By Edward D. Levin, Ph.D., Duke University (edlevin@duke.edu)
Toxicologists have made significant progress in identifying some toxic chemical exposures that cause adverse health consequences. However, only a relatively small number of the many tens of thousands of chemicals produced world wide have been investigated in depth. Most of the substances that have been investigated were first identified as chemicals of concern in epidemiological or clinical studies, and subsequently were tested using in vivo animal models and in vitro cell-based studies to determine cause-and-effect relationships and the mechanisms by which the damage occurs.
Epidemiological and clinical studies are vital, but they are essentially exercises in failure analysis; they study the damage that has already been done with the hope of minimizing future damage. Much as firefighters will always be required to quench fires, we will always need epidemiological and clinical toxicologists to limit toxic damage. However, we also need fire marshals to identify potential problems before they arise. Currently, toxicologists are making a concerted effort to use experimental animal models to test compounds before they are approved for commercial use, instead of waiting until the chemicals are already on the market and letting humans be the first “test” species.
Photograph by Sylvain Pedneault, distributed under a CC BY-SA 3.0 license.
Recently, the expense and time needed for such animal studies (most of which use a rodent model) has triggered greater investment for in vitro studies. These studies are “high throughput,” meaning that they can be used to quickly gather information about the cellular effects of a large number of compounds, but the meaningfulness of this huge cache of information remains to be determined. High throughput in vitro testing can complement, and make more efficient use of, experimental animal models, resulting in a more rapid testing process that is more useful for the regulation and reduction of human risk. Given the existence of high throughput in vitro technology, some have advocated for the eventual elimination of animal testing. Phasing out animal studies, however, would mean that humans would become the first complex test species.
Thus far, the principal aim of toxicology has been to identify and characterize “bad news” about chemical exposures with the hope of minimizing future risk. This is laudable for the protection of future generations, but what about the unfortunate folks, including us, who have been exposed to toxicants already? What about those people who are in the higher exposure groups of epidemiological studies that have identified a relationship between cognitive or emotional dysfunction and early-life lead, mercury, PCB, or pesticide exposure? Don’t they deserve to benefit from further studies that might yield possible treatments to address any impairments that they have developed from these exposures? Clinicians in our healthcare system are already treating toxicant-induced neurobehavioral dysfunction. Treatments for cognitive and emotional dysfunction are already in use. Might there be different optimal therapies for people who have neurobehavioral impairment due to toxicant exposure, in contrast to people who have impairments due to faulty biological mechanisms?
In addition to identifying problems caused by toxicants, toxicologists should aid in the discovery of therapies to reduce damage. Mechanistic studies of toxicity could be used to identify promising avenues for therapeutics. This idea does not apply solely to neurobehavioral toxicity; the same rationale is relevant for toxicant-induced damage to other organ systems, diabetes, obesity, or carcinogenesis.
Ideally, we need good experimental models before chemical approval (the proverbial “fire marshals”) to prevent toxic risks from becoming toxic reality. We still need epidemiological and clinical studies (the proverbial “fire fighters”) to quickly identify problems related to toxic chemicals and quench the fires to limit damage. We also need well-trained clinicians (the “medics”) on the scene to treat those who have suffered the ill consequences of toxicant exposure. Let’s try not only to prevent damage or limit it when we can, but also to address the needs of the many people who have already been exposed to toxicants.
Dr. Levin is Chief of the Neurobehavioral Research Lab in the Psychiatry Department of Duke University Medical Center. He directs the Neural Behavioral and Toxicity Assessment Core and the Training Core for the Duke University Superfund Research Center.