154 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS CAUSATIVE FACTORS IN LANOLIN ALLERGY With respect to the relatively few cases of allergy attributed to lano- lin it is significant to note the lack of agreement as to the causative factor involved. Some researchers have made fairly definite statements as to the nature of the allergen. However, the results have been at best con- tradictory. Sulzberger and Lazar (9), for example, in their report on four lanolin sensitive patients stated that the allergen was a constituent or constituents of the mixed alcohols. It did not seem to be present in other fractions of lanolin such as the mixed fatty acids, cholesterol, or lanosterol. Then Sulzberger et al. (10) and Warshaw (11) in their con- tinuing studies felt they had isolated the allergen in the mixed aliphatic alcohols. They also got occasional positive reactions from the extracted fatty acids of the same source which could cause some doubt both as to the purification of the fractions and to the nature of the allergen. They also reported that modification of the lanolin and the aliphatic alcohols with acetyl radical reduced the incidence in some but not in all cases. Schwarzreid (8) in his report of ten cases found that two were sensitive to lanolin and Aquaphor, four were sensitive to lanolin alone and four were sensitive to Aquaphor alone. Then, Fanburg (38) cited a case of contact dermatitis due to Aquaphor. This patient gave a positive reac- tion to "purified cholesterol esters" derived from lanolin but gave a negative reaction to lanolin itself. Following the Sulzberger et al. reports, Everall and Truter (13) tested further successive fractions on their one lanolin-sensitive patient--going beyond the Sulzberger experiments. The patient reacted negatively to extracted aliphatic alcohols on the other hand, there was a positive reaction to the crudely extracted cholesterol. Then, on purification of the cholesterol, they got a negative reaction. They finally isolated a yellow, glassy solid which they considered an impurity and to which the patient had a positive reaction. This material was not further identi- fied. Acetylation of the "impurity" gave a negative reaction. Klauder and Ellis (18) tested their five lanolin-sensitive patients with the oil solu- ble liquid fraction of lanolin. All five were negative to the liquid lanolin. They tested four of these patients with the solid waxy fraction* ob- tained from lanolin by the same process and also got negative results. Ellis tested one of the patients with wool wax fatty acids and aliphatic alcohols and got a negative reaction another gave a positive reaction to cholesterol. * Lanfrax©-Malmstrom Chemical Corp.

LANOLIN ALLERGY? 155 From the above it would seem difficult to make a positive statement concerning the nature of the causative agent involved. In the case of the fractionated lanolin, that is, fractionated into the oil soluble liquid and the waxy solid, the mixed alcohols and aliphatic alcohols must be presumed present in both fractions. If, as Truter suggests, the allergen may be an impurity, then it is conceivable that further purification or other treatment is one answer. At best, available literature does not clarify the causative factor which results in a reaction attributed to lano- lin in the relatively few subjects discovered and tested. It must be remembered, too, that lanolin is a very complex natural material which is never completely identified. It may even vary season- ally. There can be wide variations in the grades and the purity of lan- olin on the market. One cannot possibly know the effect of these vari- ables on the results of reported cutaneous reactions, attributed to lanolin. It is known, however, that lanolin and its derivatives of vastly improved purity are available on the market today as a result of newer refining techniques. SUmmARY The cosmetic chemist must be on the alert for possible allergic reac- tion to or irritation from many materials. Also, it is a generally accepted fact that no material is universally safe. In the case of lanolin, however, the bulk of the evidence seems to indicate that it is not a potent sensitizer. The known incidence of allergy attributed to lanolin as reported in the literature is extremely low. The evidence on the nature of the causative factor in so-called lanolin allergy does not seem to be conclusive. The further purification of lanolin, the fractionation of lanolin, and the devel- opment of the new derivatives may contribute to a reduction of the al- ready very low incidence of reaction. However, reduction of the rela- tively infrequent cutaneous reactions to lanolin has not been a prime objective of research, which instead is concerned with the development of new cosmetic and pharmaceutical materials. (Received October 18, 1965) REFERENCES (1) Lower, E. S., Mfg. Chem., 15, 13 and 18 (1944). (2) Priest, C. S., Australian J. Pharm., 27, 27 (1946). (3) Ramirez, M. A., and ElleL J. J., J. Allergy, 1,489 (1930). (4) Sulzberger, M. B., and Morse, J. L., J.A.M.A., 96, 2099 (1931). (5) Sezary, A., Presse Med., 93, 1880 (1936). (6) Bonnerie, P., Aetiologie Und Pathogenese Der Ekzemkrankheiten, NYT Nordisk Forlag, Copenhagen (1939).