Banking of Human issue for Biomonitoring
and Exposure Assessment: Utility for
Environmental Epidemiology and Surveillance
Lynn R. Goldman,1 Hoda Anton-Culver,t’2 Martin Kharrazi,1 and
Elinor Blake1
1California Department of Health Services, Emeryville, California; 2University of California, Irvine, California
Human tissue banking could provide a tool to address a number of public health concerns. We can potentially use it to monitor trends in human
exposures, serve as an early warning system for new environmental exposures, assess low-level exposures around hazardous waste and other
point sources of pollutants, evaluate the effectiveness of regulatory programs, and study etiologies of diseases (e.g., childhood cancer and birth
defects) that are likely to be related to the environment. This article discusses opportunities to establish human tissue banks in connection with pre-
existing public health surveillance programs for cancer and adverse reproductive outcomes. This is a cost-effective way to conduct surveillance and
enhances the ability to carry out epidemiologic studies. The article also discusses ethical issues that are particularly important for public health prac-
tice. One is the issue of risk communication and the need to explain risks in a way that provides people with the information they need to determine
appropriate action on the individual and community levels. Second is the issue of environmental justice. We recommend early involvement of com-
munities that are likely to be involved in tissue-banking projects and full explanation of individual and group social risks from their participation.
Environ Health Perspect 103(Suppl 3):31-34 (1995)
Key words: surveillance, environmental health, human tissue banking, reproductive outcomes, childhood cancer
Introduction
Some environmental epidemiologic and
health surveillance needs can be addressed
by using human tissue banking. There are
opportunities for developing tissue banks
in the context of existing public health
studies and health surveillance systems.
This not only offers possible cost savings
but also the opportunity to provide data
for future epidemiologic studies. However,
human tissue banking raises specific ethical
concerns on a community level. This arti-
cle discusses these issues and gives examples
of potential applications.
Uses of Human Tissue Banks
in Public Health Surveillance
and Epidemiology
Human tissue banking holds great promise
for improving epidemiologic surveillance of
environmental exposures. Surveillance is
defined as "the ongoing systematic collection,
This paper was presented at the Conference on
Human Tissue Monitoring and Specimen Banking:
Opportunities for Exposure Assessment, Risk
Assessment, and Epidemiologic Research held
30 March-1 April 1993 in Research Triangle Park,
North Carolina.
Address correspondence to Dr. Lynn R. Goldman,
U.S. Environmental Protection Agency, 401 M Street,
S.W. (TS-788), Washington, DC 20460. Telephone
(202) 260-2902. Fax (202) 260-1847.
analysis, and interpretation of health data
essential to the planning, implementation,
and evaluation of public health practice,
closely integrated with the timely dissemina-
tion of these data to those who need to know.
The final link in the surveillance chain is the
application of these data to prevention and
control" (1). At a minimum, a surveillance
system should allow examination of trends
over time and comparison of data between
representative subgroups or geographic areas.
Public health surveillance for environ-
mental health is limited to blood lead
reporting (2), diseases believed to be possi-
bly of environmental origin such as birth
defects (3), and environmental databases
designed primarily for other purposes
(4,5). Blood lead reporting is usually car-
ried out by states, using requirements of
clinical laboratories to report all or elevated
blood lead levels. Birth defects registries
exist in only a few states. Some use passive
surveillance methods, obtaining data from
vital records or hospital discharges only,
while others use active surveillance meth-
ods involving abstraction of full hospital
records. Environmental databases are usu-
ally developed by regulatory programs to
track the results of monitoring and compli-
ance activities, and are of varying useful-
ness in conduct of environmental
surveillance (5). No longer in existence is
the National Human Monitoring Program
(NHMP). The purpose of the NHMP,
established in 1967, was to monitor chemi-
cal exposures in the population. It included
the National Human Adipose Tissue
Survey (NHATS), which collected adipose
tissues from metropolitan areas in the
United States from 1970 to 1990 and
monitored chlorinated organic com-
pounds, such as the organochlorine pesti-
cides and the polychlorinated biphenyls
(6). The National Health and Nutrition
Examination survey (NHANES), a peri-
odic, population-based survey carried out
by the National Center for Health
Statistics, has been useful for monitoring
trends in blood lead levels (7) and special
studies of pesticides and volatile organic
compounds. A number of reviews have
been conducted of these surveillance sys-
tems; these have concluded that at present
environmental health surveillance is frag-
mentary and in an early stage of develop-
ment (4-6). Human tissue banking-
collection and storage of tissues or blood
samples from special groups or the general
population-would enhance this current
environmental health surveillance system.
