J. $oc. Cosmet. Chem., 32, 67-73 (March/April 1981) The mechanism of antiperspirant action by aluminum salts. I. The effect of cellophane tape stripping on aluminum salt-inhibited eccrine sweat glands RICHARD P. QUATRALE, PH.D., ARLENE H. WALDMAN, JANICE G. ROGERS, and CARL B. FELGER, PH.D., Gillette Research Institute, I413 Research Blvd., Rockville, MD 20850. Received September 19, 1980. Synopsis Studies were performed to determine the relative site of inhibition in the sweat gland caused by the three antiperspirants, aluminum chlorohydrate (ACH), aluminum zirconium chlorohydrate glycine complex (AZAP) and aluminum chloride (A1C13). For these studies, human forearm sweat glands were examined using the Scotch tape stripping procedure, a technique which removes the stratum corneum layer of skin and exposes the stratum granulosum layer of the viable epidermis. As judged by the degree to which sweat glands inhibited by overnight occlusive application of these antiperspirants could be restored to firing after Scotch tape stripping, ACH and AZAP acted most superficially, whereas A1C13 functioned at a level below the stratum corneum. INTRODUCTION To understand the mechanism of action by which aluminum-based antiperspirant salts inhibit eccrine sweat gland function, it is useful to know the site within the gland at which those salts function. Several regions of the gland which are potential targets for inhibition by these salts can be delineated. First, there is the neuroglandular junction. If it is impeded from releasing acetylcholine, for example by the use of an anticholinergic such as scopolamine, then sweat gland secretion itself does not occur (1). A second challenge point is the secretory coil in the derreal layer of skin. If an agent can affect or inhibit the active transport processes which are intricately involved in the secretion of salt and water, then no sweat will appear at the skin surface (2,3). The third potential site of activity is the resorptive duct portion of the gland, also in the dermis. Disruption of the integrity of this area of the sweat gland, for example, might cause extensive reabsorption of secreted sweat back into the interstitial space [the "leaky hose" hypothesis as proposed by Papa and Kligman (4)]. Finally, an aluminum salt might function by blocking the flow of sweat to the skin surface through the 67

68 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS formation of an obstructive mass or plug at some point in the gland's duct as proposed by Relier and Leudders for AICl 3 and an aluminum zirconium solution (5). This ductal blockage could occur anywhere ranging from its deepest region all the way up to its outermost poral opening in the stratum corneum. To determine at which level of the sweat gland an antiperspirant is functioning, specific experiments, both histological and physiological, can be designed and performed. For the most part, however, such studies are extensive and involved despite their high value. Alternatively, a first step in the approach to the problem is to identify the antiperspirant's site of action without prior regard to any proposed mechanism. The sweat gland secretory coil is located in the dermal layer of the integument, but its duct passes through the viable epidermis and then the outermost stratum corneum. Techniques are available to remove those latter two layers. Blistering the skin, by occlusively patching with cantharidin, separates the dermal and epidermal layers (6). Removing the blister cap exposes the dermis. Alternatively, Scotch © tape stripping is a technique that has been widely used to remove the stratum corneum layer, thereby exposing the stratum granulosum layer of the viable epidermis. In so removing one or both of the layers, one can determine whether a given sweat gland, previously inhibited by an antiperspirant, now resumes normal firing. If firing is restored, then the site of action within the gland is at the level within the layer which had been removed. In this fashion, one at least approximates the depth in the sweat gland to which the inhibition is occurring. The technique of Scotch © tape stripping has been used previously to determine the site of action of several antiperspirants. Papa and Kligman first demonstrated that human forearm sites, made anhidrotic by the overnight occlusive application of 20% aluminum chloride, still failed to sweat after the stratum corneum layer had been removed by stripping. They concluded that the site of action was deeper than within that layer (4). Their findings were subsequently confirmed by Gordon and Maibach (7). The findings of a later report by Zahejsky and Rovensky on aluminum chloride's site of action were somewhat inconsistent with the previous investigations. Their results indicated that anhidrosis is much more readily removable by stripping (8). However, the authors used a less agressive method of application of the test agent. The purpose of the studies in this communication was to determine at which skin layer sweat glands had been inhibited following treatment with the marketed conventional antiperspirant salts, aluminum chlorohydrate (ACH) and aluminum zirconium chloro- hydrate glycine complex (AZAP), as well as to repeat the observations by others for aluminum chloride (A1C13). MATERIALS AND METHODS Both male and female adults participated in these studies. Four sites, two on the volar surface of each forearm, were selected. The sites, measuring •-in. square, were marked with indelible ink. A template was used in order to ensure subsequent precise relocation of the sites. The subjects then entered an environmental chamber set at 100øF and 30-35% RH for thermal stress. A mixture of starch, castor oil and 2% iodine in ethanol, a modification of the original method described by Wada and Takajaki (9), was applied to the forearm sites to visualize the sweat droplets. At 20, 40 and 60 min