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Howard I Maibach

Publications and source records attributed to Howard I Maibach.

At least 19 recordsLinked to original sources

Occupational issues of irritant contact dermatitis.

Occupational irritant contact dermatitis (ICD), a non-immunological cutaneous inflammatory response to a workplace substance, comprises a major portion of occupational dermatoses in industrialized societies, resulting in considerable social and economic implications. The sheer morphological variety of ICD presents a diagnostic and classification challenge; ideotypes identified to date include acute, chronic and cumulative irritant dermatitis, delayed acute irritant dermatitis, irritant reaction, pustular irritant dermatitis, suberythematous irritation, sensory irritation, friction dermatitis and airborne dermatitis. Hand dermatitis is the most frequent manifestation of occupational ICD. This article reviews the various types of ICD, the epidemiological data available to date, risk factors, pathophysiology, diagnosis and management of ICD, emphasizing occupational issues.

Dermatitis, Irritant↗

Enhanced econazole penetration into human nail by 2-n-nonyl-1,3-dioxolane.

This study determines the enhancing effects of 2-n-nonyl-1,3-dioxolane on the penetration of econazole, an antifungal drug, into the deeper layers of the human nail where fungal infection resides. Aliquots (10 microL) of Econail lacquer formulation containing 0.45 mg of [(14)C]-econazole with 18% 2-n-nonyl-1,3-dioxolane (test group) or without 2-n-nonyl-1,3-dioxolane (control group) were applied twice daily for 14 days to human nails that had been washed with ethanol before each morning's application. The hydration of the nail sample was well controlled to simulate normal physiological conditions. After 14 days of dosing, the inner ventral section of the nail plate was assayed for absorbed drug content, using a micrometer-controlled drilling and nail powder removal system. The mass balance values of [(14)C]-econazole in this study were 90.8 and 96.4% for the test and control groups, respectively. The weight-normalized econazole content in the ventral/intermediate nail plate center in the test group was 6-fold greater than that in the control (p = 0.008). The total econazole absorbed into the supporting bed cotton ball in the test group was nearly 200-fold greater than that in the control group (p = 0.008) over the 14-day period. The amount of econazole after dosing in the inner part of the human nail (potential diseased area) was 11.1 +/- 2.6 (SD) microg/mg of nail powder with 2-n-nonyl-1,3-dioxolane in the lacquer and 1.78 +/- 0.32 microg/mg without 2-n-nonyl-1,3-dioxolane (p = 0.008). The surface nail contained more econazole (p = 0.004), that is, nonabsorbed drug, where 2-n-nonyl-1,3-dioxolane was not part of the dosing solution. Econazole in the support bed under the nail (the total absorbed dose) was 47.5 +/- 22.0 mg in the lacquer with 2-n-nonyl-1,3-dioxolane and 0.2 +/- 0.1 mg in the lacquer without 2-n-nonyl-1,3-dioxolane (p = 0.008). Moreover the concentration in the deep nail layer in the test group is 14,000 times higher than minimum inhibitory concentration (MIC) believed necessary to inhibit the growth of infecting fungi (Dermatophytes species). In a subsequent study, [(14)C]-dioxolane did not penetrate the nail well. Therefore, the mechanism of enhancement of econazole penetration is at the formulation/nail interface.

Administration, Topical↗

Decreasing allergic contact dermatitis frequency through dermatotoxicologic and epidemiologic based intervention?

Allergic contact dermatitis (ACD) affects millions of people worldwide. In an attempt to decrease the incidence of contact dermatitis, several countries have implemented legislations to reduce the population's exposure to known sensitizers. To determine whether these legislations have been effective, we reviewed several studies examining trends in patch test reactivity before and after implementation of these legislations. Common sensitizers studied include nickel, gluceryl monothioglycolate fragrances, chromate, and thiuram. Overall, the evidence suggests a decreasing trend of ACD with appropriate formulation changes, however some of the data may be confounded by biases, and additionally, exposure to the sensitizer may still exist via non-compliance to regulations by small manufacturers. In the future population based studies should be conducted to more accurately assess trends in ACD.

Allergens↗

A rapid, accurate, and facile method to quantify the antioxidative capacity of topical formulations.

