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Collection and Use of Personal Exposure
and Human Biological-Marker Information for
Assessing Risks to Deployed
U.S. Forces in Hostile Environments
by Morton Lippmann~
ABSTRACT
Risk management is especially important for military forces deployed in hostile and/or chemically
contaminated environments, and on-line or rapid turn-around capabilities for assessing exposures can
create viable options for preventing or minimizing incapaciting exposures or latent disease or disability
in the years after the deployment. With military support for the development, testing, and validation of
state-of-the-art personal and area sensors, telecommunications, and data management resources, the
DOD can (1) enhance its capabilities for meeting its novel and challenging tasks; and (2) create
technologies that will find widespread civilian uses.
This review assesses currently available options and technologies for productive pre-deployment
environmental surveillance, exposure surveillance during deployments, and retrospective exposure
surveillance post-deployment, and introduces some opportunities for technological and operational
advancements in technology for more elective exposure surveillance and elects management options
for force deployments in future years. The issues discussed are (1) information needs for assessing
personal exposures and risks for deployed forces; (2) options for pre-deployment baseline determina-
tions, for collection of personal exposure related data during field deployment, andfor post-deployment
personal exposure assessments; (3) maximizing elective personal exposure data resources during and
post-deployment; (4) technical capabilities for personal exposure assessment; and (5) assessing risks.
Advances in information technology have made it possible to envision the collection, maintenance,
and utilization of a deployment data resource that would enable theater commanders and medical stab
to recognize and evaluate environmental health hazards and to manage deployments so as to avoid or
1 Human Exposure and Health Effects Program, New York University School of Medicine, 57 Old Forge Road, Tuxedo,
NY 10987
2
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PERSONAL EXPOSURE AND HUMAN BIOLOGICAL-MARKER INFORMATION
3
minimize those hazards. Such data, together with a deployment sample archive, would also facilitate
future epidemiological studies that could identify additional causal relationships between environmen-
talfactors and health outcomes.
Applications can include (1) on-line access to remote sensing and continuous monitoring data for
tactical planning; (2) data review by medical sta~personnel in order to arrange for monitoring military
personnelfor possible elects of toxicant exposures, provide countermeasures during deployments, and
prioritize medical examinations and biomarker sample collections and analyses in the early post-
deployment period; (3) additional sampling and/or monitoring, or analysis of archived samples, in
order to be able to resolve ambiguities or conflicts concerning levels of exposure or environmental
contamination; and (4) review of medical and environmental data by epidemiologists post-deployment
in investigations of possible causal factors for delayed illness reports associated with service in a
specific deployment.
Each of these applications could consume large amounts of resources, and the allocations should be
decided according to pre-established priorities by an appropriate panel of peers, including military
users and state-of-the-art research investigators with expertise in the emerging technologies.
INTRODUCTION
Exposure assessment is a key element in risk assessment and risk management, and is especially
important for military forces deployed in hostile or uncharacterized environments. Furthermore, on-line
or rapid turn-around capabilities for assessing exposures can provide military commanders with viable
options for preventing or minimizing exposures that can incapacitate or degrade the on-site capabilities
of deployed forces, or that can result in latent disease or disability in the months and years after the
deployment. Delaved or latent adverse effects resulting from deployment exposures can degrade force
readiness for future deployments as well as cause pain and suffering to force members and/or create
compensatory costs needed to care for the force members and their families. Exposure assessments can
therefore be valuable and cost-effective tools of primary disease and disability protection. The military
could support and mobilize the high-technological resources that will be needed for the development,
testing, and validation of state-of-the-art personal and area sensors, telecommunications devices, and
data management resources. Such investments would not only help the Department of Defense (DOD)
enhance its capabilities for meeting the novel and challenging tasks in deploying forces in the post-cold-
war period, but also create technologies that will find productive new uses in other aspects of occupa-
tional and environmental health protection in the United States and around the world.
The military services have already established a core unit, the U.S. Army Center for Health
Promotion and Preventive Medicine (USACHPPM). It fulfills many of the functions that are outlined
in this paper through its Deployment Environmental Exposure Surveillance Program (DESP), which
was established in July 1996. The scope of this program could be expanded to include a greater
emphasis on personal exposure surveillance and the collection and archiving of environmental and
biological samples for later laboratory analyses needed to resolve emerging questions about expo-
sures and their health effects among deployed personnel. The sample archive envisioned here could
be viewed as an expansion of the Armed Forces Serum Repository established in August 1997 under
DOD Directive 6490.2 for the purpose of joint medical surveillance. The expanded repository would
include blood cells for biological-marker (biomarker) analyses, as well as air-sampling filters and
cartridges and soil and water samples.
Although this paper focuses on disease and non-battle injuries (DNBI), many of the high-techno-
logical capabilities developed for the nuclear, biological, and chemical (NBC) defense programs' spiral
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4
STRATEGIES TO PROTECT THE HEALTH OF DEPLOYED U.S. FORCES: WORKSHOP PROCEEDINGS
system developments can be envisioned as being applicable to force protection from unintentional
exposures to environmental toxicants. This is especially the case for the fully integrated and digitized
joint warning, reporting, and analysis architecture that the NBC program expects to implement in the
next 3 to 5 years. Plans to acquire very light-weight hazard sensors under the NBC program will also
advance measurement technologies that might have eventual applicability to on-site and personal detec-
tors capable of measuring much lower concentrations of agents of concern with respect to DNBI.
This paper introduces and spells out, in a conceptual sense, currently available options and technolo-
gies for productive pre-deployment environmental surveillance, exposure surveillance during deploy-
ments, and retrospective post-deployment exposure surveillance. It also introduces some opportunities
for technological and operational advancements in technology for more effective exposure surveillance
and proposes some risk management options for force deployments in future years. The discussions that
follow cover
· information needs for assessing personal exposures and risks for deployed forces,
· options for pre-deployment baseline determinations,
· options for collection of personal exposure data during field deployment,
· options for post-deployment personal exposure assessments,
· maximizing effective personal exposure data resource during deployment and post-deployment,
· current technical capabilities for personal exposure assessment, and
. · .
· assessing rlsKs.
INFORMATION NEEDS FOR ASSESSING PERSONAL EXPOSURES
AND RISKS FOR DEPLOYED FORCES
Environmental Quality Factors at Deployment Sites
The military is obligated to determine identifiable on-site risks whenever possible prior to the
deployment of forces. Contaminated sites, such as abandoned gas works, chemical manufacturing sites
and waste dumps, with the actual and potential risks of personnel contacting hazardous chemical
residues should be avoided whenever mission options permit and less contaminated or noncontaminated
alternate sites compatible with operational necessities are available.
Prescreening of potential deployment sites should be done at the candidate sites by appropriately
trained environmental specialists or industrial hygienists whenever possible. When on-site surveys are
not possible, remote sensors or scanners should be employed to the extent that they are technologically
and operationally feasible. (See NRC 1999.)
Survey personnel should prepare guidance and background data on the extent or potential of site
contamination to the military (or civilian) engineers assigned to site preparation for large-scale deploy-
ments. In turn, the military engineers should take care to prepare the site, to the extent feasible, in ways
that prevent or minimize the potential for exposure to preexisting on-site contamination. Both the site
survey and site preparation teams should create a record trail on on-site contamination that is accessible
to hygienists, medical personnel, and epidemiologists in case subsequent actions or investigations are
needed during on-site deployment or for post-deployment follow-up investigations.
