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10
Conclusions and Recommendations
SYNOPSIS OF COMMITTEE CONCLUSIONS
The committee weighed the strengths and limitations of the epidemiologic
evidence reviewed in this report and in previous Veterans and Agent Orange
(VAO) reports. Although the studies published since Update 2006 are the subject
of detailed evaluation here, the committee drew its conclusions in the context
of the entire body of literature. The contribution of recent publications to the
evidence database was substantial, but the committee did not weigh them more
heavily merely because they were new. Epidemiologic methods and analytic
capabilities have improved, but many of the recent studies were also particularly
useful for the committee’s purpose because they produced results in terms of
serum TCDD concentrations or because their findings consisted of observations
on the aging population of primary concern, Vietnam veterans. The committee
also notes that experimental data related to biologic plausibility of health condi-
tions statistically associated with exposure to the components of Agent Orange
has gradually emerged since the beginning of this series of VAO reports. These
findings now better inform decisions about how to categorize the degree of as-
sociation for individual conditions; a footnote to this effect has been added to
Table 10-1.
On the basis of its evaluation of veterans, occupational, and environmental
studies, the committee assigned each health outcome to one of four categories of
relative certainty of association with exposure to the herbicides that were used
in Vietnam or to any of their components or contaminants (with no intention of
specifying particular chemicals). Changes made by the current committee to the
61
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62 VETERANS AND AGENT ORANGE: UPDATE 2008
TABLE 10-1 Summary from Seenth Biennial Update of Findings in
Occupational, Environmental, and Veterans Studies Regarding the Association
Between Specific Health Outcomes and Exposure to Herbicidesa
Sufficient Evidence of an Association
Epidemiologic evidence is sufficient to conclude that there is a positive association. That is, a
positive association has been observed between exposure to herbicides and the outcome in studies
in which chance, bias, and confounding could be ruled out with reasonable confidence. b For
example, if several small studies that are free of bias and confounding show an association that is
consistent in magnitude and direction, there could be sufficient evidence of an association. There
is sufficient evidence of an association between exposure to the chemicals of interest and the
following health outcomes:
Soft-tissue sarcoma (including heart)
Non-Hodgkin’s lymphoma
Chronic lymphocytic leukemia (including hairy cell leukemia and other chronic
B-cell leukemias) (category clarification since Update 2006)
Hodgkin’s disease
Chloracne
Limited or Suggestive Evidence of an Association
Epidemiologic evidence suggests an association between exposure to herbicides and the outcome,
but a firm conclusion is limited because chance, bias, and confounding could not be ruled out
with confidence.b For example, a well-conducted study with strong findings in accord with less
compelling results from studies of populations with similar exposures could constitute such
evidence. There is limited or suggestive evidence of an association between exposure to the
chemicals of interest and the following health outcomes:
Laryngeal cancer
Cancer of the lung, bronchus, or trachea
Prostate cancer
Multiple myeloma
AL amyloidosis
Early-onset transient peripheral neuropathy
Parkinson’s disease (category change from Update 2006)
Porphyria cutanea tarda
Hypertension
Ischemic heart disease (category change from Update 2006)
Type 2 diabetes (mellitus)
Spina bifida in offspring of exposed people
Inadequate or Insufficient Evidence to Determine an Association
The available epidemiologic 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 control for confounding, have inadequate exposure assessment, or fail to address latency. There
is inadequate or insufficient evidence to determine association between exposure to the chemicals
of interest and the following health outcomes that were explicitly reviewed:
Cancers of the oral cavity (including lips and tongue), pharynx (including tonsils), or
nasal cavity (including ears and sinuses)
Cancers of the pleura, mediastinum, and other unspecified sites in the respiratory system
and intrathoracic organs
continued
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CONCLUSIONS AND RECOMMENDATIONS
TABLE 10-1 Continued
Esophageal cancer
Stomach cancer
Colorectal cancer (including small intestine and anus)
Hepatobiliary cancers (liver, gallbladder, and bile ducts)
