[Federal Register Volume 66, Number 8 (Thursday, January 11, 2001)]
[Proposed Rules]
[Pages 2376-2380]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 01-685]


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DEPARTMENT OF VETERANS AFFAIRS

38 CFR Part 3

RIN 2900-AK63


Disease Associated With Exposure to Certain Herbicide Agents: 
Type 2 Diabetes

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 under the authority granted by the Agent 
Orange Act of 1991 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 Type 2 diabetes. The 
intended effect of this proposed amendment is to establish presumptive 
service connection for that condition based on herbicide exposure.

[[Page 2377]]


DATES: Comments must be received on or before March 12, 2001.

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-AK63.'' All comments received will be available for public 
inspection in the Office of Regulations Management, Room 1158, between 
the hours of 8:00 a.m. and 4:30 p.m., Monday through Friday (except 
holidays).

FOR FURTHER INFORMATION CONTACT: Bill Russo, Regulations Staff, 
Compensation and Pension Service, Veterans Benefits Administration, 
Department of Veterans Affairs, 810 Vermont Avenue, NW., Washington, DC 
20420, telephone (202) 273-7210.

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 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 two years (as measured from the 
date of the first report) for a ten-year period.
    Section 2 of 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 a presumptive service connection for that disease. 
Presumptive service connection relaxes the evidentiary burden, so that 
the claimant need not provide direct evidence of a link between his or 
her disease and the claimant's exposure to Agent Orange. Instead, such 
a link is presumed and may be rebutted only if there is affirmative 
evidence to the contrary.
    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.
    (Under Section 2 of Pub. L. 102-4, any veteran who served in 
Vietnam during the Vietnam Era and has one of the diseases on the 
presumptive list codified at 38 CFR 3.309(e), is presumed to have been 
exposed to herbicides. Under current law, the Vietnam Era is defined as 
January 9, 1962 through May 7, 1975, for the purposes of such 
presumptions. 38 U.S.C. 1116.)
    Although Pub. L. 102-4 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.

I. History of Agent Orange Presumptions

    NAS issued its initial report, entitled ``Veterans and Agent 
Orange: Health Effects of Herbicides Used in Vietnam,'' (VAO) on July 
27, 1993. The Secretary subsequently determined that a positive 
association exists between exposure to herbicides used in the Republic 
of Vietnam and the subsequent development of Hodgkin's disease, 
porphyria cutanea tarda, multiple myeloma, and certain respiratory 
cancers; and that there was no positive association between herbicide 
exposure and any other condition, other than chloracne, non-Hodgkin's 
lymphoma, and soft-tissue sarcomas, for which presumptions already 
existed. A notice of the diseases that the Secretary determined were 
not associated with exposure to herbicide agents was published on 
January 4, 1994 (see 59 FR 341-46).
    NAS issued its second report, entitled ``Veterans and Agent Orange: 
Update 1996'' (Update 1996), on March 14, 1996. The Secretary 
subsequently determined that a positive association exists between 
exposure to herbicides used in the Republic of Vietnam and the 
subsequent development of prostate cancer and acute and subacute 
peripheral neuropathy in exposed persons. The Secretary further 
determined that there was no positive association between herbicide 
exposure and any other condition, other than those for which 
presumptions already existed. A notice of the diseases that the 
Secretary determined were not associated with exposure to herbicide 
agents was published on August 8, 1996 (see 61 FR 41442-49).
    NAS issued a third report, entitled ``Veterans and Agent Orange: 
Update 1998'' (Update 1998), on February 11, 1999. The focus of this 
updated review was on new scientific studies published since the 
release of Update 1996 and updates of scientific studies previously 
reviewed. The Secretary determined that there was no positive 
association between herbicide exposure and any condition other than 
those for which presumptions already existed. A notice of this 
determination was published on November 2, 1999 (see 64 FR 59232-
59243).

