[Federal Register Volume 73, Number 213 (Monday, November 3, 2008)]
[Proposed Rules]
[Pages 65280-65282]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E8-26175]


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 Proposed Rules
                                                 Federal Register
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 This section of the FEDERAL REGISTER contains notices to the public of 
 the proposed issuance of rules and regulations. The purpose of these 
 notices is to give interested persons an opportunity to participate in 
 the rule making prior to the adoption of the final rules.
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  Federal Register / Vol. 73, No. 213 / Monday, November 3, 2008 / 
Proposed Rules  

[[Page 65280]]



DEPARTMENT OF VETERANS AFFAIRS

38 CFR Part 3

RIN 2900-AN01


Presumptive Service Connection for Disease Associated With 
Exposure to Certain Herbicide Agents: AL Amyloidosis

AGENCY: Department of Veterans Affairs.

ACTION: Proposed rule.

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SUMMARY: The Department of Veterans Affairs (VA) is proposing to amend 
its adjudication regulations concerning presumptive service connection 
for a certain disease based on the most recent National Academy of 
Sciences (NAS) Institute of Medicine committee report, ``Veterans and 
Agent Orange: Update 2006 (Update 2006).'' This proposed amendment is 
necessary to implement a decision of the Secretary of Veterans Affairs 
that there is a positive association between exposure to herbicides 
used in the Republic of Vietnam during the Vietnam era and the 
subsequent development of AL amyloidosis. The intended effect of this 
proposed amendment is to establish presumptive service connection for 
AL amyloidosis based on herbicide exposure.

DATES: Comments must be received by VA on or before January 2, 2009.

ADDRESSES: Written comments may be submitted through http://www.Regulations.gov; by mail or hand-delivery to Director, Regulations 
Management (02REG), Department of Veterans Affairs, 810 Vermont Avenue, 
NW., Room 1068, Washington, DC 20420; or by fax to (202) 273-9026. 
(This is not a toll-free number.) Comments should indicate that they 
are submitted in response to ``RIN 2900-AN01--Disease Associated With 
Exposure to Certain Herbicide Agents: AL Amyloidosis.'' Copies of 
comments received will be available for public inspection in the Office 
of Regulation Policy and Management, Room 1063B, between the hours of 8 
a.m. and 4:30 p.m., Monday through Friday (except holidays). Please 
call (202) 461-4902 for an appointment. (This is not a toll-free 
number.) In addition, during the comment period, comments may be viewed 
online through the Federal Docket Management System at http://www.Regulations.gov.

FOR FURTHER INFORMATION CONTACT: Rhonda F. Ford, Chief, Regulations 
Staff (211D), Compensation and Pension Service, Veterans Benefits 
Administration, Department of Veterans Affairs, 810 Vermont Avenue, 
NW., Washington, DC 20420, (202) 461-9739. (This is not a toll-free 
number.)

