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At least 163 records · Page 9Linked to original sources

Application of the fiber-optic perfusion fluorometer to absorption and exsorption studies in hairless mouse skin.

This study was undertaken to test the fiber-optic perfusion fluorometer as a direct means of evaluating skin absorption and exsorption in hairless mice. Skin-barrier compromise was accomplished in the absorption experiments by application of dimethyl sulfoxide to the skin surface or by partial removal of the stratum corneum with sticky tape. Absorbed fluorescein was measured easily in unanesthetized control (skin-barrier intact) and experimental mice. Unabsorbed chemical did not fluoresce 15 minutes after application, although it was present on the surface of the skin as a dry powder. The time course of fluorescein elimination from the skin was related to a rapid phase (vascular removal) and a slow phase (reservoir entrapment). In the exsorption experiments the fluorescein was injected intraperitoneally. Back skin on the right side was swabbed with either dimethyl sulfoxide or 1% capsaicin in alcohol prior to the injections, and differences in skin fluorescence on the left (control) and right sides were recorded. One application of dimethyl sulfoxide or capsaicin increased the level of skin exsorption. Three applications of dimethyl sulfoxide almost doubled the amount of exsorbed dye, whereas three applications of the capsaicin inhibited the exsorption process. It was concluded that the fiber-optic perfusion fluorometer provides an excellent technique in support of other methods of investigating the skin.

Absorption↗

[Absorption of phenol from aqueous solution through the skin in rats].

The purpose of the investigation was to evaluate the skin absorption of phenol from aqueous solution in rats and the efficiency of two of my own protective creams devised for protection of skin exposed to aqueous solution of electrolytes. One of these creams was composed of hydrocarbons components, the other had in addition silicone oil and cetaceum. The creams were tested by the measurement of phenol diffusion in vitro and by the assessment of the dose of this compound absorbed through the skin of rats. Excretion of total phenol in urine was also measured. Absorption of phenol from aqueous solution was proportional to the concentration. Excretion of this compound in urine was correlated with the absorbed doses. The creams devised in our laboratory proved the reduction of phenol absorption through the skin by 36-44% when concentration of solution was 1000 mg%. The effectiveness of these creams was compared with the two brands available on the market. The two own preparations showed better protection than products of other manufactures.

Animals↗

Improvement of the experimental setup to assess cutaneous bioavailability on human skin models: dynamic protocol.

Human skin models, such as EpiDerm and Episkin, are not easily mounted into static or dynamic diffusion cells that are commonly used to perform bioavailability studies with human skin ex vivo. For various reasons, such as fragility, small sample size, and other morphological constraints, skin absorption studies with human skin models are often carried out on the delimited skin surface obtained by gluing a ring onto the reconstituted epidermis and manually exchanging the receptor solution. However, such an experimental setup is prone to artifacts. Discontinuous removal of the receptor fluid leads to alternating sink conditions, and an area of application smaller than the area in contact with the receptor fluid, as well as imperfect seal of the glued ring, may result in inaccurate penetration rates. Human skin models were shown to be relatively easily mounted into In-Line cells (PermeGear Inc.), vertical diffusion cells which appear to be appropriately designed for such a purpose. In-Line cells allowed accurate determination of solute penetration as well as automated sampling of receptor fluid. Excised human skin can be mounted into these cells as well, making it possible to compare penetration rates through different types of skin samples under identical conditions. Using mannitol as a reference compound, penetration profiles and epidermal distribution similar to those obtained with human skin ex vivo were obtained both with EpiDerm and Episkin. Under the present conditions, human skin models were more permeable to mannitol than excised human skin, which was only slightly permeable to mannitol. Due to these experimental innovations and to the good agreement with the absorption characteristics through human skin ex vivo, EpiDerm and Episkin seem to be promising human skin models for testing the cutaneous bioavailability of topical products in vitro.

Biological Availability↗

Absorption of topical tacrolimus (FK506) in vitro through human skin: comparison with cyclosporin A.

