Disease Associated with Exposure to Certain Herbicide Agents (Multiple Myeloma and Respiratory Cancers)

DEPARTMENT OF VETERANS AFFAIRS

38 CFR Part 3

RIN 2900-AG73

Disease Associated with Exposure to Certain Herbicide Agents

(Multiple Myeloma and Respiratory Cancers)

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 even though there is no record of the disease

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

multiple myeloma and respiratory cancers. The intended effect of this

proposed amendment is to establish presumptive service connection for

those conditions based on herbicide exposure.

DATES: Comments must be received on or before March 7, 1994. Comments

will be available for public inspection until March 15, 1994.

ADDRESSES: Interested persons are invited to submit written comments,

suggestions, or objections regarding this amendment to Secretary of

Veterans Affairs (271A), Department of Veterans Affairs, 810 Vermont

Avenue, NW., Washington, DC 20420. All written comments received will

be available for public inspection only in the Veterans Services Unit,

room 170, at the above address between the hours of 8 a.m. and 4:30

p.m., Monday through Friday (except holidays).

FOR FURTHER INFORMATION CONTACT: John Bisset, Jr., Consultant,

Regulations Staff, Compensation and Pension Service, Veterans Benefits

Administration, (202) 233-3005.

SUPPLEMENTARY INFORMATION: Section 2(a)(1) of the Agent Orange Act of

1991, Public Law 102-4, 105 Stat. 11 (1991), added 38 U.S.C. 1116 which

established presumptive service connection for veterans with service in

the Republic of Vietnam during the Vietnam era who subsequently

develop, to a degree of 10 percent or more, non-Hodgkin's lymphoma,

soft-tissue sarcoma (subject to specified statutory exceptions), and

chloracne or other acneform disease consistent with chloracne (within

one year of the last date of active service in the Republic of Vietnam

during the Vietnam era), even though there is no record of that disease

during military service. Final regulations implementing this statutory

provision were published in the Federal Register of May 19, 1993 (See

58 FR 29107-09).

Section 3 of Public Law 102-4 directed the Secretary to enter into

an agreement with the National Academy of Sciences (NAS) to review 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 1116(b) of 38 U.S.C. provides that whenever the Secretary

determines, based on sound medical and scientific evidence, that a

positive 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. An

association is considered ``positive'' if the credible evidence for the

association is equal to or outweighs the credible evidence against the

association. In making that determination, the Secretary is to consider

reports received from NAS as well as other available sound medical and

scientific evidence and analyses.

After reviewing approximately 6,420 abstracts of scientific or

medical articles and approximately 230 epidemiologic studies,

consulting with outside experts, and conducting public hearings, NAS

issued a report, entitled ``Veterans and Agent Orange: Health Effects

of Herbicides Used in Vietnam'', on July 27, 1993. NAS concluded that

there is sufficient evidence of an association between exposure to

herbicides used in the Republic of Vietnam and the subsequent

development of chloracne, non-Hodgkin's lymphoma, soft-tissue sarcoma,

Hodgkin's disease and porphyria cutanea tarda. VA was already paying

compensation for the first three conditions based upon the statutory

presumptions established by Public Law 102-4, and the Secretary

announced that same day that he had concluded that a positive

association exists between exposure to herbicides used in the Republic

of Vietnam and the subsequent development of Hodgkin's disease and

porphyria cutanea tarda. Proposed regulations were published in the

Federal Register on September 28, 1993 (See 58 FR 50528-30).

The Secretary also announced that VA would review the remaining

findings in the NAS report to determine whether a positive association

exists between herbicide exposure and any other conditions. That review

has been completed and the Secretary has concluded that a positive

association exists for multiple myeloma and respiratory cancers. The

NAS report found ``limited/suggestive evidence''--a category it defined

as meaning that evidence suggests an association between herbicide

exposure and a specific disease, but that chance, bias, and confounding

cannot be ruled out with confidence--of an association between

herbicide exposure and the subsequent development of multiple myeloma.

