DIFFUSION OF PRESERVATIVES 249 mostly p 0.0001), apart from EP included in the Carbopol gel versus the O/W emulsion. Parabens, analogously to most of other preservatives, can induce sensitizing effects such as allergic contact dermatitis, especially when they are included in particular topical formulations such as eyedrops, or contour eyes (8,9,16). In this respect, the method here described is proposed to control the extent of paraben diffusion from topical prepara- tions, with the aim of minimizing percutaneous absorption. CONCLUSIONS In conclusion, the results of this study show that the experimental methods presented here could be proposed (a) in preformulatory studies aiming to determine the extent of paraben diffusion from topical formulations, (b) to control the availability of parabens to microbes, (c) to perform premarketing quality controls for dermatological and cosmetic products (e.g. creams, gels, and ointments), and (d) to assure batch-to-batch uniformity. ACKNOWLEDGMENTS This work was supported by the National Research Council of Italy (target-oriented project "Biotecnologie"). REFERENCES (1) S. R. Marouchoc, Cosmetic preservation, Cosmet. TechnoL, 2, 38-44 (1980). (2) T. E. Haag and D. F. Loncrini, "Esters of Para-Hydroxybenzoic Acid," in Cosmetic and Drug Preservation, J.J. Kabara, Eds. (Marcel Dekker, New York, 1984), pp. 63-77. (3) R. L. Decker and J. A. Wenninger, Frequency of preservative use in cosmetic formulas as disclosed to FDA-1987, Cosmet. Toilerr.,102, 21-24 (1987). (4) D. Steinberg, Z. Hirschfeld, I. Tayeb, S. Ben-Yosef, A. David, and M. Friedman, The effect of parabens in a mouthwash and incorporated into a sustained release varnish on salivary bacteria, J. Dentistry, 27, 101-106 (1999). (5) A. H. Kibbe, Ed., Handbook of Pharmaceutical Excipient, 3rd ed. (2000). (6) T. R. Aalto, M. C. Firman, and N. E. Rigler, p-hydroxybenzoic acid esters as preservatives. I. Uses, antibacterial and antifungal studies, properties and determination, J. Am. Pharm. Assoc. (Sci.), 42, 449-457 (1953). (7) L. K. Golightly, S.S. Smolinske, M. L. Bennett, E. W. Sutherland, and B. H. Rumack, Pharmaceutical excipients: Adverse aspects associated with active ingredients in drug products. Part I, Med. ToxicoL, 3, 128-165 (1988). (8) J. Vilaplana and C. Romaguera, Contact dermatitis from parabens used as preservatives in eyedrops, Contact Dermatitis, 43, 248-258 (2000). (9) S.M. Cooper and S. Shaw, Allergic contact-dermatitis from parabens in a tar shampoo, Contact Dermatitis, 39, 140 (1998). (10) P. Bonnevie, Overfolsomhed for aetylparaoxybenzoat, Mycoten Nordisk Medicin, 6, 684-685, (1940). (11) L. Sarkany, Contact dermatitis from paraben, Br. J. Dermatol, 72, 345-347 (1960). (12) J. E. Nagel, J. T. Fuscaldo, and P. Fireman, Paraben allergy, JAMA, 237, 1594-1595, (1978). (13) C. H. John and H. T. Eduardo, Contact uricaria to parabens, Arch. Dermatol., 115, 1231-1232 (1979). (14) S. Carradori, A.M. Peluso, and M. Faccioli, Systemic contact dermatitis due to parabens, Contact Dermatitis, 22, 238-239 (1990).

250 JOURNAL OF COSMETIC SCIENCE (15) A.A. Fisher, The paraben paradox, Curls, 12, 830 (1973). (16) J. R. Simpson, Dermatitis due to parabens in cosmetic creams, Contact Dermatitis, 5, 311-312 (1978). (17) A. A. Fisher, Allergic paraben and benzyl alcohol hypersensitivity relationship of the delayed and immediate varieties, Contact Dermatitis, 1, 281 (1975). (18) K. Mochida, Allergen explanation, propyl paraben, Environ Dermatol., 4, 70-81 (1997). (19) E. Esposito, C. Zanella, R. Cortesi, E. Menegatti, and C. Nastruzzi, Influence of liposomal formulation parameters on the in vitro absorption of methyl nicotinate, Int. J. Pharm., 172, 255-260 (1998). (20) F. P. Bonina, L. Montenegro, N. Scrofani, E. Esposito, R. Cortesi, E. Menegatti, and C. Nastruzzi, Effects of phospholipid based formulations on in vitro and in vivo percutaneous absorption of methyl nicotinate, J. Contro//ed Release, 34, 53-63 (1995).