During force deployments, the emphasis should shift to the collection of data on personal exposures
to on-site contaminants, using personal samplers and monitors, as well as the collection of exposure
hinmarkerLs whenever appropriate equipment, sampling opportunities, analytical methods, and proce-
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PERSONAL EXPOSURE AND HUMAN BIOLOGICAL-MARKER INFORMATION
is
cures are available. Because it will seldom, if ever, be feasible to collect personal exposure data on all
members of a deployed force, a sampling strategy will be needed to identify suitable and willing
individuals within the force who can serve effectively as representatives of their group for determinating
exposure. There will also need to be plans and procedures to investigate and ameliorate the sources and
extent of detected excessive exposure, as well as procedures for feasible countermeasures for docu-
mented excessive exposures.
Exposure-Reponse Relationships and Exposure Limits for Toxicants
For chemical agents of known toxicity, it is important to have or be able to develop exposure
limits or guidelines to serve as benchmarks of excessive exposure for either short or long-term
exposures. The recently prepared TG230A Short-Term Chemical Exposure Guidelines for Deployed
Military Personnel (USACHPPM 1999a) and the RD230A Reference Document (USACHPPM l999b)
provide guidance for 1-h inhalation exposures for 43 chemicals, for 1-to 14-day exposures for 91
chemicals, and drinking-water concentration limits for 170 chemicals. Guidance for 1-h inhalation
exposure limits for other chemicals is available from the American Industrial Hygiene Association
(AIHA) in their Emergency Response Planning Guidelines (ERPGs). Currently, the U.S. Environ-
mental Protection Agency (EPA) is supporting a National Research Council (NRC) Committee on
Toxicology program to prepare Guidelines for Community Emergency Exposure Levels that will
gradually be substituted for ERPGs where appropriate. Based unon the AIHA criteria of Protection of
~ ~ , ,, · , · · , . q ~ · · . . · · · . . .. · . ... ~
nearly all 1ncllvlcluals against --ex~erlencln~ or clevelonln~ 1rreverslole or other serious health e~-
f`~.~.t.~ or .~vmntom.~ that r.~1~1 impair
v a. An v ~ ram. . . abilities to take protective action," the 1-h TG230A criteria
are all conservative by factors ranging from 2 to 80. The American Conference of Governmental
Industrial Hygenists (ACGIH) threshold limit values and biological exposure indices provide guid-
ance for 15-min exposures and longer-term (8-h) exposures.
Descriptors of Deployed Forces
Deployed forces can be expected to vary greatly in age, ethnicity, genetic susceptibilities, and prior
histories of exposures to toxicants and disease, as well as in possible allergic or stress reactions to
exposures or countermeasures. The information resource that will be used to document known expo-
sures and possible responses to these exposures should contain as much descriptive information on each
person in the force as possible to facilitate primary medical management of individuals who develop
health problems during deployment or post-deployment. It should also serve as a resource for epidemi-
ologists who might be able to utilize population distributions of exposures and responses to establish
criteria and standards that advance the military's capabilities for optimal force protection. In setting up
a computerized data resource to serve such functions, consideration must be given to limiting access of
sensitive personal information to those with an approved right-to-know.
The activity patterns of members of the force can be critically important determinants of the extent
of the internal doses received as a result of toxicant exposures by dermal contact and inhalation. Dermal
exposures can be significant during field exercises and combat situations, and inhalation doses can be
greatly affected by the amounts of air inhaled, the frequency of respiration, and the depth of penetration
of the air inhaled into the lungs. The selection of force members to serve as exposure sentinels, as noted
previously, should be influenced by their known or expected activities and by the exposures they have
encountered or are expected to encounter.
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6
STRATEGIES TO PROTECT THE HEALTH OF DEPLOYED U.S. FORCES: WORKSHOP PROCEEDINGS
Descriptors, Locations, and Access to Data Resources
The emerging technological capabilities of the Information Age create opportunities for the effec-
tive collection, storage, and utilization of relevant information on personal exposures, activities, and
constitutional risk factors of kinds and magnitudes that are unprecedented. As a result, relationships
between exposures and health outcomes that had been impossible to establish for individuals might
become apparent when the data from large numbers of exposed individuals are combined. Thus, it
might be possible to derive secondary benefits from the results of deployment sampling and dose
commitments in terms of new knowledge or insights on latent or chronic effects that can be detected
only on a population basis. Consolidation of the diverse data elements needed for such powerful
analyses will require a data-management strategy, that includes a system for reporting essential data
elements in a uniform and consistent manner across the various commands and services in a given
theater of operation.
The full potential of the database envisioned above will require coordination and discipline at all
levels. Its ultimate potential will become manifest when theater commanders can readily access on-line
area and personal monitor measurements for field-deployment decisions, and medical officers can make
timely decisions on the administration of countermeasures to ameliorate the effects of recent exposures
to contaminants. Epidemiologists will be able to optimally construct cohorts in appropriate exposure
groupings for studies of the overall impacts of the deployments on the health status of active and retired
veterans of deployment. Arrangements will need to be made to control access to all of this information
to those with a need-to-know to protect the privacy of medical records and the information on deploy-
ments for military security reasons.
Framework for Data Analyses
To achieve all of the ambitious potential applications outlined above, there will need to be
uniform frameworks for data management. The overall integration of some of the deployment risk-
assessment elements is well illustrated in Figure 1, which appeared in the Deployment Toxicology
Research and Development Master Plan in September 1997 (GEO CENTERS, Inch. An approach to
combining data resources for developing an overall exposure (and risk) assessment, developed by an
ACGIH-AIHA task group (Lippmann et al. 1996) for occupational exposure applications, is illus-
trated in Figure 2.
OPTIONS FOR PRE-DEPLOYMENT BASELINE DETERMINATIONS
Health Baseline Data
If subtle changes in symptom frequency or physiological functions result from toxicant exposures
during deployments, they will be almost impossible to detect without data on pre-deployment baseline
levels in the same individuals. This is because of the enormous range of baseline values for such
variables, even in the generally healthy young adults in the military services. If conventional batteries
of function tests are performed, along with the collection of questionnaire data on signs and symptoms
prior to deployment, comparisons of comparable data during deployment and post- deployment on a
relatively small cohort of individuals might be sufficient to determine either the short-term effects or the
long-term effects, or both.
7 of — — _ _ _ _ _ _ _ _ _ _ _ _ _ ~ _
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PERSONAL EXPOSURE AND HUMAN BIOLOGICAL-MARKER INFORMATION
it: ~
~ P S L In ks , ~
Tox. lopping
, .
· ... _
. . ~ ..
A; ! .
