Docket Number EPA-HQ-OPP-2013-0244
www.regulations.gov
^7
Ethylene Oxide
Proposed Interim Registration Review Decision
Case Number 2275
March 2023
Approved by:
Anita Pease
Director
Antimicrobials Division
Date: 03/28/2023
IV yi A p V DP A\/PC Digitally signed by MARY REAVES
IVlMrvY nLnvtj Date:2023.03.28 13:44:29-04'00'
Mary Elissa Reaves, Ph.D.
Director
Pesticide Re-evaluation Division
Date:
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Table of Contents
I. INTRODUCTION
A. Summary of EtO Registration Review Timeline
B. EtO Special Review
C. Summary of Public Comments on the Draft Risk Assessments and Agency Response.
II. USE AND US AGE
III. SCIENTIFIC ASSESSMENTS
A. Human Health Risks
Risk Summary and Characterization
Human Incidents and Epidemiology
Tolerances
Human Health Data Needs
B. Ecol ogi cal Ri sks
Risk Summary and Characterization
Ecological Incidents
Ecological and Environmental Fate Data Needs
C. Benefits Assessment
D. Alternatives for Medical Device Sterilization and Spice Fumigation
IV. INTERAGENCY CONSIDERATIONS
A. Occupational Safety and Health Administration (OSHA)
B. Food and Drug Administration (FDA)
V. PROPOSED INTERIM REGISTRATION REVIEW DECISION
A. Proposed Risk Mitigation and Regulatory Rationale
Proposed Termination of Uses
Proposed EtO Use Rate Reduction
Proposed Mitigation for Residential Bystander Risk
Proposed Mitigation for Non-Residential Bystander Risk
Proposed Mitigation for Occupational Risk
Engineering Controls for Healthcare Facilities
Label Consistency and Clarification
B. Environmental Justice
C. Tolerance Actions
D. Proposed Interim Registration Review Decision
E. Data Requirements
.. 3
.. 6
.. 8
.. 9
10
13
13
14
23
23
24
25
25
27
27
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29
34
35
39
44
44
45
47
52
54
54
54
63
64
66
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71
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F. Summary of Proposed Recordkeeping Requirements 71
G. Summary of Public Comment Requested 72
VI. NEXT STEPS AND TIMELINE 77
A. Proposed Interim Registration Review Decision 77
Appendix A: Summary of Proposed Actions for EtO 79
Appendix B: Proposed Labeling Changes for EtO Products 82
Appendix C: Listed-Species Assessment 89
Appendix D: Endocrine Disruptor Screening Program 91
Appendix E: Summary of Public Comments on the Draft Risk Assessments and Agency
Responses 93
Appendix F: Explanation of Office of Air and Radiation and Office of Pesticide Programs
Cancer Risk Thresholds 99
I. INTRODUCTION
Executive Summary
As a pesticide,1 EtO is primarily used as a sterilant for medical devices and equipment, and it is
highly valuable because it is a penetrative gas that has a high throughput capacity, is effective at
a wide range of temperatures, and is compatible with a broad range of materials. EtO is used on
approximately 50% of all sterilized medical devices, annually, including an estimated 95% of all
surgical kits. Presently, there are no viable alternatives to EtO for the sterilization of certain
medical devices and equipment. The absence of EtO for use on medical devices and equipment
would cause widespread disruption to the availability of sterile medical devices. In the U.S. EtO
is also used during the processing and reconditioning of dried herbs and spices to reduce
foodborne pathogens of concern such as Salmonella and Escherichia coli.
EtO is a known carcinogen. The registered pesticidal uses of EtO pose inhalation risks to
workers inside commercial sterilization facilities, healthcare facilities, and to those treating
beekeeping equipment in North Carolina. EtO also has the potential to pose inhalation risks to
communities near facilities where EtO is used. Therefore, EPA is proposing mitigation to
address inhalation risk concerns, including the termination of certain uses, a use rate reduction
through reduced concentrations, a series of engineering controls within commercial sterilization
facilities and healthcare facilities, respiratory protection requirements for commercial
sterilization facilities, monitoring, training, and recordkeeping requirements, as well as
establishing an action limit based on the current lowest technologically measurable (i.e.,
1 Ethylene Oxide (EtO) is a flammable, colorless gas that is primarily used to make other chemicals that are used in
making a range of products, including antifreeze, textiles, plastics, detergents, and adhesives. This Proposed Interim
Decision (PID), in accordance with the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) focuses only
on the regulation of the pesticidal uses for EtO. Other activities involving EtO, including manufacturing, may be
regulated under other statutes and/or by other agencies.
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quantifiable)limit. Additionally, at the time this Proposed Interim Decision is released for public
comment, EPA's Office of Air and Radiation (OAR) is concurrently releasing for public
comment their Proposed Rulemaking for EtO commercial sterilizers, National Emission
Standards for Hazardous Air Pollutants (NESHAP): Ethylene Oxide Emissions Standards for
Sterilization Facilities Residual Risk and Technology Review.2 OAR is proposing to revise the
NESHAP for commercial sterilization facilities by both amending existing standards and
establishing additional standards, in order to reduce EtO emissions to residential communities.
This document is the Environmental Protection Agency's (EPA or the Agency) Proposed Interim
Registration Review Decision (PID) for ethylene oxide, henceforth referred to as EtO (PC Code
042301, case 2275). In a registration review decision under the Federal Insecticide, Fungicide,
and Rodenticide Act (FIFRA), the Agency determines whether a pesticide continues to meet
FIFRA's registration standard.3 Where appropriate, the Agency may issue an interim registration
review decision before completing a registration review.4 Among other things, the interim
registration review decision may determine that new risk mitigation measures are necessary, lay
out interim risk mitigation measures, identify data or information required to complete the
review, and include schedules for submitting the required data, conducting the new risk
assessment and completing the registration review.5 For more information on EtO, see EPA's
public docket for this chemical's registration review case (EPA-HQ-OPP-2013-0244) at
www.reeulatioms. gov.
FIFRA6 mandates the continuous review of existing pesticides. All pesticides distributed or sold
in the United States must be registered by EPA based on scientific data showing that they will
not cause unreasonable adverse effects to human health or to the environment when used as
directed on product labeling. In 2006, the Agency began implementing the registration review
program. EPA generally reviews each registered pesticide every 15 years. Through the
registration review program, the Agency intends to verify that all registered pesticides continue
to meet the registration standard as the ability to assess and reduce risk evolves and as policies
and practices change. By periodically re-evaluating pesticides as science, public policy, and
pesticide-use practices change, the Agency ensures that the public can continue to use products
in the marketplace that do not present unreasonable adverse effects. For more information on the
registration review program, see http://www.epa.gov/pesticide-reevaluation.
EtO was first registered as a pesticide in the U.S. in 1966. Because it was registered before 1984,
it was subject to reregi strati on and a Reregi strati on Eligibility Decision was completed by EPA
in 2008. There is currently one technical registrant—ARC Specialty Products of Balchem
Corporation.
In addition to the registration review of EtO as a pesticide under FIFRA, the Agency also
conducts a periodic review of air emission standards for air pollutants, including EtO, through
2 EP A-HQ-0 AR-2019-0178.
3 Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) § 3(g), 7 U.S.C. § 136a(g); 40 C.F.R. § 155.57.
4 40 C.F.R. §§ 155.56, 155.58.
5 40 C.F.R. § 155.56.
6 As amended by the Food Quality Protection Act (FQPA) of 1996, Pub. L. No. 104-170, 110 Stat. 1489 and by the
Consolidated Appropriations Act, 2023, Pub L. No. 117-328, § 711, 136 Stat. 4459 (2022).
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the National Emission Standards for Hazardous Air Pollutants (NESHAP) under the Clean Air
Act. At the same time as the issuance of this Office of Pesticide Programs (OPP) Proposed
Interim Decision for EtO, the Office of Air and Radiation (OAR) is proposing updates to the
emission standard for EtO in Proposed National Emission Standards for Hazardous Air
Pollutants: Ethylene Oxide Commercial Sterilization and Fumigation Operations (EPA-HQ-
OAR-2019-0178). The proposed requirements set forth in each Agency action are
complementary in that they are intended to reduce public health risks from EtO exposure. The
OAR proposed rulemaking focuses on reducing EtO emissions released outside the facilities for
residential bystanders of commercial sterilization facilities. OPP's proposed mitigation measures
for sterilizations and other facilities that use EtO will also reduce EtO exposure to people outside
the facilities, including residential and non-residential bystanders (i.e., those who go to work or
school near facilities), as well as reduce risks to workers exposed to EtO inside the facilities.
OPP's mitigation applies to all commercial sterilization facilities in the U.S. OPP is also
proposing mitigation to healthcare facilities, and all niche uses of EtO (i.e., beekeeping
equipment; museum, library, and archival materials, cosmetics; and musical instruments).
Conversely, OAR's mitigation is focused only for the commercial sterilizers source category. At
the time of OAR's assessment on commercial sterilizers, 23 out of 85 facilities were identified as
high risk. See Appendix F.
The Agency is issuing a PID for EtO so that it can move forward with aspects of the registration
review and propose risk mitigation (see Appendices A and B). EPA is currently working with the
U.S. Fish and Wildlife Service and the National Marine Fisheries Service (the Services) to
improve the consultation process for federally listed threatened and endangered (listed) species
for pesticides under the Endangered Species Act (ESA).7 The Agency has not yet fully evaluated
EtO's risks to federally listed species. However, EPA will complete its listed-species assessment
and any necessary consultation with the Services before completing the registration review of
EtO. Before completing registration review, EPA will also complete endocrine screening for EtO
under the Federal Food, Drug, and Cosmetic Act (FFDCA).8 For more information on the listed-
species assessment and the endocrine screening for the EtO registration review, see Appendices
C and D. The EtO Registration Review case thus cannot be considered complete until the
Agency assesses the aforementioned ESA assessment and endocrine screening; however, EPA
will require mitigation to address risks to EtO following the publication of the Interim or Final
Decision, even if EPA has not yet completed its ESA obligations.
EPA has highlighted specific areas in the PID where additional information is needed. The
Agency welcomes comments on all aspects of the PID.
This document is organized in six sections:
• Introduction (summarizing the registration review milestones and responding to public
comments);
• Use and Usage (discussing how and where EtO is used);
7 Endangered Species Act (ESA) § 7, 16 U.S.C. § 1536.
8 Federal Food, Drug, and Cosmetic Act (FFDCA) § 408(p), 21 U.S.C. § 346a(p).
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• Scientific Assessments (summarizing EPA's risk and benefits assessments, updating or
revising previous risk assessments, and discussing risk characterization);
• Interagency Considerations (discussing EPA's coordination with OSHA and FDA on
EtO regulation);
• Proposed Interim Registration Review Decision (presenting EPA's proposed decision,
registration rationale, and any mitigation measures to address risks of concern); and
• Next Steps and Timeline (discussing how and when EPA intends to complete registration
review).
A. Summary of EtO Registration Review Timeline
On September 25, 2013, the Agency formally initiated registration review for EtO with the
opening of the registration review docket for the case.9 The following summary highlights the
docket opening and other significant milestones that have occurred thus far during the
registration review of EtO:
• September 2013 - EPA posted the EtO Preliminary Work Plan (PWP) (September 25,
2013) to the public docket for a 60-day public comment period. Along with the PWP, the
following documents were also posted in the ethylene oxide registration review docket
(EPA-HQ-OPP-2013 -0244):
o Ethylene Oxide (ETO): Review of Human Incidents (May 8, 2013)
o BEAD Chemical Profile for Registration Review: Ethylene Oxide (ETO) (042301)
(September 25, 2013)
• April 2014 - EPA posted the EtO Final Work Plan (FWP) (April 4, 2014) to the public
docket. The Agency received 12 comments on the PWP. Public comments on the PWP
did not change the schedule, risk assessment needs, or anticipated data requirements in
the FWP. In the FWP, EPA corrected the anticipated Registration Review schedule and
noted that no additional data were needed outside of what was required in the PWP. After
the PWP public comment period closed, the Agency received additional information from
the Ethylene Oxide Sterilization Association, Inc. that was considered in the risk
assessment phase of registration review. This additional information can be found in
docket EPA-HQ-OPP-2013-0244 at www.reeulations.eov.
• October 2014 - EPA issued a generic data call-in (GDCI) for EtO to obtain data needed
to conduct the registration review risk assessments (GDCI-042301-1428). The registrants
submitted all required data except the non-guideline study Monitoring Data on Fumigated
Commodities (required for the spice use only). The registrants submitted a waiver request
for this study (MRID 50384901) on September 8, 2017. However, this waiver request
was denied on July 17, 2018, due to a lack of information related to potential exposures
within the various channels of trade after fumigation, dissipation of EtO beyond the
facility, and the analytical method used to measure air concentrations.10 The Agency has
9 40 C.F.R. § 155.50.
10 Ethylene Oxide (EtO): Response to registrant's inhalation exposure monitoring requirements waiver request.
Decision Number 533138. June 21, 2018.
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been coordinating with the Ethylene Oxide Task Force (EOTF) to fulfill this data
requirement and is awaiting a protocol submission by EOTF. Accordingly, all data
requirements have not been satisfied. For more information, see Sections III.A. and III.B.
• November 2020 - EPA posted the Ethylene Oxide (EtO) Draft Human Health and
Ecological Risk Assessment in Support of Registration Review (2020 DRA) for a 60-day
public comment period. The Agency received 15 comments from 10 commenters. After
the DRA public comment period closed, the Agency received additional submissions
from the Ethylene Oxide Task Force and the American Chemistry Council. The Agency
determined that the submissions included information that had already been considered
during development of the DRA. All comments can be found in the docket for the EtO
case. The Agency has summarized and responded to these comments in Appendix E. The
comments did not change the risk assessments or registration review timeline for EtO.
• March 2023 - The Agency has completed the PID for EtO. The PID is posted to the
docket for a 60-day public comment period. Along with the PID, the following
documents are also posted to the EtO docket.
o Response to Public Comments for the Ethylene Oxide (EtO) Draft Risk
Assessment (DRA). March 27, 2023.
o Ethylene Oxide (EtO). Addendum to "Draft Human Health and Ecological Risk
Assessment in Support of Registration Review" - Inhalation Exposure Risk
Assessment in Support of Registration Review. March 27, 2023.
o Review of MRID 50231101. Ethylene Oxide Exposures for Ethylene Oxide
Sterilization Plant Workers Submitted in Response to the Registration Review
GDCI for EtO. March 23, 2023.
o Food and Drug Administration Center for Devices and Radiological Health
(FDA-CDRH) Medical Device Benefits Statement. March 15, 2023.
o Ethylene Oxide (EtO) Spice Sterilizing Facilities. Center for Food Safety and
Applied Nutrition (CFSAN), Food and Drug Administration (FDA) responses to
questions from Office of Pesticide Programs (OPP), Environmental Protection
Agency (EPA). December 20, 2022.
o Ethylene Oxide (PC# 042301): Use, Usage, Benefits, and Impacts of
Cancellation. December 1, 2022.
o Ethylene Oxide (EtO): Response to registrant's ambient air monitoring
requirements waiver request. October 12, 2022.
o Letter from Dr. Girvin Liggans, Acting Deputy Director for Plant Derived Foods,
Office of Food Safety, Center for Food Safety and Applied Nutrition, Food and
Drug Administration to Edward Messina, Director, Office of Pesticide Programs,
Environmental Protection Agency. August 18, 2022.
o Email Response to FDA and EPA Questions. Shannen Kelly, American Spice
Trade Association (ASTA) to Aparna Tatavarthy, Office of Food Safety, Center
for Food Safety and Applied Nutrition, Food and Drug Administration. August
12, 2022.
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o Ethylene Oxide (EtO): Summary of Hazard and Science Policy Council
(HASPOC) Meeting on June 9th, 2022: Recommendations on the Need for a
Special Acute Inhalation Toxicity Study. June 14, 2022.
o Overview of Application Methods and Factors, Use, Usage, and Benefits of
Commodity and Structural Fumigants: Phosphine [(066500) including Aluminum
Phosphide (066501) and Magnesium Phosphide (066504)], Propylene Oxide
(042501), Sulfur Dioxide (077601), Sodium Metabisulfite (111409), Sulfuryl
Fluoride, (078003), Ethylene Oxide (042301), and Methyl Bromide (053201).
October 5, 2020.
o Letter from Laura Shumow, Executive Director, American Spice Trade
Association (ASTA) to Susan Bartow, Pesticide Re-evaluation Division, Office of
Pesticide Programs, Environmental Protection Agency. June 25, 2020.
o Ethylene Oxide (ETO): Response to registrant's inhalation exposure monitoring
requirements waiver request. June 21, 2018.
o Ethylene Oxide (ETO): Review of MRID 50231103 "Supplemental Information
on Ethylene Oxide Industry Usage and Product Use Information." July 19, 2018.
o Ethylene Oxide: Revised Response to Data Waiver Requests Submitted by the
Ethylene Oxide Task Force. March 9, 2018.
o Ethylene Chlorohydrin: Summary of Hazard and Science Policy Council
(HASPOC) Meeting of January 21, 2016. Recommendations on the Requirement
for a Chronic/Cancer Study. June 16, 2016.
o Ethylene Oxide: Response to Data Waiver Requests Submitted by the Ethylene
Oxide Task Force. January 21, 2016.
o Ethylene Oxide/Ethylene Chlorohydrin: Summary of Hazard and Science Policy
Council (HASPOC) Meeting of April 11, 2013. Recommendations on the need
for multiple toxicology studies. May 14, 2013.
B. EtO Special Review
As discussed above, through the registration review of EtO, EPA will determine whether EtO
continues to meet the standard for registration under FIFRA - i.e., does not cause unreasonable
adverse effects on the environment. Based on this determination, the Agency also intends to
initiate termination of its Special Review of EtO. The Special Review process predates, and is
distinct from, the registration review and reregi strati on processes. EPA may initiate the Special
Review process if EPA determines that the use of a pesticide may pose significant risks. EtO
entered EPA's Special Review process in 1978 based on concern for potential developmental
toxicity, mutagenicity, and neurotoxic effects in workers who are exposed to EtO. A Position
Document 1 (PD1) was published in the Federal Register on January 27, 1978, to announce the
initiation of the Special Review.11 In the early 1980s, the carcinogenicity of EtO became of
concern and was included for consideration in the Special Review.
To terminate the Special Review of a chemical substance, EPA must publish first a Notice of
Preliminary Determination, followed by a Notice of Final Determination, addressing the
Agency's determination of whether the use of a pesticide causes unreasonable adverse effects to
11 43 Fed. Reg. 3,801.
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human health or the environment. On October 29, 2008, the Agency announced in the Federal
Register the availability of Position Document 2/3 (PD 2/3). PD 2/3 presented the Agency's
preliminary determination to terminate the Special Review of EtO after publication of the
Reregi strati on Eligibility Decision (RED).12 The Agency has not published a final determination
terminating the Special Review of EtO, and since publication of the preliminary determination
has received additional data about EtO which EPA has incorporated into the human health
assessment for the registration review of EtO.
However, because through registration review EPA will be making a determination as to
whether the use of EtO causes unreasonable adverse effects to human health or the environment
- the same purpose for which Special Review is undertaken, EPA intends to initiate termination
of the Special Review of EtO pursuant to the Agency's Special Review regulations based on the
outcome of registration review. Following the publication of the ID or Final Decision, EPA will
publish the Notice of Preliminary Determination, then publish the Notice of Final Determination
after the public comment period on the Notice of Preliminary Determination. EPA will continue
to review the registration of EtO as part of the ongoing registration review process.
C. Summary of Public Comments on the Draft Risk Assessments and Agency Response
During the 60-day public-comment period for the EtO Draft Risk Assessment (November 20,
2020 to January 19, 2021), the Agency received 15 public comments from 10 commenters. After
the DRA public comment period closed, additional comments were submitted by the American
Chemistry Council (ACC) and the Ethylene Oxide Task Force (EOTF) on March 19, 2021. The
comments submitted by ACC and the EOTF were determined to be similar to comments received
from the Louisiana Chemical Association (LCA) and are addressed in the EPA's responses to
those commenters. Comments were submitted by representatives from government, non-profit
groups, and industry as summarized below:
• United States Department of Agriculture (USD A)
• Harris County, Texas
• Earthjustice, on behalf of Air Alliance Houston et al.
• University of California, San Francisco (UCSF) et al.
• North Carolina State University
• Louisiana Chemical Association (LCA)
• The Ethylene Oxide Sterilization Association (EOSA)
• Ethylene Oxide Task Force (EOTF)
• The American Chemistry Council (ACC)
• Elite Spice, Inc.
The Agency has summarized and responded to all substantive comments and comments of a
broader regulatory nature in Appendix E and in the Response to Public Comments for the
12 73 Fed. Reg. 64,318.
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Ethylene Oxide (EtO) Draft Risk Assessment (DRA). The Agency thanks all commenters for
participating and has considered all comments in developing this PID.13
II. USE AND USAGE
EtO was first registered as a pesticide in the U.S. in 1966. Because it was registered before 1984,
it was subject to reregi strati on, and a RED was completed by EPA in 2008. There is currently
one technical registrant—ARC Specialty Products of Balchem Corporation.
There are 16 registered FIFRA Section 3 products containing EtO as an active ingredient (a.i.),
and one FIFRA section 24(c) registration for the use of EtO in beekeeping in North Carolina.
EtO is formulated and marketed as a pressurized gas. The end-use formulations are all gas
mixtures of EtO and other gases (e.g., carbon dioxide) in varying concentrations. Table 1
below presents a summary of the registered antimicrobial and conventional uses of EtO.
Table 1. Summary of EtO Registered Uses
i:i'\
kcu \n
"..a i
I'ackauiiiu
(IK) ( oiilciili
I se Sue
36736-2
100
Bulk Cylinder
Medical or laboratory items, pharmaceuticals, and aseptic packaging,
(21 CFR 201.1(d)(5)), whole and ground spices or other seasoning
materials (40 CFR 180.151), artifacts, archival material, library
objects, cosmetics and musical instruments.
36736-3
80
Bulk Cylinder
Medical or laboratory items, pharmaceuticals, and aseptic packaging,
(21 CFR 201.1(d)(5)), whole and ground spices or other seasoning
materials (40 CFR 180.151), artifacts, archival material, library
objects, cosmetics and musical instruments.
36736-4
10
Bulk Cylinder
Medical or laboratory items, pharmaceuticals, and aseptic packaging,
(21 CFR 201.1(d)(5)), whole and ground spices or other seasoning
materials (40 CFR 180.151), artifacts, archival material, library
objects, cosmetics and musical instruments.
36736-5
20
Bulk Cylinder
Medical or laboratory items, pharmaceuticals, and aseptic packaging,
(21 CFR 201.1(d)(5)), whole and ground spices or other seasoning
materials (40 CFR 180.151), artifacts, archival material, library
objects, cosmetics and musical instruments.
36736-6
12
Bulk Cylinder
Medical or laboratory items, pharmaceuticals, and aseptic packaging,
(21 CFR 201.1(d)(5)), whole and ground spices or other seasoning
materials (40 CFR 180.151), artifacts, archival material, library
objects, cosmetics and musical instruments.
36736-7
8.5
Bulk Cylinder
Medical or laboratory items, pharmaceuticals, and aseptic packaging,
(21 CFR 201.1(d)(5)), whole and ground spices or other seasoning
materials (40 CFR 180.151), artifacts, archival material, library
objects, cosmetics and musical instruments.
36736-8
100
Technical registration14
Medical/lab items; pharmaceuticals; packaging; spices; seasonings;
artifacts, archival material, library objects
69340-2
97
Ampule (18.15 g)
Surgical instruments; hospital instruments; hospital critical equipment;
heat labile materials; oral and inhalation equipment; diagnostic
13 Response to Public Comments for the Ethylene Oxide (EtO) Draft Risk Assessment (DRA). Decision Number:
569904. EPA-HQ-OPP-2013-0244.
14 A technical product is a registered pesticide product that is solely used to formulate other pesticide products.
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Table 1. Summary of EtO Registered Uses
i:i'\
kcu. No.
".i ;i.i
kackamim
(1 !i() Coiiieiil)
I se Siie
instruments/equipment; hospital critical rubber/plastic items; hospital
materials; first aid equipment; veterinary hospital instruments;
veterinary hospital critical equipment; human face gear; contact lens.
69340-4
96
Cartridge (5 to 14 g)
Surgical instruments; hospital instruments; hospital critical equipment;
heat labile materials; oral and inhalation equipment; diagnostic
instruments/equipment; hospital critical rubber/plastic items; hospital
materials; first aid equipment; veterinary hospital instruments;
veterinary hospital critical equipment; human face gear; contact lens.
69340-5
90
Cartridge (4.5 g)
Surgical instruments; hospital instruments; hospital critical equipment;
heat labile materials; oral and inhalation equipment; diagnostic
instruments/equipment; hospital critical rubber/plastic items; hospital
materials; first aid equipment; veterinary hospital instruments;
veterinary hospital critical equipment; human face gear; contact lens.
69340-6
96
Cartridge (10.5 g)
Surgical instruments; hospital instruments; hospital critical equipment;
heat labile materials; oral and inhalation equipment; diagnostic
instruments/equipment; hospital critical rubber/plastic items; hospital
materials; first aid equipment; veterinary hospital instruments;
veterinary hospital critical equipment; human face gear; contact lens.
69340-7
97
Ampule (17.6 g)
Surgical instruments; hospital instruments; hospital critical equipment;
heat labile materials; oral and inhalation equipment; diagnostic
instruments/equipment; hospital critical rubber/plastic items; hospital
materials; first aid equipment; veterinary hospital instruments;
veterinary hospital critical equipment; human face gear; contact lens.
69340-9
97
Cartridge (17.6 g)
Surgical instruments; hospital instruments; hospital critical equipment;
heat labile materials; oral and inhalation equipment; diagnostic
instruments/equipment; hospital critical rubber/plastic items; hospital
materials; first aid equipment; veterinary hospital instruments;
veterinary hospital critical equipment; human face gear; contact lens.
7182-1
100
Cartridge
(100 to 170 g)
Medical equipment and supplies, musical instruments, library /museum
artifacts, and cosmetics.
73711-5
100
Ampule
(100 to 170 g)
Medical or laboratory items, pharmaceuticals, and aseptic packaging,
cosmetics, and artifacts, archival material or library objects.
89514-1
100
Bulk Cylinder
Medical or laboratory items, pharmaceuticals, and aseptic packaging,
cosmetics, spices or other seasoning materials, artifacts, archival
material or library objects, musical instruments.
NC140003
8.5
Bulk Cylinder
(parent label)
Special Local Need for beekeeping equipment in North Carolina. The
parent label is 36736-7.
Note: All End Use Products (EPs) and technical products are formulated as pressurized gas.
EtO is registered for sterilization of medical devices and equipment (including veterinary
equipment), laboratory items, pharmaceuticals, and aseptic packaging. EtO is registered to
reduce the microbial load on dried herbs and spices, processed vegetables that have been dried or
dehydrated, archival and museum materials, musical instruments, and cosmetics. Additionally,
EtO is registered for use under a special local needs registration in North Carolina for use on
beekeeping equipment contaminated with American foulbrood (AFB) or other pests.
EPA's Office of Air and Radiation's Office of Air Quality Planning and Standards (OAR
OAQPS) estimates that the overall EtO usage as a pesticide (sterilant) in the U.S. is 14 million
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pounds annually15. As a pesticide, the majority of EtO usage in the U.S. is for sterilization of
medical equipment. Usage of EtO for dried herb and spice fumigation is the second most
common use pattern and represents approximately 5 - 6% of the total EtO used within the U.S.
The American Spice Trade Association (ASTA) reports that the spice industry uses
approximately 800,000 pounds of EtO on an annual basis in the U.S.16. For beekeeping
equipment, the use of EtO is limited via a FIFRA section 24(c) registration to one facility in
North Carolina, and the amount of EtO used pursuant to this registration is likely to be low. The
Agency expects the total EtO usage for other registered use sites—musical instruments,
cosmetics, museum, library, and archival materials—to be very low or zero. There are 97
commercial sterilization facilities using EtO in the U.S. (86 commercial sterilization facilities
that are currently in operation and 11 research and development facilities); five of the facilities
treat only dried herbs and spices, four facilities treat both medical devices and dried herbs and
spices, and the remaining 88 facilities treat only medical devices. EtO also is used to treat
medical equipment in healthcare facilities such as hospitals, veterinarian offices, and dental
offices.
Antimicrobial Uses: EtO is primarily used as a sterilant for new, single use, and reusable
medical devices and equipment (21 C.F.R. § 201). EtO is used to sterilize 50% of all sterilized
medical devices, annually, including an estimated 95% of all surgical kits17'18'19'20. The other
registered antimicrobial uses of EtO include the fumigation/sterilization of artifacts, archival
material, library objects, cosmetics, and musical instruments. The antimicrobial products are
packaged as bulk cylinders for use in tractor trailer-sized chambers in commercial sterilization
facilities or as cartridges for use in oven-sized chambers in healthcare facilities.
The application rates are not generally listed on the labels. The FDA website indicates that two
voluntary consensus standards (ANSI AAMI ISO 11135:2014 and ANSI AAMI ISO 10993-
7:2008(R)2012) describe how to develop, validate, and control EtO sterilization processes for
15 Usage information was collected for the year for which the most recent information was available at each facility,
ranging from 2005 to 2019, and was compiled from a number of sources including Clean Air Act Section 114
Information Collection Request for Chemical Manufacturers, EPA, state, or local government inspection reports,
company reports, and facility usage logs.
16 American Spice Trade Association (ASTA). 2020. ASTA's reply to EPA questions regarding ethylene oxide use
on spices. Email from Laura Shumow, Executive Directors, ASTA to Susan Bartow, Pesticide Re-Evaluation
Division, Office of Pesticide Programs, Environmental Protection Agency. June 25, 2020.
17 Gamma Industry Processing Alliance (GIPA). 2017. A Comparison of Gamma, E-beam, X-ray and Ethylene
Oxide Technologies for the Industrial Sterilization of Medical Devices and Healthcare Products. Found at
http://gipaHiance.net/wp-content/uploads/2013/01/GIPA-WP-GIPA-iia-Sterilization-Modalities-FINAL-Version-
M iber-308772.pdf. Accessed August 2021.
18 Federal Advisory Committee Act (FACA). 2019. General Hospital and Personal Use Devices Panel of the
Medical Devices Advisory Committee Meeting Announcement, FDA Executive Summary - EtO.
https://www.fda.gov/advisorv-committees/advisorv-committee~caletMlar/irovember~6~7~2019~general~hospital~and~
personal-use-devices-pa nel~medieal~devices~advisorv~committee#event~materials. Accessed August 2021.
19 Ethylene Oxide Task Force (EOTF). 2020. Ethylene Oxide Benefits Statement submitted by B&C Consortia
Management, L.L.C. on behalf of the EOTF. EOTF email to EPA regarding benefits of ethylene oxide for medical
devices. Email sent from Lisa Campbell, Partner, Bergeson & Campbell PC to Jessica Bailey, Antimicrobial
Division, Office of Pesticide Programs, Environmental Protection Agency. May 6, 2020.
20 B&C Consortia Management, LLC. 2014. Registration Review of Ethylene Oxide Stakeholder Meeting
presentation. Docket ID: EPA-HQ-OPP-2013-0244-0018. https://www.regulations.gov/document/EPA-HO-OPP-
201.3-0244-0018. Accessed July 2022.
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medical devices and the acceptable levels of residual EtO and ethylene chlorohydrin left on a
device after it has undergone EtO sterilization.21 These standards help ensure levels of EtO on
medical devices are within safe limits for patient use. These standards also ensure devices meet
sterility assurance levels.22
Conventional Uses: EtO is a commodity fumigant/sterilant registered for use to reduce pathogen
load (such as Salmonella and Escherichia coli) on dried herbs and spices, processed vegetables
that have been dried or dehydrated, and /or other seasoning materials. ASTA estimates that
approximately 40% of dried spices in the U.S. are treated with EtO each year.23 There are eight
products currently registered for treatment of dried herbs, dried spices, dried vegetables, and
seasoning materials. All of these products are formulated as pressurized gas contained in
cylinders.
Sterilization/fumigation with EtO must be performed only in vacuum or gas tight chambers
designed for use with EtO. The maximum application rate for treatment of dried herbs and
spices, dried vegetables, and other seasonings is 500 mg/L (or 31.22 lb a.i./l,000 ft3) in a sealed
chamber.
