Aims and Mission of Regulatory Toxicology

Abstract

The aim of regulatory toxicology is to control production, use, and deposition of dangerous materials to prevent adverse effects on human health and the environment. This requires sufficient information on the hazardous properties of a chemical compound, their relevance to man, and of human and environmental exposure, which is a prerequisite for appropriate risk assessment and the decision whether regulatory consequences are warranted. The three elements of risk assessment of chemical substances are hazard identification, evaluation of dose–response relationship, and exposure assessment. The risk assessment process requires differentiation between reversible and irreversible effects, that is, identification of a “no observed adverse effect level” (NOAEL) and/or a “lowest observed adverse effect level” (LOAEL) for the most critical effect of the substance, or, in case of irreversibility, estimation of the risk at a certain exposure. Up to now, the risk of genotoxic carcinogens at a certain exposure concentration is estimated by linear extrapolation of the dose–response curve. Further, to set priorities the margin of exposure (MOE) or margin of safety (MOS) can be calculated by comparing the NOAEL with the human exposure. Additional information for the evaluation of the human relevance of experimental data are available from toxicokinetics or the mode and/or mechanism of action. In the evaluation of the existing data base, setting limit values like “acceptable daily intake” (ADI) or “derived no effect levels” (DNELs) or implementing risk management measures, the uncertainties of the database have to be described and taken into consideration. Another challenge is the evaluation and regulation of mixtures, which needs to take into account concentrations and mode of action of the individual components. The systems for classification of carcinogens used by various national and international institutions are summarized. The use of the so-called precautionary principle and of the “Threshold of Toxicological Concern” (TTC) concept for risk assessment purposes is explained. In addition, the regulations for specific chemical classes like drugs or pesticides are completed by a short description of the European Union Registration, Evaluation, Authorisation and Restriction of Chemicals (EU REACH) regulation for chemical substances.