[Federal Register Volume 85, Number 33 (Wednesday, February 19, 2020)]
[Proposed Rules]
[Pages 9441-9444]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2020-02991]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Centers for Disease Control and Prevention

42 CFR Part 88

[NIOSH Docket 094]


World Trade Center Health Program; Petition 025--Parkinson's 
Disease and Parkinsonism, Including Heavy Metal-Induced Parkinsonism; 
Finding of Insufficient Evidence

AGENCY: Centers for Disease Control and Prevention, HHS.

ACTION: Denial of petition for addition of a health condition.

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SUMMARY: On October 15, 2019, the Administrator of the World Trade 
Center (WTC) Health Program received a petition (Petition 025) to add 
``Parkinson's disease'' to the List of

[[Page 9442]]

WTC-Related Health Conditions (List). Upon reviewing the scientific and 
medical literature, including information provided by the petitioner, 
the Administrator has determined that there is insufficient evidence 
available to support taking further action at this time regarding 
Parkinson's disease and parkinsonism, including heavy metal-induced 
parkinsonism. The Administrator also finds that insufficient evidence 
exists to request a recommendation of the WTC Health Program 
Scientific/Technical Advisory Committee (STAC), to publish a proposed 
rule, or to publish a determination not to publish a proposed rule.

DATES: The Administrator of the WTC Health Program is denying this 
petition for the addition of a health condition as of February 19, 
2020.

ADDRESSES: Visit the WTC Health Program website at https://www.cdc.gov/wtc/received.html to review Petition 025.

FOR FURTHER INFORMATION CONTACT: Rachel Weiss, Program Analyst, 1090 
Tusculum Avenue, MS: C-48, Cincinnati, OH 45226; telephone (855) 818-
1629 (this is a toll-free number); email [email protected].

SUPPLEMENTARY INFORMATION: 

Table of Contents

A. WTC Health Program Statutory Authority
B. Procedures for Evaluating a Petition
C. Petition 025
D. Review of Scientific and Medical Information and Administrator 
Determination
E. Administrator's Final Decision on Whether To Propose the Addition 
of Parkinson's Disease and Parkinsonism, Including Heavy Metal-
Induced Parkinsonism, to the List
F. Approval To Submit Document to the Office of the Federal Register

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 Public Health Service (PHS) Act,\1\ 
establishing the WTC Health Program within the Department of Health and 
Human Services (HHS). The WTC Health Program provides medical 
monitoring and treatment benefits for health conditions on the List \2\ 
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). The Program 
also provides benefits 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 \3\ (survivors).
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    \1\ Title XXXIII of the PHS Act is codified at 42 U.S.C. 300mm 
to 300mm-61. Those portions of the James Zadroga 9/11 Health and 
Compensation Act of 2010 found in Titles II and III of Public Law 
111-347 do not pertain to the WTC Health Program and are codified 
elsewhere.
    \2\ The List of WTC-Related Health Conditions is established in 
42 U.S.C. 300mm-22(a)(3)-(4) and 300mm-32(b); additional conditions 
may be added through rulemaking and the complete list is provided in 
WTC Health Program regulations at 42 CFR 88.15.
    \3\ See 42 U.S.C. 300mm-5(7); 42 CFR 88.1.
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    All references to the Administrator of the WTC Health Program 
(Administrator) in this document mean the Director of the National 
Institute for Occupational Safety and Health (NIOSH) or his designee.
    Pursuant to section 3312(a)(6)(B) of the PHS Act, interested 
parties may petition the Administrator to add a health condition to the 
List in 42 CFR 88.15. Within 90 days after receipt of a valid petition 
to add a condition to the List, the Administrator must take one of the 
following four actions described in section 3312(a)(6)(B) of the PHS 
Act and Sec.  88.16(a)(2) of the Program regulations: (1) Request a 
recommendation of the STAC; (2) publish a proposed rule in the Federal 
Register to add such health condition; (3) publish in the Federal 
Register the Administrator's determination not to publish such a 
proposed rule and the basis for such determination; or (4) publish in 
the Federal Register a determination that insufficient evidence exists 
to take action under (1) through (3) above.
    More information about the WTC Health Program, including the List 
and the petition process, is available at www.cdc.gov/wtc/.