II. History of NAS Review of Type 2 Diabetes

    In VAO, Update 1996, and Update 1998, NAS placed metabolic and 
digestive disorders (including Type 2 diabetes) in the category labeled 
``Inadequate/Insufficient Evidence to Determine Whether an Association 
Exists.'' According to NAS, this means that the available studies are 
of insufficient quality, consistency, or statistical power to permit a 
conclusion regarding the presence or absence of an association. For 
example, studies fail to

[[Page 2378]]

control for confounding factors, have inadequate exposure assessments, 
or fail to address latency.
    However, after NAS released Update 1998 the National Institute of 
Occupational Safety and Health (NIOSH) published a report that detects 
an association, though not a strong association, between Type 2 
diabetes and dioxin exposure. The study does suggest a dose response 
relationship because of excess cases of Type 2 diabetes found in 
workers having the highest serum-lipid levels of dioxin (Calvert GM, 
Sweeney MH, Deddens J, Wall DK. 1999. Evaluation of Type 2 diabetes, 
Serum Glucose and Thyroid Function Among U.S. Workers Exposed to 
2,3,7,8 tetrachlorodibenzo-p-dioxin. Occupational and Environmental 
Medicine 56:270-276). The Secretary concluded that the NIOSH study was 
potentially important enough that it warranted a full review by NAS as 
soon as possible, and he directed VA to amend its contract with NAS for 
the third biennial update to require a special report on herbicide 
exposure and Type 2 diabetes, as a separate deliverable.
    In February 2000, before NAS released its report on herbicide 
exposure and Type 2 diabetes, the U.S. Air Force released data from its 
study of participants in operation Ranch Hand (the crews assigned to 
spray Agent Orange from aircraft in Vietnam) (AFHS. 2000. Air Force 
Health Study: An Epidemiologic Investigation of Health Effects in Air 
Force Personnel Following Exposure to Herbicides. 1997 Follow-up 
Examination Results. Brook AFB, TX: Air Force Research Laboratory. 
AFRL-HE-BR-TR-2000-02.) On April 10, 2000, VA asked NAS to include an 
analysis of the new Ranch Hand data in its report on Type 2 diabetes. 
NAS agreed to do so.

III. October 2000 NAS Review of Type 2 Diabetes

    NAS issued its report, ``Veterans and Agent Orange: Herbicide/
Dioxin Exposure and Type 2 Diabetes'' (VAO: Diabetes) on October 11, 
2000. NAS concluded that ``there is limited/suggestive evidence of an 
association between exposure to the herbicides used in Vietnam or the 
contaminant dioxin and Type 2 diabetes.'' (``Type 2 diabetes'' is also 
referred to as ``Type II diabetes mellitus'' or ``adult-onset 
diabetes.'') The term ``limited/suggestive evidence'' means ``evidence 
is suggestive of an association between herbicides and the outcome, but 
limited because chance, bias, and confounding could not be ruled out 
with confidence.'' NAS based its conclusion on the totality of the 
scientific evidence on this issue, not one particular study. (VAO: 
Diabetes).

Mortality Studies on Type 2 Diabetes

    In VAO: Diabetes, NAS noted that positive associations between 
herbicides and Type 2 diabetes are reported in many mortality studies. 
NAS stated that these may underestimate the incidence of Type 2 
diabetes because: (1) It is not typically fatal; (2) its known 
complications, as opposed to Type 2 diabetes itself, may be more likely 
to be listed as the cause of death on the death certificate; and (3) 
contributory causes of death are not routinely recorded on death 
certificates. In one mortality study reviewed by NAS, people living 
near the site of a 1976 industrial accident involving dioxin were found 
to have a higher risk of death from Type 2 diabetes than a reference 
population, in all exposure zones in which deaths were recorded. 
(Pesatori AC, Zocchetti C, Guercilena S, Consonni D, Turrini D, 
Bertazzi, PA. 1998. Dioxin exposure and non-malignant health effects: a 
mortality study. Occupational and Environmental Medicine. 55:126-131.) 
Two studies of a group of workers exposed to TCDD at 12 U.S. plants 
found positive, but non-statistically significant associations between 
measures of exposure and notations of Type 2 diabetes on death 
certificates, although the later paper also found a significant 
negative trend between Type 2 diabetes mortality and cumulative TCDD 
exposure. (Steenland K, Nowlin S, Ryan B, Adams S. 1992. Use of 
multiple-cause mortality data in epidemiological analyses: US rate and 
proportion files developed by the National Institute for Occupational 
Safety and Health and the National Cancer Institute. American Journal 
of Epidemiology 136(7):855-862; Steenland K, Piacetelli L, Deddens J, 
Fingerhut M, Chang LI. 1999. Cancer, heart disease and diabetes in 
workers exposed to 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin. Journal of 
the National Cancer Institute 91(9):779-786.) Another study, which 
examined workers who produced or sprayed phenoxy herbicides and 
chlorophenols, reported an elevated relative risk of mortality from 
Type 2 diabetes in exposed workers versus non-exposed referents. (Vena 
J, Boffetta P, Becher H, Benn T, Bueno-de-Mesquita HB, Coggon D, Colin 
D, Flesch-Janys D, Green L, Kauppinen T, Littorin M, Lynge E, Mathews 
JD, Neuberger M, Pearce N, Pesatori AC, Saracci R, Steenland K, 
Kogevinas M. 1998. Exposure to dioxin and nonneoplastic mortality in 
the expanded IARC international cohort study of phenoxy herbicide and 
chlorophenol production workers and sprayers. Environmental Health 
Perspectives 106 (Supplement 2):645-653.) In addition, earlier studies 
previously reviewed by NAS in and VAO, Update 1996, and Update 1998 
showed an inconsistent but weakly positive association between exposure 
measures and Type 2 diabetes.

