ABSTRACT
An exposure-or dose-response relationship defines the exposure or dose of a chemical causing a defined biological effect. In its most often used form in toxicology it is the relationship between that administered (e.g. by mouth, inhalation, etc.) and the death of the animals. The exposure causing the death of 50% of the animals exposed, LD50 (lethal dose=exposure) is a measure of the toxicity of the chemical and is widely used as a preliminary screen. The LD50 procedure has been much criticised for its large use of animals trying to produce a result of (usually) unnecessary statistical accuracy which is of limited utility. Sometimes it is used for bioassay purposes but usually only small numbers are required to obtain LD50 values of adequate accuracy (Weil, 1952). The experimental procedure is simple and the value obtained is operational but conceals much biological complexity. Many factors influence the delivery of the toxic chemical to its target and the amount to which the target is exposed is often only a fraction of that administered to the animal. Only the concentration of intoxicant causing interaction at the target and the first biological effect yields a value for dose-response uncomplicated by these other factors. Moving from primary interaction with target (stage 3 of Figure 2.1) through the later biological consequences (stage 4) to clinical signs of poisoning (stage 5), the dose-response will not remain the same. For example, although 50% reaction with the target (stage 3) may be sufficient to cause biochemical (e.g. enzyme leakage from cells, changes in the metabolism of cells or tissue) or physiological effects (e.g. changes in nerve conduction velocity, sweating, sensitivity to sound or light (stage 4)), 90% reaction may be required for clinically recognisable illness. In mechanistic terms, dose-response relationships are needed to establish cause and effect, i.e. to establish that the same degree of reaction with a target always causes the same biological effect.
