[Federal Register Volume 87, Number 90 (Tuesday, May 10, 2022)]
[Proposed Rules]
[Pages 27961-27971]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2022-09708]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

42 CFR Part 88

[Docket No. CDC-2022-0052; NIOSH-347]
RIN 0920-AA82


World Trade Center (WTC) Health Program; Addition of Uterine 
Cancer to the List of WTC-Related Health Conditions

AGENCY: Centers for Disease Control and Prevention (CDC), Department of 
Health and Human Services (HHS).

ACTION: Notice of proposed rulemaking.

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SUMMARY: Title I of the James Zadroga 9/11 Health and Compensation Act 
of 2010 amended the Public Health Service Act (PHS Act) to establish 
the World Trade Center (WTC) Health Program. The WTC Health Program 
(Program), which is administered by the Director of the National 
Institute for Occupational Safety and Health (NIOSH), within CDC, 
provides medical monitoring and treatment to eligible responders to the 
September 11, 2001, terrorist attacks in New York City, at the 
Pentagon, and in Shanksville, Pennsylvania, and to eligible survivors 
of the New York City attacks. In accordance with the WTC Health 
Program's regulations, which establish procedures for adding a new 
condition to the list of health conditions covered by the Program, this 
proposed rule would add malignant neoplasms of corpus uteri and uterus, 
part unspecified (uterine cancer) to the List of WTC-Related Health 
Conditions (List).

DATES: Comments must be received by June 24, 2022.

ADDRESSES: You may submit comments identified by Docket No. CDC-2022-
0052 and NIOSH-347 by either of the following methods:
     Federal eRulemaking Portal: https://www.regulations.gov. 
Follow the instructions for submitting comments.
     Mail: NIOSH Docket Office, Robert A. Taft Laboratories, MS 
C-34, 1090 Tusculum Avenue, Cincinnati, Ohio 45226-1998.
    Instructions: All written submissions received in response to this 
document must include the agency name and docket number (CDC-2022-0052; 
NIOSH-347) for this action. All relevant comments, including any 
personal information provided, will be posted without change to https://www.regulations.gov. Do not submit comments by email. CDC does not 
accept comments by email.

FOR FURTHER INFORMATION CONTACT: Rachel Weiss, Program Analyst, 
National Institute for Occupational Safety and Health, 1090 Tusculum 
Avenue, MS: C-46, Cincinnati, OH 45226; telephone (855) 818-1629 (this 
is a toll-free number); email [email protected].

SUPPLEMENTARY INFORMATION:

Table of Contents

I. Executive Summary
    A. Purpose of Regulatory Action
    B. Summary of Major Provisions
    C. Costs and Benefits
II. Public Participation
III. Background
    A. WTC Health Program Statutory Authority
    B. Methods Used by the Administrator To Determine Whether To Add 
Cancers to the List of WTC-Related Health Conditions
    C. History and Scope of Rulemaking
    D. Review of Evidence Supporting the Proposed Addition of 
Uterine Cancer to the List of WTC-Related Health Conditions
    E. Administrator's Decision Regarding Uterine Cancer
IV. Summary of Proposed Rule
V. Required Regulatory Analyses
    A. Executive Orders 12866 and 13563
    B. Regulatory Flexibility Act
    C. Paperwork Reduction Act
    D. Small Business Regulatory Enforcement Fairness Act
    E. Unfunded Mandates Reform Act of 1995
    F. Executive Order 12988 (Civil Justice)
    G. Executive Order 13132 (Federalism)
    H. Executive Order 13045 (Protection of Children From 
Environmental Health Risks and Safety Risks)
    I. Executive Order 13211 (Actions Concerning Regulations That 
Significantly Affect Energy Supply, Distribution, or Use)
    J. Plain Writing Act of 2010

I. Executive Summary

A. Purpose of Regulatory Action

    With this rulemaking, the Administrator of the WTC Health Program 
(Administrator) and the Secretary of HHS propose the addition of 
uterine cancer \1\ to the List. The Administrator received requests 
from WTC responders and survivors as well as a September 2020 letter 
from five of the WTC Health Program Clinical Centers of Excellence 
(CCEs) asking the Administrator to add ``uterine cancer'' to the List. 
The Administrator subsequently directed the WTC Health Program's 
Science Team to review the available scientific evidence for adding 
uterine cancer to the List under existing Program policy and 
procedures. A white paper issued by the Program's Science Team in 
September 2021 (White Paper) found that the available scientific 
evidence provided sufficient support to add uterine cancer to the List 
but only for Program members who have a certified WTC-related estrogen-
secreting tumor. The Administrator asked the WTC Health Program 
Scientific/Technical Advisory Committee (STAC) for a recommendation on 
whether a reasonable basis exists for adding uterine cancer to the 
List. Between September and November 2021, the STAC reviewed the White 
Paper and other available scientific information, considered public 
comment, and deliberated on whether there is a reasonable basis to 
recommend the addition of uterine cancer to the List. Ultimately, the 
STAC recommended that uterine cancer be added to the List and provided 
the Administrator its recommendation and rationale. Upon review, the 
Administrator decided that the STAC provided a reasonable basis for its 
recommendation to add uterine cancer to the List. Based on the STAC's 
recommendation and the scientific literature, including the White 
Paper, the Administrator has determined that the available information 
provides a sufficient evidentiary basis to propose the addition of 
uterine cancer to the List.
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    \1\ For the purposes of this action, the WTC Health Program 
defines the term ``uterine cancer'' as ICD-10 code C54, including 
the following specific malignant neoplasms: Isthmus uteri (C54.0), 
endometrium (C54.1), myometrium (C54.2), fundus uteri (C54.3), 
overlapping sites of corpus uteri (C54.8), and corpus uteri, 
unspecified (C54.9); and ICD-10 code C55, including only a single 
sub-category, malignant neoplasm of uterus, part unspecified.
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B. Summary of Major Provisions

    This rule proposes the addition of malignant neoplasms of corpus 
uteri and uterus, part unspecified (uterine cancer) to the List of WTC-
Related Health Conditions in 42 CFR 88.15(d).

C. Costs and Benefits

    The addition of uterine cancer to the List through this rulemaking 
is estimated to cost the WTC Health Program from $1,718,691 to 
$2,199,808 annually, between 2022 and 2025. All of the costs to the WTC 
Health Program are transfers.\2\ Benefits to current and future

[[Page 27962]]

WTC Health Program members are expected to include improved access to 
care and better treatment outcomes than members would have in the 
absence of Program coverage.
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    \2\ Due to the implementation of the Affordable Care Act in 
2014, and as required under the authorizing statute for the WTC 
Health Program, all current and future Program members are assumed 
to have or have access to medical insurance coverage other than 
through the WTC Health Program; therefore, all projected treatment 
costs to be paid by the WTC Health Program are considered transfers.
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II. Public Participation

    Interested persons or organizations are invited to participate in 
this rulemaking by submitting written views, opinions, recommendations, 
and data. Comments received, including attachments and other supporting 
materials, are part of the public record and subject to public 
disclosure. Comments are invited on any topic related to this proposed 
rule. Do not include any information in your comment or supporting 
materials that you consider confidential or inappropriate for public 
disclosure.
    Comments submitted electronically or by mail should be titled 
``Docket No. CDC-2022-0052; NIOSH-347'' and should identify the 
author(s) and contact information in case clarification is needed. 
Written comments can be submitted to the address provided in the 
ADDRESSES section, above. All communications received on or before the 
closing date for comments will be fully considered by the 
Administrator.
    Upon publication of this notice of proposed rulemaking, the 
Administrator has requested an independent peer review from three 
subject-matter experts of the scientific and technical evidence that 
comprises the basis of this action.\3\ The peer reviews will be posted, 
without attribution, in the rulemaking docket 30 days after the 
publication of this proposed rulemaking.
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    \3\ See Public Health Service Act, sec. 3312(a)(6)(F).
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    To provide interested parties adequate time to review the proposed 
rule, supporting scientific literature, and peer reviews, and to submit 
written comments to the docket, the Administrator has determined that 
good cause exists to extend the 30-day comment period required by the 
Program's authorizing statute \4\ to 45 days.
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    \4\ See Public Health Service Act, sec. 3312(a)(6)(D)(ii).
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III. Background

    In this action, the Administrator and the Secretary of HHS propose 
to amend 42 CFR 88.15 to add malignant neoplasms of corpus uteri and 
uterus, part unspecified (uterine cancer) \5\ to the List.
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    \5\ See supra note 1.
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A. WTC Health Program Statutory Authority

    Title I of the James Zadroga 9/11 Health and Compensation Act of 
2010 (Pub. L. 111-347, as amended by Pub. L. 114-113 and Pub. L. 116-
59), added Title XXXIII to the PHS Act \6\ establishing the WTC Health 
Program within HHS. The WTC Health Program provides medical monitoring 
and treatment benefits to eligible firefighters and related personnel, 
law enforcement officers, and rescue, recovery, and cleanup workers who 
responded to the September 11, 2001, terrorist attacks in New York 
City, at the Pentagon, and in Shanksville, Pennsylvania (responders), 
and to eligible persons who were present in the dust or dust cloud on 
September 11, 2001 or who worked, resided, or attended school, 
childcare, or adult daycare in the New York City disaster area 
(survivors).
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    \6\ Title XXXIII of the PHS Act is codified at 42 U.S.C. 300mm 
to 300mm-61. Those portions of the Zadroga Act found in Titles II 
and III of Public Law 111-347 do not pertain to the WTC Health 
Program and are codified elsewhere.
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    All references to the Administrator in this document mean the 
Director of NIOSH, within CDC, or his or her designee. Section 
3312(a)(6) of the PHS Act requires the Administrator to conduct 
rulemaking to propose the addition of a health condition to the List 
codified in 42 CFR 88.15.