_
/i
~ . T ~ . i;
___ JI Do
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. . . _—. ,, ~ .r
~=G
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. ~ ~ . ~
~ u rvailbnce ~ ~ . . ~ I
Oeb Bese
Models and ~
Assessments \ \
TOXI(: O LO GY
FIN Of ~G
ndi~f6L`~l Risk
A$~essrr~ent
`$ Yates S
INTER P RETAT10N AN O
O PERAT10 NAL ~ ISK
MANAGE ENT
~ ---
CONlhdANED ~
~--- - ~ EC 1810 NS ;
AlAea and Hand-hield PROTECTING OPERATIONAL
l~onitors CAPARELITlES;
FIGURE 1 Deployment toxicology research and development master plan. (Source: GEO-
CENTERS, Inc. 1997)
| Oemographic | | Work
I Survey ~
| Re' fort |
Occupatiorta, ' \
j * _ _~\j ~ :~
' ~ \ / ~
~\~ / ~
f~=; ~ Exposure y ,~
o~.r~t,OR ~ | E s t ~ m a t ~ I ~ Equiipm~r~t
_~ J ~ {Ou31Itative or ~ ~
~//~\~
~ Intcrmation ~ / ~ \. ~ ~ Exposur~ ~
~ / / \ \ ~
;: - : ~
~ ~ccu ps tionsi 1 I S~m~;ng an~~
hl 5 D ~ Expos u ro ~ Analytice!
tirnits I Klethods
hlein~ner~co
. _ ;_ and other
supporting
Raeorr5s
l
_ ~
O l~ata Group
| | Relatad Data 304reo
Callbration
Fit Tes{J
_ Perform~nce
: R.eorde
FIGURE 2 Data flowchart. This model illustrates the focus and scope of the recommended
data elements for the occupational exposure database. (Source: Lippmann et al. 1996)
7
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8
STRATEGIES TO PROTECT THE HEALTH OF DEPLOYED U.S. FORCES: WORKSHOP PROCEEDINGS
Collection of Biological Specimens for Archive and Future Analyses
For exposures to certain gases and aerosols producing acute responses, personal badges and moni-
tors can provide sufficient exposure information. However, for agents that can penetrate the skin after
dermal exposure, or for agents that are cumulative toxicants producing delayed effects, valuable infor-
mation can best be derived from biological monitoring using samples of blood, urine, or hair. The
analyses of these biological openings for a specific agent, its metabolites, enzymes induced, or abducts
formed in endogenous proteins or DNA can indicate the presence of the agent or its metabolites in the
body. For most, if not all of these analyses, there are likely to be broad variations in baseline levels, and
the analyses can be quite expensive (Zhitkovich and Costa 1998~.
Although analyses might be quite expensive, the collection and storage of the specimens is not, and
a prudent precautionary sample collection procedure will permit sensitive determinations of the results
of exposures that occurred during deployments. The process begins with the collection, identification,
and archiving of samples of the biological materials during the pre-deployment clinical examinations.
Comparable samples can be collected and archived during deployment or post-deployment to permit
sensitive intercomparisons of assay results for evidence of changes in biomarkers that might have
occurred as a result of exposures during the deployment, thus documenting the extent of the exposures
or the effects that they produced.
For most purposes, the biomarker analyses will be performed on components of blood or urine. For
other analyses, other biological materials that might be easier to collect in the field can also be useful;
these include hair, fingernails, and sputum. Under some circumstances, other samples, such as exhaled
air, nasal epithelium, and buccal cells might also be useful.
Exposure biomarkers are indicative of delivered toxicant doses and are focused on the early stages
of the continuum illustrated in Figure 3, and tend to have higher degrees of agent-specificity (Table 1~.
An important factor in the practical use of biomarkers is a low and consistent background level of the
biomarker response in nonexposed populations. Tight variance in biomarker measurements among
unexposed subjects indicates that the biomarker is not strongly affected by unknown factors associated
with, for example, diet or lifestyle. Sensitivity and low interindividual variability are the most important
parameters 1ntluenclng the statistical power ot a nlomarker. talon et al. (lYY4) provide a general
strategy and useful examples as to how variability of biomarkers can be estimated, and offer an equation
to calculate the minimal sample size. For example, DNA adJuct-based assays require relatively small
sample sizes, whereas gene expression biomarkers, with very large variability among unexposed indi-
viduals. require much larger populations.
, ~ , ~ ~
~ ~ — — —1 ———_ _ ___ __ _ ~ o — _ ~ _ ~
Blood biomarkers are a heterogeneous group of biological measurements, including unmodified
original chemicals, chemical-specific metabolites, stress hormones, modifications of proteins and DNA,
and serum and intracellular components, with half-lives of up to about 10 days. Blood contains large
quantities of hemoglobin and albumin, proteins that can be readily isolated in pure form. Carboxyl,
amino, and sulfhydryl groups are typical sites of adduction by electrophilic compounds. Many protein
adducts are stable under physiological conditions, providing an opportunity to assess cumulative expo-
sure, because the life span of human hemoglobin is approximately 120 days. The biological half-lives
of albumin adducts are shorter, due to a faster metabolic turnover of albumin (DeBord et al. 1992~.
Protein adducts, although not mechanistically involved in the pathway leading to disease, can be useful
as long as the relationship between surrogate and mechanistic biomarkers is known.
Peripheral blood lymphocytes are the most frequently used cells to assess biomarkers related to
nc~tentin1 ~enc~tc,.xic. exposures. Lymphocytes contain DNA and circulate throughout the human body,
r D
and therefore they are exposed to any circulating genotoxlc agent or its metabolltes. these cells can
integrate exposure over extended time intervals because they are long-lived (Braselmann et al. 1994)
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PERSONAL EXPOSURE AND HUMAN BIOLOGICAL-MARKER INFORMATION
Biomarkers of Exposure
Biomarl~ers of Effect
ONA Somatic
Me~bobte Adduce Mutation Hyperplas.s
~ t ~ ~
1~ .
| ~ Lowe Dose | I B~olos~cal
~~ \
Exposure
FIGURE 3
Costa 1998)
| Suscepti~.|
Altered ~ Oinic~
Shrew I Defeca
F~on ~
J
J
Jr
J
J
Relationship between exposure and disease. (Source: Zhitkovich and
TABLE 1 Examples of Biomarkers With Different Agent-Specificity
9
Specificity Biomarkers
Exposure
Low
Intermediate
High
Sister chromatic exchanges and chromosomal
abberations in peripheral lymphocytes
Micronuclei in buccal cells
p-oxo dG in urine or lymphocytic DNA
N-acetyl-~-D-glucosaminidase in urine
Mutagenesis at HPRT locus in lymphocytes or
glycophoryn A in erythrocytes
Urinary malonialdehyde
Serum or urinary chromium
Urinary nitrosoproline
Immunoassay for PAM-DNA adducts
1-hydroxypyrene in urine
Cholinergic muscarinic receptors or
acetylcholinesterase activity
Original substance in biologic specimens
Substance-specific metabolite
Chemical-specific DNA or protein adducts
Biologic response characteristic of specific
exposure
Clastogens
Clastogens
Radiation and many chemicals
Nephrotoxic agents
Mutagens
Agents causing lipid peroxidation
Toxic and dietary forms of chromium
Nitrosamines
PAH compounds
Organophosphorus insecticides
For example, cadmium
For example, S-phenylmercapturic acid for
benzene
For example, styrene-hemoglobin for styrene
exposure
6-Aminolevulinic acid in urine (lead exposure)
Urinary porphyrins profiles (mercury
exposure)
Source: Zhitkovich and Costa 1998
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STRATEGIES TO PROTECT THE HEALTH OF DEPLOYED U.S. FORCES: WORKSHOP PROCEEDINGS
and do not divide in viva. Many in vitro studies found that unstimulated lymphocytes have inefficient
DNA repair capabilities (Barrel et al. 1995; Freeman and Ryan 1988), permitting these cells to accumu-
late detectable DNA damage from very low exposures. Lymphocytes are also capable of metabolizing
many important xenobiotics such as p-aminohipparic acids (PAHs) to DNA-reactive species (Gupta et
al. 1988~.
