Variability in toxic response - relevance to chemical safety and risk assessment at the global level

The aim of control limits for exposure to chemicals in air, food, water, and consumer products is to protect the whole human population, including the most susceptible individuals and 'at risk' groups. The existence of susceptible individuals is a factor that must be taken into account when quantitative chemical risk assessments are being made, and should be covered in the risk characterization. Classically, when extrapolating data derived from animal experiments using homogeneous, healthy test species for human health risk assessment uncertainty factors are applied. For inter-species extrapolation an uncertainty factor of up to 10 is applied. While it is evident that this procedure provides reasonable protection for the great majority of the population there are outlyers who may not be protected under all conditions. Within a population, individual susceptibility is influenced by genetic and environmental factors. These have regional and national differences. Environmental factors that are important in many countries include 'life-style' (e.g. tobacco and alcohol consumption, diet), nutritional and health status. In the case of environmental protection similar considerations apply but the emphasis is on species rather than individuals. The International Programme on Chemical Safety, as the global programme on identifying and assessing chemical risks to human health and the environment in order to assist countries in effective management, is constantly advancing the basic science and methodology for making chemical risk assessment.