About the Toxicant and Disease Database
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
Environmental Contributors to Diseases
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, along with a few non-chemical 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 is good evidence that increases in 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 may also be associated with chemical exposures, but the evidence is limited.
Studying Effects of Chemical Exposures
The effects of chemical exposures in humans are difficult to study because controlled human experimentation isn't ethical. Limited human data are available 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 to identify causes.
Exposure assessment, a critical step in environmental epidemiologic studies, is often difficult and incomplete. 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 to multiple chemicals both in the home and work environments are common. 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 epidemiologic studies often are conducted after an association has been hypothesized based on animal data.
The accompanying database summarizes links between select chemical and other environmental risk factors and more than 200 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. The database focuses primarily on human epidemiological studies, and a comprehensive review of animal data was beyond the scope of this project. However, in some instances animal data were included and influenced the listing. This is particularly likely when an authoritative body, such as the International Agency for Research on Cancer (IARC), the National Toxicology Program, or California’s Office of Environmental Health Hazard Assessment (OEHHA), which administers the Proposition 65 program, used animal data as the primary source for their evaluations.
Other main sources of data are three major textbooks on the topic of environmental medicine and toxicology:
- Klaassen CD, Ed. Casarett and Doull's Toxicology: The Basic Science of Poisons, 6th Edition. New York: McGraw-Hill, 2001.
- LaDou J. Ed. Occupational and Environmental Medicine, 3rd Edition. New York: Lange Medical/McGraw-Hill Company, 2004.
- Rom WM. Environmental and Occupational Medicine, 3rd Edition. Philadelphia: Lippincott Williams & Wilkins Publishers, 1998.
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 disease, disease category, toxicant, CAS number or keyword. For example, if someone is interested in oncology, the user would click on "Oncology" under "Browse by disease category" and the specific diseases within this disease category will appear on the screen.
The major organ systems covered:
|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:
|Allergy (Allerg)||Development (Develop)||Geriatrics (Geriat)|
|Men's Health (Male)||Metabolism (Metab)||Oncology (Onc)|
|Women's health (Female)||Otolaryngology (ENT)||Pediatrics (Peds)|
The database was updated most recently in April 2011. Information from OEHHA’s Prop 65 database, IARC and EPA’s Integrated Risk Information Service was added. Several nonspecific disease categories (e.g. cancer, developmental delays) were added to accommodate listings from the authoritative sources. Several families of chemicals, for example, furans, polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs) were added in addition to specific members of the families. In some instances, explanatory notes were added. These are visible on the pages for specific diseases.
Strength of Evidence
Toxicants 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 toxicants for which a causal association with disease has been verified. The toxicity of these toxicants has been well accepted by the medical or scientific research communities 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 toxicants were put into this category by causal associations drawn from more recent large prospective or retrospective cohort studies. Finally, toxicants listed as Group 1 human carcinogens by the International Agency for Research on Cancer (IARC) are included in this category. These are toxicants that have been determined to have sufficient evidence for causing cancer in humans.
The "good evidence" category includes toxicants associated with a disease through epidemiological studies (cross-sectional, case-series, or case-control studies) or for toxicants 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 toxicants, those with limited evidence for causing cancer in humans and sufficient evidence in animals, also are included in this category. Similarly, toxicants listed by OEHHA’s Prop 65 program as causing cancer or reproductive/developmental disorders, based on animal data, are included in this category.
The "limited/conflicting evidence" category contains toxicants 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 toxicants. These toxicants show limited or inadequate evidence of causing cancer in humans and limited animal evidence of causing cancer.
The majority of the toxicants 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 toxicant. Animal data often provide the supporting evidence of an individual toxicant's toxicity when human data are missing or incomplete.
As more scientific research is done, some toxicants 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.
This database has significant limitations that are important to keep in mind:
- 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 and other toxicants that are not listed also may be causally associated with a disease.
- 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 on related webpages on this site.
- 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.
- Finally, this is not intended to be an authoritative database in the sense that it can be used for legal or regulatory purposes. Authoritative databases, including those at IARC, NTP, OEHHA and others, do exist and should be consulted for those purposes. In many cases, the authors of this database needed to exercise judgment when considering the strength and categorization of evidence, and in some cases others may disagree with the decisions. However, we have attempted to characterize the strength of evidence conservatively so as not to overstate the case. Comments from readers are welcome and can be sent through our Contact form.
Also, this database was last updated in early 2011. CHE recognizes that some of the information is now out of date, and the database references are not as easy to navigate as we would like. We are updating the references and exploring how to maintain this important resource for our partners.
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.