What would be wanted for environ-
mental surveillance of human exposures?
An environmental health surveillance
system should:
integrate with other data sources that con-
tain information on disease or disability;
Environmental Health Perspectives 31

GOLDMAN ETAL.
* identify pollutants and populations of
exposed individuals that require more
urgent public health intervention;
* be useful for planning and evaluation of
intervention programs;
* provide "earlywaning" ofnew environmental
problemsi
* provide data for analytic epidemiologic
studies; and
* contribute to the knowledge base of
"background" levels of contaminants in
the population to help interpret findings
from specific population studies.
Inteaion with Heal
Survillance Systems
Any system of environmental exposure sur-
veillance, including a tissue bank, should
collect data in a manner that will allow
integration of information with informa-
tion in health surveillance systems, e.g.,
vital records, registries of cancers and birth
defects, and hospital discharge data. Such
data integration allows for population-
based, hypothesis-generating studies, and
for linkages for performing epidemiologic
studies (5).
Priority Setting
Knowledge about exposures should help
establish relative priorities to be addressed
by public health and environmental regula-
tory programs. Current environmental sur-
veillance programs do not give sufficient
information about individual exposures,
particularly exposures to population sub-
groups of special concern like children,
pregnant women, and ethnic minorities.
Program Evaluation
There is very little basis for evaluating the
efficacy of environmental health and regula-
tory programs. Insofar as efficacy can be
measured by decreases in human exposure,
tissue banks can be a useful resource for this
purpose in much the same way that report-
ing of measles cases is used to monitor the
success of measles immunization programs.
EarlyWarning
Public health agencies are expected not only
to provide surveillance of known hazards
but also to identify newly emerging hazards
to assure that society can promptly and
rapidly address them. A tissue bank can be
a very useful resource for this purpose if the
tissue banking activities are linked to the
capability to use analytic techniques, not
only for identifying known compounds and
indicators of exposure, but also for broadly
screening for new exposures. The finding of
new chemicals or indicators of exposure,
either emerging over time or at a higher
level in individual population groups, may
warrant further study.
Epidemiologic Studies
Tissue banks can potentially be useful for
the conduct of epidemiologic studies. Little
is known about the etiology of a number of
diseases that are believed possibly to be
caused by environmental exposures, for
example birth defects and childhood can-
cer. The public expects that public health
agencies can explain the causes of commu-
nity outbreaks, or "clusters" of such dis-
eases; but in many cases too little is known
about etiology to even allow formation of
specific hypotheses. At the same time, there
are a number of exposures that convey
"theoretical" risks but for which we have
very little human epidemiologic evidence.
While we would attempt to reduce the
exposures based on the theoretical risks, a
human tissue bank would increase the
opportunities available to learn more about
their effects in humans.
Background Population
ExoureLvs
We lack adequate information about
"background" levels of exposure in the
population. By background, we mean what
a statistician would call "normal," that is,
the expected range of the exposures in the
general population. Public health agencies
often encounter situations in which mea-
surements were taken by others and an
interpretation is needed. For example, in
1990 a biological monitoring technique for
urinary malathion metabolites was used to
assess exposures of toddlers in a day care
center in an area in Los Angeles County
that was being treated with aerial applica-
tions of malathion. All existing informa-
tion on urinary malathion metabolites was
for pesticide workers. No data were avail-
able for the general population or for tod-
dlers. There was no information on how to
extrapolate from higher to lower exposures,
nor on how malathion metabolism might
differ in toddlers than in adults.
Toxicologists who evaluated the data used
a number of assumptions about malathion
elimination in toddlers that resulted in
extrapolated exposures that differed by
more than an order of magnitude.
Examples of other types of situations for
which "background" data on exposures are
needed are hazardous chemical spills, chem-
ical fires, pesticide drift exposures and other
incidents of pesticide misuse, hazardous
waste site exposure assessment and
consumer product contamination episodes.
Using Existing Surveillance
Systems
As mentioned above, linkage of environ-
mental with health surveillance offers a
number of important advantages in terms
of allowing assessment of health outcomes
and in maximizing resources by using
established population-based monitoring
systems rather than creating new ones.
