Chemical Contaminants and Human Disease: A Summary of Evidence

[Guest guest]

_http://www.protectingourhealth.org/corethemes/links/2004-0203spreadsheet.htm_

 

(http://www.protectingourhealth.org/corethemes/links/2004-0203spreadsheet.htm)

The essay below introduces a spreadsheet compiled by CHE member scientists

that summarizes representative knowledge about links between environmental

exposures and human diseases. While extensive, it is not an exhaustive list.

Of special value is the perspective it provides on the strength of the

scientific evidence linking a given health condition with a particular chemical

exposure.

References and footnotes are in separate sheets in the spreadsheet.

Access to the spreadsheet is available via _link below_

(http://www.protectingourhealth.org/corethemes/links/2004-0203spreadsheet.htm#sp\

readsheet)

_http://www.protectingourhealth.org/corethemes/links/environmentallinks.xls_

(http://www.protectingourhealth.org/corethemes/links/environmentallinks.xls)

,

at the end of the introductory materials. Please make sure to read about the

information's _limitations_

(http://www.protectingourhealth.org/corethemes/links/2004-0203spreadsheet.htm#li\

mitations) before making use of the database.

 

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Chemical Contaminants and Human Disease:

A Summary of Evidence

Sarah Janssen MD, PhD

Gina Solomon MD, MPH_1_

(http://www.protectingourhealth.org/corethemes/links/2004-0203spreadsheet.htm#gs\

)

Ted Schettler MD, MPH_2_

(http://www.protectingourhealth.org/corethemes/links/2004-0203spreadsheet.htm#ts\

)

_http://www.protectingourhealth.org/corethemes/links/2004-0203spreadsheet.htm_

 

(http://www.protectingourhealth.org/corethemes/links/2004-0203spreadsheet.htm)

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 in humans or

wildlife. Some of these chemicals are commonly in air, water, food, homes, work

places, 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 10-20 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 exposures often 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. 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_

(http://www.protectingourhealth.org/corethemes/links/environmentallinks.xls)

_http://www.protectingourhealth.org/corethemes/links/environmentallinks.xls_

(http://www.protectingourhealth.org/corethemes/links/environmentallinks.xls)

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 ed. (2001) McGraw-Hill publishing, New York .

* LaDou J. Ed. Occupational and Environmental Medicine, 2nd Edition

(1997) Appleton & Lange, Stamford , CT

* Rom WM, Ed. Environmental and Occupational Medicine, 3rd edition

(1998). Lippincott-Raven, Philadelphia , PA.

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 “oncâ€. The database can not be sorted by chemical names,

but

individual chemicals can be located by using the “find†function in Excel.

The major organ systems covered are:

Cardiovascular (C.V.); Endocrine (endo); Gastrointestinal (G.I.);

Genitourinary (G.U.); Hematology (Heme); Immunology (Imm);

Liver (Hepat); 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); Otolaryngology

(ENT); Pediatrics (Peds); Psychiatry (Psych).

Women's health (female);

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 are 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 that have been 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 of 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.

 

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Gina Solomon MD, MPH: Natural Resources Defense Council; University of

California San Francisco

Ted Schettler MD: Science and Environmental Health Network; Boston Medical

Center