by Sarah Janssen MD, PhD, Gina Solomon MD, MPH, Ted Schettler MD, MPH
Dr. Sarah Janssen works as a consultant for the Science and
Environmental Health Network. She is a graduate of the MD/PhD
program at the University of Illinois in Urbana-Champaign. Her
doctoral research was in male reproductive biology and involved
studying the physiological role of estrogen in sperm maturation. She
recently completed an internship in general surgery at UCSF and will
enter a residency program in Occupational and Environmental Medicine
this July at UCSF.
Dr. Gina Solomon is a senior scientist at the Natural Resources
Defense Council and an assistant clinical professor of Medicine at UC San Francisco, where she is also an attending physician at the UC
Pediatric Environmental Health Specialty Unit. She is a coauthor of
the book, Generations at Risk: Reproductive Health and the
Environment, published by MIT Press in 1999.
Dr. Ted Schettler serves on the medical staff of Boston Medical
Center and has a clinical practice at the East Boston Neighborhood
Health Center. He is science director for the Science and
Environmental Health Network at
www.sehn.org, and co-chair of
Greater Boston Physicians for Social Responsibility. Dr. Schettler
coauthored Generations at Risk (MIT Press, 1999), which examines the
reproductive health effects of exposure to a variety of
environmental toxicants, and In Harm's Way-Toxic Threats to Child
Development, which examines the impacts of environmental
contaminants on children's neurological development.
Human disease results from complex interactions among genes and the
Chemical, physical and biological agents may cause or
otherwise influence the onset of various illnesses or disorders in
susceptible individuals. Nutritional status and socioeconomic
conditions also alter disease susceptibility. Personal lifestyle
factors, such as diet, smoking, alcohol use, level of exercise and
UV exposure, are often the primary focus when considering
preventable causes of disease.
However, exposures to chemical
contaminants on the job, at home, in the outdoors, and even in utero
are increasingly recognized as important contributors to human
disease. These exposures are the focus of this project.
Toxic effects of chemical agents are often not well understood or
appreciated by health care providers and the general public. Some
chemicals, such as asbestos, vinyl chloride and lead, are known to
cause human disease. Other studies suggest that increases in the
incidence of some cancers, asthma and developmental disorders also
can be attributed to chemical exposure, particularly in young
More than 80,000 chemicals have been developed, used,
distributed and discarded into the environment over the past 50
The majority of them have not been tested for potential toxic
effects on humans or wildlife. Some of these chemicals are commonly
in air, water, food, homes, workplaces, and communities. Whereas the
toxicity of one chemical may be incompletely understood, an
understanding of the impacts from exposure to mixtures of chemicals
is even more deficient.
Chemicals may have opposing, additive, or
even synergistic effects. In one example of a synergistic effect,
tobacco smoking coupled with asbestos exposure increases the risk of
lung cancer by 25-fold-a risk much higher than that resulting from
the sum of the risks of the individual agents.
The effects of chemical exposures in humans are difficult to study
because human experimentation is generally unethical. Therefore,
much of the information is gathered from accidental exposures,
overdoses, or studies of workers exposed occupationally.
Epidemiologic studies in the general population can also be useful
though they often have limitations.
Many diseases, such
may not appear until 10 to 20 years after an exposure has occurred,
making it difficult for causal associations to be drawn. Exposure
assessment, a critical step in environmental epidemiologic studies,
is also often difficult. Retrospective exposure assessment usually
requires estimates and considerable judgment and is subject to
An individual's exposure may change over time,
and often is actually exposure to multiple chemicals in both the
home and work environments. It is difficult for individuals to
remember what they have been exposed to and, moreover, most people
are unaware of what degree of exposure they had.
The effects of chemical exposures may vary, depending on the age of
exposure (in utero, childhood, adult), the route of exposure
(ingestion, inhalation, dermal), amount and duration of exposure,
exposures to multiple chemicals simultaneously, and other personal
susceptibility factors, including genetic variability.
experimentation provides important data about the toxicity of
chemicals and adds biological credibility to suspected causal
associations in humans.
The accompanying database (which appears on page 15 and represents
only one page of 54 on the our website) summarizes many links
between chemical contaminants and about 200 human diseases,
disorders or conditions.
We have designed this database to reflect
the current state of knowledge about toxicants and human disease,
organized by disease categories. Although the database focuses
mainly on specific diseases, some clinical symptoms also have been
included where clinical knowledge is lacking.
For example, few
chemicals are directly associated with the clinical syndrome of
attention deficit hyperactivity disorder, but a larger number are
associated with decreased attention span.
Data were obtained from three major textbooks on the topic of
Environmental Medicine and Toxicology.
