PETROLATUM AND COMEDOGENICITY 45 PETROLEUM JELLY CREAM: ß Two recorded no change. ß Six recorded mild improvement. ß Two recorded moderate improvement. The dermatologists' assessments at eight weeks roughly corresponded to the patients' estimates, except that the grades were somewhat lower. No case of worsening was observed. DISCUSSION The salient finding in this study is that Vaseline petroleum jelly was not comedogenic when applied twice daily to adolescents with active acne. The emulsion containing 30% petrolatum behaved similarly. It is well known that acne patients will develop comedones fairly rapidly when potent comedogens, such as crude coal tar, are applied (8). We have found that even moderately comedogenic substances such as esters of fatty acids (for example, undiluted isopropyl myristate) will induce microcomedones on the forehead of patients with active acne when applied twice daily for eight weeks (unpublished observations). The discussion that follows is an attempt to bring some perspective into what has been an area of frustrating contentiousness. In the 1972 "acne cosmetica" study, the test formulations were inserted inside the ear canal, based on the fact that the follicles there are larger and more numerous. What was not appreciated at the time was that in this protected site loose horny material is commonly retained in the follicular lumens, mimicking comedones. We failed to dis- tinguish between the dense compact horn that comprises a microcomedo, a pathologic impaction, and the normal accumulation of loose horny squames. A more serious error was our failure not to biopsy the opposite untreated ear. This is a necessary control in order to provide a reference for judging the amount of horny material in the treated ear. Without a control biopsy, many materials will be falsely labeled as comedogenic. Our current guidelines are as follows: The test substances are applied to the underside of the pinna in the concave area just external to the ear canal (7). An inch-long ellipse is excised for histologic evaluation, followed by semi-serial sectioning. This allows many more follicles to be visualized. It should be noted that the follicular population is heterogeneous. As in humans, individual follicles vary considerably in size and respon- siveness. The final grading is a global estimate of all the follicles within the section. This is, of course, a subjective estimate. Quantification can be obtained by preparing whole, heat-separated epidermal mounts (13). The diameters of all the follicles can be scanned, enabling calculation of the mean diameter. The daily exposures have been extended from two to three weeks. Using this new procedure, including proper controls, petrolatum was reevaluated for comedogenicity. None of five samples from different producers, including yellow and white petrolatums, were found to be comedogenic. It is reassuring for the validity of the method that "red veterinarian petrolatum," used as a sunscreen in World War II was found to be strongly comedogenic. This is an

46 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS extremely crude grade of petrolatum. It is also reassuring that certain lanolin derivatives such as acetylated lanolin were also comedogenic. These examples validate the specificity of the revised assay. Attention is called to the reliability of the cyanoacrylate follicular biopsy, assisted by image analysis, for identifying comedogenic substances in humans. When applied twice daily for eight weeks to the foreheads of oily, acne-prone persons, comedogenic materials such as acetylated lanolin and isopropyl myristate increased both the density and size of horny casts (unpublished observations). Thus, there is encouraging evidence that the results of rabbit and human tests are congruent. There is too little awareness that the risk of inducing comedones is concentration-dependent. Substances that are strongly comedogenic when tested neat or in high concentrations become non-comedogenic after sufficient dilution. Neat isopropyl myristate and neat acetylated lanolin are definitely comedogenic. However, the concentrations in facial products are generally well below 15%. At this level, neither agent was found to be comedogenic in either the rabbit or human model (unpublished observations). One cannot determine from a reading of the ingredients whether a given product will be acnegenic or not. What matters solely is the behavior of the product itself. In the current study both petrolatum and the 30% petrolatum emulsion product sig- nificantly reduced the number of papulo-pustules. This is a fairly typical result for non-medicated vehicles. It is of surpassing interest that in double-blind, vehicle- controlled, anti-acne studies, the beneficial effect of the vehicle often approaches that of the active agent! Mills and Kligman reviewed worldwide reports on the efficacy of dozens of anti-acne medicaments (14). There was not a single instance in which the test substance was found to be without benefit. Acne nearly always improves under medical care, regardless of the agent. This is the reason why so many marginally effective agents can be sold in large quantities. Soreness and tenderness is a frequent complaint of patients who have many inflammatory lesions. Most of the patients in this study volunteered that soreness was moderated by both products. For over a century petrolatum has been extensively used to treat a variety of skin ailments such as burns, abrasions, rashes, and dry skin. Petrolatum also has protective actions against soap and solvent damage and against irritating drugs like tretinoin (unpublished observations). These uses probably reflect its ability to enhance the barrier function of the stratum corneum and perhaps to promote healing. It has been shown that petrolatum becomes incorporated into the intercellular lipid domains be- tween corneocytes, thereby becoming part of the structure of the horny layer (15). In the original, "acne cosmetica" report, half of the cosmetics were found to be come- dogenic. This was proffered as the explanation for the relatively high frequency of acne in post-adolescent women. Several studies have shown that as many as one-third of adult women suffer from "breakouts" especially premenstrually (16,17). "Breakouts" are typical acne lesions, mostly incited by the rupture of microcomedones (18). It is now highly questionable whether cosmetics are the chief cause of post-adolescent female acne. Reputable manufacturers of a great variety of facial skin care products, moisturizers, sunscreens, foundations, lotions, and toners routinely screen their prod- ucts for comedogenicity. Women have been taught to look carefully at the label to make sure that the product is "non-comedogenic." Despite these efforts, the prevalence of post-adolescent female acne has, in my experience, increased rather than decreased (19).