Measurements of biomarkers in urine samples generally reflect recent exposures, and can be useful
for assessing accidental overexposures and psychological or physiological stresses. Analyses of spot
urinary samples can be used to estimate exposures in Copulations. whereas individual exposures are best
assessed using 24-h collections. Urinary b~omarker measurements are corrected tor a dilution factor by
normalizing all determinations for a creatinine content. Most analyses of urine samples are based on
detection of chemical exposure, and involve measurement of an original substance or its metabolite. A
smaller group of urinary bioassays can also estimate a biologically effective dose. Exposure to a
majority of carcinogens results in the formation of DNA abducts that later can be excised by cell-repair
systems. For some chemicals, excised abducts are then excreted in urine, and determinations of these
abducts can provide a measure of biologically effective doses.
Hair samples can provide a temporal history of peak exposures to toxic or trace metals and some
organic species or DNA that are incorporated into the growing hair shaft. For personnel who do not get
frequent military-style haircuts, hair samples can provide good evidence of previous exposure over
periods of many months. In practice, this might apply primarily to female members of the force.
In selecting any biological marker, one should consider the predictive value, specificity, sensitivity,
and occurrence of false positives and false negatives. The factors to consider are:
Does the test measure or evaluate exposure to an agent?
Does the test provide reproducible results?
Is analytical error and biological variability small?
Is the test quantitatively relatable to the relevant range of exposure?
· Have the convenience and risk factors (associated with administering the test) been considered?
· Are the concentrations of the agent measured quantitatively relatable to an adverse health effect
or stress that could impair performance of critical tasks?
Actual analyses of samples from the archive would be done on a limited number of individuals,
samples when evidence of effects points to the need for such analyses, and would initially be focused on
the specific kinds of biomarkers that are likely to be most informative. Depending on the findings of
such exploratory analyses, and their potential significance to the future health of the force members, a
further expansion of the analysis program might be warranted, looking for other biomarkers and at
samples from other individuals in the cohort. Some analyses might be indicated in the near term
following deployment, and others might be needed far into the future for evidence of delayed chronic
health effects that became apparent from epidemiological follow-ups, or when appropriate and more
sensitive assays become available to answer questions that could not be resolved on the basis of the
original assay analyses.
Environmental Quality
It might be possible to collect samples of air, soil, and surface waters, and to measure levels of
background radiation prior to deployment to determine whether the deployment of forces at a given
location would be unsafe or unwise. If such analyses do not indicate risks of contamination, and
deployment is subsequently initiated, it would be prudent to store pre-deployment environmental samples
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PERSONAL EXPOSURE AND HUMAN BIOLOGICAL-MARKER INFORMATION
11
in the deployed forces archive, and to collect and store additional samples during deployment and post-
deployment to be able to determine if contamination occurred during deployment, either as a result of
hostile actions or as a result of the deployment activities themselves. If evidence of such contamination
is found, a determination will need to be made about whether it is sufficient to warrant decontamination
or investigations of exposures to deployed forces or indigenous populations.
OPTIONS FOR COLLECTION OF DATA DURING
FIELD DEPLOYMENTS
Remote Sensing
Remote sensing of air-contaminant levels and abnormal patterns of ground and vegetation surfaces
associated with the presence of soil or water pollution can occur at various levels of spatial resolution
using current military intelligence techniques and equipment. Civilian-sector technologies for measur-
ing air concentrations in point- source plumes by LIDAR and by long-path infrared (JR) and ultraviolet
(UV) spectroscopy can also be harnessed for air monitoring at deployment sites.
Personal Sampling and Monitoring by Field-Line or Duty Corpsmen
When one wants to know the exposure of an individual to chemical contaminants inhaled in the air,
there is no good substitute for sampling or monitoring the air in the breathing zone of that individual.
The breathing zone is typically defined as the space within about 1 foot (30 cm) of the nose or mouth,
and small sampling heads or passive sampling badges are typically mounted on the lapel to monitor the
breathing zone. When comparisons are made between the concentrations in the breathing zone and
concentrations in the general area of the individual being monitored, personal exposure is often consid-
erably higher than the concentration in the area, especially when the individual is engaged in activities
that release or resuspend the chemicals from soil in the area or from accumulated contamination on the
clothing of the individual. For collecting such samples from field personnel there will need to be well-
trained field-line corpsmen responsible for issuing, collecting, labeling the sample, storing in short and
long-term archives and assuring appropriate means of their delivery to appropriate laboratories for
analysis.
Collection of Biological Specimens by Medical Personnel
Biological specimens collected in the field will also need to be collected by well-trained corpsmen,
nurses, or other medical corps personnel. It is imperative that the samples are not contaminated by soil
on the hands, that low-background sealable containers are used to contain the specimens, and that all
samples are carefully and appropriately identified, for example, by unique bar code. For blood and urine
samples, it is quite important to record the time of day that the collection took place in relation to recent
activities and exposures, and to take appropriate precautions in sample handling and storage to preserve
the integrity of the samples for both transit to a laboratory or preservation in a sample archive.
Collection of Samples of Environmental Media
If pre-deployment samples or direct measurements of air, soil, water, and background radiation
were collected, and their subsequent analyses indicated potentially serious toxicant exposures, then
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2
STRATEGIES TO PROTECT THE HEALTH OF DEPLOYED U.S. FORCES: WORKSHOP PROCEEDINGS
comparable samples should be collected at one or more times during force deployment. These should
then be analyzed for the toxicants of concern to assess the effect of deployment activities on the nature
and extent of toxicant exposures to the troops, and the extent of the dispersion of the on-site toxicants
from their initial reservoirs into the environmental media.
If pre-deployment samples did not indicate a serious concern for toxicant exposures during deploy-
ment, it still might be prudent to collect comparable samples for an archive to be able to determine
whether deployment activities either uncovered previously undetected contamination, or created or
released to the environment toxicants that should be cleaned up prior to departure. The samples might
also be needed to document the results of intentional releases of toxicants by hostile forces during the
deployment.
Performance Measures
Neurobehavioral performance measures can be used as biomarkers of exposure and biomarkers of
operationally important responses to exposures. In either case, they can only be properly interpreted as
changes in measures from baseline levels, as discussed previously. Exposures to some solvents, pesti-
cides, and metals might alone, or together, or in combination with vaccines and prophylactic drugs,
produce altered cognitive functions in the absence of clinical signs or symptoms, and signal the need for
confirmatory evidence of exposure through assays of environmental media, air samples, or biological
fluids. The effects produced by exposures to neurotoxicants among military personnel might be espe-
cially important to the performance of their assigned missions and to their ability to effectively and
responsibly manage the weapons at their disposal.
The performance measures that can be quickly self-administered might be the only feasible means
for many individuals in the deployed forces. Hand-held computers can be programmed to (1) administer
appropriate tests of mental capacity, reaction times, or agility; (2) calculate performance indices; and (3)
telemeter the results to a central medical evaluation unit. For further information on the state-of-the-art
for assays of neurobehavioral performance in humans, see Anger et al. (1998~.
It should also be noted that the U.S. Geological Survey is engaged in the development of physiologi-
cal and behavioral measures of acute chemical neurotoxicity in aquatic organisms as part of the deploy-
ment toxicology research program, and that the indicators that they have developed could be used to
assess environmental contamination and associated risks at deployment sites.