SUPPLEMENTARY INFORMATION: Section 3 of the Agent Orange Act of 1991, 
Public Law 102-4, 105 Stat. 11, directed the Secretary to seek to enter 
into an agreement with NAS to review and summarize the scientific 
evidence concerning the association between exposure to herbicides used 
in support of military operations in the Republic of Vietnam during the 
Vietnam era and each disease suspected to be associated with such 
exposure. Congress mandated that NAS determine, to the extent possible: 
(1) Whether there is a statistical association between the suspect 
diseases and herbicide exposure, taking into account the strength of 
the scientific evidence and the appropriateness of the methods used to 
detect the association; (2) the increased risk of disease among 
individuals exposed to herbicides during service in the Republic of 
Vietnam during the Vietnam era; and (3) whether there is a plausible 
biological mechanism or other evidence of a causal relationship between 
herbicide exposure and the suspect disease. Section 3 of Public Law 
102-4 also required that NAS submit reports on its activities every 2 
years (as measured from the date of the first report) for a 10-year 
period. The Veterans Education and Benefits Expansion Act of 2001 
(Benefits Expansion Act), Public Law 107-103, Sec.  201(d), extended 
through October 1, 2014, the period for submission of NAS reports.
    Section 1116(b) of title 38, United States Code, as enacted by the 
Agent Orange Act of 1991, Public Law 102-4, provides that whenever the 
Secretary determines, based on sound medical and scientific evidence, 
that a positive association (i.e., the credible evidence for the 
association is equal to or outweighs the credible evidence against the 
association) exists between exposure of humans to an herbicide agent 
(i.e., a chemical in an herbicide used in support of the United States 
and allied military operations in the Republic of Vietnam during the 
Vietnam era) and a disease, the Secretary will publish regulations 
establishing presumptive service connection for that disease. If the 
Secretary determines that a presumption of service connection is not 
warranted, he is to publish a notice of that determination, including 
an explanation of the scientific basis for that determination. The 
Secretary's determination must be based on consideration of the NAS 
reports and all other sound medical and scientific information and 
analysis available to the Secretary.
    Although 38 U.S.C. 1116(b) does not define ``credible,'' it does 
instruct the Secretary to ``take into consideration whether the results 
[of any study] are statistically significant, are capable of 
replication, and withstand peer review.'' Simply comparing the number 
of studies which report a positive relative risk to the number of 
studies which report a negative relative risk for a particular 
condition is not a valid method for determining whether the weight of 
evidence overall supports a finding that there is or is not a positive 
association between herbicide exposure and the subsequent development 
of the particular condition. Because of differences in statistical 
significance, confidence levels, control for confounding factors, bias, 
and other pertinent characteristics, some studies are clearly more 
credible than others, and the Secretary has given the more credible 
studies more weight in evaluating the overall weight of the evidence 
concerning specific diseases.
    Section 2 of the Agent Orange Act of 1991, Public Law 102-4, 
provided that the congressional mandate that the Secretary establish 
presumptions of service connection under 38 U.S.C. 1116(b) would expire 
10 years after the first day of the fiscal year in which the NAS 
transmitted its first report to VA. The first NAS report was 
transmitted to VA in July 1993, during the fiscal year that began on 
October 1, 1992. Accordingly, under the Agent Orange Act of 1991, 
Public Law 102-4, the mandate for VA to issue regulatory

[[Page 65281]]

presumptions as specified in section 1116(b) expired on September 30, 
2002. In December 2001, however, Congress enacted the Benefits 
Expansion Act, section 201(d) of which extended the mandate under 
section 1116(b) through September 30, 2015. Pursuant to the Benefits 
Expansion Act, Public Law 107-103, VA must issue new regulations 
between October 1, 2002, and September 30, 2015, establishing 
additional presumptions of service connection for diseases that are 
found to be associated with exposure to an herbicide agent.

I. History of Agent Orange Presumptions

    Pursuant to 38 U.S.C. 1116 and prior NAS reports received between 
July 1993 and March 2005, VA regulations contain presumptions of 
service connection for eleven categories of disease based on exposure 
to an herbicide agent. Those diseases are listed in 38 CFR 3.309(e) as 
follows: Chloracne or other acneform disease consistent with chloracne, 
Type 2 diabetes (also known as Type II diabetes mellitus or adult-onset 
diabetes), Hodgkin's disease, Chronic lymphocytic leukemia, Multiple 
myeloma, Non-Hodgkin's lymphoma, Acute and subacute peripheral 
neuropathy, Porphyria cutanea tarda, Prostate cancer, Respiratory 
cancers (cancer of the lung, bronchus, larynx, or trachea), and Soft-
tissue sarcoma (other than osteosarcoma, chondrosarcoma, Kaposi's 
sarcoma, or mesothelioma).
    If a veteran who was exposed to an herbicide agent in service 
subsequently develops one of the presumptive diseases, VA will presume 
the disease was caused by the exposure to an herbicide agent in service 
for purposes of establishing entitlement to service-connected benefits. 
To qualify for this presumption, chloracne, porphyria cutanea tarda, 
and acute and subacute peripheral neuropathy must become manifest to a 
degree of disability of 10 percent or more within 1 year after the date 
of last exposure. The other conditions are presumed service connected 
if they are manifest to a degree of disability of 10 percent or more at 
any time after exposure. 38 U.S.C. 1116(a)(2). VA presumes that any 
veteran who served in the Republic of Vietnam during the period 
beginning on January 9, 1962, and ending on May 7, 1975, was exposed to 
an herbicide agent during such service. 38 U.S.C. 1116(f).

