Neurobehavioral methods used in neurotoxicology.
The use of neurobehavioral techniques in toxicology has increased dramatically over the past several years. Several national and international groups have recommended that neurobehavioral tests be included in the initial stages of hazard identification, and regulatory agencies have responded by preparing testing guidelines or requiring behavioral tests data for premarket approval of environmental and pharmaceutical chemicals. In addition, neurobehavioral data have been used to set exposure limits in the workplace. In the future, neurobehavioral data will be used more frequently in the area of risk assessment, which has been defined as the "characterization of the potential adverse effects of human exposure to environmental hazards" (National Academy of Sciences 1983). Good risk assessment depends on the ability to determine whether a particular agent is or is not causally linked to a particular health effect and on the availability of dose-response data for quantitative risk assessment. Neurobehavioral techniques used in animal behavioral toxicology measure neurobiological functions similar to those measured in humans. In addition, neurobehavioral procedures can be used in longitudinal studies where the onset and duration of effects of chemical exposure can be measured in the same animal. Neurobehavioral techniques are also amenable to the study of tolerance and compensation following repeated exposure or following recovery of function that can occur following cessation of exposure. Therefore, neurobehavioral procedures provide a valuable tool for research designed to reduce major uncertainties associated with the risk assessment process, such as animal to human extrapolation (homology of animal models) and dosing issues (i.e., high-to-low dose, acute vs. repeated dosing, and continuous vs. episodic dosing). Although the use of neurobehavioral procedures has had a significant impact on neurotoxicology, their use in the risk assessment process and in monitoring populations for possible subtle changes in neurobiological function will be limited if additional research is not done to understand the neural substrates underlying neurobehavioral endpoints. The ability to link chemically induced behavioral changes to alterations at the neurophysiological, neurochemical, and neuroanatomical levels will lead to a greater acceptance of the validity and reliability of neurobehavioral endpoints in defining adverse effects of chemicals on the nervous system.
Tilson
H A
HA
Neurotoxicology Division (MD-74B), U.S. Environmental Protection Agency, Health Effects Research Laboratory, Research Triangle Park, NC 27711.
D000818:Animals; D001519:Behavior / Q000187:drug effects*; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000187:drug effects*; D003213:Conditioning, Psychological / Q000187:drug effects; D006801:Humans; D009043:Motor Activity / Q000187:drug effects; D012677:Sensation / Q000187:drug effects; D014116:Toxicology / Q000379:methods*