Use of Protective Measures
The military has carefully developed specifications for the purchase, supply, distribution, and
maintenance of personal protective devices, such as respirators, faceshields and goggles, and protec-
tive clothing, which are issued to deployed forces in anticipation of expected exposures. Records of
their actual use by individuals in the field should be part of their personnel records to facilitate such
retrospective exposure assessments that might be needed in the post-deployment period. On days
when there are indications that potentially damaging exposures might have occurred, it should be
possible to arrange for the collection and archiving of respirator canisters or samples of protective
gear for later laboratory analyses, with appropriate notation of the user's identification, times and
locations where the protective device was worn or used, and remarks concerning known contaminant
sources or releases relevant to the potential exposure. Analyses of these samples and associated
information could prove invaluable to the military for determining (1) actual exposures of deployed
individuals to specific agents; (2) indications of likely exposure to other individuals in the same
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PERSONAL EXPOSURE AND HUMAN BIOLOGICAL-MARKER INFORMATION
13
general operational area who are not being monitored; and (3) the efficacy of the personal protective
gear being provided to the forces for reducing or eliminating the uptake of toxicants from the working
environment.
Records of Activity Profiles
Environmental exposure is an essential determinant of the amount of the contaminant taken up by an
individual in that environment. However, uptake is also dependent on the individual's activities and the
effect of any barriers to mass transfer from the environment to systemic uptake by the individual.
Uptake of air contaminants is strongly dependent on the volumes inhaled and the lung depths to which
it is drawn, which, in turn, is dependent on the activity level of the individual. It is also dependent on the
use and effectiveness of any respiratory protective device that is supplied to the individual. It should be
recognized that it might not be possible to attain the ultimate protective capacity of a demand-type
respirator under the stress and exertion levels encountered by military personnel in the field.
Similarly, dermal exposure represents a potential for uptake that can be strongly modified by
contact area, contact times, and the integrity of the skin barrier. Ingestion exposure is governed largely
by the amounts consumed, and uptake from any contaminated food and drink that might be consumed
by deployed forces is also affected by the amounts and nature of other elements of the diet. Thus, to the
extent that it is feasible to collect and retain data on daily activities and meals for the deployed forces,
such data might prove to be very useful in determining exposure profiles and estimating toxicant uptake
for retrospective health risk evaluations.
OPTIONS FOR POST-DEPLOYMENT
EXPOSURE ASSESSMENTS
The late deployment and early post-deployment period can be critically important for the collection
ot samples and data that can help the military draw the most important lessons about toxicant exposures
that might have taken place during the deployment. This period is usually a time when the military
emergency or urgent situation justifying a deployment is past and there might be time and resources
available during the phase-down for filling data and knowledge gaps that could not be addressed when
there were more urgent priorities and when access to deployed personnel for the collection of biological
samples and activity logs was infeasible.
Collection of Biological Samples
Evidence for toxicant exposures during deployment will often be possible in the weeks and months
after the exposure has taken place for those toxicants that (1) have cumulative effects; (2) accumulate in
the body; or (3) produce metabolites or effects that persist in cells that remain in the blood stream, are
excreted in the urine, or are fixed in growing hair. The results of post-deployment analyses can be of
special significance and value when comparable samples are collected and analyzed or archived before
and during the active phases of the deployment, because baseline values might vary greatly from person
to person.
In any case, post-deployment biological samples that are collected soon after the deployment is
completed could be very useful, even in the absence of pre-deployment reference samples, for analysis
of the population distribution of exposures. A special opportunity to collect large numbers of samples
can arise when the force is relocated on transport ships. Samples could be collected by unit corpsmen
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STRATEGIES TO PROTECT THE HEALTH OF DEPLOYED U.S. FORCES: WORKSHOP PROCEEDINGS
using the support available from the ship's facility for sample collection, processing, and storage. For
troops being relocated by air, there might be opportunities for sample collection at intermediate sites
with clinical facilities, or upon arrival at new duty sites.
Collection of Environmental Media Post-Deployment
The collection of samples of environmental media post-deployment can fill several potentially
important needs. By comparison of the analyses of comparable samples collected pre-deployment,
during deployment, and post-deployment, it might be possible to document the extent of unavoidable or
avoidable exposures, due to the presence of background levels of toxicants in the environment. They
may also make it possible to document the extent of environmental toxicant burdens created during the
deployment, and thereby the need for or extent of remediation of deployment sites or following their
return to local control.
Analyses and Comparisons of Pre-Deployment and
Post-Deployment Samples
Sensitive and specific analyses of the contents of all of the biological and environmental samples
that are archived during the pre-deployment, deployment, and post-deployment periods would be un-
economical and unwarranted. A strategic plan that sets priorities in the selection of samples for analysis
will be needed. The priorities will be determined by the information needed to protect the health,
welfare, and readiness of the forces that are deployed.
Samples that might warrant a high priority for early analysis include:
· Pre-deployment environmental media samples needed to determine whether there are likely to be
exposures that could compromise the health of the forces and could be avoided or minimized.
· Biological and environmental samples collected during and immediately following deployment
needed to determine if serious toxicant exposures have taken place, based on evidence such as unusual
illness patterns, alarms sounded by areawide chemical or biological agent sensors, and suspicious
activities by hostile forces.
· Biological samples collected during deployment and the early post-deployment period needed to
investigate any unexplainable health problems that turn up among previously deployed forces, as hap-
pened with Gulf War Syndrome.
Depending upon the results obtained in such screening assays, analyses of additional samples from the
archive, or analyses of additional analyses in the samples, might be warranted to obtain a fuller picture of
the nature, extent, and significance of the exposures that might have occurred during deployment.
In developing a strategic plan for the maintenance and management of a sample archive, consider-
ation must be given to the criteria for the disposal of unneeded samples at appropriate times after the
deployment to be able to accommodate the needs for archiving samples in future deployments.
Analyses of Cumulative Exposures
Acute toxicant exposures and their consequences are expected to be obvious to area commanders
and their medical support staffs. However, the effects of more slowly acting toxicants might not become
evident during the deployment, and the exposure index might be more closely related to cumulative
exposure than to peak exposure. Estimates of cumulative exposure can be derived from biomarker
analyses. For inhalation exposures, estimates can also be derived or established from cumulative
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PERSONAL EXPOSURE AND HUMAN BIOLOGICAL-MARKER INFORMATION
15
concentration-time products, with allowance for variable uptake due to activity level and deposition
rates. Because continuous records of ambient air-concentrations are not likely to be available at any
location, let alone for all individuals in the force, exposure models will need to be employed in making
useful estimates of cumulative exposure using air concentration data.
Case-Control Studies
Case-control studies can be powerful forensic tools for elucidating causal relations between out-
comes and exposures when reasonable and plausible exposure groupings can be identified. Unfortu-
~,
. . ~ . . . . . .
nately, this proved not to be possible in the investigations of the Gulf War Syndrome because of the lack
of any useful data on the agents that might have been responsible or the means of retrospectively
determining the exposures to those agents. Should such a mysterious pattern of post-deployment illness
occur in the future, and if archived biological and environmental samples are available as outlined
above, it should be possible to compare indices of exposure in those with illness with those in matched
control populations, without illness, thereby identifying the exposure characteristics most closely asso-
ciated with the pattern of illness.
