Disease Detection: The Effects of Contaminants on
Understanding the effects chemical contaminants have on human health
is not a simple or straightforward process. One reason for this
challenge is because there are approximately 15,000 chemicals produced
and less than half of those have ever been tested to determine their
impact on human health. Add to the quantity of chemicals, the many
possible interrelationships between all of the chemicals and the
unique genetic and environmental circumstances of every human, predicting
or confirming that a disease has been caused by a chemical contaminant
is extremely complicated. This page will describe contaminant-based
disease detection, discuss epidemiology, describe the weight-of-evidence
cancer categories, and provide additional web links.
Contaminant-Based Disease Detection
One of the biggest fears of exposure to contaminants is cancer.
Some contaminants are known carcinogens while others are only suspected.
An example of a known carcinogen is asbestos; a suspected carcinogen
is DEHP [di(2-ethylhexyl)phthalate] - a component of plastic. For
many contaminants, scientists do not always know how much exposure
will cause harm or disease. Scientists do not know about the risk
to humans because many studies are conducted on rats and mice rather
than on humans. (It would be unethical to purposefully expose humans
to high doses of these chemicals.) In human studies, knowing how
much exposure has occurred is a significant challenge.
Environmental contaminant exposures can be related to other diseases
in addition to cancer. Such diseases include immune deficiencies
(from polychlorinated biphenyls or PCBs), asthma (from particulates),
reproductive disorders (from DEHP), neurological (brain and nerve)
disorders (from lead), blood disorders (from benzene), liver disorders
(from dioxins) and other health problems such as endocrine, gastrointestinal
or skin conditions. There are many other conditions that are suspected
as being caused by contaminants, but physicians and scientists are
not certain of the cause. Most physicians are not trained in the
complex analysis of chemical exposures. In addition, special testing
by select laboratories is needed to test blood or tissue for many
of the suspected causative agents (chemicals). This uncertainty
can make citizens anxious and angry that their conditions are not
being considered seriously. It is important to describe your concerns
to your physician and ask for a referral to a specialist.
Some people might think hazardous chemicals should be eliminated
entirely. However, it is difficult, to weigh the possible harm of
exposure versus the need for the chemical. For example, asbestos
is an important substance in fire protection and cannot be completely
eliminated from use. Therefore, means to protect human health from
exposure has become a priority.
The Centers for Disease Control and Prevention (CDC) has a department
called the Agency for Toxic Substances and Disease Registry (ATSDR).
ATSDR will actually conduct exposure investigations using an Exposure-Dose
Reconstruction Analysis (EDRA). ATSDR takes environmental samples
and conducts a computer model to estimate exposure levels. The State
Health Department may also conduct these analyses under contract
with the ATSDR.
ATSDR typically requires additional information in the following
categories (ATSDR, 1994):
- Contaminant concentrations in all off-site media to which the
public may be exposed;
- An appropriate detection limit and level of quality assurance/quality
control (QA/QC) in samples to ensure the resulting data are adequate
for assessing possible human exposures;
- Discrete samples that reflect the potential range of exposure
of the public;
- Surface soil and sediment samples not deeper than 3 inches;
- More extensive biota studies, and analyses of edible portions
- More ambient and indoor air sampling; and
- Lists of physical hazards and barriers to site access.
Finally, citizens can help look for disease clusters themselves.
A cluster is an unusually high number of health events found at
similar times in a given location. If you suspect you or your community
has been exposed, it is important to gather information to help
identify a cluster.
The ATSDR can provide guidance about the kind of environmental data
needed to assess public health related to toxic substances. This
website provides the details of an environmental
public health assessment.
Disease clusters are often of interest to communities that have
hazardous waste sites. It often seems that there is more cancer
in the community than there should be. Public health departments
and epidemiologists can help a community identify if there is a
link between disease and environmental exposure. "Epidemiology
is the study of the distribution of disease, or other health-related
states and events in human populations, as related to age, sex,
occupation, ethnicity, and economic status in order to identify
and alleviate health problems and promote better health" (EPA).
However, epidemiology is challenged by the uneven ways diseases
and illnesses affect populations. Environmental epidemiologists
have the added complexity of determining if the people that have
the disease were ever exposed to an environmental contaminant.
Some of the unevenness in exposure can be related to individual
susceptibility to contaminants, "dose" of exposure (length,
frequency, amount), and geographic differences that can include
climate or populations relocating. Therefore, tracking environmental
diseases in populations is a challenge. It is especially challenging
to understand how much exposure to a contaminant any individual
has received. For example, in a location that is affected by air
pollutants, some individuals may reside in the community all day
while others may commute away from the area for work. Distance from
the pollutant source may make a difference in the response to an
exposure, as can age, sex, susceptibility or the presence of other
disease processes. Combinations of unrelated exposures may also
complicate epidemiology. Such combinations might include smoking,
diet or workplace exposures that can add to an individual's risk
from an environmental exposure.
Environmental epidemiology may begin when an unusual number of
health problems (cluster) is identified in a population that seem
unexplained. Epidemiology may also begin by recognizing that an
exposure has occurred, for example, discovering arsenic in a population's
wells. When the health problems are identified first, epidemiologists
typically work "backwards" to find the people with the
disease and obtain detailed information about past exposures. When
an exposure is identified, epidemiologists may observe the population's
health into the future to determine if disease occurs.