III. SCIENTIFIC ASSESSMENTS
A. Human Health Risks
The Agency has summarized the human health sections of the 2020 DRA and 2023 DRA
Addendum below. The Agency used the most current science policies and risk assessment
methodologies to prepare the risk assessment and addendum in support of the registration review
of EtO. For additional details on the 2020 DRA and 2023 DRA Addendum, see Ethylene Oxide
(EtO) Draft Human Health and Ecological Risk Assessment in Support of Registration Review
and Ethylene Oxide (EtO). Addendum to "Draft Human Health and Ecological Risk Assessment
in Support of Registration Review " - Inhalation Exposure Risk Assessment in Support of
Registration Review in EPA's public docket (EPA-HQ-OPP-2013-0244).
Definition of terms
For purposes of the registration review of EtO, EPA is using the following definitions for
describing the different groups of individuals exposed to EtO:
• Occupational handler: A person who is directly involved in EtO sterilization, in
commercial sterilization facilities, healthcare facilities or beekeeping operations. This
21 Ethylene chlorohydrin is a reaction product of EtO. See ANSI AAMI ISO 10993-7:2008(R)2012.
22 For additional information on sterilization for medical devices, please see: https://www.fda.gov/medical-
devices/general-hospital-devices-and-supplies/ethvlene-oxide-sterilization-inedical-devices.
23 American Spice Trade Association (ASTA). 2020. ASTA's reply to EPA questions regarding ethylene oxide use
on spices. Email from Laura Shumow, Executive Directors, ASTA, to Susan Bartow, Pesticide Re-Evaluation
Division, Office of Pesticide Programs, Environmental Protection Agency. June 25, 2020.
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employee, for example, would be loading or unloading sterilization or aeration
chambers/areas.
• Occupational bystander: A person who, by nature of their employment, could be
exposed to EtO. This includes employees within a facility or area where EtO is used, but
who do not directly handle EtO (for example, employees in control rooms or storage
warehouses). This also includes persons employed at other workplaces nearby facilities
or areas where EtO is used, who would spend a significant amount of time at that location
(e.g., 8 hours per day, 5 days per week). An occupational worker who is employed nearby
a facility in another workplace may also be referred to as a "non-residential bystander"
(see below).
• Non-residential bystander: A person who may be exposed to EtO who does not live near
a facility or area where EtO is used, but who may otherwise spend a significant amount
of time near the facility. For example, children in schools or daycares who typically
spend several hours per day and five days per week in that location.
• Residential bystander: A person who may be exposed to EtO who lives nearby a facility
or area where EtO is used.
Risk Summary and Characterization
Under the Federal Insecticide Fungicide and Rodenticide Act, OPP applies a "no unreasonable
risk" standard for both dietary and non-dietary exposures in making a risk management decision.
To help initially identify chemicals which may pose such unreasonable risks, OPP considers
whether the risks from a chemical exceed a specified level of concern. If a given risk exceeds
this level, OPP decides what further action, if any, is needed. OPP generally seeks to reduce the
risk to less than 1 x 10"6 (1 in 1 million) for both occupational and residential exposures. In some
cases, when it is not possible to mitigate to this level of risk and benefits of the pesticide are
high, a risk target of up to 1 x 10"4 (100 in 1 million) may be used for occupational exposures.
As explained in the following sections, The EtO concentration at which the cancer risk equals a
certain target level (1 x 10"4 or 1 x 10"6) was back calculated from the inhalation unit risk (IUR)
for adults. OPP generally seeks to reduce the risk to less than 1 x 10"6 (1 in a million) for both
occupational and residential exposures. At that level, OPP generally considers risks to be
negligible and would not pursue additional risk mitigation measures. In the case of EtO given its
high benefits, for occupational exposures, OPP also examines risks in the range of 1 x 10"4 (100
in 1 million) to determine whether benefits of use outweigh the risks and whether mitigation is
appropriate to reduce those risks. For EtO, risks exceed 100 in 1 million; however, the
corresponding benefits outweigh the risks, as explained in Section V.D. For occupational
bystanders employed in commercial sterilization facilities, healthcare facilities, and beekeeping
equipment treatment areas, EPA is establishing a risk threshold of 100 in 1 million. For
occupational bystanders employed in workplaces (i.e., non-residential bystanders) nearby EtO
treatment facilities, EPA is establishing a risk threshold of 1 in 1 million. Calculations in all
scenarios indicate EtO concentrations would have to be extremely low in order to meet either
risk threshold. As explained in the following sections, this calculation indicates that if the EtO
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exposure for workers in contract sterilization facilities in these areas does not exceed 0.19 ppb as
an 8-hour time-weighted average (TWA), the cancer risk will not exceed 1 x 10"4 (100 in 1
million). If the EtO exposure for workers employed in nearby workplaces (i.e., not the
commercial sterilization facility) does not exceed 0.0019 ppb, the cancer risk will not exceed 1 x
10"6 (1 in 1 million). This calculation of 0.0019 ppb is relevant to both the antimicrobial and
conventional uses of EtO.
EtO is a colorless, highly reactive gas. The primary route of exposure is by inhalation. Once
absorbed, EtO is distributed throughout the body and metabolized to ethylene glycol and to
glutathione conjugates. EtO is an electrophilic agent and alkylates (introduces an alkyl radical to)
nucleophilic groups in macromolecules such as hemoglobin and deoxyribonucleic acid (DNA).
EtO is genotoxic in almost all available studies, and the weight of evidence supports a mutagenic
mode of action for carcinogenicity of EtO. For workers employed in EtO-manufacturing
facilities and in sterilizing facilities, there is evidence of an increased association with cancer of
the lymphohematopoietic system and of breast cancer mortality in females. While there is
agreement on the association of EtO exposure with cancer of the lymphohematopoietic system,
the assessments presented in the qualitative 2020 Ethylene Oxide Draft Risk Assessment differ in
conclusions concerning the association of EtO exposure with breast cancer. However, the 2023
DRA Addendum includes a quantitative risk assessment based on the 2016 EPA Integrated Risk
Information System (IRIS) cancer assessment, which includes breast cancer risk.
Neurotoxicity is also observed in repeat dose toxicity studies with EtO in experimental animals
and from exposure in humans. Peripheral neuropathy, impaired hand-eye coordination and
memory loss have been reported in workers exposed to EtO for longer periods.
OPP collaborated with the Office of Research and Development's (ORD) and Office of Air and
Radiation (OAR) during their assessment process of EtO to further inform the cancer evaluation
characterization and ongoing work to characterize and mitigate exposures in the sterilizer
industry. Additionally, as part of the pesticide registration review process, OPP routinely meets
with stakeholders, including the EtO industry, and federal agencies such as the Occupational
Safety and Health Administration (OSHA) and the Food and Drug Administration (FDA). See
Section IV.
In the 2020 Ethylene Oxide Draft Risk Assessment, OPP presented multiple perspectives on
cancer evaluations for EtO but did not choose a single value for risk extrapolation, nor did OPP
provide a critical review of the available approaches. In the 2020 DRA, OPP recognized that,
despite several years of study by EPA and various stakeholders, there are different approaches
for addressing the cancer dose-response assessment for EtO. Nevertheless, based on the range of
cancer inhalation unit risks (IUR) provided in the qualitative assessment, OPP believed that
additional mitigation of EtO exposure would be necessary to address cancer risk from inhalation
exposure to EtO.
In the 2023 DRA Addendum, OPP updated a portion of the EtO risk characterization by
providing a quantitative risk assessment that used the inhalation unit risk (IUR) value from the
2016 EPA IRIS cancer assessment to assess inhalation cancer risk to workers and bystanders.
The 2016 IRIS assessment went through "unusually extensive processes for the consideration of
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public comment and external peer review," and is considered by ORD to be the "best available
scientific information regarding cancer risks from EtO." Further, since the publication of the
2020 DRA, EPA has repeatedly expressed favorable views of the IRIS assessment, including in
comparison to the other EtO cancer inhalation risk characterization approaches cited in the 2020
DRA.24 Therefore, the 2023 DRA Addendum updates the EtO 2020 DRA for the human health
inhalation risk assessment using the IUR values from the IRIS Assessment to characterize the
cancer risk from inhalation exposure.25
For the conventional dried spice fumigation use of EtO, the assessment included EtO and its
reaction products ethylene bromohydrin (EBH), ethylene chlorohydrin (ECH), and ethylene
glycol (EG). Formation of EBH and ECH results from fumigation of foods with EtO due to
interaction with natural bromides and chlorides present in the food. Formation of EG results
from high sterilization concentrations of EtO, where EtO reacts with moisture to form EG. The
2020 DRA primarily focused on EtO (for the inhalation route) and ECH (for the dietary route)
since (1) residue level comparisons from sterilization studies and toxicity comparisons from
literature reports indicate that dietary assessments of ECH are protective for residues of EG, (2)
residue levels of EBH are insignificant compared to the residue levels of ECH, and thus it is
sufficient to regulate only residues of ECH for dietary exposure, and (3) measurements of EtO
from a spice sterilization study indicate that it dissipates rapidly after sterilization and is unlikely
to be found in spices available for consumption. EPA has concluded that dietary risks from
exposures to EtO and its reaction products in food and drinking water are not of concern. The
2023 DRA Addendum did not change OPP's conclusions about residues.
Dietary (Food + Water) Risks
In the 2020 DRA, EPA did not identify any dietary risks of concern for EtO or ECH. A
quantitative dietary assessment was not conducted for EtO since sterilization studies26 show that
EtO residues disappear rapidly after sterilization and are unlikely to be found in spices available
for consumption. EtO residues are expected to be present on commodities immediately after the
fumigation process (e.g., 24 hours) and may be present as the commodity enters the channels of
trade; therefore, a tolerance for EtO is needed and was established with 2005 residue data for the
single chamber fumigation process required on product labels. However, the EtO residues are
expected to completely dissipate by the time the commodity is available for consumption (e.g., 2
months)2728 and thus a quantitative dietary assessment for EtO was not conducted. Because
exposures to residues of EtO in food and drinking water are expected to be minimal to none, no
dietary risks are expected.
24 US EPA, 2021a. EPA Should Conduct New Residual Risk and Technology Reviews for Chloroprene- and
Ethylene Oxide-Emitting Source Categories to Protect Human Health, Report No. 21-P-0129, US EPA Office of
Inspector General, May 6, 2021.
25 87 Fed. Reg. 77, 985 (Dec. 21, 2022).
26 MRID 46625301. Magnitude of the Residue of Ethylene Oxide and Ethylene Chlorohydrin in/on Spices. Wright,
M. (2005). Study sponsored by American Spice Trade Association. 829 p.
27 MRID 46625301. Magnitude of the Residue of Ethylene Oxide and Ethylene Chlorohydrin in/on Spices. Wright,
M. (2005). Study sponsored by American Spice Trade Association. 829 p.
28 Memorandum. Ethylene Oxide. Case 2275. Results of Trade Practices Survey on Spices & Anticipated Residues
for Dietary Exposure Assessment. Leung Cheng, Health Effects Division. March 26, 1997.
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ECH is a reaction product formed during the EtO fumigation. ECH residues are present on
commodities immediately after the fumigation process and when the commodities are available
for consumption. Therefore, both tolerances and a dietary assessment are needed for ECH. A
food-only chronic dietary risk assessment was conducted for ECH using the Dietary Exposure
Evaluation Model - Food Consumption Intake Database (DEEM-FCID, ver. 3.16) which
incorporates food consumption data from the United States Department of Agriculture (USD A)
National Health and Nutrition Examination Survey, What We Eat in America
(NHANES/WWEIA; 2003-2008). EPA did not conduct a quantitative acute dietary risk
assessment as toxicological effects attributable to a single dose were not present (i.e., no acute
endpoint identified). In addition, a separate cancer dietary risk assessment was not conducted
because the chronic assessment adequately accounts for all chronic toxicity, including potential
carcinogenicity. The conservative chronic dietary risk assessment assumed 100% of registered
dried spices were treated with EtO post-harvest, and that the ECH residues on such crops
reflected tolerance-level residues.29 All processing factors were set to 1 since drying procedures
are performed prior to sterilization. No residues were included in the dietary exposure
assessment for drinking water, as uses of EtO for indoor food and nonfood uses will result in
negligible exposures from drinking water because EtO is a volatile gas and its use in sterilization
chambers is unlikely to result in EtO residues in groundwater or surface water. Moreover,
residential exposures to ECH are not expected because ECH is a reaction product that forms on
the surface of the treated commodity during EtO fumigation. ECH is not volatile and will remain
on the commodity; therefore, the only relevant exposure pathway is through dietary sources. The
resulting chronic exposure estimates do not exceed the Agency's level of concern (LOC; 100%
of the chronic population adjusted dose (cPAD)); children 3-5 years old were the most highly
exposed population subgroup at 6.6% the cPAD, while that for the U.S. population was 2.7%
cPAD. The 2023 DRA Addendum did not change OPP's conclusions about dietary risks.
Commercial Sterilization Facilities: Residential Bystander Exposures and Risks
There is the potential for EtO exposure to children and adults who live near sterilization
facilities. These exposures are also being addressed by the proposed OAR rulemaking.30 The
EtO average daily concentration at which the cancer risk is 1 x 10"6, and therefore not considered
by OPP to be of concern for non-occupational exposures, was back calculated from the IUR for
lifetime exposure. This is assuming continuous exposure (i.e., 24 hours a day for seven days a
week) for a 70-year lifetime starting at birth. This calculation indicates that if the average daily
concentration in these areas does not exceed 0.00011 ppb (0.11 ppt), the cancer risk will not
exceed 1 x 10"6 (1 in 1 million). This is below the limit of detection (LOD) of 20-90 ppt for EtO
in ambient air.
Commercial Sterilization Facilities: Non-Residential Bystander Exposures and Risks (Daycare
Centers and Schools)
29 40 CFR §180.151.
30 US EPA, 2022. Reconsideration of the 2020 National Emission Standards for Hazardous Air Pollutants:
Miscellaneous Organic Chemical Manufacturing Residual Risk and Technology Review. FR Doc. 2022-01923,
Filed: 02/03/2022.
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Non-residential bystander exposures can occur at a variety of facilities such as daycare centers,
schools, retail establishments, restaurants, gyms, swimming pools, music studios, movie theatres,
etc., that are between the fence line of a sterilization facility and the nearest residence. Exposures
to children attending daycare centers and schools are protective of other non-residential
bystander exposures because they occur more frequently and with a longer daily duration. In
addition, EtO is a mutagen that requires the use of age dependent adjustment factors (ADAFs) to
assess childhood exposures. The EtO concentration at which the cancer risk equals 1 x 10"6 was
back calculated from the IUR assuming children attend daycare 8 hours per day for 240 days per
year for 6 years and school for 6 hours a day for 180 days per year for 12 years near a
sterilization facility. These calculations indicate that the cancer risk is 1 x 10"6 (1 in 1 million) for
children who attend daycare and school where the average daily EtO concentration is 0.0012 ppb
(1.2 ppt). This is below the LOD of 20-90 ppt for EtO in ambient air.
To get a better understanding of how the back-calculated concentrations that exceed risks of
concern for non-residential bystanders (e.g., children who attend school) relate to concentrations
around facilities, the air concentrations developed by the Office of Air and Radiation (OAR) in
their recent proposed rulemaking were considered.31 Air concentrations were modeled around
each sterilization facility and annual average air concentrations were derived by OAR. The
model results indicate that there is a potential for EtO concentrations to exceed the level of 1.2
ppt that corresponds to a cancer risk of 1 x 10"6 for children in schools/daycares that are in non-
residential areas near sterilization facilities. This is below the LOD of 20-90 ppt for EtO in
ambient air.
Health Care Facilities: Residential and Non-Residential Bystander Exposures
Since 2010, healthcare sterilization facilities have been required to utilize all-in-one sterilizers
(i.e., materials are treated and aerated in the same chamber to reduce worker exposure) in
accordance with the EtO RED.32 These facilities sterilize material in oven-sized chambers using
4.5 to 170 grams of EtO per load (in comparison, EtO usage is much smaller in healthcare
facilities compared to commercial sterilization facilities, where fumigation takes place in tractor
trailer sized chambers). The exhaust from the chambers is typically routed to an air pollution
control device and the room air is typically ventilated though an exhaust stack to minimize
exposures as recommended in the American National Standard Institute/Association for the
Advancement of Medical Instrumentation (ANSI/AAMI) standard ST41.33 Given this
information, exposures to residential and non-residential bystanders near health care facilities are
expected to be minimal, but the exact concentrations are not known and therefore the risks were
not quantitatively assessed in the 2020 DRA or 2023 DRA Addendum. It is known, however,
that the exposures that would result in a cancer risk of 1 in 1 million are the same as those
calculated for contract sterilization facilities (i.e., 0.11 ppt for residential areas and 1.2 ppt for
31 See OAR's residual risk assessment for the commercial sterilization facilities source category document in
support of the 2022 Risk and Technology Review Proposed Rule. This document is currently an internal draft and
will be posted to Regulations.Gov for Docket Number: EPA-HQ-OAR-2019-0178 when it is finalized.
32 Reregistration Eligibility Decision for Ethylene Oxide. March 31, 2008.
33 ANSI/AAMI, 2018. American National Standard: Ethylene Oxide Sterilization in Health Care Facilities: Safety
and Effectiveness. ANSI/AAMI ST41:2008/(R)2018. American National Standards Institute/Association for the
Advancement of Medical Instrumentation (ANSI/AAMI). 2018.
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children in schools and daycares). EPA-OPP does not have monitoring data from health care
facilities to confirm potential exposure concentrations to bystanders. The NESHAP for Hospital
Ethylene Oxide Sterilizers addresses EtO emissions from hospitals where EtO is used, and OAR
plans to evaluate the risks from hospital sterilizers in an upcoming regulatory review of this
NESHAP.
Beekeeping Equipment Fumigations in North Carolina: Residential and Non-Residential
Bystander Exposures and Risks
For the FIFRA section 24(c) beekeeping equipment fumigation use in North Carolina, there is
the potential for both residential and non-residential non-occupational bystander exposure. A
quantitative residential non-occupational bystander assessment, assuming someone lives near a
fumigation chamber for a full lifetime (24 hours/day for four or eight exposure days per year for
70 years of exposure per lifetime), was conducted using the Probabilistic Exposure and Risk
Model for Fumigants (PERFUM)34. This assessment would be protective of any non-residential
exposures which would have a shorter exposure duration (e.g., 35 working years vs. 70 lifetime
years). Two application rates were modeled as provided on the product label: 28.3 lb. ai/1,000 ft3
and 46.5 lb. ai/1,000 ft3. The concentration distribution output from PERFUM for various
percentiles (50th, 75th, 80th, 85th, and 90th) was used to calculate cancer risk estimates assuming
four or eight exposure days (24 hrs./day) per year and 70 years of exposure per lifetime. The
IRIS inhalation unit risk for environmental exposures for a full lifetime [5.0 x 10"3 per [j,g/m3
(9.15 x 10"3 per ppb)] was used to estimate cancer risks.
The distances from the fumigation chamber at which the cancer risk estimates are less than 1 x
10"6 increase from lower to higher percentiles. For example, at the 75th and 80th percentiles, the
distance from the fumigation chamber at which the cancer risk is less than 1 x 10"6 is only 10
meters, while at the 90th percentiles, distances of 300 meters or more are necessary to reach
cancer risk estimates less than 1 x 10"6. A specific percentile has not been selected for regulation
(and correspondingly a buffer distance from the fumigation chamber has not been established)
since the Agency is proposing to terminate the use of EtO on beekeeping equipment in North
Carolina (see Section V. A for details).
Occupational Bystander and Occupational Post Application Risk
OPP considers the potential for exposure to occupational bystanders who work in non-processing
areas of treatment facilities, healthcare facilities, or beekeeping equipment treatment areas; in
downstream facilities such as warehouses where the treated product is shipped and stored; or in
other workplaces that are near the treatment facilities, healthcare facilities, or beekeeping
equipment treatment areas.
To get a better understanding of how the back-calculated EtO concentrations that exceed risks of
concern for occupational bystanders (adults who work near sterilization facilities) relate to
34 US EPA, 2019. User's Guide for the Probabilistic Exposure and Risk model for FUMigants PERFUM Version
3.0. Prepared by Exponent, 1800 Diagonal Road, Suite 500 Alexandria, VA 22314. Sponsored by US EPA, OPP,
Health Effects Division (HED). October 28, 2019.
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concentrations around facilities, the air concentrations modeled by the Office of Air and
Radiation (OAR) in their recent proposed rulemaking were considered.35 Air concentrations
were modeled around each sterilizing facility and annual average air concentrations were derived
by OAR. The model results indicate that there is a potential for EtO concentrations to exceed the
level of 0.0019 ppb (1.9 ppt) that corresponds to cancer risk of 1 x 10"6 for adults who work near
facilities modeled by OAR.
Aggregate Risks
In an aggregate assessment conducted to support the safety of EtO tolerances, EPA considers the
combined pesticide exposures and risks from three major sources: food, drinking water, and
residential / non-occupational exposures. In the context of discussing the FFDCA aggregate
assessment, EPA is using the term "residential" to reflect the FFDCA requirement to consider
non-occupational sources of exposure to the pesticide chemical residue. The Agency sums the
exposures from these sources and compares the aggregate exposure to quantitative estimates of
hazard. EPA considers the route and duration of exposure when assessing aggregate risks.
EtO
EPA did not conduct a quantitative aggregate assessment for EtO, although it has determined
that exposures to EtO will not result in aggregate risks of concern for purposes of supporting the
EtO tolerances. EPA has concluded that dietary risks from exposures to EtO in food and drinking
water are not of concern. This conclusion is based on residue data showing that there is no
expectation of residues of EtO on food when consumed. Although residue data show that there
are residues on food treated with EtO following fumigation, for 24 hours, the available data
indicates that most spices are not available for purchase until at least 2 months after treatment, at
which time, extrapolated residues indicate no residues of EtO on food.3637 Moreover, EPA does
not expect any residues in drinking water, because EtO is a volatile gas and its use in sterilization
chambers is unlikely to result in EtO residues in groundwater or surface water.
Under EPA's General Principles for Performing Aggregate Exposure and Risk Assessments,
EPA considers many factors in determining whether to aggregate exposures. For example, EPA's
guidance says that exposure scenarios should not be combined when there are different
toxicological effects via different routes of exposure. Moreover, EPA may consider the temporal
nature of exposure to residues and the likelihood of co-occurrence of those exposures.
Although there may be some residues of EtO in or on food soon after treatment, EPA does not
expect consumption of those spices while parent EtO residues persist. At the time of
consumption of treated food commodities, there will be no residues of parent EtO in or on
35 See OAR's residual risk assessment for the commercial sterilization facilities source category document in
support of the 2022 Risk and Technology Review Proposed Rule. This document is currently an internal draft and
will be posted to Regulations.Gov for Docket Number: EPA-HQ-OAR-2019-0178 when it is finalized.
36 MRID 46625301. Magnitude of the Residue of Ethylene Oxide and Ethylene Chlorohydrin in/on Spices. Wright,
M. (2005). Study sponsored by American Spice Trade Association. 829 p.
37 Memorandum. Ethylene Oxide. Case 2275. Results of Trade Practices Survey on Spices & Anticipated Residues
for Dietary Exposure Assessment. Leung Cheng, Health Effects Division. March 26, 1997.
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food.38'39 At that time, there is no co-occurrence of residues in or on food with any potential
residential exposures; therefore, there cannot be an additive effect. The FFDCA requires
aggregation to ensure that residues in or on food are safe; if people are not being exposed to
residues in or on their food, then there is no risk from exposures on food with which to aggregate
risks from other exposures.
Based on the lack of dietary risk and the nonadditive nature of any negligible residues on food
with residential exposures, EPA concludes that the aggregate risk from exposure to EtO consists
only of exposures to residues on food, of which there are none at the time of consumption.
Therefore, aggregate risk does not exceed the Agency's level of concern.
EtO Reaction Products
For the reaction products of EtO (ECH and EG), there are no water or non-dietary residential
exposures; the only exposure route is through food. Thus, the aggregate risk from exposure to
ECH is equal to the risk from dietary exposure alone; a separate aggregate assessment was not
conducted for ECH or EG. Since dietary exposure alone does not exceed EPA's risks of concern,
aggregate exposure does not exceed the Agency's level of concern.
Cumulative Risks
EPA has not made a common-mechanism-of-toxicity finding for EtO and any other substance.
EtO does not appear to produce a toxic metabolite produced by other substances. Therefore, EPA
has premised this PID and the underlying risk assessments on the belief that EtO does not have a
common mechanism of toxicity with other substances.
Occupational Handler Risks
Antimicrobial Uses in Commercial Sterilization Facilities. The cancer risks for the antimicrobial
uses were calculated using the arithmetic mean of the submitted exposure data for commercial
sterilizer and healthcare facilities. Since these facilities operate on a continuous basis, the
submitted exposure data were assumed to represent a 35-year occupational exposure between
ages 20 and 55 years (8 hours per day, 40 hours per week). The cancer risks for the exposure
were, therefore, estimated using the table in the 2016 IRIS assessment titled "Extra Risk Est. for
Total Cancer Incidence for Occupational Exposure Levels" found in the IRIS cancer assessment
(and referenced in table 9 of the 2020 DRA). The Maximum Likelihood [Risk] Estimate (MLE)
and upper-bound cancer risk estimates range from 4 x 10"2 (1 in 25) to 1 x 10"1 (1 in 10),
depending upon which facility type and cancer risk estimate are considered. The upper-bound
cancer risks are approximately twice the MLE cancer risks. For commercial sterilization
facilities, the MLE cancer risk is 1 in 17 and the upper bound cancer risk is 1 in 10. EPA expects
the mitigation in Section V. A. to reduce exposures from commercial sterilization facilities.
38 MRID 46625301. Magnitude of the Residue of Ethylene Oxide and Ethylene Chlorohydrin in/on Spices. Wright,
M. (2005). Study sponsored by American Spice Trade Association. 829 p.
39 Memorandum. Ethylene Oxide. Case 2275. Results of Trade Practices Survey on Spices & Anticipated Residues
for Dietary Exposure Assessment. Leung Cheng, Health Effects Division. March 26, 1997.
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Antimicrobial Uses in Healthcare Facilities. In healthcare facilities, the MLE cancer risk is 1 in
25 and the upper bound cancer risk is 1 in 12. Since 2010, health care sterilization facilities have
been required to operate on an all-in-one basis in accordance with the EtO Reregi strati on
Eligibility Decision12. These facilities sterilize material in oven-sized chambers using 4.5 to 170
grams of EtO per load. The exhaust from the chambers is typically routed to an air pollution
control device and the room air is typically ventilated though an exhaust stack (ANSI/AAMI,
2018). Given this information, exposures to residential and non-residential bystanders near health
care facilities are expected to be minimal, but the exact concentrations are not known and
therefore the risks were not quantitatively assessed in the 2020 DRA or 2023 DRA Addendum. It
is known, however, that the exposures that would result in a cancer risk of 1 in 1 million are the
same as those calculated for contract sterilization facilities (i.e., 0.11 ppt for residential areas and
1.2 ppt for children in schools and daycares). EPA-OPP does not have monitoring data from
health care facilities to confirm potential exposure concentrations to bystanders. The NESHAP
for Hospital Ethylene Oxide Sterilizers addresses EtO emissions from hospitals where EtO is
used, and OAR plans to evaluate the risks from hospital sterilizers in an upcoming regulatory
review of this NESHAP. Recognizing that risks to bystanders from healthcare facilities were not
quantitatively assessed, EPA expects the mitigation proposed in Section V.A., abatement
devices, to reduce exposures, and therefore any risks, to bystanders.
Conventional Uses in Commercial Sterilization Facilities. The cancer risks for the use of EtO on
dried herbs and spices (i.e., conventional uses) in commercial sterilization facilities were
calculated using the arithmetic mean of the submitted exposure data for the commercial spice
facilities. Since these facilities operate on a continuous basis, the submitted exposure data were
assumed to represent a 35-year occupational exposure between ages 20 and 55 years. Since the
exposure is less than 0.1 ppm, the cancer risks were calculated using the formulas listed in
Section 4, page 111 of the IRIS assessment.40
Submitted exposure data from commercial sterilization facilities indicate that some of the
workers did not wear respirators during the time that they were monitored when they were doing
activities for which a respirator was not required. Therefore, when calculating exposures,
respiratory protection factors were only applied to concentrations measured during activities
when a respirator was worn. Concentrations measured during activities when no respirator was
worn (and is not required to be worn according to the product labels) were not adjusted for any
respiratory protection factors. Cancer risks range from 3 x 10"2 (1 in 36) for the MLE to 6 x 10"2
(1 in 16) for the upper bound.
Beekeeping Equipment Use in North Carolina. Monitoring data specific to the beekeeping
equipment fumigation use are not available; however, based on the label directions and
requirements for the Special Local Need (SLN) beekeeping equipment use (related to EPA Reg.
# 36736-7), it is anticipated that the ASTA monitoring data for the commercial spice facilities
would be protective of the beekeeping use and was used as a surrogate. Cancer risks for the
beekeeping equipment use were calculated using the arithmetic mean of the submitted exposure
40 US EPA, 2016. Evaluation of the Inhalation Carcinogenicity of Ethylene Oxide, (CASRN 75-21-8), In Support of
Summary Information on the Integrated Risk Information System (IRIS). EPA/635/R-16/350Fa. NCEA, ORD, US
EPA, Washington, DC. December 2016.
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data for the commercial spice facilities. To account for the differences in potential exposure
between workers in an indoor commercial spice sterilization facility and workers fumigating
beekeeping equipment in an outdoor chamber, the activities reported were limited to those that
would likely occur during outdoor beekeeping equipment fumigation (see Appendix A in the
2023 DRA Addendum for details). Since the beekeeping fumigation exposures are considered
"intermittent occupational exposures," a lifetime average concentration (LAC) was calculated,
assuming either four or eight exposure days per year, and then the cancer risks were calculated
using the LAC and the adult specific IUR of 5.5 x 10"3 per ppb. Cancer risks range from 2 x 10"4
(1 in 5,000) when assuming four exposure days per year to 4 x 10"4 (1 in 2,500) when assuming
eight exposure days per year. These risk estimates, which also assume that self-contained
breathing apparatus (SCBA) PPE is in use, exceed the Agency target of 1 x 10"4 for occupational
risks.
Human Incidents and Epidemiology
EPA reviewed EtO incidents reported to the Incident Data System (IDS). As of EPA's latest
search on December 1, 2022, the IDS showed nine medium- to high-severity incidents from
March 1, 2008 to December 1, 2022. Six of these incidents were in an international setting using
a U.S. EPA-registered product in Barbados, Sri Lanka, Korea (two), Taiwan, and Thailand. Two
incidents, which occurred in the U.S., involved a spill and a misuse of the product, which were
associated with acute symptoms such as headache, light-headedness, and racing heart. The
remaining incident in the U.S. described a hospital employee who was diagnosed with leukemia
after six years of employment. Although EtO is a known carcinogen, it is not possible to
determine if the cancer in this incident was caused by EtO exposure and/or some other factor(s)
based on the available information. The Agency intends to monitor human incidents for EtO and
will conduct additional analyses if necessary.41
Tolerances
EtO is registered for uses that result in residues in or on food. Generally, a tolerance or tolerance
exemption must cover the residues, or the affected food is considered adulterated.42 EPA has
determined that the Agency established most of the necessary tolerances for residues resulting
from EtO's legal use.
The Agency has established tolerances for EtO and the EtO reaction product, ethylene
chlorohydrin (ECH), under 40 C.F.R. § 180.151. However, during the risk assessment process,
EPA determined that revisions to the tolerances and tolerance expressions are necessary. EtO and
ECH tolerances need to be revised for several commodities to reflect updated commodity
definitions. The 2020 DRA notes that the tolerance expressions for EtO and ECH need to be
updated per current practice concerning tolerance expressions. In the 2020 DRA, the Agency
determined that the EtO tolerance for walnuts needs to be revised to reflect the lower residues
resulting from the required single chamber process. The 2020 DRA also states an ECH tolerance
41 OSHA additionally has publicly available information on EtO incidents and enforcement, which can be accessed
at https://www.osha.gov/data
42 21 U.S.C. §§ 342, 346(a).
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for walnuts needs to be established based on the documented level of quantification (LOQ).
However, the Agency is not aware of current EtO use on walnuts and none of the EtO products
are currently labeled for use on walnuts. Based on the information currently before EPA, the use
of EtO on walnuts is unlikely to meet the standard for registration under FIFRA because (1) the
lack of usage of EtO on walnuts suggests that there are alternatives (e.g., nonchemical, propylene
oxide [PPO]) available for the fumigation of walnuts and (2) the occupational cancer risk
estimates for EtO use in commercial sterilization facilities exceed the Agency's threshold of 1 x
10"4 Therefore, the Agency intends to exercise its authority under the FFDCA to revoke the
walnut tolerance. Tolerance changes will be proposed through a separate rulemaking process.