These sources are:
Klaassen CD, ed. Casarett and Doull's
Toxicology: The Basic Science of Poisons, 6th
edition. New York: McGraw-Hill
LaDou J, ed. Occupational and Environmental Medicine, 2nd
edition. Stamford, Conn: Appleton & Lange; 1997
Rom WM, ed. Environmental and Occupational Medicine, 3rd
Philadelphia, Penna: Lippincott-Raven;1998
Literature searches for epidemiological studies and reviews of
disease topics were carried out to supplement and update information
from the textbooks. These additional manuscripts are referenced in
The database is designed in Microsoft Excel and is sortable by organ
system categories. For example, if someone is interested in
oncology, the diseases can be sorted by "onc."
The database cannot
be sorted by chemical names, but individual chemicals can be located
by using the "find" function in Excel.
The major organ systems covered are:
Other categories included are:
Men's Health (Male)
The three columns to the right of each disease or disorder list the
corresponding categories as noted above by the abbreviations in
parentheses. For example, uterine cancer is placed in the categories
of oncology (Onc), genitourinary (G.U.), and women's health
References for and notes on each condition are found in
the far right columns.
Strength of Evidence
Chemicals that have been linked to a condition are placed in one of
three categories based on the strength of evidence for the
The "strong evidence" category is reserved for chemicals where a
causal association to disease has been verified. The toxicity of
these chemicals has been well accepted by the medical community and
noted in textbook references as,
"It is well known that x chemical
causes y condition" or "There is strong evidence that x compound
causes y disease."
Other chemicals were put into this category by
causal associations drawn from more recent large prospective or
retrospective cohort studies.
Finally, chemicals listed as Group 1
human carcinogens by the International Agency for Research on Cancer
(IARC) are included in this category. These are chemicals determined
to have sufficient evidence for causing cancer in humans.
The "good evidence" category is for associations of chemicals and
disease drawn from smaller epidemiological studies (cross-sectional,
case-series, or case-control studies) or for chemicals with some
human evidence and strong corroborating animal evidence of an
association. The strength of these associations is assumed from the
texts where no indication of a causal association in human studies
IARC Group 2A chemicals, those with limited evidence for
causing cancer in humans and sufficient evidence in experimental
animals, also are included in this category.
The "limited/conflicting evidence" category contains chemicals that
have been weakly associated with human disease by reports from only
a few exposed individuals (case reports), or from conflicting human
epidemiological studies that have given mixed or equivocal results.
In some cases, reports demonstrating toxicity in animals were used
but the animal toxicity literature was not comprehensively reviewed.
Also included in this category are IARC Group 2B chemicals and EPA
Group B2 chemicals.
These chemicals show limited or inadequate
evidence of causing cancer in humans and limited animal evidence of
causing cancer. Many of these chemicals in this category were found
in the studies published since the textbooks were last updated.
The majority of the chemicals in the database fall into this limited
evidence category. This is because, as noted above, human
epidemiological studies are very complex and difficult to design and
interpret. Exposures to mixtures of compounds, such as pesticides or
solvents, can provide hints of possible associations with disease
and direct future research efforts but often cannot provide strong
evidence of causation. Most toxicity research is conducted in
laboratory animal or test tube (in vitro) studies.
epidemiologic studies are conducted only after an association has
been hypothesized, based on other sources.
As more scientific
research is done, some chemicals in the database may be found to
have stronger evidence for causing disease, new chemicals will be
added, and others may be found to have no association with a disease
and fall off the list entirely.
This database has significant limitations that are important to keep
First, the chemicals listed are a representation of
toxicants that contribute to human disease and disorders.
not an exhaustive or comprehensive list and includes primarily
chemicals and diseases found in major textbooks and medical
literature reviews. Other chemicals that are not listed may also be
causally associated with a disease.
Second, the database does not address the route, timing, duration,
or amount of exposure required to result in a particular condition.
Some chemicals may only be toxic if inhaled, whereas others need to
be ingested in order to be toxic.
Some diseases result from only
high-dose exposures whereas low-level exposures may be less
important. Moreover, variations in the susceptibility to toxic
effects, depending on the timing and duration of exposure, are not
regularly addressed. For example, a fetus or developing child is
often more susceptible to a given exposure than an adult.
details on the dose, timing, duration, and route of exposure, etc.,
the reader is referred to the textbooks and the references included
in the database.
Third, the database makes no attempt to quantify the proportion of
the individual diseases that are caused or contributed to by
specific environmental factors.
For example, mesothelioma, a rare
form of cancer, is almost entirely due to exposure to asbestos. In
contrast, the proportion of more common kinds of lung cancer cases
caused by asbestos exposure is relatively small compared to the
number of cases caused by tobacco smoking or radon.
Finally, this is a work in progress. In many cases, the authors
exercised judgment when considering the strength and categorization
Comments from readers are welcome.