B. Methods Used by the Administrator To Determine Whether To Add 
Cancers to the List of WTC-Related Health Conditions

    In accordance with the Program's authorizing statute as well as 
regulations in 42 CFR part 88, the Administrator may decide to propose 
the addition of a health condition to the List in response to a 
petition from an interested party \7\ or at his or her own 
discretion.\8\ Under 42 CFR 88.16, the Administrator has established a 
process by which health conditions may be considered for addition to 
the List in Sec.  88.15. Pursuant to sec. 3312(a)(6)(D) of the PHS Act, 
whenever the Administrator determines that a condition should be 
proposed for addition to the List, the Administrator is required to 
publish a notice of proposed rulemaking and allow interested parties to 
comment on the proposed rule.
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    \7\ PHS Act, sec. 3312(a)(6)(B); 42 CFR 88.16(a).
    \8\ PHS Act, sec. 3312(a)(6)(A); 42 CFR 88.16(b).
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    The Program also developed the Policy and Procedures for Adding 
Types of Cancer to the List of WTC-Related Health Conditions (Policy 
and Procedures) to describe the evaluation of evidence of a causal 
association between 9/11 exposures and a type of cancer. Pursuant to 
these procedures, a type of cancer may be proposed for addition to the 
List if the available evidence meets at least one of the following four 
methods: \9\
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    \9\ John Howard, Administrator of the WTC Health Program, Policy 
and Procedures for Adding Types of Cancer Conditions to the List of 
WTC-Related Health Conditions, revised Nov. 18, 2021, https://www.cdc.gov/wtc/pdfs/policies/WTCHP_PP_Addn_Cancer_11182021-508.pdf.
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    Method 1. Epidemiologic Studies of September 11, 2001-Exposed 
Populations.
    The peer-reviewed, published epidemiologic studies of 9/11-exposed 
populations are assessed by applying the following criteria 
extrapolated from the Bradford Hill criteria,\10\ as appropriate:
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    \10\ See Hill AB [1965], The Environment and Disease: 
Association or Causation? Proc R Soc Med 58:295-300.
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    a. Strength of the association between a 9/11 exposure and a type 
of cancer (including the precision of the risk estimate); \11\
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    \11\ Precision of the risk estimate describes the uncertainty 
inherent in estimating the strength of association (the effect size) 
between exposure and health effect from observational data. It is 
often expressed as a confidence interval illustrating a range of 
values that contains the true effect size. A narrow confidence 
interval indicates a more precise measure of the effect size and a 
wider interval indicates greater uncertainty.
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    b. Consistency of the findings across multiple studies. If only a 
single published epidemiologic study is available for assessment, the 
consistency of findings cannot be evaluated, and more emphasis will be 
placed on evaluating the strength of the association and the precision 
of the risk estimate;
    c. Biological gradient, or dose-response relationships between 9/11 
exposures and the type of cancer; and
    d. Plausibility and coherence with known facts about the biology of 
the type of cancer.
    Method 2. Established Causal Associations.
    A type of cancer may be added to the List if there is well-
established scientific support published in multiple peer-reviewed 
epidemiologic studies for a causal association between a condition 
already on the List and that cancer.
    Method 3. Review of Evaluations of Carcinogenicity in Humans.
    A type of cancer may be added to the List under Method 3 only if 
both of the following criteria are satisfied:
    3A. Published Exposure Assessment Information. A 9/11 agent \12\ 
included in

[[Page 27963]]

the Inventory of 9/11 Agents \13\ is identified; and
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    \12\ Chemical, physical, biological, or other hazards reported 
in a published, peer-reviewed exposure assessment study of 
responders, recovery workers, or survivors who were present in the 
New York City disaster area, or at the Pentagon site, or the 
Shanksville, Pennsylvania site, as those locations are defined in 42 
CFR 88.1, as well as those hazards not identified in a published, 
peer-reviewed exposure assessment study, but which are reasonably 
assumed to have been present at any of the three sites. WTC Health 
Program, Development of the Inventory of 9/11 Agents, published Jul. 
17, 2018, https://wwwn.cdc.gov/ResearchGateway/Content/pdfs/Development_of_the_Inventory_of_9-11_Agents_20180717.pdf.
    \13\ The Inventory of 9/11 Agents is composed of those agents 
identified in Tables 1-4 of the document, Development of the 
Inventory of 9/11 Agents. Id.
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    3B. Evaluation of Carcinogenicity in Humans from Scientific 
Studies. NTP [the National Toxicology Program] has determined that the 
9/11 agent is known to be a human carcinogen or is reasonably 
anticipated to be a human carcinogen, and the IARC [the World Health 
Organization's International Agency for Research on Cancer] has 
determined that there is sufficient or limited evidence in humans that 
the 9/11 agent causes the type of cancer.
    Method 4. Review of Information by the WTC Health Program 
Scientific/Technical Advisory Committee (STAC).
    A type of cancer may be added to the List if the STAC recommends 
the addition and provides a reasonable basis for the 
recommendation.\14\ To assist the Administrator in understanding 
whether the STAC's recommendation has a reasonable basis, the STAC must 
describe in detail the basis for its recommendation and, if applicable, 
any evidentiary sources it has used to support its recommendation.
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    \14\ The STAC may base its recommendation and reasonable basis 
on criteria other than those outlined in Methods 1-3.
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C. History and Scope of Rulemaking

    In September 2012, the Administrator published a final rule adding 
most types of cancer to the List,\15\ codified at 42 CFR 88.15(d). The 
2012 rulemaking added malignant neoplasm of the ovary (ovarian cancer) 
to the List pursuant to Method 3, described above; rare cancers were 
also added to the List pursuant to Method 4. In a follow-up rulemaking 
conducted in February 2014,\16\ the Program clarified the definition of 
``rare cancers'' to include any type of cancer that occurs in less than 
15 cases per 100,000 persons.\17\ As a result of this rulemaking 
other--but not all--types of malignant neoplasms of female genital 
organs,\18\ including cervix uteri (invasive cervical cancer) and 
uterine sarcomas, were found to meet the revised definition of rare 
cancers.\19\ Uterine cancer \20\ was not added to the List because the 
scientific evidence available at the time of the 2012 and 2014 
rulemakings did not provide sufficient support for its inclusion; nor 
did it meet the definition of rare cancer.
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    \15\ WTC Health Program final rule, Addition of Certain Types of 
Cancer to the List of WTC-Related Health Conditions, 77 FR 56138 
(Sept. 12, 2012).
    \16\ WTC Health Program interim final rule, Amendments to List 
of WTC-Related Health Condition; Cancer; Revision, 79 FR 9100 (Feb. 
18, 2014).
    \17\ A cancer is considered to be on the List if it meets the 
definition of rare cancers in 42 CFR 88.15(d)(24), which is any type 
of cancer * that occurs in less than 15 cases per 100,000 persons 
per year in the United States.
    * Based on 2005-2009 average annual data age-adjusted to the 
2000 U.S. population. See Glenn Copeland, Andrew Lake, Rick Firth, 
et al. (eds), Cancer in North America: 2005-2009. Volume One: 
Combined Cancer Incidence for the United States, Canada and North 
America, Springfield, IL: North American Association of Central 
Cancer Registries, Inc., June 2012.
    See also the Administrator's Policy and Procedures for Rare 
Cancers, https://www.cdc.gov/wtc/pdfs/policies/WTCHP_PP_RareCancers05052014-508.pdf.
    \18\ Although the List does not identify health condition 
medical diagnostic codes, the Program uses ICD-10 codes internally 
to track certified conditions. Malignant neoplasms of female genital 
organs comprise ICD-10 codes C51-C58 and include malignant neoplasms 
of the female genital organs: Vulva (C51), vagina (C52), cervix 
uteri (C53), corpus uteri (C54), uterus, part unspecified (C55), 
ovary (C56), other and unspecified female genital organs (C57), and 
placenta (C58). Uterine sarcomas are included in ICD-10 C55. ICD-10 
codes C54 and C55 are not currently considered WTC-related health 
conditions. World Health Organization (WHO) [1997], International 
Classification of Diseases, Tenth Edition.
    \19\ See supra note 17.
    \20\ See supra note 1.
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    Since 2012, the WTC Health Program has received eight submissions 
requesting the addition of endometrial or uterine cancer to the List. 
Only one of these submissions, Petition 023, received in 2019 and 
requesting the addition of ``endometrial cancer,'' \21\ was determined 
to be a valid petition.\22\ In response, the Program conducted a 
literature search and identified and evaluated seven published, peer-
reviewed, epidemiologic studies about uterine cancer, including 
endometrial cancer, in the 9/11-exposed population. Ultimately, in 
2019, the Administrator determined that the evidence was insufficient 
to support adding uterine cancer, including endometrial cancer, to the 
List.\23\
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    \21\ The endometrium is the layer of tissue that lines the 
uterus. National Cancer Institute, Dictionary of Cancer Terms, 
https://www.cancer.gov/publications/dictionaries/cancer-terms/def/endometrium. Endometrial cancer accounts for nearly 90 percent of 
uterine cancer cases. See also American Society of Clinical Oncology 
[2021], Uterine Cancer: Statistics, https://www.cancer.net/cancer-types/uterine-cancer/statistics.
    \22\ Interested parties may petition the Administrator to add 
health conditions to the List. To be considered a valid petition, a 
submission must meet the criteria established in 42 CFR 88.16(a)(1) 
and further described in the Policy and Procedures for Handling 
Submissions and Petitions to Add a Health Condition to the List of 
WTC-Related Health Conditions, https://www.cdc.gov/wtc/pdfs/policies/WTCHPPPPetitionHandlingProcedures14May2014-508.pdf.
    \23\ WTC Health Program Federal Register document, Petition 023-
Uterine Cancer, Including Endometrial Cancer; Finding of 
Insufficient Evidence, 84 FR 49954 (Sept. 24, 2019).
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    On September 11, 2020, the Administrator received a submission from 
five of the Program's CCEs, requesting the addition of uterine cancer 
to the List. Although the Program determined that the submission was 
not a valid petition, the Administrator thought that it raised 
important questions about the potential association between endocrine 
disrupting chemicals (EDCs) and hormone-related tumors such as 
endometrial cancer. The CCEs noted that the WTC Health Program's 
scientific literature evaluation conducted for Petition 023 did not 
include consideration of the relationship between EDCs and uterine 
cancer, despite some EDCs being included in the Inventory of 9/11 
Agents.\24\ The CCEs argued that research that has emerged since 2012 
suggests EDCs may have a role in the development of estrogen-related 
diseases such as endometrial cancer. Moreover, the CCEs noted the low 
numbers of female \25\ WTC responders in the occupational studies of 
the health effects of 9/11 exposure and expressed concern that this may 
lead to gaps in the research.
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    \24\ Inventory of 9/11 Agents means those 9/11 agents identified 
as being present at a 9/11 site and included in Tables 1-4 of the 
WTC Health Program publication, Development of the Inventory of 9/11 
Agents, Jul. 17, 2018, https://wwwn.cdc.gov/ResearchGateway/Content/pdfs/Development_of_the_Inventory_of_9-11_Agents_20180717.pdf. EDCs 
in the Inventory of 9/11 Agents include persistent organic 
pollutants and other industrial substances such as cadmium, dioxins, 
perfluoroalkyl and poly fluoroalkyl substances (PFAS), phthalates, 
polybrominated diphenyl ethers (PBDE), and polychlorinated biphenyls 
(PCB). None of these 9/11 agents have been found by NTP or IARC to 
be known to cause or reasonably anticipated to cause uterine cancer.
    \25\ Although this rulemaking refers to uterine cancer in 
females, the WTC Health Program recognizes that some individuals who 
identify as male may also be at risk for uterine cancer.
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    The Administrator determined that a more thorough evaluation of the 
scientific information regarding uterine cancer available since 2012 
was needed and asked the WTC Health Program Science Team (Science Team) 
to conduct a review of the available scientific evidence to determine 
whether it might now support adding uterine cancer to the List. The 
Science Team conducted a literature review and issued a White Paper 
(discussed below) documenting its findings in September 2021. The White 
Paper describes the

