Principles of identifying and characterizing neurotoxicity.
There is currently considerable interest in the neurotoxic effects of environmental pollutants. Some of this interest is due to epidemiological, clinical and laboratory studies showing that the nervous system is a target for many toxic substances. The interest is also due to a realization of how little is actually known about the neurotoxicity of most environmental pollutants. Laboratory research in neurotoxicology can be viewed as having two distinct approaches that focus on either the identification or the characterization of neurotoxic substances. Research on the identification of neurotoxicity deals mainly with the screening of chemicals for neurotoxicity. There has been a long-standing tradition of screening chemicals for neurotoxicity. There have, however, been several recent developments that are likely to improve our ability to identify neurotoxic substances, including more detailed assessments of a variety of behavioral and neurological functions. Research on the characterization of neurotoxicity deals mainly with efforts to discover the mechanism(s) of action of neurotoxic substances. This type of research has in some cases significantly advanced our knowledge of neurotoxic effects (e.g., acrylamide, n-hexane). Characterization-based research addresses many of the extrapolation issues of concern in toxicology (e.g., acute to chronic, high-dose to low-dose), and specifically attempts to interrelate the cellular, molecular and functional (neurophysiological, neurobehavioral) effects of toxic substances. These two research approaches represent critical elements of a tiered testing approach that could ultimately lead to more efficient testing protocols and a more comprehensive understanding of pollutant-induced neurotoxic risk in human populations.
MacPhail
R C
RC
Neurotoxicology Division, Health Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711.
D000818:Animals; D006801:Humans; D009420:Nervous System / Q000187:drug effects*; D014116:Toxicology / Q000379:methods*