Defining thresholds in occupational and environmental toxicology

When a chemical causes a defined form of toxicity, the threshold is the maximum exposure when this toxicity does not occur. It is an operational parameter and is limited in its interpretation and applicability. The aim of this paper is to consider biological parameters which influence exposure-response relationships. Biomonitoring of dose and effects has much potential for defining thresholds in human exposure; extension of their use in experimental studies on new compounds should help predictions to thresholds for human exposure. Intoxication initiated by both reversible and covalent interactions with targets are discussed and, as exposure is reduced and the time of exposure extended, changes in the shape of the dose-response curves examined for acute and delayed neuropathy (axonopathy) and for carcinogenesis.