Morbidity Studies on Type 2 Diabetes

    In VAO: Diabetes, NAS noted that, ``Positive associations are 
reported in most of the morbidity studies identified by the [NAS 
Committee to Review the Evidence Regarding the Link Between Exposure to 
Agent Orange and Diabetes].'' NAS discussed a number of epidemiological 
studies. In a study of a population near an Arkansas plant that 
manufactured pesticides, researchers found that insulin levels were 
significantly higher in the group with high dioxin levels. The study 
authors concluded that this was evidence that dioxin may cause insulin 
resistance. (Cranmer M, Louie S, Kennedy RH, Kern PA, Fonseca VA. 2000. 
Exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is associated 
with hyperinsulinemia and insulin resistance. Toxicological Sciences 
56(2): 431-436.) A survey of Australian Vietnam veterans found a 
statistically significant excess of self-reported Type 2 diabetes--
2,391 cases were reported when 1,780 were expected. (Commonwealth 
Department of Veterans Affairs. 1998a. Morbidity of Vietnam Veterans: A 
Study of the Health of Australia's Vietnam Veteran Community. Volume 1: 
Male Vietnam Veterans Survey and Community Comparison Outcomes. 
Canberra: Commonwealth Department of Veterans Affairs.)
    The 1999 NIOSH study (Calvert et al., 1999) reported an elevated 
incidence of Type 2 diabetes in individuals who had high levels of 
serum dioxin relative to others examined in that study. A study of the 
Ranch Hand comparison group, reported in 1999 and published in 2000, 
showed similar findings. (Longnecker MP, Michalek JE. 2000. Serum 
dioxin level in relation to Type 2 diabetes among Air Force veterans 
with background levels of exposure. Epidemiology 11(1):44-48.) The Air 
Force's subsequent analysis of Ranch Hand data (AFHS, 2000) showed 
almost identical Type 2 diabetes incidence in Ranch Hand and the 
matched comparison group. However, this study did show significant 
dose-response relationships between dioxin levels and Type 2 diabetes 
incidence, controlling for confounding variables.

[[Page 2379]]

Biological Plausibility

    Regarding biologic plausibility, NAS concluded in VAO: Diabetes 
that animal, laboratory, and human studies constitute ``reasonable 
evidence that TCDD exposure could affect Type 2 diabetes risk in 
humans.'' This conclusion is based mainly on three studies. (Michalek 
JE. 1999. Oral presentation: Workshop on the Evidence Regarding a Link 
Between Exposure to Agent Orange and Diabetes. Washington, DC: 
Institute of Medicine, July 23; Longnecker MP and Michalek JE. 2000. 
Serum Dioxin Level in relation to Type 2 diabetes among Air Force 
veterans with background levels of exposure. Epidemiology 11(1):44-48; 
Cranmer M, Louie S, Kennedy RH, Kern PA, Fonseca VA. 2000. Exposure to 
2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is associated with 
hyperinsulinemia and insulin resistance. Toxicological Sciences 56(2): 
431-436.)

IV. The Secretary's Determination on Diabetes

    NAS reviewed all known relevant scientific and medical articles 
published since Update 1998, and prior studies, as an integral part of 
the process that resulted in VAO: Diabetes. In VAO: Diabetes, NAS 
observed that, ``Although some of the risk estimates in the studies 
examined by the committee are not statistically significant and, 
individually, studies can be faulted for various methodological 
reasons, the accumulation of positive evidence is suggestive.''
    After considering all of the evidence, the Secretary has determined 
that there is a positive association between exposure to herbicides and 
Type 2 diabetes and, therefore, a presumption of service connection is 
warranted.

