[Federal Register Volume 82, Number 133 (Thursday, July 13, 2017)]
[Proposed Rules]
[Pages 32312-32315]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2017-14559]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

42 CFR Part 88

[NIOSH Docket 094]


World Trade Center Health Program; Petitions 016 and 017--
Parkinson's Disease and Parkinsonism, Including Manganese-Induced 
Parkinsonism; Finding of Insufficient Evidence

AGENCY: Centers for Disease Control and Prevention, HHS.

ACTION: Denial of petitions for addition of health conditions.

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SUMMARY: On February 22, 2017, the Administrator of the World Trade 
Center (WTC) Health Program received a petition (Petition 016) to add 
Parkinson's disease and parkinsonism, including manganese-induced 
parkinsonism, to the List of WTC-Related Health Conditions (List). On 
May 10, 2017, the Administrator received a second petition (Petition 
017) to add the same health conditions to the List. Upon reviewing the 
scientific and medical literature, including information provided by 
the two petitioners, the Administrator has determined that the 
available evidence does not have the potential to provide a basis for a 
decision on whether to add Parkinson's disease and/or parkinsonism, 
including manganese-induced parkinsonism, to the List. 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 these 
petitions for the addition of health conditions as of July 13, 2017.

FOR FURTHER INFORMATION CONTACT: Rachel Weiss, Program Analyst, 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

A. WTC Health Program Statutory Authority
B. Petition 016 and Petition 017
C. Review of Scientific and Medical Information and Administrator 
Determination
D. Administrator's Final Decision on Whether to Propose the Addition 
of Parkinson's Disease and/or Parkinsonism, Including Manganese-
Induced Parkinsonism, to the List
E. 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), added Title 
XXXIII to the Public Health Service (PHS) Act,\1\

[[Page 32313]]

establishing the WTC Health Program within the Department of Health and 
Human Services (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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    \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.
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    All references to the Administrator of the WTC Health Program 
(Administrator) in this notice 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 (2017). Within 90 days after receipt of a 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 42 CFR 88.16(a)(2): (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. In accordance with 42 CFR 88.16(a)(4), the 
Administrator may consider more than one petition simultaneously when 
the petitions propose the addition of the same health condition(s) and 
the required Federal Register notices may respond to more than one 
petition.
    In addition to the regulatory provisions, the WTC Health Program 
has developed policies to guide the review of submissions and 
petitions,\2\ as well as the analysis of evidence supporting the 
potential addition of a non-cancer health condition to the List.\3\ In 
accordance with the aforementioned non-cancer health condition addition 
policy, the Administrator directs the WTC Health 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. The 
literature review includes a search for peer-reviewed, published, 
epidemiologic studies (including direct observational studies in the 
case of health conditions such as injuries) about the health condition 
among 9/11-exposed populations. The Program evaluates the scientific 
quality limitations 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 \4\ to be causally associated 
with 9/11 exposures. If the evaluation of evidence provided 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 \5\ 
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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    \2\ 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, http://www.cdc.gov/wtc/pdfs/WTCHPPPPetitionHandlingProcedures14May2014.pdf.
    \3\ See WTC Health Program [2017], Policy and Procedures for 
Adding Non-Cancer Conditions to the List of WTC-Related Health 
Conditions, February 14, https://www.cdc.gov/wtc/pdfs/WTCHP_PP_Adding_NonCancers_14_February_2017.pdf.
    \4\ 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.
    \5\ 9/11 agents are chemical, physical, biological, or other 
agents or hazards reported in a published, peer-reviewed exposure 
assessment study of responders or survivors who were present in the 
New York City disaster area, at the Pentagon site, or at the 
Shanksville, Pennsylvania site, as those locations are defined in 42 
CFR 88.1.
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B. Petition 016 and Petition 017