BACKGROUND/AIMS: Various methodologies have been developed to quantify antioxidant activity. A simple, rapid and accurate method is demanded. This study examined the antioxidative status of a pH balanced vitamin E containing formulation versus its vehicle control utilizing a photochemiluminescence device. METHODS/RESULTS: A pH balanced 5% Vitamin E containing formulation and its vehicle control were tested. The quantity of antioxidant capacity for the pH balanced vitamin E formulation and its vehicle control were 2.28 +/- 0.05 and 0.16 +/- 0.03, respectively. The pH balanced vitamin E formulation showed a significant (P < 0.001) higher antioxidant capacity compared to its vehicle control. CONCLUSIONS: This method not only provides quantitative data, but also is rapid, accurate, and facile in performance. The in vitro data obtained in this study require validation by in vivo studies to properly place them in context to alternate methods.

Administration, Topical↗

Water, salts and skin barrier of normal skin.

BACKGROUND: We recently reported that open application of seawater for 20 min ameliorated experimental irritant contact dermatitis induced by sodium lauryl sulphate (SLS) cumulative irritation. The efficacy was overall contributed by 500 mm of sodium chloride (NaCI) and 10 mm of potassium chloride (KCl), which are consistent with the each concentration in seawater. Although the usefulness of mineral water with 500 mm NaCl and 10 mm KCl to treat atopic dermatitis (AD) or irritated skin was considered, seawater or its components would induce a feel of stinging in patients with AD. Furthermore, 20 min application was thought to be too long to use everyday as a treatment. OBJECTIVE: We report the effects of 3 types of mineral water with NaCl and KCl to check the further efficacy with lesser stinging by 2 min application. RESULTS: A mineral water with 250 mm NaCl and 50 mm KCl was the most effective water to prevent disruption of skin barrier and stratum corneum water content after cumulating irritation by SLS. Moreover, improvement of skin dryness and pruritus were shown 2 weeks after the application of the mineral water to a 6-year-old boy with atopic dermatitis. CONCLUSION: Our results suggested the possible usefulness of the mineral water with 250 mm NaCl and 50 mm KCl as the therapy of atopic dermatitis of other chronic dermatitis. Although the mineral water would not cure those skin diseases, it could be an adjunctive therapy. Further controlled clinical trials with evaluation by TEWL and capacitance are required to declare the efficacy of the mineral water in the treatment of patients with AD or other chronic dermatitis.

Adult↗

Coefficient of friction: tribological studies in man - an overview.

BACKGROUND/PURPOSE: Compared to other studies of skin, relatively few studies have focused on the friction of skin. This work reviews existing skin friction, emphasizing test apparatuses and parameters that have added to information regarding the friction coefficient. This review also outlines what factors are important to consider in future friction studies. METHODS: Past studies have utilized numerous designs for a test apparatus, including probe geometry and material, as well as various probe motions (rotational vs. linear). Most tests were performed in vivo; a few were performed in vitro and on porcine skin. RESULTS: Differences in probe material, geometry and smoothness affect friction coefficient measurements. An increase in skin hydration, either through water or through moisturizer application, increases its friction coefficient; a decrease in skin hydration, either through clinical dermatitis or through alcohol addition, decreases the coefficient. Differences are present between anatomical sites. Conflicting results are found regarding age and no differences are apparent as a result of gender or race. CONCLUSION: Skin friction appears to be dependent on several factors - such as age, anatomical site and skin hydration. The choice of the probe and the test apparatus also influence the measurement.

Body Water↗

Friction coefficient of skin in real-time.

BACKGROUND/PURPOSE: Friction studies are useful in quantitatively investigating the skin surface. Previous studies utilized different apparatuses and materials for these investigations but there was no real-time test parameter control or monitoring. Our studies incorporated the commercially available UMT Series Micro-Tribometer, a tribology instrument that permits real-time monitoring and calculation of the important parameters in friction studies, increasing the accuracy over previous tribology and friction measurement devices used on skin. METHODS: Our friction tests were performed on four healthy volunteers and on abdominal skin samples. A stainless steel ball was pressed on to the skin with at a pre-set load and then moved across the skin at a constant velocity of 5 mm/min. The UMT continuously monitored the friction force of the skin and the normal force of the ball to calculate the friction coefficient in real-time. Tests investigated the applicability of Amonton's law, the impact of increased and decreased hydration, and the effect of the application of moisturizers. RESULTS: The friction coefficient depends on the normal load applied, and Amonton's law does not provide an accurate description for the skin surface. Application of water to the skin increased the friction coefficient and application of isopropyl alcohol decreased it. Fast acting moisturizers immediately increased the friction coefficient, but did not have the prolonged effect of the slow, long lasting moisturizers. CONCLUSION: The UMT is capable of making real-time measurements on the skin and can be used as an effective tool to study friction properties. Results from the UMT measurements agree closely with theory regarding the skin surface.