Opportunities for human tissue banking
exist in several areas using established pub-
lic health surveillance programs. Two pilot
studies have been conducted by the
California Department of Health Services
to take advantage of disease registries and
genetic disease screening programs. By
using pre-existing surveillance systems as a
base, one can ensure that the sample is
representative with respect to the general
population of persons with diseases such as
cancer or birth defects.
In planning any human tissue banking
effort, one should consider what tissues
might already or potentially be available,
and their utility for tissue banking. There
is much "throwaway" tissue that may be
usable, such as discarded tissue blocks and
serum samples. There are also diagnostic
specimens from surgery that may require
obtaining informed consent. Some of this
tissue cannot be used for specific purposes.
For example, formalin-preserved samples
have altered chemical constituencies.
However, with development of new analyt-
ical techniques, new uses may be found for
any tissues that might be available. For
example, the California Department of
Health Services obtains a capillary blood
spot on a piece of blotter paper for almost
100% of births; these blood spots have
been retained and archived for years.
Recently, methods have been developed to
use them for DNA amplification studies.
When linked with our birth defects surveil-
lance program, this should prove to be a
very valuable resource. Usability involves
not only the ability to analyze the specimen
but also the ability to secure, archive, and
document the tissue.
Population-based birth defects and can-
cer registries are potentially of great useful-
ness. An enormous amount of effort is
already expended to collect large amounts
of data on persons with these diseases. Since
3% of births involve a birth defect and 25
to 30% of persons are expected to develop
cancer, these registries cover a large number
of people in the areas they serve. Childhood
cancer has been a particular issue of
concern in California, where childhood
cancer "dusters" in the agricultural Central
Valley have led to concerns about pesticides
Environmental Health Perspectives32

HUMAN TISSUE BANKSAND ENVIRONMENTAL EPIDEMIOLOGY
and other environmental exposures. There
are a wealth of epidemiologic studies that
suggest potential roles for parental occupa-
tional exposures to solvents and pesticides
for a number of specific cancer types, but
most of these studies suffer from poor expo-
sure assessments. Typically, exposures are
based on paternal and maternal occupa-
tional codes; a few studies have used
questionnaires and there are rarely measure-
ments of chemicals or biologic markers of
exposure. Birth defects are a major cause of
infant mortality and account for many of
total potential years of life lost. Although a
number of chemicals can be shown to cause
malformations in laboratory animals, there
may not be concordance between the type
of malformation caused in animals and the
type caused in humans, so that we cannot
rely solely on animal studies to identify
human teratogens. Only a small fraction of
childhood cancers and birth defects, less
than 10%, can be attributed to known
environmental and genetic etiologies.
California conducted a pilot study with
the University of California at Irvine (UCI)
Cancer Surveillance Program of Orange
County (CSPOC) and the Children’s
Hospital of Orange County, to set up a tissue
bank for childhood cancer cases for Orange
County. We rapidly ascertained new cases of
cancer at the childhood cancer center at UCI,
which diagnoses and treats virtually all child-
hood cancer cases in Orange County.
Ascertainment included identifying new cases
and obtaining blood samples and tumor tis-
sue from the patient before initiation of treat-
ment. This was important because we wanted
to avoid the biologic changes caused by
chemotherapy and radiation treatment,
which might be similar to markers of envi-
ronmental exposures. We also obtained
blood samples from parents and siblings and
interviewed parents, not only because other
family members might be expected to share
environmental exposures, but also to look for
genetic traits. UCI separated the lymphocytes
and preserved them in a viable state. Later,
chromosome breakage studies were under-
taken. In the pilot study, it was possible to
obtain comparable information from both
hospital-based and "friend" controls and we
suspect that it would also be possible to
obtain population-based controls as well.
Although we piloted this technique for child-
hood cancers, it would be a reasonable
approach for birth defects as well. In that
case, one would be less concerned about the
timing of case ascertainment. Over time,
such a resource would be useful for conduct-
ing population-based environmental and
genetic etiologic studies.
Another area of much environmental
epidemiologic interest is in looking at other
reproductive outcomes. Vital records sys-
tems contain valuable information about
birthweight; gestational age; fetal and
neonatal death, age, ethnicity, and educa-
tion of parents; and use of prenatal care.
They also contain information about the
mother’s residence. However, they contain
very little information about exposure.
