Nicholas Blickenstaff

Biology of percutaneous penetration.

Abstract Background: Percutaneous penetration is a passive process that can occur following skin exposure to chemicals used in agriculture, industry, pharmaceuticals, cosmetics, and in the household. Once a penetrant is absorbed into the skin it may cause a local reaction or enter systemic circulation to produce widespread effects. Improved understanding of the skin barrier and biological aspects that impede absorption of topical substances is essential for advancing the fields of dermatotoxicology and dermatopharmacology as they pertain to percutaneous penetration. Methods: Pubmed search results for “percutaneous penetration”, “absorption”, “stratum corneum”, “xenobiotics”, “skin factors”, “decontamination”, and “transdermal” were reviewed from 1965 to 2014. Relevant articles discussing the influence of biological factors on percutaneous penetration of topical substances were included. Results: Absorption of a topical substance across the skin is most notably influenced by concentration, contact duration, frequency, and the surface area exposed. The interplay between these factors, along with skin biology and the physiochemical properties of the penetrant, can lead to enhanced percutaneous penetration. Conclusion: Percutaneous penetration is a highly complicated and dynamic process influenced by numerous skin and environmental factors. Although research over the last few decades has provided plenty of new insights to improve our understanding of percutaneous penetration, many areas lack clarity due to conflicting data.

Metrics and clinical relevance of percutaneous penetration and lateral spreading.

Background: Percutaneous penetration of urea in vivo in man has been documented. If urea can penetrate the skin, it may also move laterally. Lateral spreading of topical substances leads to unpredictable penetration dynamics and increased skin surface area exposure. Methods: The ability of urea, a low molecular-weight hydrophilic model, to penetrate the stratum corneum (SC) and spread outside the application site was investigated in vitro using tape stripping with spectroscopy. The parameters investigated were the following: time between urea application and tape stripping, formulations containing urea and use of a petrolatum-covered ring barrier around the marked application area. Results: The percentage of urea was determined in and around the application site. The spreading of topically applied urea to neighboring areas occurred and was time but not formulation dependent. A significant difference between protocols with and without the petrolatum ring was observed. Conclusion: These results suggest the clinical importance of lateral spreading, occurring predominately on the skin surface. SC thickness varies between anatomical sites, predisposing areas such as the face and scalp margins to increased percutaneous penetration of topical products. The use of a protective petrolatum ring can inhibit lateral spreading of hair dye in individuals allergic to hair dye, limit systemic absorption and increase accuracy when assessing penetration dynamics.

Dermatotoxicologic clinical solutions: textile dye dermatitis patch testing.

Abstract The authors provide a framework for working up and counseling a patient with suspected textile dermatitis, focusing on identifying which textile materials are most likely to be the cause of the eczematous lesions, the current clinical guidelines, the utility and appropriateness of patch testing, the limitations of these guidelines, and our pro tempore recommendations. While there are many challenges to correctly identify and counsel patients on how to avoid the offending textile products in a patient with suspected textile dye dermatitis, there is value in following the guidelines set forth to help identify the causative textile(s). Although patch tests can be useful, dermatologists should understand the limitations of standardized patch testing for patients with suspected textile dye-induced dermatitis. These guidelines are expected to increase the likelihood of identifying the causative textile(s), so that patch testing can be supplemented with swatch testing and chemical dye extraction to help discover the allergenic dye.

Textile allergic contact dermatitis: current status.

Abstract Materials and methods: We conducted a thorough review of Pubmed search results for “textile percutaneous penetration” and “textile absorption”. We also determined relevant articles that discussed percutaneous penetration of textiles into the skin and their associated disease states. Limitations: Due to limitations in current and past publications, we are uncertain of the extent of the clinical problem; however, for patients allergic to textile dye, it is of practical importance, both clinically and in their everyday life. Conclusions: There are many challenges to correctly identifying the offending textile products in a patient with suspected textile dye dermatitis. Different populations may exhibit varying degrees of allergic contact dermatitis (ACD), but more studies must be done to draw further conclusions. This is further complicated when counseling the patient on how to avoid the textile products most likely to cause a recurrence of ACD skin lesions.

Percutaneous absorption of water in skin: a review

Abstract Background: The stratum corneum has a wide variety of important functions, including host protection from foreign chemicals and bacteria, water loss prevention, and body temperature regulation. While water absorption studies on healthy intact skin are abundant, data on the percutaneous absorption of water in diseased skin are less common. Methods: We reviewed Pubmed search results for “stratum corneum”, “absorption”, “percutaneous” and “water”, and determined relevant articles that discussed percutaneous penetration of water into skin. Results: Both percutaneous absorption of water and transepidermal water loss (TEWL) rates increase when the stratum corneum is damaged. Conclusions: Heating the skin increases the rate of percutaneous penetration of water, while freezing does not alter the absorption of water. Patients with diseases like psoriasis and atopic dermatitis have increased TEWL compared with disease-free individuals.

Skin and the environment.