V. Compliance With the Congressional Review Act, the Regulatory 
Flexibility Act, and Executive Order 12866

    We estimate that the five-year cost of this proposed rule from 
appropriated funds would be $3.3 billion in benefits costs and $62 
million in government operating expenses. Since it is likely that the 
adoption of the proposed rule may have an annual effect on the economy 
of $100 million or more, the Office of Management and Budget has 
designated this proposed rule as a major rule under the Congressional 
Review Act, 5 U.S.C. 802, and a significant regulatory action under 
Executive Order 12866, Regulatory Planning and Review. The following 
information is provided pursuant to E.O. 12866.
    This proposed rule is necessary to comply with the Agent Orange Act 
of 1991, which requires VA to establish a presumption of service 
connection if the Secretary finds 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 any particular 
disease. As explained above, the Acting Secretary has found that there 
is such an association regarding Type 2 diabetes. There are no feasible 
alternatives to this proposed rule, since the Agent Orange Act of 1991 
requires the Secretary to promulgate it once he finds the positive 
association described above. The adoption of the proposed rule would 
not interfere with state, local or tribal governments in the exercise 
of their governmental functions.

Benefits Costs

    Historical statistics indicate that the total number of veterans 
who served in the Republic of Vietnam or its surrounding waters was 
about 2.6 million. We estimate that about 2.3 million of these veterans 
are alive today. Using information gained from VAO: Diabetes and VA's 
Office of Planning and Analysis, VA applied a prevalence rate of 9% to 
the current population to determine the number of veterans who might 
have Type 2 diabetes today. VA assumes that over five years, about 90% 
of these same veterans would file a diabetes-related claim. We expect 
that 8 out of 10 claims will be made by first time applicants 
(original) and that 2 out of 10 will come from veterans already service 
connected for some other issue (reopened). The average monthly award 
made on account of diabetes or its ancillary conditions for original 
and reopened claims is estimated to be $462 and $786, respectively. 
These figures are based on average benefits to current beneficiaries 
for all conditions and include dependents' benefits and unemployability 
benefits where applicable. A moderate number of DIC and burial claims 
have also been factored into this estimate.
    VA estimates the cumulative totals of benefits awards to claimants 
for years 2001-2005 as follows: 10,199, 80,526, 129,988, 159,198 and 
178,356. Benefits costs (in $ million) for years 2001-2005 are as 
follows: $16.6, $303, $720.1, $1,010.7, and $1,205.3, for a total cost 
of $3.3 billion over five years. This cost estimate also provides for a 
nominal number of DIC payments and burial awards. Anticipated cost-of-
living allowances (COLA's), per current economic assumptions, were 
factored into this estimate; however, no retroactive payments were 
considered.

Administrative Costs.

    The administrative workload caused by this proposed rule is 
expected to be 13,361 claims filed in 2001 and more than 220,000 over 
five years. Full time employee resources devoted to processing claims 
in years one through five would be 128, 378, 311, 185, and 123, 
respectively. Administrative workloads assume that not all claims would 
be granted; it is probable that diabetes related claims will be 
received from veterans who never served in the Republic of Vietnam. GOE 
costs (in $ million) for years 2001-2005 are as follows: $6.4, $18.6, 
$16.5, $11.9, and $8.2, for a total GOE cost of $62 million over five 
years.
    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, 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 
64.100, 64.101, 64.104, 64.105, 64.106, 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: December 6, 2000.
Hershel W. Gober,
Acting 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 ``Type 2 diabetes (also known as Type II diabetes mellitus or 
adult-onset diabetes)'' between ``Chloracne or other acneform disease 
consistent with chloracne'' and ``Hodgkin's disease'' to read as 
follows:

[[Page 2380]]

Sec. 3.309  Diseases subject to presumptive service connection.

* * * * *
    (e) * * *
    Type 2 diabetes (also known as Type II diabetes mellitus or adult-
onset diabetes)
* * * * *
[FR Doc. 01-685 Filed 1-8-01; 8:45 am]
BILLING CODE 8320-01-P