Neglect of function and obsession with structure in toxicity testing

Abstract

The discrimination against the use of functional measurements in favour of pathomorphological investigations goes back to the very beginnings of drug toxicology studies. Since pharmacologists had the lead in drug development, they kept for themselves most of the activities necessary in the preparation of therapeutic trials, and only delegated to the toxicologists those safety studies required to exclude organdirected, cumulative adverse effects. Originally, these consisted of repeated-dose experiments with special attention to haematology, autopsy and histopathological examination of the organs. Later, an ever growing battery of clinical pathological tests was added. Together, these investigations resulted in a dossier of impressive dimensions which inspired confidence, not only because of its sheer size, but also because of the nature of the data, which could be easily compared with those usually obtained in patients. Pharmacologists still maintained an interest in acute disturbances of organ functions, but gladly relinquished the responsibility for long-term safety testing to toxicologists.