Comprehensive neurotoxicity assessment

Significant progress has been made in recent years in terms of both the conceptualization of neurotoxicity assessment strategies as well as in the development of behavioral techniques for evaluating neurotoxic exposures. A tiered approach, for example, has been advocated as an assessment strategy in which testing would proceed in a stepwise fashion from general screening using simple behavioral methods and neuropathology (tier 1) to the characterization of effects (tier 2) using more specific testing techniques. With respect to tier-1 testing, behavioral observational methods have been standardized for screening purposes, and these technically simple techniques, together with automated methods for motor activity assessment, are being increasingly incorporated into chemical and drug safety evaluations for regulatory purposes. With respect to tier-2 testing, more technically sophisticated techniques and behavioral paradigms are available for characterizing the behavioral effects of chemical exposures on motor, sensory, and cognitive processes. Paradigms involving learned and unlearned behavior, for example, have been described for quantifying a variety of clinical signs of motor impairment including paretic gait disorders, tremor, and coordination deficits. Likewise, robust noninvasive behavioral methods capable of tracking changes in visual, auditory, and somatosensory thresholds during the course of exposure are also available. With respect to cognitive testing, numerous maze and operant techniques and paradigms measuring different aspects of performance, learning, and memory have been elaborated. This paper presents an overview of behavioral techniques currently used to assess neurotoxicity in adult laboratory animals and discusses their application to hazard identification and other areas of risk assessment.