REACTIONS TO ARTIFICIAL COLOURING MATERIALS 221 of having produced sensitivity secondly one wonders whether this sensitization after a long period of time is not in fact triggered off by some other extraneous factor of which we have no knowledge and which we cannot reproduce in our animal experi- ments. I would be interested to hear what you have to say, and whether you can think what these precipitating factors could be. In other fields of toxicology there are innumerable instances, particularly with drugs, where a patient can be taking the same drug year in and year out with no apparent harm, and then suddenly some catas- trophic incident occurs which is attributed to the drug. THE LECTURER: It is certainly a difficult point. Many physicians would agree that in the vast majority of cases where a patient is taking a drug for a long time, the first two or three months are most critical in other words, if patients are going to develop adverse reactions they usually do so in the first two or three months. MR. A. H. NETaERWOOD: Tetrachlorsalicylanilide which was mentioned a few minutes ago illustrates one of Dr. Golberg's points quite nicely I think it is very probable that tetrachlorsalicylanilide in itself is not a primary cause of irritation, but when this material is exposed to light it almost certainly gets degraded into something like a chlorinated aniline and probably a chlorinated phenyl, and possibly these secondary degradation products cause the trouble. It is my experience that someone somewhere is allergic to practically any raw material one cares to name. Has there been any ruling in the cosmetic field as to what is an acceptable level of irritation in a cosmetic product? MR. T. A. BROCK: You raise the question of the reaction of individuals to perfume, is this in fact the perfume or some other raw materiM in the product? Some years ago we were marketing a complete range of non-perfumed products in which we left the rest of the product exactly as it was. We found that a very large number of individuals who did show reaction to the original product, were able to use the non- perfumed product without any further trouble whatsoever. This would seem to indicate that the reaction was only to the perfume and not to any other ingredient in the product. We have not experienced nail staining with shades of polish at all in this country but I know that about four years ago in the U.S.A. they were deve- loping a new range of nail polish shades, and they did find some individuals who very definitely were stainers they set up a programme using these individuals as guineapigs to find which pigment was responsible and by elimination of that pigment they were still able to obtain an acceptable shade range without any staining problem. THE LECTURER: I would be very grateful if you could put me in touch with that information. I take your point about non-perfumed products. The problem is, as you have admitted, that the evidence is purely circumstantial, and I am sure every- body has met this difficulty over cosmetics. MR. J. C. MCCARTHY: In page 217 you refer :•to one patient who developed a dermatitis from lipstick and a face powder at the same time. You then go on to say that she also experienced a rash from nylon stockings and from the black lining material of a coat. She gave a positive patch test to the coat lining, but you were unable to trace the dye. Have you actually done patch tests on the dye itself, or could it not be some treatment which the lining of this coat has undergone that caused this reaction? What I am trying to say is that it need not necessarily be the black dyestuff.

222 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS THv_ LECTURER: It need not be, but in the majority of cases that do react to lining materials it is due to the dye. MR. J. C. MCCARTItY: We have been trying to run a series of tests to find exactly what constitutes a non-allergic lipstick, and we have asked a whole series of women what shades of their present range they find or do not find themselves allergic to. We have found that with a completely eosin-free lipstick there are women who claim to be allergic to one shade of lipstick, say a pink, and then find they are non-allergic to the red lipstick in which the same dyestuffs have been used. Have you any comment on this? THE Lv-CTURER: I have met it, and I do not know the explanation. MR. D. F. ANSTEAD: I was particularly interested in your remarks on the trans- parent yellow lake. The colour is the one we were familiar with as F.D. & C. Yellow 1. I think it was descheduled about seven or eight years ago to external D. & C. Yellow 7, which is employed in small quantities for external application. Has any work been done on the much more widely used F.D. & C. Yellow 5 lake in nail polishes? This is a sulphonated colour and in my experience there is far less likelihood of staining with this than with the one you have commented on. THE Lv-CTURER: You think it would be more likely with the Yellow 5, not less? MR. D. F. ANSTEAD: Yes. THE LECTURER: I have not carried out work with that compound. I hoped that somebody would tell me whether I was correct in saying that this particular lake did bleed rather readily, and the staining could be associated with this. MR. K. MCLAREN: There seems to be some suggestion that there could be positive correlation between a compound being fluorescent and having an adverse effect. I consider this completely impossible, although it is not really known at all why compounds are fluorescent there is no common factor linking fluorescent compounds which could possibly have any medical irritation effect. I seem to get the impression that you think that fluorescent brightening agents are related chemically to fluorescein they are not - the only thing they have in common is this fluorescent characteristic which is due to a particular method of decay of an excited state which I shall be dealing with (4). MR. K. M. GODFREY: We have heard that people are sensitive to almost any raw material, we have heard of perfume sensitizing, both real and unreal. Would you care to give some indication what you consider the level of complaint at which the cosmetic chemist must sit up and take notice. THE LECTURER: People in my position, and my colleagues, are constantly worried about this. The things that determine acceptable levels vary so much. It is something of a generalization to say that any chemical can produce sensitivity. There are many compounds which have never been known to and are never likely to, because of their chemical structure. In the case of a life saving drug, we may accept a 10 or 20 per cent reaction rate. (41 Mclaren, K. J. Soc. Cosmetic Chemists 18 245 (1967).