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Science Team's conclusion that insufficient evidence exists to support 
a decision to add uterine cancer to the List under Methods 1 or 3 of 
the Policy and Procedures described above; evidence considered under 
Method 2 supports adding uterine cancer to the List, but only for those 
Program members who have a certified WTC-related estrogen-secreting 
tumor.
    Pursuant to Method 4 of the Policy and Procedures, the 
Administrator exercised his discretion to request a recommendation from 
the STAC \26\ regarding whether the available evidence provides a 
reasonable basis exists for adding uterine cancer to the List. The 
Administrator convened the STAC on September 28-29, 2021, and gave the 
Committee the following charge:
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    \26\ See PHS Act, sec. 3312(a)(6)(A).

    As you are aware, the WTC Health Program currently covers all 
major types of cancer, except for uterine cancer. I welcome the 
Committee's evaluation and recommendation on whether there is a 
reasonable scientific basis to support adding uterine cancer to the 
List of WTC-Related Health Conditions.\27\
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    \27\ Administrator's Charge to the World Trade Center Health 
Program Scientific/Technical Advisory Committee, https://www.cdc.gov/wtc/pdfs/stac/STAC_AdmCharge_Revised20210928-P.pdf.

    At the September 2021 meeting, the Science Team presented the White 
Paper describing the available scientific evidence for an association 
between uterine cancer and 9/11 exposures. The STAC heard public 
comment and deliberated on the evidence presented in the White Paper. 
The Committee ultimately decided to create a workgroup to ``write a 
report describing the committee's conclusion, scientific rationale, and 
supporting evidence for adding uterine cancer as a WTC-related health 
condition.'' \28\ At a follow-up meeting on November 18, 2021, the 
workgroup presented their draft report to the Committee. Following 
deliberation, the 12 STAC members present \29\ voted unanimously to 
approve the report and recommend that the Administrator add uterine 
cancer to the List. Both the White Paper and the STAC recommendation 
are discussed below.
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    \28\ World Trade Center Health Program Scientific/Technical 
Advisory Committee, Executive Summary of Meeting, September 28-29, 
2021, https://www.cdc.gov/wtc/pdfs/stac/WTCHP_STACmeetingMinutes_20210928-29.pdf.
    \29\ Per STAC bylaws, a quorum consists of a majority of the 
committee's membership. Based on the membership at the time of the 
meeting, the required number of members for a quorum was nine. Four 
members were unable to attend the November 18, 2021, meeting, 
however 12 members were in attendance and quorum was maintained 
throughout the meeting.
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D. Review of Evidence Supporting the Proposed Addition of Uterine 
Cancer to the List

1. WTC Health Program Science Team Review
    As discussed above, the Administrator asked the Science Team to 
assess the scientific evidence currently available to determine whether 
a basis exists under the Policy and Procedures for proposing the 
addition of uterine cancer to the List. The Science Team reported its 
findings in the White Paper entitled, Scientific Considerations for 
Potential Addition of Uterine Cancer to the List of Covered Conditions 
by the World Trade Center Health Program (Revised): Preliminary 
Assessment for the World Trade Center Health Program Scientific/
Technical Advisory Committee.\30\ The White Paper describes the scope 
of the Science Team's query as well as the literature search and 
inclusion criteria, and summarizes the studies identified that describe 
the available evidence on causal relationships between 9/11 exposures 
and uterine cancer.
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    \30\ WTC Health Program [2021], Scientific Considerations for 
Potential Addition of Uterine Cancer to the List of Covered 
Conditions by the World Trade Center Health Program (Revised): 
Preliminary Assessment for the World Trade Center Health Program 
Scientific/Technical Advisory Committee. The Science Team's White 
Paper is available in the docket for this rulemaking and on the WTC 
Health Program website, at https://www.cdc.gov/wtc/pdfs/stac/ScientificConsiderationsUterineCancer_STAC_20210928.pdf.
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    Pursuant to Method 1, the Science Team conducted a literature 
search in April 2021. As described in the White Paper, the Science Team 
identified and summarized nine studies: Six which were previously 
evaluated in the Petition 023 Federal Register document,\31\ one that 
recapitulated the results of two of those previously evaluated studies, 
and two additional studies published since the Petition 023 literature 
search and evaluation were conducted. Ultimately, five studies were 
found to be relevant for further evaluation, including some of the 
earlier studies which have been recently updated by their authors.\32\ 
With regard to Method 1, the Science Team concluded:
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    \31\ A seventh study was evaluated in the Petition 023 review 
but was not considered in the Science Team's evaluation for reasons 
described in the White Paper, id. at 8.
    \32\ See full discussion of the Science Team's literature review 
and findings regarding Method 1 in the White Paper, id. at 8-17.

    Five relevant peer-reviewed, published, epidemiologic studies 
were identified and reviewed. The studies do not provide consistent 
evidence of elevated uterine cancer incidence or mortality among WTC 
responders and survivors. The studies also do not report a dose-
response relationship between 9/11 exposures and uterine cancer and 
the study designs may be susceptible to selection bias. As a result, 
collectively, these studies do not demonstrate a potential to 
provide a basis for a decision on whether to add uterine cancer to 
the List.\33\
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    \33\ Id. at 6-7.

    Pursuant to Method 2, the Science Team explored whether a causal 
association exists between uterine cancer and a health condition 
already on the List. The Science Team found that uterine cancer may be 
medically associated with estrogen-secreting tumors, which are 
considered rare cancers in the Program. Studies reviewed by the Science 
Team demonstrate support for a causal association between granulosa 
cell tumors of the ovary (the most common type of estrogen-secreting 
tumor) and uterine cancer.\34\ With regard to Method 2, the Science 
Team concluded:
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    \34\ See full discussion of the Science Team's review of the 
scientific literature and findings regarding Method 2 in the White 
Paper, supra note 30, at 17-18.