No tolerance changes are anticipated for international harmonization. Codex has not set
Maximum Residue Limits (MRLs) for EtO or ECH. Canada has not set MRLs for walnut for
EtO or ECH. Canada has set MRLs for herbs and spices (and sesame seed) for both EtO and
ECH. As these levels match the U.S. tolerances, there are no international harmonization issues
at this time. For more information on tolerances, see Section V.C, below.
Human Health Data Needs
The human health database for EtO is not considered complete. Although not all human health
data requirements have been completely met, EPA has determined that available data were
sufficient to conduct the 2020 HHRA and the 2023 DRA Addendum and are sufficient to support
this PID. Based on the occupational risk estimates for EtO, EPA believes that further mitigation
of EtO exposure is required. The Agency intends to continue working with the registrants to
satisfy the data requirements under the existing DCI notice (GDCI-042301-1428).
One data requirement is still outstanding and will be used to inform future risk assessments. The
following study is outstanding for the EtO GDCI-042301-1428:
- Non-Guideline Study Monitoring Data on Fumigated Commodities
This study is required to evaluate emission rates for EtO from treated commodities/materials and
the potential for occupational exposure due to those emissions in the channels of trade after
fumigation activities are complete. The registrants submitted a waiver request for this study
(MRID 50384901) on September 8, 2017. However, this waiver request was denied on July 17,
2018, due to a lack of information related to potential exposures within the various channels of
trade after fumigation, dissipation of EtO beyond the facility, and the analytical method used to
measure air concentrations.43
Further, EPA proposes that registrants submit OCSPP GLN 875.1400 Inhalation Exposure
Indoor for worker monitoring data for both the medical device sterilization and spice fumigation
uses. To quantify the effect of mitigation on worker exposure in commercial sterilization
facilities, EPA proposes to issue a Data Call-In (DCI) for OCSPP GLN 875.1400 Indoor
Inhalation and require a protocol before monitoring begins. Based on non-specificity and lacking
43 Ethylene Oxide (EtO): Response to registrant's inhalation exposure monitoring requirements waiver request.
Decision Number 533138. June 21, 2018.
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detail of previously submitted worker monitoring data in commercial sterilization facilities
treating medical devices, EPA proposes to require, through a DCI, air monitoring of the
occupational handlers specifically involved in fumigation activities (e.g., loading and unloading
chambers, routine maintenance, product transfer), documentation of what activities each worker
did while monitored, and whether they were wearing a respirator or not (and what type) for all
commercial sterilization facilities. For non-handlers in the facility (e.g., office workers,
warehouse workers), EPA proposes to also require air monitoring data through a DCI. The
Agency proposes that registrants follow the OSHA Method 1010 as the monitoring method.44
EPA proposes that the DCI to be issued would require registrants to submit this data following
implementation of all mitigation. The Agency would issue a DCI to establish a timeline for
submitting these data.
To reduce worker exposure, EPA is proposing that respirator requirements be based on a
technologically measurable (i.e., quantifiable) EtO concentration of ambient air for real time
measurements, which by the Agency's understanding is 10 ppb. See Section V.A.
B. Ecological Risks
The Agency assessed ecological risks in the 2020 DRA, which are summarized below. EPA did
not reassess ecological risks as part of the 2023 DRA Addendum, which focused on human
health risks. The Agency used the most current science policies and risk assessment
methodologies to prepare a risk assessment in support of the registration review of EtO.45 For
additional details on the 2020 DRA, see Ethylene Oxide (EtO) Draft Human Health and
Ecological Risk Assessment in Support of Registration Review in EPA's public docket (EPA-
HQ-OPP-2013 -0244).
The EPA is currently working with its federal partners and other stakeholders to improve the
consultation process for federally-listed species and their designated critical habitats. The
Agency has not yet fully evaluated EtO's risks to listed species. However, EPA will complete its
listed-species assessment and any necessary consultation with the Services before completing the
EtO registration review. See Appendix C for more details. As such, potential risks for non-listed
species only are described below.
Risk Summary and Characterization
The Agency assessed ecological risks in the 2020 DRA, which are summarized below. All
ecological data requirements were waived as part of a waiver response dated March 9, 2018, as
explained below. EPA did not reassess ecological risks as part of the 2023 DRA Addendum.
44 OSHA Method 1010 (revised 2014) can be found at https://www.osha.gov/sites/defanlt/files/methods/osha-
1010.pdf.
45 The 2020 Eco DRA only addresses potential risks to species not listed under the Endangered Species Act. EPA is
working with its federal partners and other stakeholders to implement a Revised Method (EPA-HQ-OPP-2019-0185-
0054) for assessing potential risk to listed species and their designated critical habitats. The Agency will complete
EtO's listed-species assessment once EPA has fully implemented the scientific methods necessary to complete listed
species' risk assessments. For more details, see Appendix C.
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EtO sterilization is performed indoors in vacuum or gas tight chambers. Sterilization in large-
and medium-sized commercial sterilization facilities must follow National Emissions Standards
for Hazardous Air Pollutants (NESHAP) requirements for emissions control. Approximately 1%
of the EtO used for sterilization is used in medium-sized facilities and approximately 0.1% of the
EtO used for sterilization is used in small-sized facilities.46 Exposures to EtO from large- and
medium-sized facilities with controls achieving greater than or equal to 99% reduction in
emissions—consistent with the applicable NESHAP requirements for emissions control at the
time of the OPP ecological assessment—are not of concern.47'48 Therefore, with approximately
99% of sterilization occuring in large- and medium-sized facilities with emissions controls
achieving greater than or equal to 99% emissions reductions, any exposure to wildlife from the
use of EtO will likely be limited, with the possible exception of the aforementioned low
percentage of small-sized facilities that are not subject to the NESHAP requirements for
emissions controls and may not achieve 99% emissions reductions. OPP notes that OAR is
proposing updates to the NESHAP for the Commercial Sterilization Facilities source category to
require more stringent controls for EtO emissions. OPP expects that these more stringent
emissions controls and OPP's proposed rate reductions (if finalized) will further reduce exposure
to nontarget species.
For both the spice and medical uses in small-sized commercial sterilization facilities, terrestrial
organisms in the vicinity or downwind of a treatment vent may be at risk from EtO vapor
exposure due to the fugitive emissions. Due to the potential risks to terrestrial organisms, the
Agency is not able to make a 'no effects' determination for federally-listed species or their
designated critical habitats. For aquatic organisms, risks are not expected due to limited exposure
potential since uses of EtO are not expected to create a significant pathway for deposition,
runoff, or leaching into water bodies. EPA has determined that emissions of EtO uses from
small-sized facilities may present risks of concern to birds, mammals, honey bees, or plants
when considering currently available data; however, emissions of EtO uses from large- and
medium-sized facilities (after controls achieving > 99% reduction in emissions) do not present
risks of concern to non-target organisms.49'50 In the absence of toxicity studies, there is greater
uncertainty regarding risk near EtO commercial sterilization facilities that either have no or
limited (< 99% reduction) emission controls, which was the NESHAP requirement at the time of
the OPP ecological assessment. In those cases, especially for those facilities without emission
controls, risk cannot be precluded for terrestrial organisms in adjacent areas around EtO
treatment facilities. OPP notes that OAR is proposing updates to the NESHAP for the
Commercial Sterilization Facilities source category to require more stringent controls for EtO
46 The size of the facility is determined by the amount of EtO emitted in accordance with section 112 of the Clean
Air Act. See https://www.epa.gov/stationare-sonrces-air-poHntion/ethvlene-oxide-emissions-standards-sterilization-
facilities
47 Ethylene Oxide: Revised Response to Data Waiver Requests Submitted by the Ethylene Oxide Task Force. March
9, 2018.
48 Ethylene Oxide (EtO). Draft Human Health and Ecological Risk Assessment in Support of Registration Review.
November 3, 2020.
49 Ethylene Oxide: Revised Response to Data Waiver Requests Submitted by the Ethylene Oxide Task Force. March
9, 2018.
50 Ethylene Oxide (EtO). Draft Human Health and Ecological Risk Assessment in Support of Registration Review.
November 3, 2020.
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emissions. OPP expects that these more stringent proposed emissions controls and rate
reductions (if finalized) will further reduce exposure to nontarget species.
Ecological Incidents
EPA reviewed EtO incidents reported to the Incident Data System (IDS). As of EPA's latest
search on January 18, 2023, IDS showed zero incidents reported from March 1, 2008 to January
18, 2023. The Agency intends to monitor ecological incidents for EtO and will conduct
additional analyses if necessary.
Ecological and Environmental Fate Data Needs
The ecological and environmental fate dataset for EtO is considered complete._The Agency does
not anticipate any further data needs for EtO as part of this registration review cycle.
EPA did not identify a risk concern for acute exposure of adult honeybees to EtO. However,
chronic risks to adult honeybees and acute risks to larval honeybees have not been defined at this
time based on current available information. Additional data may be necessary to fully evaluate
risks to non-target terrestrial invertebrates, especially pollinators, based on the Guidance for
Assessing Pesticide Risks to Bees (June 2014).51
The ecological and environmental fate data requirements in GDCI-042301-1428 included GLN
850.4150 Vegetative Vigor, Non-guideline study Honeybee Acute Vapor Exposure, and Non-
guideline study Avian Acute Inhalation Toxicity. On June 10, 2015, EPA received waiver
requests for all three data requirements from the Ethylene Oxide Task Force (EOTF) (MRIDs
49648401, 49648402, and 49688601). In May 2017, EOTF submitted information to fulfill the
Product Use Information data requirement (GLN 875.1700) which was also considered when
evaluating the ecological data requests. EtO sterilization is performed indoors in vacuum or gas
tight chambers. Approximately 1% of the EtO used for sterilization is used in medium-sized
facilities and approximately 0.1% of the EtO used for sterilization is used in small-sized
facilities. Exposures to EtO from large- and medium-sized commercial sterilization facilities
with controls achieving greater than or equal to 99% reduction in emissions—consistent with the
applicable NESHAP requirements (according to section 112 of the Clean Air Act) for emissions
control at the time of the OPP ecological assessment—are not of concern. Therefore, with
approximately 99% of sterilization occuring in large- and medium-sized facilities with emissions
controls achieving greater than or equal to 99% emissions reductions, any exposure to wildlife
from the use of EtO will likely be limited with the possible exception of the aforementioned low
percentage of small-sized facilities that are not subject to the NESHAP requirements for
emissions controls and may not achieve 99% emissions reductions. Consequently, EPA waived
the data requirements GLN 850.4150 Vegetative Vigor; Non-guideline study Honeybee Acute
Vapor Exposure; and Non-guideline study Avian Acute Inhalation Toxicity on March 9, 2018.52
OPP notes that OAR is proposing updates to the NESHAP for the Commercial Sterilization
51 https://www.epa.gov/sites/production/files/2014-
06/doeuments/pottinator risk assessment guidance 06 .1.9 14.pdf.
52 Ethylene Oxide: Revised Response to Data Waiver Requests Submitted by the Ethylene Oxide Task Force.
(Orrick, 2018).
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Facilities source category to require more stringent controls for EtO emissions. OPP expects that
these more stringent emissions controls (if finalized) will further reduce exposure to nontarget
species.
C. Benefits Assessment
EtO is primarily used as a sterilant for new, single use, and reusable medical devices and
equipment. EtO is highly valuable in the industrial sterilization setting - or any setting that has
the objective of destroying, inactivating, or physically removing all microorganisms to meet
defined sterility assurance standards - because it is a penetrative gas that has a high throughput
capacity, is effective at a wide range of temperatures, and is compatible with a broad range of
materials. EtO is used on approximately 50% of all sterilized medical devices, annually,
including an estimated 95% of all surgical kits. A key benefit of EtO is its ability to sterilize
medical devices in their final packaging as it is able to penetrate palletized materials, cardboard,
and other cellulosic packaging material. Presently, there are no viable alternatives to EtO for the
sterilization of certain medical devices and equipment because gamma irradiation and e-beam
irradiation, the next most commonly employed methods for medical device sterilization, cannot
be used on certain materials. Other technologies (e.g., hydrogen peroxide, chlorine dioxide,
vaporized peracetic acid) are limited due to issues with material compatibility, scalability, and
because they lack accepted validation measures for sterility assurance. The absence of EtO for
use on medical devices and equipment would cause widespread disruption to the availability of
sterile medical devices including feeding tubes used in neonatal intensive care units, drug-eluting
cardiac stents, catheters, shunts, and other implantable devices.
In the U.S., EtO is used during the processing and reconditioning of dried herbs and spices to
reduce food safety pathogens of concern such as Salmonella and Escherichia coli. The presence
of moisture alone may be sufficient for the development of pathogens such as Salmonella and
keeping moisture out of dried herbs and spices can be challenging during processing, handling,
shipping, and storage activities. Additionally, most spices are imported from overseas, which
creates more opportunity for pathogens to be introduced due to differing sanitation and food
handling practices and regulations. EtO is advantageous as it has minimal impact on the
desirable characteristics of an herb or spice including its aromatics, color, flavor, or texture.
There are a few alternatives to EtO for the sanitization of dried herbs and spices from pathogens
and filth; however, alternatives may not be viable for every situation, pathogen, or consumer
market. The absence of EtO for use on dried herbs and spices may result in an increased rejection
of imported spices, an increased prevalence of foodborne illnesses from an increased risk of
pathogens being present among imported dried herbs and spices, and, potentially, disruptions in
product availability.
EtO is also registered for niche uses in beekeeping to manage American foulbrood on equipment
(in North Carolina only); the preservation of library, museum, and archival materials against
bacteria, fungi, and insects; on musical instruments to prevent the transmission of human
diseases, and for the sterilization of cosmetics. For the beekeeping equipment, the use of EtO is
limited via a FIFRA section 24(c) registration to one facility in North Carolina. There are
alternative chemical, cultural, and mechanical controls available to manage American foulbrood
disease on beekeeping equipment. EtO is no longer used for treatment of museum, library, or
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archival materials due to concerns over human health risks associated with off-gassing from
treated materials. Alternatives for the museum, library, and archival materials include freezing,
anoxia (oxygen deprivation), and irradiation. For the musical instrument uses, other disinfectant
products are available for use that are more practical, low cost, and easily accessible. EPA
expects that EtO is likely no longer used in the cosmetics industry. Gamma irradiation is a viable
alternative for cosmetics. Therefore, in these use sites, EtO provides minimal benefits based on
the availability of alternatives and/or limited to no current EtO usage. The absence of EtO for use
on these use sites is unlikely to impact these industries.
For more information on the benefits of EtO, see Ethylene Oxide (PC# 042301): Use, Usage,
Benefits, and Impacts of Cancellation and the letter from Dr. Girvin Liggans to Edward Messina
(dated August 18, 2022)53 in this docket (EPA-HQ-OPP-2013-0244).
D. Alternatives for Medical Device Sterilization and Spice Fumigation
As described above, the Agency estimates that EtO use results in cancer risks of concern to
occupational handlers as well as risks to occupational and non-occupational bystanders.
However, EPA recognizes that EtO products are registered for uses which are extremely
beneficial and have no currently registered alternatives that can completely replace EtO. Under
its Reduced Risk Policy, OPP encourages the submission of applications for pesticides which
offer a reduced risk alternative and will give priority consideration to the review of such
applications. The registration of such a reduced risk alternative pesticide would allow OPP to
achieve greater risk reduction.54 Even though there is one registered alternative active ingredient
for spice fumigations (propylene oxide) and there are no registered alternative pesticide active
ingredients for medical device sterilization, there are a variety of alternative sterilization methods
described below. However, the current field of alternatives are insufficient to completely replace
EtO for reasons described below.
Medical Devices
Some medical devices can only be sterilized with EtO. However, there are several alternative
methods used to sterilize medical devices: gamma irradiation, X-ray sterilization, electron beam
sterilization, and steam; as well as alternative sterilization methods in development including
vaporized hydrogen peroxide, nitrogen dioxide, chlorine dioxide, and vaporized peracetic acid.
Despite the availability of alternative sterilization methods, EPA understands the limitations of
alternative sterilization methods for use with medical devices due to their lack of compatibility
with materials and/or packaging; and also due to their lack of scalability or capacity, application
method, and/or lack of validation measures for sterility assurance or efficacy data. See Section
IHC. and Ethylene Oxide (PC# 042301): Use, Usage, Benefits, and Impacts of Cancellation in
this docket. Despite these limitations, EPA is seeking to pursue identifying alternatives to EtO
sterilization as a long-term risk reduction strategy.
53 Letter from Dr. Girvin Liggans, Acting Deputy Director for Plant Derived Foods, Office of Food Safety, Center
for Food Safety and Applied Nutrition, Food and Drug Administration to Edward Messina, Director, Office of
Pesticide Programs, Environmental Protection Agency. August 18, 2022.
54 https://www.epa.gov/pesticide-registration/conventional-rednced-risk-pesticide-prograin.
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FDA's Center for Devices and Radiological Health (CDRH) assures that patients and providers
have timely and continued access to safe, effective, and high-quality medical devices. Before
most sterile medical devices are on the market, FDA reviews premarket submissions such as
premarket approval applications (PMAs) and premarket notifications (referred to as 510(k)s) to
determine if the sterility information is consistent with the sterility assurance under which the
device is labeled and intended for use (e.g., in accordance with internationally agreed upon
voluntary consensus standards that FDA recognizes). See Section IV.B. for more information on
FDA's jurisdiction over recognizing sterilization modalities and verifying sterility assurance for
medical devices.
As part of interagency collaboration, EPA-OPP and FDA-CDRH have held discussions on
pursuing alternatives to EtO sterilization and have identified regulatory and logistical limitations
in prescribing which sterilization modality must be used on specific medical devices. These
regulatory and logistical limitations, and additional background regarding FDA's regulatory
oversight over medical devices, are described below:
• Given that medical device material makeup varies from manufacturer to manufacturer
(even for the same device type), it is not possible to prescribe which types of medical
devices must use which sterilization modality, due to material compatibility issues. For
example, catheters from different manufacturers could be made from different materials,
some of which may or may not be compatible with alternative sterilization modalities.
• The FFDCA authorizes FDA to exercise regulatory oversight over medical devices,
including through its implementing regulations.55 In the context of devices labeled as
sterile, the FFDCA does not authorize FDA to require sponsors/manufacturers of these
devices to provide a justification as to why a certain sterilization modality is used to
support marketing authorization rather than another. Rather, the information provided to
FDA as support for a device sterilization claim must show that the selected sterilization
method for a subject device conforms to the labeling and intended use of the device,
which may include any applicable FDA-recognized consensus standards or an equivalent
sterilization method. A more detailed description of FDA's regulatory oversight in this
space is provided below.
o With respect to devices that are intended to be sterilized using EtO, sponsors may
choose to reference certain FDA-recognized standards that include EtO exposure
potential information based on the applicable standards and their allowable limits
for residual EtO.56 Accordingly, information related to the EtO exposure potential
of a subject device, both during the manufacturing and sterilization process and at
the time the device is used by an end user (such as a healthcare professional or
patient), is generally reviewed and compared to any applicable International
55 FD&C Act Section 501 et seq.; 21 CFR Part 800 el seq.
56 ANSI A AMI ST41:2008/fRĄ2018): ISO 10993-7. 2nd Ed. 2008-10-15. Additionally, depending on the premarket
Mbfiits^ regulations ttgrtjirt^^^ how gfionsors should
submit sterilization data.
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Standards defining allowable limits of EtO residuals and exposures.
o As part of FDA's regulatory oversight, FDA is also required to evaluate whether a
subject device, prior to its introduction in the market, offers a reasonable
assurance of safety and effectiveness upon the imposition of certain regulatory
controls.57 Fundamental to this evaluation is, among other things, the weighing of
any probable benefits to health from the use of a device against any probable risks
of injury or illness from such use (i.e., analyzing clinical risks and clinical
benefits for a given device).58 For example, if EtO as a device sterilizing agent
poses a cancer exposure risk to an end user or to manufacturing or sterilization
staff, FDA is obligated to review that information, together with other probable
risks, against the probable benefits offered by the finished sterile device. If FDA
determines that the probable benefits from use of the device outweigh the
probable risks of such use, this specific risk information alone would be unlikely
to lead FDA to conclude that a device should not be cleared or approved.
o Separately, since the Food and Drug Administration Modernization Act of 1997
(FDAMA) (Public Law 105-115),59 Congress has directed FDA to take a least
burdensome approach to medical device premarket evaluation in a manner that
eliminates unnecessary burdens that may delay the marketing of beneficial new
products, while maintaining the statutory requirements for clearance and
approval. In practice, FDA defines least burdensome to refer to the minimum
amount of information necessary to address regulatory questions in line with the
statutory and regulatory requirements applicable to a subject device, and
encourages industry to refer to least burdensome principles in compiling
information for premarket review by the FDA.60 Consequently, if certain
information was not provided in a premarket submission, but that information is
not needed to support a determination that the device meets the applicable
57 See FFDCA Section 513(a)(1).
58 The safety and effectiveness of a device is determined, among other things, by "weighing any probable benefit to
health from the use of the device against any probable risk of injury or illness from such use" FFCDA Section
513(a)(2)(C)). To aid this process, sponsors submit valid scientific evidence, which FDA reviews to determine
whether "the device will have the effect it purports or is represented to have under the conditions of use prescribed,
recommended, or suggested in the labeling of the device" FFCDA Section 513(a)(3)(A).
59 Congress enacted additional least burdensome provisions to the FFCDA through the FDA Safety and Innovation
Act (Public Law 112-144) and the 21st Century Cures Act (Public Law 114-255).
60 See, e.g., FFCDA Section 513(i)(l)(D)(i) ("Whenever the Secretary requests information to demonstrate that
devices with differing technological characteristics are substantially equivalent, the Secretary shall only request
information that is necessary to making substantial equivalence determinations. In making such request, the
Secretary shall consider the least burdensome means of demonstrating substantial equivalence and request
information accordingly."); FFCDA Section 513(a)(3)(D)(ii) ("Any clinical data, including one or more well-
controlled investigations, specified in writing by the Secretary for demonstrating a reasonable assurance of device
effectiveness shall be specified as a result of a determination by the Secretary that such data are necessary to
establish device effectiveness. The Secretary shall consider, in consultation with the applicant, the least burdensome
appropriate means of evaluating device effectiveness that would have a reasonable likelihood of resulting in
approval."); see also FDA Guidance entitled "The Least Burdensome Provisions: Concept and Principles," available
at https://www.fda.gov/regulatorv-iixformation/search-fda-guidance-dociiiiients/least-biirdensome-provisions-
concept-and-principles.
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statutory and regulatory standards for marketing authorization, FDA does not
request such information.
• EPA's authority under FIFRA does not allow for OPP to prescribe on pesticide product
labels FDA's process for validation assessment of sterilization modalities for medical
devices. As noted above, FDA's role in this regard under the FFCDA and its
implementing regulations is to evaluate whether the sterilization data (irrespective of
method) submitted for premarket review is adequate to support a claim that a subject
device is sterile as part of the overall benefit/risk assessment carried out on all FDA-
regulated devices.
Despite these limitations, EPA still seeks to pursue identifying alternatives to EtO sterilization as
a long-term risk reduction strategy and will continue to collaborate with FDA on their work
through the Innovation Challenge: Identify New Sterilization Methods and Technologies. See
Section IV.B for more information on the steps FDA is taking to identify alternatives to EtO
sterilization.
Spices
Spices or herbs discussed in this document refer only to the dried forms, not fresh forms, of
herbs and/or spices. Limiting the use of EtO to specific dried herbs and spices where its use is
deemed critical for food safety and where alternative treatment methods are not available also
would result in fewer EtO applications overall, and thus less exposure to workers (including
handlers and occupational bystanders), residential bystanders, and non-residential bystanders.
There are several alternatives used to treat dried herbs and spices: irradiation, heat, steam, and
propylene oxide. However, these alternatives may not be viable for every spice, spice form (e.g.,
dried leafy-type, ground/powdered), spice blend, or target pathogen61. See Section III.C. and
Ethylene Oxide (PC# 042301): Use, Usage, Benefits, and Impacts of Cancellation in this docket.
Pesticides can be used to treat food commodities in the U.S. if the commodity is listed on the
product label (i.e., the pesticide is registered for use on the commodity), and there is an
established tolerance or tolerance exemption for the pesticide on the commodity. As stated on the
EtO product labels, EtO is currently registered to reduce the microbial load on various whole and
ground spices (except basil), dried vegetables, and seasonings. Tolerances are established for
EtO and ECH for various dried herbs and spices, dried vegetables, and walnuts (see Table 2 for
all commodities with EtO and ECH tolerances). Seasonings are blends of dried herbs and spices.
If a seasoning/spice blend is treated with EtO, it can only include commodities identified in
Table 2.
Table 2. Current Commodities with Tolerances for EtO ant
Herbs (crop subgroup |9.\)
Spices (crop subgroup I'MJ)
Other I'ooil commodities in 40
C I k § 180.151
Angelica
Allspice
Licorice, roots
ECH in the U.S.
61 American Spice Trade Association (ASTA). 2020. ASTA reply to EPA questions regarding ethylene oxide use on
spices. Email from Laura Shumow, Executive Directors, ASTA, to Susan Bartow, Pesticide Re-Evaluation Division,
Office of Pesticide Programs, Environmental Protection Agency. June 25, 2020.
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Balm
Anise (seed)
Peppermint, tops, dried
Borage
Anise, star
Sesame seed
Burnet
Annatto (seed)
Spearmint, tops, dried
CamomileA
Caper (buds)
Vegetable, driedD
Catnip
Caraway
WalnutE
Chervil (dried)
Caraway, black
Chive
Cardamom
Chinese chive
Cassia (buds)
Clary
Celery (seed)
Coriander (leaf)
Cinnamon
Costmary
Clove (buds)
Culantro (leaf)
Coriander (seed)
Currv (leaf)
Culantro (seed)
Dillweed
Cumin
Horehound
Dill (seed)
Hvssop
Fennel, common
Lavender
Fennel, Florence (seed)
Lemongrass
Fenugreek
Lovage (leaf)
Grains of paradise
Marigold
Juniper (berry)
Marjoram (Origanum spp.)B
Lovage (seed)
Nasturtium
Mace
Parsley (dried)
Mustard (seed)
Pennyroyal
Nutmeg
Rosemary
Pepper, black0
Rue
Pepper, white
Sage
Poppv (seed)
Savory (summer and winter)
Saffron
Sweet bay
Vanilla
Tansv
Tarragon
Thvme
Wintergreen
Woodruff
Wormwood
A - Camomile includes both German and Hungarian (46694 Federal Register / Vol. 74, No. 175 / Friday,
September 11, 2009).
B - Oregano is covered by the preferred term maijoram (46694 Federal Register / Vol. 74, No. 175 / Friday,
September 11, 2009).
C - Also includes pink peppercorns (46694 Federal Register / Vol. 74, No. 175 / Friday, September 11, 2009).
D - Dried vegetables include capsicums, ginger, horseradish, paprika, garlic, onion, turmeric, and arrowroot
(46694 Federal Register / Vol. 74, No. 175 / Friday, September 11, 2009).
E - Walnut is not listed on current product labels.
Based on discussions with industry and FDA, EPA understands the limitations of the alternative
treatment methods due to compatibility with spices and/or their packaging, scalability, and lack
of validation measures or efficacy data. Despite these limitations, due to the inhalation risk
estimates associated with the use of EtO, EPA still seeks to identify alternatives to EtO spice
treatments, as well as specific spices where EtO use is critical for food safety. The Agency is
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soliciting comments on the specific commodities in Table 2 for which there is a critical need for
the use of EtO and for which there are no viable alternatives to EtO (e.g., steam, irradiation, or
propylene oxide cannot be used for pathogen control on a particular spice, spice form, or spice
blend). Any commodities without documented support for continued treatment with EtO will be
considered for a phased-out cancellation to reduce exposure to workers (including handlers and
occupational bystanders), residential bystanders, and non-residential bystanders. The Agency
intends to include language in the Interim Decision (ID) stating that registrants should submit
requests to voluntarily terminate uses on these commodities (see Section V.A.).
Based on information submitted to the Agency, EPA understands that the following spices often
have high pathogen loads— black pepper, paprika, celery seed, coriander, turmeric, and thyme62'
63. The Agency is seeking public comment on alternative treatment options for those spices and
target pathogens (e.g., Salmonella, E. coli ). In addition, the Agency would like to know if there
are other commodities that typically have high pathogen loads for which there are not efficacious
treatment options besides EtO. The Agency is also seeking information regarding the importance
of EtO to spice blends (e.g., seasonings) and the specific spices in the blends for which EtO
fumigation is critical.
None of the EtO products are currently labeled for use on walnuts and the Agency is not aware
of current EtO use on walnuts. Based on the information currently before EPA, the use of EtO on
walnuts is unlikely to meet the standard for registration under FIFRA because (1) the lack of
usage of EtO on walnuts suggests that there are alternatives available for the fumigation of
walnuts (e.g., nonchemical, PPO) and (2) the occupational cancer risk estimates for EtO use in
commercial sterilization facilities exceed the Agency's threshold of 1 x 10"4 Therefore, the
Agency intends to exercise its authority under the FFDCA to revoke the walnut EtO tolerance.
Tolerance changes will be proposed through a separate rulemaking process.
IV. INTERAGENCY CONSIDERATIONS
The federal government has taken an all-agency approach to addressing concerns about the use
of EtO since the establishment of the Ethylene Oxide Interagency Task Force in February 2020.
Members of the Task Force include EPA Office of Pesticide Programs (EPA-OPP), EPA Office
of Air and Radiation (EPA-OAR), EPA Office of Research and Development (EPA-ORD), the
Centers for Disease Control and Prevention and Agency for Toxic Substances and Disease
Registry (CDC-ATSDR), the Occupational Safety and Health Administration (OSHA), the Food
and Drug Administration Center for Food Safety and Applied Nutrition (FDA-CFSAN), and the
Food and Drug Administration Center for Devices and Radiological Health (FDA-CDRH).
Members meet monthly to discuss the on-going regulatory concerns for EtO. In particular, for
the regulation of the pesticidal registrations of EtO, OPP is working closely with OSHA and
62 EOTF email to EPA regarding benefits of ethylene oxide for medical devices. Email sent from Lisa Campbell,
Partner, Bergeson & Campbell PC to Jessica Bailey, Antimicrobial Division, Office of Pesticide Programs,
Environmental Protection Agency. May 6, 2020.
63 American Spice Trade Association (ASTA). 2017. Clean, Safe Spices, Guidance from the American Spice Trade
Association, 2017 Update, https://www.astaspice.org/food-safetv-techiiical-giiidance/best-practices-and-
guidance/clean-safe-spices-guidance-document/. Accessed September 2020.
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FDA on the registration review risk mitigation to address risks to workers and nearby
communities, as discussed below. EPA thanks all federal partners for their collaboration.
A. Occupational Safety and Health Administration (OSHA)
OSHA standards are issued pursuant to the OSH Act and are found in title 29 of the Code of
Federal Regulations (CFR). There are separate standards for general industry, construction,
maritime and agriculture activities, as well as general standards applicable to a number of sectors
(e.g., OSHA's Respiratory Protection standard). OSHA has numerous standards that could apply
to pesticidal uses of chemicals, including the OSHA standard 29 CFR 1910.1047 Ethylene
Oxide.64
OSHA sets legally enforceable limits on the concentrations of hazardous chemicals in the air in a
workplace, referred to as permissible exposure limits (PELs), to protect workers against the
health effects of exposure to such chemicals (29 CFR 1910 Subpart Z, 1915 Subpart Z, 1926
Subparts D and Z). Under section 6(a) of the OSH Act, OSHA was permitted an initial two-year
window after the passage of the Act to adopt "any national consensus standard and any
established Federal standard." 29 U.S.C. 655(a). OSHA used this authority in 1971 to establish
PELs that were adopted from federal health standards originally set by the Department of Labor
through the Walsh-Healy Act, pursuant to which approximately 400 occupational exposure limits
were selected based on the American Conference of Governmental Industrial Hygienists
(ACGIH) 1968 list of Threshold Limit Values (TLVs). In addition, about 25 exposure limits
recommended by the American Standards Association (now called the American National
Standards Institute (ANSI)) were adopted as PELs.
