Authors S.M. Barlow, J.B. Greig, J.W. Bridges, A. Carere, A.J.M. Carpy, C.L. Galli, J. Kleiner, I. Knudsen, H.B.W.M. Koeter, L.S. Levy, C. Madsen, S. Mayer, J.-F. Narbonne, F. Pfannkuch, M.G. Prodanchuk, M.R. Smith, P. Steinberg
Abstract
This paper is one of several prepared under the project ''Food Safety In Europe: Risk Assessment of Chemicals in Food and Diet'' (FOSIE), a European Commission Concerted Action Programme, organised by the International Life Sciences Institute, Europe (ILSI). The aim of the FOSIE project is to review the current state of the science of risk assessment of chemicals in food and diet, by consideration of the four stages of risk assessment, that is, hazard identification, hazard characterisation, exposure assessment and risk characterisation. The contribution of animal-based methods in toxicology to hazard identification of chemicals in food and diet is discussed. The importance of first applying existing technical and chemical knowledge to the design of safety testing programs for food chemicals is emphasised. There is consideration of the presently available and commonly used toxicity testing approaches and methodologies, including acute and repeated dose toxicity, reproductive and developmental toxicity, neurotoxicity, genotoxicity, carcinogenicity, immunotoxicity and food allergy.
They are considered from the perspective of whether they are appropriate for assessing food chemicals and whether they are adequate to detect currently known or anticipated hazards from food. Gaps in knowledge and future research needs are identified; research on these could lead to improvements in the methods of hazard identification for food chemicals. The potential impact of some emerging techniques and toxicological issues on hazard identification for food chemicals, such as new measurement techniques, the use of transgenic animals, assessment of hormone balance and the possibilities for conducting studies in which common human diseases have been modelled, is also considered.
Research needs:
There needs to be a better understanding of the background to the use of animal-based models, including the roles that genetic make-up, nutritional health, microbial disease status, normal gut microflora and life stage may play in variation in toxic responses. The generation and use of physico-chemical data on food chemicals for the prediction of possible toxicity by QSAR at an early stage should be expanded. Improved animal models of acute adverse reactions to food chemicals in humans should be developed.
Analysis of existing toxicity data on food chemicals should be conducted to allow a science-based decision on optimum duration(s) of repeated dose tests. The reliability and significance of changes in clinical chemistry observed in animal studies for the identification of toxicological effects and the distinction of these from adaptive changes requires study. There needs to be a better understanding of differences of in fertility potential, reproductive processes and postnatal development between animals and humans in order to assess their implications for the reliability and relevance of animal-based hazard identification. Chemicals in food and diet that may exert endocrine disrupting activity need to be identified and prioritised for further testing. Better knowledge is needed of the mechanisms by which endocrine disrupting chemicals are acting. There is a need for research into the mechanisms of neurotoxicity, the most susceptible developmental stages and the relevance of observations in animals for humans.
Improved methods to detect delayed onset toxicity and models for human neuropsychological syndromes are required. Validation of in vivo/in vitro tests for genotoxicity that that require fewer animals but can identify genotoxic effects in particular tissues and development of tests requiring fewer animals for detection of mutations in germ cells are needed.
Investigation of the influence on tumour development of nutrition per se and of the introduction of macroingredients, such as novel foods, into the diet is needed. Reconsideration is needed of what should determine the maximum dose level to be tested in carcinogenicity studies on food chemicals. Better knowledge of the effect of toxicants on the developing immune system is needed. The development of an animal model for food allergy is needed. The development of sensitive new techniques for the detection of changes in the biochemical and physiological status of animals will make it critical that there is a background of research providing an improved understanding of the factors affecting such parameters and the toxicological relevance of such changes. Research is required on naturally-occurring oestrogens in the diet in developing and adult organisms in terms of their influence on the development of the brain and other likely target tissues and organs. There is a need for additional research into the use of transgenic animal models for hazard identification and the interpretation of results obtained from such models. The potential value of new animal models for common human disease states that may affect the toxicity of food chemicals should be investigated.
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