    A thorough review of the scientific literature found that 
estrogen-secreting tumors are associated with endometrial cancer, 
but that these estrogen-secreting tumors are rare. Because estrogen-
secreting tumors fall under the category of ``rare cancers'' in the 
List, uterine cancer [may be considered a medically associated 
condition and thus] . . . added to the List only for members who 
have a certified estrogen-secreting tumor.\35\
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    \35\ Id. at 7.

    Pursuant to Method 3, the Science Team considered the evaluations 
of carcinogenicity published by NTP and IARC of those EDCs that are 9/
11 agents identified in the Inventory of 9/11 Agents. With regard to 
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Method 3, the Science Team concluded:

    Four EDCs listed in the Inventory of 9/11 Agents are considered 
carcinogenic to humans by NTP or IARC: (1) 2,3,7,8-
tetrachlorodibenzodioxin (TCDD); (2) 2,3,4,7,8-
pentachlorodibenzofuran; (3) polychlorinated biphenyls (PCB); and 
(4) cadmium. None of these agents is considered to have sufficient 
or even limited evidence of uterine carcinogenicity [based on IARC's 
Monographs]. Further review of epidemiologic studies published after 
. . . [IARC's Monographs] did not identify additional evidence of 
carcinogenicity to the uterus.\36\
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    \36\ Id. at 7.

    In addition, since Method 4 allows a cancer to be proposed for 
addition to the List if the STAC provides a reasonable basis, the 
Science Team presented

[[Page 27965]]

supplementary evidence that was reviewed but found not to be applicable 
to Methods 1, 2, or 3 for the STAC's consideration. First, the Science 
Team described the commonalities between the mechanisms of development 
for uterine cancer and other types of cancer, including ``estrogen, an 
abnormal mismatch repair (MMR) system, genetic abnormalities, and 
aberrant methylation of DNA and microRNA.'' \37\ Next, the Science Team 
presented evidence from studies in non-9/11-exposed populations that 
demonstrate associations between uterine cancer and the 9/11 agents 
TCDD, PCBs, cadmium, and asbestos (known EDCs). Additionally, the 
Science Team noted that most studies of EDC exposure are conducted 
among occupational cohorts, including few or no women. Finally, the 
Science Team presented evidence that some EDCs in the Inventory of 9/11 
Agents, including 2,3,7,8-tetrachlorodibenzodioxin and PCBs, are 
considered by NTP and IARC to be known or probable human carcinogens 
associated with types of cancer other than uterine cancer (e.g., 
melanoma, breast cancer, lymphoma, and leukemia), supporting the 
inference that some EDC 9/11 agents may also be linked to uterine 
cancer.
---------------------------------------------------------------------------

    \37\ Id. at 27.
---------------------------------------------------------------------------

2. WTC Health Program Scientific/Technical Advisory Committee Review
    After being presented with the White Paper at the September 28-29, 
2021, STAC meeting, the Committee created a workgroup to ``write a 
report describing the committee's conclusion, scientific rationale, and 
supporting evidence for adding uterine cancer as a WTC-related health 
condition.'' \38\ Following the deliberation of the full committee at 
the November 18, 2021, meeting, the STAC voted to recommend that 
uterine cancer be added to the List. The Chair of the STAC sent a 
letter with the Committee's formal recommendation and rationale to the 
Administrator, which he received on November 29, 2021.\39\
---------------------------------------------------------------------------

    \38\ WTC Health Program STAC, Executive Summary of Meeting, 
September 28-29, 2021, https://www.cdc.gov/wtc/stac_meeting.html, at 
2.
    \39\ Letter from Dr. Elizabeth Ward, Chair of the STAC, to the 
Administrator, regarding the STAC's resolution on the addition of 
uterine cancer to the List of WTCHP Covered Conditions, received 
November 29, 2021. The letter from Dr. Ward, including the STAC's 
recommendation is available in the docket for this rulemaking and on 
the WTC Health Program website, at https://www.cdc.gov/wtc/pdfs/stac/STAC.Recommendation.Received.29.November.2021.pdf.
---------------------------------------------------------------------------

    The STAC recommendation is grounded in evidence and principles 
first developed by the STAC in its 2012 recommendation to the 
Administrator concerning the addition of cancers to the List.\40\ The 
2021 STAC recommendation quotes the 2012 STAC recommendation, which 
described those principles as including an understanding that 
``exposures resulting from the collapse of the World Trade Center were 
unlike any other exposures in intensity and variety in history. . . . 
Compounding the uniqueness of the exposures is the absence of any data 
on air contaminant levels or the composition of the dust and fumes in 
the first four days after the attack, and the presence of multiple and 
complex exposures.'' \41\ Further, the STAC found in 2012 that ``both 
responder populations and area residents and workers had potential for 
significant exposures to toxic and carcinogenic components of WTC dust 
and smoke.'' \42\
---------------------------------------------------------------------------

    \40\ Letter from Dr. Elizabeth Ward, Chair of the STAC, to the 
Administrator, regarding the STAC's resolution on the addition of 
cancer to the List of WTC-Related Health Conditions, received Apr. 
2, 2012, https://www.cdc.gov/niosh/docket/archive/pdfs/NIOSH-248/0248-040212-Letter.pdf.
    \41\ Supra note 39, at 6.
    \42\ Id. at 7.
---------------------------------------------------------------------------

    The STAC also revisited the arguments presented in the 2012 STAC 
recommendation for the addition of all cancer types, adding that:

. . . we believe that the arguments for adding all cancers can apply 
to the question of whether to include all types of uterine cancer. 
Other than uterine cancer, all cancer types now are covered as WTC-
related conditions. Mechanisms for carcinogenesis resulting from 
endogenous and exogenous exposures are similar for most cancer 
types. It is therefore highly implausible that uterine cancer would 
be the only cancer not related to WTC exposures.\43\
---------------------------------------------------------------------------

    \43\ Id. at 2.

    In fact, in reviewing the literature, the STAC found that uterine 
cancer ``shares many of the same genetic mechanisms with cancers 
already included in [the] List of WTC-Related Health Conditions.'' \44\ 
Because exposure to endogenous and exogenous estrogen is strongly 
associated with both endometrial \45\ and breast cancer, the STAC found 
exposure to EDCs in WTC dust to be ``particularly relevant.'' Noting 
that the 2012 STAC recommendation did not review evidence supporting an 
association between EDCs and cancer types, the November 2021 
recommendation summarized the STAC's understanding of exposures to EDCs 
and their possible association with uterine cancer.\46\
---------------------------------------------------------------------------

    \44\ Id.
    \45\ In footnote 1 of its recommendation, the STAC clarifies 
that ``endometrial'' and ``uterine'' cancer are used synonymously 
and that most of the literature reviewed by the STAC relates 
specifically to endometrial cancer. The STAC recommendations pertain 
to all types of uterine cancer, including endometrial cancer.
    \46\ See supra note 39, at Attachment 1.
---------------------------------------------------------------------------

    The STAC acknowledged that ``[s]tudying the potential health 
effects of exposure to EDCs is inherently challenging and much remains 
unknown despite decade[s] of research,'' and quoted a recent review 
which described EDCs' multiple mechanisms of action, acting 
``simultaneously at the level of the receptor, hormone synthesis, and 
hormone degradation.'' \47\
---------------------------------------------------------------------------

    \47\ Id. at 8.
---------------------------------------------------------------------------

    The STAC noted that the Inventory of 9/11 Agents includes certain 
9/11 agents which are recognized as EDCs. Specifically, the STAC noted 
that elevated levels of polychlorinated dibenzo-para-dioxins and 
polychlorinated dibenzofurans (PCDD/F) were found on window surfaces 
from locations in lower Manhattan and Brooklyn six weeks after 
September 11, 2001. Other EDCs were found in WTC dust and smoke samples 
and in runoff samples from Rector Street on September 14 and 20, 2001. 
Two biomonitoring studies demonstrated significantly elevated levels of 
EDCs in 9/11-exposed cohorts: A study of perfluorochemicals in plasma 
from WTC responders working near Ground Zero between September 11 and 
December 23, 2001 found levels of perfluorooctanoic acid (PFOA) and 
perfluorohexanesulfonate (PFHxS) twice as high as in the U.S. general 
population; and a study comparing 9/11-exposed adolescents to non-9/11-
exposed adolescents found that PCDD/F levels were statistically 
significantly higher among the 9/11-exposed cohort.\48\ The STAC found 
that PBDEs, high levels of which were found in WTC dust, in particular 
have been shown to ``interfere with estrogen- . . . mediated 
processes'' and that ``some toxicologic studies provide indirect 
evidence'' for an association between PBDE exposures and uterine 
cancer.\49\
---------------------------------------------------------------------------

    \48\ See full discussion of the STAC's review of the scientific 
literature and findings in Attachment 1, sec. 2 of the STAC 
recommendation, supra note 39.
    \49\ Id. at 10.
---------------------------------------------------------------------------

    The STAC found that EDC exposure-related imbalances in sex steroid 
hormones are a ``plausible mechanism'' for the development of uterine 
cancer among WTC responders and survivors. Hormone-related cancers 
thought to be caused by EDC exposure include thyroid cancer, breast 
cancer, testicular and prostate cancers, and all female reproductive 
organ cancers, all of which are included on the List with the exception 
of uterine cancer.

