Methods of Sterilization/fumigation with ETO must be performed only in vacuum or gas 

Application: tight chambers designed for use with ETO. It is applied by commercial 

applicators only; there are no residential uses of ETO. 

Use Sites: ETO is used to sterilize medical or laboratory equipment, pharmaceuticals, 

and aseptic packaging (21CFR §201), or to reduce microbial load on musical 

instruments, cosmetics, whole and ground spices or other seasoning materials 

(40 CFR §180) and artifacts, archival material or library objects. In North 

Carolina, ETO is also used to fumigate beehive equipment (e.g., woodenware 

Page 14 of 68 
boxes and frames) and wax or plastic combs that are contaminated with the 

bacteria Paenibacillus larvae, the cause of American Foulbrood Disease. 

Estimated A maximum of approximately 8.2 million pounds of ETO are used annually 

Usage: in the United States for commercial fumigation/sterilization. Approximately 

7.4 million pounds are used annually for sterilization of medical and 

laboratory items/equipment. ETO treatment is the principal method used to 

reduce bacterial levels in spices/herbs and black walnuts. An estimated 

maximum of approximately 800,000 pounds are used annually for fumigation 

of herbs and spices. All other uses combined account for less than 1 percent 

of the total annual usage. 

Approximately 1,900 hospitals have 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. Approximately 30 contract sterilization facilities exist in the United 

States; 21 of those facilities represent 90 percent of the contract medical device sterilization 

capacity in the United States. In addition, many manufacturers of medical devices use ETO inhouse to sterilize their products. 

There are 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 has 2 to 3 workers that are actively involved in the ETO treatment 

process in some capacity. Therefore, approximately 45 workers in the United States are exposed 

to the potential risks from the fumigation of spices. 

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 15 of 68 
III. ETO Occupational Risk Assessments 

EPA has held three public comment periods for the ETO risk assessments. Based on 

public comments received during the three public comment periods, worker exposure monitoring 

data from the medical and spice contract sterilization facilities and new information that the 

Agency has received, the occupational risk assessments have been revised for ETO. These 

assessments demonstrate potential human health cancer risks of concern for workers resulting 

from all uses of ETO. In addition, potential non-cancer health risks have been identified for 

workers who are exposed to the ambient ETO levels in the facility but not the aeration/unloading 

rooms. These workers do not wear a respirator at any time during the day. A summary of 

potential risk concerns is presented below. The revised occupational risk assessments for ETO, 

dated March 24, 2008 (spice and beekeeping uses), and March 26, 2008 (medical, musical 

instrument, library and museum artifact, and cosmetics uses), respectively, are available in the 

public docket EPA-HQ-OPP-2005-0203 located on-line at <http://www.regulations.gov>. 

The target occupational margin of exposure (MOE) for ETO is 30. It is based on the 

uncertainty factor of 30X (3X interspecies factor and 10X intraspecies factor). When conducting 

inhalation risk assessments, the magnitude of the uncertainty factors applied is dependent on the 

methodology used to calculate risk. For studies in this risk assessment with inhalation data, 

uncertainty factors are based on the RfC (reference concentration) methodology developed by 

the ORD for the derivation of inhalation RfCs and human equivalent concentrations (HECs) for 

use in MOE calculations. Since the RfC methodology takes into consideration the 

pharmacokinetic (PK) differences but not the pharmacodynamic (PD) differences, the 

uncertainty factor for interspecies extrapolation may be reduced to 3X (to account for the PD 

differences) while the uncertainty factor for intraspecies variation is retained at 10X. Thus, the 

uncertainty factor when using the RfC methodology is customarily 30X. 

Table 1 presents the non-cancer and cancer endpoints. The Agency’s ORD is currently 

analyzing ETO’s carcinogenicity based on human epidemiological data. In the interim, the 

Agency has considered the range of rodent unit risk estimates from 2.22 x 10-2 (mg/m3

)

-1 to 2.67 

x 10-3 (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 for risk assessment purposes. This eight-fold 

selected range of unit risk estimates provides a comparison of both common and rare tumors in 

both sexes of rats and mice. 

Exact information regarding daily/weekly/yearly usage of ETO is only available for the 

beekeeping use. ETO is used for beekeeping uses in North Carolina for approximately 40 days 

per year. Therefore it is assumed that there is potential for short- and intermediate-term 

exposures. Cancer risk calculations for the beekeeping use are based on an exposure frequency 

of 40 days per year. Occupational exposure duration was assumed to be 35 years over a 70-year 

lifespan. 

Page 16 of 68 
Table 1. Summary of Toxicological Doses and Endpoints for Occupational Exposure to ETO. 

Exposure 

Scenario 

Dose Used in 

Risk 

Assessment, UF 

Level of Concern 

for Risk 

Assessment Study and Toxicological Effects 

Inhalation 

Short-Term 

(1 - 30 days) 

IntermediateTerm 

(1 - 6 months) 

NOAEL= 50 ppm 

(37.5 ppm, or 68 

mg/m3

 adjusted 

for occupational 

exposure) 

Occupational 

MOE = 30 

Subchronic Inhalation Toxicity Study in Mice 

(Snellings et al., 1984) 

• LOAEL = 100 ppm based on neurological effects 

(altered gait, decreased motor activity, and abnormal 

righting reflex) and absolute and relative spleen 

weight decreases in females. 

Inhalation 

Long-Term 

(> 6 months) 

Occupational 

Exposure 

NOAEL = 10 

ppm (7.5 ppm, or 

13.5 mg/m3 

adjusted for 

occupational 

exposure) 

Occupational 

MOE = 30 

Two Generation Reproduction Study, Inhalation 

Exposure, Rats (Chun and Neeper-Bradley, 1993) 

• 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) 

High end URF based on lung adenomas/carcinomas in male B6C3F1 mice = 2.22 E-02 (mg/m3

)

-1 (0.040 

(ppm)-1). 

Low end URF based on brain tumors in male F344 rats = 2.67 E-03 (mg/m3

)

-1 (0.0048 (ppm)-1). 

UF = uncertainty factor, NOAEL = no observed adverse effect level, LOAEL = lowest observed adverse effect level, MOE = 

margin of exposure, URF = Unit Risk Factor 

Note: Study NOAEL and LOAEL are adjusted to human equivalent doses for occupational scenario only. For example, the 

animal NOAEL of 10 ppm (6h/day, 5d/week)) is adjusted to human NOAEL of 7.5 ppm (8 h/day, 5d/week), assuming the 

regional gas dose ratio (RGDR) is similar between animals and humans (10 ppm x 6h/8h =7.5 ppm); In case of any continuous 

exposures (e.g., RfC), rat NOAEL of 10 ppm would be converted to human equivalent dose of 1.79 ppm [10 ppm x (6h/24h) x 

(5days in week/7days in week) =1.79 ppm] assuming similar RGDR between animals and humans (USEPA,1994). 

For all other uses of ETO, EPA assumed that there is potential for all exposure durations 

(i.e., short (1-30 days)-term, intermediate (1-6 months)-term, long (> 6 months)-term). For 

cancer risk calculations it was assumed that exposure frequency (the number of days per year 

workers are exposed to ETO) was 240 days per year, and occupational exposure duration was 35 

years over a 70 year lifespan. Though facilities that use ETO potentially do so year-round 

(hence the 240 day work-year assumption), it is recognized that these are likely conservative 

estimates. However, EPA has no additional information for further refinement. 

A. Medical Use (Hospitals and Contract Sterilization Facilities) 

As discussed in Section 5.0 of the Review of Calculated Ethylene Oxide Exposures for 

Ethylene Oxide Sterilization Plant Workers (MRID No. 47331801) Submitted in Support of the 

Occupational Exposure Assessment of the Antimicrobial Uses of Ethylene Oxide for the 

Reregistration Eligibility Decision (RED) (found at <http://www.regulations.gov./>), there are 

risk estimates that exceed EPA’s level of concern from occupational exposure to workers in 

hospitals and contract sterilization facilities under some exposure scenarios. 

Page 17 of 68 
For hospital workers that are involved with the ETO sterilization process (e.g., 

load/unload ETO chamber, change/maintain ETO tanks), short- and intermediate-term MOE 

estimates are not of concern (MOEs are 77), but long-term non-cancer risks are of concern 

(MOEs are 15). Using a range of unit risk factors, the potential cancer risks associated with ETO 

use in hospitals range from 2.6 x 10-4 to 2.1 x 10-3 which exceeds the Agency’s level of concern 

of 1 x 10-6. 

In contract sterilization facilities, the workers who are actually working with ETO and are 

involved directly with the ETO sterilization process wear respirators at some point during the 

day (i.e., when performing an activity where the OSHA PEL could be exceeded such as chamber 

unloading, tank maintenance, etc.). These workers have non-cancer MOE estimates that are not 

of concern (short- and intermediate-term MOEs are 250 and long-term MOEs are 50) for noncancer risks. However, based on ambient air monitoring data in facilities, other staff (e.g., 

workers unloading and loading vehicles and office workers who are not engaged in sterilization 

activities requiring respirator use) could have long-term non-cancer MOEs of 25 assuming they 

are in the building 8 hours per day for 240 days each year. 

Using a range of unit risk factors, the potential cancer risks associated with the contract 

sterilization use range from 7.9 x 10-5 to 1.3 x 10-3, which exceeds the Agency’s level of concern 

of 1 x 10-6. 

B. Musical Instrument Use 

Musical instruments are sterilized in contract sterilization facilities. Therefore, risks 

described above for the medical contract sterilization facilities apply to the musical instrument 

use. 

C. Library and Museum Artifact Use 

Library and museum artifacts are sterilized in contract sterilization facilities. Therefore, 

risks described above for the medical contract sterilization facilities apply to the library and 

museum artifact use. 

D. Cosmetics Use 

Cosmetics are sterilized in contract sterilization facilities. Therefore, risks described 

above for the medical contract sterilization facilities apply to the cosmetics use. 

E. Spice Use 

As discussed in Section 3.2 of the Addendum to the Occupational and Residential 

Exposure Assessment and Recommendations for the Reregistration Eligibility Decision (RED) 

for Ethylene Oxide (found at <http://www.regulations.gov./>), there are risk estimates that 

exceed EPA’s level of concern from occupational exposure to workers in spice sterilization 

facilities. 

Page 18 of 68 
EPA anticipates the following spice industry-related activities to result in potential 

worker exposure to ETO and its reaction products. 

• Inhalation exposure to ETO during sterilization activities; 

• Dermal exposure to EG and the halohydrins during post-sterilization activities; 

• Inhalation exposure to off-gassed ETO from treated spices during post-sterilization 

activities. 

It is reasonable to assume that handling of the actual treated materials during poststerilization activities is limited and dermal exposure is negligible. In addition, it is assumed that 

exposures and risks to off-gassed ETO from residue levels will be no higher than those from 

chamber re-entry or opening the chamber door. Non-cancer risk estimates for inhalation 

exposure to ETO during sterilization activities, calculated as MOEs, are not of concern. Workers 

involved in the ETO sterilization process have short- and intermediate-term MOEs of 380 and 

long-term MOEs of 190 for non-cancer risks. However, based on ambient air monitoring data in 

facilities, other staff (e.g., workers unloading and loading vehicles and office workers who are 

not engaged in sterilization activities requiring respirator use) could have short- and 

intermediate-term MOEs of 44 and long-term non-cancer MOEs of 40 assuming they are in the 

building 8 hours per day for 240 days each year. These risk estimates are not of concern. 

However, potential cancer risks for workers from inhalation of ETO range from 2.1 x 10-5 to 8.4 

x 10-4, which exceeds 1 x 10-6 risk. 

F. Beekeeping Use 

Exposures and risks associated with fumigation of beekeeping equipment are expected to 

be similar to those described above for spice fumigation considering the similarities in the 

fumigation process (e.g., chamber loading, gas introduction). 

Based on the limited number of ETO applications (30 to 40 times per year) for the North 

Carolina beekeeping use, ETO exposure for this use is not of chronic duration. Therefore the 

short-/intermediate-term endpoint for the non-cancer assessment would apply to this use. Noncancer risk estimates, calculated as MOEs are not of concern (i.e., short- and intermediate-term 

MOEs are 69). 

Since worker exposures are considered similar to spice fumigation, the beekeeping use 

information (i.e., 30 to 40 times per year) is applied to recently submitted worker exposure data 

for spice industry workers. This yields an estimated cancer risk range of 1.1 x 10-5 to 9.2 x 10-5 

which exceeds EPA’s level of concern. 

Table 2 presents a summary of the non-cancer and cancer risk estimates for the various 

uses of ETO for both the workers that are actively involved with ETO sterilization activities and 

the workers who are not engaged in sterilization activities requiring respirator use. 

Page 19 of 68 
Table 2. Summary of Non-cancer and Cancer Risk Estimates for ETO Uses 

Use Non-cancer Risk Estimate1 Cancer Risk Estimate2 

Hospitals (approx. 1,900): 

(1) Medical Use 

Short- and Int-term MOE = 77 

Long-term MOE = 15 

(Avg. of 11 SIC codes) 

2.6 x 10-4 to 2.1 x 10-3 

(Avg. of 11 SIC codes) 

Contract Sterilization (approx. 30 facilities): 

(1) Medical Use 

(2) Musical Instrument Use 

(3) Library and Museum Artifact Use 

(4) Cosmetics Use 

Workers (respirator): 

Short- and Int-term MOE = 250 

Long-term MOE = 50 

Workers (no respirator): 

Short- and Int-term MOE = 130 

Long-term MOE = 25 

Workers (respirator): 

7.9 x 10-5 to 6.6 x 10-4 

Workers (no respirator): 

1.6 x 10-4 to 1.3 x 10-3 

Contract Sterilization (approx. 15 facilities): 

(1) Spice Use 

Workers (respirator): 

Short- and Int-term MOE = 380 

Long-term MOE = 190 

Workers (no respirator): 

Short- and Int-term MOE = 44 

Long-term MOE = 40 

Workers (respirator): 

2.1 x 10-5 to 1.7 x 10-4 

Workers (no respirator): 

1.0 x 10-4 to 8.4 x 10-4 

Beekeeping Use (1 facility) 

Short-term MOE = 69 

Int-term MOE = 69 

Long-term – N/A 

1.1 x 10-5 to 9.2 x 10-5 

1

 Target MOE = 30. 

