From clinical to human toxicology: linking animal research and risk assessment in man

Abstract

Since the 1960s, clinical toxicologists have primarily focused on acute poisonings. This proved very successful as the prognosis markedly improved with the use of resuscitation methods, evidence-based management and new antidotes. This latter area was the first major instance linking animal research and clinical toxicology, as illustrated with N-acetyl-cysteine or specific antibodies. Simultaneously the evolution of poison centers was a critical turning point as ‘2nd generation’ centers are increasingly involved in risk assessment and toxicovigilance. Human toxicology is a broader area in that it is also involved in the toxicity evaluation of xenobiotics with the resulting need to link animal research and risk assessment to match the results of preclinical studies with clinical observations. However, this is not an easy task as experimental and clinical toxicologists seldom share ideas and expertise. Immunotoxicology is an example of this situation. Most of the available data on immunosuppression was obtained in animals and not in man, whereas allergic reactions have been extensively investigated in man, but overlooked in animals until recently. One of the major challenges facing toxicology is to bridge the gap between animal research and risk assessment in man. Human toxicology is expected to play a role in taking up this challenge.