VA, however, found the evidence concerning multiple myeloma, a

malignant proliferation of plasma cells which are derived from B

lymphocytes, to be convincing. Most of the studies reviewed by NAS

showed an increased risk, although in most cases it was not a

statistically significant increase. One occupational study (Fingerhut

M.A., Halperin W.E., Marlow D.A., Piacitelli L.A., Honchar P.A.,

Sweeney M.H., Greife A.L., Dill P.A., Steenland K., Suruda A.J. 1991.

Cancer mortality in workers exposed to 2,3,7,8-tetrachlorodibenzo-p-

dioxin. New England Journal of Medicine 324:212-218) found a

relationship between herbicide exposure and multiple myeloma. Although

this finding was not supported by the findings of Saracci and

colleagues (Saracci R., Kogevinas M., Bertazzi P.A., Bueno De Mesquita

B.H., Coggon D., Green L.M., Kauppinen T., L'Abbe K.A., Littorin M.,

Lynge E., Mathews J.D., Neuberger M., Osman J., Pearce N., Winkelman R.

1991. Cancer mortality in workers exposed to chlorophenoxy herbicides

and chlorophenols. Lancet 338:1027-1032), the Saracci study is flawed

as a result of questions regarding exposure. Another study (Pesatori

A.C., Consonni D., Tironi A., Landi M.T., Zocchetti C., Bertazzi P.A.

1992. Cancer morbidity in the Seveso area, 1976-1986. Chemosphere

25:209-212) showed a clear association between herbicide exposure and

multiple myeloma in both males and females. Moreover, multiple myeloma

is closely related biologically to B-cell non-Hodgkin's lymphoma;

consequently, the epidemiological evidence concerning non-Hodgkin's

lymphoma gives added weight to the association between herbicide

exposure and multiple myeloma. Based on this clinical consideration and

the weight of the epidemiogical evidence, the Secretary has determined

that there is a positive association between herbicide exposure and

multiple myeloma that manifests itself to a degree of 10 percent at any

time after exposure. We are proposing to amend 38 CFR 3.309(e) to

implement the Secretary's decision. This amendment is proposed to be

effective the date of publication of the final rule, as provided by

Public Law 102-4.

The NAS report also found limited/suggestive evidence of an

association between herbicide exposure and the subsequent development

of respiratory cancers, specifically cancers of the lung, larynx, or

trachea. For study purposes, NAS included cancer of the bronchus when

it considered cancer of the lung; therefore, we are including cancer of

the bronchus within the scope of the proposed presumption.

In reviewing the NAS report, which noted that not all studies had

fully controlled for or evaluated smoking as a confounding factor, VA

gave weight to the fact that the studies found high relative risks for

respiratory cancers in production workers (Manz A., Berger J., Dwyer

J.H., Flesch-Janys D., Nagel S., Waltsgott H. 1991. Cancer mortality

among workers in chemical plant contaminated with dioxin. Lancet

338:959-964; Fingerhut et al., 1991). The Fingerhut study showed an

increased risk with the duration of exposure. VA also noted that

despite the failure of some studies to control for smoking, it is

unlikely that there were major differences in smoking patterns between

the study and control groups. Considering all of the evidence, the

Secretary has determined that the credible evidence for an association

outweighs the credible evidence against an association and that there

is, therefore, a positive association between exposure to herbicides

used in the Republic of Vietnam and the subsequent development of

respiratory cancers.

VA also found that the weight of the available evidence indicates

that chemically-induced respiratory cancers manifest within a definite

period following exposure, after which there is little effect from the

exposure (Finkelstein M.M., 1991. Use of ``time windows'' to

investigate lung cancer latency intervals at an Ontario steel plant.