2

 Based on available rodent data. ORD analysis of ETO’s carcinogenicity (based on human epidemiological data) due 

9/30/09. Cancer slope factor ranges from 0.0048 (ppm) -1 to 0.040 (ppm) -1 . 

Note: 

Air concentrations needed to obtain 1.0 x 10-4 cancer risk = 0.023 to 0.19 ppm. 

Air concentrations needed to obtain 1.0 x 10-6 cancer risk = 0.00023 to 0.0019 ppm. 

Air concentration of 0.25 ppm is represented by a range of cancer risks of 1.3 x 10-4 to 1.1 x 10-3 . 

Air concentration of 1 ppm is represented by a range of cancer risks of 5.3 x 10-4 to 4.4 x 10-3 . 

Page 20 of 68 
IV. Risk Management and Reregistration Decisions 

A. Determination of Reregistration Eligibility 

Section 4(g)(2)(A) of FIFRA calls for the Agency to determine, after submission of 

relevant data concerning an active ingredient, whether or not products containing the active 

ingredient are eligible for reregistration. The Agency has previously identified and required the 

submission of the generic (technical grade) data to support reregistration of products containing 

ETO as an active ingredient. The Agency has completed its review of generic data that pertain to 

non-food uses, and has determined that the data are sufficient to support reregistration of all 

products containing ETO provided the registrations are amended in a manner consistent with this 

document. 

ETO sterilization/fumigation is performed in vacuum or gas tight chambers. Uses of 

ETO do not include outdoor applications, nor uses on birdseed. The use of ETO for fumigating 

beekeeping equipment for the control of various honeybee pathogens is expected to benefit the 

overall health of the hive. Therefore, exposure to terrestrial wildlife, aquatic organisms from the 

exclusive registration of ETO for indoor food and nonfood uses would be considered negligible. 

Negligible exposure yields an expectation of negligible risks to non-target terrestrial wildlife, 

aquatic organisms, and plants. Further, the Agency expects that such indoor uses of ETO will 

result in insignificant exposure to drinking water resources. 

The Agency has completed its review of submitted data and its assessments of the 

occupational risks associated with the use of pesticide products containing the active ingredient 

ETO. Based on these data and public comments received on the Agency's assessments for the 

active ingredient ETO, the Agency has sufficient information on the occupational effects of ETO 

to make a decision as part of the reregistration process under FIFRA. 

Based on its evaluation of ETO, the Agency has determined that products containing the 

active ingredient ETO, unless labeled and used as specified in this document, would present 

unacceptable risks under FIFRA. The Agency assessed the benefits of ETO use and made a risk 

management decision that risks are outweighed by benefits only if certain labeling changes and 

risk mitigation measures are adopted as part of the product reregistration and labeling. 

Accordingly, should a registrant fail to implement any of the risk mitigation measures identified 

in this document, the Agency may take appropriate regulatory action to address unmitigated risk 

concerns from the use of ETO. Therefore, under FIFRA, if all changes specified in this 

document are incorporated into the product labels, the Agency concludes that the current uses of 

ETO are eligible for reregistration. 

B. Public Comments and Responses 

Through the Agency’s public participation process, EPA worked with stakeholders and 

the public to reach these regulatory decisions for ETO. The Phase 3 public comment period on 

the risk assessments, opened on August 3, 2005. Two Phase 5 public comment periods were 

held. The first opened on February 22, 2006, and requested public comments on the risk 

assessments and supporting documents for ETO. The Agency also requested additional input to 

Page 21 of 68 
use/usage information and risk management suggestions for dietary and worker concerns. The 

ETO TRED was issued July 24, 2006. The second Phase 5 public comment period opened on 

May 30, 2007. This comment period solicited comments on the risk assessments and risk 

management suggestions for occupational risks. The Agency received comments from several 

stakeholders and the technical registrants. A complete listing of these comments can be found at 

<http://www.regulations.gov./>. 

These comments were reviewed and taken into consideration in preparing the revised risk 

assessments as well as the reregistration eligibility decisions presented in this document. The 

comments and EPA’s responses, are available in their entirety in the public docket EPA-HQOPP-2005-0203 located on-line at <http://www.regulations.gov./>. 

C. Food Quality Protection Act Findings 

1. “Risk Cup” Determination 

As described in the 2006 Tolerance Reassessment Eligibility Decision (TRED), EPA has 

determined that the human health risks from exposures to ETO and its reaction products are 

within acceptable levels and the tolerances for ETO meet the safety standards under the FQPA 

amendments to Section 408(b)(2)(C) and 408(b)(2)(D) of the FFDCA after risk mitigation 

options were adopted. In reaching these determinations, EPA has considered the available 

information on the special sensitivity of infants and children. 

The Agency concluded in its 2006 TRED that risks from aggregate exposure to ETO are 

not of concern. Therefore, the tolerances for ETO and its reaction product ethylene chlorohydrin 

(ECH) were reassessed as safe. The TRED is available in the public docket EPA-HQ-OPP2005-0203 located on-line in the Federal Docket Management System (FDMS) at 

<http://www.regulations.gov>. 

2. Determination of Safety to United States Population (Including Infants and 

Children) 

The Agency has determined that there is a reasonable certainty that no harm will result to 

the general United States population, infants, children, or other major identifiable subgroups of 

consumers, from the use of ETO. The safety determination considers factors such as the toxicity, 

use practices and exposure scenarios, and environmental behavior of ETO. In determining 

whether or not infants and children are particularly susceptible to toxic effects from exposure to 

residues of ETO, the Agency considered the completeness of the hazard database for 

developmental and reproductive effects, the nature of the effects observed, and other 

information. 

Page 22 of 68 
3. Endocrine Disruptor Effects 

EPA is required under the FFDCA, as amended by FQPA, to develop a screening 

program to determine whether certain substances (including all pesticide active and other 

ingredients) “may have an effect in humans that is similar to an effect produced by a naturally 

occurring estrogen, or other such endocrine effects as the Administrator may designate.” 

Following the recommendations of its Endocrine Disruptor Screening and Testing Advisory 

Committee (EDSTAC), EPA determined that there were scientific bases for including, as part of 

the program, androgen and thyroid hormone systems, in addition to the estrogen hormone 

system. EPA also adopted EDSTAC’s recommendation that the Program include evaluations of 

potential effects in wildlife. When the appropriate screening and/or testing protocols being 

considered under the Agency’s Endocrine Disrupter Screening Program (EDSP) have been 

developed and vetted, ETO may be subjected to additional screening and/or testing to better 

characterize possible effects related to endocrine disruption. 

4. Cumulative Risks 

FFDCA Section 408(b)(2)(D)(v) requires that the Agency consider “available 

information” concerning cumulative effects of a particular pesticide’s residues and “other 

substances that have a common mechanism of toxicity” when considering whether to establish, 

modify, or revoke a tolerance for pesticide residues in food. EPA considers cumulative effects 

from pesticides and other substances because low-level exposures to multiple chemical 

substances causing a common effect by a common mechanism could lead to the same adverse 

health effect as would a higher level of exposure to each individual substance. 

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. For the purposes of this reregistration eligibility decision, 

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 Office of Pesticide Programs 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/pesticides/cumulative/>. 

D. Regulatory Rationale 

Based on an evaluation of the risks and benefits of ETO’s uses, the Agency has 

determined that products containing the active ingredient ETO are eligible for reregistration 

provided that the risk mitigation measures specified in this document are adopted and label 

amendments are made to require those mitigation measures. The following is a summary of the 

risk mitigation measures and EPA’s rationale for the decision for managing risks associated with 

the use of ETO. Where labeling revisions are warranted, label changes and language are 

specified in Section V. 

Page 23 of 68 
1. Occupational Risk Management and Mitigation 

As discussed in Section 5.0 of the Review of Calculated Ethylene Oxide Exposures for 

Ethylene Oxide Sterilization Plant Workers (MRID No. 47331801) Submitted in Support of the 

Occupational Exposure Assessment of the Antimicrobial Uses of Ethylene Oxide for the 

Reregistration Eligibility Decision (RED) and in Section 3.2 of the Addendum to the 

Occupational and Residential Exposure Assessment and Recommendations for the 

Reregistration Eligibility Decision (RED) for Ethylene Oxide (found at 

<http://www.regulations.gov./>), there are risk estimates that exceed EPA’s level of concern 

from occupational exposure to ETO. 

For hospital workers, long-term non-cancer risks are of concern (MOEs are 15) assuming 

the workers are in the building 8 hours per day for 240 days each year. Potential cancer risks 

associated with ETO use in hospitals range from 2.6 x 10-4 to 2.1 x 10-3 which exceeds the 

Agency’s level of concern of 1 x 10-6. Therefore, in order to mitigate potential non-cancer and 

cancer risk concerns for workers in hospitals exposed to ETO as a result of medical use, a single 

chamber process is needed for ETO treatment (sterilization and aeration are to occur in the same 

chamber). This mitigation measure is expected to lower ambient levels of ETO in hospitals and 

result in reduced long-term non-cancer and potential cancer risk estimates for hospital workers. 

In medical contract sterilization facilities, the workers who are actually working with 

ETO and are involved directly with the ETO sterilization process wear respirators at some point 

during the day (i.e., when performing an activity where the OSHA PEL could be exceeded such 

as chamber unloading, tank maintenance, etc.) and do not have non-cancer risks of concern. 

However, based on data on ambient levels of ETO in these facilities, other staff (e.g., workers 

unloading and loading vehicles and office workers who are not engaged in sterilization activities 

requiring respirator use) could have long-term non-cancer risks of concern assuming they are in 

the building 8 hours per day for 240 days each year over a 35-year work career. Potential cancer 

risks for all workers in medical contract sterilization facilities (including workers unloading and 

loading vehicles and office workers who are not engaged in sterilization activities requiring 

respirator use) exceeded the Agency target of 1 x 10-6 and range from 7.9 x 10-5 to 1.3 x 10-3. In 

spice contract sterilization facilities non-cancer risk estimates are not of concern. However, 

potential cancer risks for all workers in spice contract sterilization facilities (including office 

workers not engaged in sterilization activities) range from 2.1 x 10-5 to 8.4 x 10-4. 

Therefore, in order to mitigate potential non-cancer and cancer risk concerns for workers 

in contract sterilization facilities (including medical and spice contract sterilization facilities), the 

Agency is specifying that employee safety and awareness training be given to all employees 

(including office staff). Information and training is to be provided to all employees in the facility 

at the time of initial assignment and annually thereafter. This training is intended to ensure that 

all facility employees are aware of the risks associated with ambient levels of ETO from 

sterilization processes and is to include, at a minimum, the following information: 

• The most recent monitored ambient levels of ETO in the facility. 

• The potential health effects from the levels of ETO in the facility. 

• The emergency response plan and how to respond in an emergency. 

Page 24 of 68 
• The availability of the Material Safety Data Sheet and other materials related to the health 

hazards of exposure to ETO. 

In addition, the Agency encourages each facility to increase its aeration to reduce ambient 

levels of ETO. Achieving an ambient level of 0.25 ppm or less (measured as a daily timeweighted average) could eliminate potential long-term non-cancer risks to workers who do not 

wear respirators as part of their job duties. An ambient level of 0.25 ppm of ETO (measured as a 

daily time-weighted average) would also be expected to result in potential cancer risks of 1.3 x 

10-4 to 1.1 x 10-3. Achieving ambient ETO levels less than 0.25 ppm would potentially result in 

lower cancer estimates. Future monitoring efforts at contract sterilization facilities should 

include the entire facility (including office space, vehicle unloading/loading areas, and break 

areas) to have accurate information regarding exposure of employees that are not wearing 

respirators as part of their daily routine. 

Non-cancer risk estimates are not of concern for the beekeeping use in North Carolina. 

However, potential cancer risks exceed the Agency target of 1 x 10-6 and range from 1.1 x 10-5 to 

9.2 x 10-5. Therefore, in order to mitigate potential cancer risk concerns for workers sterilizing 

beekeeping equipment in North Carolina, respirators are specified to be worn during chamber 

unloading and tank change/maintenance activities. This risk mitigation measure is expected to 

lower worker exposure to ETO and result in reduced long-term non-cancer and potential cancer 

risk estimates for workers. 

2. Use-Specific Analyses 

The Agency has worked with the technical registrants, Honeywell Corporation 

(Honeywell) and ARC Specialty Products of Balchem Corporation (ARC), to reduce 

occupational exposure to ETO. Subsequently, Honeywell and ARC have agreed to the following 

risk reduction measures and to incorporate them as requirements in their affected product’s 

registration and labeling: 

• A single chamber process is required for ETO treatment (sterilization and aeration are to 

occur in the same chamber) in hospitals. This requirement is expected to lower ambient 

levels of ETO in hospitals and result in reduced long-term non-cancer and potential 

cancer risk estimates for hospital workers. 

• Employee safety and awareness training is required for all employees (including office 

staff) in contract sterilization facilities. This requirement ensures that all facility 

employees are aware of the risks associated with ambient levels of ETO from sterilization 

processes. 

• For the beekeeping use, respirators are required to be worn during chamber opening and 

unloading and tank change/maintenance activities. This requirement is expected to lower 

worker exposure to ETO and result in reduced long-term non-cancer and potential cancer 

risk estimates for workers. 

