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.
Oxygen? "I rarely use it myself, sir. It promotes rust." Robby the Robot, Forbidden Planet (1956)Indirect evidence suggests that free radicals and excited-state species play a key role in both normal biological function and in the pathogenesis of certain human diseases. For example, generation of activated species by inflammatory cells is a major microbiocidal mechanism and may also mediate important components of the inflammatory response. Activated processes may also be key components in the toxicity of many drugs, in aging, and in carcinogenesis. They may also figure in the etiology of certain ocular, neurological, and psychiatric diseases.
The evidence for a role for electronically activated species in human disease has long been prevalent. For example, Darwin repeats the well-known observation that white, blue-eyed cats are usually deaf. Similarly, the relationship between pigmentary abnormalities and human deafness (for example, in Waardenberg's or Usher's syndromes) is commonplace in audiology(4). Likewise, physicians have long recognized the association between radical-generating metals such as copper or iron and fibrotic changes, e.g., interocular fibrosis in vitreous chalcosis and liver cirrhosis in Wilson's disease and Hemochromatosis.
Further, free radicals and other activated species are so difficult to measure under biological conditions that the evidence for their role in any biological process - much less a human disease state - is normally indirect and circumstantial. This flawed scientific basis often results in heated controversy over methodology, results, and conclusions. Even less should be expected of the clinical evidence. Nonetheless, there is significant circumstantial evidence that active oxygen (Figures 1 and 2) is involved in some of the most fundamental mechanisms in pathogenesis and in the etiology of many human diseases.
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.