Increasingly, states carry out prenatal
genetic disease screening programs. In
California we conduct serum alpha fetopro-
tein (AFP) testing for about 60% of births.
This test is performed at 15 to 19 weeks of
gestation and is used to screen for neural
tube defects and other disorders. All tests
are carried out in large regional contract
laboratories under supervision of the state
laboratory. Typically, samples are discarded
after confirmatory analyses are carried out.
Rather than discarding prenatal AFP
samples, we banked all serum specimens
from an 11-county area for a month (3699
samples). The area chosen was in the
Central Valley of California which is eth-
nically diverse with an especially large
Hispanic population. After linking these
specimens with live birth or fetal death
records, there are a number of analyses
that are feasible. At present, we are using
the specimens to study the relationship of
birthweight and gestational age to mid-
pregnancy cotinine and caffeine levels. It
will be possible to look at not only active
smoking but also environmental tobacco-
smoke exposure. With very little extra
cost, programs such as the genetic disease
screening program could be modified to
archive specimens on a routine basis. This
could be useful not only for studies of
reproductive outcomes but also for a num-
ber of other developmental outcomes that
may be related to prenatal exposures.
There are a number of chemicals that can
be measured in serum, including some
metals and a number of pesticides; and
new methods are under development to
measure other substances and to find better
markers of exposure.
Cluster Investigations
We also conduct studies of space-time
clusters of diseases such as childhood can-
cer and birth defects. These studies usually
result in inconclusive results. Tissue bank-
ing holds the promise of being able to look
later for markers of exposure or pre-disease
conditions that might help elucidate the
cause of at least some of these space-time
clusters. The experience with studying
genetic etiologies of cancer can serve as an
example of the potential of this method.
Ethical Concerns
Two interrelated ethical issues are particu-
larly important for public health practice.
One is the issue of risk communication
and the need to explain risks in a way that
provides people with the information they
need to determine appropriate action on
the individual and community level.
Second is the issue of environmental jus-
tice, often referred to as environmental
equity. Environmental justice advocates
dislike the term "environmental equity"
because, as Charles Lee of the United
Church of Christ has said, "It sounds as if
we all share the problem, it’s OK" (8). It
will be very important for any national
program of adipose tissue banking, like
any program of environmental surveil-
lance, to over-sample in low income and
various racial and ethnic communities. If
past studies can serve as a guide, we can
expect that we will be more likely to find
higher exposures in these communities
(9,10). Researchers, who rarely are from
these areas, should not assume that they
understand the needs for these communi-
ties or the consequences of their findings
for the residents. Certainly, there is likely
to be less access to education, poorer
nutrition in low income areas, and cultural
differences in understanding of health and
disease. Such communities are also less
likely than a white suburban community
to have resident experts such as scientists,
physicians, attorneys, and other trained
professionals who can interpret the data
for neighbors; and they have less access to
such expertise overall. In consequence,
these communities may have more diffi-
culty in taking steps needed to deal with
any problems that might be identified, or
compelling the government to do so. In
low-income communities, food, housing
and child care may take precedence over
the environmental problems. Moreover,
identification of specific environmental
exposures could worsen discriminatory
practices, such has been seen in "redlin-
ing" practices in neighborhoods with lead
contamination. Early involvement and
participation of members of these commu-
nities in any monitoring effort are essential
to ensure sensitivity to cultural issues and
the barriers to addressing any problems
that may exist, and to identify ways to
overcome those barriers.
Informed consent needs to include not
only information about individual medical
and privacy risks but also about social risks
Volume 103, Supplement 3, April 1995 33

GOLDMAN ETAL.
for both the individual and the group as a
whole. Although involving communities in
this way may delay or even make it impos-
sible to do studies that we would like to
do, this is the only way to proceed ethically
if the ultimate goal is the protection of
public health. We have found that involv-
ing communities at the outset saves time in
explaining study results and provides for a
better ultimate outcome.
In conclusion, human tissue banking
will help address a number of public health
concerns. We can potentially use it to
a) monitor trends in human exposures;
b) serve as an early warning system for new
environmental exposures; c) assess low level
exposures around hazardous waste and
other point sources of pollutants; d) evalu-
ate the effectiveness of regulatory programs;
and e) study etiologies of diseases (e.g.,
childhood cancer and birth defects) that are
likely to be related to the environment.
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34 Environmental Health Perspectives