Dose response effect of chemical surface concentration on percutaneous penetration in human: In vivo + in vitro.

The concentration of a formulation, defined as the mass of applied chemical per unit of skin surface area, is a key variable of skin absorption. Often only one concentration is available in the literature, hence a general evidence-based theory could allow prediction of how altering the concentration would produce a linear, increased, or decreased relative permeation. Here, we group topical chemicals into groups of how they permeate the skin when we increase or decrease their concentrations per unit area and discuss why we would like to predict their permeability in ranges of studied concentrations. PURPOSE: Our research question is: How, if at all, do changes in surface chemical concentration affect percutaneous penetration/absorption in man? Specifically, as the drug concentration is relatively increased, is the rate or extent of absorption proportionally affected? And if so, how? METHODS: We searched PubMed, Google Scholar, the United States Food and Drug Administration, Scientific Committee on Consumer Safety, and the European Food Safety Authority for approved transdermal delivery systems from January 1965 to October 2020. Search terms included combinations of the following words: topical + [absorption/penetration] + cm + [human/man]. RESULTS: Of the nineteen chemicals identified, five (testosterone, hydrocortisone, benzoic acid, fluazifop-butyl and lindane) showed decreased percent absorbed with increased dose, one (2-butoxyethanol) showed decreased flux with increased concentration, and thirteen (Basic Brown 17, benzene in gasoline, benzophenone-3, benzoyl peroxide, boric acid, caffeine, climbazole, diclofenac, ethanolamines, ibuprofen, N-octylamine, 2-phenoxyethanol, 2-pyrrolidone) showed increased flux with increasing concentrations. CONCLUSION: Dermal absorption depends on the interaction between the characteristics of the substance, the vehicle, and the skin. Without experiments investigating these characteristics, we cannot accurately predict the percent absorbed or flux of a formulation without in vitro or in vivo data. More experimental data, especially in vivo, is mandated before a highly efficient prediction model will be reached for validation.

Efficacy of water skin decontamination in vivo in humans: A systematic review.

With the constant possibility of occupational exposures, chemical warfare, and targeted attacks, increased attention has been given to determining effective and timely dermal decontamination strategies. This systematic review summarises experimental studies reporting decontamination with water-based solutions of dermal chemical contaminants with in vivo human data. Embase, MEDLINE, PubMed, Web of Science, and Google Scholar databases were comprehensively searched using search terms ("cutaneous" or "skin" or "dermal" or "percutaneous") and ("decontamination" or "decontaminant" or "skin decontamination") to include 10 studies, representing 18 chemical contaminants, 199 participants, and 351 decontamination outcomes. Three studies included data from decontamination with water (10.8%, n = 38/351 decontamination outcomes), seven with soap and water (68.4%, n = 240/351 decontamination outcomes), and two with 10% isopropanol distilled water (20.8%, n = 73/351 decontamination outcomes). Results of dermal decontamination using water showed complete decontamination (CD) outcomes in 52.6% (n = 20/38) and partial decontamination (PD) in 47.4% (n = 18/38); using soap and water showed PD outcomes in 92.9% (n = 223/240) and minimal to no effect in 7.1% (n = 17/240); and using 10% isopropanol distilled water achieved PD outcomes in 100.0% (n = 73/73). Available data show that decontamination with water, soap and water, and 10% isopropanol distilled water is incomplete. Much remains to be learned about decontamination of the large variety of chemical contaminants including a range of molecular weights, lipid and water solubilities, melting points, volatility, and hydrogen bonds, as well as clinically relevant anatomic sites. A major void exists in data confirming or denying the completeness of decontamination by measuring absorption and excretion. The development of effective decontamination solutions is of high priority.

Efficacy of water-only or soap and water skin decontamination of chemical warfare agents or simulants using in vitro human models: A systematic review.

