US Environmental Protection Agency
Office of Pesticide Programs
Reregistration Eligibility Decision
for Ethylene Oxide
March 31,2008
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United States Prevention, Pesticides EPA 738-R-08-003
Environmental Protection and Toxic Substances March 2008
AgenCy (7508P)
Reregistration
Eligibility Decision for
Ethylene Oxide
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Reregistration Eligibility Decision (RED) Document
for Ethylene Oxide
ListB
Case Number 2275
Approved by:
Steven Bradbury, Ph.D.
Director
Special Review and Reregistration Division
Date: _/ ?// fi
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Table of Contents
Ethylene Oxide Reregi strati on 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 Reregi strati on 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 Disrupter 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
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Appendices
Appendix A. ETO Uses and Use-Patterns Eligible for Reregi strati on 58
Appendix B. Table of Generic Data Requirements and Studies Used to Make the ETO
Reregi strati on 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
Appendix F. EPA's Batching of ETO Products for Meeting Data Requirements for
Reregi strati on 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 Reregi strati on of ETO 47
Table 4. Summary of Labeling Changes for ETO 49
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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 Perils
Phil Ross
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Glossary of Terms and Abbreviations
ai Active Ingredient
ARC ARC Specialty Products, Balchem Corporation
ASIA American Spice Trade Association
BQA Baltimore Quality Assurance
CAS Chemical Abstracts Service
CDC Centers for Disease Control and Prevention
CFR Code of Federal Regulations
CFSAN FDA Center for Food Safety and Applied Nutrition
CSF Confidential Statement of Formulation
DCI Data Call-in
DNT Developmental Neurotoxicity
EBH Ethylene Bromohydrin
ECH Ethylene Chlorohydrin
EDSP Endocrine Disrupter Screening Program
ED STAC Endocrine Disrupter Screening and Testing Advisory Committee
EG Ethylene Glycol
EOSA Ethylene Oxide Sterilization Association
EPA Environmental Protection Agency
ETO Ethylene Oxide
EUP End-Use Product
FDA Food and Drug Administration
FDA/BVM Food and Drug Administration Bureau of Veterinary Medicine
FDMS Federal Docket Management System
FIFRA Federal Insecticide, Fungicide, and Rodenticide Act
FFDCA Federal Food, Drug, and Cosmetic Act
FQPA Food Quality Protection Act
FPLA Fair Packaging and Labeling Act
FR Federal Register
GACT Generally Available Control Technology
GAP Good Agricultural Practices
GLN Guideline Number
GMP Good Manufacturing Practices
HACPP Hazard Analysis and Critical Control Point
HEC Human Equivalent Concentration
IARC International Agency for Research on Cancer
IMIS Integrated Management Information System
IRIS Integrated Risk Information System
LOG Level of Concern
LOAEL Lowest Observed Adverse Effect Level
MACT Maximum Achievable Control Technology
|ig/g Micrograms Per Gram
|ig/L Micrograms Per Liter
mg/kg/day Milligram Per Kilogram Per Day
mg/L Milligram Per Liter
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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 Reregi strati on Eligibility Decision
RfC Reference Concentration
RfD Reference Dose
RGDR Regional Gas Dose Ratio
RQ Risk Quotient
SAP Science Advisory Panel
SCB A 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
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Abstract
This document presents the Environmental Protection Agency's (EPA's or the Agency's)
decision regarding the reregi strati on 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 reregi strati on
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.
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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 non-
occupational 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
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TRED is available in the public docket EPA-HQ-OPP-2005-0203 located on-line in the Federal
Docket Management System (FDMS) at .
This document addresses the remaining potential risks to workers and as such completes
the Agency's Reregi strati on 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 reregi strati on eligibility decision for ETO. This document consists of six
sections. Section I contains the regulatory framework for reregi strati on. 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 reregi strati on 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
.