    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 to the petitioned health condition may also provide 
sufficient medical basis for a valid petition.
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    \6\ See supra note 2.
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    On February 22, 2017, the Administrator received a petition 
(Petition 016) from a WTC responder who worked at Ground Zero, 
requesting the addition of ``young onset Parkinson Disease'' \7\ and 
``Parkinsonia Syndrome'' to the List. The petition included eight peer-
reviewed, published studies and reviews of studies of parkinsonism 
associated with manganese exposure in non-9/11-exposed populations and 
laboratory animals, and mechanistic studies of manganese-induced 
parkinsonism, discussed below.\8\ The Program noted the various terms 
used to describe the health condition in the petition and the 
references included with the petition. 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.\9\ The term ``Parkinsonia 
Syndrome,'' used by the petitioner, was likely intended to refer to 
``Parkinsonian syndrome,'' a less-commonly used term for atypical 
parkinsonism.
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    \7\ The diagnosis of young-onset Parkinson's disease is the same 
as typical Parkinson's disease, except for the age of the patient.
    \8\ See Petition 016, WTC Health Program: Petitions Received, 
http://www.cdc.gov/wtc/received.html.
    \9\ See Kwakye GF, Paoliello MMB, Mukhopadhyay S, et al. [2015], 
Manganese-Induced Parkinsonism and Parkinson's Disease: Shared and 
Distinguishable Features, Int J Environ Res Public Health 
12(7):7519-7540).
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    The first of the eight peer-reviewed, published studies provided in 
Petition

[[Page 32314]]