Water-only or water and soap are widely recommended as preferred solutions for dermal decontamination. However, limited efficacy data exist. We summarized experimental studies evaluating in vitro efficacy of water-only or soap and water in decontaminating chemical warfare agents (CWA) or their simulants from human skin models. Embase, Covidence®, MEDLINE, PubMed, Web of Science, and Google Scholar were searched for articles using water-only or soap and water decontamination methods for removal of CWA/CWA simulants in in vitro human skin models. Data extraction was completed from seven studies, yielding seven contaminants. Water-only decontamination led to partial decontamination in all skin samples (100%, n = 81/81). Soap and water decontamination led to partial decontamination in all skin samples (100%, n = 143/143). Four studies found decontamination to either paradoxically enhance absorption of contaminants or their penetration rates, known as the "wash-in" effect. Despite recommendations, water-only or water and soap decontamination were found to yield partial decontamination of CWA or their simulants in all human in vitro studies. Thus, more effective decontaminating agents are needed. Some studies demonstrated increased or faster penetration of chemicals following decontamination, which could prove deadly for agents such as VX, although these findings require in vivo validation. Heterogeneity in experimental setups limits interstudy comparison, and it remains unclear when water-only or water and soap are ideal decontaminants, which requires more studies. Pending manuscripts will summarize in vivo human and animal efficacy data. International harmonized efficacy protocol should enable more efficient public health decisions for evidence-based public health decisions.

Ability of mathematical models to predict human in vivo percutaneous penetration of steroids.

Human skin is a common route for topical steroids to enter the body. To aid with risk management of therapeutic steroid usage, the US Environmental Protection Agency estimates percutaneous penetration using mathematical models. However, it is unclear how accurate are mathematical models in estimating percutaneous penetration/absorption of steroids. In this study, accuracy of predicted flux (penetration/absorption) by the main mathematical model used by the EPA, the Potts and Guy model based on in vitro data is compared to actual human in vivo data from our laboratory of percutaneous absorption of topical steroids. We focused on steroids due to the availability of steroid in vivo human data in our laboratory. For most steroids the flux was underestimated by a factor 10-60. However, within the group itself, there was an association between the Potts and Guy model and experimental human in vivo data (Pearson Correlation = 0.8925, p = 0.000041). Additionally, some physiochemical parameters used in the Potts and Guy equation, namely log Kp (Pearson Correlation = 0.7307, p = 0.0046) and molecular weight (Pearson correlation = -0.6807, p = 0.0105) correlated significantly with in vivo flux. Current mathematical models used in estimating percutaneous penetration/absorption did not accurately predict in vivo flux of steroids. Why? Proposed limitations to mathematical models currently used include: not accounting for volatility, lipid solubility, hydrogen bond effects, drug metabolism, as well as protein binding. Further research is needed in order to increase the predictive nature of such models for in vivo flux.

Efficacy of soap and water based skin decontamination using in vivo animal models: a systematic review.

Water-only or soap and water solutions are considered a gold standard for skin decontamination. However, there is lack of conclusive data regarding their efficacy. The aim of this study was to summarize in vivo animal model data on skin decontamination using water-only, and/or soap and water. Covidence, Embase, MEDLINE, PubMed, Web of Science, and Google Scholar were searched to identify relevant articles using water-only or soap and water decontamination methods in in vivo animals. Data extraction was completed from studies, representing three animal models, and 11 contaminants. Results demonstrated water-only decontamination solutions led to complete decontamination in 3.1% (n = 16/524) protocols, incomplete decontamination in 90.6% (n = 475/524) of protocols, and mortality in 6.3% (n = 33/524) of protocols. Soap and water decontamination solutions resulted in complete decontamination in 6.9% (n = 8/116) protocols, incomplete decontamination in 92.2% (n = 107/116) of protocols, and mortality in 6.9% (n = 8/116) of protocols. Although water only, or soap and water is considered a gold standard for skin decontamination, most papers investigated found that water only, and soap and water provided incomplete decontamination. Due to the insufficient data, and limitations that hinder the applicability of available data, evidence indicates that more contemporary studies investigating skin decontamination are needed, and compared to other model species, including humans, when practical.

Comparative efficacy of Reactive Skin Decontamination Lotion (RSDL): A systematic review.

Due to threats posed by Chemical Warfare Agents (CWAs) and accidents with Toxic Industrial Chemicals (TICs), the need for highly effective skin decontamination remains relevant. Reactive Skin Decontamination Lotion (RSDL), composed of Dekon 139 and 2,3-butanedione monoxime, has been shown highly effective against CWAs and TICs. This systematic review compares RSDL efficacy to other decontaminating agents. Online search engines PubMed, Web of Science, and Embase were explored, and all literature containing quantitative data, comparing RSDL to other decontaminating agents, investigated. Year of publication, type of study (in vitro or in vivo), model (animal or human), toxin tested, and result of each relevant article were recorded. In total, 15 relevant papers, comprising a total of 18 experimental models, were identified. Nine studies concluded that RSDL was the most effective decontaminant tested against the toxin of interest. Four studies concluded that RSDL was not the most effective decontaminant tested against the toxin of interest. The remaining 5 studies concluded RSDL displayed similar efficacy to at least one of the other decontaminating agents tested against the toxin of interest. There is substantial evidence supporting the efficacy of RSDL as a decontaminating agent. However, there remains to be insufficient data on this important topic, and limitations on the usefulness of current data, when applied to the broad array of potential exposures.