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II. Chemical Overview
A. Chemical Identity
Chemical Structure:
Molecular Formula:
Common Name:
CAS Name:
Case Number:
Technical Registrants:
H2C\ /CH2
C2H4O
Ethylene Oxide
Oxirane
CAS Registry Number: 75-21-8
OPP Chemical Code: 042301
2275
Honeywell Corporation and ARC Specialty Products of Balchem
Corporation
ETO has three reaction products— ethylene bromohydrin (EBH), ethylene chlorohydrin
(ECH), and ethylene glycol (EG).
Ethylene Bromohydrin
Chemical Structure:
HO
\ /
Br
C-
H,
-C
H,
Ethylene Chlorohydrin
Chemical Structure:
HO
01
\ /
H2 H2
Ethylene Glycol
Chemical Structure:
HO
\ /
H2 H2
OH
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,
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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 reregi strati on
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 reregi strati on 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
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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
). Recently, OAR
analyzed ETO emissions from hospital sterilizers. OAR issued a final rule for hospital emissions
on December 28, 2007 (available at ). 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
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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
reregi strati on and Appendix A provides a detailed table of those uses which are eligible for
reregi strati on.
Type of
Pesticide:
Formulations:
Methods of
Application:
Use Sites:
ETO is an antimicrobial and conventional chemical. It is a biocide,
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 (Streptoccuspluton), Herpes
simplex virus, Hew (FDA/BVM), unspecified microorganisms,
Mycobacterium spp., Nosema apis, Pseudomonas spp., Rhinoviruses, storage
microorganisms, stored product insects, wax moth.
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.
Sterilization/fumigation with ETO must be performed only in vacuum or gas
tight chambers designed for use with ETO. It is applied by commercial
applicators only; there are no residential uses of ETO.
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
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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 in-
house 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.
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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 .
The target occupational margin of exposure (MOE) for ETO is 30. It is based on the
uncertainty factor of SOX (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 3 OX.
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.
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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)
Intermediate-
Term
(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
(Snellingsetal., 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 FO males and
females and Fl males during premating period.
• Reproductive LOAEL = 25 ppm based on increased
postimplantation loss (two-fold) and decreased live
pups per litter in FO generation were observed.
• Offspring LOAEL = 25 ppm based on decreased
mean pup body weight gain in both FO and Fl
generations.
generations.
High end URF based on lung adenomas/carcinomas in male B6C3F1 mice = 2.22 E-02 (mg/m )" (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).
Cancer
(Inhalation)
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, Sd/week)) is adjusted to human NOAEL of 7.5 ppm (8 h/day, Sd/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
(Sdays 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 ), 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.
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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 IxlO'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 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 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 IxlO'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 ), there are risk estimates that
exceed EPA's level of concern from occupational exposure to workers in spice sterilization
facilities.
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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 post-
sterilization 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. Non-
cancer 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.
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Table 2. Summary of Non-cancer and Cancer Risk Estimates for ETO Uses
Use
Non-cancer Risk Estimate
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)
2.6xl04to2.1xl03
(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):
2.1xl05tol.7xl04
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
I.lxl05to9.2xl05
'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"4to 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.
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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 reregi strati on. The Agency has previously identified and required the
submission of the generic (technical grade) data to support reregi strati on 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 reregi strati on 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 reregi strati on 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 reregi strati on 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
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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
.
These comments were reviewed and taken into consideration in preparing the revised risk
assessments as well as the reregi strati on eligibility decisions presented in this document. The
comments and EPA's responses, are available in their entirety in the public docket EPA-HQ-
OPP-2005-0203 located on-line at .
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-OPP-
2005-0203 located on-line in the Federal Docket Management System (FDMS) at
.
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.
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3. Endocrine Disrupter 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 Disrupter 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 reregi strati on 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 .
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 reregi strati on
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.
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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
), 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.
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• 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 time-
weighted 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.
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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
reregi strati on 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 reregi strati on 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 non-
cancer 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 ), 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
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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 USD A, 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 .
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.
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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
.
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).
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Facilities are designed to physically separate areas of ETO-treated materials and non-
ETO-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 reregi strati on 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, long-
term 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 reregi strati on 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:
> 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.
> 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 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.