016, reference 1, ``Manganese-Induced Parkinsonism Is Not Idiopathic 
Parkinson's Disease: Environmental and Genetic Evidence'' by Guilarte 
et al. [2015],\10\ is a review of various peer-reviewed and published 
epidemiologic and animal studies highlighting the difference between 
manganese-induced parkinsonism and Parkinson's disease. Reference 2, 
``Manganese-Induced Parkinsonism and Parkinson's Disease: Shared and 
Distinguishable Features'' by Kwakye et al. [2015],\11\ is also a 
review of peer-reviewed and published epidemiologic, animal, and 
mechanistic studies comparing characteristics of manganese-induced 
parkinsonism and Parkinson's disease. Reference 3, ``Inducible Nitric 
Oxide Synthase Gene Methylation and Parkinsonism in Manganese-Exposed 
Welders'' by Searles et al. [2015],\12\ is an epidemiologic study 
examining gene methylation of inducible nitric oxide synthase, an 
enzyme involved in inflammation, among manganese-exposed welders. 
Reference 4, ``[alpha]-Synuclein Protects Against Manganese Neurotoxic 
Insult During the Early Stages of Exposure in a Dopaminergic Cell Model 
of Parkinson's Disease'' by Harischandra et al. [2015],\13\ is an ex 
vivo laboratory study in rat cell lines exploring the effects of 
[alpha]-synuclein, a protein found in the brain, on manganese-induced 
dopaminergic neurotoxicity. Reference 5, ``SLC30A10 is a Cell Surface-
Localized Manganese Efflux Transporter, and Parkinsonism-Causing 
Mutations Block its Intracellular Trafficking and Efflux Activity'' by 
Leyva-Illades et al. [2014],\14\ is a mechanistic and functional cell 
culture study looking at the role of interactions between genetic and 
environmental factors in the development of parkinsonism. Reference 6, 
``Correlation Between the Biochemical Pathways Altered by Mutated 
Parkinson-Related Genes and Chronic Exposure to Manganese'' by Roth 
[2014],\15\ is a review of peer-reviewed, published studies describing 
genes involved in the development of parkinsonism and illustrating how 
the proposed mechanism of each gene may relate to the onset and 
severity of manganese toxicity. Reference 7, ``Manganese-Induced 
Atypical Parkinsonism is Associated with Altered Basal Ganglia Activity 
and Changes in Tissue Levels of Monoamines in the Rat'' by Bouabid et 
al. [2014],\16\ is a study on changes to motor and non-motor functions 
and behavior, similar to those observed in parkinsonism, in manganese-
exposed rats. Finally, reference 8, ``Neurofunctional Dopaminergic 
Impairment in Elderly After Lifetime Exposure to Manganese'' by 
Lucchini et al. [2014],\17\ is an epidemiologic study of the effects of 
manganese exposure due to emissions from nearby ferroalloy plants on 
the neurocognitive and motor functions of elderly study participants.
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    \10\ Guilarte TR, Gonzales KK [2015], Manganese-Induced 
Parkinsonism is Not Idiopathic Parkinson's Disease: Environmental 
and Genetic Evidence, Toxicol Sci 146(2):204-212.
    \11\ Supra note 9.
    \12\ Searles Nielsen S, Checkoway H, Criswell SR, et al. [2015], 
Inducible Nitric Oxide Synthase Gene Methylation and Parkinsonism in 
Manganese-Exposed Welders, Parkinsonism. Relat Disord 21(4):355-60.
    \13\ Harischandra DS, Jin H, Anantharam V, et al. [2015], 
[alpha]-Synuclein Protects Against Manganese Neurotoxic Insult 
During the Early Stages of Exposure in a Dopaminergic Cell Model of 
Parkinson's Disease, Toxicol Sci 143(2):454-468.
    \14\ Leyva-Illades D, Chen P, Zogzas CE, et al. [2014], SLC30A10 
Is a Cell Surface-Localized Manganese Efflux Transporter, and 
Parkinsonism-Causing Mutations Block Its Intracellular Trafficking 
and Efflux Activity, J Neurosci 34(42):14079-14095.
    \15\ Roth, JA [2014], Correlation Between the Biochemical 
Pathways Altered by Mutated Parkinson-Related Genes and Chronic 
Exposure to Manganese, Neurotoxicology Sep;44:314-325.
    \16\ Bouabid S, Delaville C, De Deurwaerd[egrave]re P, et al. 
[2014], Manganese-Induced Atypical Parkinsonism Is Associated With 
Altered Basal Ganglia Activity and Changes in Tissue Levels of 
Monoamines in the Rat, PLoS ONE 9(6):e98952.
    \17\ Lucchini RG, Guazzetti S, Zoni S, et al. [2014], 
Neurofunctional Dopaminergic Impairment in Elderly After Lifetime 
Exposure to Manganese, Neurotoxicology 0:309-17.
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    The eight references offered as medical basis for Petition 016 
suggested a potential association between exposure to the 9/11 agent 
manganese and manganese-induced parkinsonism and Parkinson's disease 
and established a sufficient medical basis to consider the submission a 
valid petition for manganese-induced parkinsonism. Although the 
petitioner requested the addition of ``young onset Parkinson Disease'' 
and ``Parkinsonia Syndrome,'' the medical basis provided by the 
petitioner primarily included studies concerning manganese-induced 
parkinsonism; therefore, the Administrator determined that the 
petitioner requested the addition of both Parkinson's disease and 
parkinsonism, including manganese-induced parkinsonism.
    On May 10, 2017, the Administrator received a petition from a WTC 
survivor (Petition 017), requesting the addition of ``Parkinson's 
Disease'' to the List. The petition referenced five peer-reviewed, 
published, epidemiologic studies of heavy metal exposure, including 
manganese, and Parkinson's disease or parkinsonism in non-9/11-exposed 
populations.\18\
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    \18\ See Petition 017, WTC Health Program: Petitions Received, 
http://www.cdc.gov/wtc/received.html.
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    The first of the five peer-reviewed, published, epidemiologic 
studies provided in Petition 017, reference 1, ``Increased Risk of 
Parkinsonism Associated With Welding Exposure'' by Racette et al. 
[2012],\19\ examined the prevalence and clinical characteristics of 
parkinsonism among workers exposed to welding fumes. Reference 2, 
``Inducible Nitric Oxide Synthase Gene Methylation and Parkinsonism in 
Manganese-Exposed Welders'' by Searles et al. [2015],\20\ was also 
cited as reference 3 in Petition 016, as discussed above. Reference 3, 
``Multiple Risk Factors for Parkinson's Disease'' by Gorell et al. 
[2004],\21\ evaluated the contribution of various occupational, 
lifestyle, and genetic risk factors, including manganese exposure, to 
the development of Parkinson's disease. Reference 4, ``Occupational 
Exposure to Manganese, Copper, Lead, Iron, Mercury and Zinc and the 
Risk of Parkinson's Disease'' by Gorell et al. [1999],\22\ assessed the 
association between a variety of heavy metals and Parkinson's disease. 
Finally, reference 5, ``Whole-Body Lifetime Occupational Lead Exposure 
and Risk of Parkinson's Disease'' by Coon et al. [2006],\23\ evaluated 
the role of chronic lead exposure among individuals with Parkinson's 
disease.
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    \19\ Racette BA, et al. [2012], Increased Risk of Parkinsonism 
Associated With Welding Exposure, Neurotoxicology 33(5):1356-1361.
    \20\ Supra note 12.
    \21\ Gorell JM, et al. [2004], Multiple Risk Factors for 
Parkinson's Disease, J Neurol Sci 217(2):169-174.
    \22\ Gorell JM, et al. [1999], Occupational Exposure to 
Manganese, Copper, Lead, Iron, Mercury and Zinc and the Risk of 
Parkinson's Disease, Neurotoxicology 20(2-3):239-247.
    \23\ Coon S, Stark A, Peterson E, et al. [2006], Whole-Body 
Lifetime Occupational Lead Exposure and Risk of Parkinson's Disease, 
Environ Health Perspect Dec;114(12):1872-6.
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    These five studies suggested a potential association between 
exposure to known 9/11 agents and Parkinson's disease and parkinsonism, 
including manganese-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 both Parkinson's disease and manganese-induced parkinsonism, 
the Administrator determined that the petitioner requested the addition 
of both Parkinson's disease and manganese-induced parkinsonism.
    Since the Administrator determined that the scope of both Petition 
016 and

