FRAME Recommendations for the Application of the Three Rs to the Regulatory Toxicity Testing of Food Additives

Abstract

Direct food additives are tested for genotoxicity, acute and subchronic toxicity, carcinogenicity and teratogenicity. International guidelines differ in the types of tests required, the duration of the tests, the species of animals to be used, the number of animals recommended and the method of housing experimental animals. This lack of harmonisation is wasteful in terms of animal use and creates additional and, perhaps, unnecessary work for the food industry. In addition, unlike other chemicals, food additives pose a special problem for toxicity testing due to repeated low-dose, life-time human exposure, which is difficult to model in animal studies. In an assessment of the extent to which the Three Rs (reduction, refinement and replacement) can be applied to food additive toxicity testing, it was concluded that differences in regulatory requirements and testing protocols can be improved in both the short term and longer term. Suggestions for improvements to existing alternative approaches for food toxicity testing are made.