B. Procedures for Evaluating a Petition

    In addition to the regulatory provisions, the WTC Health Program 
has developed policies to guide the review of submissions and 
petitions,\4\ as well as the analysis of evidence supporting the 
potential addition of a non-cancer health condition to the List.\5\
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    \4\ See WTC Health Program [2014], Policy and Procedures for 
Handling Submissions and Petitions to Add a Health Condition to the 
List of WTC-Related Health Conditions, May 14, 2014, http://www.cdc.gov/wtc/pdfs/WTCHPPPPetitionHandlingProcedures14May2014.pdf.
    \5\ See WTC Health Program [2017], Policy and Procedures for 
Adding Non-Cancer Conditions to the List of WTC-Related Health 
Conditions, February 14, 2017, https://www.cdc.gov/wtc/pdfs/policies/WTCHP_PP_Adding_NonCancers_14_February_2017-508.pdf.
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    A valid petition must include sufficient medical basis for the 
association between the September 11, 2001, terrorist attacks and the 
health condition to be added. In accordance with WTC Health Program 
policy, reference to a peer-reviewed, published, epidemiologic study 
about the health condition among 9/11-exposed populations or to 
clinical case reports of health conditions in WTC responders or 
survivors may demonstrate the required medical basis.\6\ Studies 
linking 9/11 agents or hazards \7\ to the petitioned health condition 
may also provide sufficient medical basis for a valid petition.
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    \6\ See supra note 4.
    \7\ 9/11 agents are 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. See WTC 
Health Program [2018], Development of the Inventory of 9/11 Agents, 
July 17, 2018, https://wwwn.cdc.gov/ResearchGateway/Content/pdfs/Development_of_the_Inventory_of_9-11_Agents_20180717.pdf.
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    After the Program has determined that a petition is valid, the 
Administrator must direct the Program to conduct a review of the 
scientific literature to determine if the available scientific 
information has the potential to provide a basis for a decision on 
whether to add the health condition to the List.\8\ The literature 
review is a keyword search of relevant scientific databases intended to 
identify peer-reviewed, published, epidemiologic studies about the 
health condition among 9/11-exposed populations. The Program evaluates 
the scientific quality of each peer-reviewed, published, epidemiologic 
study of the health condition identified in the literature search; the 
Program then compiles the scientific results of each study to assess 
whether a causal relationship between 9/11 exposures and the health 
condition is supported and evaluates whether the results of the studies 
are representative of the 9/11-exposed population of responders and 
survivors. A health condition may be added to the List if peer-
reviewed, published, epidemiologic studies provide support that the 
health condition is substantially likely \9\ to be causally associated 
with 9/11 exposures. If the evaluation of evidence provided

[[Page 9443]]

in peer-reviewed, published, epidemiologic studies of the health 
condition in 9/11 populations demonstrates a high, but not substantial, 
likelihood of a causal association between the 9/11 exposures and the 
health condition, then the Administrator may consider additional highly 
relevant scientific evidence regarding exposures to 9/11 agents from 
sources using non-9/11-exposed populations. If that additional 
assessment establishes that the health condition is substantially 
likely to be causally associated with 9/11 exposures among 9/11-exposed 
populations, the health condition may be added to the List.
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    \8\ See supra note 5.
    \9\ The ``substantially likely'' standard is met when the 
scientific evidence, taken as a whole, demonstrates a strong 
relationship between the 9/11 exposures and the health condition.
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    More information about the WTC Health Program, including the List 
and the petition process, is available at www.cdc.gov/wtc/.