Cyclosporin A (CsA) is efficacious in many dermatoses as an oral but not as a topical form, while tacrolimus (FK506) has been shown to be effective in both forms. As inadequate skin absorption has been proposed as the reason for inefficacy of topical CsA, factors contributing to percutaneous absorption of FK506 and CsA were studied. Partitioning of FK506 and CsA between octanol and water, stratum corneum and water, and stratum corneum and isopropyl myristate was determined. Absorption of FK506 and CsA through dermatomed human cadaver skin was determined with in vitro flow-through cells. In partitioning experiments, CsA was more lipophilic than FK506. Both drugs were seen in comparable amounts in skin layers, but FK506 permeated the skin to a greater extent than CsA.

Administration, Topical↗

In vivo and in vitro percutaneous absorption and skin decontamination of arsenic from water and soil.

The objective was to determine the percutaneous absorption of arsenic-73 as H3ASO4 from water and soil. Soil (Yolo County 65-California-57-8) was passed through 10-, 20-, and 48-mesh sieves. Soil retained by 80 mesh was mixed with radioactive arsenic-73 at a low (trace) level of 0.0004 microgram/cm2 (micrograms arsenic per square centimeter skin surface area) and a higher dose of 0.6 micrograms/cm2. Water solutions of arsenic-73 at a low (trace) level of 0.000024 micrograms/cm2 and a higher dose of 2.1 micrograms/cm2 were prepared for comparative analysis. In vivo in Rhesus monkey a total of 80.1 +/- 6.7% (SD) intravenous arsenic-73 dose was recovered in urine over 7 days; the majority of the dose was excreted in the first day. With topical administration for 24 hr, absorption of the low dose from water was 6.4 +/- 3.9% and 2.0 +/- 1.2% from the high dose. In vitro percutaneous absorption of the low dose from water with human skin resulted in 24-hr receptor fluid (phosphate-buffered saline) accumulation of 0.93 +/- 1.1% dose and skin concentration (after washing) of 0.98 +/- 0.96%. Combining receptor fluid accumulation and skin concentration gave a combined amount of 1.9%, a value less than that in vivo (6.4%) in the Rhesus monkey. From soil, receptor fluid accumulation was 0.43 +/- 0.54% and skin concentration was 0.33 +/- 0.25%. Combining receptor fluid plus skin concentrations gave an absorption value of 0.8%, an amount less than that with in vivo absorption (4.5%) in the Rhesus. These absorption values did not match current EPA default assumptions.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Cutaneous↗

Developmental aspects of percutaneous caffeine absorption in premature infants.

Caffeine is commonly used in the treatment of apnea of prematurity. The skin of preterm infants varies considerably in its level of maturity. To understand skin absorption in low birthweight infants (less than 1500 gm) with gestational age between 26 and 34 weeks, a group of 56 preterm babies was studied after percutaneous application of 7.5 mg twice daily of caffeine for babies with birthweight less than 1000 gm and 10 mg twice daily for babies with birthweight more than 1000 gm. The reported technique is a useful alternative method of drug administration in premature babies. This study indicates an inverse relationship between gestational age and skin absorption contributing to a better understanding of skin barrier function in the newborn.

Administration, Cutaneous↗

Absorption of hexavalent chromium by skin in man.

Absorption by skin of hexavalent chromium from aqueous solutions of sodium chromate in man was investigated. It was found that the amount of chromium absorbed was related to the concentration of Cr6+ in solution and to time of exposure. For 0.01, 0.1, and 0.2 molar solutions of chromium, skin absorption rates during 1 h exposure were 1.1, 6.5, and 10.0 micrograms/cm2/h respectively.

Adult↗

Estimates of cancer risk from chloroform exposure during showering in Taiwan.