Following the two-year window provided under section 6(a) of the OSH Act for adoption of
national consensus and existing Federal standards, OSHA has issued health standards following
the requirements in section 6(b) of the Act. OSHA has established approximately 30 PELs under
section 6(b)(5) as part of comprehensive substance-specific standards that include additional
requirements for protective measures such as establishment of regulated areas, exposure
assessment, medical surveillance, and training.
With few exceptions, OSHA's PELs have not been updated since they were first established
starting in 1971. At this time, the EtO PEL was established at 50 ppm, based on the 1968
ACGIH TLV. The PEL for EtO has not been revised since 1984, when it was set at 1 ppm. Yet,
in many instances, scientific evidence has accumulated suggesting that the current limits are not
sufficiently protective. As stated on OSHA's annotated PELs webpage, OSHA has recognized
that many of its PELs are outdated and inadequate for ensuring protection of worker health.65 In
addition, health standards issued under section 6(b)(5) of the OSH Act must reduce significant
risk only to the extent that it is technologically and economically feasible. OSHA's legal
requirement to demonstrate that its 6(b)(5) standards are technologically and economically
feasible often precludes OSHA from imposing exposure control requirements sufficient to ensure
that the chemical substance no longer presents a significant risk to workers. In sum, the great
majority of OSHA's chemical standards are outdated or do not eliminate significant risk as
64 https://www.osha.gov/laws-regs/regulations/standardnumber/1910/1910.1047.
65 https://www.osha.gov/annotated-pels.
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defined by the Supreme Court's interpretation of the OSH Act66. They would, in either case, be
unlikely to address unreasonable adverse effects to workers within the meaning of FIFRA, which
allows EPA to consider more sensitive endpoints and working populations than OSHA's risk
evaluations typically contemplate.
OSHA, under limited circumstances, has cited the General Duty Clause for worker exposure to
hazardous chemicals that are not sufficiently addressed under 29 CFR 1910 Subpart Z, 1915
Subpart Z, 1926 Subparts D and Z. To prove a violation of the General Duty Clause, OSHA must
prove employer or industry recognition of the hazard, that the hazard was causing or likely to
cause death or serious physical harm, and a feasible method was available to eliminate or
materially reduce the hazard. In rare situations, OSHA has cited employers for violation of the
General Duty Clause where exposures were below a chemical-specific OSHA PEL. In such
situations, OSHA must demonstrate that the employer had actual knowledge that the PEL was
inadequate to protect its employees from death or serious physical harm. Because of the heavy
evidentiary burden on OSHA to establish violations of the General Duty Clause, it is not
frequently used to cite employers for employee exposure to chemical hazards.
Thus, it is appropriate that EPA conduct risk assessments and, where it finds risks of concern to
workers, develop risk mitigation measures to address risks from the pesticidal uses of chemicals
that OSHA also regulates, and it is expected that EPA's findings and requirements may
sometimes diverge from OSHA's. However, it is also appropriate that EPA consider the
chemical standards that OSHA has already developed, so as to limit the compliance burden to
employers by aligning risk management approaches required by the agencies, where alignment
will ensure that the use of a pesticide will not cause unreasonable adverse effects on the
environment, including to workers.
When developing mitigation measures to address risks of concern to workers, EPA will: 1) strive
for consistency with applicable OSHA requirements and industry best practices, including
appropriate application of the hierarchy of controls (e.g., elimination, substitution, engineering
controls, administrative controls, PPE), when those measures would address risks of concern to
workers; 2) ensure the EPA requirements apply to all potentially exposed workers; and 3)
develop occupational risk mitigation measures to address any risks of concern identified by EPA.
EPA's risk assessment on EtO has found risks of concern to workers associated with the
registered uses of EtO, even when the applicable OSHA requirements are being met. EPA has,
therefore, developed risk mitigation measures beyond those included in OSHA's standards.
In the Reregistration Eligibility Decision for Ethylene Oxide (2008), OPP required registrants to
implement label amendments for respirator requirements and air monitoring requirements based
on the OSHA PEL of 1 ppm. Since 2008, there have been considerable updates to the scientific
database on EtO exposure and risk, including the 2016 IRIS assessment on EtO, OPP's 2020 EtO
DRA, and OPP's 2023 EtO DRA Addendum. EPA thus considers the OSHA PEL of 1 ppm to no
longer ensure that the use of EtO will not cause unreasonable adverse effects, including effects to
workers, as required under FIFRA and is therefore proposing to require that registrants amend
66 Am. Petroleum Inst., 448 U.S. at 655.
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their EtO labels to no longer include the OSHA PEL. See Section V.A. for details on worker
mitigation and Appendix B for EtO product label requirements.
EPA understands that OSHA's EtO PEL has not been updated since it was established in 1984,
and that health standards issued under section 6(b)(5) of the OSH Act must reduce significant
risk only to the extent that it is technologically and economically feasible.67 OSHA's legal
requirement to demonstrate that its 6(b)(5) standards are technologically and economically
feasible often precludes OSHA from imposing exposure control requirements sufficient to ensure
that the chemical substance no longer presents a significant risk to workers. Therefore, in lieu of
revising the EtO PEL of 1 ppm, EPA will work with OSHA to revise the following parts of
OSHA standard 29 CFR 1910.1047 Ethylene Oxide to align more with updated scientific
assessments on EtO:
• Engineering controls and work practices provision (29 CFR 1910.1047(f)(1))
• Hazard communication (29 CFR 1910.1047(j)(1))
• Classifying the hazards of EtO (29 CFR 1910.1047(j)(l)(ii))
• Signage and labels (29 CFR 1910.1047(j)(2)(i)) and 1047(j)(2)(ii))68
EPA will also work with OSHA to revise the OSHA Safety and Health Topics Webpage for
Ethylene Oxide to acknowledge EPA's publications.69
Alternative Exposure Limits
Internationally, an 8-hour worker exposure limit of 1 ppm for EtO is generally accepted, with
few exceptions. In Israel, for example, the exposure limit is 1 ppm for men, but 0.75 ppm for
women.70 In Germany, 1 ppm is the workplace exposure concentration corresponding to the
proposed tolerable cancer risk, while 0.1 ppm is the workplace exposure concentration
corresponding to the proposed preliminary acceptable cancer risk.71 The German Committee on
Hazardous Substances (Ausschuss fur Gefahrstoffe, or AGS) sets risk-based limits for
carcinogens based on social policy wherein there are "acceptable" and "tolerable" risks. For
occupational lifetime cancer risks, acceptable risk in Germany is 4 in 100,000, which may be
exceeded if specific measures are complied with; and tolerable risk is 4 in 1,000, which may not
be exceeded.72 The European Union EtO exposure limit of 1 ppm is a regulatory limit, which
takes into account market availability of biocidal products while ensuring a high level of
protection for human and animal health and the environment, and was established in 2017.73 The
https
//www.fede ralregister.gov/citation/49-FR-25734.
https
//www.osfaa.gov/laws-regs/regulations/standafdniiinber/1910/1910.1047
https
//www.oslia.gov/etlivlene-Qxide.
70 GESTIS International Limit Values, fattps://ti mltvahie. ifa.dgnv.de/.
71 The MAK Collection for Occupational Health and Safety 2019, Vol 4, No 3. A. Hartwig, MAK Commission,
DOI: 10.1002/3527600418.mb7521d0067.
72 Occupational Limit Values (Arbeitsplatzgrenzwerte - AGW). https://www.dguv.de/ifa/gestis/gestis-
inteniationaie-grenzwerte-fiier-cfaeniiscfae-snbstanzen-liniit-vaines-for-cfaemicai-agents/liniit-valnes-germanv-
(agsVindex.isp?auerv=webcode+e786799.
73 Directive (EU) 2017/2398 of the European Parliament and of the Council of 12 December 2017 amending
Directive 2004/37/EC on the protection of workers from the risks related to exposure to carcinogens or mutagens at
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EU also has a risk-based limit of 3 ppb, based on extrapolation from a mouse study in 2021. In
this study, exposure monitoring data from four EtO commercial sterilization facilities in Europe
were compared to the derived minimal effect level (DMEL) of 3 ppb and showed that even the
lowest monitoring value exceeded the DMEL by 400%; therefore, no acceptable worker risk was
shown.74
In the U.S., there is a recommended exposure limit (REL) from the National Institute for
Occupational Safety & Health (NIOSH) set at 0.1 ppm.75 As this is a recommended limit only, it
is not enforceable. The purpose of NIOSH RELs is to provide guidance to OSHA for forming
enforceable regulations.76
It is EPA's understanding that certain sterilization facilities in the U.S. may utilize a lower
exposure limit than what is required by OSHA to set company-specific risk policies. EPA
requests public comment on facilities that utilize lower exposure limits than the OSHA PEL, and
what practices these facilities use to achieve and measure these lower limits.
Training Requirements
Commercial Sterilization Facilities for Medical Devices and Spices
OSHA's standard for EtO, 1910.1047(j)(3)(iii) Information and Training states that employee
training shall include at least:
• Methods and observations that may be used to detect the presence or release of EtO in the
work area (such as monitoring conducted by the employer, continuous monitoring
devices, etc.);
• The physical and health hazards of EtO,77 which must include at a minimum cancer;
reproductive effects; mutagenicity; central nervous system; skin sensitization; skin, eye,
and respiratory tract irritation; acute toxicity effects; and flammability per
1910.1047(j)(l)(ii);
• The measures employees can take to protect themselves from hazards associated with
EtO exposure, including specific procedures the employer has implemented to protect
employees from exposure to EtO, such as work practices, emergency procedures, and
personal protective equipment to be used; and
• The details of the hazard communication program developed by the employer, including
an explanation of the labeling system and how employees can obtain and use the
appropriate hazard information.
work (Text with EEA relevance) can be found at https://eur~lex.europa.eii/legal~
co n te n t/EN/ALL/?nri =nri se rv: 0 i.7.345.0.t..0087.0.t..ENG
74 Norwegian Environment Agency, Oslo, Norway. 2021. Regulation (EU) NO 528/2012 Concerning the making
available on the market and Use of Biocidal Products, Ethylene Oxide. EC Number 200-849-9. CAS Number 75-21-
8.
75 https://www.cdc.gov/niosli/npg/npgd0275.htiiil.
76 https://www.cdc.gov/niosli/iipg/pgiiitrod.htiiil.
77 This includes all classified hazards as per 1910.1200, and at a minimum include at a minimum Cancer;
reproductive effects; mutagenicity; central nervous system; skin sensitization; skin, eye and respiratory tract
irritation; acute toxicity effects; and flammability as per 1910.1047(j)(l)(ii).
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For information on EPA's current and proposed training requirements, see Section V.A.
B. Food and Drug Administration (FDA)
Medical Devices
FDA's Center for Devices and Radiological Health (CDRH) assures that patients and providers
have timely and continued access to safe, effective, and high-quality medical devices.78 Before
most sterile medical devices are on the market, FDA reviews submissions to determine if the
sterility information is consistent with the sterility assurance under which the device is labeled
and intended for use (e.g., in accordance with internationally agreed upon voluntary consensus
standards that FDA recognizes).
For EtO sterilization, two voluntary consensus standards (ANSI AAMI ISO 11135:2014 and
ANSI AAMI ISO 10993-7:2008(R)2012) describe how to develop, validate, and control EtO
sterilization processes for medical devices and the acceptable levels of residual EtO and ethylene
chlorohydrin (ECH) left on a device after it has undergone EtO sterilization. FDA also inspects
industrial facilities that sterilize medical devices and medical device manufacturing facilities to
make sure that they have validated sterilization processes that meet FDA-recognized standards.
State health departments inspect healthcare facilities that use EtO to sterilize medical devices.
FDA actively works with sterilization experts, medical device manufacturers, and other
government agencies to advance innovative ways to sterilize medical devices with lower levels
of EtO and employ new agents or alternatives, while maintaining device safety and effectiveness
in order to prevent potential medical device shortages.79 In May and November 2019, FDA
engaged the infection control community at the Healthcare Infection Control Practices Advisory
Committee (HICPAC) and General Hospital and Personal Use Panel of the Medical Devices
Advisory Committee meetings, respectively, to update the public on FDA's work and
engagement with industry on sterilization modalities with devices that are normally sterilized
using EtO.80
On July 15, 2019, FDA announced two public innovation challenges to encourage development
of new approaches to medical device sterilization, which could include identifying alternatives to
EtO sterilization methods or strategies to reduce EtO emissions:
• Challenge 1: Identify New Sterilization Methods and Technologies.
• Challenge 2: Reduce Ethylene Oxide Emissions.
On November 25, 2019, FDA announced that 46 applications were received, and 12 participants
were selected for the challenges. Details on the progress of innovations are described below.
78 https://www.fda.gov/about-fda/fda-organization/center-devices-and-radiological-health.
79 https://www.fda.gov/news-events/press~annoiincements/statement~fda-commissioner~scott~gottlieb~md~steps~
aggnei:Mi^^
80 https://www.fda.gov/advisorv-committees/advisorv-committee-calendar/novemlx 19-general-hospital-
and-personal-iise-devices~panei~medical~devices~advisorv-committee.
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Innovation Challenge 1: Identify New Sterilization Methods and Technologies
The goal of this challenge is to identify safe and effective sterilization methods or technologies
for medical devices that do not rely on EtO and that meet these criteria:
• Compatibility: The method or technology is compatible with a large cross section of
materials used to manufacture or fabricate medical devices as well as packaging materials
or sterile barriers. The materials, devices, and barriers of particular interest are those that
are compatible with EtO sterilization.
• Scalability and High Throughput: The method or technology should have the potential to
be scalable and allow for the effective sterilization of large volumes of devices.
FDA selected four participants and five submissions for this challenge: NovaSterilis's
Supercritical Carbon Dioxide Sterilization; Noxilizer's Nitrogen Dioxide Sterilization; STERIS's
Accelerator-Based Radiation Sterilization; STERIS's Vaporized Hydrogen Peroxide
Sterilization; and TS03 (Stryker)'s Vaporized Hydrogen Peroxide-Ozone Sterilization.
Participants selected for this challenge are working directly with FDA to accelerate the
development and review of these innovative technologies.
Innovation Challenge 2: Reduce Ethylene Oxide Emissions
The goal of this challenge is to develop strategies or technologies to reduce emissions to as close
to zero as possible from the EtO sterilization process. Innovative strategies may entail changing
current sterilization processes or workflow, such as changes in the supply chain, transportation of
medical devices, or procedures in the sterilization site. Strategies may also include making
alterations to EtO process waste to reduce emissions.
The strategies or technologies may allow for the:
• Use of lower levels of EtO while maintaining assurance that devices are safely and
effectively sterilized.
• Capture of EtO emissions and/or transformation to harmless byproducts.
• Detection, measurement, tracking, and containment of fugitive emissions to prevent or
minimize emissions into the sterilization facility or environment.
• Safe use of EtO while minimizing harmful exposure (such as toxicity and
carcinogenicity) to sterilization workers and nearby communities.
FDA selected eight participants for this challenge: Abbott's Enhanced EtO Cycle Design and
Processes; Andersen Scientific's Use of EtO-Flexible Chamber Technology; Becton Dickinson
and Company's Enhanced EtO Cycle Design and Processes; DMB Apparatebau's Reduced
Sterilant Concentration; Medtronic's Enhanced EtO Cycle Design and Processes; Sterigenics's
Enhanced EtO Cycle Design and Processes; STERIS's Enhanced EtO Cycle Design and
Processes; and Taiwan Advanced Sterilization Technologies Inc.'s Abatement Strategy.
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Participants selected for this challenge are working directly with FDA to accelerate the
development and review of innovative technology.
Through FDA's Innovation Challenge 2, some industry participants have already implemented
their optimized cycle designs, reducing EtO use by a significant amount. Per an FDA statement,
early observations suggest that some facilities have cut emissions ranging from 20-35%, with the
potential to impact millions of devices. In general, participating manufacturers are targeting an
EtO concentration that is 11-66% less than the typical concentration range.81
Expediting Approvals for Changes to Sterilization Processes
Typically, for premarket application (PMA) approved devices, if a medical device manufacturer
changes the method, process, or the facility identified in its original PMA submission for
sterilizing its devices, the manufacturer generally needs to submit a PMA supplement so that
FDA can review these changes and determine if the sterility information remains consistent with
the sterility assurance under which the device is labeled and approved for use (e.g., in accordance
with internationally agreed-upon voluntary standards that FDA recognizes). For manufacturers
that are 510(k) holders, sterilization method, process or site modifications can be assessed as
recommended in the FDA guidance document: "Deciding When to Submit a 510(k) for a Change
to an Existing Device" for determination on whether the sterilization modifications would trigger
the need for resubmission.82
On November 26, 2019, FDA announced the Ethylene Oxide Sterilization Master File Pilot
Program for sterilization facilities and PMA holders. The EtO Pilot Program seeks to help ensure
patient access to safe medical devices while encouraging new, innovative ways to sterilize
medical devices that reduce the potential impact of EtO on the environment and on the public
health while providing a regulatory approach that would address potential device shortages. The
EtO Pilot Program is voluntary and is intended to allow companies that sterilize single-use
medical devices using fixed chamber EtO to submit a Master File when making certain changes
between sterilization sites or when making certain changes to sterilization processes that utilize
reduced EtO concentrations. Under this voluntary program, manufacturers ("Pre-Market
Application (PMA) holders") of Class III devices subject to premarket approval that are affected
by such changes may, upon FDA's permission, reference the Master File submitted by their
sterilization provider in a post approval report in lieu of submission of a premarket approval
application (PMA) supplement.83'84 The EtO Sterilization Master File Pilot Program for PMA
holders includes the following participants: Boston Scientific (accepted March 18, 2020);
81 https://www.fda. gov/news-events/press-annonncements/fda-continnes-efforts-support-innovation-medical-device-
sterilization.
82 https://www.fda.gov/medical-devices/general-hospital-devices-and-snpplies/ethvlene-oxide-sterilization-medical-
devices.
83 https://www.federalregister.gov/documents/2Q] QO.1.9-2563.1/center-for-devices-and-radiological-health-
ethvtene-oxide-steritization~master-fite-pitot-pro grain.
84 Device classification depends on the intended use of the device and also upon indications for use. A discussion of
the meaning of intended use is contained in The 510(k) Program: Evaluating Substantial Equivalence in Premarket
Notification [510(k)]. In addition, classification is risk based, that is, the risk the device poses to the patient and/or
the user is a major factor in the class it is assigned. Class I includes devices with the lowest risk and Class III
includes those with the greatest risk.
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Becton, Dickinson & Company (accepted September 11, 2020); Steris Corporation (accepted
October 25, 2021); Oscor, Inc. (accepted December 17, 2021); and Medtronic, Inc. (accepted
February 17, 2022).85
On May 20, 2022, FDA announced its 510(k) Sterility Change Master File Pilot Program. The
510(k) Sterility Pilot Program is voluntary and is intended to give interested companies that
terminally sterilize single-use devices using certain sterilization methods a pathway to submit a
Master File for FDA's review. This voluntary pilot program seeks to encourage industry to
consider new, innovative ways to sterilize devices that reduce the potential impact of EtO on the
environment and on public health, while ensuring consistent patient access to safe devices and
providing a framework for future regulatory approaches that would help address potential device
shortages related to EtO sterilization. FDA will accept a Master File into the 510(k) Sterility
Pilot Program when it determines, among other things, that there is not a likelihood that
switching from a fixed chamber EtO sterilization method to the sterilization method described in
the Master File could significantly affect the safety or effectiveness of a 510(k)-cleared device
that meets the product definition in the Master File. If a Master File is accepted into the 510(k)
Sterility Pilot Program, manufacturers of 510(k)-cleared devices may choose to reference the
Master File in internal documentation in support of a justification for not submitting a new
premarket notification. The 510(k) Sterility Change Master File Pilot Program is open to all
current 510(k) holders, and up to nine eligible sterilization providers may be selected for
participation in the 510(k) Sterility Pilot Program.86
Spices
FDA also is an important federal partner with respect to EtO fumigation of spices. FDA's Center
for Food Safety and Applied Nutrition (CFSAN) protects and promotes public health by 1)
modernizing methods to find, track, and eliminate harmful pathogens and other hazards, 2)
evaluating the safety of new ingredients for food and the safety of new color additives, 3)
strengthening manufacturing practices, 4) ensuring properly labeled food, dietary supplements,
and cosmetics, 5) fostering good nutrition and effective food safety practices, 6) investigating
causes of foodborne illness outbreaks, and 7) targeting unsafe products.87 Passage of the Food
Safety Modernization Act (FSMA) in 2011 expanded FDA's authority under the Federal Food,
Drug, and Cosmetic Act to ensure the food supply in the United States is safe. FDA's authority
covers domestically grown and produced food as well as food and ingredients imported from
abroad, except for meat; poultry; Siluriformes fish, including catfish; and certain egg products
for which the Food Safety and Inspection Service (FSIS) of the U.S. Department of Agriculture
(USDA) is responsible. FDA is responsible for ensuring that food, including spices, is not
adulterated or misbranded. Foods, including spices, can be adulterated for reasons such as they
contain pathogens or pesticide residues such as EtO or ECH at unsafe levels, or because they are
produced under unsanitary conditions.
85 https://www.fda.gov/medieat~deviees/generat~hospital~deviees~and-siippties/ethvtene~oxide~steritization~medicat-
deviees#MasterFile.
86 https://www.federalregister.gov/documents/2022/05/20/2022-10925/medical-devices-510k-sterility-change-
master-file-pilot-program.
87 https://www.fda.gov/about-fda/center-food-safetv-and-applied-nutrition-cfsan/what-we-do-cfsan
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Many spices are imported into the U.S.88'89 FDA has an import safety program that has
traditionally consisted of inspecting foreign facilities that import food into the U.S. and
inspecting shipments at the port of entry. FSMA also established prevention-based programs to
ensure the safety of imported foods before they reach the U.S.90 These include the Foreign
Supplier Verification Program and the Voluntary Qualified Importer Program, as well as
accrediting third-party certification bodies to conduct food safety audits of foreign food entities.
The Foreign Supplier Verification Program requires importers to verify the safety of the food
they import, and FDA inspects importers to make sure they are doing so. The Voluntary
Qualified Importer Program involves expedited review of food from eligible importers that meet
rigorous standards.
Treatment (including reconditioning) of spices for pathogen control
Herbs and spices can contain pathogens of public health significance. Spices may be treated for
pathogen reduction as a preventive measure to control pathogens, due to the confirmed presence
of a pathogen, such as Salmonella, or due to the appearance of adulteration. The primary
treatment options for pathogen reduction on dried herbs and spices are EtO, steam, and
irradiation; propylene oxide (PPO) also is used occasionally. When FDA detains spice shipments
for pathogens, a reconditioning proposal to bring the product into compliance can be submitted
by the responsible firm to FDA. The reconditioning proposal must identify the proposed
treatment option and treatment location. If the reconditioning proposal is accepted by FDA, the
spices are then sent to the facility for treatment. After the treatment process, the manufacturer or
importer of the lot will generally provide testing results of the treated lot for FDA review to
verify that the treatment was effective, and the product is safe.91
Of the reconditioning proposals submitted to FDA for imported spices and herbs from 2015-
2019, half of the reconditioning proposals were for EtO treatment. The other half proposed
alternative treatment methods (e.g., irradiation, steam, propylene oxide). A review of spice
reconditioning proposal applications from 2019-2022 revealed that there were 34 total
submissions including resubmissions (there were 14 original submissions), and approximately
36% (5 of the 14 original submissions) of the proposed treatments were for EtO.92 The other
reconditioning proposals were for heat treatment, steam sterilization or irradiation (gamma or
infrared drum). Some examples of spices that were submitted for reconditioning by EtO
88 FDA Center for Food Safety and Applied Nutrition (FDA CFSAN). 2017. Draft Risk Profile: Pathogens and Filth
in Spices. Center for Food Safety and Applied Nutrition, Food and Drug Administration. U.S. Department of Health
and Human Services, https://www.fda.gov/media/108126/download. Accessed August 2021.
89 American Spice Trade Association (ASTA). 2020. ASTA reply to EPA questions regarding ethylene oxide use on
spices. Email from Laura Shumow, Executive Directors, ASTA, to Susan Bartow, Pesticide Re-Evaluation Division,
Office of Pesticide Programs, Environmental Protection Agency. June 25, 2020.
90 https://www.fda.gov/food/cfsan-risk-safetv-assessments/auestions-answers-improving-safetv-spices.
91 Ethylene Oxide (EtO) Spice Sterilizing Facilities. Center for Food Safety and Applied Nutrition (CFSAN), Food
and Drug Administration (FDA) responses to questions from Office of Pesticide Programs (OPP), Environmental
Protection Agency (EPA). December 20, 2022.
92 Letter from Dr. Girvin Liggans, Acting Deputy Director for Plant Derived Foods, Office of Food Safety, Center
for Food Safety and Applied Nutrition, Food and Drug Administration to Edward Messina, Director, Office of
Pesticide Programs, Environmental Protection Agency. August 18, 2022.
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treatment were thyme, thyme leaves and black pepper. Reconditioning proposals are generally
for whole spices or single spice powders.93
FDA also may inspect commercial sterilization facilities. Firms are not required to submit
process control validation data to FDA, but FDA will review data during inspections. Regardless
of the facility location and type, FDA's review of reconditioning proposals ensures that each
treatment process for microbial reduction is effective. In addition, when a
manufacturing/processing facility is subject to the requirements for hazard analysis and
preventive controls in the Current Good Manufacturing Practice, Hazard Analysis, and Risk-
Based Preventive Controls for Human Food (PCHF) regulation in 21 CFR part 117 and is using a
certain process for pathogen reduction as a preventive control, it must validate the process to
ensure it is adequate for controlling the identified hazards (21 CFR 117.160(a)).94
The ASTA developed documents to assist sterilization facilities in developing validations for
fumigations of herbs and spices entitled, General Protocol for the Validation of Microbicidal
Processes on Pathogen Contaminated Spices and Culinary Herbs (2001) and Validation of
Microbial Reduction Processes for Spices (2013). These documents may assist commercial
sterilization facilities with complying with portions of the PCHF regulation as mandated by
FSMA. FDA is in the process of developing its own guidance, Hazard Analysis and Risk-Based
Preventive Controls for Human Food; Chapter 16: Validation of Process Controls; Draft
Guidance for Industry. EPA is not aware of any new technologies that are available for spice
microbial remediation. New technologies can take up to ten years to be implemented because
research and validation are required.95
V. PROPOSED INTERIM REGISTRATION REVIEW DECISION
A. Proposed Risk Mitigation and Regulatory Rationale
EtO is a known carcinogen. EtO is also a critical tool for the medical sterilization market and is
beneficial when used on spices to control microbes which may cause food-borne illnesses. The
registered uses of EtO pose inhalation risks to workers inside commercial sterilization facilities,
healthcare facilities, and to those treating beekeeping equipment in North Carolina. EtO also has
the potential to pose inhalation risks to communities near facilities where EtO is used. See
Section III.A.-B. above. Therefore, EPA is proposing mitigation to address inhalation risk
concerns. The Agency finds that mitigation of inhalation risk concerns is necessary for use of
EtO to meet the FIFRA standard for continued registration. To help address these concerns, EPA
is proposing the termination of certain uses, a use rate reduction through reduced concentrations,
93 Ethylene Oxide (EtO) Spice Sterilizing Facilities. Center for Food Safety and Applied Nutrition (CFSAN), Food
and Drug Administration (FDA) responses to questions from Office of Pesticide Programs (OPP), Environmental
Protection Agency (EPA). December 20, 2022.
94 Ethylene Oxide (EtO) Spice Sterilizing Facilities. Center for Food Safety and Applied Nutrition (CFSAN), Food
and Drug Administration (FDA) responses to questions from Office of Pesticide Programs (OPP), Environmental
Protection Agency (EPA). December 20, 2022.
95 Ethylene Oxide (EtO) Spice Sterilizing Facilities. Center for Food Safety and Applied Nutrition (CFSAN), Food
and Drug Administration (FDA) responses to questions from Office of Pesticide Programs (OPP), Environmental
Protection Agency (EPA). December 20, 2022.
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a series of engineering controls within commercial sterilization facilities and healthcare facilities,
respiratory protection requirements for commercial sterilization facilities, monitoring, training,
and recordkeeping requirements
The Agency discussed risk mitigation options with sterilization industry representatives,
(including the Ethylene Oxide Task force (EOTF), Steris, the American Spice Trade Association
(AST A), and AdvaMed), as well as USD A, OSHA, and FDA. The Agency also discussed the
proposed mitigation measures associated with the beekeeping equipment use in North Carolina
with the North Carolina Department of Agriculture and Consumer Services (NCDACS).
Proposed Termination of Uses
EPA proposes to terminate the following uses of EtO:
• Museum materials
• Library materials
• Archival materials
• Cosmetics
• Musical instruments
• Beekeeping equipment
Use of EtO by Commercial Sterilization Facilities for Museum. Library, and Archival Materials.
Cosmetics, and Musical Instruments
EtO is registered for use to treat museum, library, and archival materials, as well as cosmetics
and musical instruments, in commercial sterilization facilities. For occupational handlers at
commercial sterilization facilities, cancer risk estimates are estimated from 4 x 10"2 (1 in 25
workers) to 1 x 10"1 (1 in 10 workers). Cancer risks of concern are also anticipated for
occupational and non-residential and residential bystanders. Because there are viable EtO
alternatives available for these uses, continued registration of EtO provides minimal benefits.
Alternatives for the museum, library, and archival materials include freezing, anoxia (oxygen
deprivation), and irradiation. EtO is no longer used for treatment of museum, library, or archival
materials due to concerns over human health risks associated with off-gassing from treated
materials.96 Gamma irradiation is a viable alternative for cosmetics and EtO is likely no longer
used in the cosmetics industry. For the musical instrument uses, other disinfectant products are
available for use that are more practical. These products are low cost and easily accessible as
compared to EtO sterilization in commercial sterilization facilities. For additional information,
see Section III.C and Ethylene Oxide (PC# 042301): Use, Usage, Benefits, and Impacts of
Cancellation in this docket. Therefore, EPA proposes that these uses be terminated.
96 Email communication between Jessica Johnson, Head of Conservation, Museum Conservation Institute,
Smithsonian Institution and Jessica Bailey, Antimicrobial Division, Office of Pesticide Program, Environmental
Protection Agency. March 18, 2021.; Email communication between Lindsey Oakley, Director of Heritage Science
Research and Testing, U.S. National Archives and Records Administration and Jessica Bailey, Antimicrobial
Division, Office of Pesticide Program, Environmental Protection Agency. March 30, 2021.; Email communication
between Hayes Robinson III, Associate Director, Environmental Management Division, Office of Safety, Health and
Environmental Management at the Smithsonian Institution and Jessica Bailey, Antimicrobial Division, Office of
Pesticide Program, Environmental Protection Agency. March 18, 2021.
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There is low to no impact expected as a result of the termination of these uses. For more
information on the alternatives to EtO and impacts of termination of these uses, see Ethylene
Oxide (PC# 042301): Use, Usage, Benefits, and Impacts of Cancellation in this docket.
Beekeeping Equipment (in NC only)
EtO is approved for the treatment of beekeeping equipment in North Carolina under FIFRA
section 24(c) SLN registration NC140003. EtO is used for the sterilization of beekeeping
equipment to control American foulbrood (AFB) disease in the state. The North Carolina
Department of Agriculture and Consumer Services (NCDACS) currently operates one treatment
chamber in the Raleigh, NC area for this purpose. There is the potential for non-occupational
bystander exposure for people who live near the treatment chamber (residential non-occupational
bystanders) or who spend significant time in the area for non-work-related activities (e.g.,
school, daycare, shopping) (non-residential non-occupational bystanders).
The distances from the fumigation chamber at which the cancer risk estimates are less than 1 x
10"6 increase from 10 meters to 300 meters or more depending on the percentile considered (e.g.,
75th and 90th respectively). A specific percentile has not been selected for regulation (and
correspondingly a buffer distance from the fumigation chamber has not been established) since
the Agency is proposing to terminate the use of EtO on beekeeping equipment in North Carolina.
There also is the potential for occupational exposure for people who operate the treatment
chamber in NC. Cancer risks range from 2 x 10"4 (1 in 5,000) when assuming 4 exposure days
per year to 4 x 10"4 (1 in 2,500) when assuming 8 exposure days per year. These risk estimates
also assume that self-contained breathing apparatus (SCBA) PPE is in use. These cancer risk
estimates exceed the Agency target of 1 x 10"4 for occupational risks. For more information, see
section III. A above and Ethylene Oxide (EtO). Addendum to "Draft Human Health and
Ecological Risk Assessment in Support of Registration Review " - Inhalation Exposure Risk
Assessment in Support of Registration Review in this docket.