The past decade brought considerable progress in clinical medicine and environmental science related to skin. We gather here and synthesize much of the pertinent information. Looking forward we hope that clinical medicine and environmental science will forge tighter bonds to assist each other in synergistically advancing knowledge. Clinical medicine is able to contribute practical patient information and toxicologists provide advanced experimental approaches. Working together, the clinician and scientist will advance the field to new frontiers in understanding, innovation, and research. This progress in dermatotoxicology will permit greater capability in the diagnosis and prevention of toxic skin exposure. Increased knowledge and understanding of the complexity of skin penetration has expanded to include at least 15 identified steps. This has implications for the design and use of in-vitro models, with some having adapted to include more than the traditional one-step model. Further understanding will allow ever increasing accuracy in the design of in-vitro models. With current understanding of percutaneous penetration, we now know that almost all chemicals under 500 Daltons will penetrate the skin. Total systemic exposure equals or exceeds that of some oral drugs over a lifetime. This special issue on skin includes an overview on the current understanding of the biology of percutaneous penetration, and includes a review on current methods of stratum corneum sampling, as efficient methods to detect dermal exposure are important to the toxicologist and the clinician. Percutaneous penetration from soil, water, and fabric have dedicated chapters to address common exposure pathways. A chapter examines the influence of vapor pressure on dermal penetration. Three chapters review common clinical syndromes that involve the skin and environment: allergic contact dermatitis, irritant dermatitis, and contact urticaria. Specific irritancy to water, photoallergy, and airborne contact dermatoses are included. Lastly, the role of UV light in skin aging and skin cancer and UV light and arsenic exposure in the occupational setting offer the reader a broad coverage of environmental skin exposures. We would like to personally thank the editorial staff, especially Ms. Ingrid Grünberg, for their assistance in putting together this special issue on skin, without them we would only have piles of manuscripts sitting in our lab. Additionally, the reviewers, including Ann Goossens, Xiaoying Hui, Henry Lim, James Taylor and Christina Wang are appreciated for their time and thoughtful comments in editing the manuscripts. Lastly, we profusely thank the authors for their hard work and tireless dedication to the advancement of their respective fields and for writing these excellent contributions. This issue is the result of countless hours of work and determination, and we hope you find it useful and thought provoking.

Dermatotoxicologic clinical solutions: hair dying in hair dye allergic patients?

Abstract This article describes how to identify allergic contact dermatitis resulting from hair dye, and outlines interventions and prevention principles for those who wish to continue dyeing their hair despite being allergic. Hair dye chemicals thought to be the most frequent sensitizers are discussed with instructions for health care providers on how to counsel patients about techniques to minimize exposure to allergenic substances. This framework should allow many patients to continue dyeing their hair without experiencing adverse side effects.

Percutaneous absorption from soil.

Abstract Some natural sites, as a result of contaminants emitted into the air and subsequently deposited in soil or accidental industrial release, have high levels of organic and non-organic chemicals in soil. In occupational and recreation settings, these could be potential sources of percutaneous exposure to humans. When investigating percutaneous absorption from soil – in vitro or vivo – soil load, particle size, layering, soil “age” time, along with the methods of performing the experiment and analyzing the results must be taken into consideration. Skin absorption from soil is generally reduced compared with uptake from water/acetone. However, the absorption of some compounds, e.g., pentachlorophenol, chlorodane and PCB 1254, are similar. Lipophilic compounds like dichlorodiphenyltrichloroethane, benzo[A]pyrene, and metals have the tendency to form reservoirs in skin. Thus, one should take caution in interpreting results directly from in vitro studies for risk assessment; in vivo validations are often required for the most relevant risk assessment.

Repairing a Compromised Skin Barrier in Dermatitis: Leveraging the Skin's Ability to Heal Itself

Skin barrier defects play a major role in many dermatoses including irritant and allergic contact dermatitis, atopic dermatitis, dry skin, aged skin, xerosis, rosacea, acne and more. Skin barrier repair technology has heretofore focused on physiologic skin lipid replacement and skin protection without addressing the myriad other areas of compromise such as an elevated pH, balance of the microbiome, inflammation, succeptibility to infection, aberrant calcium gradients and the proclivity for contact sensitization. By changing the paradigm from physiologic skin lipid supplementation to that of supplementing the epidermis with lipids that have recently been found to be particularly deficient from the disrupted skin barrier, and by simultaneously addressing the many facets of vulnerability, the skin barrier can be effectively repaired. This model of advanced skin barrier repair wherein physiologic deficiencies are supplemented and/or augmented may be an effective method for restoring the ability of xerotic and dermatitic skin to heal itself.

Dermatotoxicologic clinical solutions: clinical management of fragrance mix #1 #2 patients?

Abstract Today’s fragrances are present in more than just perfumes, having become ubiquitous in skin care products such as creams, shampoos, sun tan lotion and deodorants. While aromatics can arouse the senses, aromatic compounds applied to skin can also cause allergic contact dermatitis. This article describes diagnosis, limitations of patch testing for fragrance mix 1 and fragrance mix 2, the relevance of fragrance concentration in products, use testing of common consumer products and our current recommendations in regards to the management of fragrance contact allergy.