Page 25 of 68 
The Agency has determined that the label changes (as specified in Table 4 in Section V), 

as agreed upon by the technical registrants Honeywell and ARC, are appropriate and needed for 

reregistration eligibility. Listed below are the specific uses for ETO along with corresponding 

cancer and non-cancer risk estimates for workers, stakeholder input on use, alternatives/benefits, 

risk reduction measures in place, and EPA’s decision regarding reregistration eligibility. As a 

general matter, the Agency has determined that there are no short-term or intermediate-term risks 

of concern to workers from the use of ETO. There is potential, however, for long-term noncancer and cancer risks to some workers depending upon their specific functions within a 

facility. The Agency determined that these risks are outweighed by the benefits expected from 

use of ETO provided the specified risk reduction measures are adopted. The Agency also 

determined that ETO does not pose risks of concern to the general population or to the 

environment. 

a. Medical Use (Hospitals and Contract Sterilization Facilities) 

Current Use Pattern 

ETO is used to sterilize new and reusable medical equipment (e.g., surgical instruments, 

hypodermic needles/syringes, surgical prosthetic parts, hemodialysis machines, heart and lung 

machines, dental instruments, veterinary instruments, heat labile material, moisture labile 

material, oral and inhalation equipment, diagnostic instruments, thermometers, surgical 

dressings, first aid equipment). Approximately 7.4 million pounds are used annually for 

sterilization of medical and laboratory items/equipment. 

Approximately 1,900 hospitals have 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. Approximately 30 contract 

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

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

manufacturers of medical devices use ETO in-house to sterilize their products. For all of these 

medical uses, ETO sterilization occurs in vacuum or gas tight chambers designed for use with 

ETO. 

Risks of Concern 

As discussed in Section 5.0 of the Review of Calculated Ethylene Oxide Exposures for 

Ethylene Oxide Sterilization Plant Workers (MRID No. 47331801) Submitted in Support of the 

Occupational Exposure Assessment of the Antimicrobial Uses of Ethylene Oxide for the 

Reregistration Eligibility Decision (RED) (found at <http://www.regulations.gov./>), there are 

risk estimates that exceed EPA’s level of concern from occupational exposure to workers in 

hospitals and medical contract sterilization facilities. 

The target MOE for ETO is 30. For hospital workers, short- and intermediate-term MOE 

estimates are not of concern (MOEs are 77), but long-term non-cancer risks are of concern 

(MOEs are 15) assuming the workers are in the building 8 hours per day for 240 days each year 

over a 35-year career. Using a range of unit risk factors, the potential cancer risks associated 

Page 26 of 68 
with ETO use in hospitals range from 2.6 x 10-4 to 2.1 x 10-3 which exceeds the Agency’s level 

of concern of 1 x 10-6. 

In medical contract sterilization facilities, the workers who are actually working with 

ETO and are involved directly with the ETO sterilization process wear respirators at some point 

during the day (i.e., when performing an activity where the OSHA PEL could be exceeded such 

as chamber unloading, tank maintenance, etc.). These workers have non-cancer MOE estimates 

that are not of concern (short- and intermediate-term MOEs are 130 to 250 and long-term MOEs 

are 50) for non-cancer risks. However, based on ambient air monitoring data in facilities, other 

staff (e.g., office workers who are not engaged in sterilization activities) could have long-term 

non-cancer MOEs of 25 assuming they are in the building 8 hours per day for 240 days each 

year. 

Using a range of unit risk factors, all of the potential cancer risks associated with the 

contract sterilization use exceeded the Agency target of 1 x 10-6 and range from 7.9 x 10-5 to 1.3 

x 10-3. 

Stakeholder Involvement/Input on Medical Use 

Since 2005, EPA has been coordinating its ETO risk assessment and management efforts 

with OSHA. In May 2005, EPA and OSHA staff met to discuss EPA’s preliminary occupational 

exposure analysis and the availability of recent worker exposure data at OSHA. In December 

2005, OSHA provided monitoring data for contract sterilization facilities from its Integrated 

Management Information System (IMIS) to be incorporated into EPA’s risk assessment. 

In June 2005, EPA staff visited the National Institute of Health (NIH) medical 

sterilization facility in Bethesda, Maryland. The site visit focused on the use of ETO for medical 

sterilization. The Agency staff observed the sterilization process and equipment used, saw 

various medical materials that had been sterilized, and discussed ETO handling occupations in 

the facility, safety protocols, and emergency procedures. 

EPA also participated in a meeting with USDA, ETO registrants, and ETO stakeholders 

in December 2005. Representatives from Honeywell Inc., ARC, American Chemistry Council, 

American Spice Trade Association (ASTA), Sterigenics, University of Iowa Hospital, Wake 

Forest University Baptist Medical Center, and 3M presented their perspectives on the importance 

of ETO and the potential impacts of the worker exposure analysis in the preliminary risk 

assessment. Meeting materials and a summary of the meeting can be found in the public docket 

EPA-HQ-OPP-2005-0203 online at <http://www.regulations.gov./>. 

In February 2006, EPA staff held a conference call with representatives from the Centers 

for Disease Control and Prevention (CDC) and the Food and Drug Administration (FDA) to 

discuss ETO use in the medical industry from a public health perspective. In summary, FDA and 

CDC agreed that ETO was a critical sterilant for the health care industry. In their opinion, ETO 

fills a reprocessing niche for medical equipment that is moisture, temperature, or radiation 

sensitive. 

Page 27 of 68 
In October 2007, EPA visited Sterilization Services of Virginia, a contract sterilization 

facility in Richmond, Virginia. The site visit focused on the use of ETO for sterilization of 

medical equipment and provided valuable information about the ETO sterilization processes at 

contract sterilization facilities. Observing existing mitigation measures in place at the facility 

was another important aspect of the site visit. 

In February 2008, EPA staff coordinated with FDA again. FDA staff reiterated their 

previous statement that ETO was a critical sterilant for the health care industry. In their opinion, 

ETO continues to fill a niche for sterilizing and reprocessing medical equipment that is moisture, 

temperature, or radiation sensitive. 

During Phases 5 and 6 of the Public Participation Process, in addition to the written 

comments received from respondents as mentioned in section IV. B. above, the Agency met with 

ARC, the Ethylene Oxide Sterilization Association (EOSA), STERIS Corporation, Sterigenics 

International, Inc., and other interested stakeholders with specific knowledge relating to ETO 

medical use. These stakeholders have provided actual worker exposure monitoring data to refine 

the risk estimates for contract sterilization facilities. In addition, these stakeholders provided 

detailed information about the ETO sterilization process and existing mitigation measures that 

are used in ETO contract sterilization facilities. 

Alternatives and Benefits 

There are several methods that are available to sterilize medical devices. Depending on 

the material composition of the device and its sensitivity to different sterilants and the use site 

(e.g., industrial, hospital, etc.) different sterilizers can be effective, including heat, ETO, gamma 

radiation, electron beam radiation, x-ray, and hydrogen peroxide plasma. Despite the fact that 

there are several methods that are available to sterilize medical devices, no currently available 

sterilization treatment can replace ETO for some uses, including certain heat-sensitive and 

irradiation-sensitive materials and some instruments and devices that require sterilization on-site 

in hospitals. 

Based on available information, EPA considers ETO critical to sterilization in the 

medical industry and necessary to protect public health. Currently, there do not appear to be any 

feasible replacements for its use in sterilizing medical devices. 

For additional information, refer to the Agency’s Qualitative Assessment of Alternatives 

for Ethylene Oxide Uses (DP316692) and the BEAD response to comments documents which 

are available in the public docket EPA-HQ-OPP-2005-0203 and located on-line at 

<http://www.regulations.gov/>. 

Risk Reduction Measures in Place 

Contract sterilization facilities use a variety of approaches to reduce the risks of ETO 

exposure to employees. These approaches include facility design, ETO chamber design, ETO 

treatment cycle protocols, respirator requirements, employee monitoring, employee training, and 

facility procedures (EOSA, 2007). 

Page 28 of 68 
Facilities are designed to physically separate areas of ETO-treated materials and nonETO-treated materials. In addition, the ventilation systems of facilities are designed to keep the 

ventilation system physically separated from the ETO treatment chambers. Aeration rooms are 

established at facilities to allow treated materials to aerate in a contained area, where ETO is 

captured and sent to an emission control device (e.g., wet-scrubber system) thereby minimizing 

potential exposure. Aeration rooms are kept at an elevated temperature to speed the removal of 

ETO that is absorbed by the treated materials. 

ETO chambers are designed with back vents to pull air into the chamber, especially as the 

chamber door is opened. Chambers are also designed with an interlock system with direct ETO 

measurement to reduce potential worker exposure to ETO. 

The treatment cycles used in ETO chambers are considered an important tool by the 

ETO-user industry to reduce worker exposure. A cycle is composed of several steps (e.g., 

removal of air by vacuum pump; introduction of steam, nitrogen, and ETO; and removal of 

ETO). Carefully timed cycles with numerous air washes and nitrogen “gas” washes to remove 

ETO at the end of a treatment cycle reduce the amount of ETO remaining in a chamber before 

the chamber is opened. 

Some facilities use an all-in-one cycle design where materials are preconditioned and/or 

aerated inside of the sterilization chamber. This all-in-one design is believed to reduce worker 

exposure because it eliminates the transfer of treated materials to a separate chamber for 

aeration. Industry claims that the all-in-one cycle “has varying impacts on ETO worker exposure 

depending on the cycle design and product.” Not all medical devices can be processed using the 

all-in-one cycle design, particularly pressure-sensitive materials (EOSA, 2007). 

Respirators are required to be worn during certain tasks such as unloading ETO treatment 

chambers, entering an aeration room (or cell), performing maintenance tasks on ETO pipes or 

equipment, sampling or accessing ETO-treatment materials, and changing ETO drums or tanks. 

Canister masks are the most commonly used respirator. Forced air masks (i.e., supplied air 

respirators) are used when entering areas with high-ETO concentrations (e.g., aeration rooms). 

Self Contained Breathing Apparatus (SCBA) is used in emergency situations and for some 

maintenance activities. 

Employee exposure monitoring is required under OSHA regulations. Employees wear 

monitoring badges at least twice per year to determine their ETO exposure. Continuous ETO 

monitors are installed throughout many facilities and handheld monitors are used as well. 

Contract sterilization facilities have established specific procedures for handling ETO 

drums/tanks. Employees at contract sterilization facilities receive ETO-specific training to 

review safety procedures and regulations. 

Hospitals use many of the same approaches to reduce the risks of ETO exposure to 

employees as described above for the contract sterilization facilities. Specifically, hospitals 

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incorporate facility design, ETO chamber design, ETO treatment cycle protocols, employee 

monitoring, employee training, and facility procedures to the extent feasible. 

Each hospital is unique and its design, equipment, protocols, and procedures may vary 

depending on the activities of the facility and the materials that are treated. Universally, ETO 

levels are continuously monitored in the rooms where ETO chambers are located. Visible and 

audible alarm systems are typically present in the chamber area. Chambers are generally 

designed with an interlock system with direct ETO measurements to reduce potential worker 

exposure to ETO. Hospitals combine the aerator and sterilizer into one unit (i.e., all-in-one 

process design) when possible. Exhaust hoods are often placed over the chambers to aid in 

capturing any ETO released when opening the chamber for unloading. 

Unlike in contract sterilization facilities, workers in hospital settings do not routinely 

wear respirators. Typically respirators are used only in emergency situations. However, 

employee exposure monitoring is required under OSHA regulations. Employees wear 

monitoring badges to determine their ETO exposure. Employees typically receive ETO-specific 

training to review safety procedures and regulations. 

EPA Decision 

Based on current worker exposure data and toxicity estimates, ETO has the potential to 

cause adverse health effects to workers through long-term inhalation exposure (i.e., greater than 

6 months of exposure) in both hospitals and medical contract sterilization facilities. 

Hospitals. In hospitals, long-term non-cancer risks (MOE of 15 with a target of 30) and 

potential cancer risks (2.6 x 10-4 to 2.1 x 10-3) are of concern. 

EPA policy for non-dietary risks in the 10-5 to 10-4 range is to determine whether the 

benefits of use outweigh the risks and to seek cost effective ways to reduce risks. This policy 

specifically allows for the consideration of the weight of scientific evidence regarding 

carcinogenicity and benefits associated with the pesticide under review. The Agency recognizes 

that the ORD is currently analyzing ETO’s carcinogenicity based on human epidemiological 

data. In the interim, the Agency believes it appropriate to use available rodent data to estimate 

cancer risks from ETO. The Agency has determined that the health benefits associated with the 

use of ETO on medical equipment are extremely high. 

Given the extremely high health benefits of ETO use and the lack of any feasible 

replacements for ETO use in sterilizing certain medical equipment/devices, the Agency has 

determined that ETO use on medical equipment in hospitals is eligible for reregistration with the 

implementation of the following mitigation. 

• A single chamber process is specified for ETO treatment (sterilization and aeration are to 

occur in the same chamber). This risk mitigation measure is expected to lower ambient 

levels of ETO in hospitals and result in reduced long-term non-cancer and potential 

cancer risk estimates for hospital workers. 

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Medical contract sterilization facilities. In medical contract sterilization facilities, longterm non-cancer risk are of concern for workers that do not wear a respirator at any time during a 

work day (MOE of 25 with a target of 30). Potential cancer risks for medical contract 

sterilization facility workers range from 7.9 x 10-5 to 1.3 x 10-3. 

As described above, the EPA policy for non-dietary risks of this nature is to determine 

whether the benefits of use outweigh the risks and to seek ways to mitigate unacceptable risks. 

The Agency has determined that the health benefits associated with the use of ETO on medical 

equipment are extremely high. 

Given the extremely high health benefits of ETO use, the lack of any feasible 

replacements for ETO use in sterilizing certain medical equipment/devices, and the extensive 

risk reduction measures already in place to protect workers, the Agency has determined that ETO 

use on medical equipment in contract sterilization facilities is eligible for reregistration with the 

implementation of the following mitigation. 