Beekeepers have several chemical and non-chemical alternatives to EtO for preventing and
disinfecting beekeeping equipment of AFB. Chemical control alternatives include antibiotics
such as terramycin, tylan (tylosin), or lincomix soluble powder. Non-chemical control tactics
include cultural and mechanical/physical controls. Examples of cultural controls include
practices such as purchasing several new frames for hives each year, sanitizing hands with
alcohol-based hand sanitizer and wearing non-leather gloves when working with a hive,
sanitizing equipment/tools with isopropyl alcohol, irradiation, or autoclave prior to working with
a hive and/or between seasons, and hive placement. Examples of mechanical controls include
fire scorching small equipment with a blowtorch followed by a bleach spray, or the burning or
destruction of infected colonies and equipment. Beekeepers can also sanitize infected equipment
including frames by boiling infected materials in sodium hydroxide (lye), although this may
involve culling the hive if the equipment is in use.
Given that the risk estimates for this use assume the use of the highest level of respiratory
protection (SCBA) and, nonetheless, exceed the Agency target of 1 x 10"4 for occupational risks,
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and that there are alternative control methods for AFB in place in the other states that are feasible
in North Carolina, the Agency proposes that the benefits of the use do not outweigh the risk.
Therefore, the Agency has determined that the use of EtO for disinfecting beekeeping equipment
does not meet the FIFRA standard and proposes that the use be terminated.
There is low to no impact expected from the proposed termination of the use to sterilize
beekeeping equipment in North Carolina (the only state with this registered use). There are
alternative chemical, cultural, and mechanical controls available to manage American foulbrood,
a contagious disease that affects honeybees. For more information on the impacts of the
cancellation of this use, see Ethylene Oxide (PC# 042301): Use, Usage, Benefits, and Impacts of
Cancellation in this docket.
EPA proposes that the registrants submit requests to voluntarily terminate the uses of EtO for
museum materials, library materials, archival materials, cosmetics, musical instruments, and
beekeeping equipment as soon as practicable, but no later than 60 days from the publication of
the Interim or Final Decision. EPA will specify the timing for submission of such requests at a
later date.
Spices
Limiting the use of EtO to specific dried herbs and spices where its use is deemed critical for
food safety and where alternative treatment methods are not available could result in fewer EtO
applications overall, and thus less exposure to workers (including handlers and occupational
bystanders), non-residential bystanders, and residential bystanders. Because of the estimated
occupational and bystander risks associated with the use of EtO to fumigate spices, the Agency is
soliciting comments on the specific commodities in Table 2 for which there is a critical need for
the use of EtO and for which there are no viable alternatives to EtO (e.g., steam, irradiation, or
propylene oxide cannot be used for pathogen control on a particular spice, spice form, or spice
blend). The Agency is considering a phased cancellation of specific spices/commodities without
documented support for continued treatment with EtO. The Agency intends to include language
in the ID stating that registrants should submit requests to voluntarily terminate uses on these
commodities. When the Agency receives requests from registrants to voluntarily cancel a
pesticide registration or terminate a use, the Agency is required to publish an FRN regarding the
cancellation request and take public comment (see 7 U.S.C. § 136d(f)(l)).
Proposed EtO Use Rate Reduction
Medical Devices
A sterilization cycle is defined as "treatment in a sealed chamber, which includes air removal,
conditioning (if used), injection of ethylene oxide, inert gas (if used), exposure to ethylene oxide,
removal of ethylene oxide and flushing (if used), and air/inert gas admission."97 A sterilization
calculation includes validated parameters such as pressure, concentration, temperature, humidity,
97 International Standard ISO 11135. Sterilization of health-care products - Ethylene oxide - Requirements for the
development, validation and routing control of a sterilization process for medical devices. 2014.
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and exposure time. Assessment of cycle validation from FDA includes specifications for
products, load configuration, packaging, and sterility assurance level.
Based on discussions with industry and FDA, it is the Agency's understanding that many
sterilization facilities sterilize medical devices using much higher concentrations of EtO than
what is required for sterility assurance - specifically, the Agency has been informed that double
the necessary concentration is often used on some devices. Furthermore, it is the Agency's
understanding, through discussions with industry, that the current EtO concentration may be as
high as 700 mg/L for medical device sterilization. The increased application rate is related to the
way in which facilities sterilize large quantities of mixed devices in order to meet demand. For
example, if a few devices in a large mixed load require 700 mg/L, then all of the devices will be
sterilized at that rate, even those that may need less EtO to ensure sterility. Surgical kits are an
example, which are pre-packaged in order to be quickly sent to operating rooms and contain a
variety of devices which require differing levels of EtO for sterilization. Batching devices in
mixed loads also helps to reduce the total number of EtO cycles run. More EtO runs may be
needed to meet device demand and could result in the need for additional chambers, staff, and
possibly more EtO.
Based on further discussions with industry, the majority of new sterilization cycles are able to
use 500 mg/L or less, if a variety of optimizations are put into place, at the time the device itself
is designed (e.g., device design, packaging, and sterilization parameters). For existing cycles, the
majority of devices are sterilized at concentrations higher than 500 mg/L, and a reduction of this
concentration limit across the industry would require extensive cycle experimentation and
redesigning of devices, as well as cycle validation and review.
EPA proposes that the EtO concentration for new cycles must be less than or equal to 500 mg/L,
and that the sterilization validation process specific to the concentration used is reviewed by
FDA. EPA seeks public comment on the feasibility of a 2-year compliance timeline for use rate
reduction through reduced concentrations of new cycles.
In order to limit the EtO concentration to 500 mg/L for existing cycles, EPA proposes a 5-year
compliance timeframe to redesign cycles, devices, or packaging and be reviewed by FDA under
applicable device authorities. EPA seeks public comment on the feasibility of a 5-year
compliance timeline for use rate reduction of existing cycles.
EPA anticipates this use rate reduction through reduced concentrations would reduce risks for all
exposure scenarios, given that currently most cycles exceed 500 mg/L. If a sterilization cycle
requires more than 500 mg/L, due to the device design, EPA proposes to require registrants
ensure that facilities maintain records that include a justification for the increased application
rate. Specifically, this justification would demonstrate the necessary calculations for determining
the application rate, through either the Cycle Calculation Approach (described below), or other
approaches found in ISO 11135 (described below). EPA further proposes to require registrants
ensure that facilities maintain records for the amount of EtO used regardless of whether the
amount used is less than or greater than 500 mg/L. All records would need to be available upon
request to any local, state, tribal, or federal pesticide enforcement personnel. Records would be
required to be maintained for two years from the date of sterilization.
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If a device has historically used more than 500 mg/L unnecessarily, there are several methods for
decreasing EtO concentration limits while ensuring sterility, including the cycle calculation
approach and cycle design optimization (e.g., with the use of the half cycle approach), as
described below.
Cycle Calculation Approach
The International Organization for Standardization (ISO) is a worldwide federation of national
standards bodies that set a standard for medical device sterilization using EtO titled ISO
11135:2014 Sterilization of health-care products — Ethylene oxide — Requirements for the
development, validation and routine control of a sterilization process for medical devices. This
standard specifies requirements for the development, validation and routine control of an EtO
sterilization process for medical devices in both the industrial and healthcare facility settings.98
Compliance with the requirements ensures that validations conducted following this international
standard will provide products that meet the defined requirements for sterile products with a high
degree of confidence." The sterilization/fumigation cycle parameters are prescribed by the
device manufacturer. Device manufacturers must also validate sterilization methods they select
to facilitate FDA review of sterility information as part of the premarket review process for
devices.
Manufacturers and applicators (i.e., end users) may, for example, follow the Cycle Calculation
Approach to determine the precise amount of EtO necessary to sterilize medical devices.
According to ISO Standard 11135, for the cycle calculation approach, the lethality of the process
on disease-causing microbes can be determined by either direct enumeration, the fraction-
negative method, or both. Once the inactivation of a known number of microorganisms has been
confirmed, the sterilization facility would determine the extent of treatment for the sterilization
process by extrapolation to a known predicted probability of a surviving microorganism. This
method consists of exposing internal process challenge devices to the experimental cycle,
removing the challenge and testing for survivors.100 This information can be used to calculate the
cycle necessary to deliver the defined sterility assurance level for the product. The recommended
number of biological indicators or process challenge devices can be based on the product volume
to be sterilized. Further guidance on the Cycle Calculation Approach can be found in ISO
98 According to ISO 11135:2014, "In terms of the initial condition of medical devices, medical device manufacturers
generally sterilize large numbers of similar medical devices that have been produced from virgin material. Health
care facilities, on the other hand, must handle and process both new medical devices and reusable medical devices of
different descriptions and with varying levels of bioburden. They are therefore faced with the additional challenges
of cleaning, evaluating, preparing and packaging a medical device prior to sterilization. In this International
Standard, alternative approaches and guidance specific to health care facilities are identified as such."
99 The development, validation and routine control of a sterilization process comprises a number of activities;
calibration, maintenance, product definition, process definition, installation qualification, operational qualification
and performance qualification. See ISO 11135:2014.
i°° process challenge devices, or PCD's, are defined as items designed to constitute a defined resistance to a
sterilization process and used to assess performance of the process.
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14161:2009 Sterilization of health care products — Biological indicators — Guidance for the
selection, use and interpretation of results
EPA acknowledges that this approach could increase the overall number of cycles that need to be
run since each device, under the Cycle Calculation Approach, will need its own cycle. This could
make it difficult for sterilization providers to maximize their output and could reduce overall
device availability for patients, as it is rare that a chamber can be completely filled with one
particular product. Due to these limitations, FDA and industry continue to research and
implement additional methods for use rate reductions through reduced concentrations that use a
more conservative ISO 11135 approach while optimizing cycle designs, as described below.
Cycle Design Optimization & Half Cycle Approach
EPA understands that most sterilization facilities employ a very conservative method for medical
device sterilization, the Half Cycle Approach. According to ISO Standard 11135, the Half Cycle
Approach is a total of three consecutive experiments resulting in total inactivation of the
biological indicators, wherein the cycle time is halved compared to the full cycle. Due to its
relative ease of use and the conservative sterility assurance level obtained, this method is
commonly used to demonstrate total inactivation of the biological indicators at a half-cycle
exposure time. As compared to the half cycle, running a full cycle may lead to a process
supporting a sterility assurance level that is higher than the device specification.102
There are methods to reduce the amount of EtO used during the Half Cycle Approach, and these
are currently being pursued by the FDA's "Innovation Challenge 2" participants (see Section
IV.B.). EPA and FDA share the same goal of reducing the overall amount of EtO used by
optimizing cycle design, through the optimization of various specifications such as dwell times,
pressure, and humidity, as well as the reduction in the amount of paper packaging which is
known to absorb EtO. Through FDA's Innovation Challenge 2, some industry participants have
already implemented their optimized cycle designs, reducing EtO use by a significant amount.
Per an FDA statement, early observations suggest that some facilities have cut emissions ranging
from 20-35%, with the potential to impact millions of devices. In general, manufacturers are
targeting an EtO concentration that is 11-66% less than the typical concentration range.103
EPA proposes that sterilization facilities use the least amount of EtO needed to meet sterility
assurance through cycle design optimization, taking into consideration that sterilization cycles
often include mixed loads of different medical devices which require different levels of EtO
concentrations. Industry has already demonstrated the ability to optimize dwell times, pressure,
and humidity, as well as the reduction in the amount of paper packaging through FDA's
Innovation Challenges.
101 ISO 14161:2009. Sterilization of health care products — Biological indicators — Guidance for the selection, use
and interpretation of results.
102 ISO 11135:2014 Sterilization of health-care products — Ethylene oxide — Requirements for the development,
Validation and routine control of a sterilization process for medical devices. Publication date: 2014-07. Technical
Committee: ISO/TC 198 Sterilization of health care products.
103 https://www.fda.gov/news-events/press-aiinoiincements/fda-continues-efforts-siipport-iiinovation-medical-
device-sterilization.
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EPA plans to collaborate with FDA on innovating improvements to EtO sterilization for medical
devices as a way to reduce potential impacts to the supply chain of critical medical devices. By
reducing the overall concentration of EtO permitted to be used in sterilization processes while
following standards for sterility assurance, risks to workers, non-residential bystanders, and
residential bystanders would be reduced. Reducing the application rate of EtO would result in
less EtO exposure.
For new cycles, use rate reduction through reduced concentrations of 500 mg/L or less should be
minimally impactful from a facility standpoint for most commercial sterilization facilities;
however, new cycle validations and potentially additional staff and/or chambers may be needed
to implement reduced concentrations. By encouraging use of the Cycle Calculation Approach or
cycle optimization for concentrations over 500 mg/L, EPA strives to direct the user community
to a more efficient use of EtO.
For existing cycles, the Agency acknowledges that there would be impacts to many commercial
sterilization facilities from implementation of use rate reduction through reduced concentrations
for medical device sterilization. Reduction of the amount of EtO used in sterilization processes
for medical devices may have high impacts to the customers of commercial sterilization
facilities. Reducing the concentration of EtO used in sterilization processes would result in some
cost savings by reducing the amount (and cost) of EtO applied as well as reducing the amount of
time a product spends in off-gassing and allowing the product to be released more quickly.
However, using less EtO may also result in the need for longer sterilization times. Additionally,
it would also require medical device manufacturers and other customers to recalculate and
revalidate the sterilization methods, including the concentration of EtO used and duration in the
chamber, for each specific product sterilized by EtO. Updating processes while guaranteeing
sterilization would result in increased labor and validation costs for customers of commercial
sterilization facilities. Additionally, technicians at EtO commercial sterilization facilities and
employees at FDA may have increased workload initially due to an increase in validation tests
needed to review new methodologies used to sterilize products. Validation tests may also take
time from the sterilization chamber schedule that was previously scheduled for another product
which could result in temporary delays in the supply of sterilized medical devices.
The Agency seeks public comment on how long is necessary for registrants to implement label
amendments requiring facilities to use less than or equal to 500 mg/L, taking into account the
compliance timeframes, impacts to the sterilization process and/or supply chain, costs on users of
EtO and customers of commercial sterilization facilities, or any other relevant impacts or factors.
EPA is proposing that this change be implemented within 5 years for existing cycles, and within
2 years for new cycles.
The Agency is also soliciting alternative proposals for reducing the amount of EtO used in
commercial sterilization facilities.
Spices
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The Agency is also interested in reducing the concentration of EtO used to fumigate spices. ISO
standard 11135 described above does not apply to spice treatments and there are no other ISO
standards in place for spice treatments as there are for sterilization of medical devices. The spice
treatment process is specified on the FIFRA product labels as follows:
"This product may not be used on or in any form of basil.
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 precondition 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 ethylene oxide and air
is compatible with the chamber design, then, introduce into the chamber a concentration
of Ethylene Oxide 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 evacuations) between 1.5 PSIA (27" Hg) and 5.0 PSIA (20" Hg) while
maintaining a minimum chamber temperature of 115°F."
Based on discussions with FDA and ASTA, it is the Agency's understanding that the actual EtO
concentration used (and validated) to treat spices in commercial sterilization facilities is
company-, chamber-, pathogen-, and spice-specific. The Agency is seeking public comment on
examples of efficacious EtO treatments for pathogen control at rates lower than the maximum
label rate, and how often facilities have completed EtO validations for EtO concentrations that
are less than 500 mg/L. The Agency is interested in establishing an alternative method for the
product labels that uses a lower rate of EtO. EPA encourages facilities and interested
stakeholders to work with the Agency to develop a new method at a lower rate that is effective
for pathogen control and continues to meet the dietary safety standards (e.g., acceptable residues
of EtO and ECH).
Proposed Mitigation for Residential Bystander Risk
Bystander exposures around commercial sterilization facilities are considered "residential" if the
exposures occur where people live (i.e., their homes).
At the time of this Proposed Interim Decision, EPA's Office of Air and Radiation (OAR) is
concurrently releasing their Proposed Rulemaking for EtO commercial sterilizers, National
Emission Standards for Hazardous Air Pollutants (NESHAP): Ethylene Oxide Emissions
Standards for Sterilization Facilities Residual Risk and Technology Review.104 OAR is proposing
to revise the NESHAP for commercial sterilization facilities by both amending existing standards
and establishing additional standards for this source category, exercising authority under multiple
provisions of section 112 of the Clean Air Act (CAA). In December 2016, the EPA's Integrated
104 EP A-HQ-0 AR-2019-0178.
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Risk Information System (IRIS) Program issued its final, updated EtO toxicological assessment,
which indicated that EtO is a far more potent carcinogen than EPA had understood at the time of
the previous risk and technology review for this source category. For the risk assessment for this
proposed rulemaking, EPA applies the revised updated cancer risk value. There are 85
commercial sterilization facilities in this source category, many of which are located near
residences, schools, and other public facilities. Many of these facilities are also located in
communities with environmental justice concerns. OAR has determined that approximately 23 of
these facilities pose elevated lifetime cancer risks to the surrounding communities, some of
which are exceptionally high.
OAR is proposing mitigation to reduce EtO emissions from commercial sterilizers to residential
populations.105'106 Specifically, OAR is proposing that emission sources in existing and new
facilities reduce emissions by a certain percentage or to a specific pound per hour, depending on
the emission source, EtO usage per year, and whether the facility is existing or new.107 OPP
notes that OAR is proposing, similar to OPP's proposal, that under certain scenarios, facilities
use less EtO per cycle while maintaining sterility assurance.
While the OAR and OPP proposals are based on different statutory authorities and mandates,
they complement each other in their shared objective of preventing the use of more EtO than
necessary to achieve sterility. In this Proposed Interim Decision, OPP is relying on OAR's
proposed mitigation to address residential bystander risks from inhalation exposure to EtO
through the emissions reductions that would result from action proposed to be taken by OAR
under the authority of the Clean Air Act. OPP believes that the emissions limits proposed by
OAR would significantly reduce residential and non-residential bystander exposure without
causing adverse impacts to the U.S. supply of sterilized medical devices needed for a variety of
medical procedures. Additionally, OPP's proposal for use rate reduction through reduced
concentrations for all medical devices in all facilities will result in reduced emissions overall and
would, therefore, be expected to reduce risk to residential bystanders.
Compliance with both Agency actions, the OPP decision and the OAR rulemaking, will impose
costs on commercial sterilization facilities. While the requirements set forth in each Agency
action may be complementary in that they may both reduce public health risks from EtO
exposure, the costs to commercial sterilization facilities to comply with both Agency actions are
additive in some respects. The Regulatory Impact Analysis for the Proposed National Emission
Standards for Hazardous Air Pollutants: Ethylene Oxide Commercial Sterilization and
Fumigation Operations (EPA-HQ-OAR-2019-0178) provides estimates of the cost to industry to
comply with the proposed OAR rule.108 As is typical of the Registration Review process under
105 The Proposed Rulemaking from OAR is based on risk to residential areas only. OPP's analysis and proposed
mitigation includes residential, non-residential, and worker exposure.
106 At the time of OAR's assessment on commercial sterilizers, 23 out of 85 facilities were identified that exceeded a
100 in 1 million risk threshold. See Appendix F.
107 Emission sources in sterilization facilities include: sterilization chamber vents, aeration room vents, chamber
exhaust vents, Group 1 room air emissions (emissions from indoor EtO storage, EtO dispensing, vacuum pump
operations, and pre-aeration handling of sterilized material), and Group 2 room air emissions (emissions from post-
aeration handling of sterilized material).
108 OAR did not include discussion of the PID and its potential costs - or costs of both actions - in the regulatory
impact analysis (RIA) for the commercial sterilizer proposed rule.
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FIFRA, OPP did not conduct a cost analysis for the proposed mitigation in this PID. However,
OPP is specifically requesting public comment on the costs of the proposed mitigation measures
included in this PID.
Proposed Mitigation for Non-Residential Bystander Risk
Bystander exposures around commercial sterilization facilities are considered "non-residential"
if the exposures occur at locations other than homes where people may spend a significant
amount of time (i.e., daycare centers, schools).
Emissions controls proposed by OAR to address risks from residential exposure to EtO would
also reduce exposure to non-residential bystanders. See Proposed Mitigation for Residential
Bystander Risk above.
Proposed Mitigation for Occupational Risk
Engineering Controls for Healthcare Facilities
Healthcare facilities such as hospitals, dental offices and veterinary facilities are expected to use
significantly smaller volumes of EtO than commercial sterilization facilities. Exposure scenarios
in healthcare facility settings differ significantly from commercial sterilization exposure
scenarios because in health care facilities, EtO sterilization is intermittent, and devices are
typically used soon after sterilization (i.e., not stored for shipping). As of the 2008 RED,
sterilization is required to be performed in all-in-one systems. However, given the low
concentration at which EtO may present inhalation cancer risks of concern, EPA now believes
additional risk mitigation measures are needed. To reduce exposure to EtO in healthcare
facilities, EPA is proposing to require the following engineering controls:
Physical separation of EtO sterilization spaces
EPA proposes to require that all-in-one EtO sterilization devices be located in a containment area
that is physically separate from all other work areas of the healthcare facility.
Negative air pressure
EPA proposes that the rooms containing all-in-one EtO sterilization devices must have a
negative pressure in comparison to the rest of the healthcare facility. This ensures that air will
not flow from the room with a higher EtO concentration through the rest of the healthcare
facility.
Ventilation of EtO through exterior ventilation stacks
EPA proposes that all exhaust from all-in-one EtO healthcare facility sterilization devices be
directed through exterior ventilation stacks. This would ensure that there is minimal EtO
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exposure for workers and bystanders within healthcare facilities. EPA's proposal would require
EtO exhaust to be vented to a dedicated exhaust ventilation system composed of local exhaust
ducts that serve the sterilizer area only (i.e., the area containing the all-in-one sterilization device,
EtO ampules, etc.) and route EtO directly to the outside of the building by maintaining a net
suction on all of the exhaust ductwork.109 The exhaust duct would also be required to terminate
away from areas where people walk or work, and the duct would be required to be located at
least 7.6 meters (25 feet) away from the building air intake source and be engineered according
to existing codes.110
Abatement Devices
EPA proposes that additional abatement devices be required to be used along with all-in-one EtO
sterilization devices in healthcare settings. Both all-in-one sterilization device manufacturers
offer accessory abatement devices that reduce EtO emissions by more than 99%. m>112 By
requiring that all EtO sterilization devices are used with dedicated abator systems, EtO levels
would be kept to a minimum both within healthcare facilities and in their outgoing emissions.
Abatement devices will reduce risks to workers inside healthcare facilities. Recognizing that
risks to bystanders from healthcare facilities were not quantitatively assessed, EPA expects
abatement devices to reduce exposures, and therefore any risks, to bystanders as well.
The Agency acknowledges that there would be impacts to healthcare facilities from
implementation of engineering controls. Through discussions with industry leaders, the Agency
determined that some engineering control measures described in this section may already be
common practice while others would impose costs from retrofitting existing facilities to meet the
new standards proposed. The cost of retrofitting includes the costs of new equipment,
installation, operation and maintenance, and the loss of revenues associated with any necessary
downtime required for installation.
The Agency seeks public comment on the cost and time necessary for registrants to implement
label amendments requiring the implementation of the proposed engineering controls. EPA is
proposing that these engineering controls be implemented within 2 years.
In addition to the proposed engineering controls, EPA is seeking public comment on the
feasibility of respirator use (supplied airline respirators or self-contained breathing apparatus
respirators) in healthcare facilities for employees who are unloading EtO sterilization equipment
from the sterilization chamber.
Engineering Controls for Commercial Sterilization Facilities
According to OSHA's hazard prevention principles, the first and best strategy is to control the
hazard at its source. Engineering controls do this, unlike other controls that generally focus on
109 https://www.cdc.g0v/niosl1/docs/i efault.html.
110 ANSI/AAMI ST41:2008/(R)2018 Section 3.9.2.6: Exhaust Ducts (pg. 15).
111 https://multimedia.3m.com/mws/media/1427940O/3m-steri-vac-sterilizer-gs-series-safety-siimmary.pdf.
112 https://www.sterilitv.com/gas-abatement-eanipment-eto-abator-sterilitv/.
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reducing exposures to the employee exposed to the hazard, such as the use of PPE. Under these
principles, the work environment and the job itself should be designed to eliminate hazards or
reduce exposure to hazards.113 The National Institute for Occupational Safety and Health
(NIOSH) states that well-designed engineering controls can be highly effective in protecting
workers.
To reduce exposure to EtO at commercial sterilization facilities, EPA is proposing to require the
following engineering controls:
• Air pressure gradient so that air is always flowing from low-EtO concentration to high-
concentration spaces.
• Separation of office and sterilization area HVAC systems.
• Ventilation of storage areas.
• Automation of movement of sterilized and aerated materials.
• All-in-one processing (combination sterilizers).114
Air pressure gradient
EPA proposes to require that the indoor air pressure gradient in commercial sterilization facilities
using EtO is continuously flowing from low-EtO concentration to high-concentration spaces.
Under this proposal, areas where EtO is processed must have slightly negative pressure
compared to non-processing areas, which must have positive pressure. The highest level of
negative pressure would have to be in the sterilization chamber. The negative pressure is caused
when the exhaust fan airflow is less than the supply fan airflow. The air is discharged through the
exhaust duct to outside the building.
HVAC systems
EPA proposes the HVAC systems in commercial sterilization facilities be separated. EtO
processing areas would have to have separate HVAC systems from non-processing areas, such as
office space and control rooms.
Ventilation
EPA proposes to require that commercial sterilization facilities that use EtO have adequate
ventilation in spaces where EtO-sterilized product is stored. EPA is soliciting public comment on
the number of air exchanges per hour that would adequately ventilate product storage areas.
Understanding that not all EtO could be removed from post-sterile product areas, due to the
absorbent nature of pallets, cardboard, and packaging, EPA proposes any storage area be
properly ventilated. EPA is soliciting public comment on the use of netting rather than plastic
surrounding pallets of treated medical devices to increase aeration and prevent EtO from
becoming trapped in plastic wrap or other packaging.
113 https://www.osha.gov/sites/defanlt/files/2018-12/fv.1..1. sh-223.1.8-1.1. Mod 3 HazardPrevention.pdf.
114 All-in-one systems would only be required in facilities that do not sterilize pressure sensitive devices.
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Automation
In traditional EtO treatment configurations, sterilization and aeration are performed in two
separate chambers. In these systems, employees may transfer post-treatment materials from the
sterilization chamber to the aeration chamber via forklift. EPA is aware that in some sterilization
facilities, post-treatment materials are instead transferred via enclosed conveyor system, to
reduce employee exposure. EPA proposes that all EtO commercial sterilization facilities with a
traditional sterilization configuration implement an enclosed conveyor to transport sterilized
materials from the sterilization chamber to the aeration chamber.
Additionally, EPA proposes that all EtO commercial sterilization facilities implement an
enclosed conveyor to transport aerated materials from aeration chamber/room to storage/shipping
areas, in both traditional sterilization (multi-chamber) scenarios and all-in-one sterilization
(single chamber) scenarios. This would apply to both medical device sterilization and spice
fumigation processes. EPA is seeking public comment on the feasibility and cost of a conveyor
system from the aeration area to the storage/shipping area of EtO commercial sterilization
facilities.
All-in-one processing
All-in-one processing (also known as single chamber processing or combination sterilizers) is
defined as EtO sterilization chambers where the sterilization and aeration occur within the same
chamber, thereby eliminating product transfer from a separate sterilization chamber to an
aeration chamber.
Since August 1, 2008, EtO products applied to or on spices, dried vegetables or seasonings have
been required to utilize an EtO sterilization method that uses a single sterilization chamber to
pre-condition and aerate with an alternating vacuum and aeration purging procedure. As of
February 28, 2010, a single chamber process has been required for EtO treatment in hospitals
and healthcare facilities.
For commercial sterilization facilities treating medical devices, it is the Agency's understanding
that there are instances where an all-in-one sterilization chamber could be utilized, rather than
the traditional sterilization configuration wherein sterilization and aeration are performed in two
separate chambers. However, EPA also understands that there are certain pressure-sensitive
devices that cannot be sterilized in all-in-one systems. Further, EPA acknowledges that there
could be capacity constraints on the volume of medical devices that could be sterilized in all-in-
one systems, which typically have a longer processing time within the chamber.
The Agency is proposing to require all-in-one sterilization systems in commercial sterilization
facilities that do not sterilize pressure sensitive devices.115 EPA further proposes that registrants
ensure facilities keep records that document there are pressure sensitive devices being sterilized
and are therefore unable to be processed in all-in-one systems, if applicable. All records would
115 Pressure sensitive devices could include, for example, any device with a cap and plug, or other configuration
which changes in pressure could result in shattering or otherwise compromising the elements of the device.
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need to be available upon request to any local, state, tribal, or federal pesticide enforcement
personnel. Records would be required to be maintained for two years from the date of
sterilization. If an all-in-one system is not feasible, the facility would be required to implement a
covered conveyor systems as described above.
The Agency acknowledges that there would be impacts to commercial sterilization facilities from
implementation of engineering controls. Through discussions with industry leaders, the Agency
determined that some facility-level engineering control measures described in this section may
already be common practice while others would impose significant costs to retrofit existing
facilities to meet the new proposed engineering controls. The cost of retrofitting would include
the costs of new equipment, installation, operation and maintenance, and the loss of revenue
associated with any necessary downtime required for installation. EPA also acknowledges the
corresponding potential impacts on the supply chain of sterilized medical devices related to the
costs and potential downtime of sterilizing equipment.
The Agency seeks public comment on the cost and time necessary for registrants to implement
label amendments requiring the proposed engineering controls. EPA is proposing that these
changes be implemented within 3 years following the publication of the Interim or Final
Decision. EPA is also seeking public comment on whether to implement each of the
aforementioned engineering controls for all existing facilities, or for only new facilities. EPA
further seeks public comment on whether these engineering controls would require state or local
permits before the renovations could take place, and the timing associated with that permitting
process. Finally, the Agency seeks public comment on potential impacts on the supply chain of
sterilized medical devices related to the potential downtime of sterilizing equipment during
renovation.
Lowered Action Limit for Commercial Sterilization Facilities
As noted in Section IV. A., EtO product labels currently cite the OSHA PEL of 1 ppm to trigger
the requirement that EtO handlers in commercial sterilization facilities wear a respirator. Since
the publication of the RED in 2008, there have been considerable updates to the scientific
database on EtO exposure and risk, including the 2016 IRIS assessment on EtO, OPP's 2020 EtO
Draft Risk Assessment (DRA), and 2023 EtO DRA Addendum. EPA thus considers the OSHA
PEL of 1 ppm to no longer ensure that the use of EtO will not cause unreasonable adverse
effects, including effects to workers, as required under FIFRA, and is, therefore, proposing to
require registrants to amend the EtO labels to no longer include the OSHA PEL. EPA
understands that OSHA's EtO PEL has not been updated since it was established in 1984, and
that health standards issued under section 6(b)(5) of the OSH Act must reduce significant risk
only to the extent that it is technologically and economically feasible.116 OSHA's legal
requirement to demonstrate that its 6(b)(5) standards are technologically and economically
feasible often precludes OSHA from imposing exposure control requirements sufficient to ensure
that the chemical substance no longer presents a significant risk to workers.
116 https://www.federalregister.gov/citatlon/49-FR-25734.
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To reduce worker exposure, EPA is proposing that respirator requirements be based on a
technologically measurable (i.e., quantifiable) EtO concentration of ambient air for real time
measurements, which by the Agency's understanding is 10 ppb, using either gas chromatograph
systems, Fourier Transform Infrared Spectroscopy (FTIR), or mass spectrometers. Facilities
would be required to monitor both processing and non-processing areas, for which the
monitoring system would have a visual and audio alarm to alert employees when 10 ppb air
concentration is exceeded. Therefore, in addition to the respirator requirements described in the
following section, EPA proposes that Self Contained Breathing Apparatus (SCBA) or supplied
airline respirators be required when EtO concentrations in a sterilization facility exceed 10 ppb,
and proposes adding any associated fit test, training, and medical evaluation requirements.
Understanding that respirator use for all employees may not be feasible, if EtO levels exceed 10
ppb, EPA is also proposing to require that employees would have the option to vacate the
premises until the levels return to below 10 ppb.
The Agency proposes that facilities maintain records of indoor EtO concentration levels. EPA
further proposes that facilities maintain records of employee respirator wear time and/or
evacuation time. All records would need to be available upon request to any local, state, tribal, or
federal pesticide enforcement personnel. Records would be required to be maintained for two
years from the date of sterilization.