II. Prior Actions Concerning AL Amyloidosis

    VA identified AL amyloidosis as a concern after the publication of 
Veterans and Agent Orange: Update 1998. AL amyloidosis was considered 
by the NAS in its reports: Veterans and Agent Orange: Update 2000, 
Veterans and Agent Orange: Update 2002, and Veterans and Agent Orange: 
Update 2004. In these reports, NAS concluded that there was inadequate 
or insufficient evidence to determine whether there was an association 
between exposure to the compounds of interest and AL amyloidosis. After 
reviewing each of those reports, the Secretary determined that the 
credible evidence against an association between exposure to an 
herbicide agent and the occurrence of AL amyloidosis in exposed persons 
outweighed the credible evidence for such an association, and that a 
positive association therefore did not exist. 72 FR 32395, 32405 (June 
12, 2007); 68 FR 27630, 27640 (May 20, 2003); 67 FR 42600, 42607-08 
(June 24, 2002).

III. Latest NAS Review of AL Amyloidosis

    In Update 2006, VA specifically requested a focused review of the 
evidence related to whether the occurrence of acute myeloid leukemia, 
tonsil cancer, AL amyloidosis, and lupus may be associated with 
exposure to the components of herbicides used by the military in 
Vietnam and requested explicit indication of the appropriate category 
of association for all forms of cancer. NAS issued its report, 
``Veterans and Agent Orange: Update 2006'' on July 27, 2007. In 
pertinent part in that report, NAS concluded that ``there is limited or 
suggestive evidence of an association between exposures to the 
compounds of interest and AL amyloidosis.'' The term ``limited or 
suggestive evidence of an association,'' as explained in the NAS 
report, means that the evidence suggests an association between 
exposure to herbicides and the outcome considered, but the evidence is 
limited because chance, bias, and confounding could not be ruled out 
with confidence. For example, a well-conducted study showing a positive 
association combined with less compelling results from studies of 
populations with similar exposures could constitute such evidence.
    In Update 2006, NAS re-categorized the section on AL amyloidosis 
from its position in the previous reports, where it was grouped with a 
variety of non-neoplastic health conditions, and placed it closer to 
related conditions, such as multiple myeloma and some types of B-cell 
lymphoma. The conditions share several biological features, most 
notably clonal hyperproliferation of B-cell-derived plasma cells and 
production of abnormal amounts of immunoglobulins. NAS found that 
because AL amyloidosis is a rare condition, there is little 
epidemiologic literature. One study indicates that AL amyloidosis and 
non-Hodgkin's lymphoma are closely related. Another study reviewed the 
relationship between AL amyloidosis and other plasma cell disorders. It 
describes AL amyloidosis as a clonal plasma cell disorder characterized 
by low tumor burden but profound multisystemic disease. The observation 
of common chromosomal abnormalities in AL amyloidosis and multiple 
myeloma and of ``progression'' from AL amyloidosis to multiple myeloma 
support the biologic plausibility of linking AL amyloidosis with 
multiple myeloma. It is known that AL amyloidosis is associated with B-
cell diseases and roughly 15-20 percent of the time it occurs with 
multiple myeloma. Other diagnoses associated with AL amyloidosis 
include B-cell lymphomas (which are types of non-Hodgkin's lymphoma), 
monoclonal gammopathies, agammaglobulinemia, and monoclonal gammopathy 
of undetermined significance. Thus, AL amyloidosis can result from such 
medical conditions as multiple myeloma and B-cell lymphomas for which 
there is evidence of association with exposure to the compounds of 
interest. The NAS committee's conclusion that there is limited or 
suggestive evidence of an association between herbicide exposure and AL 
amyloidosis is predicated primarily on the evidence of a 
pathophsyiological association between AL amyloidosis and these other 
diseases, which have previously been found to be associated with 
herbicide exposure.

IV. The Secretary's Determination on AL Amyloidosis

    After considering all of the evidence, the Secretary has determined 
that there is a positive association between exposure to herbicide 
agents and the occurrence of AL amyloidosis.
    The biological and pathophysiological features of AL amyloidosis 
link it to multiple myeloma and some lymphomas that are associated with 
herbicide exposure in pervious NAS reports. Establishing presumptive 
service connection for AL amyloidosis is consistent with existing VA 
recognition of multiple myeloma and some lymphomas as presumptively 
service connected based on exposure to an herbicide agent. Although 
there is relatively little direct epidemiological evidence concerning 
the relation of AL amyloidosis to herbicide exposure, the Secretary 
notes that NAS considered the evidence linking AL amyloidosis to

[[Page 65282]]

multiple myelomas and lymphomas to be significant, if indirect, 
evidence of an association. Therefore, the Secretary concludes that the 
credible evidence for an association between exposure to an herbicide 
agent and the occurrence of AL amyloidosis in humans outweighs the 
credible evidence against such an association. Accordingly, the 
Secretary has determined that a presumption of service connection for 
AL amyloidosis is warranted pursuant to 38 U.S.C. 1116(b).
    This proposed rule does not reflect determinations concerning any 
disease other than AL amyloidosis. The Secretary's determinations 
concerning other diseases discussed in the Update 2006 report will be 
addressed in future documents published in the Federal Register.