• Employee safety and awareness training is required for all employees (including office 

staff). Information and training is to be provided to all employees in the facility at the 

time of initial assignment and annually thereafter. This training is intended to ensure that 

all facility employees are aware of the risks associated with ambient levels of ETO from 

sterilization processes and is to include, at a minimum, the following information: 

3⁄4 The most recent monitored ambient levels of ETO in the facility. 

3⁄4 The potential health effects from the levels of ETO in the facility. 

3⁄4 The emergency response plan and how to respond in an emergency. 

3⁄4 The availability of the Material Safety Data Sheet and other materials related to 

the health hazards of exposure to ETO. 

• Increased facility aeration is encouraged to reduce ambient levels of ETO. Achieving an 

ambient level of 0.25 ppm or less (measured as a daily time-weighted average) could 

eliminate potential long-term non-cancer risks to workers that do not wear respirators as 

part of their job duties. An ambient level of 0.25 ppm of ETO (measured as a daily timeweighted average) would also be expected to result in potential cancer risks of 1.3 x 10-4 

to 1.1 x 10-3. Achieving ambient ETO levels less than 0.25 ppm would potentially result 

in lower cancer estimates. Future monitoring efforts at contract sterilization facilities 

should include the entire facility (including office space, vehicle unloading/loading areas, 

and break areas) to have accurate information regarding exposure of employees that are 

not wearing respirators as part of their daily routine. 

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b. Musical Instrument Use 

Current Use Pattern 

ETO is used to sterilize musical instruments in a vacuum-sealed treatment chamber, 

using the same treatment facilities where medical and dental instruments are treated. The 

application rate of ETO used to treat musical instruments varies based on the type of sterilization 

chamber used. The sterilization process used by medical device manufacturers and contract 

sterilizers is largely automated with workers outside the chambers altering temperature and 

pressures within the chambers as needed. Each of the cycles has been pre-validated by the 

manufacturer for temperatures, pressures, ETO concentrations, and run times. Afterwards, the 

medical devices are aerated for up to 12 hours to reduce or eliminate ETO residues. It should be 

noted that industrial sterilizers frequently utilize hot cells and altered chamber cycles to reduce 

ETO residuals more effectively. 

Typical sterilization chambers to treat musical instruments and used by medical device 

manufacturers or contract sterilizers are approximately 660 cubic feet and hold 550 cubic feet of 

medical products (i.e., 6 pallets) (Knee, 2001). The chambers are vacuum-sealed and ETO is 

injected into the chamber to the desired concentration, where the concentrations can range from 

0.02 to 0.080 lbs of ETO per cubic feet of sterilized devices (i.e., 16 to 40 lbs per load). 

Risks of Concern 

Since musical instruments are treated with ETO in contract sterilization facilities, it is 

assumed that estimated exposures and risks for the medical contract sterilization facilities cover 

the musical instrument use. 

Stakeholder Involvement 

During Phase 5 of the Public Participation Process, the Agency received a total of 31 

comments expressing support of the continued ETO registration for use in sterilizing musical 

instruments. Thirty of these letters were expressing general support for the continued 

registration of ETO. Additional information supporting the continued registration was submitted 

by Encore, Etc., the distributor for the ETO musical instrument treatment, EPA Registration 

number 36736-2. In addition, the Agency met with representatives from Encore, Etc. All 

comments are available in EPA’s public docket <www.regulations.gov> (EPA-HQ-OPP-2005-

0203). 

Alternatives and Benefits 

Every year hundreds of thousands of students receive used musical instruments loaned to 

them from their schools, rented from local school music dealers, or purchased over the internet. 

The use of ETO to sterilize musical instruments was developed to eliminate microorganisms 

from the entire instrument before a new user receives it. Traditionally, only the mouthpiece of 

an instrument is cleaned with soap, water and possibly alcohol between student rentals. 

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Information submitted by Encore, Etc., Inc. included a report of a test conducted by 

Sterigenics, a contract sterilization company. The test compared "sterilization efficacy" of eight 

treatment methods. The treatments used in this evaluation were: ETO; VHP (vaporized 

hydrogen peroxide); ozone; alcohol; bleach; boiling; ultrasound with phosphoric acid; and liquid 

sterilant immersion (unidentified). 

The Agency evaluated the submitted information and concluded that bacteria were 

recovered several weeks after being placed in instruments and mouthpieces. When new and 

previously used instruments were screened for the presence of microorganisms, none of the 

numerous species identified were pathogens. However, ETO is an effective antimicrobial 

treatment that likely will decontaminate musical instruments. 

Musical instruments are treated in the same contract facilities that sterilize medical and 

dental instruments. Because a relatively low volume of instruments are sterilized with ETO, no 

additional facilities are needed to treat musical instruments at this time. Although there may be 

benefits associated with using ETO for sterilizing musical instruments, the Agency is unable to 

quantify them at this time. 

Risk Reduction Measures in Place 

Since ETO use on musical instruments occurs in contract sterilization facilities, risk 

reduction measures described above for medical contract sterilization facilities would be the 

same for this application. 

EPA Decision 

ETO use has the potential for a slight exceedance for long-term non-cancer inhalation 

risks for workers (MOE=25, target MOE=30). These potential risks are for workers exposed to 

background air concentrations within the facility, not wearing respirators. Cancer risks for 

workers exceed the level of concern for workers in contract facilities (i.e., risks range from 7.9 x 

10-5 to 1.3 x 10-3). For occupational cancer risks between 1x10-6 and 1x10-4, EPA carefully 

evaluates exposure scenarios to seek cost effective ways to reduce cancer risks to the greatest 

extent feasible, preferably to a risk of 1x10-6 or less. 

Although there is the potential for an exceedance of long-term, non-cancer risks, any 

increase in air exchanges in the treatment facility should alleviate this concern. In addition, the 

increased air exchanges will likely decrease the cancer risk for all occupational activities. It 

should be noted that treatment of musical instruments are not expected to increase worker 

exposure to ETO in contract treatment facilities since these facilities simultaneously sterilize 

medical instruments. 

Since its inception in 2006, Encore, Etc. has processed four chamber loads of musical 

instruments, representing approximately 3,000 cubic feet of processing capacity. It is estimated 

that sterilizing 3,000 cubic feet of musical instruments consumed 0.002 percent of the industry 

capacity available in 2003. In their comments, Encore Etc. estimated a one hundred fold 

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increase in instrument sterilization would use approximately 0.197 percent of the total industry 

capacity. 

The Agency does not currently have enough information to quantify the benefits of ETO 

use to sterilize musical instruments; however, ETO is an effective antimicrobial treatment that 

likely will decontaminate musical instruments. Because of the low volume of contract treatment 

capacity needed to treat the musical instruments, the Agency believes there is no appreciable 

increase in risk to workers beyond what they experience while sterilizing medical instruments. 

However, if the demand for sterilization of musical instruments increases significantly 

(i.e., the number of contract sterilization facilities increases to accommodate the increased 

demand), the registrant must notify the Agency, initiating further evaluation of the risks 

associated with the increased ETO use. In addition, the Agency needs data to further document 

the presence of pathogens in the internal surfaces of musical instruments. The registrant has 

agreed to submit a study of this nature to the Agency. The Agency finds the sterilization of 

musical instruments eligible for reregistration. 

As stated above, to protect workers who do not perform tasks for which a respirator is 

required to be worn on a daily basis in a contract sterilization facility, the Agency is specifying 

an employee safety and awareness training to be given to all employees (including office staff), 

and encourages each facility to increase its aeration to reduce ambient levels of ETO. 

To reduce potential long-term non-cancer and cancer risks to workers who did not enter 

the aeration rooms (i.e., those who did not wear respirators), the Agency encourages contract 

facilities to use Best Management Practices to provide additional aeration in treatment facilities. 

c. Library and Museum Artifact Use 

Current Use Pattern 

Library and museum artifacts are treated with ETO to control various pests, such as fungi 

and insects. Current use of ETO for archival material appears to be infrequent and limited to 

important preservation needs when alternatives are considered ineffective. This use accounts for 

less than 1 percent of the total annual usage of ETO for commercial fumigation/sterilization. 

ETO treatment of library and museum artifacts generally occurs in contract sterilization 

facilities located across the United States. Application occurs in vacuum or gas tight chambers 

designed for use with ETO. 

Risks of Concern 

Since library and museum artifacts are treated with ETO in contract sterilization 

facilities, it is assumed that estimated exposures and risks for the medical contract sterilization 

facilities cover the library and museum artifact uses. 

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Stakeholder Involvement 

In April 2007, EPA staff consulted with the preservation specialist at the Library of 

Congress to discuss ETO use for library and museum articles. The Library of Congress 

occasionally sends mold-infested collection items to contract sterilization facilities for ETO 

fumigation. The Library of Congress also stipulates requirements for aeration of the ETO treated 

materials. Insect infested materials are treated at a Library of Congress fumigation chamber 

where infested collections are subjected to a strong vacuum for a few days to kill the insects and 

their eggs. ETO is not used in this situation. 

No written comments were submitted to the Agency regarding ETO use on library and 

museum artifacts during any phases of the public participation process. 

Alternatives and Benefits 

Insects and molds are problems for library and museum artifacts. Prevention is the most 

desirable means of controlling pests. Managing temperature and humidity and light are standard 

measures. In addition, various non-chemical treatments are often used and chosen depending on 

the artifacts and pests. Methods include cold treatment, heat treatment, microwave treatment, 

and natural substances, such as exposure to cedar products. When pesticides are required, 

usually standard pesticides available to homeowners are used. However, sometimes an artifact is 

considered to need fumigant treatment. Common fumigants have been methyl bromide, sulfuryl 

fluoride, carbon dioxide, and ETO. Fumigants are chosen based on the fumigant and artifact 

characteristics. 

The current use of ETO for archival material and museum artifacts appears to be 

infrequent and limited to important preservation needs where alternatives are considered 

ineffective. Similarly, museums appear to use ETO only when other treatments are not 

acceptable. It appears that museum pieces are sent to contract sterilization facilities when ETO 

is used. 

For additional information, refer to the Agency’s Qualitative Assessment of Alternatives 

for Ethylene Oxide Uses (DP316692) and the BEAD response to comments documents which 

are available in the public docket EPA-HQ-OPP-2005-0203 located on-line at 

<http://www.regulations.gov/>. 

Risk Reduction Measures in Place 

Since ETO use on library and museum artifacts generally occurs in contract sterilization 

facilities, risk reduction measures described above for medical contract sterilization facilities 

would be the same for this application. In addition, the Library of Congress suggests that 

material designated for ETO-treatment should be conducted by contract sterilization facilities in 

accordance with EPA and OSHA safety regulations. The National Park Service also 

recommends to conservation specialists that they ensure safety regulations are followed when 

ETO is used. 

Page 35 of 68 
EPA Decision 

ETO treatment of library and museum artifacts occurs in contract sterilization facilities 

with risk reduction measures in place. However, ETO has the potential to cause adverse health 

effects to workers. Given the infrequent use of ETO for library and museum artifacts and its 

very minor contribution to the total annual usage of ETO for commercial fumigation/sterilization 

(less than 1 percent), EPA believes that the benefit to society of preserving historical artifacts for 

future generations outweighs potential risks of ETO for this use. Given that, the Agency has 

determined that ETO use on library and museum artifacts in contract sterilization facilities is 

eligible for reregistration. 

As stated above, to protect workers who do not perform tasks for which a respirator is 

required to be worn on a daily basis in a contract sterilization facility, the Agency is specifying 

an employee safety and awareness training to be given to all employees (including office staff), 

and encourages each facility to increase its aeration to reduce ambient levels of ETO. 

To reduce potential long-term non-cancer and cancer risks to workers who did not enter 

the aeration rooms (i.e., those who did not wear respirators), the Agency encourages contract 

facilities to use Best Management Practices to provide additional aeration in treatment facilities. 

d. Cosmetics Use 

Current Use Pattern 

ETO is used during the processing of some gums and dyes in manufacturing cosmetics to 

reduce microbial activity of organisms that can contaminate ingredients. In addition, other 

associated products such as packaging material for cosmetics may be treated with ETO. 

Ingredients that are treated with ETO are sent to contract sterilizing facilities for the fumigation 

treatment (Czerkowicz et al., 1996). This use accounts for less than 1 percent of the total annual 

usage of ETO for commercial fumigation/sterilization. 

Risks of Concern 

Since cosmetic ingredients are treated with ETO in contract sterilization facilities, it is 

assumed that estimated exposures and risks for the medical contract sterilization facilities cover 

the cosmetics uses. 

Stakeholder Involvement 

In February 2008, EPA staff coordinated with FDA on ETO’s use in the cosmetics 

industry. FDA provided information on the role of ETO as an ethoxylating agent for the 

synthesis of ethoxylated surfactants that are used in cosmetic products. FDA is aware of the 

potential for residual ETO to be present in ethoxylated surfactants and cosmetic products 

containing these ingredients. FDA is developing an analytical method to measure ETO and 1,4-

dioxane (a reaction product of ETO formed during the ethoxylation process in cosmetics). In 

addition, there are many cosmetic ingredients that are derivatives of EG. Some unreacted EG 

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present in a cosmetic ingredient may also be present in a finished cosmetic product (e.g., 

polyethylene glycol ingredients that are commonly found in cosmetics may have some unreacted 

EG present). 

No written comments were submitted to the Agency regarding ETO’s use in the 

cosmetics industry during any phase of the public participation process. 

Alternatives and Benefits 

Previous OPP analyses from 1996 suggested that while some ingredients in cosmetics are 

treated with ETO, effective alternatives exist for at least some ingredients. These alternatives 

include irradiation and dry heat. 