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Petition 017 include requests for the addition of Parkinson's disease 
and parkinsonism, including manganese-induced parkinsonism, the 
Administrator decided to exercise his discretion, as permitted by 42 
CFR 88.16(a)(4), to combine consideration of the petitions and issue a 
single Federal Register notice.

C. Review of Scientific and Medical Information and Administrator 
Determination

    In response to Petition 016 and Petition 017, and pursuant to the 
Program policy on the addition of non-cancer health conditions to the 
List,\24\ the Program conducted reviews of the scientific literature on 
Parkinson's disease and parkinsonism, including manganese-induced 
parkinsonism.\25\
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    \24\ Supra note 3.
    \25\ Databases searched include: Embase, NIOSHTIC-2, ProQuest 
Health & Safety, PsycINFO, PubMed, Scopus, Toxicology Abstracts, and 
TOXLINE.
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    Neither the references provided in the petitions nor the literature 
search conducted by the Program identified any peer-reviewed, 
published, epidemiologic studies of either Parkinson's disease or 
parkinsonism, including manganese-induced parkinsonism, in 9/11-exposed 
populations. Since no peer-reviewed, published, epidemiologic studies 
of Parkinson's disease or parkinsonism, including manganese-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.

D. Administrator's Final Decision on Whether To Propose the Addition of 
Parkinson's Disease and/or Manganese-Induced Parkinsonism to the List

    Because no peer-reviewed, published, epidemiologic studies of 
Parkinson's disease or parkinsonism, including manganese-induced 
parkinsonism, in 9/11 populations were identified, the Administrator 
has determined that insufficient evidence is available to take further 
action at this time, including either proposing the addition of 
Parkinson's disease or parkinsonism, including manganese-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 016 and Petition 017 
requests to add Parkinson's disease and/or parkinsonism, including 
manganese-induced parkinsonism, to the List of WTC-Related Health 
Conditions are denied.

E. 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. Anne 
Schuchat, M.D., Acting Director, CDC, and Acting Administrator, ATSDR, 
approved this document for publication on July 6, 2017.

John 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. 2017-14559 Filed 7-12-17; 8:45 am]
 BILLING CODE 4163-18-P