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The development of the European legislation on chemicals must be viewed against the background of general developments in politics and society. Chemical accidents have played a triggering role, especially the catastrophe at Seveso in 1976. As a response, the "Seveso Directives" 82/501/EEC, 96/82/EEC, and 2003/105/EEC were passed. This also promoted general intentions to better comply with chemical hazards. The very first initiative of European institutions considering chemical compounds dates back to 1967 with Directive 67/548/EEC. Its amendments were later developed into the core of European legislation on chemicals. Other important fields of European legislation concerning chemicals, which were developed further, are environmental protection, consumer protection and occupational safety.

Modern toxicology investigates a wide array of both old and new health hazards. Priority setting is needed to select agents for research from the plethora of exposure circumstances. The changing societies and a growing fraction of the aged have to be taken into consideration. A precise exposure assessment is of importance for risk estimation and regulation. Toxicology contributes to the exploration of pathomechanisms to specify the exposure metrics for risk estimation. Combined effects of co-existing agents are not yet sufficiently understood. Animal experiments allow a separate administration of agents which can not be disentangled by epidemiological means, but their value is limited for low exposure levels in many of today's settings. As an experimental science, toxicology has to keep pace with the rapidly growing knowledge about the language of the genome and the changing paradigms in cancer development. During the pioneer era of assembling a working draft of the human genome, toxicogenomics has been developed. Gene and pathway complexity have to be considered when investigating gene-environment interactions. For a best conduct of studies, modern toxicology needs a close liaison with many other disciplines like epidemiology and bioinformatics.

There is increasing discussion that children might be considered as a specific subgroup in public health regulations which could be more sensitive than the average "adult" human being. Differences between children and adults, with regard to susceptibility towards toxicants, may result from a combination of toxicokinetic, toxicodynamic and exposure factors. Kinetic factors are of importance mainly in the early postnatal period, largely as the result of immature elimination systems, i.e. metabolising enzymes and/or renal function. Specific vulnerability may prevail during several time periods, related to the development and maturation of organs (for example, brain, bone, endocrine system). For some substances, it has been shown that children at a specific age are less sensitive than adults. Specific exposures of toddlers to environmental chemicals may be high due to their moving behaviour and hand-to-mouth activities. Existing scenarios and models for exposure of children should be improved, in particular with respect to different ages. The outcome of model calculations must be verified by human biomonitoring analysis. At present, there is ongoing discussion of toxicological test models suitable to delineate human postnatal development. Experience with infant-orientated test systems is scarce (for example in developmental neurotoxicity). In general, tools for predicting toxicological sensitivity of children must be further improved. Regulators should also be aware that reduction of lifestyle-related toxic exposures such as smoking and drug abuse in children and adolescents is now an increasing public health problem in many countries.

In view of recent public reproaches against medical animal experimentation this article describes the present status of animal experimentation in the field of toxicology. Possible perspectives and the limitations of "alternative" methods are reviewed. Toxicological methods which are based on cell culture and metabolic in vitro-systems, as well as "short-term-tests" for mutagenicity and/or carcinogenicity are invaluable for screening purposes. However, a risk assessment, i.e., evaluation of hazard of chemical compounds to man, must be based on animal experiments. Further efforts must be directed towards improvement of extrapolation of toxicological results from one species to the other.