ANTIPERSPIRANT ACTION OF ALUMINUM SALTS 361 COMMENT Rubbing a 20% solution of A1C12 on the skin results in only a modest degree of anhidrosis 24 hr later. Following evaporation of water the salt crystallizes out on the surface and is no longer available. An occlusive dressing markedly enhanced the anhidrotic effect. Hydration keeps the salt in solution and promotes diffusion into the ducts. Likewise, occlusive application of soaked patches keeps the aluminum ion mobilized and provides a reservoir for the salt. Repeated open applications increase the antiperspirant effect, but only up to a maximum of about 75%. Our experience is similar to that of Tronnier & Rentschief (4): they failed to obtain complete suppression even after five daily exposures. On the other hand, occlusive exposures, either repeatedly for short terms or continuously for longer periods, will induce almost complete anhidrosis in nearly everyone. In a given person individual sweat units have different susceptibilities some become blocked much earlier than others. It is the concentration of aluminum within each duct that determines whether an obstruction will occur. The depth of the block, which affects the duration of anhidrosis, is mainly determined by both the length of the exposure and occlusivity. Short-term exposure creates a rather shallow obstruction which is comparatively short-lived. Each treatment affects only the ducts unaltered by previous exposures, that is, only the ones that are still open. Once formed, the block evidently cannot be deepened by further treatments. Procedures which expose the sweat orifices to high concentrations of solubilized aluminum for prolonged periods are invariably the most effective ones. To our great surprise, iontophoresis of various salts of aluminum for 5 min at various concentrations was a dismal failure. Five minutes is more than sufficient time to produce complete anhidrosis with anti-cholinergic drugs (5). Iontophoresis for two 15-min periods, at low current densities, on consecutive days resulted in only moderate enhancement as compared to occlusive application alone. The inhibition was far from complete though it was generally double the control values. Since iontophoresis of saline had no effect, this result is probably not due to ductal injury. A pilot study using iontophoresis of hydrochloric acid, pH 2.0, was also without effect. High current densities will damage the acrosyringium and induce an anhidrosis several days later (6). The ineffectiveness of iontophoresis is puzzling and inexplicable. STUDY 2. THE EFFECT OF SURFACTANTS ON ALUMINUM ANHIDROSIS Previous investigators felt that the antiperspirant activity of metallic salt solutions could be enhanced by surfactants, especially for the treatment of axillary hyperhidro- sis. Herrmann & Sulzberger (7) recommended aluminum chloride with the nonionic detergent Triton X-100. Hunzicker & Brun (8) and Brun (9) also thought that Triton X-100 added considerably to efficacy. In his monograph, Fiedler (10) mentioned quaternary ammonium compounds as useful additives, but no data were provided. Theoretically, surfactants might augment antiperspirants by facilitating their penetra- tion into and down the sweat ducts. Since controlled experimental studies were lacking, we investigated the effect of nonionic, anionic and cationic detergents.

362 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS METHODS Ten percent solutions of A1C13 containing the surfactants were occlusively applied via Duhring chambers for 3 hr to two groups of six subjects each. Sweat suppression was estimated 24 hr later. The detergents were: 1) anionic--2.5% sodium lauryl sulfate (Fisher Scientific Co., Chemical Manufacturing Division, Fairlawn, N.J.) 2) cationic- 5% cetyl pyridinium chloride (ACETO Chemical Co., Flushing, N.Y.), 5% Hyamine 2389 (Rohm & Haas Co., Phila., Penn.), 5% benzalkonium chloride (ICN Pharmaceuti- cals, Inc., Plainview, N.Y.), 10% cetyltrimethylammonium bromide (supplied courtesy of Shulton, Co., Clifton, N.J.), and 10% tetramethylammonium chloride (supplied, courtesy of Shulton Co., Clifton, N.J.) 3) nonionics--10% Triton X-100 (Rohm & Hass Co., Phila., Penn.), 10% Tween-80 (Fisher Scientific Co., Chemical Manufacturing Div., Fairlawn, NJ.) and 10% Pluronic L-35 (BASF Wyandotte Corp., Wyandotte, Mich.). The plain detergent solutions and 10% aluminum chloride comprised the controls. RESULTS An average suppression of about 50% was produced by 10% A1C13 alone. SLS enhanced the anhidrosis by about 25%, accompanied by a mild inflammatory reaction. Among the cationic surfactants, only cetyltrimethylammonium bromide and tetramethylam- monium chloride exhibited appreciable augmentation, 20% and 15% respectively, again with visible irritation. The nonionic detergents resulted in only slight improvements, ranging from 15% for Triton X-100 to 7.5% for Pluronic L-35. These latter increases are not statistically different from the increases of the controls. Used alone, the detergents had no antiperspirant activity with the exception of SLS, which produced a 34% inhibition accompanied by irritation. COMMENT Ionic surfactants are chemically reactive substances which are potentially quite irritating to the skin. We deliberately selected sub-irritating concentrations, but even so, mild erythema and scaling often occurred at control sites. The irritant reaction was worsened in the presence of aluminum chloride, itself a potential irritant. Past studies have shown that damaging the skin in various ways, including chemical insults, can lead to miliaria. Injury to the acrosyringium underlies anhidrosis produced in different ways. Accordingly, the enhancement of aluminum anhidrosis by anionic and cationic surfactants is probably a non-specific damaging effect unrelated to surface tension or wetting properties of the solutions. The nonionic non-irritating surfactants were mostly without effect. STUDY 3. EFFECT OF PRE-TREATMENTS It is controversial whether removal of the surface lipids aids antiperspirant activity. Brun (9) and Schmid et al. (11) obtained a greater degree of sweat inhibition on sites delipidized by swabbing with ether-ethanol. Kligman (12) denied any enhancement of anhidrosis by lipid removal. We sought to improve effectiveness by a variety of pretreatment maneuvers even though certain of these are quite impractical.