UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

WASHINGTON, D.C. 20460 

FEB 2 6 2013 

MEMORANDUM 

OFFICE OF CHEMICAL SAFETY 

AND POLLUTION PREVENTION 

SUBJECT: BEAD Chemical Profile for Registration Review: Ethylene oxide (ETO) (042301) 

FROM: Leonard 

Biological 

Yourman, 

Analysis 

Plant 

Branch 

Pathologist f~ 

~ • 

Sepehr Haddad, Environmental Protection Specialist ~~ / / ~ • - _ A 

Science Information and Analysis Branch f t, ~~ 

John 

Economic 

Biological 

Faulkner, 

Analysis 

and Economic 

Economist 

Branch 

Analysis 

(/" 

~ 

Division 

... ' 

~ 

(7503P) 

THRU: Arnet Jones, Chief /) ~ · 1 

Biological Analysis Branch~/ 

Diann Sims, Chief 

Science Information and Analysis Branch 

Economic 

Timothy Kiely, 

Analysis 

Chief 

Branch 

VJ..._~ 

Biological and Economic Analysis ivision (7503 

TO: Susan Bartow, Chemical Review Manager 

Risk Management and Implementation Branch 4 

Pesticide Re-evaluation Division (7508P) 

Seiichi Murasaki, Chemical Review Manager 

Regulatory Management Branch II 

Antimicrobial Division (751 OP) 

Product Review Panel date: January 30,2013 

INTRODUCTION 

The purpose of this document is to convey usage information and a broad overview of the pest 

management roles of pesticides that are beginning to undergo registration review. The 

anticipated audience consists of EPA staff currently evaluating the registration status of ethylene 
oxide (ETO) and, eventually, the general public. The document is based on information and data 

available to BEAD as of January, 2013. 

In the U.S., ETO is primarily used to sterilize medical equipment, pharmaceuticals, and aseptic 

packaging. It is also used to reduce microbial populations on whole and ground spices and dried 

vegetables. Sterilization or fumigation with ETO must be performed in vacuum chambers with 

outside venting designed for use with ETO. It is applied by commercial applicators only; there 

are no residential uses of ETO. ETO has three reaction products- ethylene bromohydrin 

(EBH), ethylene chlorohydrin (ECH), and ethylene glycol (EG) .. 

COMMON FORMULATIONS AND APPLICATION METHODS 

ETO is formulated as pressurized gas. ETO must be applied within specialized vacuum and 

pressurized chambers. 

USE SITES 

Agricultural Use Sites 

Processed herbs and spices (except basil), and processed vegetables (dried/dehydrated). 

Non-agricultural Use Sites 

Hospital critical items (surgical instruments), hospital semi-critical items (catheters, inhalation 

equipment), medical and veterinary sterilization, and nonfood commodities (temporary storage). 

USAGE 

BEAD has little new information regarding ETO usage. A maximum of approximately 8.2 

million pounds ofETO were used annually in the U.S. for commercial fumigation/sterilization of 

laboratory items and equipment (EPA, 2008). ETO treatment has been used to reduce microbial 

populations in whole or ground spices (however, ETO use for basil was excluded in the RED due 

to risk mitigation-EPA, 2008). An estimated 800,000 pounds ofETO (approximatelylO% of 

total ETO use) are used annually for fumigation of herbs and spices (ASTA, 2005). 

Approximately 40-85% of spices consumed in the U.S. are treated with ETO annually (ASTA, 

2005). The use for vegetable processing comprises less than 1% of the total annual usage. 

HISTORY OF BEAD ASSESSMENTS FOR ETHYLENE OXIDE 

BEAD assessments for the 2008 RED are Y ourman, 2005; Y ourman and Donaldson, 2006a; 

Yourman and Donaldson, 2006b; Yourman and Donaldson, 2007; Yourman and Donaldson, 

2008; Donaldson et al., 2006. 

2 
BIOLOGICAL ASPECTS RELEVANT TO ETHYLENE OXIDE 

BEAD conducted several assessments and responses to comments during the Registration 

Eligibility Decision (RED) process from 2006 to 2008 (see citations in the History section, 

above). The following highlight some aspects of those memos. 

Spices 

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. ETO has 

been considered desirable for spice decontamination because it generally leaves the volatile spice 

components intact. However, many countries have banned the use ofETO on spices due to its 

classification as a known human carcinogen and genotoxic agent (FAO!UNEP, 2001). 

In the U.S., treatment methods that are used to reduce microbial and insect activity in spices 

include heat, irradiation, good agricultural practices, ETO, and propylene oxide (PPO). 

Propylene oxide (PPO) has been used as an insecticide or antimicrobial on some spices 

(Chandgoyal, 2006), but as with ETO, it has been banned in many countries. Irradiation can be 

an effective treatment for some spices, and is permitted by numerous countries, but it has not 

been adopted widely in the U.S. 

The threat of food-borne contamination and the potential for serious illness has been a concern to 

the Agency. Most reported cases of microbial contamination of foods occur on fresh and 

processed fruits and vegetables, meats, seafood, dairy, and eggs (CDC, 2011). Few food recalls 

in the U.S. have involved spices when compared to other foods, such as meat and vegetables. 

However, in 2009, 42 people reported illness from contaminated white pepper (Flynn, 2010). 

The U.S. imports spices from more than 6,100 manufacturers in 129 countries (Vij et al., 2006). 

Of the few recalled spices most were contaminated with Salmonella serotypes (Zweifel and 

Stephan, 2012; Vij et al., 2006). It is not known if the recalled spices were, or were not, treated 

with ETO. A review of spice recalls that were recorded by the FDA Center for Food Safety and 

Applied Nutrition, from 1969 through 2003, recorded a total of21 spice-recalls-five recalls 

occurred between 1971 and 1996, and 16 recalls occurred between 2001 and 2003 (Vij et al., 

2006). It was not known if any illnesses were associated with the contaminated spices. the 

CDC has estimated that for every reported case of contamination there are likely many more that 

go unreported. Consequently, it would be difficult to estimate the extent to which ETO may 

prevent potential food-borne illness associated with herbs and spices. 

