CONTACT SENSITIZATION DUE TO PERFUMERY RAW MATERIALS SOME ASPEGTS OF GONTAGT SENSITIZATION DUE TO PERFUMERY RAW MATERIALS P. H. WITJENS, Dr. ir.* Presented at the Symposium on "Perfumery", organised by the Society at Cheltenham, Glos., on 14th November 1962. Different factors which might influence the occurrence of contact sensitization due to pergumery chemicals are discussed. SENSITIZATION OF MAN by contact of the skin with perfumery chemicals is fortunately a phenomenon of relatively rare occurrence. It is for this reason that older pubhcations only occasionally report cases of dermatitis caused by allergic reactions due to specific odoriferous chemicals or essential oils. The increase in the use of cosmetics, and particularly of synthetic detergents and similar products, is reflected in an increasing number of published case histories, reaching a peak during, and shortly after, the period 1940-1945, when impurities in the raw materials as a result of their prevailing scarcity have been in part responsible for the occurrence of dermatitis •. While these publications on the whole helped to augment the number of recorded cases, there is a distinct tendency in a number of recent studies, in which odoriferous chemicals were also partly considered as eczematogene noxes, to study incidental sensitization reactions against a more general background, both in relation to the medico-biological, and to the chemical, aspects of the sensitization process. It is particularly when studying the theoretical backgrounds that the rarity of the occurrence of contact sensitization in human beings renders the experimental treatment difficult to a degree. Nevertheless, the ever- increasing degree in which man is brought into contact with organic com- pounds possessing, in most cases, completely new structural constellations, makes it imperative to study the possibility of contact sensitization, in addition to other toxicological data, from a point of general hygiene. The field of synthetic perfumery chemicals is no exception, and in fact it may be more desirable for this study since these products are functionally predisposed to an intensive contact with the skin, with a duration of application which can extend over the better part of a man's lifetime. The study of the phenomenon of sensitization from a chemical point of view will in the first instance be centred around the investigation of the molecular structures which are a condition for eliciting contact sensitization. *International Flavors & Fragrances (Nederland) N.V., Zaandam, Netherlands.

JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS The medico-biological approach of the problem which will not be dealt with has recently been referred to by Calnan 2, where methods of biological determination were discussed. Experimental evidence clearly shows the necessity for the low molecular sensitizing agent to form a high molecular compound with proteins, or protein derivatives of the organism, before sensitization takes place a. For the time being, however, this part of the mechanism of sensitization does not give much of a clue with regard to the structural condition with which the sensitizer must comply, for chemical reactions with proteins can be brought about by numerous organic compounds which have never been known to cause sensitization. There is no doubt that apart from the presence of specific reactive functional groups, other structural requirements will have to be met. An important part, for instance, will be played by such factors as steric hindrance and spacial structure, a part which, how- ever, can only be made understandable in its relation to the molecular structure of the proteins involved. For the time being too little is known about the changes in properties which a protein has to undergo before it can act as an antigene for contact sensitization. Only when this knowledge has been extended can conclusions be drawn with respect to the requirements for the structure of organic sensitizers a. It is true, though, that certain indications of a limited scope have been obtained about this aspect by the study of the phenomenon of cross- sensitization or group-reactions. Whilst sensitization reactions are in general brought about only by specific contact with the product with which the organism has been sensitized, this reaction can in certain cases also be brought about by contact with compounds which are chemically allied to the sensitizing agent. The structural problem can be approached by the study of this relationship which can easily be carried out experimentally, although it has already been clearly established that in human beings individual differences in reactions in cross-sensitization occur. In several recent investigations the relationship between the sensitizing action, and the chemical structure, by means of cross-sensitization has been the subject of a study by Fregert 4 on sensitization of a group of products allied with stilbestrol, and by Hjorth 5 concerning balsam of Peru, and constituents thereof. In tests carried out on persons who showed a distinct sensitization for these products, the reaction capacity in respect of products which showed a specific structural relationship, was investigated. In judging the results of this type of experiment, a clear distinction should be made between compounds which are converted into the original sensitizing agent either by means of a chemical reaction or as a result of enzymatic processes in the skin, and products which possess a structural analogy with the allergene 6.