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The use of food preservatives, such as benzoic acid, nitrites, and sulphites, as antimicrobials, and butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), ascorbic acid and tocopherols, as antioxidants, has probably changed food production patterns and eating habits more than has the use of any other class of food additive. These food preservative chemicals confer substantial benefits on man, not only by the preservation and increased palatability of food, but also by affording protection against the pathological effects of reactive oxygen species (ROS) which are associated with cancer, cardiovascular disease and aging. Nevertheless, although most preservatives are now considered to be without potential adverse effects and are classified as GRAS, there have been problems concerning the safety of some of these chemicals, including the possibility of allergies from benzoic acid and sulphites, the formation of carcinogenic nitrosamines from nitrites, and the possible rodent carcinogenicity of BHA and BHT. The mechanisms of this toxicity at high dosage, the roles of the cytochromes P450, and the generation and scavenging of ROS in the toxicity of these chemicals, are reviewed and discussed.

Quantitative structure-activity relationships between chemical structure and Ames mutagenicity for a group of 24 food mutagens, including 17 cooked-food heterocyclic amines, have been determined. For the TA98 strain of Salmonella typhimurium (frameshift mutagens) the best correlation of mutagenicity is with molecular diameter (R = 0.91), while for the TA 100 strain (base-pair mutations) the best correlation is with δE, the energy difference between the lowest unoccupied and highest occupied molecular orbitals. High mutagenicity is related to high values of molecular diameter, hence to planarity and to high values of the COMPACT ratio ([area/depth2]/δE). High mutagenicity is also related to low values of δE. Consequently, highly mutagenic and potentially carcinogenic food chemicals can readily be identified as substrates of cytochrome P4501 (CVP1) and may therefore be detected by the COMPACT procedure. Highly mutagenic compounds also exhibit high values of dipole moment.

The aetiology of autoimmune, chronic inflammatory disease is reviewed, together with the contributing roles of oxygen radicals, the cytochromes P450, the eicosanoids, the interleukins, and the corticosteroids and estrogens. The importance of drug metabolism in the formation of reactive intermediates of drugs and environmental chemicals, and hence in the production of neoantigens, autoantibodies and autoimmune disease is considered, together with the possible involvement of genetic variations in sulphoxidation, sulphotransferase and acetyltransferase activities in predisposing patients to rheumatoid arthritis, lupus and other autoimmune diseases.