The purpose of this study was to compare the cancer risk with chloroform exposure during showering. The study concentrated on the three major metropolitan areas of Taiwan. Total exposure was measured based on a combination of ingestion, inhalation and skin absorption. A total of 137 tap water samples were taken from 26 locations within the Taipei (north), Taichung (central) and Kaohsiung (south) areas. Analysis of VOC compounds was performed according to the US EPA Method 524. Chloroform concentrations were highest in Kaohsiung (60.19 micrograms/l), followed by Taipei (18.83 micrograms/l) and Taichung (17.55 micrograms/l). Based on the two-resistance theory to volatilization in showers, when air flow rate is increased, chloroform concentrations in the air significantly decrease. A 10-min shower would result in chloroform exposure with a 3:4:3 ratio (ingestion, inhalation, skin absorption). However, that changes to 1:7:2 for a 20-min shower under the same conditions. The cancer risk was highest in Kaohsiung at 17.59 per million for a 10-min shower and 64.77 per million for a 20-min shower. The lowest cancer risk was found in Taichung at 4.99 and 11.50 per million for a 10- and 20-min shower, respectively. Although ingestion is commonly considered to be the primary source of exposure to chloroform from tap water, inhalation and skin absorption exposure concentrations were found to be even higher.

Administration, Inhalation↗

Percutaneous absorption and skin irritation of JP-8 (jet fuel).

JP-8 is the major jet fuel used by US Army and Air Force. The purpose of the present study was to investigate the percutaneous absorption of JP-8 across pig ear skin and human skin in vitro and to study the effect of JP-8 exposure on the skin barrier function and irritation in Yucatan minipigs. JP-8 spiked with 5.0 microCi of radiolabeled (14C) tridecane, nonane, naphthalene or toluene (selected components of JP-8) was used for the in vitro percutaneous absorption studies with excised pig ear skin and human skin. For in vivo studies, 250 microl of JP-8 or two of its components (toluene or nonane) was placed in a Hill top chamber(R) and affixed over the marked treatment area for 24 h. Transepidermal water loss (TEWL), skin capacitance (moisture content) and skin irritation (erythema and edema) were evaluated before treatment and at 1,2 and 24 h after removal of the patches. The components of JP-8 such as tridecane, nonane, naphthalene and toluene permeated significantly through pig ear skin and human skin and the permeation rates were found to be proportional to their composition in JP-8. The steady state flux values of tridecane across pig ear skin and human skin did not differ significantly (P>0.05). Though the steady state flux values of nonane, naphthalene and toluene were statistically different between porcine and human skin (P<0.01), the values were close considering the large variations usually observed in the percutaneous absorption studies. Application of toluene, nonane or JP-8 increased the TEWL, JP-8 being the highest (3.5 times at 24 h compared to baseline level). The skin moisture content decreased after the application of JP-8, though it was not significantly different (P>0.05) from the baseline level. JP-8 caused a moderate erythema and a moderate to severe edema. Though the edema decreased after 24 h, the degree of erythema remained about the same until 24 h. The skin irritation caused by JP-8 was greater than neat toluene or nonane. The TEWL data of toluene, nonane and JP-8 correlated well with the skin irritation data (erythema and edema). Exposure of JP-8, which contains hundreds of aliphatic and aromatic hydrocarbons, caused significant changes in the barrier function of the skin as indicated by an increase in TEWL and produced a significant erythema and edema in minipigs. Furthermore, the disruption of barrier function of skin, as indicated by increased TEWL after exposure to JP-8 might result in increased permeation of its own components and/or other chemicals exposed to skin. The present study provides further evidence that pig ear skin may be used as a model for predicting the rates of permeation of chemicals through human skin.

Administration, Cutaneous↗

Urinary excretion of acetylcyanamide in rat and human after oral and dermal application of hydrogen cyanamide (H2NCN).

The main urinary metabolite of hydrogen cyanamide (syn.: cyanamide) in rat and man is acetylcyanamide (syn.: N-acetylcyanamide). An analytical method was developed to determine acetylcyanamide in the urine with a limit of quantification of less than 10 micrograms/l (mean recovery 96.1% using spikes of 20 micrograms/l; relative standard deviation less than 4%). This methodology is based upon ion chromatography using column-switch techniques and UV detection. It could be demonstrated that in rats an average of 45.6% of oral applied cyanamide (10 mg/kg) was excreted in the urine as acetylcyanamide. In male human volunteers a mean of 40% of oral administered cyanamide (mean dose 0.25 mg/kg body weight) was excreted via the urine as acetylcyanamide. The same group of volunteers participated in a skin absorption study with dermal application of the above cyanamide dose onto a skin surface area of 32 cm2. Within an application period of 6 h an average cyanamide quantity of 2.3 mg was available for skin absorption. A mean portion of 7.7% of this quantity was found as acetylcyanamide in the urine of the participants. Findings from literature state that cyanamide is metabolized in vitro to cyanide. According to examinations performed in vivo, however, such a metabolic pathway seems to be irrelevant for man. In comparison with the control values there was no significant increase of both the cyanide concentrations in the blood and the thiocyanate concentrations in the urine of the above volunteers after the described oral cyanamide administration.