In a survey of 12 cosmetic companies conducted by Mitre Corporation nearly 30 years 

ago, 58 percent rated ETO “essential” to reducing microbial contamination, while 33 percent 

said ETO was “moderately essential” (referenced in Czerkowicz et al., 1996). It is not known 

whether the survey results reflect the current attitude towards ETO use in the cosmetics industry. 

No updated information is available. 

Risk Reduction Measures in Place 

Since ETO use on cosmetic ingredients generally occurs in contract sterilization facilities, 

risk reduction measures described above for medical contract sterilization facilities would be the 

same for this application. 

EPA Decision 

ETO treatment of cosmetics occurs in contract sterilization facilities with risk reduction 

measures in place. However, ETO has the potential to cause adverse health effects to workers. 

Given the minor contribution to the total annual usage of ETO for commercial 

fumigation/sterilization (less than 1 percent) from cosmetics treatment, EPA believes that the 

benefit to society of reducing potential infection from the application of cosmetic products 

outweighs potential risks of ETO for this use. Given that, the Agency has determined that ETO 

use on cosmetics in contract sterilization facilities is eligible for reregistration. 

As stated above, to protect workers who do not perform tasks for which a respirator is 

required to be worn on a daily basis in a contract sterilization facility, the Agency is specifying 

employee safety and awareness training to be given to all employees (including office staff), and 

encourages each facility to increase its aeration to reduce ambient levels of ETO. 

To reduce potential long-term non-cancer and cancer risks to workers who did not enter 

the aeration rooms (i.e., those who did not wear respirators), the Agency encourages contract 

facilities to use Best Management Practices to provide additional aeration in treatment facilities. 

Page 37 of 68 
e. Spice Use 

Current Use Pattern 

ETO is used in the United States during the processing of spices to reduce microbial and 

insect activity. Several pathogens have been identified as contaminants of herbs and spices, most 

commonly: Bacillus spp., Clostridium perfringens, Escherichia coli, Salmonella spp., Klebsiella 

pneumoniae, and Staphylococcus aureus (e.g., CDC, 2001; ANZFA, 2002; Vij et al., 2006). 

Most prominent for concern in spices is contamination by Salmonella, especially when spices are 

applied to uncooked food or applied to food after the food has been cooked. 

Each year in the United States approximately 32 percent of whole spices (including 

herbs) are treated with ETO. ETO treatment primarily depends on whether microbial or insect 

contamination has been found above acceptable levels and specific spice characteristics. 

Treatment includes spices grown domestically as well as those imported into the United States. 

An estimated maximum of approximately 800,000 pounds are used annually for fumigation of 

herbs and spices. This represents about 10 percent of the total ETO sterilization market. 

The ETO fumigation process for spices is essentially identical to the sterilization process 

used for medical equipment/devices. Despite the fact that the sterilization process is so similar, 

the same chamber cannot be used for both medical equipment/devices and spice fumigation. 

Chambers used to treat spices retain the odors associated with these commodities and these odors 

are often transferred to materials treated subsequently in the same chamber. In addition, if the 

packaging for herbs and spices is damaged, herbs and spices can spill in the treatment chamber. 

Contract sterilizers avoid having residual herbs and spices and medical devices in the same area. 

For these reasons, the treatment of spices and medical equipment/devices are distinct and 

separate (Abt, 2006). 

Spice treatments generally occur in bulk at contract sterilization facilities that handle 

multiple pallet sterilizations located across the United States. The American Spice Trade 

Association (ASTA) has stated that there are 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. ETO treatment occurs in vacuum or gas tight 

chambers designed for use with ETO. 

Risks of Concern 

As discussed in Section 3.2 of the Addendum to the Occupational and Residential 

Exposure Assessment and Recommendations for the Reregistration Eligibility Decision (RED) 

for Ethylene Oxide, non-cancer risk estimates, calculated as MOEs are not of concern (i.e., short-

/intermediate- and long-term MOEs > 30). However, ETO has the potential to cause adverse 

health effects to workers. Potential cancer risks for workers range from 2.1 x 10-5 to 8.4 x 10-4. 

Page 38 of 68 
Stakeholder Involvement 

In March 2005, EPA conducted a site visit of the Baltimore Quality Assurance (BQA) 

spice sterilization facility in Baltimore, Maryland. The site visit focused on the use of ETO for 

spice sterilization. Agency staff observed ETO sterilization equipment, the loading of a 

sterilizer, spice packaging materials and various spice handling occupations in the facility. 

Safety protocols, emergency procedures, and alternative sterilization options were discussed. 

In December 2005, OSHA provided monitoring data for spice treatment facilities from its 

IMIS to be incorporated into EPA’s risk assessment. 

EPA also participated in a meeting with USDA, ETO registrants and ETO stakeholders in 

December 2005. Representatives from Honeywell Inc., ARC, American Chemistry Council, 

ASTA , and medical interests presented their perspectives on the importance of ETO and the 

potential impacts of the worker exposure analysis in the preliminary risk assessment. 

In March 2008, EPA staff coordinated with FDA on ETO’s use in the spice industry from 

a public health perspective. In summary, FDA representatives agreed that ETO was an important 

tool for controlling Salmonella on spices although FDA representatives discussed the relatively 

low risk of public outbreak associated with contaminated spices because spices are not consumed 

in large quantities and spices are usually cooked prior to consumption. 

During Phases 5 and 6 of the Public Participation Process, in addition to the written 

comments received from respondents as mentioned in section IV. B. above, the Agency met with 

and received comments from the ASTA with specific knowledge relating to ETO use on spices. 

In particular, these stakeholders have provided actual worker exposure monitoring data to refine 

the risk estimates for spice sterilization facilities and a description of existing mitigation 

measures that are used in ETO contract sterilization facilities. 

Alternatives and Benefits 

Methods of treating spices depend on the particular characteristics of the spice and 

whether the spice can withstand a particular treatment without significant degradation in quality. 

In the United States, various methods are available to reduce microbial and insect activity in 

spices including heat, irradiation, good agricultural practices, ETO, and propylene oxide. 

• Heat. Spices require intact volatile compounds, which can be destroyed by heat. There 

must be a balance between managing pathogens with heat and maximizing flavor. 

Depending on the spice, heat may or may not be an effective treatment. 

• Irradiation. According to the Food and Agricultural Organization of the United Nations, 

approximately 80,000 metric tons of spices were irradiated worldwide in 2000. 

However, while registered for use on spices in most of Europe, Australia, and the United 

States, irradiation currently appears to be an underused technology, due primarily to 

consumer perceptions of adverse health side-effects. Organic certification standards in 

Page 39 of 68 
the United States (NOP, 2002) do not allow the use of irradiation for herbs and spices. 

McCormick, the largest United States spice dealer, does not irradiate its products. 

• Good Agricultural Practices (GAPs). Procedures such as GAP, Good Manufacturing 

Practices (GMP) and principles of Hazard Analysis and Critical Control Point (HACPP) 

for food safety are used by many food industries throughout the world and are generally 

accepted by the spice industry in the United States. GAP, GMP and HACPP standards 

are well-established in the meat, poultry, dairy, and egg industries and in production of 

fresh fruits and vegetables to ensure food safety for particularly susceptible products. 

These procedures serve to meet FDA and industry requirements. GAP, GMP, and 

HACPP practices, which include high standards for clean production and harvesting 

practices, clean post-harvest practices, appropriate drying and storage facilities, are the 

first line of defense against contaminated products. Spices are routinely cleaned 

mechanically to remove unacceptable and contaminating material. 

• Propylene Oxide (PPO). Another fumigant used on spices, PPO, may be effective 

against some insect infestations, but is not regarded as effective in reducing microbial 

contamination. Further PPO has been banned for use on spices in the European Union. 

Many countries have banned the use of ETO on spices and other food due to concerns for 

public exposure to ETO and its reaction products. Countries have banned the food use of ETO 

due to its classification as a known human carcinogen and genotoxic agent. According to the 

Decision Guidance Document on Ethylene Oxide for the Operation of the Interim Prior Informed 

Consent (PIC) Procedure for Banned or Severely Restricted Chemicals in International Trade 

(FAO/UNEP, 2001), some of the countries that have banned the use of ETO on spices (and other 

foods) include: Belize, China, the European Union (EU, currently numbering 25 countries), 

Australia, and Japan. EPA assessed ETO and its reaction products (EBH, ECH, and EG) for 

dietary (oral) exposure and risk in the 2006 TRED. In the TRED, the Agency determined that 

dietary risk to ETO and its reaction products are below the Agency’s level of concern after risk 

mitigation options were adopted. In addition, the Agency concluded that risks from aggregate 

exposure to ETO are not of concern and the tolerances for ETO and its reaction product, ECH, 

were reassessed as safe. 

Because a single end-product decontamination treatment is not sufficient to address both 

microbial contamination and preservation of spice quality, “[A] combination of preventative 

hygiene control measures at the production level, and end-product treatments is needed” 

(ANZFA, 2002). Since most countries no longer allow the use of ETO, or the import of spices 

that have been treated with ETO, the most commonly used alternatives to ETO for spices are 

non-chemical, including improved agricultural practices, product selection, and with some 

commodities, heat. Irradiation can be an effective treatment, and is permitted by numerous 

countries, but has not been universally adopted primarily due to consumer questions of the 

process. 

The threat of food-borne contamination and the potential for serious illness is a concern 

for government agencies, food manufacturers, and the general public. Most reported cases of 

microbial contamination of foods occur on fresh and processed fruits and vegetables, meats, 

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seafood, dairy, and eggs (CDC, 2001). Few foods recalls in the United States have involved 

spices. It is not known if the recalled spices were, or were not, treated with ETO. The United 

States imports spices from more than 6,100 manufacturers in 129 countries. Of the few recalled 

spices most were contaminated with Salmonella serotypes (Vij et al., 2006). A review was 

recently conducted of spice recalls that were recorded by the FDA Center for Food Safety and 

Applied Nutrition (CFSAN) from 1969 through 2003. A total of 21 recalls were reported, five 

recalls occurred between 1971 and 1996, and 16 recalls occurred between 2001 and 2003. 

Twelve spices (including sesame seeds) were involved in the recalls (Vij et al., 2006). One 

contaminated spice batch (bay leaves) was infested with Listeria monocytogenes, 20 batches of 

various spices were infested with nine Salmonella serotypes. Of the known origin of 15 of the 

recalled spices, 12 were imported to the United States and three were grown domestically. It is 

not known if any illnesses were associated with the contaminated spices, although these spices 

could have caused illnesses that were not reported. The CDC estimates that for every case of 

Salmonella that is diagnosed there are 38 cases undiagnosed or reported (Mead, et al., 1999). 

Consequently, it is difficult to estimate the extent to which ETO prevents potential food-borne 

illness associated with untreated herbs and spices. 

For additional information, refer to the Agency’s Qualitative Assessment of Alternatives 

for Ethylene Oxide Uses (DP316692) and the BEAD response to comments documents which 

are available in the public docket EPA-HQ-OPP-2005-0203 located on-line at 

<http://www.regulations.gov/>. 

Risk Reduction Measures in Place 

As described above, the ETO fumigation process for spices is essentially identical to the 

sterilization process used for medical equipment/devices and occurs in contract sterilization 

facilities. As such, most of the risk reduction measures discussed for medical contract 

sterilization facilities are used in spice only contract sterilization facilities. In addition, spice 

only contract sterilization facilities typically use single chamber technology as specified in the 

2006 TRED. As such, the treatment cycles are designed to use more air or nitrogen washes than 

many facilities using conventional ETO treatment processes. 

Other measures typically in place in spice sterilization facilities includes a ventilation 

design that moves air from areas of low potential risk toward areas of potentially higher risk. 

Offices in the spice sterilization facilities are generally positively pressurized to prevent airborne 

concentrations from entering the office work areas. Facilities also establish clearly signed 

“restricted areas” to prevent workers or visitors from entering areas where they are not 

authorized and could be exposed to a higher risk for sterilization activities (Ruckert, 2008). 

EPA Decision 

Based on current worker exposure data and toxicity estimates, ETO has the potential to 

cause adverse health effects to workers through long-term exposure. Potential cancer risks for 

spice workers range from 2.1 x 10-5 to 8.4 x 10-4. 

EPA policy for non-dietary risks in the 10-5 to 10-4 range is to determine whether the 

benefits of use outweigh the risks and to seek ways to mitigate unacceptable risks. This policy 

Page 41 of 68 
specifically allows for the consideration of the weight of scientific evidence regarding 

carcinogenicity, number of people exposed, and benefits associated with the pesticide under 

review. 

In the case of the use of ETO on herbs and spices, this use makes up 10 percent of total 

ETO use for pesticidal purposes. 

Although many countries have banned the use of ETO on spices and other food due to 

dietary concerns for public exposure to ETO and its reaction products, EPA believes that use of 

ETO on spices is safe. The Agency analyzed the dietary risks associated with ETO and its 

reaction products as part of the 2006 TRED. These risks were considered not of concern after 

risk mitigation options were adopted. One of the risk mitigation options adopted in the TRED is 

the transition of the spice industry to single chamber fumigation facilities that have demonstrated 

to result in residue levels which are lower than those that result from sterilization using 

conventional sterilization methods. It is also believed that single chamber fumigation has the 

potential to reduce worker exposure to ETO. 

Food-borne illness is a concern of the Agency. As stated above, there were 21 spice 

recalls reported between 1969 and 2003, five recalls occurred between 1971 and 1996, and 16 

recalls occurred between 2001 and 2003. Most of the recalled spices were contaminated with 

Salmonella serotypes. The CDC estimates that for every case of Salmonella that is diagnosed 

there are 38 cases undiagnosed or reported (Mead, et al., 1999). Consequently, it is difficult to 

estimate the extent to which ETO prevents potential food-borne illness associated with untreated 

herbs and spices. The Agency has not received information that identifies ETO as primarily 

responsible for the relatively low contamination rates attributed to spices. However, since ETO 

treatment of herbs and spices is effective in reducing microbial activity, it is assumed that it also 

reduces the potential of food-borne illness. 

