UNITED STATES ENVIRONMENTAL PROTECTION AGENCY WASHINGTON, D

.C

. 20460 

### FEB 26 2013

MEMORANDUM OFFICE OF CHEMICAL SAFETY AND POLLUTION PREVENTION

SUBJECT: BEAD Chemical Profile for Registration Review: Ethylene oxide (ETO) (042301) FROM: Leonard Yourman, Plant Pathologist

# f~ Biological Analysis Branch

## ~ • Sepehr Haddad, Environmental Protection Specialist

# ~~ / /

# ~ • - _ 

## A Science Information and Analysis Branch 

# f

# t,**~~** John Faulkner, Economist

# ~**~** Economic Analysis Branch (/"

... ' Biological and Economic Analysis Division (7503P) THRU: Arnet Jones, Chief /)

# ~ · 1 Biological Analysis

## Branch~/ Diann Sims, Chief Science Information and Analysis Branch Timothy Kiely, Chief

# VJ..._**~** Economic Analysis Branch 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 (751OP) Product Review Panel date: January 30,2013

INTRODUCTION The purpose ofthis document is to convey usage information and a broad overview ofthe pest management roles ofpesticides that are beginning to undergo registration review. The anticipated audience consists ofEPA staffcurrently evaluatingthe registration status ofethyleneoxide (ETO) and, eventually, the general public. The document is based on information and data available to BEAD as ofJanuary, 2013. Inthe U.S., ETO is primarily used to sterilize medical equipment, pharmaceuticals, and aseptic packaging. Itis 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. Itis applied by commercial applicators only; there are no residential uses ofETO. 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), andprocessed 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 informationregarding ETO usage. A maximum ofapproximately 8.2 millionpounds ofETO were used annually inthe U.S. for commercial fumigation/sterilization of laboratory items and equipment (EPA, 2008). ETO treatment has been used to reduce microbial populations in whole orground spices (however, ETO use for basil was excluded inthe RED due to risk mitigation-EPA, 2008). Anestimated 800,000 pounds ofETO (approximatelylO% of total ETO use) are used annually for fumigation ofherbs and spices (ASTA, 2005). Approximately 40-85% ofspices consumed in the U.S. are treated with ETO annually (ASTA, 2005). The use for vegetable processing comprises less than 1% ofthe total annual usage.

HISTORY OF BEAD ASSESSMENTS FORETHYLENE OXIDE BEAD assessments for the 2008 RED are Yourman, 2005; Yourman and Donaldson, 2006a; Yourman and Donaldson, 2006b; Yourman and Donaldson, 2007; Yourman and Donaldson, 2008; Donaldson et al., 2006.

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### BIOLOGICALASPECTS RELEVANT TOETHYLENE OXIDE BEAD conducted several assessments and responses to comments during the Registration Eligibility Decision (RED) process from 2006 to 2008 (see citations inthe History section, above). The following highlight some aspects ofthose memos. Spices Methods oftreating spices depend on the particular characteristics ofthe spice and whether the spice can withstand a particulartreatment 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). Inthe 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 beenused as an insecticide or antimicrobial on some spices (Chandgoyal, 2006), but as with ETO, ithas been banned in many countries. Irradiation canbe an effective treatment for some spices, and is permitted by numerous countries, butithas not been adopted widely in the U.S. The threat offood-borne contamination and the potential for serious illness has been a concern to the Agency. Mostreported cases ofmicrobial contamination offoods occur on fresh and processed fruits and vegetables, meats, seafood, dairy, and eggs (CDC, 2011). Fewfood recalls inthe U.S. have involved spices when comparedto otherfoods, 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). Ofthe few recalled spices most were contaminated with Salmonella serotypes (Zweifel and Stephan, 2012; Vij et al., 2006). Itis notknown ifthe recalled spices were, orwere not, treated with ETO. A review ofspice recalls that were recorded by the FDA Centerfor Food Safety and Applied Nutrition, from 1969 through 2003, recorded a total of21 spice-recalls-fiverecalls occurred between 1971 and 1996, and 16 recalls occurred between 2001 and 2003 (Vij et al., 2006). It was notknown ifany illnesses were associated with the contaminated spices. the CDC has estimated that for every reported case ofcontamination there are likely many more that go unreported. Consequently, it would be difficult to estimate the extentto which ETO may preventpotential food-borne illness associated with herbs and spices. Medical Devices The Agencyhas considered ETO importantto the medical device industry and hospitals and necessary to protectpublic health. Currently, there do not appear to be any reliable replacements for ETO in sterilizing the range ofmedical devices for which it is useful. The choice ofsterilant depends onthe material composition ofthe device and its sensitivityto different sterilants and the use site (e.g., industrial, hospital, etc.). While there are other sterilizationmethods for treating some medical devices, no currently available sterilization treatment has been accepted as a replacement for ETO for some importantuses, including heat-sensitive and**irra~iation** sensitive materials and some instruments and devices thatrequire sterilization on-site in