Medical Devices 

The Agency has considered ETO important to the medical device industry and hospitals and 

necessary to protect public health. Currently, there do not appear to be any reliable replacements 

for ETO in sterilizing the range of medical devices for which it is useful. The choice of sterilant 

depends on the material composition of the device and its sensitivity to different sterilants and 

the use site (e.g., industrial, hospital, etc.). While there are other sterilization methods for 

treating some medical devices, no currently available sterilization treatment has been accepted as 

a replacement for ETO for some important uses, including heat-sensitive and irra~iationsensitive materials and some instruments and devices that require sterilization on-site in 

3 
hospitals. In some situations alternative sterilants can be effective, including heat, gamma 

radiation, electron beam radiation, x-ray, and hydrogen peroxide plasma. 

INFORMATION THAT MAY BE USEFUL FOR BEAD'S FUTURE WORK ON 

ETHYLENE OXIDE 

1. Updated information on efficacy of alternatives for spices. BEAD identified possible 

alternatives to ETO, including heat, irradiation, and sanitary practices. Have recent 

surveys or research been conducted comparing efficacy of various alternatives against 

important pathogens? 

2. With regard to recent (January, 2013) proposed rules by FDA issued under The Food 

Modernization Safety Act (FMSA) of 2011. Do new standards of food safety affect the 

spice industry and choices for providing safe as well as acceptable spice products? 

(http://www.fda.gov/Food/FoodSafety/FSMA/default.htm; 

http://www.fda.gov/Food/FoodSafety/FSMA/ucm334114.htm) 

3. Updated information on any recent advances in alternatives for sterilizing medical 

devices. BEAD has previously highlighted potential alternatives for sterilizing medical 

devices (e.g., Yourman and Donaldson, 2007). Guidelines for hospital needs were 

published in 2008 (CDC, 2008). Is there new information concerning efficacy and 

availability ofnon-ETO sterilization methods such as smaller gamma radiation sterilizers, 

low temperature vapor-phase hydrogen peroxide sterilizers, and machine-driven x-ray 

sterilizers? 

CONCLUSION 

In previous memos, BEAD has noted that ETO has been important for various medical 

sterilization needs, including on-site hospital uses. Further investigation and consultation with 

experts in this area would have to be undertaken to identify any other sterilization methods that 

may now be available that would be considered acceptable as alternatives to ETO for some uses. 

For ETO spice uses, BEAD does not know if there are alternative methods for some uses that 

might be currently available. It is also not known how, or if, new food safety guidelines under 

FMSA will affect the needs of the spice industry with regard to ETO. 

REFERENCES 

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

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

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

CDC. 2011. Investigating Food borne Outbreaks. 

http://www .cdc. gov I outbreaknet/investigations/; 

http://www.cdc.gov/outbreaknet/surveillance data.html; 

http:/ /www.cdc.gov/foodborneburden/20 11-foodborne-estimates.html 

4 
CDC. 2008. Guideline for Disinfection and Sterilization in Healthcare Facilities, 2008. 

http://www.cdc.gov/hicpac/pdf/guidelines/Disinfection Nov 2008.pdf 

Chandgoyal, Tara, 2006. Propylene Oxide (PPO) Alternatives Assessment for Use on Spices to 

Reduce Bacterial and Mold Contamination (DP # 325399). 

Donaldson, D., Yourman, L., and Chandgoyal, T. 2006. Impact Assessment of Propylene Oxide 

and Alternatives on Almonds, Pecans, Walnuts and Spices (DP# 316567). 

EPA. 2008. Reregistration Eligibility Decision for ETO, 2008. Online at 

http://www.epa.gov/oppsrrd1/REDs/ethylene-oxide-red.pdf 

FAOIUNEP, 2001, 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/PIC/Download/DGDs/ETO-en.pdf 

Flynn, D. 2010. Pepper suspected in Salmonella outbreak. Food Safety News, Jan. 26, 2010. 

http://www .foodsafetynews.com/20 1 0/0 1/pepper-is-on-the-suspect -list/ 

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 

predominance of Salmonellae. Journal ofFood Protection 69:233-237. 

http://www .ingentaconnect.com/ content/iafp/j fp/2006/00000069/0000000 1 I art0003 6 

http://www.ncbi.nlm.nih.gov/pubmed/16416926 

Yourman, L. and Donaldson, D. 2008. Response to Public Comments on the Benefits and Use 

of Ethylene Oxide as a Sterilizing Agent and Antimicrobial Fumigant (DP# 342896) 

Yourman, L. and Donaldson, D. 2007. Qualitative Assessment of Alternatives for Ethylene 

Oxide Uses (DP316692) 

Yourman, L. and Donaldson, D. 2006a. BEAD Response to Phase 5 Public Comments for Use 

of Ethylene Oxide by the Spice Trade (DP329664) 

Yourman, L. and Donaldson, D. 2006b. Use of Ethylene Oxide and Alternatives for 

Antimicrobial Activity on Spices and As a Sterilizing Agent for Medical Devices (DP326471) 

Y ourman, L. 2005. International Use of Ethylene Oxide as an Agricultural Pesticide and 

Sterilant of Medical Devices 

Zweifel, C. and Stephan, R. 2012. Spices and herbs as source of Salmonella-related foodborne 

diseases. Food Research International45(2):765-769. 

http:/ /www.sciencedirect.com/science/article/pii/S0963996911 001268 

5