[[Page 27966]]

    The STAC also commented on the likely inability of existing and 
future epidemiologic studies in the 9/11-exposed responder population--
the most studied 9/11-exposure cohort--to accurately capture uterine 
cancer incidence because of the small number of female responders. 
Moreover, the STAC noted that studies of carcinogens reviewed by IARC 
and other authoritative bodies typically represent industrial cohorts, 
which often include few or no females, making finding an association 
between a 9/11 agent and uterine cancer highly unlikely and thus 
potentially foreclosing Method 3 as a basis for adding uterine cancer 
to the List.
    Finally, the STAC considered public comment as well as the strong 
support of the WTC Health Program CCEs for the addition of uterine 
cancer to the List, noting that many Program members and advocates feel 
the exclusion of uterine cancer from the List is ``illogical and unfair 
and may cause tangible harm.'' The STAC cited a recent study \50\ 
supporting the argument that WTC responders and survivors diagnosed 
with uterine cancer will experience better cancer survival if uterine 
cancer is covered by the Program due to treatment coverage and high-
quality care.
---------------------------------------------------------------------------

    \50\ See full discussion of the STAC's review of the scientific 
literature and findings in Attachment 1, sec. 2 of the STAC 
recommendation, supra note 39.
---------------------------------------------------------------------------

    After reviewing the available evidence and hearing comment from 
both the public and the WTC Health Program's CCEs, the STAC concluded 
that:

    In view of the strong rationale for adding all types of uterine 
cancer to the list of WTC-related cancers and the potential benefits 
to affected WTC responders, WTC survivors, and providers caring for 
these patients, we recommend that all types of uterine cancer be 
added to the list of WTC-related cancers and urge the Administrator 
to make all feasible efforts to do so as quickly as policies and 
procedures allow.\51\
---------------------------------------------------------------------------

    \51\ Id. at 5.

E. Administrator's Decision Regarding Uterine Cancer

    After reviewing the available body of scientific evidence 
describing the causal relationship between 9/11 exposures and uterine 
cancer, including certain 9/11 agents which are known EDCs, as well as 
evaluating the STAC's comprehensive rationale and recommendation, the 
Administrator concludes that the totality of available information 
provides a sufficient evidentiary basis to propose adding uterine 
cancer \52\ to the List.
---------------------------------------------------------------------------

    \52\ ICD-10 codes C54 and C55. See supra note 1.
---------------------------------------------------------------------------

    In accordance with the Program's Policy and Procedures, the 
Administrator evaluated the available information under the four 
methods developed for determining whether to add a type of cancer to 
the List. First, he assessed whether there was sufficient evidence in 
peer-reviewed, published, epidemiologic studies of 9/11-exposed 
populations to support adding uterine cancer to the List under Method 
1. The Administrator concurs with the Science Team's evaluation of the 
literature pursuant to Method 1 and finds that the available literature 
does not provide sufficient support for the addition of uterine cancer 
to the List under Method 1.
    Next, he looked at Method 2 which permits an addition to the List 
if multiple peer-reviewed epidemiologic studies establish a causal 
association between a condition already on the List and that cancer. 
The Administrator agrees with the Science Team's finding that there is 
evidence of a causal association between estrogen-secreting tumors, 
which are considered rare cancers in the Program, and uterine cancer. 
Thus, the Administrator finds that uterine cancer may be proposed for 
addition to the List pursuant to Method 2, but such an addition would 
be limited to only those Program members who have a certified WTC-
related estrogen-secreting tumor.
    The Administrator also examined NTP and IARC evaluations of 
carcinogenicity under Method 3, which permits an addition to the List 
if NTP has determined that a specific 9/11 agent is known to be a human 
carcinogen or is reasonably anticipated to be a human carcinogen, and 
IARC has determined that there is sufficient or limited evidence in 
humans that the 9/11 agent causes the type of cancer. The Administrator 
reviewed the NTP and IARC evaluations of those EDCs that are on the 
Inventory on 9/11 Agents (i.e., TCDD, 2,3,4,7,8-
pentachlorodibenzofuran, PCB, and cadmium) and concurs with the Science 
Team's finding that there is insufficient support for the addition of 
uterine cancer pursuant to Method 3.
    Finally, the Administrator reviewed the recommendation of the STAC 
to determine if uterine cancer could be added to the List pursuant to 
Method 4, which permits an addition where the STAC recommends such an 
addition and provides a reasonable basis for the recommendation. The 
Administrator finds that the STAC's recommendation provides a 
reasonable basis for the addition of uterine cancer under Method 4 and 
this recommendation is further supported by the supplemental 
information presented by the Science Team in the White Paper.
    Specifically, the Administrator agrees with the STAC's finding that 
mechanisms of initiation and progression of uterine cancer are similar 
to those for several other cancers on the List.\53\ In particular, the 
evidence showing similar gene mutations and abnormal mismatch repair 
proteins among many cancers, including uterine cancer, strongly 
supports shared etiology and pathogenesis between uterine cancer and 
other cancer types on the List. For example, gene mutations found in 
low-grade, endometrioid endometrial cancer (which accounts for 80 
percent of all endometrial cancers) include those in PTEN (phosphatase 
and tensin homolog deleted on chromosome 10), CTNNB1 ([beta]-catenin), 
and K-RAS. PTEN inactivation is similarly found in malignant melanoma, 
brain tumors, and ovarian, thyroid, breast, and prostate cancers, while 
CTNNB1 and K-RAS mutations are found in a variety of human cancers. 
High-grade endometrial cancers are associated with mutations in 
oncogene ERBB2 (HER-2/neu) and tumor suppressor gene TP53. ERBB2 gene 
mutations are also found in breast and ovarian cancers; likewise, TP53 
is frequently mutated in a variety of human cancers, including high-
grade serous ovarian and basal-like breast cancers.\54\ Finally, 
studies have shown that several microRNAs (miRNAs), including miR-152 
which plays a role as a tumor suppressor, can be epigenetically 
silenced by hyper-methylation of their respective DNA locus in 
endometrial cancer.\55\ Aberrant methylation of miR-152 has also been 
reported for other cancers, including acute lymphoblastic leukemia, 
gastrointestinal cancer, and cholangiocarcinoma. Recent pan-cancer 
molecular studies \56\ have found shared

[[Page 27967]]

molecular features among invasive breast carcinoma and several 
gynecologic tumors, such as high-grade serous ovarian 
cystadenocarcinoma, uterine corpus endometrial carcinoma, cervical 
squamous cell carcinoma and endocervical adenocarcinoma, and uterine 
carcinosarcoma.\57\ The Administrator agrees with the STAC's finding 
that the shared etiology and pathogenesis described in the scientific 
literature suggest it would be unlikely that uterine cancer would be 
the only cancer type not related to 9/11 exposures.
---------------------------------------------------------------------------

    \53\ Banno K, Yanokura M, Iida M, Masuda K, Aoki D [2014], 
Carcinogenic Mechanisms of Endometrial Cancer: Involvement of 
Genetics and Epigenetics, J Obstet Gynaecol Res 40(8):1957-1967; 
Urick ME and Bell DW [2019], Clinical Actionability of Molecular 
Targets in Endometrial Cancer, Nat Rev Cancer 19, 510-521.
    \54\ Levine DA and the Cancer Genome Atlas Research Network 
[2013], Integrated Genomic Characterization of Endometrial 
Carcinoma, Nature 497(7447):67-73.
    \55\ Favier A, Rocher G, Larsen AK, Delangle R, Uzan C, Sabbah 
M, Castela M, Duval A, Mehats C, Canlorbe G [2021], MicroRNA as 
Epigenetic Modifiers in Endometrial Cancer: A Systematic Review, 
Cancers (Basel) 6;13(5):1137.
    \56\ Pan-cancer molecular studies examine the similarities and 
differences among the genomic and cellular alterations found across 
diverse tumor types. Weinstein JN, Collisson EA, Mills GB, Mills 
Shaw KR, Ozenberger BA, Ellrott K, Shmulevich I, Sander C, Stuart JM 
[2013]. The Cancer Genome Atlas Pan-Cancer analysis project, Nature 
Genetics. 45 (10): 1113-1120.
    \57\ Berger AC et al. [2018], A Comprehensive Pan-Cancer 
Molecular Study of Gynecologic and Breast Cancers, Cancer Cell 
33(4):690-705.
---------------------------------------------------------------------------

    The Administrator also finds that an association between exposure 
to EDCs in WTC dust and uterine cancer risk is plausible. EDCs can 
mimic endogenous hormones and interfere with endogenous hormone 
homeostasis, which may lead to a variety of adverse health outcomes, 
including cancer (e.g., estrogen imbalances are a key risk factor for 
uterine cancer). There is extensive evidence from human studies of an 
etiologic role of estrogens in cancer. However, finding a causal 
association between an EDC 9/11 agent and uterine cancer is highly 
unlikely given the potentially long latency between exposure and 
disease. Moreover, the low number of women included in epidemiologic 
studies examining EDC carcinogenic risks in occupational cohorts 
increases the difficulty in finding conclusive evidence of a causal 
association with uterine cancer. Given the growing body of scientific 
evidence suggesting that exposure to EDCs may be a risk factor for 
female reproductive organ cancers (e.g., breast, ovarian, and 
endometrial cancers), it is reasonable to assume that exposure to EDCs 
in WTC dust may contribute to uterine cancer risk.
    Finally, the Administrator recognizes that the disproportionally 
low representation of women in the most studied cohorts of exposed 
responders makes it epidemiologically unlikely that a definitive 
association between 9/11 exposures and the occurrence of uterine cancer 
will be identified during the lifetime of even the most highly exposed 
Program members.
    The Administrator has determined that the available scientific 
evidence and rationale provided by the STAC in its recommendation, 
supported by the supplemental information presented by the Science Team 
in the White Paper, offers a plausible rationale for an association 
between uterine cancer and EDCs in the Inventory of 9/11 Agents. 
Moreover, the cohorts relevant to understanding uterine cancer in the 
9/11-exposed population are too small to allow a definitive decision 
about whether uterine cancer is causally associated with 9/11 exposure. 
For these reasons, the Administrator finds that a reasonable basis has 
been provided by the STAC under Method 4 and, accordingly, proposes to 
add uterine cancer to the List of WTC-Related Health Conditions.