2-Propanol↗

Enhanced human nail drug delivery: nail inner drug content assayed by new unique method.

The purpose of this study was to develop an assay method of the human inner nail plate and to compare nail drug penetration by a penetrating enhancing formulation (the test carrier formulation). The test carrier and saline formulations were tested using radiolabeled urea, ketoconazole, and salicylic acid. After twice dosing daily for 7 days on human nail plates, the under inner section of the nail plate was assayed for absorbed drug content using a unique drilling/removal system. Results show that the weight-normalized radioactivity contents of three chemicals in the inner intermediate nail plate center in the carrier formulation were two fold higher than those from saline (p < 0.05). Total radioactivity recovery of dosed [(14)C]-salicylic acid was 89 +/- 2% in the carrier formulation and 88 +/- 5% in saline. In saline formulation, salicylic acid showed greater binding to the outer nail, making it less bioavailable for the inner nail area. This didn't occur with carrier formulation. In conclusion, topical treatment of nail diseases such as onychomycosis is not yet sufficiently effective, likely because of minimal drug penetration into the inner nail plate where the disease perpetuates. The assay system has the unique characteristic of being able to assay the inner part of the nail where the disease resides.

Absorption↗

Polymers effect on estradiol partition coefficient between powdered human stratum corneum and water.

Macromolecules have gained interest as drug entities unto themselves and as transport facilitators to alter initial phases of percutaneous absorption. Two macromolecular polymers (MW 2081 and 2565) were designed to hold cosmetics and drugs to the skin surface by altering initial chemical and skin partitioning. The effect of these polymers on the partition coefficient (PC) of estradiol with powdered human stratum corneum (PHSC) and water was determined. There was no statistically significant effect on the PC when the concentration of estradiol was increased 100-fold (0.028-2.8 microg/mL), when the incubation time was increased from 0 to 24 h, or when PHSC was delipidized. The addition of a liphophilic polymer had no effect on the PC; however, the hydrophilic polymer showed a significant polymer concentration-dependent increase (p < 0.01) in log PC for estradiol concentrations. Thus, a macromolecular chemical has the potential to alter the partitioning of chemical into the outer layers of skin, the first step in percutaneous absorption.

Drug Carriers↗

Comparison of skin distribution of hydrolytic activity for bioconversion of beta-estradiol 17-acetate between man and several animals in vitro.

We have investigated the distribution of hydrolytic enzymes which metabolize beta-estradiol 17-acetate (EA) to beta-estradiol (E) in man and animal skins in vitro. The distribution of hydrolytic enzymes in human cadaver, hairless dog, rat and hairless mouse skin, was investigated by a skin-slicing technique. We performed histological studies with hematoxylin and eosin stain. The highest amount of metabolite (E) appeared in the layers of 80-120 microm from the skin surface, the basement layer in human skin, while the amount of metabolite was distributed evenly in the hairless dog skin from 0 to 180 microm. In the rat and hairless mouse skin, on the other hand, peak levels of metabolite were observed in the basement layer of dermis, the surrounding area of the cutaneous plexus. The total metabolic activities in the area of epidermis in human, hairless dog and hairless mouse skin were 2.59, 8.03 and 0.33 x 10(-4) microg/ml/microm/h, respectively. The values in whole skin layers in the hairless dog and hairless mouse skin were 3.35 and 1.85 x 10(-4)microg/ml/microm/h, respectively. EA transported across the human and hairless dog skin can be effectively metabolized before entering the capillary. Among animal models investigated, hairless dog skin might be the most facile model in simulating drug metabolism for human skin under the clinical (in vivo) conditions. Hairless mouse skin, on the other hand, was also an excellent model in excised human skin under in vitro conditions.

Adult↗

Irritant contact dermatitis: is there an immunologic component?