Pancreatic cancer
Bone and joint cancer
Melanoma
Nonmelanoma skin cancer (basal cell and squamous cell)
Breast cancer
Cancers of reproductive organs (cervix, uterus, ovary, testes, and penis; excluding
prostate)
Urinary bladder cancer
Renal cancer (kidney and renal pelvis)
Cancers of brain and nervous system (including eye)
Endocrine cancers (thyroid, thymus, and other endocrine organs)
Leukemia (other than all chronic B-cell leukemias, including chronic lymphocytic
leukemia and hairy cell leukemia)
Cancers at other and unspecified sites
Infertility
Spontaneous abortion (other than after paternal exposure to TCDD, which appears not
to be associated)b
Neonatal or infant death and stillbirth in offspring of exposed people
Low birth weight in offspring of exposed people
Birth defects (other than spina bifida) in offspring of exposed people
Childhood cancer (including acute myelogenous leukemia) in offspring of exposed
people
Neurobehavioral disorders (cognitive and neuropsychiatric)
Neurodegenerative diseases, excluding Parkinson’s disease
Chronic peripheral nervous system disorders
Respiratory disorders (wheeze or asthma, chronic obstructive pulmonary disease, and
farmer’s lung)
Gastrointestinal, metabolic, and digestive disorders (changes in hepatic enzymes, lipid
abnormalities, and ulcers)
Immune system disorders (immune suppression, allergy, and autoimmunity)
Circulatory disorders (other than hypertension and ischemic heart disease)
Endometriosis
Effects on thyroid homeostasis
This committee used a classification that spans the full array of cancers. However, reviews for
nonmalignant conditions were conducted only if they were found to have been the subjects of
epidemiologic investigation or at the request of the Department of Veterans Affairs. By default, any
health outcome on which no epidemiologic information has been found falls into this category.
Limited or Suggestive Evidence of No Association
Several adequate studies, which cover the full range of human exposure, are consistent in not
showing a positive association between any magnitude of exposure to the herbicides of interest and
the outcome. A conclusion of “no association” is inevitably limited to the conditions, exposures,
and length of observation covered by the available studies. In addition, the possibility of a ery
small increase in risk at the exposure studied can neer be excluded. There is limited or suggestive
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64 VETERANS AND AGENT ORANGE: UPDATE 2008
TABLE 10-1 Continued
evidence of no association between exposure to the herbicides of interest and the following health
outcomes:
Spontaneous abortion after paternal exposure to TCDD
a Herbicides indicates the following chemicals of interest: 2,4-dichlorophenoxyacetic acid (2,4-D),
2,4,5-trichlorophenoxyacetic acid (2,4,5-T) and its contaminant 2,3,7,8-tetrachlorodibenzo- p-dioxin
(TCDD, or dioxin), cacodylic acid, and picloram. The evidence regarding association was drawn from
occupational, environmental, and veteran studies in which people were exposed to the herbicides used
in Vietnam, to their components, or to their contaminants.
b Evidence for an association is strengthened by experimental data supporting biologic plausibility,
but its absence would not detract from the epidemiologic evidence.
categorizations determined by the committee for Update 2006 (as presented in
Table 1-1) are noted in boldface in Table 10-1.
After considering information related to the Department of Veterans Affairs
(VA) question about hairy cell leukemia, the committee concluded that not just
hairy cell leukemia—like chronic lymphoid leukemia (CLL)—but all chronic
B-cell leukemias belong in the category of “sufficient evidence of an associa-
tion” with Hodgkin’s disease and non-Hodgkin’s lymphoma (NHL). Because the
committee for Update 2006 could not reach consensus, ischemic heart disease
had remained in the category of “inadequate or insufficient evidence to determine
an association,” but accruing evidence convinced the present committee to move
ischemic heart disease from the category of “inadequate or insufficient evidence
to determine an association” to the category of “limited or suggestive evidence
of an association” with hypertension. The committee for Update 2006 had also
been unable to reach consensus about whether the evidence of an association with
herbicide exposure reached the level of “limited or suggestive,” but the present
committee did not find new evidence to justify moving either melanoma or breast
cancer out of the category of “inadequate or insufficient evidence.” Several pieces
of new information specifically about the chemicals of interest led the committee
to decide that there is now “limited or suggestive” evidence of association for
Parkinson’s disease (PD).