IV. Summary of Proposed Rule

    For the reasons discussed above, the Administrator proposes to 
amend 42 CFR 88.15 by adding a new paragraph (d)(15) to include 
malignant neoplasms of corpus uteri and uterus, part unspecified \58\ 
on the List of WTC-Related Health Conditions. The existing paragraph 
(d)(15)--malignant neoplasm of the ovary--and the remainder of the 
cancer types identified in existing paragraphs (d)(16) through (24)--
rare cancers--are renumbered paragraphs (d)(16) through (25), 
accordingly. Adding uterine cancer to the List would allow the WTC 
Health Program to offer treatment services to members whose uterine 
cancers are certified as WTC-related.
---------------------------------------------------------------------------

    \58\ See supra note 1.
---------------------------------------------------------------------------

V. Required Regulatory Analyses

A. Executive Order 12866 (Regulatory Planning and Review) and Executive 
Order 13563 (Improving Regulation and Regulatory Review)

    Executive Orders (E.O.) 12866 and 13563 direct agencies to assess 
all costs and benefits of available regulatory alternatives and, if 
regulation is necessary, to select regulatory approaches that maximize 
net benefits (including potential economic, environmental, public 
health and safety effects, distributive impacts, and equity). E.O. 
13563 emphasizes the importance of quantifying both costs and benefits, 
reducing costs, harmonizing rules, and promoting flexibility.
    This proposed rule has been determined not to be a significant 
regulatory action under sec. 3(f) of E.O. 12866, and therefore has not 
been reviewed by the Office of Management and Budget (OMB). The 
addition of uterine cancer proposed by this rulemaking is estimated to 
cost the WTC Health Program between $1,718,691 and $2,199,808 per annum 
for 2022-2025.\59\ All costs to the WTC Health Program will be 
transfers due to the implementation of provisions of the Patient 
Protection and Affordable Care Act (Pub. L. 111-148) in 2014 and as 
required under the authorizing statute for the WTC Health Program.\60\ 
The rule would not interfere with state, local, or tribal governments 
in the exercise of their governmental functions.
---------------------------------------------------------------------------

    \59\ As discussed in this section, NIOSH estimated lower and 
upper bound estimates to reflect the uncertainty in the Agency's 
ability to predict the expected number of cancer cases in three 
years after this rulemaking. The low bound reflects the general U.S. 
population cancer rate and uses undiscounted costs for 2022 and 
costs for 2023-2025 discounted at the 7% discount rate. The upper 
bound reflects the U.S. population cancer rate + 21%, based on a 
study by Li et al. [2021], infra note 69, and uses undiscounted 
rates for 2022 and costs for 2023-2025 discounted at the 3% discount 
rate. Although, if added to the List, uterine cancer would be 
considered a covered condition for the duration of the WTC Health 
Program (currently authorized through FY 2090), the dates 2022-2025 
were chosen in order to provide a snapshot of uterine cancer costs 
in the coming years.
    \60\ Because sec. 3331(c)(3) of the PHS Act requires WTC Health 
Program members to maintain minimum essential insurance coverage all 
treatment costs to be paid by the WTC Health Program are considered 
transfers.
---------------------------------------------------------------------------

Population Estimates
    The WTC Health Program has, as of September 30, 2021, enrolled 
approximately 82,000 WTC responders and approximately 32,000 survivors, 
or approximately 114,000 individuals in total. Of that total 
population, approximately 60,000 individuals were participants in 
previous WTC medical programs and were enrolled as ``Legacy'' members 
in the WTC Health Program established by Title XXXIII of the PHS Act. 
For the purpose of calculating a baseline estimate of cancer prevalence 
only, the Administrator assumed that a steady rate of enrollment would 
continue, based on the trend in enrollees through September 2021.
    According to WTC Health Program data, 12 percent of the current 
responder members (approximately 10,000 individuals) and 50 percent of 
survivor members (approximately 16,000 individuals) are female.\61\ The 
Administrator acknowledges that some uterine cancer cases in this 
population may not have been caused by 9/11 exposures. The 
certification of individual cancer diagnoses will be conducted on a 
case-by-case basis, as required by the Zadroga Act. For the purpose of 
this economic analysis, however, the Administrator assumes that all 
diagnosed uterine cancers will be certified for treatment by the WTC 
Health Program. Finally, because there are no existing data on cancer 
rates related to 9/11 exposures at either the Pentagon or in 
Shanksville, Pennsylvania, the Administrator has

[[Page 27968]]

used only data from studies of individuals who were responders or 
survivors in the New York City disaster area.
---------------------------------------------------------------------------

    \61\ See supra note 25.
---------------------------------------------------------------------------

Cost of Uterine Cancer Treatment
    The Administrator estimated the treatment costs associated with 
covering uterine cancer in this rulemaking. The costs of treatment are 
divided into three treatment phases: The first year of treatment 
following diagnosis; the intervening years or continuing treatment 
after the first year; and treatment during the last year of life. The 
first-year costs of cancer treatment are higher due to the initial need 
for aggressive medical care (e.g., radiation or chemotherapy) and 
surgical care. The costs during the last year of life are often 
dominated by increased hospitalization costs.\62\ Therefore, three 
different treatment phase costs were used to provide a best estimate of 
treatment costs in conjunction with expected incidence and long-term 
survival rates for uterine cancer. Average treatment costs for uterine 
cancer are in Table A, below.
---------------------------------------------------------------------------

    \62\ Yabroff KR, Lamont EB, Mariotto A, Warren JL, Topor M, 
Meekins A, Brown ML [2008], Cost of Care for Elderly Cancer Patients 
in the United States, J Natl Cancer Inst 100(9):630-41.

      Table A--Average Costs of Treatment for Uterine Cancer, 2021$
------------------------------------------------------------------------
 
------------------------------------------------------------------------
Stage of treatment:
  Initial (first 12 months after diagnosis)..................    $39,638
  Continuing (annual)........................................      2,066
  Last year of life (last 12 months of life).................    118,058
------------------------------------------------------------------------

    These cost figures were based on a study of cancer patients from 
the Surveillance, Epidemiology, and End Results (SEER) program 
maintained by the National Cancer Institute and using Medicare 
files.\63\ The average costs of treatment described above are given in 
2021 prices adjusted using the Medical Consumer Price Index for all 
urban consumers.\64\
---------------------------------------------------------------------------

    \63\ Surveillance, Epidemiology, and End Results (SEER) Program 
(www.seer.cancer.gov) SEER*Stat Database: Incidence--SEER 9 Regs 
Research Data, Nov 2020 Sub (1975-2018), National Cancer Institute, 
DCCPS, Surveillance Research Program, Surveillance Systems Branch, 
released Apr. 2021, based on the Nov. 2020 submission. Although 
patients who are Medicare members are age 65 and older, cancer 
treatment costs are not expected to vary with age.
    \64\ Bureau of Labor Statistics, Consumer Price Index, https://fred.stlouisfed.org. Accessed on Apr. 28, 2021.
---------------------------------------------------------------------------

Incident Cases of Cancer
    The Administrator estimated the expected number of cases of cancer 
that would be observed in a cohort of responders and survivors followed 
for cancer incidence after September 11, 2001, using U.S. population 
cancer rates. Demographic characteristics of the cohort were assigned 
since the actual data are not available for individuals in the 
responder and survivor populations who have not yet enrolled in the WTC 
Health Program. Sex and age (at the time of exposure) distributions for 
responders and survivors were assumed to be the same as current members 
in the WTC Health Program. Because uterine cancer occurs only in 
females,\65\ all calculations only consider female WTC Health Program 
members.
---------------------------------------------------------------------------

    \65\ See supra note 25.
---------------------------------------------------------------------------