MAXIMIZING EFFECTIVE USE OF SAMPLE AND
DATA RESOURCES
Information technology developed in both the military and civilian sectors in recent years has made
it possible to envision the construction, maintenance, and utilization of a deployment data resource that
would enable theater commanders and medical staff to recognize and evaluate environmental health
hazards and to manage deployments to avoid or minimize those hazards. Together with a deployment
sample archive, it would also facilitate future epidemiological studies that could identify additional
causal relationships between environmental factors and health outcomes, and thereby stimulate the
development of means of recognizing additional risk factors warranting exposure controls in future
deployments.
To take maximal advantage of these new technological capabilities. it is imperative that the biolo~i-
O 0 1 1 0
. . .
cat and environmental samples and data elements that are needed for such applications are collected and
maintained in uniform and readily interpretable forms, and that they are accessible to all authorized
users. Applications will include:
· on-line access of deployment decision-makers to remote sensing and continuous monitoring data
that they could consider in tactical planning;
· data review by medical staff personnel to arrange for monitoring military personnel for possible
effects of toxicant exposure; provide countermeasures during deployments; and set priorities for medi-
cal examinations and biomarker sample collections and analyses in the early post-deployment period;
· on-line access and data review by industrial hygienists and environmental assessment specialists
to arrange for additional sampling and monitoring, or analysis of archived samples, to resolve ambigu-
ities or conflicts concerning levels of exposure or environmental contamination; and
· review of medical and environmental data by epidemiologists in post-deployment investigations
of possible causal factors for delayed-illness reports associated with service in a specific deployment.
However, to accommodate all of these needs in a timely and efficient manner, it will be necessary to
have a flexible system for sample and data management that can be adopted and applied uniformly by all
of the military services. It could be an extension of the Defense Occupational Health Readiness System.
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STRATEGIES TO PROTECT THE HEALTH OF DEPLOYED U.S. FORCES: WORKSHOP PROCEEDINGS
Constructing a Sample Archive
As noted earlier, USACHPPM's DESP is a logical repository for an expanded sample archive, as
proposed here. It could incorporate an expanded version of the existing Armed Forces Serum Reposi-
tory, as well as samples of blood cells, urine, hair, air sampling filters and vapor-collection canisters,
soil, and locally available drinking water. Blood cells and urine and hair samples can provide DNA for
future molecular-level biological assays, which might be critical in forensic toxicology investigations of
possible delayed health effects that might occur among deployed force personnel. The strategic aspects
of the design, maintenance, accessibility for sample analyses, minimal analytical efforts justifying use
of the archived samples, and reporting data from the analyses should be established by USACHPPM
staff with appropriate input from an external scientific advisory committee with expertise in exposure
assessment, toxicology, epidemiology, analytical chemistry, molecular biology, and clinical medicine.
Constructing a Data Resource
There are a number of essential features for a data resource that can effectively serve a variety of
primary and secondary users. The primary users must first be satisfied with data format, data reduction
paradigms, and data access because they will be providing the financial and logistical support for data
collection and entry. When the different branches of the military services are engaged in joint deploy-
ments, it is also essential that a harmonized array of data elements are adopted, so that the data sets can
be merged and the results of data analyses can be uniformly interpreted.
In setting up a data-management system and defining a commonly agreed upon set of well-defined
data elements, it is important to also consider the analytical needs of secondary users of the data
resource. They might need more descriptive background information on the geography, topography,
meterology, and history of the deployment sites than do the military command or medical units. Some
of the considerations involved in setting up comprehensive and harmonized databases for personal
exposures that could facilitate primary and secondary data users were described in detail by an ACGIH-
AIHA task group (Lippmann et al. 1996) and by a European Community task group (Rajan et al. 1997)
for occupational exposure data. In the environmental arena, the EPA (1998) has recently described a
major initiative to facilitate increased use of its environmental data resources by secondary users.
In defining its essential data elements and constructing a format and procedure for entering, main-
taining, and accessing its own data on exposure and health outcome related factors, the designers of the
military databases should consider opportunities for commonalities with the database developments
currently under way in the civilian arenas in the occupational health and environmental fields. This
examination of recent ongoing activities should, of course, include the efforts already undertaken within
each of the military services to broaden, expand, and utilize their own data resources on occupational
exposures, and should bring in the perspectives of the services' own professionals who will be second-
ary users of the data resource.
Engaging Industrial Hygiene Expertise for
Cumulative Exposure Assessments
There might need to be a component of the data resource devoted to the assessment of the cumula-
tive exposure of each member of the deployed force to each of the toxicants encountered during the
deployment that might account for excess illness observed among the cohort in the post-deployment
period. Such assessments will involve the combination of measurement data, exposure models, and
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PERSONAL EXPOSURE AND HUMAN BIOLOGICAL-MARKER INFORMATION
17
expert judgments. It might also involve the selection of air, biological, or environmental samples from
the archive for follow-up analyses to fill in data gaps that limit such assessments. Thus, the creation of
files on cumulative exposure assessment might be an iterative process that involves collaboration among
hygienists, toxicologists, and epidemiologists.
Engaging Toxicological Expertise for Interpreting Biomarker Data
Currently, there are relatively few biomarkers that are specifically identified with toxic agents or
stresses likely to be encountered during military deployments, and therefore few environmental or
biological samples collected prior to, or during, a deployment are likely to be analyzed routinely. Most
samples will be retained in the archive, to be analyzed when it is necessary to confirm or quantify
exposures that are suspected of causing adverse effects. In deciding which samples to analyze and what
analyses are appropriate and feasible, there will need to be input by toxicological experts, who will also
be needed to interpret the analytical results obtained. They will need access to other parts of the
database in forming their judgments about the extent and significance of the exposures indicated from
the biomarker analyses, and the lessons they learn from each analysis might be useful in iterative
upgrades of the data elements in the overall database and in its management.
Engaging Epidemiological Expertise for Data Analyses
Because the envisioned database is expected to be an unprecedently bountiful resource for military
epidemiologists, it should be provided with significant input into the selection and format for certain of
its data elements by them. This will be especially important for the construction of appropriate summa-
ries of exposures for use in the exploration and definition of exposure-response relationships.
CURRENT TECHNOLOGICAL CAPABILITIES FOR
PERSONAL EXPOSURE ASSESSMENT
Personal exposures can be measured continuously on-line for a limited number of gases and vapors,
determined from time-integrated samples that are subsequently analyzed for a much broader array of
agents in both gaseous and particulate forms, and inferred, albeit with greater uncertainty, from mea-
sured exposures to others in the same general area or from exposure models utilizing measured environ-
mental levels and activity patterns within the monitored area. Estimates of personal exposure can also
be developed from biomarker measurements when consideration is given to systemic uptake from the
environment, knowledge of metabolic fate in relation to times of exposure and sample collection, and
other knowledge about retention sites and half-lives in internal organs.
Personal Air Sample Collection
The technology for collecting personal air samples over periods ranging from hours to days is
relatively well developed, and reliable devices for such sampling are widely available and relatively
inexpensive. The easiest to use and most unobtrusive devices are the passive samplers for gases and
vapors that collect the agent penetrating a diffusion barrier onto an adsorption surface at a rate depen-
dent only on concentration and diffusion coefficient. The devices are small and easily worn on a lapel.