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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 Ibs of ETO per cubic feet of sterilized devices (i.e., 16 to 40 Ibs 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 (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 IxlO"6 and IxlO"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 IxlO"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 reregi strati on.
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
.
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.
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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 reregi strati on.
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 reregi strati on.
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.
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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., Clostridiumperfringens, 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.
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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 USD A, 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
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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
.
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
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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 reregi strati on 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:
> The most recent monitored ambient levels of ETO in the facility.
> The potential health effects from the levels of ETO in the facility.
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> The emergency response plan and how to respond in an emergency.
> 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 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, break areas) to have accurate
information regarding exposure of employees who are not wearing respirators as part of
their daily routine.
/ 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. Non-
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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
io-5.
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.
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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
.
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
io-5.
EPA policy for non-dietary risks in the IO"5 to IO"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 reregi strati on with
the implementation of the following mitigation.
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• 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.
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V. What Registrants Need to Do
The Agency has determined that products containing the active ingredient ETO are
eligible for reregi strati on 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 reregi strati on. For product-
specific 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 reregi strati on, 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 reregi strati on 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. Data Requirement for the Reregistration of ETO.
Data Requirement
Documentation of Presence of Pathogens in Internal Surfaces of Musical
Instruments
New OPPTS Guideline Number
(GLN)
Special Study
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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 reregi strati on, 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.
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In order to be eligible for reregi strati on, amend all product labels to incorporate the risk mitigation measures outlined in Section IV.
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 ,
Placement on Label -
'•/•- ••-. ' '-.,, _ ' •• '"'.•','• •' ''_ManufacturirigTJse'Pro(iucts ' '',;.. v ''•'; •'',',',!" ''•-.'. . '. . "
For all Manufacturing
Use Products
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
Environmental Hazards
Statements Required
by the RED and
Agency Label Policies
"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]."
"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)."
"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."
Directions for Use
Directions for Use
Precautionary Statements
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 following/below
Precautionary Statements: Hazards to
Humans and Domestic Animals
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"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) positive-
pressure 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 full-
facepiece supplied-air respirator equipped with an auxiliary positive-
pressure 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."
PPE Requirements for
beekeeping use
"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."
"All handlers must wear at a minimum:
In the PPE section of the label
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User Safety
Requirements
User Safety
Recommendations
User Safety
> 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.
1 . Follow the respirator manufacturer's user's instructions for changing
canisters.
2. Respirators must be fit-tested and fit-checked using a program that
conforms to OSHA's requirements (see 29CFRPart 1910.134).
3 . Respirator users must be trained using a program that confirms to
OSHA's requirements (see 29CFRPart 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 29CFRPart 1910.134).
"Follow manufacturer's instructions for cleaning/maintaining PPE. If no
such instructions for washables exist, use detergent and hot water. Keep
and wash PPE separately from other laundry."
"User Safety Recommendations
In the PPE section of the label
Precautionary Statements: Hazards to
Humans and Domestic Animals
immediately following the PPE
requirements
Precautionary Statements under:
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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 Humans and Domestic
Animals immediately following
Engineering Controls
(Must be placed in a box.)
Environmental Hazards
"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 Statements immediately
following the User Safety
Recommendations
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
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library/museum
artifacts, cosmetics,
and 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."
Other Application
Restrictions for
products with
directions for use in
contract sterilization
facilities: spice use
(Risk Mitigation)
"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
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evacuations) between 1.5 PSIA (27" Hg) and 5.0 PSIA (20" Hg) while
maintaining a minimum chamber temperature of 115° F."
Other Application
Restrictions for
products with
directions for use in
beekeeping
(Risk Mitigation)
"Do not treat combs containing honey."
Directions for Use
Other Application
Restrictions
Currently required in
the 29 CFR
Employers in facilities that use ETO must comply with all of the
requirements for ETO use specified in 29 CFR 1910.1047.
Directions for Use
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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 spice s].
.
Centers for Disease Control and Prevention (CDC). 2001. Outbreaks: 2001 diseases outbreaks
due to bacterial etiologies.
