Adjudication; pensions, compensation, dependency, etc.: Chronic lymphocytic leukemia; presumptive service connection,

[Federal Register: March 26, 2003 (Volume 68, Number 58)]

[Proposed Rules]

[Page 14567-14570]

From the Federal Register Online via GPO Access [wais.access.gpo.gov]

[DOCID:fr26mr03-14]

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.

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 ``OGCRegulations@mail.va.gov''.

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

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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.

1. 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).

2. 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).

3. 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%

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   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.

4. 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) * * *

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      Chronic lymphocytic leukemia * * * * *

      [FR Doc. 03-7221 Filed 3-25-03; 8:45 am]

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