UNITED STATES ENVIRONMENTAL PROTECTION AG E NCY WASHINGTON, 

### D.C
. 20460 OF F ICE O F C HE MICAL SA F ETY AND POLLUT I ON P R E V E N T ION



### MEMO RANDUM Da t e : May 8, 2013 SUBJECT: Eth yle n e Oxide (ETO) : Rev i ew of Human Inc id ents PC C od e: 04230 1 D P Bar c ode: D4 1 1127 Dec i s ion N o .: 471088 Petit ion No. : NA Reg ist r ation No. : NA R eg ul ator y Action : NA Case No.: NA Ri s k Assess men t T ype: NA TX R No .:NA CAS No.: 75-21-8 40 C FR : NA M RID No
. : NA 

### F ROM: Shanna R eco re, In dus trial Hyg ienist T oxicology and Epidemio l ogy Bra nch Health Effects D iv i si on (7509P) and Elizabeth Evans, Envi ronmental Protection Spec ialist Toxicology and Epidem iology Branch Ver.Apr.08

Health Effects D ivision (7509 P) 

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## fl181 · 'LcJ,3 T H R O UG H : D avid J. M ill e r, Acti n g B ran ch Chief 1

### /If~ T ox icology and Ep i demiol ogy B ra nch Health Effects D i vi sio n ( 75 09P) 

### T O: J essica Kidwe ll , Ri sk Assessor Ri sk Assessment Branch IV Health Effects Divis i on (7509P) and Susan Bartow , Chem i cal R eview Manager Risk Management & Imp le mentati on Bra n ch 4 Pesti c i de Re-evalu ation Di v isio n (7508P) Summa ry and Conclu s i o ns Based on th e low frequency and severity of incident cases rep orted for ethylene ox ide in both ID S and NIO SH SENSOR- Pesticides, there does not appear to be a concern at this time that would warrant further investigati on. The Agency will conti nue to monitor the incident information and if a concern is trigger ed, additional analys is will be included in the ri sk assessment.
P age 1 of5The Agricultural Health Study (AHS) i s also a potential source of information associated with human health effects associated with certain pesticides. Ethylene oxide is not included in the AHS, and therefore this study does not provide information for this report . Detailed Review 

### I. ACTION REQUESTED This review i s intended to fulfill our requirement to docket summar ies of incident data that were reported to the Agency , as well as to ensure human incident data and the Agricultural Health Study (AHS) are part of the problem formulation phase of registration review. Reports of adverse health effects allegedly due to a specific pesticide exposure (i.e., an "incident") are largely self-reported and therefore, generall y speaking, neither exposure to a pesticide or reported symptom (or the connection between the two) is validated or otherwise confirmed. T yp icall y, causation cannot be determined based on inc ident data. However, incident information can be an important source of feedback to the Agency: incidents of severe outcome, or a suggested pattern or trend among less severe incidents, can signal the Agency to further investigate a particular chemical or product. Observa t i onal ep idemi ology stud ie s re late the risk of disease, 

### e.g., cancer, and exposure to an agent such as a pesticide product in the general population or specific sub-groups like pesticide applicators. 

### II. BACKGROUND In the U.S., ETO is prima rily used to sterilize medical equipment, phannaceuticals, and aseptic packaging. However, ETO is also used to reduce microbial populations on who le and ground spices and dried vegetables. Fumigation with ETO must be performed in vacuum chambers with outside venting designed for use with ETO
. It is applied by commercial applicators only; th ere are no residential uses ofETO. ETO has three reaction products- ethylene bro mohydrin (EBH), ethylene chlo rohydrin (ECH), and ethylene glyco l (EG). For this evaluat ion , both OPP Incident Data System (IDS) and the Centers for Disease Control and Pre vention/National Institute for Occupational Safety and Health (CDC/NIOSH) Sentinel Event Notification System for Occupational Risk-Pesticides (SENSOR) databases were consulted for pesticide incident data on the active ingredient ethylene ox ide (PC Code: 042301). The purpose of the database search is to identify potential patterns in the frequency and severity of the health effects attributed to ethylene oxide exposure. In addition, findings from th e Agricultural Health Study (AHS) were reviewed. The AHS is a high quality, prospective epidemiology study evaluating the link between pesticide use and various health outcomes including cancer. Ethylene oxide is not included in the AHS, and th erefore this study does not provide information for this report.


