TEST METHODS FOR SCREENING FRAGRANCES 63 roetics. A dose-response curve was plotted for each compound tested, and the irritant and/or allergenic activity of each compound was established in terms of concentration in percent. The proposed procedure is simple, yields quantitative data, minimizes sub- jective factors when evaluating the results, and simulates the conditions in human use. A total of 32 compounds described in the literature as being allergenic for man were tested by the OET technique and, for the purpose of comparison, by three intradermal techniques, namely, the DT, the MT and the FCAT. Most of the compounds described as being allergenic for man were found to be allergenic for the guinea pig in the OET and in ! or more of the 3 intradermal tests. A few of the compounds tested, however, were found to be allergenic only in the OET, and a few others only in the DT, MT and/or FCAT. In' the OET, a high degree of correlation was found between the aller- genicity of the tested compounds for the guinea pig and their allergenicity for man. REFERENCES (1) (2) (3) (4) (5) (6) (7) (8) (9) (lO) (11) ß . (12) (13) .: (14) '::' (15) (16) (17) :.: (18) :' (19) (20) ': (21) (22) A.M. Kligman, The identification of contact allergens by human assay, J. Invest. Dermatol., 47,369-74 (1966). A.M. t(digman, The identification of contact allergens by human assay. II. Factors influencing the in- duction and measurement of allergic contact dermatitis, ibid., 47, 375-92 (1966). A.M. t(digman, The identification of contact allergens by human assay. III. The maximization-test: a procedure for screening and rating con tact sensitizers, ibid., 47, 393- 409 (1966). B. Magnusson and A.M. Kligman, The identification of contact allergens by animal assay. The guinea pig maximization-test, ibid., 52,268-76 (1969). B. Magnusson and A.M. Kligman, Allergic contact dermatitis in the guinea pig, Charles C. Thomas, Springfield, Illinois, 1970. K. Landsteiner and J. Jacobs, Studies on the sensitization of animals with simple chemical compounds, II, J. Exp. Med., 64,625-39 (1936). L. Schwartz and S. M. Peck, The patch test in contact dermatitis, Pub. Health Rep., 59,546-57 (1944). M. J. Brunner and A. Smilj anic, Procedure for evaluation skin sensitizing power of new materials, Arch. Dermatol. Syphilol., 66, 703-9 (1952). H. A. Shelanski and M. V. Shelanski, A new technique of human patch tests, Proc. Sci. Sect. Toilet Goods Ass., 19, 46 (1953). E. F. Traub, T. W. Tusing, and H. J. Spoor, Evaluating of derreal sensitivity, Arch. Dermatol. Syphilol., 69, 399-409 (1954). J. H. Draize, Appraisal of the safety of chemicals in foods, drugs and cosmetics. Dermal toxicity, The Assoc. of Food and Drug Officials of the United States, Texas State Dept. of Health, Austin, 1959, Pp. 46- 59. A. Rostenberg, Predictive procedures for eczematous hypersensitivity, Arch. Ind. Health, 20, 181-93 (1959). A. Rostenberg, Methods for the appraisal for the safety of cosmetics, Drug Cosmetic Ind., 88, 552-4, 592-4,681-6 (1961). FederalRegisterAmendment, Sept. 17, 29 F.R. 13009 (1964). R. Dohr-Lux and G. Lietz, Pharmakologisch-toxikologische und dermatologische Untersuchungs- methoden, Parfiim. Kosmet., 46, 1.Teil 256-9, 2.Teil 289-93, 3.Teil 323-6 (1965). Ch. Gloxhuber, Toxikologische Pr•i(ung yon Kosmetika, J. Soc. Cosmet. Chem., 18, 737-50 (1967). D. Kastner, ParfLim und Allergie, ibid., 19,807 (1968). B. Idson, Topical toxicity and testing, J. Pharm. Sci., 57, 1-1 ! (1968). N. Hunziker, Experimental studies on guinea pig's eczema, Springer-Verlag, Berlin-Heidelberg, 1969. G. Agrup and E. Cronin, Contact Dermatitits X, Brit. J. Dermatol., 83,516-7 (1970). G. Hopf, Empfehlungen f•ir Hautvertr•gl[chkeitsprLifungen von K6rperpfiegemitteln (kosmetische Er- zeugnisse), Fette, Seifen, Anstrichm., 73,467-8 (1971). L. A. Greenberg and D. Lester, Handbook of Cosmetic Materials, Interscience Publications, Inc. New York, 1954.