As mandated by Public Law (PL) 102-4, the distinctions among categories
are based on statistical association, not on strict causality. The committee was
directed to review the scientific data, not to recommend VA policy; therefore,
conclusions reported in Table 10-1 are not intended to imply or suggest policy
decisions. The conclusions are related to associations between exposure and out-
comes in human populations, not to the likelihood that any individual’s health
problem is associated with or caused by the chemicals in question.
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6
CONCLUSIONS AND RECOMMENDATIONS
COMMITTEE RECOMMENDATIONS
As part of its charge, the committee was asked to make recommendations
concerning the need, if any, for additional scientific studies to resolve uncertainties
concerning the health effects of the chemicals of interest sprayed in Vietnam: 2,4-
dichlorophenoxyacetic acid (2,4-D), 2,4,5-trichlorophenoxyacetic acid (2,4,5-T)
and its contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), picloram, and
cacodylic acid. This chapter summarizes the committee’s recommendations.
Although great strides have been made over the last several years in un-
derstanding the health effects of exposure to the chemicals of interest and in
elucidating the mechanisms underlying them, gaps in our knowledge remain.
The scope of potential research on the chemicals is wide, and what follows here
is not an exhaustive list of future research that might have value. There are many
additional opportunities for progress in such subjects as toxicology, exposure
assessment, the conduct of continuing or additional epidemiologic studies, and
systematic and comprehensive integration of existing data that have not been
explicitly noted here. It is the committee’s conviction, however, that work needs
to be undertaken promptly, particularly to address questions regarding several
health outcomes, most urgently tonsil cancer, melanoma, paternally mediated
transgenerational effects, and PD.
• The current definition of Vietnam service is not supported by existing
data.
The evidence that this committee has reviewed makes limiting Vietnam ser-
ice to those who set foot on Vietnamese soil seem inappropriate. The ongoing
series of hearings and appeals in the US Court of Appeals for Veterans Claims
(Haas . Nicholson) reflect the controversy. As discussed in Chapter 3, there is
little reason to believe that exposure of US military personnel to the herbicides
sprayed in Vietnam was limited to those who actually set foot in the Republic
of Vietnam. Having reviewed the Australian report (NRCET, 2002) on the fate
of TCDD when seawater is distilled to produce drinking water, the committee is
convinced that this use of seawater would provide a feasible route of exposure
of personnel in the Blue Water Navy, which might have been supplemented by
drift from herbicide spraying.
The epidemiologic evidence itself supports a broader definition of Vietnam
serice to serve as a surrogate for presumed exposure to Agent Orange or other
herbicides sprayed in Vietnam. For instance, the Centers for Disease Control and
Prevention (CDC, 1990) study of selected cancers in Vietnam veterans found
that the risk of the “classic AO cancer” NHL was highest and most significant in
Blue Water Navy veterans. More recently, the Air Force Health Study (AFHS)
has demonstrated that TCDD concentrations in Vietnam-era veterans deployed to
Southeast Asia, not just the “Vietnam veteran” Ranch Hand subjects, are gener-
ally higher than US background concentrations (although notably lower than in
Ranch Hand sprayers themselves).
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66 VETERANS AND AGENT ORANGE: UPDATE 2008
The present committee notes that all previous VAO committees have consid-
ered information on naval Vietnam veterans to pertain to possible Agent Orange
exposure when evaluating the full spectrum of health outcomes. The present
committee finds that exposure assignment to be appropriate. No new studies con-
sidered in this update contained Navy-specific information, but such information
has been factored into the evolving conclusions of VAO committees.
