The use of agrochemicals like crop protecting agents, veterinary disinfectants, and wood preservatives may result in (un)intentional exposure of the environment, animals and man. This paper deals with current testing strategies to assess the potential health risks for humans exposed to these chemicals during production or application or via consumption of foods containing pesticide residues. Principles and procedures for safety assessment of pesticide residues in food as developed by WHO/FAO are described. Different types of toxicity studies in mammalian test animal species are discussed and a strategy is outlined in order to characterize the toxicity profile of a compound and the relationship between applied doses and adverse effects. Safety testing of agrochemicals should be carried out in relation to its intended use, and in particular attention will be paid to toxicity testing of residues of pesticides in food. Extraplation of results from animal studies to humans and the use of safety factors is discussed. Besides the use of animal protocol studies for safety testing of agrochemicals, the potential use of in-vitro models derived from organs and tissues of animals is discussed. Data on the in-vitro metabolism of thiabendazole, aldicarb and alachlor are discussed in order to demonstrate that such data may complement or partly substitute whole animal experimentation. Principles and procedures for safety testing of residues of agrochemicals in foods as applied during the last three decades, constitute a 'safety-first' approach, providing sufficient safety margins for the consumer of foods which may contain low levels of residues of agrochemicals.