General considerations in assessing neurotoxicity using neuroanatomical methods.

Abstract

Neurotoxicology is a major focus of scientists and policy makers. Neurotoxicological investigations provide vital information needed by regulatory scientists to protect public health and can also elucidate fundamental mechanisms governing nervous system function and enhance our understanding of neurodegenerative diseases as well. A definition of neurotoxicity, developed by the Interagency Committee on Neurotoxicology, includes both permanent and reversible adverse effects on the nervous system. There are a number of factors that can greatly affect the outcome of any study designed to assess neurotoxicity, such as the choice of animal species, dose and dosage regimen, and route of administration. In considering neuroanatomical methodologies for assessing neurotoxicity, it is important to evaluate each technique for such factors as: limits of detection (sensitivity and signal to noise ratio), ability to be quantified, sampling problems, what is being measured and what can interfere with this measurement. Other questions relating to the strengths and weaknesses of neuroanatomical techniques that should be addressed include: is the technique difficult to perform? Is it reproducible? Which elements of the nervous system are best evaluated? Does the technique reveal the neuronal circuitry involved in the neurotoxic effect? Is successful application of the technique dependent on timing factors? Clearly, there are many factors that can influence the assessment of neurotoxicity so that it is best to base this assessment on converging data based on complementary techniques.