Given the available evidence, the committee recommends that members of
the Blue Water Navy should not be excluded from the set of Vietnam-era veterans
with presumed herbicide exposure.
• VA should evaluate possibilities for studying health outcomes in Vietnam-
era veterans by using the existing administrative and health-services
databases.
The original VAO committee recommended that the Department of Defense
(DOD) and VA identify Vietnam service in the computerized index of records.
Linking that information with the VA electronic medical-record and associated
administrative databases, such as discharge-diagnosis and pharmacy-use records,
should make it possible to assemble epidemiologic information on common
health conditions for evaluation of possible associations with military service in
Vietnam.
Particular attention should be paid to the feasibility of conducting epide-
miologic studies of conditions that have been noted to be of special interest but
on which the current evidence is inadequate or insufficient to determine whether
there is an association with herbicide exposure (such as tonsil and breast can-
cers, melanoma, amyotrophic lateral sclerosis, lupus, ischemic heart disease,
and stroke). For very uncommon health outcomes, a case–control design would
probably be most appropriate.
Although applications for compensation and appeals constitute a nonrepre-
sentative, self-selected sample that is influenced by which conditions are already
judged to be service-related, an effort to use existing VA information should
include a more systematic review of the distribution of health outcomes in the
database.
To evaluate whether Vietnam veterans actually have experienced an increase
in tonsil cancer, the next logical step would be for VA to identify the veterans
with tonsil cancer that are already in the system and examine the biopsy results to
classify the form (origin) of tonsil cancer better. Given the low incidence of this
rare condition, a typical epidemiologic study in the general population would not
be useful. Determining whether the lymphatic nature of the tonsil plays a role in
a substantial proportion of tonsil cancers would guide planning of the next steps
for research.
A portion of the Neurotoxin Exposure Treatment Research Program (NETRP)
is related to the pathogenesis and etiology of several conditions, including PD,
and has been funded since 1997. Originally housed in the US Army Military
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6
CONCLUSIONS AND RECOMMENDATIONS
Operational Medicine Research Program, the NETRP has recently moved to the
Telemedicine and Advanced Technology Research Center under the US Army
Medical Research and Materiel Command. Perhaps coordination with that effort
and with the resources of VA’s appeals and medical records would be a produc-
tive means of addressing whether an increased risk of PD is being manifested in
Vietnam veterans.
• Available information should be gleaned from existing cohort studies.
The present committee joins the committee for Update 2006 in concurring
with the recommendations of the Committee on the Disposition of the Air Force
Health Study (IOM, 2006). The latter committee made strong recommendations
regarding the retention of all data from the AFHS and suggested mechanisms
by which the data could be made available to researchers. We reiterate that
committee’s statement that “no other epidemiologic dataset on Vietnam veterans
contains as detailed information over as long a time period, the data appear to be
of high quality and the specimens well preserved, and analysis of the assets has
contributed to the literature addressing the health of Vietnam veterans.” Congress
directed the Institute of Medicine (IOM) Medical Follow-up Agency (MFUA) to
become custodian of the data and biologic specimens in 2006 (PL 109-364; 120
Stat. 2290); the specimens are now in storage at the Wright-Patterson Air Force
Base under the MFUA’s aegis. The MFUA is pursuing the funding that PL 110-
389, §803 directed VA to provide to IOM to maintain and manage the materials
and make them available as a resource for research. What is required is a strong
commitment by the federal government to provide sufficient funds to develop the
infrastructure necessary to meet the goals of further research using this invaluable
database. Moreover, dedicated funding is required so that focused analyses can
be carried out by independent investigators, especially as related to the research
questions that concerns the present committee. The investment would be a small
fraction of the $143 million invested to date in the AFHS. Such research could
clarify the various issues and would reap substantial benefits in the understand-
ing of health issues of Vietnam veterans exposed to herbicides. Comprehensive
longitudinal analysis of the data collected in the various medical-cycle examina-
tions, data on medical interventions (such as hospitalizations and emergency-
department visits), data on cancer incidence, data on mortality, and other data
on exposure could be used profitably to investigate further some of or all of the
health outcomes that may be associated with the exposures under consideration
in this report. The present committee believes strongly that a complete analysis of
the melanoma findings should be performed because an unambiguous interpreta-
tion is not possible on the basis of the papers published to date (Akhtar et al.,
2004; Pavuk et al., 2005).
