CONTACT SENSITIZATION DUE TO PERFUMERY RAW MATERIALS 317 Investigations carried out by Schulz* have shown that cross-sensitization can cause over-sensitiveness to a specific product, e.g. ammonium thio- glycolate, in persons who have been in prolonged contact with this material, without spontaneous sensitization taking place. Under the influence of sensitization for the related thioglycolic hydrazide Voss 8 was able to prove these phenomena both on test persons and in guinea pigs for the same type of compounds. Inasmuch as the number of human test objects who are sensitized for a specific compound is nearly always limited, the more or less identical reaction in guinea pigs in cross-sensitization constitutes a very valuable addition to the test material. This is all the more true as cross- sensitization can be highly individual, and a group of test persons sensitized by a primary allergene can react very differently among themselves to a series of secondary allergenes, i.e. allergenes which produce cross-sensitization reactions. When a larger group of secondary allergenes is tested, one will observe distinctly individual reaction patterns. The occurrence of this individual pattern is explained by Sulzberger 9, who assumes that different functional groups of one sensitizing agent may give rise to different allergenes of which only homologous secondary allergenes may lead to cross-sensitiza- tion, whereas no reaction will occur in the absence of this related allergene. On the one hand there exists a group allergy whereby many facts can be concealed from experimental observation as a result of a very individual reaction pattern. On the other hand, there is the possibility of the forma- tion of over-sensitiveness for already known low, or non-sensitizing, products by primary sensitization due to new structurally related chemicals. This leaves the perfumery chemist with a problem which will continue to claim his attention in research, because structures from practically the entire field of organic chemistry play an important part in perfumery. With our limited, and frequently fragmentary, knowledge of the relationship between chemical structures and sensitizing capacity, it is almost impossible to draw correlations between them in prospective odoriferous chemicals. The biological experiment will therefore always have to supply the necessary data and such an experiment is greatly complicated by the phenomena discussed above. The formation of an allergene from a low-molecular organic chemical takes place by the reaction of the organism of the test object with a protein or a derivative thereof. As a result, this protein acquires specific properties which distinguishes it from the body protein and against which the organism builds up its anti-bodies. There are indications that the proteins from which the allergenes are formed, are in a removed position from the epidermic surface, so that the synthesis of the allergene must be preceded by a process of transport in or through the epidermis a. The extent in which this penetration, and this transport of the sensitizing

318 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS agent, can take place will be determined by its chemical configuration. The great differences between the sensitizing action of related compounds, such as those found by Sulzberger 9 for sulfadiazine and sodium sulfadiazine, could possibly be accounted for in this manner. It is also to be expected that the carrier in which the sensitizing agent has been incorporated, and in which the contact with the skin takes place, will play a part in the speed of transport to the protein components of the allergene. This can be of considerable importance because of the possibility of a sensitizing potential produced by some perfumery chemicals, as the contact of the skin with these chemicals frequently takes place in the presence of products which are highly surface-active. This statement is justified on the grounds that perfumery chemicals largely make contact with the skin in the presence of soaps, detergents and cosmetics which, in general, contain surface-active agents. This influence of the vehicle can be demonstrated by the results of human patch tests with 2-cuminyl-propanal, where on changing the type of emulsion of the carrier from an o/w to a w/o emulsion, an impressive change in dermatological response was observed. The positive reactions obtained with the o/w emulsion base almost completely disappeared when similar tests were made in a w/o base •ø. In the above tests, the problem is clearly one of transportation of the product in question, brought about by differences in contact, so!ubility, etc. The change of the reactivity of the skin under the influence of a previous (or simultaneous) contact with detergents or soap TM becomes, however, a more complicated matter. While certain detergents themselves may cause skin irritation previous treatment of the skin with less aggressive surface-active agents may also lead to a considerable lowering of the threshold value for sensitization with other chemicals. Thus, it might well be possible that unexpected allergic reactions will occur, if, in the dermatological examination, insufficient attention is paid to changes in the properties of the epidermis, which may result from continued contact with highly surface-active material. This may also apply with respect to perfumery raw materials and only a properly conducted test programme with the completed product will give evidence for the safety of use. (Received: 26th September 1962) REFERENCES Klarman, E.G. Ann. Allergy 16 425 (1958) Cainan, C. D. _Proceedings of Second Congress of the International Federation of Societies of Cosmetic Chemists London, July 1962. In press (Pergamon Press Ltd., Oxford) Eisen, H.N.y. Exp. Med. 108 773 (1958) ibid. 110 187 (1959) ibid. 112 1195 (1960) Fregert, S. Acta Dermato-Venereol. 40 206 (1960) Hjorth, N. Eczematous allergy to balsams, Dissertation (1961)