64 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS (23) R. G. Harry, Cosmetic Materials, Vol. 2, Leonard Hill (books) Ltd., London, 1963. (24) J. Foussereau and CI. Benezra, Les Ecz•mas AIlergiques Pro)•ssionnels, Masson et Cie., •diteurs, Paris, 1970. (25) N. Hjorth, Eczematous allergy to balsams, allied perfumes and flayouting agents, Acta Dermato- VenereoI. SuppI., 41, 46 (1961). (26) G. Agrup, Hand eczema and other hand dermatoses in south Sweden, ibid., 49, 61 (1969). (27) S. Fregert, Sensitization to phenylacetaldehyde, Dermatologica, 141, 11-4 (1970). (28) G. Kahn, Intensified contact sensitization to benzyl salicylate, Arch DermatoI. Syphilol., 103, 497-500 (1971). (29) H. Thiers, Les cosm•ttques. Pharmacologie et Biologie, Masson & Cie., •diteurs, Paris, 1962. (30) A. A. Fisher, Contact Dermatitis, Lea & Febiger, Philadelphia, 1967. (31) V. Pirilae, Pattern of sensitivity to different terpenes, Contact Dermatitis Newsletter, 3, 11-2 (1968). (32) J.-M. Paschoud, Externe Kontaktallergene. Alphabetisch geordnete Uebersicht der Fachliteratur 1960 bis 1965, Hautarzt, 18, 97-101 (1967). (33) J.-M. Paschoud, Quelques cas d'ecz•ma de contact avec sensibilisation de groupe, Dermatologica, 127, 349-64(1963). (34) H. L Baer, Perfume dermatitis, J. Amer. Med. Ass., 104, 1926 (1935). (35) F. Griepentrog, Allergiestudien mir einfachen chemischen Substanzen. Allerg. Asthma, 5, 224-6 (1959). (36) M.J. Hoffmann and J. Peters, Dermatitis due to facial cream caused by methyl heptine carbonate, J. Amer. Med. Ass., 104, 1072 (1935). (37) E.G. Klarmann, Perfume dermatitits, Ann. Allerg. 16,425-34 (1958). (38) W. Leifer, Contact dermatitis due to cinnamon, Arch. DermatoI. SyphiloL, 64, 52-5 (1951). (39) H. W. Rothenborg and N. Hjorth, Allergy to perfumes from toilet soaps and detergents in patients with dermatitis, ibid., 97,417-21 (1968). (40) C. Z. Berry, S. I. Shapiro, and R. L. Dahlen, Dermatitis venenata from phacelia crenulata, ibid., 85, 737-9 (1962). (41) N. Hjorth, Perfume dermatitis, Contact Dermatitis Newsletter, 1, 2- 5 (1967). (42) W. Grimm and H. Gries, Untersuchungen iiber die Terpentin61-Allergie. BeruJSdermatosen, 16, 190- 203 (1968). (43) S. Hellerstr6m, N. Thyresson, and G. Widmark, Chemical aspects on turpentine eczema, Dermatologica, 115,277-86 (1957). (44) S. Fregert and N. Hjorth, Results of standard patch tests with substances abandoned, Contact Der- matiris Newsletter, 5, 85-6 (1969). (45) F. Rantuccio and C. L. Meneghini, Results of patch testing with cosmetic components in consecutive eczematous patients, Contact Dermatitis Newsletter, 7, 156-• (1970). (46) H. L. Baer, Lipstick dermatitis, Arch. Dermatol. Syphilol., 32,726-34 (1935). (47) N. Greif, Cutaneous safety of fragrance material as measured by the maximization-test, Amer. Perfum. Cosmet., 82, 54-7 (1967). (485 L. Schwarzt, L. Tulipan, and D. J. Birmingham, Occupational Diseases of the Skin, Lea and Febiger, Philadelphia, 1957. (49) M. B. Sulzberger, DermatoIogic Allergy, Chas. C. Thomas, Baltimore, 1940. (50) H. Nakayama, H. Hanaoka, and A. Ohshiro, AlIergen Controlled System (ACS), Kanehara Shuppan Co. Ltd., Tokyo, 1974. (51) P. Bonnerie, Some experiences of wartime industrial dermatoses, Acta Dermato-Venerol. Suppl., 28, 231 (1948). (52) ¾. Puglisi, Le dermatose de limonene, G. Ital. Dermatol., 92,237-84 (1951). (53) H. Keil, Contact dermatitis due to oil of Citronella. J. Invest, Dermatol., 8, 327-34 (1947).
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