Alternatives to ETO exist for antimicrobial treatment of spices (e.g., heat, irradiation, 

PPO), although none of the alternatives can be considered a single replacement for ETO for all 

spices and pests currently treated by ETO. 

Given the range of potential risk following worker exposures that require 35 years of 

ETO exposure and in light of the benefit of reducing potential food-borne illness, the lack of a 

single replacement for ETO, and risk reduction measures already in place, the Agency has 

determined that ETO use on herbs and spices is eligible for reregistration with the 

implementation of the following mitigation. 

• Employee safety and awareness training is required for all employees (including office 

staff). Information and training is to be provided to all employees in the facility at the 

time of initial assignment and annually thereafter. This training is intended to ensure that 

all facility employees are aware of the risks associated with ambient levels of ETO from 

sterilization processes and is to include, at a minimum, the following information: 

3⁄4 The most recent monitored ambient levels of ETO in the facility. 

3⁄4 The potential health effects from the levels of ETO in the facility. 

Page 42 of 68 
3⁄4 The emergency response plan and how to respond in an emergency. 

3⁄4 The availability of the Material Safety Data Sheet and other materials related to 

the health hazards of exposure to ETO. 

• Increased facility aeration is encouraged to reduce ambient levels of ETO. Achieving an 

ambient level of 0.25 ppm or less (measured as a daily time-weighted average) could 

eliminate potential long-term non-cancer risks to workers that do not wear respirators as 

part of their job duties. An ambient level of 0.25 ppm of ETO (measured as a daily timeweighted average) would also be expected to result in potential cancer risks of 1.3 x 10-4 

to 1.1 x 10-3. Achieving ambient ETO levels less than 0.25 ppm would potentially result 

in lower cancer estimates. Future monitoring efforts at contract sterilization facilities 

should include the entire facility (including office space, break areas) to have accurate 

information regarding exposure of employees who are not wearing respirators as part of 

their daily routine. 

f. Beekeeping Use 

Current Use Pattern 

The use of ETO for beehive material currently is limited to a state-managed facility in 

North Carolina via a Special Local Needs (SLN) registration. It is used to fumigate beehive 

equipment (e.g., woodenware boxes and frames) and wax or plastic combs that are contaminated 

with the bacteria Paenibacillus larvae, the cause of American Foulbrood Disease. The 

beekeeping use accounts for less than 1 percent of the total annual usage of ETO for commercial 

fumigation/sterilization. 

The North Carolina Department of Agriculture and Consumer Affairs (NCDA&CS) uses 

2 vacuum tight chambers designed for use with ETO. One chamber (48” x 54” x 84”) is located 

outside on a covered concrete pad. A second chamber, 1/3 the size of the larger chamber, also is 

located outside. 

Beekeeping equipment is treated 30 to 40 times per year in North Carolina. Most of the 

treatments are done between December and March. The larger chamber is loaded manually by 

one licensed state employee and occasionally assisted by one of four associates. A different 

licensed state employee is the primary operator of the smaller chamber. A total of 6 employees 

in NC are involved with the ETO use for sterilization/fumigation of beekeeping equipment. 

Risks of Concern 

Exposures and risks associated with fumigation of beekeeping equipment are expected to 

be similar to those described above for spice fumigation considering the similarities in the 

fumigation process (e.g., chamber loading, gas introduction). 

Based on the limited number of ETO applications (30 to 40 times per year) for the North 

Carolina beekeeping use, ETO exposure for this use is not of chronic duration. Therefore the 

short-/intermediate-term endpoint for the non-cancer assessment would apply to this use. NonPage 43 of 68 
10-5 

cancer risk estimates, calculated as MOEs are not of concern (i.e., short- and intermediate-term 

MOEs > 30). 

Since worker exposures are considered similar to spice fumigation, the beekeeping use 

information (i.e., 30 to 40 times per year) is applied to the recently submitted worker exposure 

data for spice industry workers. This yields an estimated cancer risk range of 1.1 x 10-5 to 9.2 x 

. 

Stakeholder Involvement 

In April 2007, EPA staff consulted with the state apiarists in Maryland and Maine to get 

information about their previous ETO use, and with the NCDA&CS to learn more about the 

current use of ETO in North Carolina. State representatives described specifically what is 

treated (or was historically treated in the case of Maryland and Maine) with ETO, when 

treatments occur, how treatments typically occur, and alternatives to ETO when disease is 

present. 

EPA has also coordinated with the United States Department of Agriculture – 

Agricultural Research Service (USDA-ARS), Bee Research Laboratory. In July 2007, the 

USDA-ARS Bee Research Laboratory provided information on methods used to control and 

decontaminate infected bee equipment, including the use of ETO. The USDA-ARS Bee 

Research Laboratory views ETO as a useful tool to the beekeeping industry for fumigating 

beekeeping equipment contaminated with American Foulbrood disease. 

During Phases 5 and 6 of the Public Participation Process, the Agency received 

comments from the Maryland Department of Agriculture, NCDA&CS, and the North Carolina 

State Beekeepers Association, with specific knowledge relating to ETO use on beekeeping 

equipment. In particular, the North Carolina Department of Agriculture and Consumer Affairs 

provided detailed information on the ETO treatment process used in North to refine the risk 

estimates for the beekeeping use. 

Alternatives and Benefits 

Alternatives are available to manage the American Foulbrood Disease effectively, and are 

used throughout the United States. The alternatives to ETO consist of scorching the supers, tops, 

and bottoms with a portable propane torch. Contaminated frames and combs are burned. 

Another method is to boil all hive material, including frames, combs, and supers in a lye 

solution. To retain the use of hive material, some choose to fumigate with ETO, where available. 

Cost saving is a major reason for beekeepers to use ETO, because some hive material 

may have to be destroyed in severe cases of American Foulbrood Disease. The use of ETO for 

beehive material may be useful for severely infested hives where destruction of frames, as an 

alternative, would be costly. However, alternatives are clearly available to manage the disease 

effectively, as shown by the small use of ETO for beekeeping purposes in the United States. 

Page 44 of 68 
10-5 

For additional information, refer to the Agency’s Qualitative Assessment of Alternatives 

for Ethylene Oxide Uses (DP316692) and the BEAD response to comments documents which 

are available in the public docket EPA-HQ-OPP-2005-0203 located on-line at 

<http://www.regulations.gov/>. 

Risk Reduction Measures in Place 

NCDA&CS vents the ETO treatment chamber prior to unloading. A vacuum is drawn on 

the chamber and fresh air is released into the chamber 3 times. It is vented through an 80 foot 

PVC pipe stack 80 feet from the valve and approximately 20 feet above the ground. During the 

unloading process, the chamber door is always located between the employee and the chamber 

opening. The door serves as a partial barrier between the employee and any ETO remaining in 

the chamber. 

NCDA&CS allows the beehives to aerate in the ETO chamber for 60 minutes after the 

chamber door is opened. This delay allows ETO to dissipate from the wood and the honey 

combs. In addition, after the beehives are removed from the chamber, they are further aerated 

before they are returned to their owner. 

No respirators or other personal protective equipment are worn during the ETO treatment 

process. 

EPA Decision 

ETO has the potential to cause adverse health effects to workers. Potential cancer risks 

for workers associated with the beekeeping use in North Carolina range from 1.1 x 10-5 to 9.2 x 

. 

EPA policy for non-dietary risks in the 10-5 to 10-4 range is to determine whether the 

benefits of use outweigh the risks and to seek ways to mitigate unacceptable risks. This policy 

specifically allows for the consideration of the weight of scientific evidence regarding 

carcinogenicity, number of people exposed, and benefits associated with the pesticide under 

review. 

In the case of the use of ETO on beekeeping equipment, this use makes up less than 1 

percent of total ETO use for pesticidal purposes. There are 2 chambers currently used to treat 

beekeeping equipment in North Carolina. 

The Agency has determined that there are economic benefits of ETO use on beekeeping 

equipment and, as specified above, losing its use would involve additional costs to beekeepers in 

North Carolina, some of which can be quantified. Given the infrequent use of ETO for 

beekeeping, its very minor contribution to the total annual usage of ETO for commercial 

fumigation/sterilization (less than 1 percent), and the cost savings seen in North Carolina, the 

Agency has determined that ETO use on beekeeping equipment is eligible for reregistration with 

the implementation of the following mitigation. 

Page 45 of 68 
• Respirators to be worn during chamber opening and unloading and tank 

change/maintenance activities. This risk mitigation measure is expected to lower worker 

exposure to ETO and result in reduced long-term non-cancer and potential cancer risk 

estimates for workers. 

It should be noted that in the future if additional states receive SLN registrations for the 

use of ETO on beekeeping equipment, the Agency will require any such registrations to include 

the mitigation measures stated above. 

Page 46 of 68 
V. What Registrants Need to Do 

The Agency has determined that products containing the active ingredient ETO are 

eligible for reregistration provided that the risk mitigation measures outlined in this document 

are adopted and label amendments are made to reflect these measures. The Agency intends to 

issue DCIs for generic (technical grade) data and product-specific data. Generally, registrants 

will have 90 days from receipt of a generic DCI to complete and submit response forms or 

request time extension and/or waiver requests with a full written justification. The DCIs will 

include specific requirements and instructions on how to respond. Table 3 below presents the 

additional generic data the Agency intends to require for ETO to confirm the decision that 

products containing the active ingredient ETO are eligible for reregistration. For productspecific DCIs, registrants will have eight months from receipt of the DCI to submit data and to 

submit amended labels. In order for products containing the active ingredient ETO to be eligible 

for reregistration, all product labels must be amended to incorporate the specific changes and 

language presented in Table 4 below. Table 4 also describes how the required language should 

be incorporated. 

A. Manufacturing-Use Products 

1. Additional Generic Data Requirements 

The generic database supporting the reregistration of ETO has been reviewed and 

determined to be substantially complete. However, EPA is requiring the following additional 

data to confirm the decisions presented in this RED. The Agency intends to issue a generic DCI 

for these data. 

Documentation of the presence of pathogens will provide useful information to the 

Agency to determine the types of pathogens that would remain and flourish inside of a musical 

instrument. The presence of these pathogens inside the instrument would make them potentially 

available for a musician to inhale into their lungs, possibly causing an illness. These data will be 

used to further refine the benefits analysis, allowing the Agency to understand the types of 

pathogens present inside of the musical instruments. 

After review and evaluation of the data, the Agency will be able to further refine the 

benefits analysis for ETO use to sterilize musical instruments. These data will inform the 

Agency about the types of pathogens that would remain inside the instrument without the ETO 

sterilization treatment. Although a DCI will be sent to the technical registrant, Encore, Etc., the 

distributor for the ETO musical instrument treatment, has agreed to conduct and submit the 

results of this study to the Agency. 

Table 3. . 

(GLN) 

Special Study 

Data Requirement for the Reregistration of ETO

Data Requirement New OPPTS Guideline Number 

Documentation of Presence of Pathogens in Internal Surfaces of Musical 

Instruments 

Page 47 of 68 
2. Labeling for Manufacturing-Use Products 

To ensure compliance with FIFRA, labeling for all manufacturing-use products (MUPs) 

should be revised to comply with all current EPA regulations, PR Notices, and applicable 

policies. The MUP labeling should bear the specific language presented in Table 4 below. 

B. End-Use Products 

1. Additional Product-Specific Data Requirements 

Section 4(g)(2)(B) of FIFRA calls for the Agency to obtain any needed product-specific 

data regarding the pesticide after a determination of eligibility has been made. The registrant 

must review previous data submissions to ensure they meet current EPA acceptance criteria and 

if not, commit to conduct new studies. If a registrant believes that previously submitted data 

meet current testing standards, then the study MRID numbers can be cited according to the 

instructions in the Requirement Status and Registrations Response Form provided for each 

product. The Agency intends to issue a separate product-specific DCI outlining specific data 

requirements. 

2. Labeling for End-Use Products 

To be eligible for reregistration, labeling changes are necessary to implement measures 

outlined in Section IV above. The specific changes and language are presented in Table 4 below. 

Generally, conditions for the distribution and sale of products bearing old labels/labeling will be 

established when the label changes are approved. However, specific existing stocks time frames 

will be established case-by-case, depending on the number of products involved, the number of 

label changes, and other factors. 

Page 48 of 68 
In order to be eligible for reregistration, amend all product labels to incorporate the risk mitigation measures outl

The following table describes how language on the labels should be amended. 

Table 4. Summary of Labeling Changes for ETO 

Description Amended Labeling Language for Manufacturing Use Products Placem

Manufacturing Use Products 

For all Manufacturing Use Products 

“Only for formulation into a biocide, fungicide, fumigant, herbicide, insecticide, or rodenticide for the following use(s) [fill blank only with those uses that are being supported by MP registrant].” 

Directions for Use 

One of these statements may be added to a label to allow reformulation of the product for a specific use or all additional uses supported by a formulator or user group 

“This product may be used to formulate products for specific use(s) not listed on the MP label if the formulator or user group has complied with U.S. EPA submission requirements regarding support of such use(s).” “This product may be used to formulate products for any additional use(s) not listed on the MP label if the formulator or user group has complied with U.S. EPA submission requirements regarding support of such use(s).” 

Directions for Use 

Environmental Hazards Statements Required by the RED and Agency Label Policies 

"Do not discharge effluent containing this product into lakes, streams, ponds, estuaries, oceans, or other waters unless in accordance with the requirements of a National Pollution Discharge Elimination System (NPDES) permit and the permitting authority has been notified in writing prior to discharge. Do not discharge effluent containing this product to sewer systems without previously notifying the local sewage treatment plant authority. For guidance contact your State Water Board or Regional Office of the EPA." 