Paperwork Reduction Act

    This document contains no provisions constituting a collection of 
information under the Paperwork Reduction Act (44 U.S.C. 3501-3521).

Regulatory Flexibility Act

    The Secretary hereby certifies that this proposed rule will not 
have a significant economic impact on a substantial number of small 
entities as they are defined in the Regulatory Flexibility Act, 5 
U.S.C. 601-612. This proposed rule would not affect any small entities. 
Only VA beneficiaries could be directly affected. Therefore, pursuant 
to 5 U.S.C. 605(b), this proposed rule is exempt from the initial and 
final regulatory flexibility analysis requirements of sections 603 and 
604.

Executive Order 12866

    Executive Order 12866 directs agencies to assess all costs and 
benefits of available regulatory alternatives and, when regulation is 
necessary, to select regulatory approaches that maximize net benefits 
(including potential economic, environmental, public health and safety, 
and other advantages; distributive impacts; and equity). The Executive 
Order classifies a ``significant regulatory action,'' requiring review 
by the Office of Management and Budget (OMB), as any regulatory action 
that is likely to result in a rule that may: (1) Have an annual effect 
on the economy of $100 million or more or adversely affect in a 
material way the economy, a sector of the economy, productivity, 
competition, jobs, the environment, public health or safety, or State, 
local, or tribal governments or communities; (2) create a serious 
inconsistency or otherwise interfere with an action taken or planned by 
another agency; (3) materially alter the budgetary impact of 
entitlements, grants, user fees, or loan programs or the rights and 
obligations of recipients thereof; or (4) raise novel legal or policy 
issues arising out of legal mandates, the President's priorities, or 
the principles set forth in the Executive Order.
    The economic, interagency, budgetary, legal, and policy 
implications of this proposed rule have been examined and it has been 
determined to be a significant regulatory action under the Executive 
Order because it is likely to result in a rule that may raise novel 
legal or policy issues arising out of legal mandates, the President's 
priorities, or the principles set forth in the Executive Order.

Unfunded Mandates

    The Unfunded Mandates Reform Act of 1995 requires, at 2 U.S.C. 
1532, that agencies prepare an assessment of anticipated costs and 
benefits before issuing any rule that may result in the expenditure by 
State, local, and tribal governments, in the aggregate, or by the 
private sector, of $100 million or more (adjusted annually for 
inflation) in any year. This proposed rule would have no such effect on 
State, local, and tribal governments, or on the private sector.

Catalog of Federal Domestic Assistance Numbers and Titles

    The Catalog of Federal Domestic Assistance program numbers and 
titles for this proposed rule are 64.109, Veterans Compensation for 
Service-Connected Disability, and 64.110, Veterans Dependency and 
Indemnity Compensation for Service-Connected Death.

List of Subjects in 38 CFR Part 3

    Administrative practice and procedure, Claims, Disability benefits, 
Health care, Veterans, Vietnam.

    Approved: September 30, 2008.
Gordon H. Mansfield,

Deputy Secretary of Veterans Affairs.
    For the reasons set out in the preamble, VA proposes to amend 38 
CFR part 3 as follows:

PART 3--ADJUDICATION

Subpart A--Pension, Compensation, and Dependency and Indemnity 
Compensation

    1. The authority citation for part 3, subpart A continues to read 
as follows:

    Authority: 38 U.S.C. 501(a), unless otherwise noted.


Sec.  3.309  [Amended]

    2. In Sec.  3.309(e) the listing of diseases is amended by adding 
``AL amyloidosis'' immediately preceding ``Chloracne or other acneform 
disease consistent with chloracne.''

 [FR Doc. E8-26175 Filed 10-31-08; 8:45 am]
BILLING CODE 8320-01-P