Administration, Oral↗

[Neonatal accidental burn by isopropyl alcohol].

Antiseptic solutions are commonly used for skin care but are not always safe. In preterm infants, application of antiseptic solutions can lead to serious burns. We report the case of a premature newborn who developed severe burns at 35 weeks post-conceptional age, after his mother used disposable antiseptic towels containing isopropyl alcohol for his skin care. Burns outcome led to diffuse skin burn and death of the baby. Several cases of isopropyl alcohol poisoning through skin absorption have been reported in neonate and infants. Because of its neonatal toxicity, isopropyl alcohol has been excluded from composition of antiseptic solutions commonly used in neonatology. However, isopropyl alcohol is still available in many housecleaning and cosmetic products, while its toxic effects in children are not clearly mentioned. A specific mention "toxic for infants and children" should appear on mass consumption products containing isopropyl alcohol. Moreover, health workers may individually inform parents about possible hazards of poisoning through skin absorption.

2-Propanol↗

Effect of enhancers and retarders on percutaneous absorption of flurbiprofen from hydrogels.

The effect of enhancers/retarders on the transdermal absorption of flurbiprofen from cellulose hydrogels was studied in vitro. The release rate of flurbiprofen and the viscosity of hydrogel matrices were also examined. The flux of flurbiprofen from cellulose hydrogels approximated that from aqueous buffers, whereas the skin reservoir of flurbiprofen was lower with hydrogels. Incorporation of the cosolvents, propylene glycol (PG) and ethanol, did not significantly increase skin absorption of flurbiprofen. Ethanol even reduced the skin reservoir of the drug. Oleic acid, an unsaturated fatty acid, produced the largest skin reservoir of the drug when incorporated into the hydrogels. D-Limonene, a cyclic monoterpene, showed the greatest ability to enhance the flux of flurbiprofen. However, phospholipids as retarders markedly reduced the skin absorption of flurbiprofen. The mechanisms by which enhancers/retarders govern flurbiprofen permeation were elucidated by in vitro permeation studies using various skin types (enhancers/retarders-pretreated skin, stratum corneum (SC)-stripped skin, and delipidized skin) and histological examination. The results suggest different mechanisms and skin structural modifications caused by different enhancers/retarders.

Administration, Cutaneous↗

Kinetics of finite dose absorption through skin 2: volatile compounds.

A diffusion model to account for the disposition of an arbitrary dose of a (potentially) volatile compound applied to skin from a volatile vehicle is presented. In its most general form, the model allows for variable diffusivity of the permeant in the stratum corneum (SC) and must be solved numerically. However, for permeants having a constant diffusivity, absorption, and evaporation is characterized in terms of four dimensionless parameters-a reduced time tau, a fractional deposition depth in the SC f, a ratio of membrane capacity for the permeant to the applied dose beta, and a ratio of evaporative mass transfer coefficient to diffusive permeability chi. An important combination of these parameters arises as the reduced dose M(r) = (fbeta)(-1). Two cases are distinguished. In Case 1, corresponding to M(r) < or = 1, the dose is less than that required to saturate the upper layers of the SC, and the shape of the absorption and evaporation profiles is independent of the dose. Analytical solutions to Case 1 may be derived for arbitrary initial distributions of the permeant; the solution for a square wave is presented. In Case 2, corresponding to M(r) > 1, absorption and evaporation approach steady-state values as the dose is increased. Numerical evaluations of this behavior are shown. Limiting behavior for the case of a highly volatile solvent applied to skin is discussed. A companion paper discusses the application of the model to the absorption and evaporation of benzyl alcohol from human skin in vitro.