Precautionary Stat

End Use Products Intended for Occupational Use 

PPE Requirements for all products 

“Personal Protective Equipment (PPE)” “Some materials that are chemical-resistant to this product are” (registrant inserts correct chemical-resistant material). “If you want 

more options, follow the instructions for category” [registrant inserts A,B,C,D,E,F,G,or H] “on an EPA chemical-resistance category selection chart." 

Immediately followPrecautionary StatHumans and Dom

Page 49 of 68 
PPE Requirements for 

beekeeping use 

“All handlers must wear at a minimum:> Long-sleeved shirt and long pants, > Shoes plus socks, > Chemical-resistant gloves, and > when the ambient ETO concentration is 1 to 50 ppm, full-facepiece respirator with ETO approved canister, front or back mounted, > when the ambient ETO concentration is 50 to 2,000 ppm, (1) positivepressure supplied-air respirator equipped with full-facepiece, hood, or helmet; or (2) continuous-flow supplied-air respirator (positive-pressure) equipped with hood, helmet, or suit, > when the ambient ETO concentration is >2,000 ppm or unknown (e.g., emergency situations), (1) positive-pressure self-contained breathing apparatus equipped with full-facepiece; or (2) positive-pressure fullfacepiece supplied-air respirator equipped with an auxiliary positivepressure self-contained breathing apparatus. When handlers could have eye or skin contact with ETO or ETO solutions, such as during maintenance and repair, vessel cleaning, or cleaning up spills, they must wear: > Chemical-resistant attire, such as an apron, protective suit, or footwear that protects the area of the body that might contact ETO or ETO solutions, and >Face-sealing goggles, a full face shield, or a full-face respirator.”

“Personal Protective Equipment (PPE)” In the PPE section 

“Some materials that are chemical-resistant to this product are” (registrant inserts correct chemical-resistant material). “If you want 

more options, follow the instructions for category” [registrant inserts A,B,C,D,E,F,G,or H] “on an EPA chemical-resistance category selection chart." 

“All handlers must wear at a minimum: 

Page 50 of 68 
> Long-sleeved shirt and long pants, 

> Shoes plus socks, and > Chemical-resistant gloves. > When opening and unloading a chamber and during tank change/maintenance activities, a full-facepiece respirator with ETO approved canister that is front or back mounted is required. 

User Safety Requirements 

1. Follow the respirator manufacturer’s user’s instructions for changing 

canisters. 

In the PPE section 

2. Respirators must be fit-tested and fit-checked using a program that 

conforms to OSHA’s requirements (see 29CFR Part 1910.134). 

3. Respirator users must be trained using a program that confirms to 

OSHA’s requirements (see 29CFR Part 1910.134). 

4. Respirator users must be examined by a qualified medical 

practitioner to ensure physical ability to safely wear the style of respirator to be worn. A qualified medical practitioner is a physician or other licensed health care professional (PLHCP) who will evaluate the ability of a worker to wear a respirator. The initial evaluation consists of a questionnaire that asks about medical conditions (such as a heart condition) that would be problematic for 

respirator use. If concerns are identified, then additional evaluations, such as a physical exam, might be necessary. The initial evaluation must be done before respirator use begins. It does not need to be repeated unless the health status or respirator use conditions change (see 29CFR Part 1910.134). 

User Safety “Follow manufacturer's instructions for cleaning/maintaining PPE. If no Precautionary StatRecommendations such instructions for washables exist, use detergent and hot water. Keep Humans and Dom

and wash PPE separately from other laundry.” immediately follow

requirements 

User Safety “User Safety Recommendations Precautionary Stat

Page 51 of 68 
Recommendations 

Users should wash hands before eating, drinking, chewing gum, using tobacco, or using the toilet. Users should remove clothing/PPE immediately if pesticide gets inside. Then wash thoroughly and put on clean clothing. Users should remove PPE immediately after handling this product. Wash the outside of gloves before removing. As soon as possible, wash thoroughly and change into clean clothing.” 

Hazards to HumanAnimals immediatEngineering Contr(Must be placed in 

Environmental Hazards "Do not discharge effluent containing this product into lakes, streams, 

ponds, estuaries, oceans, or other waters unless in accordance with the 

Precautionary Statfollowing the User 

requirements of a National Pollution Discharge Elimination System (NPDES) permit and the permitting authority has been notified in writing 

Recommendations 

prior to discharge. Do not discharge effluent containing this product to sewer systems without previously notifying the local sewage treatment plant authority. For guidance contact your State Water Board or Regional Office of the EPA." 

Other Application Restrictions for products with directions for use in hospitals and healthcare facilities (Risk Mitigation) 

“In hospitals and healthcare facilities, Sterilization/fumigation with ETO must be performed only in vacuum or gas tight chambers designed for use with ETO. After February 28, 2010, a single chamber process is required for ETO treatment (sterilization and aeration are to occur in the same chamber) in hospitals and healthcare facilities.” 

Directions for Use 

Other Application Restrictions for products with directions for use in contract sterilization facilities (including medical, musical instruments, 

“In contract sterilization facilities, including facilities treating medical equipment and supplies, musical instruments, library/museum artifacts, cosmetics, and spices the following requirements must be followed: Sterilization/fumigation with ETO must be performed only in vacuum or gas tight chambers designed for use with ETO. 

Directions for Use 

Page 52 of 68 
library/museum 

artifacts, cosmetics, and spice use) (Risk Mitigation) Other Application Restrictions for products with directions for use in contract sterilization facilities: spice use (Risk Mitigation) 

Safety and awareness training is required for all employees including office staff. Information and training must be provided to all employees in the facility at the time of initial assignment and annually thereafter. The safety training must include, at a minimum, the following information: 1. the most recent monitored ambient levels of ETO in the facility; 2. the potential health effects from the levels of ETO in the facility; 3. the emergency response plan and how to respond in an emergency; 4. the availability of the Material Safety Data Sheet and other materials 

related to the health hazards of exposure to ETO. 

In order to reduce ambient levels of ETO, lengthy facility aeration is encouraged. Achieving an ambient level of 0.25 ppm (measured as a daily time-weighted average) greatly reduces potential long-term risks to employees not directly involved in the ETO applications. Air monitoring should include the entire facility including office space, break areas, and loading/unloading areas.” “After August 1, 2008, this product may only be applied to or on spices, dried vegetables or seasonings utilizing an ETO sterilization method that uses a single sterilization chamber to pre-condition and aerate with an alternating vacuum and aeration purging procedure. If you wish to employ an alternative method to that described below, you must contact the Environmental Protection Agency Office of Pesticide Programs for instruction on how to receive authorization.” “Place spices in the treatment chamber. Assure that the mixture of ETO and air is compatible with the chamber design, then, introduce into the chamber a concentration of ETO not to exceed 500 mg/L, with a dwell time not to exceed 6 hours. Then evacuate the gas from the chamber using a sequence of not less than 21 steam washes (injections and 

Directions for Use 

Page 53 of 68 
evacuations) between 1.5 PSIA (27” Hg) and 5.0 PSIA (20” Hg) while 

maintaining a minimum chamber temperature of 115° F.” 

Other Application “Do not treat combs containing honey.” Directions for Use Restrictions for products with directions for use in beekeeping (Risk Mitigation) Other Application Employers in facilities that use ETO must comply with all of the Directions for Use Restrictions requirements for ETO use specified in 29 CFR 1910.1047. Currently required in the 29 CFR 

Page 54 of 68 
VI. References 

Abt Associates, Inc. (Abt). 2006. Preliminary Evaluation of the Potential Adoption of the 

EOExpress® Method of Ethylene Oxide Sterilization of Medical Equipment, Spices, Herbs, 

and Seasonings. Prepared by Abt Associates, Inc. for the United States Environmental 

Protection Agency, Office of Pesticide Programs. January 17, 2006. 

Australia New Zealand Food Authority (ANZFA). 2002. Draft Assessment—Maximum Residue 

Limits of Application A445 [emergency use for ethylene oxide in herbs and spices]. 

<http://www.foodstandards.gov.au/_srcfiles/A445_FARs37.pdf>. 

Centers for Disease Control and Prevention (CDC). 2001. Outbreaks: 2001 diseases outbreaks 

due to bacterial etiologies. 

<http://www.cdc.gov/foodborneoutbreaks/us_outb/fbo2001/bacterial01.htm>. 

Chun, J. and T. Neeper-Bradley. 1993. Two-Generation Reproduction Study of Inhaled Ethylene 

Oxide Vapor in DC Rats: Lab Project Number: 91N0058. Unpublished study prepared by 

Bushy Run Research Center. 572 p. (MRID 42788101). 

Crowley, Matthew. 2008. Addendum to the Occupational and Residential Exposure Assessment 

and Recommendations for the Reregistration Eligibility Decision (RED) for Ethylene Oxide. 

Health Effects Division memorandum to Special Review and Reregistration Division. March 

24, 2008. 

Czerkowicz, T.J., Maurer, E.J., and Szymanski, C. 1996. Summary of benefits of ethylene oxide 

uses and evaluation of alternatives. United States Environmental Protection Agency, Office 

of Pesticide Programs, Biological and Economic Analysis Division memorandum to Special 

Review and Reregistration Division. January 17, 1996. 

Ethylene Oxide Sterilization Association (EOSA). 2007. Ethylene Oxide Sterilization: The 

Process and the Equipment. October 24, 2007. 

Food and Agriculture Organization of the United Nations (FAO), United Nations Environmental 

Programme (UNEP). 2001. Operation of the interim Prior Informed Consent (PIC) 

procedure for banned or severely restricted chemicals in international trade. Decision 

Guidance Document—Ethylene Oxide. Interim Secretariat for the Rotterdam Convention on 

the Prior Informed Consent Procedure for Certain Hazardous Chemicals and Pesticides in 

International Trade. Rome/Geneva, February, 2001. 

<http://www.fao.org/ag/AGP/AGPP/Pesticid/Default.htm>. 

Havery, Donald. 2008. Email providing information on the use of ETO in the cosmetics 

industry. Don Havery, Supervisory Chemist, Office of Cosmetics and Colors, Center for 

Food Safety and Applied Nutrition, United States Food and Drug Administration, 

Department of Health and Human Services, College Park, Maryland. February 22, 2008. 

Page 55 of 68 
Knee, Elizabeth. Ethylene Oxide SMART Meeting Minutes. United States Environmental 

Protection Agency, Office of Pesticide Programs, Special Review and Reregistration 

Division. July 16, 2001. 

Leighton, T. and C. Walls. 2008. Review of Calculated Ethylene Oxide Exposures for Ethylene 

Oxide Sterilization Plant Workers (MRID No. 47331801) Submitted in Support of the 

Occupational Exposure Assessment of the Antimicrobial Uses of Ethylene Oxide for the 

Reregistration Eligibility Decision (RED). United States Environmental Protection Agency, 

Office of Pesticide Programs, Antimicrobials Division memorandum to Special Review and 

Reregistration Division. March 26, 2008. 

Mead, P.S., L. Slutsker, V. Dietz, L.F. McCaig, J.S. Bresee, C. Shapiro, P.M. Griffin, and R.V. 

Tauxe. 1999. Food-Related Illness and Death in the United States. Emerging Infectious 

Diseases. Vol. 5, No. 5, September-October 1999. 

Murphy, Sheila. 2006. Letter from Dr. Sheila Murphy, Branch Chief, Infection Control Devices 

Branch, Division of Anesthesiology, General Hospital, Infection Control and Dental Devices, 

Office of Device Evaluation, Center for Devices and Radiological Health, United States Food 

and Drug Administration, Rockville, Maryland, to Dr. Debra Edwards, Director, Special 

Review and Reregistration Division, Office of Pesticide Programs, United States 

Environmental Protection Agency, Washington, DC. May 5, 2006. 

National Organic Program (NOP). 2002. Q & A (posted 10/16/2002). Agricultural Marketing 

Service, United States Department of Agriculture. 

<http://www.ams.usda.gov/nop/Q&A.html>. 

Ruckert, Edward. 2008. Letter from Edward Ruckert, Counsel to the American Spice Trade 

Association, Washington, DC, to Susan Bartow, Chemical Review Manager, Special Review 

and Reregistration Division, Office of Pesticide Programs, United States Environmental 

Protection Agency, Washington, DC. March 14, 2008. 

Snellings, W. M., C.S. Weil, and R.R. Maronpot. 1984. A subchronic inhalation study on the 

toxicologic potential of ethylene oxide in B6C3F1 mice. Toxicol and Appl. Pharmacol., 

76:510–518. 

United States Environmental Protection Agency (USEPA). 1994. Methods for derivation of 

inhalation reference concentrations and application of inhalation dosimetry. EPA/600/8-

90/066F. 

USEPA. 2005. Residual Risk Assessment for the Ethylene Oxide Commercial Sterilization 

Source Category. United States Environmental Protection Agency, Office of Air and 

Radiation, Emission Standards Division. August 10, 2005. 

Vij, V., Ailes, E., Wolyniak, C., Angulo, F.J. and Klontz, K.C. 2006. Recalls of spices due to 

bacterial contamination monitored by the U.S. Food and Drug Administration: The 

Page 56 of 68 
predominance of Salmonellae. Journal of Food Protection 69:233-237. 

<http://www.cdc.gov/foodborne/publications/380_vij_2005.pdf>. 

Yourman, L. and D. Donaldson. 2007. Qualitative Assessment of Alternatives for Ethylene 

Oxide Uses (DP316692). United States Environmental Protection Agency, Office of 

Pesticide Programs, Biological and Economic Analysis Division memorandum to Special 

Review and Reregistration Division. May 4, 2007. 

Page 57 of 68 
Appendix A. ETO Uses and Use-Patterns Eligible for Reregistration 

Use Pattern LIMITATIONS 

Medical ETO may be used only to sterilize medical or laboratory items, pharmaceuticals, and aseptic 

packaging. or to reduce microbial load on cosmetics, whole and ground spices or other 

seasoning materials, artifacts, archival material or library objects. 

