Expanded clinical observations in toxicity studies: historical perspectives and contemporary issues

Abstract

Recent or proposed changes in major testing guidelines require expanded clinical observations (ECOs) for a wide variety of toxicity studies in animals. ECOs supplement the simple cageside and hand-held observations traditionally employed during such studies. The new guidelines specify out-of-cage observations [e.g., posture, gait, and reactivity to various stimuli (e.g., auditory, tactile, noxious)] using defined scales and are intended as a Tier 1 screen for neurotoxicity. These new guidelines imply an elevation in the status of clinical observations to equivalency with other major categories of toxicity end points, such as anatomic and clinical pathology. The increased importance of neurological end points in routine studies indicates that there will be a need for many trained professionals to generate and interpret the results of ECOs. However, currently there is wide variation in the training and experience of individuals who conduct and interpret ECOs. The value of ECO data will be increased when industry standards for conducting and interpreting ECOs are systematized and elevated to the level of those for anatomic and clinical pathology.