[Federal Register Volume 68, Number 58 (Wednesday, March 26, 2003)]
[Proposed Rules]
[Pages 14567-14570]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 03-7221]


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DEPARTMENT OF VETERANS AFFAIRS

38 CFR Part 3

RIN 2900-AL55


Disease Associated With Exposure to Certain Herbicide Agents: 
Chronic Lymphocytic Leukemia

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 certain diseases for which there is no record during service. 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 chronic lymphocytic 
leukemia. The intended effect of this proposed amendment is to 
establish presumptive service connection for that condition based on 
herbicide exposure.

DATES: Comments must be received on or before May 27, 2003.

ADDRESSES: Mail or hand-deliver written comments to: Director, Office 
of Regulations Management (02D), Department of Veterans Affairs, 810 
Vermont Ave., NW., Room 1154, Washington, DC 20420; or fax comments to 
(202) 273-9289; or e-mail comments to ``[email protected]''. 
Comments should indicate that they are submitted in response to ``RIN 
2900-AL55.'' All comments received will be available for public 
inspection in the Office of Regulations Management, Room 1158, between 
the hours of 8 a.m. and 4:30 p.m., Monday through Friday (except 
holidays).

FOR FURTHER INFORMATION CONTACT: David Barrans, Staff Attorney (022), 
Office of General Counsel, Department of Veterans Affairs, 810 Vermont 
Avenue, NW., Washington, DC 20420, (202) 273-6332.

SUPPLEMENTARY INFORMATION: Section 3 of the Agent Orange Act of 1991, 
Pub. L. 102-4, 105 Stat. 11, directed the Secretary to seek to enter 
into an agreement with the National Academy of Sciences (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

[[Page 14568]]

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 Pub. L. 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.
    Section 1116(b) of title 38, United States Code, as enacted by the 
Agent Orange Act of 1991, Pub. L. 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 Secretary's authority to 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, VA's authority to 
issue regulatory presumptions as specified in section 1116(b) expired 
on September 30, 2002. In December 2001, however, Congress enacted the 
Veterans Education and Benefits Expansion Act of 2001 (Benefits 
Expansion Act), Public Law 107-103. Section 201(d) of that Act extended 
VA's authority under section 1116(b) through September 30, 2015. 
Pursuant to the Benefits Expansion Act, Public Law 107-103, VA may 
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 April 2001, VA regulations contain presumptions of 
service connection for ten 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, 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 and porphyria cutanea tarda 
must become manifest to a degree of disability of 10 percent or more 
within one year after the date of last exposure. The other conditions 
are presumed service connected if they are manifest to a degree of 
disability of ten 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 Leukemia

    In each of its four previous biennial reports under the Agent 
Orange Act of 1991, the NAS concluded that there was ``inadequate/
insufficient'' evidence to determine whether an association exists 
between exposure to an herbicide agent and the subsequent occurrence of 
leukemia in exposed persons. 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 leukemia 
in exposed persons outweighed the credible evidence for such an 
association, and that a positive association therefore did not exist. 
67 FR 42600, 42604 (June 24, 2002); 64 FR 59232, 59238 (Nov. 2, 1999); 
61 FR 41442, 41445 (Aug. 8, 1996); 59 FR 341, 344 (Jan. 4, 1994).

III. Latest NAS Review of Chronic Lymphocytic Leukemia

    After receiving and reviewing the last prior NAS report in 2001, 
the Secretary asked that NAS' next report separately review the 
scientific evidence concerning the association between herbicide 
exposure and one particular form of leukemia, known as chronic 
lymphocytic leukemia (CLL). NAS issued its report, ``Veterans and Agent 
Orange: Update 2002,'' on January 23, 2003. In that report, NAS 
concluded that ``there is sufficient evidence of an association between 
exposure to at least one of the chemicals of interest (2,4-D, 2,4,5-T 
or its contaminant TCDD, picloram, or cacodylic acid) and CLL.'' The 
term ``sufficient evidence of an association,'' as explained in the NAS 
report, means that a positive association has been observed between 
herbicides and the outcome in studies in which chance, bias, and 
confounding could be ruled out with reasonable confidence.
    NAS discussed several studies that reported findings regarding the 
incidence of CLL as distinguished from other types of leukemia. One 
study of site-specific cancer incidence among 7,016 males and females 
in a rural farming community found a standard incidence ratio of 1.8, 
with a 95%

[[Page 14569]]