ETO may be used only in facilities that meet the requirements of 29 CRF 1910.1047 in nonportable vacuum or gas-tight chambers designed for use with ETO and carbon dioxide. ETO 

may only be used by persons who have been trained in accordance with 29 CRF 1910.1047. 

When used by healthcare providers to sterilize health care items, ETO must be used in nonportable ethylene oxide gas sterilizers that meet FDA regulatory requirements and in 

accordance with directions supplied by the sterilizer manufacturer. 

Musical 

Instruments 

Library and 

Museum 

Artifacts 

Cosmetic 

Spice 

Beekeeping 

Page 58 of 68 
Appendix B. Table of Generic Data Requirements and Studies Used to Make the ETO 

Reregistration Decision 

Guide to Appendix B 

Appendix B contains listing of data requirements which support the reregistration for active 

ingredients covered by the ETO RED. It contains generic data requirements that apply to ETO 

in all products, including data requirements for which a "typical formulation" is the test 

substance. 

The data table is organized in the following formats: 

1. Data Requirement (Column 1). The data requirements are listed in the order in which 

they appear in 40 CFR part 158. The reference numbers accompanying each test refer to 

the test protocols set in the Pesticide Assessment Guidance, which are available from the 

National technical Information Service, 5285 Port Royal Road, Springfield, VA 22161 

(703) 487-4650. 

2. Use Pattern (Column 2). This column indicates the use patterns for which the data 

requirements apply. The following letter designations are used for the given use patterns. 

A. Terrestrial food 

B. Terrestrial feed 

C. Terrestrial non-food 

D. Aquatic food 

E. Aquatic non-food outdoor 

F. Aquatic non-food industrial 

G. Aquatic non-food residential 

H. Greenhouse food 

I. Greenhouse non-food 

J. Forestry 

K. Residential 

L. Indoor food 

M. Indoor non-food 

N. Indoor medical 

O. Indoor residential 

3. Bibliographic Citation (Column 3). If the Agency has acceptable data in its files, this 

column list the identify number of each study. This normally is the Master Record 

Identification (MIRD) number, but may be a "GS" number if no MRID number has been 

assigned. Refer to the Bibliography appendix (Appendix C) for a complete citation of the 

study. 

Page 59 of 68 
Guideline 

Number 

Requirement Use Pattern Bibliographic Citation(s) 

(MRID) 

Occupational/Residue Exposure 

Special Study ETO Specific Worker Monitoring Study to 

Support the Medical Sterilization Uses 

L,M,N 47331801 

Special Study ETO Specific Worker Monitoring Study To 

Support the Spice Sterilization Use 

L,M,N 47338301 

Toxicology 

830.7800 2-Generation Reproduction – Rat L,M,N 42788101 

Page 60 of 68 
Appendix C. Technical Documents to Support the ETO RED 

Additional documentation in support of this RED is maintained in the OPP docket EPA-HQOPP-2005-0203. This docket may be accessed in the OPP docket room located at Room S-4900, 

One Potomac Yard, 2777 S. Crystal Drive, Arlington, VA. It is open Monday through Friday, 

excluding Federal holidays, from 8:30 a.m. to 4:00 p.m. All documents may be viewed in the 

OPP docket room or downloaded or viewed via the Internet at the following site: 

<http://www.regulations.gov>. 

The docket initially contained preliminary risk assessments, supporting documents, and technical 

(or manufacturing-use) registrant error comments for ETO as of August 3, 2005. After a sixtyday public comment period, EPA considered the public comments that were submitted to the 

docket and revised the risk assessments as necessary. The revised risk assessments, any 

supporting documents that needed to be revised, impact assessments, and memos describing the 

Biological and Economic Assessment Division (BEAD), the Antimicrobials Division (AD), and 

Health Effects Division (HED) response to public comments will be added to the docket when 

the RED is posted in April 2008. 

The Agency documents in the docket will include: 

1. Review of Calculated Ethylene Oxide Exposures for Ethylene Oxide Sterilization Plant 

Workers (MRID No. 47331801) Submitted in Support of the Occupational Exposure 

Assessment of the Antimicrobial Uses of Ethylene Oxide for Reregistration Eligibility 

Decision (RED). PC Code 042301. DP Barcode 348868. March 26, 2008. 

2. Ethylene Oxide: Addendum to the Occupational and Residential Exposure Assessment 

and Recommendations for the Reregistration Eligibility Decision (RED) for Ethylene 

Oxide. March 24, 2008. 

Page 61 of 68 
Appendix D. Generic Data Call-In (GDCI) 

Note that a complete generic DCI, with all pertinent instructions, will be sent to registrants under 

separate cover. 

Page 62 of 68 
Appendix E. Product-Specific Data Call-In (PDCI) 

Note that a complete product-specific DCI, with all pertinent instructions, will be sent to 

registrants under separate cover. 

Page 63 of 68 
Appendix F. EPA’s Batching of ETO Products for Meeting Data Requirements for 

Reregistration 

In an effort to reduce the time, resources and number of animals needed to fulfill the acute 

toxicity data requirements for reregistration of products containing ETO as the active ingredient, 

the Agency has batched products which can be considered similar for purposes of acute toxicity. 

Factors considered in the sorting process include each product's active and inert ingredients 

(identity, percent composition and biological activity), type of formulation (e.g., emulsifiable 

concentrate, aerosol, wettable powder, granular, etc.), and labeling (e.g., signal word, use 

classification, precautionary labeling, etc.). Note that the Agency is not describing batched 

products as "substantially similar" since some products within a batch may not be considered 

chemically similar or have identical use patterns. 

Note: A complete batching index will be sent to registrants under separate cover. 

Page 64 of 68 
Appendix G. List of Available Related Documents and Electronically Available Forms 

Pesticide Registration Forms are available at the following EPA internet site: 

<http://www.epa.gov/opprd001/forms/>. 

Pesticide Registration Forms (These forms are in PDF format and require the Acrobat reader) 

Instructions: 

1. Print out and complete the forms. (Note: Form numbers that are bolded can be filled out 

on your computer then printed.) 

2. The completed form(s) should be submitted in hardcopy in accord with the existing 

policy. 

3. Mail the forms, along with any additional documents necessary to comply with EPA 

regulations covering your request, to the following address for the Document Processing 

Desk: 

Document Processing Desk (distribution code)* 

Office of Pesticide Programs (7504P)

 Environmental Protection Agency 

1200 Pennsylvania Ave, NW

 Washington, DC 20460-0001 

* Distribution Codes are as follows: 

(APPL) Application for product registration

(AMEND) Amendment to existing registration 

(CAN) Voluntary Cancellation

(EUP) Experimental Use Permit 

(DIST) Supplemental Distributor Registration 

(SLN) Special Local Need

(NEWCO) Request for new company number 

(NOTIF) Notification 

(PETN) Petition for Tolerance 

(XFER) Product Transfer 

DO NOT fax or e-mail any form containing “Confidential Business Information” or “Sensitive 

Information.” 

If you have any problems accessing these forms, please contact Nicole Williams at (703) 308­

5551 or by e-mail at williams.nicole@epamail.epa.gov. If you want these forms mailed or faxed 

to you, please contact Lois White, white.lois@epa.gov or Floyd Gayles, gayles.floyd@epa.gov. 

If you have any questions concerning how to complete these forms, please contact OPP’s 

ombudsperson for conventional pesticide products: Linda Arrington, (703) 305-5446. 

The following Agency Pesticide Registration Forms are currently available via the Internet at the 

following locations: 

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8570-1 Application for Pesticide 

Registration/Amendment http://www.epa.gov/opprd001/forms/8570-1.pdf 

8570-4 Confidential Statement of Formula http://www.epa.gov/opprd001/forms/8570-4.pdf 

8570-5 Notice of Supplemental Registration of 

Distribution of a Registered Pesticide 

Product 

http://www.epa.gov/opprd001/forms/8570-5.pdf 

8570-17 Application for an Experimental Use 

Permit http://www.epa.gov/opprd001/forms/8570-17.pdf 

8570-25 Application for/Notification of State 

Registration of a Pesticide To Meet a 

Special Local Need 

http://www.epa.gov/opprd001/forms/8570-25.pdf 

8570-27 Formulator's Exemption Statement http://www.epa.gov/opprd001/forms/8570-27.pdf 

8570-28 Certification of Compliance with Data 

Gap Procedures http://www.epa.gov/opprd001/forms/8570-28.pdf 

8570-30 Pesticide Registration Maintenance Fee 

Filing http://www.epa.gov/opprd001/forms/8570-30.pdf 

8570-32 Certification of Attempt to Enter into an 

Agreement with other Registrants for

Development of Data 

http://www.epa.gov/opprd001/forms/8570-32.pdf 

8570-34 Certification with Respect to Citations of 

Data (in PR Notice 98-5) http://www.epa.gov/opppmsd1/PR_Notices/pr98-5.pdf 

8570-35 Data Matrix (in PR Notice 98-5) http://www.epa.gov/opppmsd1/PR_Notices/pr98-5.pdf 

8570-36 Summary of the Physical/Chemical 

Properties (in PR Notice 98-1) http://www.epa.gov/opppmsd1/PR_Notices/pr98-1.pdf 

8570-37 Self-Certification Statement for the 

Physical/Chemical Properties (in PR

Notice 98-1) 

http://www.epa.gov/opppmsd1/PR_Notices/pr98-1.pdf 

Page 66 of 68 
Pesticide Registration Kit available at <http://www.epa.gov/pesticides/registrationkit/>. 

Dear Registrant: 

For your convenience, we have assembled an on-line registration kit which contains the 

following pertinent forms and information needed to register a pesticide product with the U.S. 

Environmental Protection Agency's Office of Pesticide Programs (OPP): 

1. The Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) and the Federal Food, 

Drug and Cosmetic Act (FFDCA) as Amended by the Food Quality Protection Act 

(FQPA) of 1996. 

2. Pesticide Registration (PR) Notices 

a. 83-3 Label Improvement Program-Storage and Disposal Statements 

b. 84-1 Clarification of Label Improvement Program 

c. 86-5 Standard Format for Data Submitted under FIFRA 

d. 87-1 Label Improvement Program for Pesticides Applied through Irrigation Systems 

(Chemigation) 

e. 87-6 Inert Ingredients in Pesticide Products Policy Statement 

f. 90-1 Inert Ingredients in Pesticide Products; Revised Policy Statement 

g. 95-2 Notifications, Non-notifications, and Minor Formulation Amendments 

h. 98-1 Self Certification of Product Chemistry Data with Attachments (This document 

is in PDF format and requires the Acrobat reader.) 

Other PR Notices can be found at <http://www.epa.gov/opppmsd1/PR_Notices.> 

3. Pesticide Product Registration Application Forms (These forms are in PDF format and 

will require the Acrobat reader.) 

a. EPA Form No. 8570-1, Application for Pesticide Registration/Amendment 

b. EPA Form No. 8570-4, Confidential Statement of Formula 

c. EPA Form No. 8570-27, Formulator's Exemption Statement 

d. EPA Form No. 8570-34, Certification with Respect to Citations of Data 

e. EPA Form No. 8570-35, Data Matrix 

4. General Pesticide Information (Some of these forms are in PDF format and will require 

the Acrobat reader.) 

a. Registration Division Personnel Contact List 

b. Biopesticides and Pollution Prevention Division (BPPD) Contacts 

c. Antimicrobials Division Organizational Structure/Contact List 

d. 53 F.R. 15952, Pesticide Registration Procedures; Pesticide Data Requirements (PDF 

format) 

e. 40 CFR Part 156, Labeling Requirements for Pesticides and Devices (PDF format) 

f. 40 CFR Part 158, Data Requirements for Registration (PDF format) 

g. 50 F.R. 48833, Disclosure of Reviews of Pesticide Data (November 27, 1985) 

Page 67 of 68 
Before submitting your application for registration, you may wish to consult some 

additional sources of information. These include: 

1. The Office of Pesticide Programs' Web Site. 

2. The booklet "General Information on Applying for Registration of Pesticides in the 

United States", PB92-221811, available through the National Technical Information 

Service (NTIS) at the following address: 

National Technical Information Service (NTIS) 

5285 Port Royal Road

 Springfield, VA 22161 

The telephone number for NTIS is (703) 605-6000. Please note that EPA is currently in

the process of updating this booklet to reflect the changes in the registration program 

resulting from the passage of the FQPA and the reorganization of the Office of Pesticide 

Programs. 

3. The National Pesticide Information Retrieval System (NPIRS) of Purdue University's 

Center for Environmental and Regulatory Information Systems. This service does charge

a fee for subscriptions and custom searches. You can contact NPIRS by telephone at

(765) 494-6614 or through their website. 

4. The National Pesticide Telecommunications Network (NPTN) can provide information 

on active ingredients, uses, toxicology, and chemistry of pesticides. You can contact 

NPTN by telephone at (800) 858-7378 or through their website: <http://npic.orst.edu>. 

The Agency will return a notice of receipt of an application for registration or amended 

registration, experimental use permit, or amendment to a petition if the applicant or 

petitioner encloses with his submission a stamped, self-addressed postcard. The postcard

must contain the following entries to be completed by OPP: 

• Date of receipt 

• EPA identifying number 

• Product Manager assignment 

Other identifying information may be included by the applicant to link the 

acknowledgment of receipt to the specific application submitted. EPA will stamp the 

date of receipt and provide the EPA identifying File Symbol or petition number for the 

new submission. The identifying number should be used whenever you contact the 

Agency concerning an application for registration, experimental use permit, or tolerance 

petition. 

To assist us in ensuring that all data you have submitted for the chemical are properly coded and 

assigned to your company, please include a list of all synonyms, common and trade names, 

company experimental codes, and other names which identify the chemical (including "blind" 

codes used when a sample was submitted for testing by commercial or academic facilities). 

Please provide a CAS number if one has been assigned. 

Page 68 of 68