Irritant contact dermatitis (ICD) describes a multifactorial disease resulting from exposure to occupational irritants. Though often characterized as a localized reaction, there are at least 10 forms of ICD, several of which possess systemic involvement. The exact mode of irritant action in ICD is not completely understood, but recent literature suggests that an immunologic-like component may be present. The correlation between the morphology, clinical manifestations and chemokines involved in allergic contact dermatitis and irritant contact dermatitis will be discussed and studies indicating an irritant "immunologic-like" response will be reviewed and analyzed.

Animals↗

Dosage considerations in patch testing with liquid allergens.

This study examines reproducibility of water and ethanol drop volumes from plastic squeeze dropper bottles, examines the difference in drop volumes between commonly used liquid patch test solutions, and evaluates the volumes of water and ethanol needed to saturate Finn and IQ Chamber filter papers. 2 plastic squeeze dropper bottles recommended for use in patch testing have poor reproducibility compared to other bottles tested. 3 aqueous allergens tested (formaldehyde 1%, methylchloroisothiazolinone/methylisothiazolinone 0.01%, and dimethylol dihydroxyethyleneurea 4.5%) have drop volumes equivalent to water. Smaller drop volumes are produced by ethanol, hydrocortisone butyrate 1% in ethanol, cocamidopropyl betaine 1% a.q., and propylene glycol 30% a.q. Filter paper saturation volumes using distilled water are 16-19 micro L in standard Finn Chambers and 29-35 micro L in IQ Chambers. Ethanol saturation volumes are slightly lower. Previously recommended volumes of application for aqueous allergens of 15 micro L for standard Finn Chambers and 25 micro L for IQ Chambers (slightly below the filter paper saturation points) are appropriate. Selection of dropper bottles should consider drop volume reproducibility, differing drop volumes for different allergens, and the patch test chamber system being used.

Allergens↗

Occlusion vs. skin barrier function.

BACKGROUND/AIMS: Skin occlusion may increase percutaneous absorption of applied chemicals, with some exceptions. It also obstructs the normal ventilation of the skin surface and increases stratum corneum hydration and hence compromises skin barrier function. METHODS/RESULTS: This review focuses the effects of occlusion on skin barrier function, in particularly, as defined with objective skin bioengineering technology. CONCLUSIONS: The effects of occlusion on skin barrier function have been defined with various techniques. Optimal hydrocolloid materials can absorb excess water and reduce the unfavourable effects of occlusion.

Administration, Cutaneous↗

Hydration vs. skin permeability to nicotinates in man.

BACKGROUND/AIMS: Prolonged skin occlusion increases stratum corneum water content and often increases skin permeability and irritant dermatitis. As skin wetness from wearing diapers is considered an important factor favouring the onset of diaper dermatitis, optimal diapering might decrease skin hyperhydration and dermatitis. Our aim is to define the quantitative relationship between nicotinate ester (a model penetrant) skin permeability and hydration, as measured by water evaporation rate (WER), decay curves (at individual time points) and WER-area under the curve (WER-AUC); and also to determine the level of skin hydration and skin permeability to nicotinates following a diapering simulation. METHODS/RESULTS: Nine healthy Caucasian adult women were enrolled after a prescreening procedure (time to peak redness response to nicotinate); each received three wet occlusive patches for different exposure times (10 min, 30 min, and 3h) and two wet model diapers (3 and 8 h). Prior to patching or diapering of forearms, basal values of WER, skin blood flow volume (BFV), capacitance (Cap) and redness (a*) were measured on premarked sites (a, b, c and d). Immediately, following occlusive patch or diaper removal, 20 microL of each nicotinate (methyl and hexyl nicotinate) was applied to its respective site (a or b). The WER and Cap readings were recorded at designated sites (c and d) with the following intervals after nicotinate applications: 0, 5,10,15 and 20 min. The a* and BFV measurements were made on each nicotinate challenged site (a and b) with the following intervals after nicotinate applications: 5, 10, 15, 20, 30, 40, and 60 min. RESULTS: WER-AUC and thus, skin hyperhydration, increased with occlusive patch and diaper exposure time, but there was no statistical difference between 3 and 8h diaper sites. All patched sites had significantly (P<0.05) increased hydration in comparison to control sites (undiapered or unpatched skin). Cap increased with occlusion time with patches, but not with diapers. The degree and time-course of redness from nicotinates did not vary with extent of skin hydration, but was significantly increased compared to non-hydrated skin. BFV-AUC did not show a significant increase between diapers at 3 and 8h sites; the BFV-AUC values varied on the patched sites, but some were significantly (P<0.05) higher than control site. CONCLUSION: Wet patches and diapers increased skin hyperhydration proportional to exposure time. Permeation of nicotinates was increased for hydrated skin vs. control, even after only 10 min of patch exposure. For these model permeants, we found no evidence of increased permeation rates with increased hyperhydration, once a relatively low threshold of hyperhydration was achieved (e.g. that reached after a 10 min wet patch). The data showed no meaningful differences in permeation following either diapering simulation and also suggested that the WER-AUC method was superior to capacitance for measuring the absolute extent of hyperhydration. We believe this is a suitable model for evaluating the quality of diaper product performance, as well as in pharmacologic assays of occlusive therapy.