### III. RESULTS/DISCUSSION
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### a. IDS (Incident Data S ys tem) OPP 's IDS includes reports of alleged human health inc id ents from various sources, inclu ding mandatory Federal Insecticide, Fungicide and Rodentic id e Act (FIFRA) Section 6 (a)(2) reports from regi strants, other federal and state health and environmental agencies, and individual consumers. Since 1 992, OPP has compiled these report s in IDS
. ID S contains re ports from across the U.S. and most incidents have all rel evant product information recorded. Repo rts submitted to the IDS represent anecdotal reports or a ll egations o n ly, unless ot herw ise stated in the report. IDS records incidents in one of two modules: Main ID S and Aggregate ID S:
o Main IDS contains inci dents resulting in hi g her severity outcomes and provides more detail with regard to cas e specific. Thi s s y stem sto res incident data for death, major and moderate inc id en ts, and it includes information about the location, date and nature of the incident. Main IDS incidents involving only one pesticide are cons idered to provide more certain informat i on about t he pote ntial effects of exposure from the pesticide.
o Aggregate IDS contains incidents resulting in less severe human incidents (minor, unknown, o r no effects outcomes). These are reported by re g istrants only as counts in what are aggregate summaries. For the Main ID S, from January 1 , 2008 to February 19 , 2013, there was 1 incident reported in the database. This incident was classified as major severity. 

### This incident is described further in Table 1. Overall , there are few incidents involving ethylene ox ide reported to ID S. In Aggregate ID S, from January 1 , 2008 to February 19, 2013, there were 3 reporte d i ncidents invo lv ing et hylene oxide. These incidents were classified as minor sever ity
. T bl 1 M . ID S M . .d 

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a e a m a] or nc1 ents or t e smg le c em t ca t 1y1en e 0 .d x 1 e Human Incident Chemica l: Eth y len e Oxide 

## I PC Code : 04230 I Incid e nt Package Incident Reg Exposure Report Date Location N umb er Prod u ct Name Severity* Incident DescriJ>tion An employee attributes Acute Promyleocytic Leuke mi a to his exposure to ethylene oxide gas ( SterGas Cartridge) in his 6 yrs of employment as sterili za tion personnel. His workers compens ation cla im was denied

. He was ab le to show that he was exposed to ETO bu t not a connection 023423 SPOKANE, 007182- STERI-GAS between his exposure and

- 00001 9/1/2011 WA 00001 CARTRIDGE HB his diagnos i s. Page 3 of 5

### b
. SENSOR-Pesticides The SENSOR-Pesticides database covers 11 states from 1998-2009, a lthough r eporting varies from state to state. Cases of pesticide-related illnesses are ascertained from a varie ty of sources, including: reports from l ocal Poison Control Centers, s tate Department of Labor wo rke r s' compensati on claims when reported by phys i c i ans, reports from State Departments of Agricultur e, and physician reports to state Departments of Health. Although both occupational and non-occupational i ncidents are included 

### in the database, SENSOR-Pesticides focuses on occupational pesticide inci d ents, and is of part i cular value in provid ing that informati on. The state coordinator at the 11 respective state D epartments of Health conducts case follow-up acti vities such as obtaining medical records to verify symptoms and severity. Using standa rdized protocol and case d efinitions derived from poison center reporti ng, the state SENSOR

- Pesticide coordinator enters the i nc i dent information into the state
- based system which is sent to NIOSH annually t o be aggregated. A query of SENSOR-Pesti c i des 1998-2009 i dentifies 9 cases, stemming from 5 events, involving ethy l ene oxide. All cases/events invo l ved a single ai. One case was classified as moderate severity and eight cases were classified as low in severity. Eight of nine cases were workrelated; seven of nine cases were exposed in a hospital. The moderate severity case narrative states "case was exposed to ethy l ene oxide at hospital where she works while she and ano ther coworker were doing ro u tine work"
. One event that occurred i n Michigan in 2006 (Event ID # MI00693) resu l ted i n 4 SENSOR case reports . Event information states "A partially used ethylene oxide (ETO) canister, which had been improperly p l aced on the ETO machine, fell to the floor of the surgical processing room . It cracked & released ETO. 15 people were evacuated from the area & decontaminated. Six individuals with symptoms were sent to occupational health
. '' The reported health effects for these cases are summarized in T able 2.

Table 2. SENSOR-Pesticides 1998-2009:

Reported Health Effects for Ethylene O x id e Cases (N=9)

Health Effec t #of Times Reported Dermal I Ocular 2 Respiratory 6 Gastrointestinal 5 Renal 0 Nervous System 7 Cardiovascular 0 Misc. 1



### * Cases may report multiple health effects Page 4 of5

### c. Agricultural Health Study (AHS) The AHS is a hi gh quality, prospective epidemiology study evaluating the link between pesticide use and various health outcomes including cancer. The AHS includes private and commercial pesticide applicators and thei r spouses. If there are AHS findings relevant to a particular pesticide going through registration review, the Agency will ensure they are considered in the problem formulation/scoping phase of the process and, if appropriate, fully reviewed in the risk assessment phase of the process. The AHS includes information on use of 50 different pesticide activ e ingredients commonly used in agric ulture
. Ethylene oxide is not included in the AHS, and therefore this study does not provide information for this report. 

### IV . CONCLUSION Based on the low frequency and severity of incident cases reported for ethylene oxide in both IDS and NIOSH SENSOR-Pesticides, there does no t appear to be a concern at this t ime t hat would warrant further investigation. The Agency will continue to moni tor the incident inf ormati on and if a concern is triggered, additional analysis will be included in the risk assessment.

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