Recor~keeping requirements for sample collection are limited to the person wearing the device, the
times when the cover of the sampler is opened and closed, and the activities of the wearer during the
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STRATEGIES TO PROTECT THE HEALTH OF DEPLOYED U.S. FORCES: WORKSHOP PROCEEDINGS
time it was open for sample collection. In many cases, the samples can be analyzed subsequently in a
field laboratory. In others, more sophisticated central laboratory analyses might be required. When the
rate of sample collection is too low to determine the concentrations of the agent interest, active samplers
that collect samples at higher rates might be needed.
An active sampler requires a battery-powered air mover and a flow meter as well as a sampling
substrate, all of which increase the cost and complexity of the sampler and the burden on the wearer by
at least a few pounds. However, active samplers sample air at much higher rates (up to ~ 5 Liming,
permitting more sensitive assays with a broader range of analyses. Gases and vapors can be collected on
adsorptive granules packed within presealed tubes or on chemically pretreated filters, and particles can
be collected on a filter disc compatible with the analyses to be performed. Membrane filters are used to
collect samples on their surfaces and are scanned by microscopy, x-ray fluorescence, or radioactivity,
for viable organisms after incubation in an appropriate growth media. Aerosol samplers can also have
an inertial precollector to collect samples restricted to specific aerodynamic particle sizes based on
deposition probabilities in functionally distinct regions of the human respiratory tract. In any case,
industrial hygiene or other field personnel will be needed to dispense and collect personal samplers and
to check out the validity of sample start and end times, flow metering (if active sampling), the temporal
and spatial coordinates of the sampling intervals, and the notation of relevant conditions and activities.
Personal Monitors With Electrical Signal Outputs
Opportunities to use personal sensors and transducers to identify gaseous chemical exposures of
deployed forces will be increasing in the near future as the inherent capabilities of miniature sensors,
circuits, and telecommunications devices mature and are developed in the form of conveniently usable
hardware. Recent symposia have highlighted applications of miniaturized electrochemical sensors and
interferometers to make sensitive and specific concentration measurements that can be telemetered,
along with spatial location coordinates, to central sites, such as military command posts and medical
commands, for their surveillance and appropriate responses. Position transducers are already available
commercially, whereas the chemical sensors will need further refinement and validation before they are
ready for widespread use by military forces.
Biological Sample Collection
The collection of biological samples, such as blood, urine, and hair, is best done under controlled
conditions in which scrupulous sanitary and contamination-free control conditions can be exercised.
For regularly scheduled collections in noncombatant environments, this might be possible for troops
who are accessible to medical personnel. For those in more remote locations, it might be necessary to
equip a military ambulance to go to the vicinity of the troops for sample collections and to have the
facilities within them for sample identification, processing, and storage. The personnel collecting the
samples must also be sensitive to the need to carefully collect the coordinate data on the recent activities
and experiences of the individual providing the samples to help interpret the results of any analyses that
are performed on the sample.
Temporal Considerations of Analytical Laboratory Capabilities
For each deployment, there will need to be at least one laboratory that collects and processes
samples of air, soil, water, and biological fluids for either on-site analyses or transferral to theater-area
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PERSONAL EXPOSURE AND HUMAN BIOLOGICAL-MARKER INFORMATION
19
labs in mobile army hospitals, modular field medical units, or hospital ships offshore, or to more remote
central laboratories. For samples that can be adequately processed in the theater-area, the results can be
fed back, within days, to field personnel for guiding further sampling, relocation of personnel or
activities, or therapeutic interventions.
For analyses that require more sensitive or sophisticated laboratory facilities or specialized analy-
ses, the turn-around time will be longer, and there will be fewer opportunities for prompt feedback to
deployed forces for additional timely sample collection or reduction of ongoing exposures. There will
be, however, significant advantages in terms of documenting the full nature and extent of agents that
were present at very low concentrations.
Detection Limits of Analytical Laboratory Capabilities
The practical detection limits for a given sample depends on a number of factors whose influences
will vary greatly from agent to agent and from one analysis to another. These factors relate to analytical
sensitivity and specificity, the interferences produced by co-contaminants in the samples and compo-
nents of the sampling substrates, the level and constancy of background readings of the sensing ele-
ments, the frequency and reliability of periodic recalibrations for span and zero readings, and the care
taken to avoid sample and equipment contamination by the analysts. Thus, it is essential that the
quality-assurance and quality-control procedures of the laboratory meet the highest standards of good
laboratory practice.
Interpretation of Biomarker Changes
Exposure of biomarkers offer so many potential advantages over direct measures of exposure that
they must eventually become more routinely used and more readily interpretable. However, it is
essential that those relying on biomarker-based exposure estimates are fully aware of their inherent
strengths and their fundamental limitations.
One major strength of biomarkers, especially for military deployment applications, is that they are
influenced by past exposures, as opposed to direct measures of exposure over a given sampling interval.
Thus, biomarker samples that are collected shortly after a suspected exposure has taken place can be
used to "look back in time" to establish whether, in fact, the exposure actually occurred for the indi-
vidual providing the sample and, by implication, for other individuals in the same group or area.
Another, sometimes realized, potential strength of biomarker analyses is the high degree of sensitiv-
ity that is possible. This is especially true for biomarkers based on characteristic responses to the
exposure rather than the exposure agent itself. Highly sensitive tests for immunological responses and
changes in DNA or protein structure are often much more sensitive than chemical analyses, and are
longer lasting indicators of past exposures. A further potential advantage of exposure biomarkers is the
relative absence of concern about stray contamination of the sample by the original exposure agent
during the sample collection in the field. When reaction products are being measured, it is less likely
that they will be produced during the sample processing or laboratory analysis. However, they might
not be compound-specific.
The major limitations of biomarkers as indices of exposure involve the issues of the interpretability
of the measurements that are made. One major potential limitation can be the absence of a benchmark
or background level of the index being measured. This need not be a major problem for personnel in
military deployments when pre-deployment background biomarker samples are collected, properly
stored, and accessible for comparative evaluations.
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STRATEGIES TO PROTECT THE HEALTH OF DEPLOYED U.S. FORCES: WORKSHOP PROCEEDINGS
In the absence of pre-deployment biomarker samples, the utility of biomarker samples collected
during post-deployment will depend on the kinds of information that might be needed. If background
levels of the biomarker of interest are very low, or if exposures are very high, the absence of a pre-
deployment sample will not be important. For the more typical situation in which relatively low levels
of exposure to an agent that can produce long-term chronic disease are known or suspected, there are
several possibilities. One is to confine the analysis of the exposure to those individuals who have
provided pre-deployment samples, and use their biomarker changes as indicative of others believed to
be similarly exposed. Another possibility is to compare the distribution of biomarker levels in a large
number of members of the deployed force with the distribution of levels in a matched population that
has not been engaged in the same deployment. In this case, the level measured in a given member of the
deployed force might not provide a personal index of disease risk, but the analyses might still provide
valuable information on the average exposure of the deployed population and some indication on its
distribution. The population approach might only be feasible, however, for assays that are reasonably
. .
Inexpensive.
One unavoidable limitation of biomarker samples, however, is the fact that they are inherently
"grab" samples collected at specific points in time. This is a relatively manageable problem for
interpreting a brief peak exposure that occurred over a known time interval and in which the metabolic
and translocation times are known, but it can be a major problem when the temporal pattern and extent
of the relevant exposure is unknown. This is because the measured parameter can be highly variable
over time and there is only one measurement made of a sample collected at an unknown time after the
exposure. Thus, the analysis might be adequate to establish that an exposure took place, but unable to
characterize the level of exposure. The problem is most severe for intermittent peak exposures whose
timing is otherwise unknown, and least severe for steady-state exposures on which internal biomarker
levels reach relatively stable levels.