Members of the Army Chemical Corps (ACC) constitute the largest cohort of
Vietnam veterans exposed directly to herbicides and TCDD. They were involved
in the handling and distribution of the chemicals in Vietnam. ACC veterans who
reported spraying herbicides as part of their duties have been shown to have
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68 VETERANS AND AGENT ORANGE: UPDATE 2008
increased serum TCDD concentrations; this highly exposed population has also
been shown to be at increased risk for several diseases. The population should be
the focus of additional study, with new resources devoted to it, because it repre-
sents our best opportunity to understand the health effects of exposure to TCDD
and the herbicides used in Vietnam.
Few data on the women who served in Vietnam are available. The cohort of
nurses studied by Kang et al. (2000) largely exhausted the source population. The
mortality study of the population (Cypel and Kang, 2008) reviewed in the present
update was helpful, but additional follow-up of the health status of the group and
determination of their TCDD concentrations would be worthwhile.
At the direction of Congress, the National Vietnam Veterans Readjustment
Study (1986–1988) investigated primarily psychiatric sequelae in a representative
cohort of about 1,600 men and women. In 2000, Congress mandated (PL 106-
419) that VA assess the current physical and mental well-being of the members
of that cohort. In 2001, VA contracted for the work, named the National Vietnam
Veterans Longitudinal Study (NVVLS), but progress ceased within 2 years.
VA’s Inspector General (VAOIG, 2005) ruled that “the Study was not properly,
planned, procured, or managed,” but directed that it be completed and that provi-
sions be made to avoid the previous problems. Because baseline information is
available on symptoms and chronic health problems in the original cohort, the
committee thinks that completion of the NVVLS could generate useful informa-
tion for future updates and concurs that serious consideration should be given to
restarting the study.
Starting in 1978, the National Institute for Occupational Safety and Health
(NIOSH) began to study US workers potentially exposed to TCDD. A total of
5,132 workers in 12 large manufacturing companies were included in the NIOSH
cohort. The cohort has been a source of data extremely valuable in assessing the
health effects associated with TCDD exposure. The studies have included high-
quality exposure assessment, and evaluations of a wide array of health outcomes
have been published. Given its value as an important source of epidemiologic
data, the committee recommends that studies of the NIOSH cohort be extended.
Although the committee concluded that there is limited or suggestive evi-
dence that the occurrence of Parkinson’s disease is associated with the chemicals
of interest, it would still be desirable to investigate whether the apparent incon-
sistencies in the results for incident and prevalent cases in the Agricultural Health
Study (Kamel et al., 2007b) could be resolved. The committee recommends
that the researchers conducting that ongoing study apply the analytic method
described in Copas and Farewell (2008) to this dataset.
The committee also notes that future analyses of health outcomes in those
and other important study populations should be as specific as possible because
generic findings, such as those for “all respiratory outcomes,” are not useful in
addressing the committee’s charge of determining associations of herbicide ex-
posures with specific health conditions.
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CONCLUSIONS AND RECOMMENDATIONS
• The exposure-reconstruction study should be put to use.
IOM’s Committee on the Assessment of Wartime Exposure to Herbicides
in Vietnam oversaw the development of a model of herbicide exposure of Viet-
nam veterans (the “Stellman model”), which has been described in detail (IOM,
2003a,b). The present committee endorses the finding in the recent report (IOM,
2008) of the Committee on Making Best Use of the Agent Orange Reconstruc-
tion Model that the model should be incorporated into new epidemiologic studies
where feasible.
• Studies of the Vietnamese population would be worthwhile.