C. Petition 025

    On October 15, 2019, the Administrator received a petition 
(Petition 025) requesting the addition of ``Parkinson's disease'' to 
the List.\10\ The Program has determined that the scope of the Petition 
025 review should include not only ``Parkinson's disease'' but also 
``parkinsonism, including heavy metal-induced parkinsonism,'' \11\ 
because the references provided in the petition address the association 
between copper, iron, and manganese and the health condition, as 
described below.
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    \10\ See Petition 025, WTC Health Program: Petitions Received, 
http://www.cdc.gov/wtc/received.html.
    \11\ ``The general term `Parkinsonism' refers to a category of 
neurological diseases exhibiting disturbance in the dopamine systems 
of the basal ganglia, which leads to the symptoms characterizing the 
disease: Tremors, slowness of movement, and stiffness. Classic 
(idiopathic) Parkinson's disease is the most common and treatable 
form of parkinsonism; non-idiopathic types are considered atypical 
and referred to by the more general term ```parkinsonism.' One type 
of atypical parkinsonism, manganese-induced parkinsonism, has been 
found to be caused by elevated and prolonged exposure to 
manganese.'' World Trade Center Health Program; Petitions 016 and 
017--Parkinson's Disease and Parkinsonism, Including Manganese-
Induced Parkinsonism; Finding of Insufficient Evidence, 82 FR 32312 
at 32313, July 13, 2017.
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    The petition's validity was established by references to four web 
articles \12\ which, in turn, referenced six peer-reviewed, published 
epidemiologic studies and literature reviews identifying a positive 
association between 9/11 agents and Parkinson's disease and/or 
parkinsonism (although none of the studies were conducted in the 9/11-
exposed population). A quote provided in the petition is attributed to 
a seventh peer-reviewed, published epidemiologic study. Because the web 
articles reference scientific sources identifying a positive 
association between 9/11 agents and the petitioned condition, the 
petition provides the necessary medical basis to require the 
Administrator to conduct an evaluation of the petition. The referenced 
studies and literature reviews each individually establishing a medical 
basis are as follows:
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    \12\ Adams C. [2018], Parkinson's Disease Linked to Exposure to 
Heavy Metals, https://www.realnatural.org/parkinsons-disease-linked-to-exposure-to-heavy-metals/; The Parkinson's Plan [2018], Heavy 
Metals, Neurotoxins, and Parkinson's Disease, https://www.theparkinsonsplan.com/blog/heavy-metals-and-parkinsons-disease/; 
Iowa State University News Service [2019], Researchers Explore Link 
Between Metal Exposure and Parkinson's Symptoms, https://www.news.iastate.edu/news/2019/03/12/manganeseparkinsons; Wilson L 
[2019], Parkinson's Disease, https://drlwilson.com/Articles/PARKINSON.htm.>
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    [ssquf] Heavy Metals and the Etiology of Parkinson's Disease and 
Other Movement Disorders, by Montgomery [1994],\13\ is a peer-reviewed, 
published literature review discussing the role of heavy metals (iron 
and manganese) in Parkinson's disease and speculating on possible 
mechanisms of pathogenesis.
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    \13\ Montgomery EB [1994], Heavy Metals and the Etiology of 
Parkinson's Disease and Other Movement Disorders, Toxicology 97(1), 
https://doi.org/10.1016/0300-483X(94)02962-T.
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    [ssquf] *Metals, Oxidative Stress and Neurodegenerative Disorders, 
by Jomova et al. [2010],\14\ is a peer-reviewed, published review 
article discussing the role of iron, copper, and zinc in the oxidative 
stress-related etiology of Parkinson's disease (the theory that heavy 
metals cause oxidative stress, which in turn leads to the 
neurodegeneration that characterizes Parkinson's disease).
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    \14\ Jomova K, Vondrakova D, Lawson M, Valko M [2010], Metals, 
Oxidative Stress and Neurodegenerative Disorders, Mol Cell Biochem 
345(1-2), 91-104.