ASSESSING RISKS FROM PERSONAL EXPOSURES
Within the broad spectrum of risks encountered by deployed U.S. forces on foreign soil, this paper
has focused on the risks related to exposures to chemical compounds in environmental media at deploy-
ment sites. It has not dealt with chemical warfare agents for which the military services have long had
plans for force protection and countermeasures. As a result of this distinction, the risks are generally
more likely to be less obvious to the forces on the ground and more likely to produce delayed health
effects than promptly observable effects. When delayed effects are seen, they are likely to be nonspe-
cific in origin or causation and the search for causality might require careful sifting through records
relating troop activities to areas having environmental contamination and personal exposures and relat-
ing those exposures to nonexposed or less-exposed matched control populations. The nature of the
risks, and their often unanticipated relationships to exposures on foreign terrains, accounts for the
emphasis in this paper on sample and record collection and retention for follow-up investigations to
establish causal, dose-related relationships.
Combining Exposure Data with Exposure-Response Relationships
When sample analyses or environmental monitoring data indicate exposures to agents of known
toxicity having established exposure limits, the risk analysis is relatively straightforward. If exposures
exceed established standards or guidelines for such agents, the medical management of overexposed
individuals should also be relatively routine. However, for exposure to agents that produce effects that
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PERSONAL EXPOSURE AND HUMAN BIOLOGICAL-MARKER INFORMATION
21
have not previously been well characterized and whose long-term prognosis is uncertain, then prudent
concern for the future health of the deployed force members warrants careful study and follow-up by
military and Veteran' s Department medical personnel and epidemiologists. Depending on the nature of
the effects and their progression over time, this might require regularly scheduled clinical examination,
biomarker sample collections, questionnaire responses, checks on vital status and, for the deceased,
cause of death.
Research Needs
This paper envisions a long-term iterative process of exposure and health-status monitoring to
identify and characterize health risks to military personnel during noncombat deployments on sites
where characteristics of chemical agent exposures are unknown or poorly known. Initially the techno-
logical means for pre-deployment environmental or on-line personal exposure assessments are expected
to be limited to the detection and characterization of a limited number of chemical toxicants, and
quantitative exposure assessments will be delayed by the time it takes for sample collection and labora-
tory analyses, and by the sensitivity and specificity of the analyses that can be performed.
Table 2, from the Deployment Toxicology Research and Development Master Plan of September
1997 (GEO CENTERS, Inc. 1997), provides a thorough inventory of the technical challenges of
exposure assessment for deployed forces and the kinds of advances that could be made through invest-
ments in research. Investments in further technological developments in miniature chemical sensors,
microprocessors, and telecommunications devices could lead, within a relatively few years, to much
greater technological capabilities for long-path area measurements and personal monitoring of a broad
range of toxic gases and vapors, which would provide military commanders with options for force
deployment that prevent or at least reduce times of exposures to toxic agents.
Investments in biomarker research, development, and validation could provide extraordinarily sen-
sitive means of documenting exposures to toxicants as well as aspects of the biological responses to such
exposures. To the extent that measured biomarker responses lie along a pathway leading directly to
long-term changes and chronic disease, then it might be possible to prescribe therapeutic interventions
that prevent, forestall, or ameliorate such late effects of the exposures.
Investments in the creation, management, and utilization of accessible sample and data archives
related to exposures and their health consequences are also needed for various analytical and research
purposes. These include (1) use of on-line exposure information for deployment decision-making; (2)
use of on-line and sample analyses data for early actions on further sample collection needs and medical
interventions for overexposed personnel; (3) identification of military personnel acccording to exposure
category for future clinical or epidemiological follow-up; (4) identification of agents for which new
sampling or analytical techniques are most urgently needed for risk-assessment purposes; and (5)
identification of archived samples and sample analyses that can resolve issues that might arise from
delayed reports of unusual illness patterns following deployments.
Each of these categories of research could consume large amounts of resources, and the allocations
should be decided according to preestablished priorities by an appropriate panel of peers, including
military users and state-of-the-art research investigators with expertise in the emerging technologies.
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STRATEGIES TO PROTECT THE HEALTH OF DEPLOYED U.S. FORCES: WORKSHOP PROCEEDINGS
TABLE 2 Exposure Assessment Issues and Near- and Far-Term Capabilities
Technical Issues and Challenges
Capabilities (Near-Term)
Long-Term Vision
Personal Samplers and Monitors
Instantaneous
Grab
Periodic
Re al - time/C o ntinuou s
Passive
Area Samplers and Monitors
Real-time results
Remote vs. Local
Media Sampled (air, water, soil)
Statistical considerations
Data Transfers
Relevance to human uptake
Hand-held
Biomarkers of Exposure
Simple vs. Complex
Recent vs. Past vs. Continuous
Validation biological relevance
Sample: breath, urine, blood,
dermal, transcutaneous, hair,
etc.
Contaminant
Form: gas, vapor, particulate,
aerosol, fume, dissolved,
suspended
Mixtures
S tability/Transformation
Relevance of form to toxicity
Sources of exposure
Rates and Distance
Changing compositions
Exposure vs. Dose
Exposure route contributions
Absorption factors and rates
Differential uptake or deposition
Individual characteristics
Respiratory rates/Activity
Exposure elimination
Countermeasures vs. performance
decrements
Military-unique exposure standards
Predeployment screening
Retrospective exposure tracking
Sensor Technologies
Miniaturization
Weight reduction
Biosensors
Artificial nose
Passive dosimeters
Ultrasonic Flexural Plate Wave
Devices
ELFFS
Computer Tomography/FTIR
Mini GC/MS
Computer Hardware
Greater capacity and speed
Miniaturization
Portability
Computer Software
Modeling and Simulations
Artificial intelligence
Available catalogs/databases
Networks & Communications
Linking for data collection,
transfer, and analysis
Remote/stand off capability
Ready access to experts and
databases
On call/on demand data
Molecular Biology
More and better biomarkers of
exposure
Exposure models to extrapolate from
limited exposure measurements
to large study populations and
incorporate short-duration, high
intensity exposures.
Improved field methods for
characterizing simultaneous
exposures.
Personal monitoring online
Personal to population extrapolation
Combined risk information systems
Warning
Summary statements
Risk avoidance
Relationships of exposures to
indicators of health effects
database (extensive)
Single biomonitoring device
integrating measures of
exposure and dose
Exposure-Dose models that can
anticipate associated problems
with introduction of new
chemical and bio toxins
Personal Status Monitor (PSM):
physiological stress indicators
Genetic engineering for sensitive
populations
Universal micro-environmental suits
Validated methods for measuring
relevant exposure and total dose
data directly from biological
samples taken by non-invasive
techniques
Replacement breathing systems
Biologically-based exposure
assessment systems
Technological advances that measure
low concentration of chemicals
and biomarkers in biological
specimens linked to internal
dose concentrations at target
. .
Orlglns
Source: GEO-CENTERS, Inc. 1997.
OCR for page 23
PERSONAL EXPOSURE AND HUMAN BIOLOGICAL-MARKER INFORMATION
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Representative terms from entire chapter:
deployed forces