Adult↗

Relationship of occupation to contact dermatitis: evaluation in patients tested from 1998 to 2000.

BACKGROUND: Both irritant and allergic contact dermatitis can be influenced by occupational and nonoccupational environmental exposures. OBJECTIVE: The aim of this study is to compare the occupations and allergens of occupational contact dermatitis cases with nonoccupational contact dermatitis cases. METHODS: Diagnostic patch testing was conducted with the 50 screening allergens of the North American Contact Dermatitis Group and occupational coding by the Surveillance Branch of the National Institute of Occupational Safety and Health. RESULTS: Of the 5,839 patients patch tested for contact dermatitis, 1,097 (19%) were deemed to be occupationally related. Of the occupational cases, 60% were of allergic and 32% were of irritant origin. The hands were the primary body part affected in 64% of allergic occupational cases and 80% of irritant occupational cases. Epoxy resin was the only allergen tested that was associated more with an occupational exposure than nonoccupational exposure. The allergens encountered most frequently in the occupational cases were carba mix, thiuram mix, epoxy resin, formaldehyde, and nickel. The medical field is overrepresented in the data compared with other occupations. CONCLUSIONS: Occupational contact dermatitis frequently was found to be multifactorial and associated with several specific allergens and occupations.

Adult↗

Allergic contact dermatitis to detergents: a multicenter study to assess prevalence.

BACKGROUND: Allergic contact dermatitis (ACD) to optical brighteners and enzymes in laundry detergents was the focus of numerous reports in the early 1970s. Subsequently, there has been little published on the incidence of allergic reactions to chemicals in laundry detergents. Nonetheless, consumers and physicians continue to ascribe allergic contact reactions to laundry detergents. OBJECTIVE: This article reports the findings of a multicenter study on the prevalence of patch test reactions to a liquid and a granular laundry detergent provided by Procter & Gamble Company (Cincinnati, Ohio). METHODS: Patients referred to members of the North American Contact Dermatitis Group for evaluation of potential ACD were invited to participate in the study, which involved the placement of 2 patch tests (a 0.1% aqueous dilution of a granular laundry detergent and a 0.1% aqueous dilution of a liquid laundry detergent). Whether the patients had atopic dermatitis and whether they or their physicians felt that their dermatitis might be related to laundry detergents were noted. Reactions to the laundry detergents were correlated with allergic reactions to the following screening chemicals: fragrances, nickel, and potassium dichromate. Patients who experienced a reaction to at least one of the laundry detergents could enter phase II of the study, which involved testing to varying dilutions of the laundry detergents, to 0.1% sodium lauryl sulfate (as an irritant control), and to laundered patches of cotton. Patients positive in phase II could enter phase III, which involved wearing a garment laundered with the detergent. Phases II and III were double blinded. RESULTS: Of the 3120 patients seen by members of the North American Contact Dermatitis Group during the 2 years of this study, 738 patients volunteered to enroll. Enrollment was not statistically randomized. Of these 738, 5 (0.7%) had positive patch test reactions to granular laundry detergent (0.1%, aqueous); 3 of these 5 also had positive reactions to the liquid laundry detergent (0.1%, aqueous). In 4 of the 5 patients, the reaction to detergent was thought to have present relevance to their dermatitis; in 1 of the 5, the reaction was deemed to have past relevance. One of these 5 patients had allergy to fragrances. None of the patients was positive to nickel or chromate. Two of the 5 entered phases II and III. Of these 2 patients, 1 had essentially negative repeat dilutional patch testing and "use testing" suggesting that the earlier reaction patterns may have been irritant. The remaining patient had positive dilutional reactions to both the liquid and granular laundry detergent; however, she also had a positive reaction to sodium lauryl sulfate and to a swatch from a T-shirt laundered without detergent. Upon "use testing" in phase III, this latter patient experienced diffuse dermatitis under both the half of the T-shirt laundered with detergent and that laundered without detergent. CONCLUSION: Laundry detergents appear to be a rare cause of ACD. Among 738 patients with dermatitis, 5 (0.7%) reacted to a 0.1% aqueous dilution of a laundry detergent. Only 2 of these 5 patients could be evaluated in greater detail to differentiate allergic from irritant patch test reactions to detergents. Upon further testing in 2 patients, the reaction in 1 of 2 could not be reduplicated and the reaction in the other was invoked both by the detergents and the controls. Thus, whether our study patients were truly allergic and, if so, what the allergenic material(s) in detergents might be, remains unknown. Therefore the reported incidence rate for detergent-induced allergy of 0.7% in dermatitic patients may be too high, possibly because of false-positive irritant reactions.