Hair dyes: a systematic review of pertinent in vivo human studies.

What is the safety of hair dyes in human use? To address this, the penetration of hair dyes into human bodies must be quantified. This article provides a critical overview to update work published in the area of in vivo hair dye penetration in humans. Studies are in humans, with one including rhesus monkey and one including in vitro human skin. MEDLINE, PubMed, Embase, Scopus, Web of Science, and Google Scholar databases were searched from 2004 to October 2019 for articles with experimental methodology on in vivo percutaneous absorption of hair dyes in humans and six studies were included. Findings indicate that percutaneous penetration occurs with hair dye use, with less absorbed in hairdressers. However, much remains unknown about the penetration of the over 200 commercially available hair dyes. A major void exists in data confirming or denying the completeness of excretion once absorbed.

Lateral spread and percutaneous penetration: An overview.

Lateral spread, a phenomenon with significance for percutaneous application of drugs or chemicals but often overlooked, is a competitive process to drug or chemical penetration into stratum corneum and beyond. Its effect may vary depending on factors such as physicochemical properties, formulation, skin surface topography etc. It may impact clinical use of topical drugs or percutaneous research including bioequivalence studies. Consequences may include less drug absorbed systemically or reduced rate of absorption. For quantitation studies and risk assessment, lateral spread may need to be incorporated as a "correction factor".

Organic compounds percutaneous penetration in vivo in man: Relationship to mathematical predictive model.

Human skin is a common pathway through which chemicals in our environment enter the body. To aid with risk management of environmental chemicals, the US EPA utilizes mathematical models to estimate percutaneous penetration when experimental data is not available. Here, the accuracy of predicted flux by the Potts and Guy model based on in vitro penetration is compared to human in vivo data of percutaneous absorption of various organic compounds. For most chemicals, the flux was over- or underestimated by a factor 10-100. In vitro flux was significantly correlated to experimental human in vivo flux; however, the physiochemical parameters used in the Potts and Guy equation, Kp, Koctanol, and molecular weight, did not correlate significantly with in vivo flux. We discuss possible explanations for why the computer model did not accurately predict in vivo flux. Further research is needed with different types of chemicals encountered in the environment, and/or as used in clinical practice. This manuscript discusses limitations to the mathematical models currently used, and why the models should be further refined for use.

Twenty Clinically Pertinent Factors/Observations for Percutaneous Absorption in Humans.

At least 20 clinically relevant factors affect percutaneous absorption of drugs and chemicals: relevant physico-chemical properties, vehicle/formulation, drug exposure conditions (dose, duration, surface area, exposure frequency), skin appendages (hair follicles, glands) as sub-anatomical pathways, skin application sites (regional variation in penetration), population variability (premature, infants, and aged), skin surface conditions (hydration, temperature, pH), skin health and integrity (trauma, skin diseases), substantivity and binding to different skin components, systemic distribution and systemic toxicity, stratum corneum exfoliation, washing-off and washing-in, rubbing/massaging, transfer to others (human to human and hard surface to human), volatility, metabolic biotransformation/cutaneous metabolism, photochemical transformation and photosensitivity, excretion pharmacokinetics, lateral spread, and chemical method of determining percutaneous absorption.

Influence of an interprofessional HIV/AIDS education program on role perception, attitudes and teamwork skills of undergraduate health sciences students.

PURPOSE: An evaluation study of an undergraduate HIV/AIDS interprofessional education program for medical, nursing and pharmacy students was undertaken to assess changes in role perception, attitudes towards collaboration, self-reported teamwork skills and satisfaction with a shared learning experience. METHODS: A combined one group pretest-posttest and time-series study design was used. Several survey instruments and observation checklists were completed by students and tutors before, during and after the educational program. RESULTS: Students reported greater awareness of roles and the continuous exposure to interprofessional learning led to improved attitudes towards teamwork. Standardized patients were effective in fostering an experience of realism and motivating collaboration between students. CONCLUSION: A problem-based learning approach combined with standardized patients was effective in enhancing HIV/AIDS interprofessional role perception, enhancing attitudes towards collaboration and interprofessional approaches to HIV/AIDS care and fostering confidence in teamwork skills among pre-licensure health sciences students.