EPA requests public comment on the feasibility of real time monitoring to a 10 ppb level (i.e.,
the lowest quantifiable level), as well as the possible impacts on the daily operations of
commercial sterilization facilities from requiring respirators at the 10 ppb level.
It is EPA's understanding that certain commercial sterilization facilities may already utilize a
lower exposure limit than what is required by OSHA (1 ppm) to set company-specific risk
policies. EPA requests public comment on facilities that utilize lower exposure limits than the
OSHA PEL, and what practices these facilities use to achieve these lower limits.
EPA understands that the supply of monitoring systems may be limited, and so the compliance
timeframe may be affected by equipment availability. The Agency seeks public comment on the
cost and how long is necessary for registrants to implement label amendments requiring
compliance with this respirator requirement and the corresponding monitoring and recordkeeping
requirements. EPA is proposing that this change be implemented within 2 years.
Personal Protective Equipment for Commercial Sterilization Facilities and Data Call-In
Requirement
New Respirator Requirement for EtO Handlers: The Agency proposes to require the addition to
EtO product labels of a respirator statement to mitigate potential inhalation exposure risks to
workers involved in the EtO commercial sterilization process and proposes adding any
associated fit test, training, and medical evaluation requirements117 for the following:
117 Pursuant to 40 C.F.R. pt. 170, EPA requires fit testing (29 C.F.R. § 1910.134), training (29 C.F.R. §
1910.134(k)(l)(i)-(vi)), and medical evaluations (29 C.F.R. § 1910.134)—conducted in accordance with the cited
OSHA regulations—for all handlers that are required to wear respirators and whose work falls within the scope of
the WPS. Label Review Manual at Ch. 10, App. A, https://www.epa.gov/pesticide-registration/label-review-mannaL
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• Supplied air/airline (SAR) respirators or self-contained breathing apparatus (SCBA)
respirators (full facepiece) for employees connecting and disconnecting EtO containers
from sterilization process equipment.
• SAR or SCBA (full facepiece) for employees unloading processed products from the
sterilization chamber, whether at the end of a cycle for an all-in-one process, or, for a
conventional process, prior to moving product to the aeration area.
• SAR or SCBA (full facepiece) for employees loading and unloading product from the
aeration area.
• SAR or SCBA (full facepiece) for employees removing validation test materials from
processed product at any time prior to the completion of aeration.
• SAR or SCBA (full facepiece) for employees opening process lines or equipment that
may contain EtO (e.g., for repairs or routine maintenance tasks).
Current PPE requirements are triggered by the OSHA PEL of 1 ppm, which EPA determined is
not protective based on the Agency's updated risk analysis, and thus are not sufficient to ensure
that the use of EtO will not cause unreasonable adverse effects to workers. The new respirator
requirements outlined above are anticipated to reduce inhalation risk to workers involved with
the EtO sterilization process at points when the potential for exposure is highest. To quantify the
effect of mitigation on worker exposure in commercial sterilization facilities, EPA proposes to
issue a Data Call-In (DCI) for OCSPP GLN 875.1400 Inhalation Exposure Indoor, requiring a
protocol before monitoring for the study begins. Based on previously submitted worker
monitoring data that lacked specificity and detail, EPA proposes to require, through a DCI air
monitoring of the handlers specifically involved in activities related to the
sterilization/fumigation (e.g., loading and unloading chambers, routine maintenance, product
transfer, etc), documentation of the activities each worker performed while monitored, and
whether they were wearing a respirator (and what type of respirator). For non-handlers in the
facility (e.g., office workers, warehouse workers), EPA also proposes to require, through a DCI,
air monitoring data to monitor their exposures. The Agency proposes that registrants follow the
OSHA Method 1010 as the monitoring method.118 EPA proposes that the DCI to be issued would
require registrants to submit these data following implementation of all mitigation.
EPA further proposes to issue a DCI for data on commercially available technologies that can
monitor below 10 ppb in real time, while also documenting other instruments that can quantify
levels around 0.19 ppb, which is the Agency's concentration of concern for worker exposure.
This includes the air inside of EtO commercial sterilization facilities, as well as warehouses that
store sterilized devices. It is the Agency's understanding that current measurement technology is
able to measure down to 10 ppb, which is the lowest quantifiable level. Since EPA's assessment
118 OSHA Method 1010 (revised 2014) can be found at https://www.osha.gov/sites/defaiilt/fites/methods/osha~
1010.pdf.
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shows that risks to workers are not of concern where workers are exposed at a level of 0.19 ppb,
the Agency proposes that the DCI to be issued would require registrants to submit data to
demonstrate the advancements in technologies that are capable of monitoring EtO levels as close
to this level as possible. The Agency proposes issuing a DCI for the development of lower
measurement methodologies/technologies on a two-year timeframe. The Agency is soliciting
comments on the feasibility of a two-year DCI timeframe. Once these data become available, the
Agency may promptly initiate the next cycle of Registration Review.
Requiring a respirator and any associated fit testing, training, and medical evaluation could
impose a cost on handlers or employers. Per Agency discussions with industry leaders, use of the
SCBA or SAR systems may already be standard industry practice for the performance of several
of the tasks for which a SCBA or SAR system is proposed to be required; therefore, the overall
impacts from this requirement are expected to be low. However, use of a SCBA or SAR system
may not currently be part of current practice for some of the tasks at some facilities, meaning that
facilities would need to purchase additional SCBA or SAR systems. Prices for an industrial-use
SCBA system range from $2,300 to $9,300 depending on the duration of air supply needed (30
or 60 minutes), cylinder pressure, tank material (typically aluminum or carbon fiber), and mask
size119' 120'121. In addition to the original SCBA system purchase, replacement air cylinders range
in price from $600 to $3,500122' 123'124. Facilities may also opt to purchase on-site tank air
cylinder fill stations to refill cylinders on site instead of purchasing additional replacements.
Complete SAR systems range from $1,500 to $4,100 depending on hose length, air pump
horsepower, and mask size125' 126'127 SCBA or SAR systems can only be used by a single person
that has been fit for the system, so these costs are per user. Facilities with multiple users would
have to incur these costs for every individual they employ that may require the system.
Additional costs may also arise from the maintenance of SCBA or SAR systems and necessary
replacement parts. Applicators may also incur additional costs of training and fit testing.
119 AirGas. 2022. Respiratory Protection, https://www.airgas.com/Safetv-Prodiicts/Respiratorv-
Protection/eategorv/177. Accessed December 2022.
120 Fisher Science. 2022. Atmosphere-Supplying Respirators.
https://www.fishersci.com/iis/en/browse/90411025/atmosphere~siipplving~respirators. Accessed December 2022.
121
Grainger. 2022. Respiratory Protection, https://www.grainger.com/categore/safetv/respiratore-protection.
Accessed December 2022.
122
AirGas. 2022. Respiratory Protection, https://www.airgas.com/Safetv-Prodiicts/Respiratorv-
Protection/categorv/177. Accessed December 2022.
123
Fisher Science. 2022. Atmosphere-Supplying Respirators.
https://www.fishersei.eom/iis/en/browse/90411025/atinosphere~siipptving~respirators. Accessed December 2022.
124
Grainger. 2022. Respiratory Protection, https://www.grainger.eom/eategore/safetv/respiratore-proteetion.
Accessed December 2022.
125 AirGas. 2022. Respiratory Protection, https://www.alrgas.eom/Safetv-Prodiiets/Respiratore-
Proteetion/eategory/177. Accessed December 2022.
126 Fisher Science. 2022. Atmosphere-Supplying Respirators.
https://www.fishersei.eom/ns/en/browse/90411025/atinosphere~snpplying~respirators. Accessed December 2022.
127
Grainger. 2022. Respiratory Protection, https://www.grainger.com/eategore/safetv/respiratore-proteetion.
Accessed December 2022.
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EPA's 2023 DRA Addendum assumes National Institute for Occupational Safety and Health
(NIOSH) protection factors128 in estimating the inhalation risks and the risk reduction associated
with different respirators.129 If the respirator does not fit properly, EPA's proposed PPE
mitigation for EtO may not reduce risks and thus the use of EtO may result in unreasonable
adverse effects for the pesticide handler and others involved in the sterilization process.
Training Requirements
Commercial Sterilization Facilities Training Requirements
In commercial sterilization facilities, labels on EtO products registered by EPA require safety
and awareness training 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:
• The most recent monitored ambient levels of EtO in the facility.130
• 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.131
EPA proposes that the registrants ensure that the requirements to train employees on the potential
health effects from the levels of EtO in the facility and the availability of materials related to the
health hazards of exposure to EtO be reflective of the occupational risks expected based on the
2016 IRIS IUR, and not be based on the OSHA PEL. Specifically, the Maximum Likelihood
Exposure (MLE) cancer risk for EtO handlers for medical devices is 1 in 17, and the upper
bound cancer risk for EtO handlers for medical devices is 1 in 10. The MLE cancer risk for EtO
handlers for spices is 1 in 36, and the upper bound cancer risk for EtO handlers for spices is 1 in
16. See section III.A.
Healthcare Facilities Training Requirements
In healthcare facilities, training is currently recommended for personnel who work with EtO
sterilization devices by the Association for the Advancement of Medical Instrumentation
(AAMI) in their EtO Standard (ANSI/AAMI ST41:2008/(R)2018). It is common industry
practice that healthcare facilities follow the guidelines in the AAMI Standard - Personnel
Considerations. Specifically, ANSI/AAMI ST41 states: Education and training materials and
information are available from the sterile processing vendors, associations and journals; in
128 NIOSH protection factors assume that respirators are used according to OSHA's standards.
129 Proper fit and use of respirators is essential to accomplish the protections respirators are intended to provide.
Respirator fit tests are currently required by the Occupational Safety and Health Administration (OSHA) for other
occupational settings to ensure proper protection. 29 C.F.R. § 1910.134.
130 The most recent monitored ambient levels would be available to the employees by real time monitoring. See
section V.A.
131 EtO Reregistration Eligibility Decision. 2008.
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addition, OSHA has education materials available for loan.132 Personnel may receive in-service
training for all new instrumentation, devices and equipment. All orientation, on-the-job and in-
service training may be documented.133
Similar to the training requirements for commercial sterilization facilities, EPA proposes to
require registrants ensure employees be trained on the potential health effects from the levels of
EtO in the healthcare facility and the availability of materials related to the health hazards of
exposure to EtO, and that training be reflective of the occupational risks expected based on the
2016 IRIS value. Specifically, the Maximum Likelihood Exposure (MLE) cancer risk for EtO
handlers in healthcare facilities is 1 in 25, and the upper bound cancer risk for EtO handlers in
healthcare facilities is 1 in 12. See section III. A.
EPA proposes a requirement for registrants to ensure that commercial sterilization and healthcare
facilities maintain records on employee training. Specifically, documentation of the training
materials provided to employees upon assignment and annually thereafter, and records of the
dates individual employees are trained must be kept. All records would need to be available upon
request to any local, state, tribal, or federal pesticide enforcement personnel. Records would be
required to be maintained for the duration that the trainee is employed, or for two years from the
date of training if the trainee leaves the place of employment before two years.
EPA proposes that the registrants submit label amendments to implement the aforementioned
training requirements within 60 days.
Label Consistency and Clarification
The Agency is proposing to require several label changes for consistency and clarification as
specified in Appendix B. These label changes are directionally correct with respect to reducing
the amount of EtO exposure to workers and to those near commercial sterilization facilities that
use EtO.
• Current EtO labels contain general/undefined terms for use on dried herbs and spices and
the language used is not consistent within the product labels. Specifically, the Directions
for Use section of the labels say, "This product may be used only.. .to reduce microbial
load on cosmetics, whole and ground spices or other seasoning materials (see 40 CFR
180.151)..." The same section also states, "After August 1, 2008, this product may only
be applied to or on spices, dried vegetables or seasonings.
To clarify the acceptable use sites on the product labels, the Agency is proposing to
standardize the label language within each label (and as a result across all the labels) to
reflect registered uses. The Agency proposes to require that registrants amend EtO
product labels to specifically identify the dried herbs, dried spices, and dried vegetables
on the label for which EtO use is registered following the receipt of documentation
regarding the specific commodities in Table 2 for which there is current critical use of
132 https://www.osha.gov/etools/hospitals/central-snpplv/tiazardons-chemicals
133 ANSI/AAMI ST41:2008/(R)2018. Page 20.
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EtO and for which there are no viable alternatives to EtO. The Agency intends to include
language in the Interim Decision (ID) stating that registrants should submit requests to
voluntarily terminate uses on those specific spices/commodities not identified.
In addition, the phrase "other seasoning materials" on the labels is vague and undefined.
The Agency proposes deleting the use of "other seasoning materials" since this is a blend
of the dried commodities specified in the newly added list of dried herbs, spices, and
vegetables on the label.
• Currently, EtO product labels contain references to the OSHA Permissible Exposure
Limit (PEL), OSHA Excursion Limit (EL), and the OSHA regulations at 29 CFR
1910.1047 which establish the OSHA PEL and EL levels. However, since the
establishment of the OSHA PEL and EL in 1984, there have been considerable updates to
the scientific database on EtO exposure and risk, including the 2016 IRIS assessment on
EtO, OPP's 2020 EtO DRA, and OPP's 2023 EtO DRA Addendum. EPA thus considers
the OSHA PEL of 1 ppm and the EL of 5 ppm to no longer adequately address worker
risk under the requirements of FIFRA and is therefore proposing to require registrants to
amend the EtO labeling to no longer include references to the OSHA PEL, EL, or the
OSHA regulations that define them (i.e., 29 CFR 1910.1047). The removal of these
references to the OSHA regulations from the EtO product labels would not alter the
obligations of employers subject to these OSHA regulations.
• Current labels do not clearly specify the type of facility in which an EtO product is
intended to be used. Since the application rate and method for sterilization in healthcare
settings compared to commercial sterilization settings differ greatly (e.g., in small oven
sized systems versus large chambers), the Agency is proposing to clarify which products
are intended to be used in which settings. EPA is proposing to require that the following
statement be added to EtO product labels: "This product is intended only for use in
commercial sterilization facilities. This product may not be used in healthcare facilities
(hospitals, veterinary facilities, dental offices, etc.)."
The Agency also is proposing to clarify which products are intended to be used in
healthcare facilities by requiring that the following statement be added to EtO product
labels: "This product is intended only for use in single chamber sterilization/aeration
devices in healthcare facilities (e.g., hospitals, veterinary facilities, dental offices, etc.)"
B. Environmental Justice
EPA seeks to achieve environmental justice, the fair treatment and meaningful involvement of all
people, regardless of race, color, national origin, or income, in the development, implementation,
and enforcement of environmental laws, regulations, and policies. Throughout the registration
review process, EPA has sought to include all communities and persons, including minority,
low-income, and indigenous populations who may be disproportionately overburdened by the
exposure to EtO.
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EPA's Office of Air and Radiation (OAR) conducted an in-depth Environmental Justice analysis
as part of the National Emission Standards for Hazardous Air Pollutants (NESHAP): Ethylene
Oxide Emissions Standards for Sterilization Facilities Residual Risk and Technology Review.134
OAR examined the potential for the 97 facilities that were assessed to pose concerns to
environmental justice (EJ) communities both in the baseline and under the control options
considered in their proposal. Overall, the results of this proximity demographic analysis indicate
that the percent of the population living within 10 km of the 97 facilities that is Hispanic or
Latino is substantially higher than the national average, driven largely by the seven facilities in
Puerto Rico. The baseline proximity analysis indicates that the proportion of other demographic
groups living within 10 km of commercial sterilizers is closer to the national average. The
baseline risk-based demographic analysis, which focuses on those specific locations that are
expected to have higher cancer risks as identified by OAR (defined by OAR for the purpose of
this analysis as cancer risks greater than or equal to 1-in-l million, greater than or equal to 50-in-
1 million, and greater than 100-in-l million), suggests that African Americans are
disproportionally represented at the higher risk levels. The post-control risk-based demographic
analysis focuses on how the options considered in OAR's proposed regulatory action would
affect the distribution of risks identified in the baseline. The post-control options from OAR's
proposed rulemaking show a substantial reduction in the number of individuals at each risk level,
as well as a significant reduction in the proportion of individuals that are African American that
experience higher risk levels from facilities in this source category. OAR projects that the
majority of the individuals that would remain at risk after implementation of the proposed
standards are Hispanic or Latino, driven largely by the sterilization facilities in Puerto Rico.
These three distinct but complementary analyses indicate the potential for EJ concerns associated
with this source category in the baseline, as well as the substantial benefits OAR's proposed
standards would have in reducing EtO emissions and associated health risks in communities with
EJ concerns.
OPP has identified risks to workers handling EtO or who may be exposed to EtO within the
facilities where it is used. Because people tend to live and work within their community,
individuals who would be employed in these facilities could be disproportionally drawn from the
Hispanic or Latino communities, as identified by OAR, since many facilities are located in
Puerto Rico.
Additionally, according to the 2021 U.S. Bureau of Labor Statistics, people working in
warehousing and storage, such as those who would be employed in these facilities, moving
materials into and out of chambers for fumigation, could be disproportionally drawn from
communities of concern. The national average of employed persons working in warehousing and
storage are about 22% Black or African American and 36% Hispanic or Latino.135
The Agency requests information on any other groups or segments of the population who, as a
result of their proximity and exposure to pesticides, unique exposure pathway (e.g., as a result of
cultural practices), location relative to physical infrastructure, exposure to multiple stressors and
cumulative impacts, lower capacity to participate in decision making, or other factors, may have
134 EP A-HQ-0 AR-2019-0178.
135 U.S. Bureau of Labor Statistics. Household Data Annual Averages: Employed persons by detailed industry, sex,
race, and Hispanic or Latino ethnicity. 2022. Accessed January 19, 2023. https://www.bls.gov/cps/cpsaat.18.htm.
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unusually high exposure to EtO compared to the general population or who may otherwise be
disproportionately affected by the use of EtO as a pesticide.
C. Tolerance Actions
The Agency plans to exercise its FFDCA authority to update the tolerance expressions to
appropriately cover the metabolites and degradates of EtO and the EtO reaction product, ethylene
chlorohydrin (ECH), and to specify the residues to be measured for each commodity for
enforcement purposes. EPA anticipates amending the tolerance expressions to read as follows:
(a) General.
(1) Tolerances are established for residues of the antimicrobial agent and insecticide EtO,
including its metabolites and degradates, in or on the commodities in the table below.
Compliance with the tolerance levels specified below is to be determined by measuring
only EtO in or on the commodity.
(2) Tolerances are established for residues of the EtO reaction product ethylene
chlorohydrin, including its metabolites and degradates, in or on the commodities in the
table below. Compliance with the tolerance levels specified below is to be determined by
measuring only ethylene chlorohydrin (2-chloroethanol), in or on the commodity.
The Agency also plans to exercise its FFDCA authority to modify certain commodity definitions
associated with the tolerances for EtO and ECH and to revoke the EtO tolerance for walnuts, as
summarized in Table 3, below. The tolerances listed in Table 3 only include those for which
changes are recommended.
EtO. EPA is proposing to revise the commodity definitions for Peppermint, dried leaves; and
Spearmint, dried leaves. In addition, EPA proposes to revise the commodity definition for Herb
and spice group 19, dried leaves (except basil), although depending on what information is
submitted to the Agency concerning the importance of EtO for treatment of various dried herbs
and spices, EPA would propose to remove tolerances for those herbs and spices for which uses
may be cancelled. Ultimately, tolerances would remain for only those herbs and spices for which
it is determined that use on those commodities does not present unreasonable adverse effects and
that are safe. These revisions would not substantively change the established tolerance of 7 ppm
for each of these commodities, as listed in 40 C.F.R. § 180.151. The 2020 DRA recommended
that the EtO tolerance for walnuts be revised to reflect the lower residues resulting from the
single chamber process required for the treatment of spices, dried vegetables or seasonings with
EtO. However, the Agency is not aware of current EtO use on walnuts and none of the EtO
products are currently labeled for use on walnuts. In addition, based on the information currently
before EPA, the use of EtO on walnuts is unlikely to meet the standard for registration under
FIFRA because (1) the lack of usage of EtO on walnuts suggests that there are alternatives (e.g.,
nonchemical, PPO) available for the fumigation of walnuts and (2) the occupational cancer risk
estimates for EtO use in commercial sterilization facilities exceed the Agency's threshold of 1 x
10"4. The Agency does not believe this tolerance is necessary and intends to take action under the
FFDCA to revoke the walnut tolerance, rather than revise it consistent with the recommendation
in the 2020 DRA.
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ECH. EPA is proposing to revise the commodity definitions for Peppermint, dried leaves; and
Spearmint, dried leaves. In addition, EPA proposes to revise the commodity definition for the
Herb and spice group 19, dried leaves (except basil), although depending on what information is
submitted to the Agency concerning the importance of EtO for treatment of various dried herbs
and spices, EPA would propose to remove tolerances for those herbs and spices for which uses
may be cancelled. Ultimately, ECH tolerances would remain for only those herbs and spices for
which it is determined that EtO fumigations do not present unreasonable adverse effects and are
safe. These revisions would not substantively change the established tolerance of 940 ppm for
each of these commodities, as listed in 40 C.F.R. § 180.151. The 2020 DRA recommends that an
ECH tolerance for walnuts be established based on the documented level of quantification
(LOQ). However, the Agency is not aware of current EtO use on walnuts and none of the EtO
products are currently labeled for use on walnuts. The Agency intends to take action under the
FFDCA to revoke the EtO walnut tolerance and does not propose to establish an ECH tolerance
for walnuts.
Table 3. Summary of Anticipated r
"olerance
Actions (40 C.F.R. § 180.151)
1 >l;ihlislio.l
\nliap;ilal
Tnler;iik.v
ThIciiiiicc
(ppm)
ippim
( oininenis
40 CFR § 180.
151(a)(1) ethylene oxide
Herb and spice group 19, dried
leaves, except basil
—
7
Commodity definition revision.
Herb and spice, group 19, dried,
except basil
7
remove
Peppermint, dried leaves
—
7
Commodity definition revision.
Peppermint, tops, dried
7
remove
Spearmint, dried leaves
--
7
Commodity definition revision.
Spearmint, tops, dried
7
remove
Walnut
50
remove
Walnut use is not on current product labels and
occupational risk estimates of concern.
40 CFR § 180.151
a)(2) ethylene chlorohydrin
Herb and spice group 19, dried
leaves, except basil
--
940
Commodity definition revision.
Herb and spice, group 19, dried,
except basil
940
remove
Peppermint, dried leaves
--
940
Commodity definition revision.
Peppermint, tops, dried
940
remove
Spearmint, dried leaves
—
940
Commodity definition revision.
Spearmint, tops, dried
940
remove
D. Proposed Interim Registration Review Decision
The Agency is issuing this PID in accordance with 40 C.F.R. §§ 155.56 and 155.58. The Agency
has made the following proposed interim decision: (1) EPA proposes that registrants submit
OCSPP GLN 875.1400 Inhalation Indoor Exposure data and a special study on commercially
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available technologies that can measure below 10 ppb in real time; and (2) EPA proposes that
EtO does not meet the registration standard without changes to the affected registrations and
their labeling. EPA proposes that the mitigation specified in Sections V and Appendix B are
sufficient to address certain concerns. EPA intends to reevaluate EtO more frequently than the
typical 15-year registration review timeframe, based on new data that becomes available after
issuance of the Interim or Final Decision.
FIFRA requires that a pesticide "will not generally cause unreasonable adverse effects on the
environment" before EPA can register the pesticide. "Unreasonable adverse effects on the
environment" is defined by FIFRA to be "any unreasonable risk to man or the environment,
taking into account the economic, social, and environmental costs and benefits." To determine
whether there are any unreasonable risks under FIFRA from the registration of a product, EPA's
Office of Pesticide Programs conducts a risk-benefit analysis. The Agency weighs the benefits
(e.g., sterilization of medical devices) of the use of a pesticide against the potential ecological
and human health risks and proposes a decision about the use of a pesticide considering these
factors. Risk-benefit analysis is conceptually equivalent to more traditional benefit-cost analysis
(BCA) conducted elsewhere in the Agency. Risk-benefit analysis and benefit-cost analysis need
not exhaustively quantify costs in monetary terms. EPA guidance advises that "benefits and costs
that cannot be quantified should be presented qualitatively."136 The Office of Management and
Budget's Circular A-4, which defines good regulatory analysis and standardizes the way benefits
and costs of Federal regulatory actions are measured and reported, advises that "if you are not
able to quantify the [cost or benefit] effects, you should present any relevant quantitative
information along with a description of the unquantified effects"137 Through implementation of
risk-benefit analysis, OPP meets the FIFRA section 2(bb) mandate by taking into account the
"economic, social, and environmental costs and benefits of the use of any pesticide." EPA is
specifically requesting public comment on the cost of the proposed mitigation measures and will
include this information as part of the Interim or Final Decision.
The Agency conducted a DRA in 2020, as well as a detailed Addendum to the DRA in 2023. In
these risk assessments, EPA identified inhalation risks for workers and nearby communities from
continuing to register EtO. For occupational handlers at commercial sterilization and healthcare
facilities, cancer risk estimates are estimated from 4 x 10"2 (1 in 25) to 1 x 10"1 (1 in 10). Cancer
risks of concern are also anticipated for occupational, residential, and non-residential bystanders.
Although an ESA determination has not yet been completed for EtO, any exposure to wildlife
from the use of EtO will likely be limited, given the current and upcoming emissions controls
from OAR's NESHAP. These risks are not quantified in dollars, but they represent the Agency's
assessment of risk from the use of EtO. To help address these risks, EPA is proposing the
termination of certain uses, a use rate reduction through reduced concentrations, a series of
engineering controls within commercial sterilization facilities and healthcare facilities, respirator
protection requirements for commercial sterilization facilities, training requirements, monitoring
136 Environmental Protection Agency (EPA). 2010. Guidelines for preparing economic analyses. Accessed online on
January 6, 2023 at: https://www.epa.gov/environmental-economics/guidelines-preparing-economic-analyses.
137 Office of Management and Budget (OMB). 2003. Executive Office of the President, OMB Circular A-4,
Regulatory Analysis.
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requirements, and recordkeeping requirements, as well as requiring data from the registrants.
These proposed mitigation measures would reduce risks to workers and residential and non-
residential bystanders. EPA has not conduced a quantitative analysis of the risk reduction that
would result from these measures; however, the proposed required monitoring data after
implementation of mitigation would provide the Agency with information on risk reduction.
After this information is obtained, EPA can re-initiate registration review of EtO and take further
action if necessary. Since the risk reduction is not quantitatively assessed, and since the air
concentrations need to be very low to meet risk thresholds, the Agency is taking an approach of
"as low as reasonably achievable" (ALARA) for EtO use and application. Under FIFRA,
cancellation is an option for achieving risk reduction; however, in the case of EtO, using the
"ALARA" approach would result in a reasonable level of reduction, considering the benefits of
EtO and the current unavailability of alternatives, particularly for medical device sterilization.
EPA expects inhalation cancer risks of concern to remain for workers inside sterilization and
healthcare facilities, and residential and non-residential bystanders, even after the
implementation of the proposed mitigation.138 Ambient air data are normally used to provide
context for the exposures and risks that are being assessed. In the case of EtO, however, there are
risks of concern for levels that are below the levels of detection and/or quantification for the
methods that are used to measure EtO in ambient air. To achieve a residential population cancer
risk that is less than 1 in 1 million, for example, the lifetime average EtO concentration would
need to be less than 0.11 ppt. This level is less than the detection limit of 20-90 ppt and this
detection limit can only be achieved under optimum conditions.139 EPA is proposing to require
registrants to submit data on commercially available technologies that can monitor below 10 ppb
in real time.
The Agency has determined that despite these risks, EtO remains a critical pesticide for certain
uses. EPA is also proposing to determine that continuing to register EtO provides extensive
benefits to public health, as it is critical for the sterilization of new and reusable medical devices,
instruments, and equipment. Industrial EtO sterilization has a high throughput capacity, broad
material compatibility, low cost, and effective bactericidal, sporicidal, and virucidal activity. EtO
is used to sterilize 50 percent of all sterilized medical devices, or 20 billion devices, annually.
EPA has investigated alternatives to EtO for sterilizing medical devices, including engaging in
discussions with FDA about pursuing alternatives to EtO. EPA understands that, while there are
alternative sterilization methods for some medical devices, there are currently no available
alternatives—pesticidal or non-pesticidal—for some devices due to challenges such as material
compatibility, scalability, and capacity. Therefore, if commercial sterilization and healthcare
facilities no longer had access to EtO to sterilize medical devices, the result would likely be a
disruption to the medical device supply chain, which could in turn result in a nationwide public
health crisis. There is also a public health benefit to continuing to register EtO for spice
fumigation. The threat of food-borne contamination from pathogens such as Salmonella and
138 OPP notes that for residential bystander risk, even though OAR and OPP have different thresholds for when
residential cancer risks are considered to be of concern (100 in a million and 1 in a million, respectively), OPP
believes that the emissions controls proposed by OAR would significantly reduce bystander exposure without
causing adverse impacts to the U.S. supply of sterilized medical devices needed for a variety of medical procedures.
139 Ethylene Oxide (EtO). Addendum to "Draft Human Health and Ecological Risk Assessment in Support of
Registration Review" - Inhalation Exposure Risk Assessment in Support of Registration Review.
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Escherichia coli, and the potential for serious illness from exposure to these pathogens, is a
concern for the Agency, food manufacturers, and the general public. EtO is used in the U.S.
during the processing of herbs and spices to reduce microbial activity. As with medical devices,
EPA has investigated the availability of alternatives to EtO in spice fumigation, including
discussing potential alternatives with FDA. EPA understands that while alternatives may be
available to treat certain spices, EtO may be the only viable option for the treatment of certain
spices and spice forms. See Section III.C. Therefore, EPA is proposing to determine that the risk
from the use of EtO that is expected to remain following implementation of the proposed
mitigation measures would be outweighed by the significant public health benefits of the
continued use of EtO.
During registration review, EPA considers whether a pesticide registration "continues to satisfy
the FIFRA standard for registration."140 Here, EPA proposes that EtO does not meet the FIFRA
registration standard without the changes to the affected registrations and their labeling described
in Section IV. A and Appendices A and B.
EPA has determined that there is no human dietary risk from registered uses of EtO that is
inconsistent with the FFDCA safety standard. An aggregate assessment for EtO was not
conducted since there are no food or drinking water exposures to EtO. For the reaction products
of EtO (ECH and EG), there are no water or non-dietary residential exposures; the only exposure
route is through food. Thus, an aggregate assessment was not conducted for ECH or EG. For
more information, see Ethylene Oxide (EtO) Draft Human Health and Ecological Risk
Assessment in Support of Registration Review (2020 DRA) in this docket.
EPA concludes that there is a reasonable certainty that no harm will result from dietary exposure
to EtO or ECH. Therefore, the EtO and ECH residues are safe. EPA intends to leave the
tolerances in place (except for the walnut tolerance) as well as make several non-substantive
modifications, as EPA's analysis indicates that such actions would be safe.
In this PID, the Agency is not making any human health or environmental safety findings
associated with the Endocrine Disruptor Screening Program (EDSP) screening of EtO. Similarly,
the Agency is not making a complete endangered species finding, though the proposed
mitigation is expected to reduce the extent of environmental exposure and may reduce risk to
listed species whose range or critical habitat co-occur with the use of EtO. The Agency will
complete a listed-species assessment and any necessary Endangered Species Act (ESA) Section
7 consultation with the Services, and make an EDSP determination before issuing a final
registration review decision for EtO. For more information, see Appendices C and D.
140 40 C.F.R. § 155.40(a); 7 U.S.C. § 136a(c)(5); see also 7 U.S.C. §§ 136(bb) (defining "unreasonable adverse
effects on the environment" as encompassing both "any unreasonable risk to man or the environment, taking into
account the economic, social, and environmental costs and benefits of the use of any pesticide" [FIFRA's risk-
benefit standard] and "a human dietary risk from residues that result from a use of a pesticide in or on any food
inconsistent with the [FFDCA safety standard]"). In a PID, EPA sets out a proposed interim decision that includes
EPA's "proposed findings with respect to the FIFRA standard for registration and describe the basis for such
proposed findings." 40 C.F.R. §§ 155.56, 155.58(b)(1).