As discussed in earlier updates, the Vietnamese are an under studied popula-
tion. Although there are likely to be serious logistical challenges, the many Viet-
namese people who had substantial exposure constitute a potentially informative
study sample. It will be important to include appropriate exposure measures,
such as tissue TCDD concentrations, in studying Vietnamese residents. Because
such research has the potential to close a number of gaps in the understanding
of the long-term health consequences of exposure to TCDD and the herbicides
used in Vietnam, the committee endorses action toward developing collaborative
programs of research.
• Possible effects in offspring of exposed people merit further
investigation.
The assessment of any link between exposure of Vietnam veterans to the
chemicals of interest and birth defects or developmental disease in their offspring
presents distinct challenges. VA should review all the possible cognitive and
developmental effects in offspring of veterans. Such a review should include the
possibility of effects in grandchildren, which are of growing concern to veterans
and their families. A recent meta-analysis of Agent Orange exposure and birth
defects in both Vietnamese and non-Vietnamese populations (Ngo et al., 2006)
found the studies of non-Vietnamese subjects (that is, Vietnam veterans) overall
showed significant association, pointing to the need to examine closely both the
biologic plausibility of paternally mediated birth defects and the existing epide-
miologic evidence. Reviews have also focused on epidemiologic studies of data
from birth-defects registries and from parental reports of birth defects. Those
studies often exclude alterations in function that could appear later in a child’s
life, such as alterations in neurologic function, endocrine function, or reproduc-
tive capacity. The findings of the AFHS on birth defects in veterans’ offspring
have not yet been (and, if funding is not provided, may never be) formally and
systematically integrated and analyzed in a longitudinal fashion.
Most etiologic research has focused on the effects of maternal and fetal
exposures, but some work addressing paternal exposures has been discussed in
previous reviews. With increasing concern about male reproductive function,
increasing numbers of epidemiologic studies of the role of paternal exposures in
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660 VETERANS AND AGENT ORANGE: UPDATE 2008
the risk of birth defects are being published. This work is particularly relevant
in assessing health outcomes in offspring of a largely male service population.
The plausibility of birth defects arising from parental exposure, especially from
paternal exposure, merits careful review in light of newly hypothesized epigen-
etic mechanisms (such as heritable forms of gamete imprinting) that might make
paternal transmission of a TCDD effect more plausible. The committee recom-
mends that an ad hoc group be established to review current mechanistic studies
that could further knowledge of a possible paternally mediated link between ex-
posure to the chemicals of interest and health conditions (including birth defects)
in offspring. Given the sparseness of the data on birth defects in the children of
Vietnam veterans, the committee also recommends that the ad hoc group conduct
meta-analyses of existing epidemiologic studies of male populations exposed to
TCDD, 2,4-D, or 2,4,5-T and the risk of birth defects in their offspring.
• Potential emergence of metabolic syndrome should be analyzed.
Within the study populations reviewed, the committee recognized a possible
interrelationship among the reported associations of serum concentrations of
dioxin-like compounds with certain health outcomes, including hypertriglyceri-
demia, type 2 diabetes, hypertension, and ischemic heart disease. The first three
of those outcomes are key criteria for the diagnosis of metabolic syndrome, and
the fourth is a major consequence of it. Thus, the committee recommends that—
in addition to analysis of the association of exposure to the chemicals of interest
with individual health outcomes—the incidence of multiple health outcomes that
define metabolic syndrome should be analyzed as a group.
• There is a need for new animal models to elucidate mechanisms of dis-
eases and disease progression.