    The Administrator assumed race and ethnic origin distributions for 
responders and survivors, respectively, according to distributions in 
the WTC Health Registry cohort: \66\ 57 percent non-Hispanic white, 15 
percent non-Hispanic black, 21 percent Hispanic, and 8 percent other 
race/ethnicity for responders; 50 percent non-Hispanic white, 17 
percent non-Hispanic black, 15 percent Hispanic, and 18 percent other 
race/ethnicity for survivors. Registry follow-up for cancer morbidity 
for each person began on January 1, 2002, or age 15 years, whichever 
was later. Age 15 was considered because the cancer incidence rate file 
did not include rates for persons less than 15 years of age. Follow-up 
ended on December 31, 2016, or the estimated last year of life, 
whichever was earlier. The estimated last year of life was used since 
not all persons would be expected to remain alive at the end of 2016. 
The estimated last year of life was based on U.S. gender, race, age, 
and year-specific death rates from CDC WONDER.\67\ A life-table 
analysis program, LTAS.NET, was used to estimate the expected number of 
incident cancers for uterine cancer.\68\ The Administrator calculated 
cancer incidence rates using data through 2018 from the SEER Program 
and estimated rates for 2002-2025.\69\ The Program applied the 
resulting gender, race, age, and year-specific cancer incidence rates 
to the estimated person-years at risk to estimate the expected number 
of cancer cases for uterine cancer starting from year 2002, the first 
full year following the September 11, 2001, terrorist attacks, to 2025.
---------------------------------------------------------------------------

    \66\ Jordan HT, Brackbill RM, Cone JE, Debchoudhury I, Farfel 
MR, Greene CM, Hadler JL, Kennedy J, Li J, Liff J, Stayner L, 
Stellman SD [2011], Mortality Among Survivors of the Sept 11, 2001, 
Word Trade Center Disaster: Results from the World Trade Center 
Health Registry Cohort, Lancet 378:879-887. Note: percentages may 
not sum to 100 percent due to rounding.
    \67\ Centers for Disease Control and Prevention, National Center 
for Health Statistics, Compressed Mortality File 1999-2016 on CDC 
WONDER Online Database, released June 2017. Data are from the 
Compressed Mortality File 1999-2016 Series 20 No. 2U, 2016, as 
compiled from data provided by the 57 vital statistics jurisdictions 
through the Vital Statistics Cooperative Program. http://wonder.cdc.gov/cmf-icd10.html. Accessed May 29, 2021.
    \68\ Schubauer-Berigan MK, Hein MJ, Raudabaugh WM, Ruder AM, 
Silver SR, Spaeth S, Steenland K, Petersen MR, and Waters KM [2011], 
Update of the NIOSH Life Table Analysis System: A Person-Years 
Analysis program for the Windows Computing Environment, Am J Ind Med 
54:915-924.
    \69\ See supra note 62.
---------------------------------------------------------------------------

Prevalence of Cancer
    To determine the potential number of persons in the responder and 
survivor populations with cancer, the Administrator used the number of 
incident uterine cancer cases described above for each year starting 
with 2002 and estimated the prevalence of uterine cancer using survival 
rate statistics for each incident cancer group through 2025.\70\ Using 
the incident cases and survival rate statistics, the Administrator 
estimated the prevalence (number of persons living with cancer) of 
cases during the 23-year period (2002-2025) since September 11, 2001. 
For the purposes of illustrating an upper bound incidence rate and 
prevalence estimate, the Administrator assumed that the rate of cancer 
in the WTC Health Program exceeds the general U.S. population rate by 
21 percent due to 9/11 exposures. The peer-reviewed literature supports 
the use of a 21 percent excess risk of cancer in the 9/11-exposed 
population over the U.S. population cancer rate; a 2021 study by Li et 
al.\71\ reported an adjusted hazard ratio of 1.21 (95 percent CI: 1.12, 
1.31) for all cancer sites and used a within-cohort comparison less 
affected by healthy worker selection bias. The resulting Table B 
summarizes those results for each year from 2022 through 2025, the 
number of new cases occurring in that year (incidence), the number of 
persons surviving up to 23 years beyond their first diagnosis 
(prevalence), and the number of individuals who might be expected to 
die from their cancer in that year.\72\
---------------------------------------------------------------------------

    \70\ Id.
    \71\ Li J, Yung J, Qiao B, Takemoto E, Goldfarb DG, Zeig-Owens 
R, Cone JE, Brackbill RM, Farfel MR, Kahn AR, Schymura MJ, Shapiro 
MZ, Dasaro CR, Todd AC, Kristjansson D, Prezant DJ, Boffetta P, Hall 
CB [2021], Cancer Incidence in World Trade Center Rescue and 
Recovery Workers: 14 Years of Follow-Up, J Natl Cancer Inst https://doi.org/10.1093/jnci/djab165.
    \72\ The 23-year survival limit is imposed based on the analytic 
time horizon.

[[Page 27969]]



                          Table B--Estimated Incidence and Prevalence of Uterine Cancer
                                                   [2022-2025]
----------------------------------------------------------------------------------------------------------------
                                                       2022            2023            2024            2025
----------------------------------------------------------------------------------------------------------------
                                  Responders (based on ~10,000 female members)
----------------------------------------------------------------------------------------------------------------
New cases.......................................            6.69            6.92            7.14            7.27
Live cases from previous years..................           29.46           30.78           32.09           33.33
Deaths..........................................            5.09            5.37            5.61            5.90
                                                 ---------------------------------------------------------------
    Total cases.................................           36.15           37.70           39.23           40.60
----------------------------------------------------------------------------------------------------------------
                                   Survivors (based on ~16,000 female members)
----------------------------------------------------------------------------------------------------------------
New cases.......................................           10.91           10.91           10.91           10.91
Live cases from previous years..................           53.70           54.72           55.49           56.17
Deaths..........................................            9.60            9.90           10.17           10.31
                                                 ---------------------------------------------------------------
    Total cases.................................           64.61           65.63           66.40           67.08
----------------------------------------------------------------------------------------------------------------
                       Total (based on ~26,000 female WTC responder and survivor members)
----------------------------------------------------------------------------------------------------------------
New cases.......................................            17.6           17.83           18.05           18.18
Live cases from previous years..................           83.16           85.50           87.58           89.50
Deaths..........................................           14.69           15.27           15.78           16.21
                                                 ---------------------------------------------------------------
    Total cases.................................          100.76          103.33          105.63          107.68
----------------------------------------------------------------------------------------------------------------

Cost Computation
    To compute the costs for uterine cancer, the Administrator assumes 
that the individuals diagnosed with uterine cancer will be certified by 
the WTC Health Program for treatment and monitoring services. The 
treatment costs for the first year of treatment (Table A, year 
adjusted) were applied to the predicted newly incident (Year 1) cases 
for each year. Likewise, the costs of treatment for the last year of 
life were applied in each year to the number of people predicted to die 
from their cancer in that year. The costs of continuing treatment from 
Table A were applied to the number of prevalent cases who had survived 
their cancers beyond their year of diagnosis, for each year of survival 
(Year 2-23).
    The estimated treatment costs for responders and survivors were re-
computed under the following two assumptions: (1) The rate of cancer in 
the WTC Health Program is equal to the rate of cancer observed in the 
general U.S. population; and (2) the rate of cancer in the WTC Health 
Program exceeds the general U.S. population rate by 21 percent, as 
discussed above. Costs for future years are discounted at both 7 
percent and 3 percent to reflect net present value.\73\
---------------------------------------------------------------------------

    \73\ See OMB Circular A-94, Guidelines and Discount Rates for 
Benefit-Cost Analysis of Federal Programs. https://www.whitehouse.gov/sites/whitehouse.gov/files/omb/circulars/A94/a094.pdf.
---------------------------------------------------------------------------

    The sum of the annual costs in the table for the years 2022 through 
2025 represents the estimated treatment costs to the WTC Health Program 
for coverage of uterine cancer for the 12 percent of approximately 
82,000 WTC responders who are female and the 50 percent of 
approximately 32,000 WTC survivors who are female.
Summary of Costs
    Because HHS lacks data to account for recoupment from workers' 
compensation insurance or primary payment by either private health 
insurance or Medicare/Medicaid payments, the estimates offered here are 
reflective of estimated WTC Health Program costs only and assume the 
Program is the primary payer. This analysis offers an assumption about 
the number of individuals who might enroll in the WTC Health Program 
and estimates the impact of both a low rate of cancer (U.S. population 
average rate) and an increased rate (21 percent greater than the U.S. 
population average) on the number of cases and the resulting estimated 
treatment costs to the WTC Health Program. This analysis does not 
include administrative costs associated with certifying additional WTC-
related uterine cancers that might result from this action.
    Since the implementation of provisions of the Affordable Care Act 
on January 1, 2014, all members and future members are assumed to have 
or have access to medical insurance coverage other than through the WTC 
Health Program.\74\ Therefore, all treatment costs to be paid by the 
WTC Health Program from 2022 through 2025 are considered transfers.
---------------------------------------------------------------------------

    \74\ Sec. 3331(c)(3) of the PHS Act requires WTC Health Program 
members to maintain minimum essential insurance coverage.

                Table C--Medical Treatment Cost for Uterine Cancer Cases During 2022-2025, 2021$
----------------------------------------------------------------------------------------------------------------
 
----------------------------------------------------------------------------------------------------------------
                                         2022 costs, undiscounted, 2021$       2023-2025          2023-2025
                                                                              costs,* 7%          costs, 3%
                                                                             discount rate      discount rate
                                     ---------------------------------------------------------------------------
                                                   Cancer rate
                                                   Cancer rate
                                     ---------------------------------------------------------------------------
                                       U.S. average    U.S. average + 21%    U.S. average    U.S. average + 21%
----------------------------------------------------------------------------------------------------------------
Responders..........................        $749,741              $907,187      $2,145,844            $2,801,474

[[Page 27970]]

 
Survivors...........................       1,067,098             1,291,189       2,912,084             3,799,381
                                     ---------------------------------------------------------------------------
    Total...........................       1,816,839             2,198,376       5,057,928             6,600,855
----------------------------------------------------------------------------------------------------------------
* Since this table summarizes the lowest and highest cost estimates for treatment of uterine cancer, values
  representing 2023-2025 costs at the 7% discount rate and at the increased cancer rate and 2023-2025 costs at
  the 3% discount rate and at the U.S. population average rate were not included.