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E. Data Requirements
EPA proposes that registrants submit worker monitoring data as outlined in OSCPP GLN
875.1400 Inhalation Exposure Indoor. To quantify the effect of mitigation on worker exposure in
commercial sterilization facilities, EPA proposes to issue a Data Call-In (DCI) for OCSPP GLN
875.1400 Inhalation Exposure Indoor data and require a protocol before monitoring for the study
begins. Based on previously submitted worker monitoring data that lacked specificity and detail,
EPA proposes to require, through a DCI, badge monitoring of the handlers specifically involved
in activities related to the sterilization/fumigation (e.g., loading and unloading chambers, routine
maintenance, product transfer, etc), documentation of the activities each worker performed while
monitored, and whether they were wearing a respirator (and what type of respirator was worn).
For non-handlers in the facility (e.g., office workers, warehouse workers), EPA proposes to also
require air monitoring data, through a DCI, to monitor their exposure to EtO. The Agency
proposes that registrants follow the OSHA Method 1010 as the monitoring method.141 EPA
proposes that the DCI to be issued would require registrants to submit following implementation
of all mitigation. The Agency will issue a DCI to establish a timeline for submitting these data.
EPA further proposes to issue a DCI for methods to improve measurement technologies inside of
EtO commercial sterilization facilities, as well as warehouses that store sterilized devices. It is
the Agency's understanding that current measurement technology is able to measure down to 10
ppb, which is the lowest quantifiable level. Since EPA's assessment shows that risks to workers
are not of concern where workers are exposed at a level of 0.19 ppb, the Agency proposes that
the DCI to be issued would require registrants to submit data to demonstrate the advancements in
technologies that are capable of monitoring EtO levels as close to this level as possible. The
Agency proposes issuing a DCI to collect data on commercially available technologies that can
monitor below 10 ppb in real time, on a two-year timeframe. The Agency is soliciting comments
on the feasibility of a two-year DCI timeframe. Once these data become available, the Agency
may promptly initiate the next cycle of Registration Review.
F. Summary of Proposed Recordkeeping Requirements
Application Rates
EPA proposes that the EtO application rate must be less than or equal to 500 mg/L while still
meeting FDA sterility requirements. If sterilization of a device requires more than 500 mg/L, due
to the device design, EPA proposes to require facilities maintain records for a justification for the
increased application rate. Specifically, this justification would demonstrate the necessary
calculations for determining the application rate, through either the Cycle Calculation Approach,
or other approaches found in ISO 11135. EPA further proposes a facility recordkeeping
requirement for the amount of EtO used regardless of whether the amount used is less than or
greater than 500 mg/L. All records would need to be available upon request to any local, state,
tribal, or federal pesticide enforcement personnel. Records would be required to be maintained
for two years from the date of sterilization.
141 OSHA Method 1010 (revised 2014) can be found at https://www.osha.gov/sites/defaiilt/fites/methods/osha~
1010.pdf.
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Pressure Sensitive Devices
The Agency is proposing to require all-in-one sterilization systems in commercial sterilization
facilities that do not sterilize pressure sensitive devices. EPA further proposes that registrants
ensure facilities keep records that show there are pressure sensitive devices being sterilized, and
are, therefore, unable to be processed in all-in-one systems, if applicable. All records would need
to be available upon request to any local, state, tribal, or federal pesticide enforcement personnel.
Records would be required to be maintained for two years from the date of sterilization.
Indoor EtO Concentrations and Corresponding Worker Protection Measures
To reduce worker exposure, EPA is proposing that respirator requirements be based on a
technologically measurable (i.e., quantifiable) EtO concentration of ambient air, which by the
Agency's understanding is 10 ppb for real time measurements.142 Understanding that respirator
use for all employees may not be feasible, if EtO levels exceed 10 ppb, EPA is also proposing to
require that employees would have the option to vacate the premises until the levels return to
below 10 ppb. The Agency proposes that facilities maintain records of indoor EtO concentration
levels, including the daily average concentration, and minimum and maximum concentrations.
EPA further proposes that facilities maintain records of employee respirator wear time and/or
evacuation time. All records would need to be available upon request to any local, state, tribal, or
federal pesticide enforcement personnel. Records would be required to be maintained for two
years from the date of sterilization.
Employee Training
EPA proposes a requirement for commercial sterilization and healthcare facilities to maintain
records on employee training. Specifically, what training materials are provided to employees
upon assignment and annually thereafter, and records of the dates individual employees are
trained. All records would need to be available upon request to any local, state, tribal, or federal
pesticide enforcement personnel. Records would be required to be maintained for the duration
that the trainee is employed, or for two years from the date of training if the trainee leaves the
place of employment before two years.
G. Summary of Public Comment Requested
In addition to general areas on which persons may wish to comment, there are some areas
identified in this PID which the Agency specifically seeks comments and information. Interested
stakeholders are encouraged to include additional information on the following topics, and the
Agency welcomes comments on all aspects of the proposed mitigation.
Use Rate Reduction through Reduced Concentrations for Medical Device Sterilization
142 The limit of quantification (LOQ) of 10 ppb is for real-time instruments. These instruments respond within
minutes to changes in EtO levels. The OSHA method for air sampling has a limit of detection (LOD) of 1 ppb for a
4-hour sample. See OSHA Method 1010 (revised 2014) which can be found at
https://www.osha.gov/sites/default/files/methods/osha-1010.pdf.
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EPA proposes that the EtO concentration must be less than or equal to 500 mg/L while still
meeting FDA sterility requirements. For existing cycles, EPA proposes a 5-year compliance
timeframe to limit the EtO concentration to 500 mg/L. EPA seeks public comment on the
feasibility of a 5-year compliance timeline for use rate reduction through reduced concentrations
of existing cycles. EPA proposes a 2-year compliance timeframe to limit the EtO concentration
to 500 mg/L for new cycles and seeks public comment on the feasibility of a 2-year compliance
timeline for use rate reduction through reduced concentrations of new cycles. EPA also seeks
public comment on alternative limits that may differ from 500 mg/L.
Commercial Sterilization Facilities Engineering Controls (Medical Device and Spice Use)
All-in-one systems
The Agency is seeking additional information on the feasibility of all-in-one processing
(combination sterilizers) for the treatment of medical devices by commercial sterilization
facilities. With all-in-one systems, sterilization and aeration occur in the same chamber. EPA
understands that all-in-one systems may not be appropriate for use to sterilize pressure-sensitive
materials. Additionally, each all-in-one processing chamber is utilized for a greater amount of
time when compared to traditional sterilization configurations, potentially limiting the
throughput in a facility. EPA seeks public comment on feasibly of upgrading facilities to use all-
in-one systems, and the potential impacts on the medical device supply chain.
Ventilation ofproduct storage areas and product packaging
EPA is soliciting public comment on the number of air exchanges per hour that would
adequately ventilate product storage areas. The Agency is also soliciting public comment on the
use of netting rather than plastic surrounding pallets of treated medical devices to increase
aeration and prevent EtO from becoming trapped in plastic wrap or other packaging.
Automation via covered conveyor for transported aerated materials to shipping/storage areas
In traditional EtO treatment configurations, sterilization and aeration are performed in two
separate chambers. In these systems, employees may transfer post-treatment materials from the
sterilization chamber to the aeration chamber via forklift. EPA is aware that in some sterilization
facilities, post-treatment materials are instead transferred via enclosed conveyor systems, to
reduce employee exposure. EPA is seeking public comment on the feasibility of reconfiguring
existing EtO commercial sterilization facilities to use an enclosed conveyor system from the
aeration area to the storage/shipping area. Note that in facilities that have all-in-one systems,
EPA is proposing automation via covered conveyor from the aeration area to the shipping and
storage area.
Other engineering and process controls not proposed as part of this PID
It is EPA's understanding that there are other methods and controls available that could reduce
worker exposure to EtO that are not included in this PID. The Agency seeks further information
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on all engineering controls and/or work practices that would result in lowered EtO exposure for
workers (for example, internal capture and emissions controls like dry beds or filters, increased
air turns and cascade pressure systems, or others). In multi-chamber systems, process controls
like minimizing the time and transfer length that is taken from the sterilization to aeration area,
or the elimination of a staging area, may reduce worker exposure. As EPA is proposing
automation in these areas, the Agency seeks information on the comparative exposure reductions
of the aforementioned process controls.
Implementation time and cost for all engineering controls
EPA recognizes implementation of the proposed engineering controls would require a longer
timeframe than typically provided by the Agency for the implementation of risk mitigation
measures, given the limited availability of new equipment, increased demand, and the potential
for disrupting the supply chain if facilities need to close to make these upgrades. EPA is seeking
public comment on a reasonable timeframe for registrants to submit label amendments to
implement the proposed engineering controls, as well as cost information. EPA further seeks
public comment on whether these engineering controls would require state or local permits
before the renovations could take place, and the timing associated with that permitting process.
Finally, the Agency seeks public comment on potential impacts on the supply chain of sterilized
medical devices related to the potential downtime of sterilizing equipment during renovation.
Engineering controls for existing (all or subset) versus new facilities
EPA is seeking public comment on whether to implement the engineering controls proposed in
this PID to be for all existing facilities, a subset of existing facilities, or for only new facilities.
Personal Protective Equipment (Medical Device and Spice Use)
Respiratory protection logistical limitations
EPA recognizes there are logistical limitations to Self-Contained Breathing Apparatus (SCBA)
respirators and Supplied Air Respirators. The typical maximum wear time for a SCBA respirator
is 45 minutes before the cylinder must be changed. Supplied air systems are affixed to walls with
a hose running to the supplied air respirator worn by the sterilization worker. While this system
provides an unlimited supply of air which eliminates the need to change cylinders, the hose can
limit worker mobility. EPA seeks public comment on facility layout and typical employee work
shifts, as it relates to the proposed personal protective equipment requirement in Section V. A.
Technologies for Worker Monitoring and Respirator Requirement
This PID proposes that all workers (including both handlers and occupational bystanders) in
commercial sterilization facilities be required to wear respirators when EtO concentrations in the
facilities exceed 10 ppb. EPA requests public comment on the feasibility of continuous, real-time
monitoring to a 10 ppb level inside of commercial sterilization facilities and the possible impacts
of the daily operations of commercial sterilization facilities. EPA understands that the supply of
monitoring systems may be limited, and so the compliance timeframe may be affected by
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equipment availability. The Agency seeks public comment on the cost and how long is necessary
for registrants to implement label amendments requiring compliance with this respirator
requirement and the corresponding monitoring and recordkeeping requirements. EPA is
proposing that this change be implemented within 2 years.
Alternative Sterilization Methods for Medical Devices
Some medical devices can only be sterilized with EtO. However, there are several FDA-
recognized methods used to sterilize medical equipment: gamma irradiation, X-ray sterilization,
electron beam sterilization, and steam; as well as the alternative sterilization methods in
development including hydrogen peroxide, vaporized hydrogen peroxide, nitrogen dioxide,
chlorine dioxide, and vaporized peracetic acid. EPA understands there are limitations of
comparable sterilization methods due to compatibility with materials and/or packaging,
scalability or capacity, and lack of validation measures or efficacy data. EPA seeks public
comment on more information about the existing limitations of available alternatives. EPA also
seeks public comment on existing and emerging alternative methods for medical device
sterilization that are scalable and could most effectively replace EtO.
Technologies to Lower Detection Limits for Ambient Air
When assessing risks from exposure to a pesticide, EPA normally uses ambient air data to
provide context for the exposures and risks that are being assessed. In the case of EtO, however,
there are risks of concern for levels of EtO that are below the levels of detection for the methods
that are used to measure EtO in ambient air. To achieve a residential population cancer risk that
is less than 1 x 10"6, for example, the lifetime average EtO concentration would need to be less
than 0.11 ppt. This level is less than the detection limit of 20-90 ppt and this detection limit can
only be achieved under optimum conditions. EPA's Office of Research and Development (ORD)
is actively working in this area to improve sampling methods for ambient levels of EtO.143 EPA
seeks public comment on advancements in technologies to lower detection limits for EtO.
OSHA's Permissible Exposure Limit (PEL)
EPA understands that OSHA's EtO PEL has not been updated since it was established in 1984,
and that health standards issued under section 6(b)(5) of the OSH Act must reduce significant
risk only to the extent that it is technologically and economically feasible.144 Given that EPA has
identified risks for workers at levels below the OSHA PEL, EPA does not consider the current
OSHA PEL to be protective of workers. EPA is seeking public comment to determine if facilities
have voluntarily set lower exposure limits to better protect workers.
Environmental Justice
The Agency requests information on any other groups or segments of the population who, as a
result of their proximity and exposure to pesticides, unique exposure pathway (e.g., as a result of
143 Ethylene Oxide (EtO). Addendum to "Draft Human Health and Ecological Risk Assessment in Support of
Registration Review" - Inhalation Exposure Risk Assessment in Support of Registration Review.
144 https://www.federalregister.gov/citation/49-FR-25734.
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cultural practices), location relative to physical infrastructure, exposure to multiple stressors and
cumulative impacts, lower capacity to participate in decision making, or other factors, may have
unusually high exposure to EtO compared to the general population or who may otherwise be
disproportionately affected by the use of EtO as a pesticide.
Healthcare Facilities
Healthcare facilities engineering controls
EPA is proposing to require the following engineering controls in healthcare facilities: physical
separation of EtO sterilization spaces; negative air pressure in rooms containing EtO sterilization
devices; ventilation of EtO exhaust through exterior ventilation stacks; and abatement devices to
capture excess EtO. The Agency seeks public comment on the cost and time necessary for
registrants to implement label amendments requiring the implementation of the proposed
engineering controls. EPA is proposing that these engineering controls be implemented within 2
years.
Respirator use in healthcare facilities
EPA is seeking public comment on the feasibility of respirator use (supplied airline respirators or
self-contained breathing apparatus respirators) in healthcare facilities for employees who are
unloading EtO sterilization equipment from the sterilization chamber.
Spice Fumigation Use
Use Rate Reduction for Spice Treatments
The EtO product labels provide detailed use directions, including a maximum use rate, for the
EtO use on herbs and spices. The Agency is seeking public comment on examples of efficacious
EtO treatments for pathogen control at rates lower than the maximum label rate, and how often
facilities have completed EtO validations for EtO concentrations that are less than 500 mg/L.
The Agency is interested in establishing an alternative method for the product labels that use a
lower rate of EtO. EPA encourages facilities and interested stakeholders to work with the
Agency to develop a new method at a lower rate that is effective for pathogen control and
continues to meet the dietary safety standards (e.g., acceptable residues of EtO and ECH).
Alternative fumigation methods for spices
Because of the estimated occupational and bystander risks associated with the use of EtO to
fumigate spices, the Agency is considering a phased cancellation of specific spices/ commodities
without documentation showing that alternatives are not viable and the need for EtO is critical to
food safety. The Agency intends to include language in the ID stating that registrants should
submit requests to voluntarily terminate uses on commodities for which there are viable
alternatives (see Section III.D). When the Agency receives requests from registrants to
voluntarily cancel a pesticide registration or terminate a use, the Agency is required to publish an
FRN regarding the cancellation request and take public comment (see 7 U.S.C. § 136d(f)(l)).
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There are several alternatives to EtO that are used to treat herbs and spices for pathogen control.
These are irradiation, heat, steam, and propylene oxide. However, EPA understands that these
alternatives may not be viable for every spice, spice form (e.g., leaf, ground), spice blend, or
target pathogen. EPA seeks public comment on specific spices/commodities listed in Table 2
(see section III.D. above) for which EtO use is deemed critical for food safety and for which
there are no viable alternatives to EtO (e.g., steam, irradiation, or propylene oxide cannot be used
for pathogen control on a particular spice, spice form, or spice blend). The information provided
should include why the alternative methods are not effective and include the amount of a
commodity treated with EtO (lbs./year). All information provided should be specific and
detailed.
Based on information submitted to the Agency, EPA understands that the following spices often
have high pathogen loads: black pepper, paprika, celery seed, coriander, turmeric, and
thyme.145 146 The Agency is seeking public comment on alternative treatment options for those
spices and target pathogens (e.g., Salmonella, E. coli). In addition, the Agency would like to
know if there are other commodities that typically have high pathogen loads for which there are
not efficacious treatment options besides EtO. The Agency is also seeking information regarding
the importance of EtO to spice blends (e.g., seasonings) and the specific spices in the blends for
which EtO fumigation is critical.
VI. NEXT STEPS AND TIMELINE
A. Proposed Interim Registration Review Decision
A Federal Register Notice will announce the availability of the EtO PID and open a 60-day
comment period. The Agency may issue an Interim Registration Review Decision (ID) for EtO
after the close of this comment period, as long as the Agency would not have reason to change
the proposed interim decision in Section IV.D, above. The Agency may make a final registration
review decision for EtO without previously issuing an ID. However, a final registration review
decision for EtO will only be made after EPA completes (1) an endangered species determination
and any necessary consultation with the Services, and (2) an EDSP determination.
EPA is proposing that registrants would submit label amendments within 60 days after the
decision. The Agency would review such label amendments as expeditiously as feasible and is
proposing that products distributed by registrants would have to bear the revised labeling within
the timeframes outlined in the mitigation section of this PID after EPA has approved the revised
labeling. For certain mitigation measures, the time period exceeds 12 months for compliance,
145 American Spice Trade Association (ASTA). 2017. Clean, Safe Spices, Guidance from the American Spice Trade
Association, 2017 Update, https://www.astaspice.org/food~safetv-techiiical~guidance/best~practices~and~
guidance/clean-safe-spices-guidance-document/. Accessed September 2020.
146 Ethylene Oxide Task Force (EOTF). 2020. Ethylene Oxide Benefits Statement submitted by B&C Consortia
Management, L.L.C. on behalf of the EOTF. EOTF email to EPA regarding benefits of ethylene oxide for medical
devices. Email sent from Lisa Campbell, Partner, Bergeson & Campbell PC to Jessica Bailey, Antimicrobial
Division, Office of Pesticide Programs, Environmental Protection Agency. May 6, 2020.
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taking into consideration the costs, impacts to the supply chain, and other logistical elements. As
noted throughout the PID, EPA is seeking public comment on compliance timelines of the
proposed mitigation measures.
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Appendix A: Summary of Proposed Actions for EtO
Registration Review Case #: 2215
PC Code: 042301
Chemical Type: Fumigant
Chemical Family: Oxirane
Mode of Action: Alkylation
Affected Population(s)
Source of
Route of Exposure
Duration of
Potential
Proposed Actions
Comment
Exposure
Exposure
Risk(s) of
Concern
Occupational handler
Air
Inhalation
Lifetime
Cancer
• Delete uses for which
alternatives exist.
• Reduce application rate.
• Require engineering
controls for automation,
air pressure gradient,
HVAC systems, and
ventilation.
• Require SCBA or
supplied air respirators
for specific tasks and
when EtO
concentrations exceed
10 ppb.
• Real time indoor air
monitoring to the
lowest technologically
measurable (i.e.,
quantifiable) level (10
ppb).
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• Recordkeeping
requirements of
application rates, types
of devices sterilized
(noting pressure-
sensitive devices),
indoor EtO
concentrations and
corresponding worker
protection measures,
and employee training.
Occupational
bystander
Air
Inhalation
Lifetime
Cancer
• Delete uses for which
alternatives exist.
• Reduce application rate.
• Require engineering
controls for automation,
air pressure gradient,
HVAC systems, and
ventilation.
• Require SCBA or
supplied air respirators
for specific tasks and
when EtO
concentrations exceed
10 ppb.
• Real time indoor air
monitoring to the
lowest technologically
measurable (i.e.,
quantifiable) level (10
ppb).
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• Recordkeeping
requirements of
application rates, types
of devices sterilized
(noting pressure-
sensitive devices),
indoor EtO
concentrations and
corresponding worker
protection measures,
and employee training.
By-standers
(residential and non-
residential)
Air
Inhalation
Lifetime
Cancer
• Delete uses for which
alternatives exist.
• Reduce application rate.
• Emissions reductions as
would be required per
OAR's Proposed EtO
Emissions Standards
for Sterilization
Facilities.147
147 EPA-HQ-2019-0178.
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Appendix B: Proposed Labeling Changes for EtO Products
Description
Proposed Label Language for EtO Products148
Placement on
Label
Technical and Manufacturing Use Products
Use Deletion
Remove the following use sites: Museum materials, Library materials, Archival
materials, Cosmetics, Musical instruments, Beekeeping equipment.
Directions for Use
Spice Use
Definition/Identification
: Specifying allowable
spices and herbs from
Crop Group 19
Deletions are shown with a strikethrough and insertions are shown with an
underline.
"As A Sterilant and Fumigant Gas
This product may be used only to sterilize medical or laboratory items,
pharmaceuticals, and aseptic packaging, (see 21 CFR 201.1(d)(5)), or to reduce
microbial load on cosmetics, whole and ground spicos or other seasoning
Directions for Use
HlulLlldl j ^JCC lu v/T J\ lOU. I J 1 J ullU ul Uluvlj, dl vlll V dl HldlLlldl U1 llUlclljy UUJLvIj
TLIST OF SPICES1."
End Use Products
Use Deletion
Remove the following use sites from the label: Museum materials, Library
materials, Archival materials, Cosmetics, Musical instruments, Beekeeping
equipment.
Directions for Use
Spice Use
Definition/Identification
: Specifying allowable
Deletions are shown with a strikethrough and insertions are shown with an
underline.
Directions for Use
148 Unless otherwise specified, the proposed requirements are effective 60 days from the publication of the Interim / Final Decision.
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spices and herbs from
Crop Group 19
"As A Sterilant and Fumigant Gas
This product may be used only to sterilize medical or laboratory items,
pharmaceuticals, and aseptic packaging, (see 21 CFR 201.1(d)(5)), or to reduce
microbial load on cosmetics, whole and ground spices or other seasoning
lllulvl 1 ul J ^JVV 1 L/ V/F Fv 1 W V. 1 J 1 J ullU ul Uluvlj^ ul vlll v ul lllulvl 1 ul U1 11 L/l ul y U UJ vvlj
TLIST OF SPICES1."
"This product may only be applied to or on spices, dried vegetables or
seasonings ILIST OF SPICES1 utilizing an ETO sterilization method that uses a
single sterilization chamber for pre-conditioning, sterilization and aeration ..."
Removal of OSHA 1
ppm Permissible
Exposure Limit (PEL)
and 5 ppm Excursion
Limit (EL)
Remove OSHA citations for 1 ppm Permissible Exposure Limit (PEL) and 5
ppm Excursion Limit (EL) (OSHA 29 CFR 1910.1047).
Directions for Use
Use Rate Reduction
through Reduced
Concentrations for
Medical Device
Sterilization
"As of [2 years from the publication of the Interim / Final Decision] commercial
sterilization facilities are required to limit the application rate to less than or
equal to 500 mg/L for new cycles. As of [5 years from the publication of the
Interim / Final Decision] commercial sterilization facilities are required to limit
the application rate to less than or equal to 500 mg/L for existing cycles.
The sterilization/fumigation cycle parameters are prescribed by the equipment
manufacturer. Safety and efficacy must be validated by FDA and are the
responsibility of the user."
Directions for Use
Engineering Controls in
Commercial
Sterilization Facilities:
Air Pressure Gradient
"To reduce exposure to EtO at commercial sterilization facilities, EPA requires
the following engineering control by [2 years from the publication of the Interim
/ Final Decision]:
Air pressure gradient so that air is continuously flowing from low-EtO
concentration to high-concentration spaces. Non-processing areas must have
Directions for Use
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positive pressure compared to slightly negative pressure of processing areas. The
highest level of negative pressure must be in the sterilization chamber."
Engineering Controls in
Commercial
Sterilization Facilities:
HVAC Systems
"To reduce exposure to EtO at commercial sterilization facilities, EPA requires
the following engineering control [2 years from the publication of the Interim /
Final Decision]:
Separation of office and sterilization area HVAC systems. Non-processing areas,
such as office space and control rooms, must have separate HVAC systems from
EtO processing areas."
Directions for Use
Engineering Controls in
Commercial
Sterilization Facilities:
Ventilation of Storage
Areas
"To reduce exposure to EtO at commercial sterilization facilities, EPA requires
the following engineering control [by 2 years from the publication of the Interim
/ Final Decision]:
Adequate ventilation of EtO-sterilized product storage spaces. All storage areas
must be properly ventilated since not all EtO could be removed from post-sterile
product areas, due to the absorbant nature of pallets, cardboard, and packaging."
Directions for Use
Engineering Controls in
Commercial
Sterilization Facilities:
Automation of movement
of sterilized and aerated
materials via covered
conveyor.
"To reduce exposure to EtO at commercial sterilization facilities, EPA requires
the following engineering control [by 2 years from the publication of the Interim
/ Final Decision]:
All EtO medical device sterilization facilities with a traditional multi-chamber
sterilization configuration must utilize an enclosed conveyor to transport
sterilized materials from the sterilization chamber to the aeration chamber.
Additionally, all EtO medical device and spice sterilization facilities must utilize
an enclosed conveyor to transport aerated materials from the aeration
chamber/room to storage/shipping areas, in both traditional sterilization
scenarios (multi-chamber) and all-in-one sterilization (single chamber)
scenarios."
Directions for Use
Engineering Controls in
Commercial
Sterilization Facilities:
All-in-one processing
"To reduce exposure to EtO at commercial sterilization facilities, EPA requires
the following engineering control [by 2 years from the publication of the Interim
/ Final Decision]:
Directions for Use
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(combination sterilizers)
where feasible.
For the sterilization of medical devices by commercial sterilization facilities, all-
in-one processing (combination sterilizers) where sterilization and aeration occur
in the same chamber is required if the facility does not sterilize pressure
sensitive devices.
EtO products applied to or on [LIST OF SPICES] are required to use an EtO
sterilization method that uses a single sterilization chamber for pre-conditioning,
sterilization and aeration.
A single chamber process is required for EtO treatment in hospitals and
healthcare facilities."
Physical separation of
EtO sterilization spaces
in Healthcare Facilities
"All EtO single chamber sterilization/aeration devices in healthcare facilities
(hospitals, veterinary facilities, dental offices, etc.) must be located in a
containment area that is physically separate from all other work areas of the
healthcare facility by [2 years from the publication of the Interim / Final
Decision]."
Directions for Use
Use of Abatement
Devices in Healthcare
facilities
"Healthcare facilities (hospitals, veterinary facilities, dental offices, etc.) using
EtO single chamber sterilization/aeration devices must utilize an abatement
device in order to reduce EtO emissions. Refer to sterilization device
manufacturer for information on abatement devices by [2 years from the
publication of the Interim / Final Decision]."
Directions for Use
Venting of Healthcare
Facilities
"All EtO sterilizers in healthcare facilities (hospitals, veterinary facilities, dental
offices, etc.) must be vented out of the workplace to the outside atmosphere. A
separate exhaust duct to the outside is required. The exhaust duct should
terminate away from areas where people walk or work. The duct should be
located at least 7.6 meters (25 feet) away from the building air intake source and
must be engineered according to existing codes by [2 years from the publication
of the Interim / Final Decision]."
Directions for Use
Pressure Differential in
Healthcare Facilities
"EtO sterilization areas must be kept at a negative pressure differential
compared to the ambient air pressure of the healthcare facility (hospitals,
veterinary facilities, dental offices, etc.) by [2 years from the publication of the
Interim / Final Decision]."
Directions for Use
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Specification of Use Site
for Healthcare Facility
Products
"This product is intended only for use in single chamber sterilization/aeration
devices in healthcare facilities (e.g., hospitals, veterinary facilities, dental
offices, etc.)."
Directions for Use
Specification of Use Site
for Commercial
Sterilization Facilities
"This product is intended only for use in commercial sterilization facilities. This
product is not intended for use in healthcare facilities (hospitals, veterinary
facilities, dental offices, etc.)."
Directions for Use
Updated Respirator
Language for
Commercial
Sterilization Facilities149
"To reduce exposure to EtO at commercial sterilization facilities, supplied
air/airline (SAR) respirators or self-contained breathing apparatus (SCBA)
respirators (full facepiece) be worn by all workers in a commercial sterilization
facility by workers engaged in the following tasks, regardless of the EtO
concentration in the facility:
• Connecting and disconnecting EtO containers from sterilization process
equipment.
• Unloading processed products from the sterilization chamber, whether at
the end of a cycle for an all-in-one process, or, for a conventional
process, preparatory to moving product to the aeration area.
• Loading and unloading product from the aeration area.
• Removing validation test materials from processed product at any time
prior to the completion of aeration.
• Opening process lines or equipment that may contain EtO (e.g., for
repairs or routine maintenance tasks.
In the Personal
Protective
Equipment (PPE)
within the
Precautionary
Statements
149 Task-based respirator use is required 60 days from the publication of the Interim / Final Decision. The concentration-based respirator use is required 2 years
from the publication of the Interim / Final Decision, taking into account the time needed for facilities to update their monitoring systems.
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Additionally, if not vacating the premises, SAR or SCBA respirators must be
worn by all employees when EtO concentrations in the facility exceed 10 ppb by
[2 years from the publication of the Interim / Final Decision]."
Decrease Action Level
"Commercial sterilizer facilities must continuously monitor, in real time, down
to a minimum of 10 ppb by [2 years from the publication of the Interim / Final
Decision], Monitoring areas include processing and non-processing (i.e. office
spaces, control rooms, warehouses, etc,) areas. This data must be made available
to all employees in real time."
Directions for Use
Respirator Fit Testing
Requirements for Non-
WPS Uses
"Respirator fit testing, medical qualification, and training
Using a program that conforms to OSHA's requirements (see 29 CFR Part
1910.134), employers must verify that any worker who uses a respirator is:
• Fit-tested and fit-checked,
• Trained, and
• 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 healthcare professional 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. Handlers must be
reexamined by a qualified medical practitioner if their health status or respirator
style or use conditions change.
Upon request by local/state/federal/tribal enforcement personnel, employers
must provide documentation demonstrating how they have complied with these
requirements."
In the Personal
Protective
Equipment (PPE)
within the
Precautionary
Statements
Training Requirements
in Commercial
Sterilization Facilities
"For Commercial Sterilization Facilities: Employees must be trained upon
assignment and annually thereafter on the potential health effects from the levels
of EtO in the facility and the availability of materials related to the health
hazards of exposure to EtO. Specifically, the Maximum Likelihood Exposure
(MLE) cancer risk for EtO handlers for medical devices is 1 in 17, and the upper
bound cancer risk for EtO handlers for medical devices is 1 in 10. The MLE
Directions for Use
under the heading
"Training
Requirements"
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cancer risk for EtO handlers for spices is 1 in 36, and the upper bound cancer
risk for EtO handlers for spices is 1 in 16."
Training Requirements
in Healthcare Facilities
"For Healthcare Facilities: Employees must be trained upon assignment and
annually thereafter on the potential health effects from the levels of EtO in the
healthcare facility and the availability of materials related to the health hazards
of exposure to EtO. Specifically, the Maximum Likelihood Exposure (MLE)
cancer risk for EtO handlers in healthcare facilities is 1 in 25, and the upper
bound cancer risk for EtO handlers in healthcare facilities is 1 in 12."
Directions for Use
under the heading
"Training
Requirements"
Recordkeeping
Requirements
"Recordkeeping Requirements: All records must be maintained for two years
from the date of sterilization, or in the case of training materials, 2 years from
the date of training. Records must be made available upon request to any local,
state, tribal, or federal pesticide enforcement personnel.
Application Rates: Facilities must maintain records for the amount of EtO used.
If sterilization of a device requires more than 500 mg/L, due to the device
design, facilities must maintain records for a justification for the increased
application rate. Specifically, this justification would demonstrate the necessary
calculations for determining the application rate, through either the Cycle
Calculation Approach, or less conservative approaches found in ISO 11135.
Indoor EtO Concentrations and Corresponding Worker Protection Measures:
Facilities must maintain records of indoor EtO concentration levels, and records
of employee respirator wear time and/or evacuation time.
Employee Training: Facilities must maintain records on training materials
provided to employees upon assignment and annually thereafter, and records of
the dates individual employees are trained."
Directions for Use
under the heading,
"Recordkeeping
Requirements"
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Appendix C: Listed-Species Assessment
This Appendix provides general background about the Agency's assessment of the effects of
pesticides on listed species and designated critical habitats under the Endangered Species Act
(ESA).