Adult↗

The effect of race and ethnicity on patch test results.

BACKGROUND: Allergic contact dermatitis is a condition that may be affected by differences in genetic and environmental factors. Race and ethnicity are possible examples of the former. OBJECTIVE: The objective of this study was to examine the differences in patch test results between white and black individuals tested by the members of the North American Contact Dermatitis Group from July 1, 1992, to June 30, 1998. METHODS: Patients evaluated in our patch test clinics were exposed to a standardized patch testing technique involving a standard series of 41 allergens in total. The standard series we used varied over the 6 years of the study in 2-year cycles. The series was the same at all centers during each of these 2-year cycles: 1992-94, 1994-96, and 1996-98. Over a 6-year period, our group tested 9624 patients. Of those individuals, 8610 (89.5%) were white and 1014 (10.5%) were black. RESULTS: Allergic contact dermatitis and irritant contact dermatitis were the final diagnoses assigned by the investigators to individuals of the 2 races: 49% and 16%, respectively, for the white patients and 46% and 15%, respectively, for the black patients. In at least one of the three 2-year periods, testing in white patients revealed higher rates of sensitization to formaldehyde, glutaraldehyde, and a number of the formaldehyde-releasing preservatives, as well as lanolin, epoxy resin, thioureas, and balsam of Peru. Black patients exhibited higher rates of sensitization to para-phenylenediamine, cobalt chloride, thioureas, and p-tert-butylphenol formaldehyde resin in at least one of the 2-year periods. CONCLUSION: In this test population, we found no differences in the overall response rate to allergens. There were some differences between white and black patients in their response to specific allergens. These differences, although possibly related to genetic factors based on race, are more likely related to differences in allergen exposure determined by ethnicity.

Allergens↗

PBPK modeling of the percutaneous absorption of perchloroethylene from a soil matrix in rats and humans.

Perchloroethylene (PCE) is a widely used volatile organic chemical. Exposures to PCE are primarily through inhalation and dermal contact. The dermal absorption of PCE from a soil matrix was compared in rats and humans using real-time MS/MS exhaled breath technology and physiologically based pharmacokinetic (PBPK) modeling. Studies with rats were performed to compare the effects of loading volume, concentration, and occlusion. In rats, the percutaneous permeability coefficient (K(P)) for PCE was 0.102 +/- 0.017, and was independent of loading volume, concentration, or occlusion. Exhaled breath concentrations peaked within 1 h in nonoccluded exposures, but were maintained over the 5 h exposure period when the system was occluded. Three human volunteers submerged a hand in a container of PCE-laden soil for 2 h and their exhaled breath was continually monitored during and for 2.5 h following exposure. The absorption and elimination kinetics of PCE were slower in these subjects than initially predicted based upon the PBPK model developed from rat dermal kinetic data. The resulting K(P) for humans was over 100-fold lower than for the rat utilizing a single, well-stirred dermal compartment. Therefore, two additional PBPK skin compartment models were evaluated: a parallel model to simulate follicular uptake and a layered model to portray a stratum corneum barrier. The parallel dual dermal compartment model was not capable of describing the exhaled breath kinetics, whereas the layered model substantially improved the fit of the model to the complex kinetics of dermal absorption through the hand. In real-world situations, percutaneous absorption of PCE is likely to be minimal.

Administration, Cutaneous↗