3hospitals. In some situations alternative sterilants can be effective, including heat, gamma radiation, electron beamradiation, x-ray, and hydrogen peroxide plasma.

INFORMATION THAT MAY BE USEFUL FORBEAD'S FUTURE WORK ON ETHYLENE OXIDE 1. Updated information onefficacy ofalternatives for spices. BEAD identified possible alternatives to ETO, including heat, irradiation, and sanitarypractices. Have recent surveys or research been conducted comparing efficacy ofvarious alternatives against important pathogens? 2. With regard to recent (January, 2013) proposed rules by FDA issued under The Food Modernization Safety Act (FMSA) of2011. Do new standards offood 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 haspreviously 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 gammaradiation sterilizers, low temperature vapor-phase hydrogen peroxide sterilizers, and machine-driven x-ray sterilizers?

CONCLUSION Inprevious 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 inthis 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 ifthere are alternative methods for some uses that might be currently available. Itis also not known how, or if, new food safety guidelines under FMSA will affect the needs ofthe spice industry with regard to ETO.

REFERENCES ASTA (American Spice Trade Association). 2005. Public comments to Phase 3 ofthe reregistration risk assessment ofethylene 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.govIoutbreaknet/investigations/; http://www.cdc.gov/outbreaknet/surveillance data.html; http:/ /www.cdc.gov/foodborneburden/2011-foodborne-estimates.html

4CDC. 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 ofPropylene 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 onthe 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/201 0/01/ pepper-is-on-the-suspect-list/ Vij, V., Ailes, E., Wolyniak, C., Angulo, F. J., and Klontz, K. C., 2006. Recalls ofspices due to bacterial contaminationmonitored by the U.S. Food and Drug Administration: The predominance ofSalmonellae. Journal ofFood Protection 69:233-237. http://www.ingentaconnect.com/ content/iafp/jfp/2006/00000069/00000001

### Iart00036 http://www.ncbi.nlm.nih.gov/pubmed/16416926 Yourman, L. and Donaldson, D. 2008. Response to Public Comments onthe Benefits and Use ofEthylene Oxide as a Sterilizing Agent and Antimicrobial Fumigant (DP# 342896) Yourman, L. and Donaldson, D. 2007. Qualitative Assessment ofAlternatives for Ethylene Oxide Uses (DP316692) Yourman, L. and Donaldson, D. 2006a. BEAD Response to Phase 5 Public Comments for Use ofEthylene Oxide by the Spice Trade (DP329664) Yourman, L. and Donaldson, D. 2006b. Use ofEthylene Oxide and Alternatives for Antimicrobial Activity on Spices and As a Sterilizing Agent for Medical Devices (DP326471) Yourman, L. 2005. International Use ofEthylene Oxide as an Agricultural Pesticide and Sterilant ofMedical Devices Zweifel, C. and Stephan, R. 2012. Spices and herbs as source ofSalmonella-related foodborne diseases. Food Research International45(2):765-769. http:/ /www.sciencedirect.com/science/article/pii/S0963996911001268

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