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    [ssquf] *Metal Emissions and Urban Incident Parkinson Disease: A 
Community Health Study of Medicare Beneficiaries by Using Geographic 
Information Systems, by Willis et al. [2010],\15\ is a peer-reviewed, 
published epidemiologic study demonstrating increased Parkinson's 
disease incidence in urban counties with high levels of environmental 
copper or manganese.
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    \15\ Willis AW, Evanoff BA, Lian M, Galarza A, Wegrzyn A, 
Schootman M, Racette BA [2010], Metal Emissions and Urban Incident 
Parkinson Disease: A Community Health Study of Medicare 
Beneficiaries by Using Geographic Information Systems, Am J 
Epidemiol 172(12):1357-1363.
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    [ssquf] *Association of Parkinson's Disease with Altered Serum 
Levels of Lead and Transition Metals among South Indian Subjects, by 
Kumudini et al. [2014],\16\ is a peer-reviewed, published epidemiologic 
(case-control) study demonstrating the positive association of 
Parkinson's disease with plasma levels of iron and copper in urban and 
rural populations in India. The authors speculate that increased iron 
levels induce oxidative stress which leads to Parkinson's disease.
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    \16\ Kumudini N, Uma A, Devi YP, Naushad SM, Mridula R, 
Borgohain R, Kutala VK [2014], Association of Parkinson's Disease 
with Altered Serum Levels of Lead and Transition Metals among South 
Indian Subjects, Indian J Biochem Biophys 51(2):121-126.
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    [ssquf] *A Revised Picture of the Cu (II)- [alpha]-Synuclein 
Complex: The Role of N-Terminal Acetylation, by Moriarty et al. 
[2014],\17\ is a peer-reviewed, published in vitro study suggesting new 
avenues of investigation into copper-mediated neurodegeneration in 
Parkinson's disease pathology.
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    \17\ Moriarty GM, Minetti CA, Remeta DP, Baum J [2014], A 
Revised Picture of the Cu (II)--[alpha]-Synuclein Complex: The Role 
of N-Terminal Acetylation, Biochemistry 53(17), 2815-2817.
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    [ssquf] *Inflammasomes: An Emerging Mechanism Translating 
Environmental Toxicant Exposure into Neuroinflammation in Parkinson's 
Disease, by Anderson et al. [2018],\18\ is a peer-reviewed, published 
literature review positing that exposure to heavy metals, which are 
known to cause cellular stress, may do so by triggering intracellular 
inflammasomes (cytosolic assemblies of proteins) which in turn lead to 
neurodegeneration and Parkinson's disease.
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    \18\ Anderson FL, Coffey MM, Berwin BL, Havrda MC [2018], 
Inflammasomes: An Emerging Mechanism Translating Environmental 
Toxicant Exposure into Neuroinflammation in Parkinson's Disease, 
Toxicol Sci 166(1), 3-15.
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    [ssquf] *Manganese Promotes the Aggregation and Prion-Like Cell-to-
Cell Exosomal Transmission of [alpha]-Synuclein, by Harischandra et al. 
[2019],\19\ is a peer-reviewed, published experimental study 
demonstrating in cell cultures and animal models that manganese 
exposure promotes the pathological propagation of [alpha]-synuclein (a 
neuronal protein found in the brain) leading to Parkinson's disease 
through neuroinflammation and neurodegeneration.
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    \19\ Harischandra DS, Rokad D, Neal ML, Ghaisas S, Manne S, 
Sarkar S, Panicker N, Zenitsky G, Jin H, Lewis M, Huang X, 
Anantharam V, Kanthasamy A, Kanthasamy AG [2019], Manganese Promotes 
the Aggregation and Prion-Like Cell-to-Cell Exosomal Transmission of 
[alpha]-Synuclein, Sci Signal 12(572).
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    These seven studies suggest a potential association between 
exposure to 9/11 agents (specifically copper, iron, and manganese) and 
Parkinson's disease and parkinsonism, including heavy metal-induced 
parkinsonism, and thus provided a sufficient medical basis to consider 
the submission a valid petition. Because the medical basis provided by 
the petitioner included studies concerning parkinsonism