    The Administrator found the cost estimate range by adding the low 
2023-2025 estimate in Table C (7 percent discount rate, U.S. cancer 
rate average) and the low estimate for 2022 (U.S. cancer rate average) 
and dividing the sum by four to find the annual low-cost estimate 
(i.e., $1,718,691). The same calculation was done for the annual high-
cost estimates, adding the higher numbers in Table C (3 percent 
discount rate, U.S. cancer rate average +21 percent) to the high 
estimate for 2022 (U.S. cancer rate average +21 percent) and dividing 
the sum by four (i.e., $2,199,808).
Examination of Benefits (Health Impact)
    This section qualitatively describes the potential benefits of this 
rulemaking to add uterine cancer to the List of WTC-Related Health 
Conditions in terms of the expected improvements in the health and 
health-related quality of life of potential uterine cancer patients 
treated through the WTC Health Program, compared to not conducting the 
rulemaking.
    The Administrator does not have information on the health of the 
population that may have experienced 9/11 exposures and is not 
currently enrolled in the WTC Health Program. In addition, the 
Administrator has only limited information about health insurance and 
healthcare services for uterine cancers potentially caused by 9/11 
exposures and suffered by any population of responders and survivors, 
including responders and survivors currently enrolled in the WTC Health 
Program and responders and survivors not enrolled in the Program. For 
the purposes of this analysis, the Administrator assumes that all 
unenrolled responders and survivors are now covered by health insurance 
due to access provided by the Affordable Care Act and may be receiving 
treatment outside the WTC Health Program.
    Although the Administrator cannot quantify the benefits associated 
with the WTC Health Program, members with uterine cancer are expected 
to experience better treatment outcomes as Program members than non-
members. A recent study found that ``WTC-exposed responder cancer 
patients enrolled in the MMTP [WTC Medical Monitoring and Treatment 
Program, a predecessor to the WTC Health Program] had higher survival 
rates compared with those not enrolled in the MMTP.'' \75\ Moreover, 
under other insurance plans, patients would have deductibles and 
copays, which impact access to care and, particularly, its 
timeliness.\76\ WTC Health Program members have first-dollar coverage 
and hence are likely to seek care sooner, when indicated, resulting in 
improved treatment outcomes.
---------------------------------------------------------------------------

    \75\ Goldfarb DG, Zeig-Owens R, Kristjansson D, Li J, Brackbill 
RM, Farfel MR, Cone JE, Kahn AR, Qiao B, Schymura MJ, Webber MP, 
Dasaro CR, Lucchini RG, Todd AC, Prezant DJ, Hall CB, Boffetta P 
[2021], Cancer Survival among World Trade Center Rescue and Recovery 
Workers: A Collaborative Cohort Study, Am J Ind Med 64(10):815-826.
    \76\ Wharam JF, Galbraith AA, Kleinman KP, Soumerai SB, Ross-
Degnan D, Landon BE [2008], Cancer Screening before and after 
Switching to a High-Deductible Health Plan, Ann Intern Med 
148(9):647-655.
---------------------------------------------------------------------------

    Finally, during public meetings, Program members have expressed 
that the lack of social and clinical support, and lack of recognition 
that their diagnosed uterine cancer is a WTC-related health condition, 
have had a significant negative impact on their morale and quality of 
life.
Limitations
    The analysis presented here was limited by the dearth of verifiable 
data on the uterine cancer status of responders and survivors who have 
yet to apply for enrollment in the WTC Health Program. Because of the 
limited data, the Administrator was not able to estimate benefits in 
terms of averted healthcare costs; nor was the Administrator able to 
estimate administrative costs, or indirect costs, such as averted 
absenteeism, short- and long-term disability, and productivity losses 
averted due to premature mortality.

B. Regulatory Flexibility Act

    The Regulatory Flexibility Act (RFA), 5 U.S.C. 601 et seq., 
requires each agency to consider the potential impact of its 
regulations on small entities, including small businesses, small 
governmental units, and small not-for-profit organizations. The 
Administrator certifies that this proposed rule has ``no significant 
economic impact upon a substantial number of small entities'' within 
the meaning of the RFA.

C. Paperwork Reduction Act

    The Paperwork Reduction Act (PRA), 44 U.S.C. 3501 et seq., requires 
an agency to invite public comment on, and to obtain OMB approval of, 
any regulation that requires 10 or more people to report information to 
the agency or to keep certain records. The Administrator has determined 
that this rulemaking does not contain any new information collection 
requirements or recordkeeping requirements; thus, the PRA does not 
apply to this rulemaking. Data collection and recordkeeping 
requirements for the WTC Health Program are approved by OMB under 
``World Trade Center Health Program Enrollment, Appeals & 
Reimbursement'' (OMB Control No. 0920-0891, exp. December 31, 2021, 
currently under OMB review).

D. Small Business Regulatory Enforcement Fairness Act

    As required by Congress under the Small Business Regulatory 
Enforcement Fairness Act of 1996, 5 U.S.C. 801 et seq., HHS will report 
the promulgation of this rule to Congress prior to its effective date.

E. Unfunded Mandates Reform Act of 1995

    Title II of the Unfunded Mandates Reform Act of 1995, 2 U.S.C. 1531 
et seq., directs agencies to assess the effects of Federal regulatory 
actions on state, local, and tribal governments, and the private sector 
``other than to the extent that such regulations incorporate 
requirements specifically set forth in law.'' For purposes of the 
Unfunded Mandates Reform Act, this proposed rule does not include any 
Federal mandate that may result in increased annual expenditures in 
excess of $100 million in 1995 dollars by state, local, or tribal 
governments in the aggregate, or by the private sector.

F. Executive Order 12988 (Civil Justice)

    This proposed rule has been drafted and reviewed in accordance with 
Executive Order 12988, ``Civil Justice Reform,'' and will not unduly 
burden the Federal court system. This rule has

[[Page 27971]]

been reviewed carefully to eliminate drafting errors and ambiguities.

G. Executive Order 13132 (Federalism)

    The Administrator has reviewed this proposed rule in accordance 
with Executive Order 13132 regarding federalism and has determined that 
it does not have ``Federalism implications.'' The rule does not ``have 
substantial direct effects on the states, on the relationship between 
the national government and the states, or on the distribution of power 
and responsibilities among the various levels of government.''

H. Executive Order 13045 (Protection of Children From Environmental 
Health Risks and Safety Risks)

    In accordance with Executive Order 13045, the Administrator has 
evaluated the environmental health and safety effects of this proposed 
rule on children. The Administrator has determined that the rule would 
have no environmental health and safety effect on children.

I. Executive Order 13211 (Actions Concerning Regulations That 
Significantly Affect Energy Supply, Distribution, or Use)

    In accordance with Executive Order 13211, the Administrator has 
evaluated the effects of this proposed rule on energy supply, 
distribution, or use, and has determined that the rule will not have a 
significant adverse effect.

J. Plain Writing Act of 2010

    Under Public Law 111-274 (October 13, 2010), Executive Departments 
and Agencies are required to use plain language in documents that 
explain to the public how to comply with a requirement the Federal 
Government administers or enforces. The Administrator has attempted to 
use plain language in promulgating the proposed rule consistent with 
the Federal Plain Writing Act guidelines and requests public comment on 
this effort.

List of Subjects in 42 CFR Part 88

    Aerodigestive disorders, Appeal procedures, Cancer, Healthcare, 
Mental health conditions, Musculoskeletal disorders, Respiratory and 
pulmonary diseases.

    For the reasons discussed in the preamble, the Administrator and 
HHS Secretary propose to amend 42 CFR part 88 as follows:

PART 88--WORLD TRADE CENTER HEALTH PROGRAM

0
1. The authority citation for part 88 is revised to read as follows:

    Authority: 42 U.S.C. 300mm to 300mm-61.

0
2. Amend Sec.  88.15 as follows:
0
a. Redesignate paragraphs (d)(15) through (24) as paragraphs (d)(16) 
through (25).
0
b. Add new paragraph (d)(15).
0
c. In newly redesignated paragraph (d)(24), remove ``Childhood 
cancers:'' and add ``Childhood cancers:'' in its place.
0
d. In newly redesignated paragraph (d)(25), remove ``Rare cancers:'' 
and add ``Rare cancers:'' in its place.
    The addition reads as follows:


Sec.  88.15  List of WTC-Related Health Conditions.

* * * * *
    (d) * * *
    (15) Malignant neoplasms of corpus uteri and uterus, part 
unspecified.
* * * * *

John J. Howard,
Administrator, World Trade Center Health Program and Director, National 
Institute for Occupational Safety and Health, Centers for Disease 
Control and Prevention, Department of Health and Human Services.
Xavier Becerra,
Secretary, Department of Health and Human Services.
[FR Doc. 2022-09708 Filed 5-9-22; 8:45 am]
BILLING CODE 4163-18-P