The committee believes that experimental research in the mechanisms that
underlie human health outcomes (particularly cardiovascular disease and trans-
generational effects) could provide valuable information related to the risk of
disease in Vietnam veterans. The central role of the aryl hydrocarbon receptor
(AHR) in animal models is clear, and AHR gene differences in animals clearly af-
fect susceptibility to the effects of TCDD. Although work on the AHR in humans
has been sparse, variations in this specific genetic factor alone are likely to affect
human susceptibility to the toxic effects of TCDD, dioxin-like chemicals, and
herbicide formulations that contain these chemicals. In addition, recent research
makes it clear that variations in the genetic regulation of the expression or activ-
ity of other factors, including proteins that interact with the AHR and the gene
products that are regulated by the AHR, are critical in determining susceptibility
to the effects of TCDD and the types of toxic effects observed. Studies addressing
the identification, distribution, and functional consequences of polymorphisms of
the AHR and the other cofactors in human populations should be pursued. The
committee expects that investigations of mitochondrial disease and epigenetic
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661
CONCLUSIONS AND RECOMMENDATIONS
mechanisms will have important implications for health effects of concern in
Vietnam veterans.
The committee notes that although its predecessors have made similar rec-
ommendations, there has been little or no action toward implementing several
investigations that the committee regards as imperative. Those projects need to
be undertaken to address veterans concerns and to meet the scientific needs of
future VAO committees to resolve outstanding questions, particularly with regard
to PD, tonsil cancer, and melanoma. VA and DOD are in the unique position
of being able to study the very population that is of concern. Focused study of
Vietnam veterans themselves would be especially appropriate for extremely rare
conditions, such as tonsil cancer, which appears anecdotally to be occurring at
an unusual rate in Vietnam veterans and in connection with which the study of
surrogate populations (even with a case–control design) might exclude factors
that are important for the military situation.
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Akhtar FZ, Garabrant DH, Ketchum NS, Michalek JE. 2004. Cancer in US Air Force veterans of the
Vietnam war. Journal of Occupational and Enironmental Medicine 46(2):123–136.
CDC (Centers for Disease Control and Prevention). 1990. The association of selected cancers with
service in the US military in Vietnam. I. Non-Hodgkin’s lymphoma. Archies of Internal Medi-
cine 150:2473–2483.
Copas AJ, Farewell VT. 2008. Incorporating retrospective data into an analysis of time to illness.
Biostatistics 2(1):1–12.
Cypel Y, Kang H. 2008. Mortality patterns among women Vietnam-era veterans: Results of a retro-
spective cohort study. Annals of Epidemiology 18(3):244–252.
IOM (Institute of Medicine). 2003a. Characterizing Exposure of Veterans to Agent Orange and Other
Herbicides Used in Vietnam: Interim Findings and Recommendations. Washington, DC: The
National Academies Press.
IOM. 2003b. Characterizing Exposure of Veterans to Agent Orange and Other Herbicides Used in
Vietnam: Final Report. Washington, DC: The National Academies Press.
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Press.
IOM. 2008. The Utility of Proximity-Based Herbicide Exposure Assessment in Epidemiologic Studies
of Vietnam Veterans. Washington, DC: The National Academies Press.
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Langston J, Ross G, Sandler D. 2007b. Pesticide exposure and self-reported Parkinson’s disease
in the Agricultural Health Study. American Journal of Epidemiology 165(4):364–374.
Kang HK, Mahan CM, Lee KY, Magee CA, Mather SH, Matanoski G. 2000. Pregnancy out-
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1Throughout the report the same alphabetic indicator following year of publication is used con-
sistently for the same article when there were multiple citations by the same first author in a given
year. The convention of assigning the alphabetic indicator in order of citation in a given chapter is
not followed.
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Ngo AD, Taylor R, Roberts CL, Nguyen TV. 2006. Association between Agent Orange and birth
defects: Systematic review and meta-analysis. International Journal of Epidemiology 35(5):
1220–1230.
NRCET (National Research Centre for Environmental Toxicology). 2002. Examination of the Poten-
tial Exposure of Royal Australian Nay (RAN) Personnel to Polychlorinated Dibenzodioxins
and Polychlorinated Dibenzofurans Via Drinking Water. Brisbane, Australia.
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service in Southeast Asia increase the risk of cancer in Air Force Vietnam veterans who did not
spray Agent Orange? Journal of Occupational and Enironmental Medicine 47(4):335–342.
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Practices for the National Vietnam Veterans Longitudinal Study (Report No. 04-02330-212).
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