It is helpful to understand some of the terms that epidemiologists
use in their attempts to understand the epidemiology of environmental
Incidence Rate: An incidence rate is the change
in health status in a population over time. A rate is generally
measured and reported annually. For example a death rate or birth
rate is the number of deaths or births in a year. In epidemiology,
the number of "cases" in a year would be the rate. It
is important to know how the rate was calculated because rates use
different population sizes for reference. For instance, the difference
between 5 cases in 1000 population is quite different from 5 cases
in 1,000,000 population. Rates allow comparisons between populations
because the population size is controlled. If people recover from
the disease or die from the disease, they are still counted in the
incidence rate. One example of a rate is the breast cancer rate
in the US population - 134 cases/100,000 in 1999 http://www.cdc.gov/cancer/npcr/npcrpdfs/USCSreport.pdf.
This figure means that for every 100,000 people in the US in 1999,
134 of them had breast cancer.
Prevalence: Prevalence is the percentage of a
disease in a population. This measure only provides a description
at a particular point in time. The prevalence will decline if people
recover (or die) from the disease because of the "snapshot"
nature of the prevalence measurement. For example, the prevalence
of cigarette smoking among those 18 years of age and older was 25%
in 1990, and has declined since then http://www.cancer.org/downloads/STT/CAFF2003PWSecured.pdf.
This figure means that among all people 18 and older in the US,
25% of them smoked in 1990.
Mortality Rate: Similar to an incidence rate,
a mortality rate provides a rate of deaths (mortality) over time
(typically a year). As with incidence rate, it is important to know
the population size, such as 100,000 or 1,000, 000. Often the mortality
rate will be described in relation to a particular disease, such
as the mortality rate for breast cancer. For example, the breast
cancer mortality rate for African American females is 37.3/100,000
population from 1992-1999 http://www.cancer.org/downloads/STT/CAFF2003PWSecured.pdf.
This figure means that every for every 100,000 African American
women, 37.3 of them died from breast cancer every year between 1992-1999.
Epidemiology often considers relationships between environmental
exposures and disease. Establishing the cause of disease is difficult
because exposure to the contaminant is so uncertain. To try to establish
causal relationships, exposure must be certain. Animal models are
used for this purpose and the animal studies must then be "translated"
or extrapolated so they apply to human populations. These studies
have wide variations in exposure conditions as well. Therefore,
the EPA uses the "weight of evidence" to determine exposure
levels that will likely cause (or not cause) disease. This process
is described below.
Weight of Evidence for Cancer Risk Assessment
The EPA reviews the scientific literature and studies to determine
how to classify chemicals in terms of their potential for causing
cancer. These classifications are determined based on the "weight
of evidence" that examines laboratory, animal and human epidemiological
studies. In 1986 an alpha-numeric system was used and many web sources
still display this system. This system considered primarily the
chemical's ability to cause tumors. In 1996, a three-category system
was approved. It considers additional information, such as knowledge
about similar chemicals and chemical behavior as part of the classification.
Both systems are described below.
The new system uses the categories of Known/Likely, Cannot
Be Determined, or Not Likely. A narrative description
accompanies the category that describes the evidence available and
how the conclusion was reached to categorize the chemical in a certain
way. Chemicals may be Known/Likely carcinogens for an inhalation
route of exposure, but Not Likely for an oral route of
exposure. This narrative system helps make such distinctions clear.
Limitations in the data are also part of the narrative. A lengthy
document about this change can be found on their website.
- Known/Likely: The data are convincing that the agent
may cause cancer in humans. Tumor evidence and epidemiologic data
are used. A chemical may be classified Known/ Likely
for one route of exposure, but not another.
- Cannot Be Determined: Data about tumor effects are
incomplete, but the evidence does not confirm the risk. If there
are no data, the agent would be classified here.
- Not Likely: There is adequate evidence to demonstrate
there is no basis for human cancer concern. Agents may be classified
Not Likely if the evidence shows cancer in animals only
at very high doses or by certain routes. A chemical may be classified
Not Likely for one route of exposure, but not another.
The older system is described at the Penn
State web site. These categories are:
- Group A: Human Carcinogen. Used when there is sufficient
evidence from epidemiologic studies to support a causal association
between exposure to the agent and cancer.
- Group B: Probable Human Carcinogen. Used when epidemiologic
data are limited and when the weight of evidence of carcinogenicity
from animal studies is sufficient.
- Group B1: Used when agents have limited evidence
from epidemiologic studies. Evidence of carcinogenicity in
animals is considered supporting evidence of risk in humans.
- Group B2: Used when there is sufficient evidence
from animal studies but inadequate or no evidence from epidemiologic
- Group C: Possible Human Carcinogen. Used when there
is limited animal evidence and no human evidence to support carcinogenicity.
Problems in experimental design or statistical significance make
the evidence less certain.
- Group D: Not Classifiable as to Human Carcinogenicity.
Used when there is inadequate evidence in humans or animals about
- Group E: Evidence of Non-Carcinogenicity for Humans.
This group is used for agents that show no evidence for carcinogenicity
in at least two animal tests in different species or in both adequate
epidemiologic and animal studies. It is based on available evidence
and is not a definitive conclusion that the agent will not be
a carcinogen under any circumstances.
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