Administration, Cutaneous↗

Predicted chemical warfare agent VX toxicity to uniformed soldier using parathion in vitro human skin exposure and absorption.

Chemical warfare agents (CWA) are easily and inexpensively produced and are a significant threat to military forces and the public. Most well-known CWAs are organophosphorus compounds, a number or which are used as pesticides, including parathion. This study determined the in vitro percutaneous absorption of parathion as a CWA simulant through naked human skin and uniformed skin (dry and sweated). Parathion percentage dose absorbed through naked skin (1.78 +/- 0. 41) was greater than dry uniformed skin (0.29 +/- 0.17; p = 0.000) and sweated uniformed skin (0.65 +/- 0.16; p = 0.000). Sweated and dry uniformed skin absorption were also different (p = 0.007). These relative dry and sweated uniformed skin absorptions were then applied to VX skin permeability for naked skin (head, neck, arms, and hands) and the remaining uniformed skin over the various regions of the human body. Risk assessment shows VX 50% lethality within the first hour for a soldier wearing a sweated uniform. By 8 h postexposure to naked skin plus trunk area predicted lethality for both dry and sweated uniform, and, at 96 h postexposure, all body regions individually exposed would produce lethality. Military uniform and public clothing provide some immediate protection but absorption through cloth and skin does occur. Immediate safety response to skin and clothing is required.

Administration, Cutaneous↗

Water-activated, pH-controlled patch in transdermal administration of timolol. II. Drug absorption and skin irritation.

The feasibility of the water-activated, pH-controlled silicone reservoir devices for transdermal administration was investigated using timolol maleate as a model drug. Timolol patches were applied to the arm of 12 volunteers for 81 h, two patches per subject. Timolol absorption from patches was compared to that from a peroral timolol tablet formulation (Blocanol((R)) 10 mg). Furthermore, in vivo plasma levels of timolol were compared with those predicted by kinetic simulations. Skin irritation induced by timolol patches was assessed by visual scoring and color reflectance measurements. With water-activated, pH-controlled patches both steady-state concentrations of timolol in plasma and its duration could be controlled. However, a considerable, inter-individual variability in the transdermal absorption of timolol was observed. This is due to the high fractional skin control in timolol delivery. Timolol patches were well tolerated by subjects. Skin irritation induced by the combination of timolol with long-term occlusion was mild, and after removal of the patches, skin changes were practically reversed in 24 h. Simulation model was useful in prediction of timolol levels in plasma after transdermal administration.

Administration, Cutaneous↗

Inter- and intralaboratory variation of in vitro diffusion cell measurements: an international multicenter study using quasi-standardized methods and materials.

In vitro measurements of skin absorption are an increasingly important aspect of regulatory studies, product support claims, and formulation screening. However, such measurements are significantly affected by skin variability. The purpose of this study was to determine inter- and intralaboratory variation in diffusion cell measurements caused by factors other than skin. This was attained through the use of an artificial (silicone rubber) rate-limiting membrane and the provision of materials including a standard penetrant, methyl paraben (MP), and a minimally prescriptive protocol to each of the 18 participating laboratories. "Standardized" calculations of MP flux were determined from the data submitted by each laboratory by applying a predefined mathematical model. This was deemed necessary to eliminate any interlaboratory variation caused by different methods of flux calculations. Average fluxes of MP calculated and reported by each laboratory (60 +/- 27 microg cm(-2) h(-1), n = 25, range 27-101) were in agreement with the standardized calculations of MP flux (60 +/- 21 microg cm(-2) h(-1), range 19-120). The coefficient of variation between laboratories was approximately 35% and was manifest as a fourfold difference between the lowest and highest average flux values and a sixfold difference between the lowest and highest individual flux values. Intralaboratory variation was lower, averaging 10% for five individuals using the same equipment within a single laboratory. Further studies should be performed to clarify the exact components responsible for nonskin-related variability in diffusion cell measurements. It is clear that further developments of in vitro methodologies for measuring skin absorption are required.

Clinical Laboratory Techniques↗