Confounding factors in toxicity testing

The necessity for understanding normal human functions and the mechanisms w hich underlie dysfunction in these processes is essential in the promotion of a healthier lifestyle. To achieve this goal utilization of a suitable an imal model is necessary in order to develop new pharmaceutical agents to al leviate diseases or chemicals to enhance the quality of life. It is incumbe nt upon investigators to choose a species in which pharmacokinetic principl es are established and it is important that these phenomena resemble those of the humans. The choice of rats has specific advantages in that these rod ents possess similar pharmacodynamic parameters to humans. Other advantages include availability, low cost, ease of breeding, and an extensive literat ure data-base to enable comparisons to present findings. However, in the in terpretation of data from animals to humans, there are factors which need t o be recognized as playing important roles in chemical-induced outcomes. Th e confounding factors include strain, supplier, age, gender, hormonal statu s and dietary intake. The aim of this article is to demonstrate that there are differences in the responsiveness of rat stock/strains to chemicals and that lack of consideration of confounding factors yields inappropriate con clusions regarding risk assessment for humans. (C) 2001 Elsevier Science Ir eland Ltd. All rights reserved.