CHE Toxicant and Disease Database
Database---> http://database.healthandenvironment.org/index.cfm
Sarah Janssen MD, PhD, MPH
University of California, San Francisco

Gina Solomon MD, MPH
Natural Resources Defense Council; University of California San Francisco

Ted Schettler MD, MPH
Science and Environmental Health Network; Boston Medical Center

Human disease results from complex interactions among genes and the
environment. Environmental exposures to chemical, physical, and
biological agents may cause or contribute to disease in susceptible
individuals. Personal lifestyle factors, such as diet, smoking,
alcohol use, level of exercise, and UV exposure, often are a 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
and preventable contributors to human disease. These exposures are the
focus of this project.

More than 80,000 chemicals have been developed, distributed, and
discarded into the environment over the past 50 years. The majority of
them have not been tested for potential toxic effects in humans or
animals. Some of these chemicals are commonly found in air, water,
food, homes, work places, and communities. Whereas the toxicity of one
chemical may be incompletely understood, an understanding of the
effect from exposures to mixtures of chemicals is even less complete.
Chemicals may have opposing, additive, or even synergistic effects.
One example of a synergistic effect is tobacco smoking coupled with
asbestos exposure, which 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.

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 well
established as causes of human disease. There also is good evidence to
suggest increases in the incidence of some cancers, asthma, and
developmental disorders can be attributed to chemical exposure,
particularly in young children. Other diseases, such as ALS or Gulf
War Syndrome have been hypothesized to be associated with chemical
exposures, but the evidence is limited.

The effects of chemical exposures in humans are difficult to study
because controlled human experimentation isn't ethically feasible.
There is limited human data obtained from accidental exposures,
overdoses, or studies of workers exposed occupationally. Environmental
exposure studies in the general population also can be useful, though
they often have limitations. Many diseases, such as cancer, may not
appear until decades after an exposure has occurred making it
difficult for causal associations to be identified. Exposure
assessment, a critical step in environmental epidemiologic studies, is
difficult. Retrospective exposure assessment usually requires
estimates and considerable judgment and is subject to significant
error. An individual's exposure may change over time, and exposures
occur to multiple chemicals both in 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 their exposures were.

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.

Because of these challenges, most toxicity research is conducted in
animal studies. Although animal studies are not the emphasis of this
database, animal studies contribute important toxicological
information and can provide strong evidence of disease without human
epidemiological studies if the mechanism of action is relevant. Many
regulatory decisions to limit or ban a chemical's use are based on
animal data. Furthermore, human epidemiology studies often are
conducted after an association has been hypothesized based on animal data.

The accompanying database summarizes links between chemical
contaminants and ~180 human diseases or conditions. We have designed
this database to reflect the current state of knowledge about
toxicants and human disease, organized by disease categories. Because
the database focuses primarily on human epidemiological studies and a
comprehensive review of animal data was beyond the scope of this
project, animal data were included for only a few diseases.

Data for the database were obtained from three major textbooks on the
topic of environmental medicine and toxicology. These sources are:

1. Klaassen CD, Ed. Casarett and Doull's Toxicology: The Basic
Science of Poisons, 6th edition. (2001) McGraw-Hill publishing, New York.
2. LaDou J. Ed. Occupational and Environmental Medicine, 3rd
edition (2004), Lange Medical/McGraw-Hill, New York.
3. Rom WM, Ed. Environmental and Occupational Medicine, 3rd edition
(1998). Lippincott-Raven, Philadelphia, PA.

Literature searches for human epidemiological studies and reviews of
disease topics were carried out to supplement and update textbook
information.

The database is searchable by organ system categories and by chemical
names on the right hand column of the database page. For example, if
someone is interested in oncology, the user would click on "Oncology"
under "Browse by disease category" and the toxicants associated with
this disease category will appear on the screen.

The major organ systems covered are:
Cardiovascular (CV) Endocrine (Endo) Gastrointestinal (GI)
Genitourinary (GU) Hematology (Heme) Immunology (Immuno)
Liver (Liver) Musculoskeletal (Msk). Neurology (Neuro)
Respiratory (Resp) Renal (Renal) Skin (Derm)

Other categories included are:
Allergy (Allerg) Development (Develop) Geriatrics (Geriat)
Men's Health (Male) Metabolism (Metab) Oncology (Onc)
Women's health (Female) Otolaryngology (ENT) Pediatrics (Peds)
Psychiatry (Psych).

The database is searchable by toxicant, or by specifying a disease
category.
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 association.

The "strong evidence" category is reserved for chemicals where a
causal association with disease has been verified. The toxicity of
these chemicals has been well-accepted by the medical community and is
noted in the 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 that have
been determined to have sufficient evidence for causing cancer in humans.

The "good evidence" category includes chemicals associated with a
disease through 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. Textbook
statements such as, "There is evidence for an association between
exposure to x compound and y disease." assumed good evidence. IARC
Group 2A chemicals, those with limited evidence for causing cancer in
humans and sufficient evidence in animals, also are included in this
category.

The "limited/conflicting evidence" category contains chemicals weakly
associated with human disease by reports from only a few exposed
individuals (case reports), from conflicting human epidemiological
studies that have given mixed or equivocal results, or in a few cases,
from reports clearly demonstrating toxicity in animals where no human
data exist. 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.

The majority of the chemicals in the database fall into the
"limited/conflicting" evidence category. This is because human
epidemiological studies are very complex, difficult to design and
interpret, and cannot be easily repeated. Health outcomes linked to
exposures to mixtures of compounds, such as pesticides or solvents,
sometimes provide hints of causal associations and direct future
research efforts but usually cannot provide strong evidence,
especially for one particular chemical. Animal data often provide the
supporting evidence of an individual chemical's toxicity when human
data are missing or incomplete.

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 of the list entirely.
Database limitations

This database has significant limitations that are important to keep
in mind.

1. The chemicals listed are a representation of toxicants that
contribute to human disease and disorders. This is not an exhaustive
or comprehensive list and includes primarily chemicals and diseases
found in major textbooks and medical literature reviews. Chemicals
that are not listed also may be causally associated with a disease.

2. 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 addressed. For
example, a fetus or developing child is often more susceptible to a
given exposure than an adult. For details on the dose, timing,
duration, and route of exposure, etc. the reader is referred to the
textbooks, references, and the attached web-links.

3. The database makes no attempt to quantify the proportion of disease
that is 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 lung
cancer cases caused by asbestos exposure is relatively small compared
to the number of cases caused by tobacco smoking or radon.

4. Finally, this is a work in progress. In many cases, the authors
exercised judgment when considering the strength and categorization of
evidence. Comments from readers are welcome and should be sent to
Sarah Janssen at sarahjanssen@....
Toxicant and Disease
Database----->http://database.healthandenvironment.org/index.cfm


Disclaimer and Acknowledgement: This publication was supported by
cooperative agreement numbers U5O/CCU922449 and U5O/CCU923293 from the
Centers for Disease Control and Prevention (CDC) as part of a national
environmental public health tracking program its contents are solely
the responsibility of the authors and do not necessarily represent the
official views of the CDC.