confidence interval (CI) of 0.8-3.2 for CLL. (Waterhouse D et al. 1996. 
Cancer incidence in the rural community of Tecumseh, Michigan: a 
pattern of increased lymphopoietic neoplasms. Cancer 77(4): 763-770). A 
population-based case-control study in an agricultural area of Italy 
noted an increased risk of CLL among farmers (Odds Ratio (OR) = 1.6, CI 
= 0.5-5.2) and animal breeders (OR = 3.1 CI = 1.1-8.3), although no 
information was provided on herbicide exposure in the study population. 
(Amadori D et al. 1995. Chronic lymphocytic leukaemias and non-
Hodgkin's lymphomas by histological type in farming-animal breeding 
workers: a population case-control study based on job titles. 
Occupational and Environmental Medicine 52(6): 374-379). A study of 
cancer risk in Danish male gardeners reportedly exposed to pesticides 
and herbicides showed a significant increase in CLL (relative risk = 
2.8, CI = 1.0-6.0), although no specific data on herbicide exposure 
were given. (Hansen ES et al. 1992. A cohort study on cancer incidence 
among Danish gardeners. American Journal of Industrial Medicine 21(5): 
651-660). One study showed a significant increase in mortality due to 
CLL among farmers in Nebraska from 1957-1974 (OR = 1.7), although no 
data regarding herbicide exposure were given. (Blair A, White DW. 1985. 
Leukemia cell types and agricultural practices in Nebraska. Archives of 
Environmental Health 40(4): 211-214).
    Two epidemiologic studies reported specifically on herbicide 
exposure and CLL. In a study of 1,675 white Iowa males who died of 
leukemia, CLL was significantly increased in farmers (OR = 1.9, CI=1.2-
3.1). (Burmeister LF et al. 1982. Leukemia and farm practices in Iowa. 
American Journal of Epidemiology 115(5): 720-728). Further analysis 
showed a strong relationship of CLL deaths in counties with acres 
treated with herbicides. In a population-based case-control interview 
study of 578 white men with leukemia and 1,245 controls, CLL mortality 
was higher in farmers than nonfarmers. (Brown LM et al. Pesticide 
exposures and other agricultural risk factors for leukemia among men in 
Iowa and Minnesota. Cancer Research 50(20): 6585-6591). When risk was 
calculated for CLL subtype, odds ratios were significantly increased 
for use of any herbicide (OR = 1.4). The risk of CLL in farmers who 
ever handled 2,4-D was 1.3. The risk of CLL in men who first handled 
2,4,5-T at least 20 years before interview was significantly increased 
(OR = 3.3, CI = 1.2-8.9).
    NAS also noted that a recent follow-up study of residents of 
Seveso, Italy found no increased risk of lymphocytic leukemia. 
(Bertazzi PA et al. 2001. Health effects of dioxin exposure: a 20-year 
mortality study. American Journal of Epidemiology 153(11): 1031-1044).
    NAS stated that the epidemiologic studies indicate that farming 
occupation is associated with significant risk of CLL, especially when 
there is exposure to the herbicides 2,4-D and 2,4,5-T. NAS further 
noted that CLL shares more traits with non-Hodgkin's lymphoma (NHL) 
than with other types of leukemia and could have a common etiology, and 
that many studies support the hypothesis that herbicide exposure can 
contribute to the risk of NHL. NAS also concluded, as in its prior 
reports, that a connection between exposure to TCDD, a contaminant of 
2,4,5-T, and human health effects is considered biologically plausible.

IV. The Secretary's Determination on Chronic Lymphocytic Leukemia

    After considering all of the evidence, the Secretary has determined 
that there is a positive association between the exposure of humans to 
an herbicide agent and the occurrence of CLL in humans. The studies 
cited by NAS consistently show an increased risk of CLL among 
agricultural workers and two of the studies show a significantly 
increased risk among farmers who were exposed to herbicides. Some of 
the findings noted by NAS are statistically significant, and the 
consistency of the findings overall supports the view that an 
association exists. Under these circumstances, the Secretary concludes 
that the credible evidence for an association between exposure to an 
herbicide agent and the occurrence of CLL in humans outweighs the 
credible evidence against such an association. Accordingly, the 
Secretary has determined that a presumption of service connection for 
CLL is warranted pursuant to 38 U.S.C. 1116(b).
    This proposed rule does not reflect determinations concerning any 
disease other than CLL. The Secretary's determinations concerning other 
diseases discussed in the current NAS report will be addressed in 
future documents published in the Federal Register.

Unfunded Mandates

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

Paperwork Reduction Act

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

Executive Order 12866

    This document has been reviewed by the Office of Management and 
Budget under Executive Order 12866.

Regulatory Flexibility Act

    The Secretary hereby certifies that this regulatory amendment will 
not have a significant economic impact on a substantial number of small 
entities as they are defined in the Regulatory Flexibility Act (RFA), 5 
U.S.C. 601-612. The reason for this certification is that these 
amendments would not directly affect any small entities. Only VA 
beneficiaries could be directly affected. Therefore, pursuant to 5 
U.S.C. 605(b), these amendments are exempt from the initial and final 
regulatory flexibility analysis requirements of sections 603 and 604.
    The Catalog of Federal Domestic Assistance program numbers are 
64.109 and 64.110.

List of Subjects in 38 CFR Part 3

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

    Approved: February 27, 2003.
Anthony J. Principi,
Secretary of Veterans Affairs.

    For the reasons set forth in the preamble, 38 CFR part 3 is 
proposed to be amended 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.

    2. In Sec.  3.309, paragraph (e) the listing of diseases is amended 
by adding ``Chronic lymphocytic leukemia'' between ``Hodgkin's 
disease'' and ``Multiple myeloma'' to read as follows:


Sec.  3.309  Diseases subject to presumptive service connection.

* * * * *
    (e) * * *


[[Page 14570]]


Chronic lymphocytic leukemia
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[FR Doc. 03-7221 Filed 3-25-03; 8:45 am]
BILLING CODE 8320-01-P