Developing Approaches for ESA Assessments and Consultation for FIFRA Actions
In 2015, EPA, along with the Services—the U.S. Fish and Wildlife Service (FWS) and the
National Marine Fisheries Service (NMFS)—and the United States Department of Agriculture
(USDA) (referred to as "the agencies") released their joint Interim Approaches150 for assessing
the effects of pesticides to listed species. The agencies jointly developed these Interim
Approaches in response to the 2013 National Academy of Sciences' recommendations that
discussed specific scientific and technical issues related to the development of assessments of
pesticides' effects to listed species. Since that time, the agencies have been continuing to work to
improve the approaches for assessing effects to listed species. After receiving input from the
Services and USDA on proposed revisions to the interim method and after consideration of
public comments received, EPA released an updated Revised Methodfor National Level Listed
Species Biological Evaluations of Conventional Pesticides ("Revised Method") in March
2020.151
The agencies also continue to work collaboratively through a FIFRA Interagency Working
Group (IWG). The IWG was created under the 2018 Farm Bill to recommend improvements to
the ESA section 7 consultation process for FIFRA actions and to increase opportunities for
stakeholder input. This group is led by EPA and includes representatives from NMFS, FWS,
USDA, and the Council on Environmental Quality (CEQ). The IWG outlines its
recommendations and progress on implementing those recommendations in reports to
Congress.152
Consultation on Chemicals in Registration Review
EPA initially conducted biological evaluations (BEs) using the interim method on three pilot
chemicals representing the first nationwide pesticide consultations (final pilot BEs for
chlorpyrifos, malathion, and diazinon were completed in January 2017). These initial pilot
consultations were envisioned as the start of an iterative process. Later that year, NMFS issued a
final biological opinion for these three pesticides. In 2019, EPA requested to reinitiate formal
consultation with NMFS on malathion, chlorpyrifos and diazinon to consider new information
that was not available when NMFS issued its 2017 biological opinion. EPA received a final
malathion biological opinion153 from FWS in February 2022 and a final biological opinion from
150 https://www.epa.gov/endangered-species/interim-approaches-pesticide-endangered-species-act-assessments-
151 https://www.epa.gov/endangered-species/revised-method-national-level-listed-species-biological-evaliiations-
conventional
152 https://www.epa.gov/endangered-species/reports-congress-improving-consiiltation-process-iinder-endangered-
species-act.
153 https://www.epa.gov/endangered-species/biological-opin.ions-available-piiblic-cotn.ment-and-links-final-opin.ions.
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NMFS on malathion, chlorpyrifos and diazinon in June 2022.154 The Agency plans to implement
both biological opinions according to the 18-month timeframes specified in the biological
opinions.
In 2020, EPA released draft BEs for the first two chemicals conducted using the 2020 Revised
Method—carbaryl and methomyl. Subsequently, EPA has used the Revised Method to complete
final BEs for carbaryl, methomyl, atrazine, simazine, glyphosate, clothianidin, imidacloprid, and
thiamethoxam. EPA is currently in consultation with the Services on these active ingredients.
EPA's New Actives Policy and the 2022 Workplan
In January 2022, EPA announced a policy155 to evaluate potential effects of new conventional
pesticide active ingredients to listed species and their designated critical habitat and initiate
consultation with the Services, as appropriate, before registering these new pesticides. Before the
Agency registers new uses of pesticides for use on pesticide-tolerant crops, EPA will also
continue to make effects determinations. If these determinations are "likely to adversely affect",
the Agency will not register the use unless it can predict that registering the new use would not
have a likelihood of jeopardizing listed species or adversely modifying their designated critical
habitats. EPA will also initiate consultation with the Services as appropriate.
In April 2022, EPA released a comprehensive, long-term approach to meeting its ESA
obligations, which is outlined in Balancing Wildlife Protections and Responsible Pesticide
Use.156 This workplan reflects the Agency's most comprehensive thinking to date on how to
create a sustainable ESA-FIFRA program that focuses on meeting EPA's ESA obligations and
improving protection for listed species while minimizing regulatory impacts to pesticide users
and collaborating with other agencies and stakeholders on implementing the plan.
On November 16, 2022, EPA released the ESA Workplan Update: Nontarget Species Mitigation
for Registration Review and Other FIFRA Actions.157 As part of this update, EPA announced its
plan to consider and include, as appropriate, a menu of FIFRA Interim Ecological Risk
Mitigation intended to reduce off-target movement of pesticides through spray drift and runoff in
its registration review and other FIFRA actions. These measures are intended to reduce risks to
nontarget organisms efficiently and consistently across pesticides with similar levels of risks and
benefits. EPA expects that these mitigation measures may also reduce pesticide exposures to
listed species.
154 https://www.epa.gov/endangered-species/biological-opin.ions-available-pnblic-cotn.ment-and-links-final-opin.ions.
155 https://www.epa.gov/newsreleases/epa-aiinoniices-endangered-species-act-protectlon-policv-new-pesticides.
156 httesiAW
157 https://www.epa.gov/svstem/files/docnments/2022-ll/esa-workplan-npdate.pdf.
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Appendix D: Endocrine Disruptor Screening Program
As required by FIFRA and FFDCA, EPA reviews numerous studies to assess potential adverse
outcomes from exposure to chemicals. Collectively, these studies include acute, sub-chronic and
chronic toxicity, including assessments of carcinogenicity, neurotoxicity, developmental,
reproductive, and general or systemic toxicity. These studies include endpoints which may be
susceptible to endocrine influence, including effects on endocrine target organ histopathology,
organ weights, estrus cyclicity, sexual maturation, fertility, pregnancy rates, reproductive loss,
and sex ratios in offspring. For ecological hazard assessments, EPA evaluates acute tests and
chronic studies that assess growth, developmental and reproductive effects in different
taxonomic groups. As part of its most recent registration decision for EtO, the EPA reviewed
these data and selected the most sensitive endpoints for relevant risk assessment scenarios from
the existing hazard database. However, as required by FFDCA §408(p), EtO is subject to the
endocrine screening part of the Endocrine Disruptor Screening Program (EDSP).
EPA has developed the EDSP to determine whether certain substances (including pesticide
active and other ingredients) may have an effect in humans or wildlife similar to an effect
produced by a "naturally occurring estrogen, or other such endocrine effects as the Administrator
may designate." The EDSP employs a two-tiered approach to making the statutorily required
determinations. Tier 1 consists of a battery of 11 screening assays to identify the potential of a
chemical substance to interact with the estrogen, androgen, or thyroid (E, A, or T) hormonal
systems. Chemicals that go through Tier 1 screening and are found to have the potential to
interact with E, A, or T hormonal systems will proceed to the next stage of the EDSP where EPA
will determine which, if any, of the Tier 2 tests are necessary based on the available data. Tier 2
testing is designed to identify any adverse endocrine-related effects caused by the substance, and
establish a dose-response relationship between the dose and the E, A, or T effect.
Under FFDCA § 408(p), the Agency must screen all pesticide chemicals. Between October 2009
and February 2010, EPA issued test orders/data call-ins for the first group of 67 chemicals,
which contains 58 pesticide active ingredients and 9 inert ingredients. The Agency has reviewed
all of the assay data received for the List 1158 chemicals and the conclusions of those reviews are
available in the chemical-specific public dockets. A second list of chemicals identified for EDSP
screening was published on June 14, 2013,159 and includes some pesticides scheduled for
Registration Review and chemicals found in water. Neither of these lists should be construed as a
list of known or likely endocrine disruptors. EtO is not on either list. For further information on
the status of the EDSP, the policies and procedures, the lists of chemicals, future lists, the test
guidelines and the Tier 1 screening battery, visit the EPA website.160
EPA's EDSP is actively pursuing the application of new approach methods (NAMs) to create a
more efficient and robust screening program. In October 2020, EPA underwent a reorganization
and the EDSP was moved to the Office of Pesticide Programs. This reorganization provides
158 See https://www.regulations.gov/document/EPA-HO-OPPT-2004-0109-008Q for the Final First List of
Chemicals for Tier 1 Screening in the EDSP.
159 See https://www.regiilations.gov/docnment/EPA-HO-OPPT-2()()9-()477-()()74 for the Final Second List of
Chemicals for Tier 1 Screening in the EDSP.
160 https://www.epa.gov/endocrine-dismption.
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better alignment of the EDSP with the procedures and methods used by the program offices. On
July 28, 2021, the Office of Inspector General (OIG) released its new report on the EDSP and
made ten recommendations. EPA looks forward to working with stakeholders and the scientific
community to accelerate the implementation of this important program into pesticide risk
assessments and decision making.
In this PID, EPA is making no human health or environmental safety findings associated with the
EDSP screening of EtO. Before completing this registration review, the Agency will make an
EDSP FFDCA §408(p) determination.
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Appendix E: Summary of Public Comments on the Draft Risk
Assessments and Agency Responses
During the 60-day public-comment period for the EtO Draft Risk Assessment (November 20,
2020 to January 19, 2021), the Agency received 15 public comments from 10 commenters. After
the DRA public comment period closed, the Agency received additional information from the
Ethylene Oxide Task Force and the American Chemistry Council that was considered in the risk
assessment phase of registration review. Comments were submitted by representatives from
government, non-profit groups, and industry as summarized below:
• United States Department of Agriculture (USD A)
• Harris County, Texas
• Earthjustice, on behalf of Air Alliance Houston et al.
• University of California, San Francisco (UCSF) et al.
• North Carolina State University
• Louisiana Chemical Association (LCA)
• The Ethylene Oxide Sterilization Association (EOSA)
• Ethylene Oxide Task Force (EOTF)
• The American Chemistry Council (ACC)
• Elite Spice, Inc.
The Agency has summarized and responded to all substantive comments and comments of a
broader regulatory nature below and in the Response to Public Comments for the Ethylene Oxide
(EtO) Draft Risk Assessment (DRA). The Agency thanks all commenters for participating and has
considered all comments in developing this PID.161
Extension Requests on Public Comment Period
Comment: EPA received requests to extend the DRA public comment period by 60 days from
the American Chemistry Council (ACC), the Ethylene Oxide Task Force (EOTF), Earthjustice,
the Ethylene Oxide Sterilization Association (EOSA), Elite Spice, and the Harris County
Environmental Division.162
EPA Response: The request for extension was denied for all parties, as EPA plans to move
toward mitigation for EtO as efficiently as possible. However, OPP informed all requestors that
comments submitted after the close of the official comment period may be considered at any
point during the registration review of EtO.
Industry's Information Submitted Outside the Public Comment Period
161 Response to Public Comments for the Ethylene Oxide (EtO) Draft Risk Assessment (DRA). Decision Number:
569904. EPA-HQ-OPP-2013-0244.
162 See comments EPA-HQ-OPP-2013-0244-0024, EPA-HQ-OPP-2013-0244-0025, EPA-HQ-OPP-2013-0244-
0026, EPA-HQ-OPP-2013-0244-0027, and EPA-HQ-OPP-2013-0244-0033 in EtO docket EPA-HQ-OPP-2013-
0244 at www.regnlations.gov.
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Comment: The Ethylene Oxide Task Force (EOTF) notified the Agency that they intended to
provide further input on the EtO DRA after the close of the public comment period, and EOTF
provided this further input on March 19, 2021. The submission included information on new
publications and new analyses on key points of the risk assessment. The Agency received several
comments from other industry groups supporting EOTF's plan to submit more detailed
comments on the EtO DRA, including the American Chemistry Council (ACC), Elite Spice,
Louisiana Chemical Association, and the Ethylene Oxide Sterilization Association (EOSA).163
EPA Response: The Agency thanks EOTF and ACC for their supplemental submission on
March 19, 2021. However, the comments have been considered and were determined to be
similar to comments received from the TCEQ and the LCA and are addressed in the EPA's
responses to those commenters.
Request to Make Publicly Available the Exponent White Paper and Slide Presentation
Comment: Earthjustice et al., LCA, and the University of California's San Francisco Program
on Reproductive Health and the Environment urged EPA to make publicly available the
Exponent White Paper, Cancer Risk Estimates for Ethylene Oxide Based on Epidemiological and
Biological Weight-of-Evidence, which was cited in the EtO DRA. Earthjustice et al. also
requested Exponent's slide presentation to the Agency on June 16 and 18, 2020 be made publicly
available.164
EPA Response: EPA has made available the Exponent White Paper, Cancer Risk Estimates for
Ethylene Oxide Based on Epidemiological and Biological Weight-of-Evidence. This document
can be found at www.regulations.gov in EtO docket EPA-HQ-OPP-2013-0244 under document
ID EPA-HQ-QPP-20.1.3-0244-0042. Exponent's slide presentation to the Agency on June 16 and
18, 2020 can be found at www.regulations.gov in EtO docket EPA-HQ-OPP-2013-0244 under
document ID EPA-HQ-QPP-20.1.3 -0244-0029.
Request to Make Publicly Available EOTF's Mitigation Proposal from February 2020
Comment: The Louisiana Chemical Association (LCA) stated that the Draft Risk Assessment
states that further mitigation of EtO exposure is required and that detailed mitigation will be
proposed in the forthcoming Proposed Interim Decision. A mitigation proposal submitted by the
EOTF to OPP in February 2020 is cited, but the proposal is not available in the docket for
review.
EPA Response: The initial mitigation proposal submitted by the Ethylene Oxide Task Force
(EOTF) in February 2020 was a preliminary draft and was shared with EPA to show industry's
on-going efforts in examining possible mitigation methods. Discussions with EOTF since
February 2020 have refined this mitigation plan. EPA would like to minimize public confusion
by not posting draft information in the public docket in advance of the PID, as these documents
163 See comments EPA-HQ-OPP-2013-0244-0031, EPA-HQ-OPP-2013-0244-0034, EPA-HQ-OPP-2013-0244-
0035, EPA-HQ-OPP-2013-0244-0036, and EPA-HQ-OPP-2013-0244-0037 at www.regnlations.gov.
164 See comments EPA-HQ-OPP-2013-0244-0027, EPA-HQ-OPP-2013 -0244-003 8, and EPA-HQ-OPP-2013-0244-
0039 at www.regiilatlons.gov.
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are not fully reflective of OPP's final mitigation plans. All documentation of mitigation
discussions will be made available upon publication of the PID. LCA and all public stakeholders
will have the opportunity to review and comment on any mitigation proposal for EtO during the
public comment period of the Proposed Interim Decision (PID). These public comments will be
taken into consideration before the Agency finalizes the mitigation for EtO.
Environmental Justice
Comment: Earthjustice et al. expressed concern over environmental justice issues for
communities located in the surrounding areas of EtO sterilization facilities. Earthjustice et al.
stated that, "the people facing health threats from ethylene oxide are disproportionately
communities of color and low-income, and the National Environmental Justice Advisory Council
has urged EPA to protect public health by following the best available science on this chemical,"
citing the May 3, 2019 letter from the National Environmental Justice Advisory Council to
former EPA Administrator, Andrew Wheeler. 165>166
EPA Response: OPP recognizes that there are certain EtO commercial sterilization facilities
that impact communities with environmental justice concerns. OPP is collaborating with EPA's
Office of Air and Radiation (OAR) in their ongoing efforts to address environmental justice
concerns for EtO. Mitigation measures to address environmental justice by OAR in their EtO
Commercial Sterilizers Rulemaking are included in OPP's registration review on EtO. See
Section V.B. of this document for detailed information on how OPP will address environmental
justice concerns for EtO.
Request to Reevaluate the Need for Mitigation
Comment: The Louisiana Chemical Association (LCA) requested that OPP reevaluate the need
for mitigation after the consideration of public comments on the DRA.167
EPA Response: EtO is a known human carcinogen. Based on the cancer inhalation unit risks
from assessments published by EPA's Office of Research and Development Integrated Risk
Information System (ORD/IRIS), EPA has identified risks of concern to workers and residential
and non-residential bystanders, and mitigation of EtO inhalation exposure is required to address
those concerns. These measures are intended to mitigate risks to both workers within EtO
sterilization facilities, as well as the communities surrounding the EtO sterilization facilities.
Detailed mitigation can be found in Section V.A. of this document and are available for 60-day
public comment upon publication of this PID.
FIFRA and FFDCA Standards
Comment: Earthjustice et al. stated that EPA must assess the health risks presented by EtO's
pesticide uses and ensure they meet the FFDCA and FIFRA standards.168
165 https://www.epa.gov/environinentalinstice/neiac-letter-regarding-ethvlene-oxide.
166 See comment EPA-HQ-OPP-2013-0244-0027 at www.regnlations.gov.
167 See comment EPA-HQ-OPP-2013-0244-0035 at www.regnlations.gov.
168 See comment EPA-HQ-OPP-2013-0244-0038 at www.regnlations.gov.
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EPA Response: The Agency agrees with Earthjustice's statement. The 2020 DRA and 2023
DRA addendum assessed human health risk. EPA did not identify dietary risks of concern. EPA
identified inhalation cancer risks of concern and is proposing that EtO does not meet the standard
for registration under FIFRA without the implementation of mitigation measures sufficient to
address these risks, as described in this PID.
Incompleteness of the 2020 DRA
Comment: The Louisiana Chemical Association (LCA) stated that certain components of the
DRA were not completed at the time the document was released for public comment,
specifically, the non-occupational bystander inhalation exposure and environmental justice
evaluations, and the common mechanism of toxicity finding. LCA asserted that no final risk
assessment should be issued until the public has adequate opportunity for review and comment
of these components.169
EPA Response: OPP is publishing a DRA Addendum with this PID, which characterizes risks
to workers and non-residential bystanders based on the EPA IRIS value for EtO. OAR's
proposed NESHAP rule will address non-occupational bystander risks and will include an
environmental justice evaluation. There will be a public comment period for this proposed rule.
Additionally, OPP's PID includes an environmental justice evaluation (Section V.B), and a
common mechanism of toxicity finding (Section III. A) and is subject to a public comment
period.
Beekeeping Equipment Use
Comment: USDA170 and North Carolina State University (NCSU) submitted comments
detailing the use and benefits of EtO for disinfecting beekeeping equipment contaminated with
the honeybee pathogen, Paenibacillus larvae (the causative agent in American foulbrood), and
other bee pathogens. NCSU stated that beekeeping and the associated pollination services add
significantly to the agricultural production of North Carolina, and they consider EtO to be
essential to maintaining a healthy beekeeping industry. NCSU noted that alternative control
measures, such as burning or boiling equipment in lye, are more expensive and present higher
risks to beekeepers. NCSU requested renewal of the EtO product registered for the beekeeping
equipment use.
EPA Response: EPA thanks USDA and NCSU for their comments and has taken them into
consideration in this PID and in the document Ethylene Oxide (PC# 042301): Use, Usage,
Benefits, and Impacts of Cancellation (December 1, 2022). The anticipated occupational
inhalation cancer risk posed by the use of EtO on beekeeping equipment in NC is higher than the
Agency's threshold for occupational risk (1 x 10"4) and the Agency has determined that the
benefits of the use do not outweigh that risk. Therefore, the Agency has determined that the use
169 See comment EPA-HQ-OPP-2013-0244-0035 at www.regnlations.gov.
170 See comment EPA-HQ-OPP-2013-0244-0030 at www.regnlations.gov.
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of EtO for disinfecting beekeeping equipment does not meet the FIFRA standard and proposes
that the use be terminated.
Use of EtO on Spices
Comment: USDA and Elite Spice, Inc.171 submitted comments on the spice use of EtO. USDA
submitted comments regarding the value of EtO in ensuring food safety. They stated that EtO is
used to fumigate both domestically produced and imported spices for the purpose of eliminating
pathogenic microbial contaminants such as Salmonella and E. coli that pose serious risks to
human health.
USDA also commented on the human health risk assessment and ecological risk assessments. In
their comments on the human health risk assessment, USDA discussed the approach taken in the
dietary, aggregate, bystander, and occupational analyses and generally agreed with the
assumptions used in them. Similarly, USDA commented on the ecological risk assessment, and
confirmed label information and the process used for treating spices. USDA stated that existing
label mitigations make exposure to non-target organisms unlikely. USDA also noted that they
would be willing to facilitate additional outreach to agricultural stakeholders on the feasibility
and practicality of any mitigation measures currently under consideration by EPA to address
human health or ecological risks.
Elite Spice, Inc. provided comments on the benefits of EtO. They noted that EtO products are
critically important to the U.S. food industry, including spice and seasoning manufacturers, to
mitigate pathogen contamination. They further noted that there are a limited number of
acceptable and effective treatment methods to address this serious food safety concern.
In addition, Elite Spice, Inc. stated that they support the comments submitted by the EOTF and
urged EPA to carefully consider those comments and revise the DRA and PID in accordance
with them. They requested that EPA continue to permit the use of EtO for the treatment of spices
and to ensure any new emissions control requirements are not overly burdensome.
EPA Response: EPA thanks USDA and Elite Spice for their comments and has taken them into
consideration in this PID and in the documents Ethylene Oxide (PC# 042301): Use, Usage,
Benefits, and Impacts of Cancellation and Response to Public Comments for the Ethylene Oxide
(EtO) Draft Risk Assessment (DRA) (December 1, 2022, and March 27, 2023, respectively).
The Agency agrees that the use of EtO for fumigating certain dried herbs and spices is important
for pathogen control and that alternatives to EtO may not be viable for every spice, spice form,
spice blend, target pathogen, or consumer market. Despite these limitations, due to the inhalation
cancer risk estimates associated with the use of EtO, EPA still seeks to identify alternatives to
EtO spice treatments as well as specific spices where EtO use is critical for food safety. The
Agency is soliciting comments on the specific commodities for which there is current critical use
of EtO and for which there are no current viable alternatives to EtO (e.g., heat, steam, irradiation,
or propylene oxide cannot be used for pathogen control on a particular spice, spice form, or spice
171 See comment EPA-HQ-OPP-2013-0244-0034 at www.regnlations.gov.
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blend). Any commodities without documented support for continued treatment with EtO will be
considered for a phased-out cancellation.
The Agency disagrees with the points raised by EOTF in their comments. Since the publication
of the 2020 DRA, and in contexts other than the registration review of EtO, EPA has continued
to consider the best approach for characterizing the cancer risk associated with inhalation
exposure to EtO. While there are some uncertainties associated with all of the approaches in
characterizing the cancer risk (as discussed in the 2020 DRA), the EPA has determined that the
2016 IRIS assessment should be used to characterize the cancer risk associated with inhalation
exposure to EtO.
As for new emissions control requirements, those requirements are under the purview of EPA's
Office of Air and Radiation and are included in their proposed rulemaking on commercial EtO
sterilizers under Section 112 of the Clean Air Act (CAA). See public docket EPA-HQ-OAR-
2019-0178 at www.reeulatioms.gov for details.
EPA's Use of Industry Analysis
Comment: Earthjustice et al. and the University of California San Francisco Program on
Reproductive Health and the Environment expressed concern that EPA should not be citing
assessments conducted by industry for the Agency's risk assessment. Earthjustice et al. stated,
"OPP treats ethylene oxide's cancer risk level as an open question, presenting EPA's own 2016
IRIS cancer risk value alongside competing values calculated by the Texas Commission on
Environmental Quality (TCEQ) and an industry consulting firm that are up to 3,500 times less
protective. [...] OPP cannot now equate EPA's 2016 IRIS value with the industry-supported
analyses that fail to follow same rigor as the IRIS external peer-review process."172 The
University of California San Francisco Program on Reproductive Health and the Environment
stated that the DRA "presents multiple approaches for cancer risk estimation without critical
analysis, treating them as if they are equally valid, which they are not. [...] The TCEQ and
EOTF assessments do not reflect any new data or hypotheses that were not available to the
Office of Research and Development's Integrated Risk Information System (ORD/IRIS) or the
Science Advisory Board (SAB) at the time of its 2016 assessment, merely analyses and
approaches that were rejected by ORD/IRIS and the SAB."173
EPA Response: Since the publication of the 2020 DRA, and in contexts other than the
registration review of EtO, EPA has continued to consider the best approach for characterizing
the cancer risk associated with inhalation exposure to EtO. While there are some uncertainties
associated with all of the approaches in characterizing the cancer risk (as discussed in the 2020
DRA), the EPA has determined that the 2016 IRIS assessment should be used to characterize the
cancer risk associated with inhalation exposure to EtO. Therefore, OPP is publishing a DRA
Addendum with this PID, which quantifies risks posed by EtO using EPA's ORD/IRIS 2016
IUR value.
172 See comment EPA-HQ-OPP-2013-0244-0038 at www.regnlations.gov.
173 See comment EPA-HQ-OPP-2013-0244-0039 at www.regnlations.gov.
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Appendix F: Explanation of Office of Air and Radiation and Office of
Pesticide Programs Cancer Risk Thresholds
EPA Clean Air Act (CAA) Residual Risk Evaluations
Section 112 of the Clean Air Act (CAA) instructs EPA to regulate hazardous air pollutants (also
known as "air toxics") by setting limits on the amount of pollution that industrial sources can
emit to the air, rather than by setting ambient standards, which are limits on the amount of a
pollutant that is allowed in the outdoor air. CAA section 112 establishes a two-stage regulatory
process for setting emission standards for hazardous air pollutants (HAP). The first stage
involves EPA establishing technology-based standards, either maximum achievable control
technology (MACT) emission standards or generally available control technology standards
(GACT). The second stage involves EPA evaluating these standards to determine whether
additional requirements are needed to address any remaining risk associated with HAP
emissions. This second stage is referred to as the "residual risk review."
EPA conducts residual risk reviews for sources of HAP in each industrial source category (e.g.,
Petroleum Refineries, Taconite Iron Ore Facilities, Aerospace Manufacturing Facilities, etc.)
subject to MACT standards in order to address any remaining or "residual" risk from HAP
emissions. Specifically, section 112(f)(2) of the CAA requires the EPA to determine whether
promulgation of additional standards or revised standards is needed for a source category to
provide an ample margin of safety to protect public health or to prevent an adverse
environmental effect.
The approach incorporated into the CAA and used by the EPA to evaluate residual risk and to
develop standards under CAA section 112(f)(2) is a peer-reviewed two-step approach.174'175 In
the first step, the EPA determines whether risks are acceptable. This determination "considers
all health information, including risk estimation uncertainty, and includes a presumptive limit on
maximum individual lifetime [cancer] risk (MIR) 1 of approximately 1 in 10 thousand." (54 FR
38045, September 14, 1989). If risks are unacceptable, the EPA must determine the emissions
standards necessary to reduce risk to an acceptable level without considering costs.
In the second step of the residual risk approach, the EPA considers whether the emissions
standards provide an ample margin of safety to protect public health "in consideration of all
health information, including the number of persons at risk levels higher than approximately 1 in
1 million, as well as other relevant factors, including costs and economic impacts, technological
feasibility, and other factors relevant to each particular decision." Id. The EPA must promulgate
emission standards necessary to provide an ample margin of safety to protect public health or
determine that the standards being reviewed provide an ample margin of safety without any
revisions. After conducting the ample margin of safety analysis, we consider whether a more
174 U.S. EPA. Risk and Technology Review (RTR) Risk Assessment Methodologies: For Review by the EPA's
Science Advisory Board with Case Studies - MACT I Petroleum Refining Sources and Portland Cement
Manufacturing, June 2009. EPA-452/R-09-006. https://www 3. epa. gov/airtoxics/rrisk/rtrpg. html.
175 Recommendations of the SAB Risk and Technology Review Methods Panel are provided in their report, which is
available at: http$://yo$emitexpa.gaw/$ab/$abproducLnsf/4AB3966E263D943A8525771F00668381/$File/EPA-SAB~
10-007-unsigned.pdf.
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stringent standard is necessary to prevent, taking into consideration costs, energy, safety, and
other relevant factors, an adverse environmental effect.
The EPA conducts a risk assessment that includes estimates of:
• Maximum individual cancer risk (MIR) posed by the HAP emissions from each source
in the source category at residential locations.
• Hazard index (HI) for chronic exposures to HAP with potential to cause chronic (or
long-term) noncancer health effects at residential locations, and
• Hazard quotient (HQ) for acute exposures to HAP with the potential to cause noncancer
health effects off-site and at locations that may be accessible to the public (e.g.,
roadways and public buildings).
The MIR is defined as the cancer risk associated with a lifetime of exposure (i.e., 70 years) at the
highest concentration of HAP where people are likely to live (i.e., residential locations). The HQ
is the ratio of the potential exposure to the HAP to the level at or below which no adverse effects
are expected; the HI is the sum of HQs for HAP that affect the same target organ or organ
system. The risk assessment also provides estimates of the distribution of cancer risks within the
exposed populations, cancer incidence and an evaluation of the potential for adverse
environmental effects.
Federal Insecticide, Fungicide, Rodenticide Act (FIFRA) Risk Assessment
For OPP, the level of concern, for a given endpoint, refers to a predetermined quantified level
above which OPP believes more detailed consideration of the risks of a pesticide is necessary.
When it appears that the use of a pesticide may pose risks greater than the level of concern, OPP
will first attempt to refine its risk assessment to obtain a more accurate characterization of the
risk. If the level of concern is still exceeded, OPP will consider a variety of measures for
reducing the risk to a level at or below the level of concern. In general, OPP will use a tiered
approach to reduce risks starting with the quickest and least expensive means. This may be
accomplished through discussions with registrants who voluntarily agree to risk reduction
measures; through required risk reduction in a Reregi strati on Eligibility Decision document or
Interim or Final Registration Review Decision document; or other means. If OPP believes that
these actions will not result in sufficient risk reduction, it may initiate a special review or take
regulatory action under FIFRA.
OPP considers dietary and non-dietary cancer risks of 10"6 and less to be negligible, and thus it
would not typically pursue risk reduction measures for such negligible risks. OPP does not allow
dietary risks to exceed 10"6, or non-dietary risks to exceed 10"4, except in those cases where it has
determined that benefits exceed the risks. OPP examines non-dietary risks in the 10"5 to 10"4
range to determine whether the benefits of use outweigh the risks and will seek ways to mitigate
unacceptable risks. OPP's policy allows for the consideration of a wide range of factors in
making a risk management decision for non-dietary risks. These factors may include: risk to
individuals, number of people exposed, weight of scientific evidence regarding carcinogenicity,
lower risk alternatives, and benefits associated with the pesticide under review. In general, OPP
tolerates less risk to individuals as the size of the exposed population increases. Therefore, for
the largest exposed populations, including residents and pesticide handlers, OPP seeks to reduce
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the individual risks to the greatest extent feasible, preferably to 10"6 or less. The goal is to ensure
that there is a minimum level of protection from exposure to pesticides for workers, residents,
bystanders and vulnerable populations, particularly children. OPP strives to ensure that this
policy is consistently applied to all pesticide program decisions.
Risks greater than 10~4. It is OPP's intent, generally, not to grant new registrations or allow the
continued registrations of existing uses which have non-dietary cancer risks greater than 10"4
(e.g., 10"3), because such risks, based on the program's experience, typically outweigh benefits
and thus will cause unreasonable adverse effects.176 If risk reduction measures do not reduce the
risk below the level of concern, OPP may initiate Special Review or take regulatory action under
FIFRA. As is the case for EtO, OPP recognizes there may be currently registered high risk uses
which are very beneficial and have no currently registered alternatives.
Risks Between 10~6 and 10~4. OPP evaluates pesticides with risks in this range and seeks ways to
reduce individual cancer risks to the greatest extent feasible, preferably to 10"6 or less. OPP will
require, as appropriate, additional protective clothing or equipment or changes in application
methods, taking benefits into account, through the reevaluation and registration processes, as
follows:
Applications for new registrations. In considering applications for new registrations with
non-dietary cancer risks, OPP carefully examines those uses with potential risks in the
10"6 to 10"4 range to seek ways of reducing those risks before registration occurs. Also,
OPP recognizes there may be currently registered high risk uses which are very beneficial
and have no currently registered alternatives. In such a case, under its Reduced Risk
Policy, OPP encourages the submission of applications for pesticides which offer a
reduced-risk alternative, and will give priority consideration to the review of such
applications. The registration of such a reduced-risk alternative pesticide might affect the
risk/benefit balance for the currently registered higher-risk chemical, allowing OPP to
achieve greater risk reduction.
Reregistration and Registration Review. For those chemicals subject to reregi strati on and
registration review, OPP carefully examines those uses with estimated risks in the 10"6 to
10"4 range to seek ways of cost-effectively reducing risks.
Ongoing examination of chemicals through reevaluation. OPP monitors registered
pesticides with risks greater than 10"6 to look for opportunities to reduce risks further,
including requiring technology changes and changes in application methods. For
example, advances in technology have had a major effect on reducing exposure to
pesticide handlers. Examples include: closed-loading systems, enclosed cabs offering
respiratory protection, containers which limit spilling, and water soluble packaging. OPP
encourages these technological improvements as they become available and requires
them in appropriate cases.
176 For EtO, the benefits are considered to exceed the risks for medical device sterilization and spice fumigation. See
Section III.C for a full description on EtO benefits.
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Risks Below 10~6. Generally, OPP does not seek risk reduction below this level unless it is cost-
effective. 177
177 Memorandum, 1996. Non-Dietary Cancer Risk Policy. Daniel M. Barolo, Director Office of Pesticide Programs.
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