306 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS (lO) (11) (12) (13) (14) (15) (16) (17) (18) (19) (20) (21) (22) (23) (24) (25) (26) (27) (28) (29) (30) (31) (32) G. F. Bryce, N.J. Bogdam, and C. C. Brown, Retinoic acids promote the repair of the dermal damage and the effacement of wrinkles in the UVB-irradiated hairless mouse,J. Invest. DermatoL, 91, 175-180 (1988). I. Kiss, S. Chen, and K. M. Tramposch, The effect of high and low ultraviolet-B dose exposure on the degree of hairless mouse skin wrinkling, P,botoc, bem. P,botobiol., 53, 109-112 (1991). S.J. Moloney, $. H. Edmonds, L. D. Giddens, and D. B. Learn, The hairless mouse model of photo- aging: Evaluation of the relationship between dermal elastin, collagen, skin thickness, and wrinkles, Photochem. Photobid., 56, 505-511 (1992). Y. Takema, T. Fujimura, H. Ohsu, and G. Imokawa, Unusual wrinkle formation after temporary skin fixation followed by UVB irradiation in hairless mouse skin, Exp. DermatoL, 5, 145-149 (1996). Z. Werb, M. J. Randa, J. H. Mckenrow, and R. A. Sandhaus, Elastase and elastin degradation,J. Invest. DermatoL, 79, 154S-159S (1982). K. A. Hasty, J. J. Jeffrey, M. S. Hibbs, and H. G. Welgus, The collagen substrate specificity of human neutrophil collagenase,J. Biol. Chem., 262, 10048-10052 (1987). M. Szendori, G. Meimon, H. Bakala, C. Frances, L. Robert, G. Godeau, and W. Hornebeck, On the presence of a metalloproteinase in human skin fibroblasts that degrades the human skin elastic fiber system, J. Invest. DermatoL, 83, 224-229 (1984). H. G. Welgus, J. J. Jeffrey, and A. Z. Eisen, Human skin fibroblast collagenase, J. Biol. Chem., 256, 9516-9521 (1981). M. J. Petersen, C. Hansen, and S. Craing, Ultraviolet A irradiation stimulates collagenase production in cultured human fibroblasts,J. Invest. Dermatol., 99, 440•444 (1992). K. Scharffetter, M. Wlaschek, A. Hogg, K. Bolsen, A. Schothorst, G. Goerz, T. Krieg, and G. Piewig, UVA irradiation induces collagenase in human dermal fibroblasts in vitro and in vivo, Arch. Dermatol. Res., 283, 506-511 (1991). G. Imokawa, Y. Yada, and M. Miyagishi, Endothelins secreted from human keratinocytes are intrinsic mitogens for human melanocytes, J. Bid. Chem., 267, 24675-24680 (1992). G. M. Murphy, D. G. Quinn, R. D. R. Camp, J. L. M. Hawk, and M. W. Greaves, In vivo studies of the action specturam and time course for release of transforming growth factor a by ultraviolet irradiation in man, Br. J. Dermatol., 125, 566-568 (1991). A. Oxholm, P. Oxholm, B. Staberg, and K. Bendtzen, Immunohistological detection of interleukin 1-like molecules and turnour necrosis factor in human epidermis before and after UVB-irradiation in vivo, Br.J. Dermatol., 118, 369-376 (1988). F. Croute, E. Delaporte, J. Y. Bonnefoy, C. Fertin, J. Thivolet, and J. F. Nicolas, Interleukin-1 b stimulates fibroblast elastase activity, Br. J. DermatoL, 124, 538-541 (1991). M. R. Duncan and B. Berman, Differential regulation of collagen, glycosaminoglycan, fibronectin, and collagenase activity production in cultured human adult dermal fibroblasts by interleukin 1-a and b and tumor necrosis factor-a and b,J. Invest. Dermatol., 92, 699-706 (1989). A. Mauviel, Y. Q. Chen, V. M. Kahari, I. Ledo, M. Wu, L. Rudnicka, and J. Uitto, Human recom- binant interleukin lb up-regulates elastin gene expression in dermal fibroblasts, J. Bid. Chem., 268, 6520-6524 (1993). V.M. Kahari, Y.Q. Chen, M.M. Bashir, J. Rosenbloom, and J. Uitto, Tumor necrosis factor-a down-regulates human elastin gene expression, J. Bid. Chem., 267, 26134-26141 (1992). K. Scharffetter-Kochanek, M. Wlaschek, K. Briviba, and H. Sies, Singlet oxygen induces collagenase expression in human skin fibroblasts, FEBS Lett., 331, 304-306 (1993). M. Wlaschek, K. Briviba, G. P. Stricklin, H. Sies, and K. Scharffetter-Kochanek, Singlet oxygen may mediate the ultraviolet A-induced synthesis of interstitial collagenase, J. Invest. Dermatol., 104, 194- 198 (1995). E. Fujimoro, Cross-linking and fluorescence changes of collagen by glycation and oxidation, Blochim. Biophys. Acta, 998, 105-110 (1989). Y. Kano, Y. Sakano, and D. Fujimori, Cross-linking of collagen by ascorbate-copper ion systems, J. Blochem., 102, 839-842 (1987). D. L. Bissett, R. Chatterjee, and D. P. Hannon, Photoprotective effect of superoxide-scavenging an- tioxidants against ultraviolet radiation-induced chronic skin damage in the hairless mouse, Photoder- matoL Photoimmunol. Photomeal., 7, 56-62 (1990). S.J. Weiss, G. Peppin, X. Ortiz, C. Ragsdale, and S. T. Test, Oxidative autoactivation on latent collagenase by human neutrophils, Science, 227, 747-749 (1985).
j. Soc. Cosmet. Chem., 48, 307-317 (November/December 1997) The skin irritation potential of quaternaries M. M. RIEGER, Morris Plains, NJ 07950. Accepted for publication November 7, 1997. Synopsis It is frequently reported that the relative skin irritancy of surfactants depends on the ionic species formed by the surfactant. Thus the irritation potential of surfactants is widely assumed to follow the pattern below in which quaternaries are the most irritating: quaternaries amphoterics anionics nonionics. The basis of this relative rating is examined below, with the conclusion that it requires modification for topically used quaternaries and surfactants in general. INTRODUCTION The evidence for the relative skin irritancy rating of surfactants--quaternaries am- photerics anionics nonionics--dates back to the period following World War II when eye and skin irritancy were assessed via the well-known Draize animal procedures [as detailed in 1959 in ref. (1)]. In addition, the potential of any surfactant to cause skin irritation can be established by a variety of alternative toxicological test procedures, as reviewed by Drobeck (2). It is the objective of this review to examine the pertinence of these and related tests for the assessment of skin irritation that may result from acci- dental or deliberate contact with quaternary surfactants. In order to complete this effort, it will be necessary to include some details of the testing of irritancy of other groups of surfactants. DEFINITION OF SKIN IRRITATION Skin irritation is defined simply as a transitory adverse response of skin to contact with the irritating species. Irritation may result from any corrosive or toxic substance, i.e., one that attacks the integument. Skin exposure to such a substance under normal cosmetic use may lead to changes in transepidermal water loss, dryness, tautness, scaling, and even erythema. The early investigators were limited to relying on erythema as the marker for skin irritation since they had no other means of assessing damage. Thus much of the data refers to the rate and level of reddening and the effect of concentration of the eliciting substance. It must be clearly recognized that erythema is a late effect of irritation, requiring that the applied substance itself reaches the dermal vasculature or that the 307
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