[[Page 9444]]

induced by copper, iron, and manganese, the Administrator determined 
that the petitioner requested the addition of both Parkinson's disease 
and parkinsonism, including heavy metal-induced parkinsonism.

D. Review of Scientific and Medical Information and Administrator 
Determination

    In response to Petition 025, and pursuant to the Program policy on 
the addition of non-cancer health conditions to the List, the Program 
conducted a review of the scientific literature on Parkinson's disease 
and parkinsonism, including heavy metal-induced parkinsonism, to 
identify peer-reviewed, published, epidemiologic studies of the health 
condition in the 9/11-exposed population.\20\
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    \20\ Databases searched include: CINAHL, Embase, NIOSHTIC-2, 
ProQuest Health & Safety, PsycINFO, PubMed, Scopus, Toxicology 
Abstracts, TOXLINE, and the WTCHP Research Compendium Endnote 
Database. Keywords/phrases used to conduct the search include: World 
Trade Center; WTC; September 11; parkinsonian disorders; parkinson*; 
manganism; supranuclear palsy, progressive; progressive supranuclear 
palsy; multiple system atrophy; multiple system atrophy; Lewy body 
disease; dementia with Lewy bodies; corticobasal degeneration; 
hypokinesia; bradykinesia; tremor; tremors; slow movement; 
stiffness; muscle rigidity; rigidity; masked face; micrographia; 
monotonous speech; loss of postural reflex; cock-walk gait; 
asymmetric dystonia; levodopa; basal ganglia; and basal ganglia 
nuclei. The literature search was conducted in English-language 
journals on December 27, 2019.
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    Neither the references provided in the petitions, including those 
described above, nor the literature search conducted by the Program 
identified any peer-reviewed, published, epidemiologic studies of 
either Parkinson's disease or parkinsonism, including heavy metal-
induced parkinsonism, in 9/11-exposed populations. Pursuant to the WTC 
Health Program's policy on the evaluation of petitions,\21\ since no 
peer-reviewed, published, epidemiologic studies of Parkinson's disease 
or parkinsonism, including heavy metal-induced parkinsonism, in 9/11 
populations were identified, the Program was unable to conduct an 
evaluation of scientific evidence to determine the likelihood of a 
causal association between 9/11 exposures and the petitioned health 
conditions.
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    \21\ See supra note 5.
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E. Administrator's Final Decision on Whether To Propose the Addition of 
Parkinson's Disease and Parkinsonism, Including Heavy Metal-Induced 
Parkinsonism, to the List

    Pursuant to PHS Act, sec. 3312(a)(6)(B)(iv) and 42 CFR 
88.16(a)(2)(iv), the Administrator has determined that insufficient 
evidence is available to take further action at this time, including 
proposing the addition of Parkinson's disease and parkinsonism, 
including heavy metal-induced parkinsonism, to the List (pursuant to 
PHS Act, sec. 3312(a)(6)(B)(ii) and 42 CFR 88.16(a)(2)(ii)) or 
publishing a determination not to publish a proposed rule in the 
Federal Register (pursuant to PHS Act, sec. 3312(a)(6)(B)(iii) and 42 
CFR 88.16(a)(2)(iii)). The Administrator has also determined that 
requesting a recommendation from the STAC (pursuant to PHS Act, sec. 
3312(a)(6)(B)(i) and 42 CFR 88.16(a)(2)(i)) is unwarranted.
    For the reasons discussed above, the Petition 025 request to add 
Parkinson's disease and parkinsonism, including heavy metal-induced 
parkinsonism, to the List of WTC-Related Health Conditions is denied.

F. Approval To Submit Document to the Office of the Federal Register

    The Secretary, HHS, or his designee, the Director, Centers for 
Disease Control and Prevention (CDC) and Administrator, Agency for 
Toxic Substances and Disease Registry (ATSDR), authorized the 
undersigned, the Administrator of the WTC Health Program, to sign and 
submit the document to the Office of the Federal Register for 
publication as an official document of the WTC Health Program. Robert 
Redfield M.D., Director, CDC, and Administrator, ATSDR, approved this 
document for publication on February 3, 2020.

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.
[FR Doc. 2020-02991 Filed 2-18-20; 8:45 am]
 BILLING CODE 4163-18-P