American Journal of Industrial Medicine 19:299-235). In our judgment,

it is reasonable to assume that respiratory cancers due to herbicide

exposure will show a risk pattern similar to other chemically-induced

respiratory cancers, and we are proposing as part of our rule that

respiratory cancer will be presumed service connected only if it is

manifest within 30 years after exposure. The longest manifestation

period noted for a respiratory cancer following herbicide exposure is

about 30 years (Zach J.A., Suskind R.R. 1980. The mortality experience

of workers exposed to tetrachlorodibenzodioxin in a trichlorophenol

process accident. Journal of Occupational Medicine 22:11-14; Zober A.,

Messerer P., Huber P. 1990. Thirty-four year mortality follow-up of

BASF employees to 2,3,7,8-TCDD after the 1953 accident. Occupational

Environmental Health 62:139-157). If future studies indicate that this

manifestation period is inappropriate, VA will amend it accordingly. We

are proposing to amend 38 CFR 3.307(a) and 3.309(e) to implement the

Secretary's decision. This amendment is proposed to be effective the

date of publication of the final rule, as provided by Public Law 102-4.

38 U.S.C. 1113 provides that where there is affirmative evidence to

the contrary, or evidence to establish that an intercurrent injury or

disease which is a recognized cause of any of the diseases for which

presumptive service connection may be allowed under the provisions of

38 U.S.C. 1112 (i.e., chronic diseases, tropical diseases, prisoner-of-

war related diseases, or diseases specific to radiation-exposed

veterans), has been suffered between the date of separation from

service and the onset of any such diseases, or the disability is due to

the veteran's own willful misconduct, presumptive service connection

will not be in order. Section 2(b) of public law 102-4 amends 38 U.S.C.

1113 so that its provisions also apply to the presumptive conditions

associated with herbicide exposure under 38 U.S.C. 1116. Consequently,

service connection for multiple myeloma or respiratory cancers based on

herbicide exposure is precluded if there is affirmative evidence that

establishes a non-service related supervening condition or event as the

cause of the multiple myeloma or respiratory cancers, or the disability

is due to the veteran's own willful misconduct (See 38 U.S.C. 1113).

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 this

amendment would not directly affect any small entities. Only VA

beneficiaries could be directly affected. Therefore, pursuant to 5

U.S.C. 605(b), this amendment is exempt from the initial and final

regulatory flexibility analysis requirements of sections 603 and 604.

The Secretary has determined that it is not feasible to allow the

60 day comment period referred to in section 6(a)(1) of Executive Order

12866 because a comment period of that length would prevent VA from

complying with the statutory requirement to publish a final rule within

90 days of publication of the proposed rule imposed by 38 U.S.C.

1116(c)(2).

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, Handicapped, Health

care, Pensions, Veterans.

Approved: December 3, 1993.

Jesse Brown,

Secretary of Veterans Affairs.

For the reasons set out in the preamble, 38 CFR part 3 is proposed

to be amended as set forth below:

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. 3.307, paragraph (a)(6)(ii), is revised to read as

follows:

Sec. 3.307 Presumptive service connection for chronic, tropical or

prisoner-of-war related disease, or disease associated with exposure to

certain herbicide agents; wartime and service on or after January 1,

1947.

(a) * * *

(6) * * *

(ii) The diseases listed at Sec. 3.309(e) shall have become

manifest to a degree of 10 percent or more at any time after service,

except that chloracne or other acneform disease consistent with

chloracne and porphyria cutanea tarda shall have become manifest to a

degree of 10 percent or more within a year, and respiratory cancers

within 30 years, after the last date on which the veteran was exposed

to an herbicide agent during active military, naval, or air service.

* * * * *

Sec. 3.309 [Amended]

3. In Sec. 3.309(e) in the listing of diseases, after the words

``Hodgkin's disease'' and before the words ``Non-Hodgkin's lymphoma'',

add the words ``Multiple myeloma''; and after the words ``Porphyria

cutanea tarda'' and before the words ``Soft-tissue sarcoma (other than

osteosarcoma, chondrosarcoma, Kaposi's sarcoma, or mesothelioma)'', add

the words ``Respiratory cancers (cancer of the lung, bronchus, larynx,

or trachea)''.

[FR Doc. 94-2402 Filed 2-2-94; 8:45 am]

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