THE TOXICOLOGY OF ARTIFICIAL COLOURING MATERIALS 431 (16) Lindstrom, H. V., Wallace, W. C., Hansen, W. H., Nelson, A. A. and Fitzhugh, O. G. Federation Proc. 22 188 (1963). (17) Tegeris, A. S. Toxicol. Appl. Pharmacol. 8 6 (1966). (18) Stokinger, H. E. and Mountain, J. T. Arch Env. Health 6 495 (1963). (19) Farmer, Madge, Grasso, P. and Colberg, L. Unpublished observations (1966). (20) Bowie, W. C., Arnault, L. T. and Lindstrom, H. V. Federation Proc. 24 392 (1965). (21) Colberg, L. Proc. Europ. Soc. Study Drugs Toxicol. 7 69 (1966). (22) BIBRA Annual Report. 22 (1965). (23) Levenstein, I. and Draize, J. H. In "Cosmetics and the Skin" Ed. by I. Lubowe and F. V. Wells, p.539 (1964). Reinhold, New York. (24) Levenstein, I. J. Soc. Cosmetic Chemists lõ 377 (1964). (25) Clayson, D. B. Chemical Carcinogenesis. 245 (1962). J. & A. Churchill, London. (26) Grice, H. C., Mannell, W. A. and Allmark, M. G. Toxicol Appl. Pharmacol. •1 509 (1961). (27) Mannell, W. A. Food Cosmet. Toxicol. 2 169 (1964). (28) Bonser, Georgians M. and Clayson, D. B. Rep. Br. Emp. Cancer Campn. No. 42. 457 (1964). (29) Grasso, P. and Colberg, L. Food Cosmet. Toxicol. 4 No. 3 in press (1966). (30) Grasso, P. and Colberg, L. Food Cosmet. Toxicol. 4 No. 3 in press (1966). (31) Hueper, W. C. and Payne, W. W. Arch. Env. Health 6 484 (1963). (32) Well, C. S., Carpenter, C. P. and Smyth, H. F. Arch. Env. Health ll 616 (1965). (33) Hansen, W. H., Fitzhugh, O. G., Nelson, A. A. and Davis, K. J. Toxicol. Appl. Phar- macol. 8 29 (1966). (34) Beck, F. and Lloyd, J. B. Adv. Teratol. 1 131 (1965). (35) Beaudoin, A. R. and Pickering, M. J. Anat. Rec. 137 297 (1960). (36) Christie, G. A. Nature 208 1219 (1965). (37) Luck, H., Walln6fer, P. and Bach, H. Pathol. g•licrobiol. 26 206 (1963). (38) Nagai, S. Science 130 1188 (1959). (39) Davis, K. J. and Fitzhugh, O. G. Toxicol. Appl. Pharmacol. 5 728 (1963). (40) Goulden, H. D. Drug Cosmetic Ind. 91 286 (1962). Introduction by the lecturer One of the weaknesses of this paper is that it makes very little reference to cosmetic colours as distinct from food colours, and there are good reasons for this: the lack of published work, of which many of you must be aware also the lack of practical experience in our own institute on these D & C and Ext. D & C colours. However, the general features are very much the same, and if one surveys the present situation there are really two key questions that one has to ask. Firstly, are the existing colourings, and particularly food colourings, capable of acting as sensitizers, and there Professor Calnan (41) gave us an indication. The question has also been raised whether colourings in cosmetics or in food are doing harm other than by causing sensitization, but of this I do not think that we have any evidence whatsoever. There are, however, differences in metabolic routes when materials of this sort are ingested or are introduced into the body by other means. For example, in the case of oral administration of tartrazine, sulphanic acid is excreted in the urine of man and the rat but no intact colouring. There is reduction of the azo-linkage in the intestinal tract by the bacterial flora, with decomposition of the molecule into two halves. When the material is given intraperitoneally there is free colouring in the urine and no sulphanilic acid, i.e. the tartrazine goes through the system intact. It is conceivable that if a colouring is absorbed from the skin, the ß (41) Cainan, C D., J. Soc. Cosinetic Chemists 18 3 (1967).

-432 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS intervention of the bacterial flora will only affect it when it is excreted in the bile. The point emerges that there is so much splitting of these azo-linkages in the intestine that it would appear advisable to make special studies of the amine moteties that are formed. The same moiety is common to a number of colourings, and by undertaking a close study of these individual moteties, as regards their further metabolism and other 'effects in the body, one would be automatically clearing the way for a better under- •standing of many of the other colourings which have not been adequately studied -hitherto. With regard to the question of specifications, a description of a colouring which was in order ten years ago is not really satisfactory today, and one has a right as a toxicologist to insist on an accurate description of these materials by the latest ß available methods. As regards toxicological standards I think that the time has passed when the 'objective of toxicological testing was to bring about a negative result which acted as an assurance that everything was all right. Much more should be expected of toxi- cological testing, viz. a set of positive findings with regard to the metabolic fate and the influence of the test material on the animal. The effects of exposure are not necessarily toxic effects, but they are always there, and they should be found, because it is only by having positive findings that one has an assurance of safety. Purely negative findings leave the possibility that something of importance has been missed. We are often in a position now to derive positive findings by special methods if we really take the trouble, and this raises the question of a programme such as that ' of the Toilet Goods Association (U.S.A.) where the •learance of a number of cosmetics colourings is involved. If one examines what it is they have set out to' do, one finds that essentially they are trying to produce negative results. I do not blame them for this. At present this is a valid procedure, but it does raise the question whether this particular approach is really sufficient. Of course, as I have mentioned, where one is dealing with colourings which are only to be applied externally, and there is little or no chance of ingestion, one obviously does not require the same standard 'of toxicological evaluation, the same stringency of examination, that is needed for 'colourings intended for food all the same I think it is important to have an approach which seeks to provide a clear idea of what is happening rather than one that produces results which are almost completely negative. There is one point which I should like to stress again, viz. the distinction between primary and secondary effects in toxicology. I have illustrated these effects by reference to subcutaneous sarcomas produced by colourings and other materials. A great many valuable colourings have thus been labelled as carcinogenic, and we in this country suffer particularly from this outlook. Another important point I made, but only very passingly, is the fact that toxi- 'cological examinations are carried out on normal animals but in the case of man there is the chemical environment to be taken into account. By chemical environment I refer to natural constituents of food, other food additives, the exposure to various substances in the atmosphere, in drinking water, in the home, the consumption of drugs or alcohol. All these exposures have effects, many of which the body probably 'overcomes by physiological adjustments. The recognition of these changes, and the ability to distinguish them from pathological toxic effects often requires much more knowledge than we possess at present.