196 JOURNAL OF COSMETIC SCIENCE with about 40% of the esters containing alphahydroxy esters, although the exact number of different esters is yet unknown. Moreover, the sensitization potential of lanolin remains still under discussion (64). Clark has proposed a reduction or purification of lanolin alcohols in order to minimize the risk of sensitization (65,66). Interestingly, an epidemiological study revealed that lanolin­ induced allergies occur in less than 0.001 % of individuals, i.e., less than 10 per million (67), while recent studies showed higher percentages of positive test reactions in children with atopic dermatitis (1.7% and 4.4%) (68,69). Kligman suggests that most of the lanolin sensitization cases represent false-positive results, and thus wool wax-containing products can be considered safe (64). Pesticide impurities and rancid lanolin grades could have contributed to some problems encountered in the past. Lanolin has known moisturizing properties (70), similar to those of petrolatum. Long­ term effects of lanolin can be detected up to 14 days after termination of treatment (70). The hydrating effect of lanolin has been shown using electrophysical measurements (71,72). While lanolin penetrates into the stratum corneum, it remains concentrated in the upper layers (73 ). Compared to a different vehicle, topically applied lanolin accel­ erated barrier recovery following an acute barrier disruption with acetone (74), i.e., 3% lanolin significantly reduced transepidermal water loss both 45 minutes and four hours following disruption. Moreover, the immediate effect of lanolin on barrier recovery was pronounced. In fact, the positive barrier effect of lanolin was comparable to that of an optimized ratio of stratum corneum lipids, i.e., a barrier formulation (discussed in more detail below) including cholesterol, ceramides, essential fatty acids, and non-essential fatty acids (ratio 3:1:1:1) (55,56,74). Finally, skin roughness is positively influenced by formulations containing lanolin in a dose-dependent manner (7 5 ). Thus, although the exact nature of contact sensitization against lanolin has not been revealed, the positive effects of this compound appears to outweigh the allergic risk. PETROLATUM AS COSMETIC VEHICLE MODEL Petrolatum (synonym: petroleum jelly) is regarded as a standard dermatological vehicle and is widely used in both therapeutic and cosmetic applications. Petrolatum is a purified material obtained from petroleum, consisting of a variety of long-chain aliphatic hydrocarbons. It has been used in skin care since the late 19th century, yet is still listed in the current pharmacopoeia (e.g., US, Germany). In practical dermatology, petrolatum is used either as a vehicle for patch testing or drug delivery and as an adjuvant cosmetic vehicle. Usually petrolatum does not contain reactive chemical bonds and, as such, has a long stability. It is considered to be an inert vehicle with no direct irritation effect. Petro­ latum is frequently used as a vehicle for patch testing, representing the classic vehicle for lipophilic compounds in this setting. Petrolatum-based formulations have shown excel­ lent stability, as there is no or only little change in incorporated compound concentra­ tions. The remarkable value and long shelf life of petrolatum are derived both from its oxidation- and degradation-resistant properties (76). Its toxicity is low, even if accu­ mulation into body organs after repeated overexposure has been reported. Recently, purified hydrocarbons of known molecular structure (branched chain hydrogenated polydecenes, food grade) have been proposed as a safer replacement for petrolatum (77).

ROLES OF VEHICLES FOR SKIN TREATMENT 197 Petrolatum can be used as a drug delivery system, especially for lipophilic agents, but also in liposomal formulations (78). When applied topically, petrolatum itself penetrates only the very superficial layers of the stratum corneum. The most important property of petrolatum is its moisturization of the stratum corneum, attributable to its relative occlusive effects (as discussed above) (5 ,79). As such, petrolatum is considered a standard vehicle for comparative testing of hydration and barrier repair (80). The hydration effect of petrolatum on the stratum corneum has been measured by a number of noninvasive methods, including capacitance, conductance, optothermal in­ frared spectrometry, and transepidermal water loss (5,7,14,72,81,82). In many studies petrolatum is used as a positive standard to demonstrate the reduction of transepidermal water loss. Petrolatum is regarded as one of the most potent occlusive vehicles (5, 7). Ghadially and colleagues reported an accelerated barrier recovery after barrier disruption using topical petrolatum (83). In this study, penetration of petrolatum was evident throughout the stratum corneum interstices, allowing a normal or even accelerated barrier recovery despite its occlusive properties (83). In addition, a petrolatum-based barrier cream for hand dermatitis has shown positive results (84). Moreover, a petrola­ tum-containing cream showed a decrease in bacteria colonization and a reduced fre­ quency of dermatitis in premature infants (85). The reported comedogenicity of petro­ latum remains controversial, as the rabbit ear model used in these studies does not accurately predict skin conditions in humans (86-88). Thus, it is clear that the derma­ tological utility of petrolatum remains high, with new claims being developed regularly. High purity standards are always recommended. For example, Morrison reports that a number of recent patents claim the utility of petrolatum for different skin care products, including one for treatment of diaper rash, a moisturizing bar with soap containing petrolatum as a major component, a skin care product to reduce wrinkles, and products for moisturization and skin conditioning (7 6). Recent publications using disposable diapers designed to deliver continuously a petro­ latum-based formulation to the skin also have shown significant reductions in the severity of erythema and diaper rash (89,90). ROLE OF PHYSIOLOGICAL LIPIDS IN DERMATOLOGICAL AND COSMETIC VEHICLE FORMULATIONS The barrier function of the skin is mediated by intercellular bilayers in the stratum corneum. Cholesterol, ceramides, and essential and non-essential fatty acids play a key role in the formation of these bilayers (91,92). Stratum corneum lipids are composed of about 40% ceramides, 25% cholesterol, and 20% free fatty acids (by weight) (92). Taking the average molecular weight of these three lipid classes into account, the normal stratum corneum has an approximately equimolar physiologic ratio of ceramides, cho­ lesterol, and free fatty acids. Following barrier disruption in hairless mice, epidermal cholesterol and fatty acid syntheses are immediately increased, while increased ceramide production is evident about six hours later (91,93-95). These key barrier lipids are delivered to the intercellular space of the stratum corneum as a mixture of precursors by the extrusion of lamellar body content at the stratum granulosum-stratum corneum interface (96,97). Fusion of the extruded lamellar contents within the lower stratum corneum leads to continuous membrane sheets, which ultimately form mature mem-