THE USE OF BIOMARKERS AS ALTERNATIVES TO CURRENT ANIMAL TESTS ON FOODCHEMICALS

Recent developments in biomarkers relating to the interrelationship of diet, disease and health were surveyed. Most emphasis was placed on b iomarkers of deleterious effects, since these are of greatest relevanc e to the subject of this review. The area of greatest activity was fou nd to be that relating to biomarkers of mutagenic, genotoxic and carci nogenic effects. This is also one of the major areas of concern in con siderations of the beneficial and deleterious effects of dietary compo nents, and also the area in which regulatory testing requires studies of the longest duration. A degree of progress has also been made in th e identification and development of biomarkers relating to certain cla sses of target organ toxicity. Biomarkers for other types of toxicity, such as immunotoxicity, neurotoxicity, reproductive toxicity and deve lopmental toxicity, are less developed, and further investigation in t hese areas is required before a comprehensive biomarker strategy can b e established. A criticism that recurs constantly in the biomarker lit erature is the lack of standardisation in the methods used, and the la ck of reference standards for the purposes of validation and quality c ontrol. It is encouraging to note the growing acknowledgement of the n eed for validation of biomarkers and biomarker assays. Some validation studies have already been initiated. This review puts forward proposa ls for criteria to be used in biomarker validation. More discussion on this subject is required. It is concluded that the use of biomarkers can, in some cases, facilitate the implementation of the Three Rs with respect to the testing of food chemicals and studies on the effects o f diet on health. The greatest potential is seen to be in the refineme nt of animal testing, in which biomarkers could serve as early and sen sitive endpoints, in order to reduce the duration of the studies and a lso reduce the number of animals required. Biomarkers could also contr ibute to establishing a mechanistic basis for in vitro test systems an d to facilitating their validation and acceptance. Finally, the increa sed information that could result from the incorporation of biomarker determinations into population studies could reduce the need for suppl ementary animal studies. This review makes a number of recommendations concerning the prioritisation of future activities on dietary biomark ers in relation to the Three Rs. It is emphasised, however, that furth er discussions will be required among toxicologists, epidemiologists a nd others researching the relationship between diet and health.