.
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.
.
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
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Knee, Elizabeth. Ethylene Oxide SMART Meeting Minutes. United States Environmental
Protection Agency, Office of Pesticide Programs, Special Review and Reregi strati on
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.
.
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
toxicologicpotential of ethylene oxide inB6C3Fl 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, FJ. and Klontz, K.C. 2006. Recalls of spices due to
bacterial contamination monitored by the U.S. Food and Drug Administration: The
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predominance of Salmonellae. Journal of Food Protection 69:233-237.
.
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 Reregi strati on Division. May 4, 2007.
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Appendix A. ETO Uses and Use-Patterns Eligible for Reregistration
Use Pattern
LIMITATIONS
Medical
Musical
Instruments
Library and
Museum
Artifacts
Cosmetic
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 non-
portable 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 non-
portable ethylene oxide gas sterilizers that meet FDA regulatory requirements and in
accordance with directions supplied by the sterilizer manufacturer.
Spice
Beekeeping
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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 reregi strati on 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.
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Guideline
Number
Requirement
Use Pattern
Bibliographic Citation(s)
(MRID)
Occupational/Residue Exposure
Special Study
Special Study
ETO Specific Worker Monitoring Study to
Support the Medical Sterilization Uses
ETO Specific Worker Monitoring Study To
Support the Spice Sterilization Use
L,M,N
L,M,N
47331801
47338301
Toxicology
830.7800
2-Generation Reproduction - Rat
L,M,N
42788101
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Appendix C. Technical Documents to Support the ETO RED
Additional documentation in support of this RED is maintained in the OPP docket EPA-HQ-
OPP-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:
.
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 sixty-
day 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 Reregi strati on 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 Reregi strati on Eligibility Decision (RED) for Ethylene
Oxide. March 24, 2008.
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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.
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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.
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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 reregi strati on 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.
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Appendix G. List of Available Related Documents and Electronically Available Forms
Pesticide Registration Forms are available at the following EPA internet site:
.
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.mcole@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 Arlington, (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
8570-4
8570-5
8570-17
8570-25
8570-27
8570-28
8570-30
8570-32
8570-34
8570-35
8570-36
8570-37
Application for Pesticide
Registration/Amendment
Confidential Statement of Formula
Notice of Supplemental Registration of
Distribution of a Registered Pesticide
Product
Application for an Experimental Use
Permit
Application for/Notification of State
Registration of a Pesticide To Meet a
Special Local Need
Formulator's Exemption Statement
Certification of Compliance with Data
Gap Procedures
Pesticide Registration Maintenance Fee
Filing
Certification of Attempt to Enter into an
Agreement with other Registrants for
Development of Data
Certification with Respect to Citations of
Data (in PR Notice 98-5)
Data Matrix (in PR Notice 98-5)
Summary of the Physical/Chemical
Properties (in PR Notice 98-1)
Self-Certification Statement for the
Physical/Chemical Properties (in PR
Notice 98-1)
http://www.epa.gov/opprd001/forms/8570-l.pdf
http://www.epa.gov/opprd001/forms/8570-4.pdf
http://www.epa.gov/opprdOO l/forms/8570-5 .pdf
http://www.epa.gov/opprd001/forms/8570-17.pdf
http://www.epa.gov/opprdOO l/forms/8570-25 .pdf
http://www.epa.gov/opprd001/forms/8570-27.pdf
http://www.epa.gov/opprd001/forms/8570-28.pdf
http://www.epa.gov/opprd001/forms/8570-30.pdf
http://www.epa.gov/opprd001/forms/8570-32.pdf
http://www.epa.gov/opppmsdl/PR Notices/pr98-5.pdf
http://www.epa.gov/opppmsdl/PR Notices/pr98-5.pdf
http://www.epa.gov/opppmsdl/PR_Notices/pr98-l.pdf
http://www.epa.gov/opppmsdl/PR Notices/pr98-l.pdf
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Pesticide Registration Kit available at .
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
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)
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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: .
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.
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