by Sarah Janssen MD, PhD, Gina Solomon MD, MPH, Ted Schettler MD, MPH

August 2006

from Sfms Website

Human disease results from complex interactions among genes and the environment.

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 children.

More than 80,000 chemicals have been developed, used, distributed and discarded into the environment over the past 50 years.

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 as cancer, 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 significant error.

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.

Animal experimentation provides important data about the toxicity of chemicals and adds biological credibility to suspected causal associations in humans.
 

The Database

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:

1. Klaassen CD, ed. Casarett and Doull's Toxicology: The Basic Science of Poisons, 6^th edition. New York: McGraw-Hill

2. LaDou J, ed. Occupational and Environmental Medicine, 2^nd edition. Stamford, Conn: Appleton & Lange; 1997

3. Rom WM, ed. Environmental and Occupational Medicine, 3^rd edition. 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.

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:

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 (Female).

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 association.

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 was made.

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.

Often, human 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.

Database Limitations

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

• First, 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. 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.

   

  For 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 of evidence.

   

  Comments from readers are welcome.