PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “Skin Absorption”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 271 records · Page 15Linked to original sources

Role of transepidermal and transfollicular routes in percutaneous absorption of steroids: in vitro studies on human skin.

Percutaneous absorption theoretically comprises two components: the transepidermal and the transfollicular routes. The aim of the present work was to confirm this hypothesis in the human skin by comparing the in vitro percutaneous absorption of four steroids through scar skin without hair follicles and sebaceous glands and through normal adjacent skin from abdominal or mammary plasties. In all cases, the absorption of the four steroids was significantly higher in normal skin than in scar skin. The cumulative percentages of progesterone and testosterone after 8 h of application were, respectively, 3.1- and 2.4-fold higher in normal skin than in scar skin. After 24 h of application, the cumulative percentages of estradiol and hydrocortisone were 1.7- and 2.4-fold higher in normal skin than in scar skin. At the end of the experiments, the quantities of drugs remaining in the skin after 8 or 24 h of application were the same in normal skin and in scar skin except for progesterone for which they were 2-fold greater in normal than in scar skin. In each case, a histological characterization of the scar skin was made in comparison with the normal adjacent skin. The main modifications observed on scar skin were the following: absence of hair follicles and sebaceous glands, thinning of the collagenous fibers with parallel orientation to the dermoepidermal junction and decrease in the number or disappearance of the elastic fibers. These experiments confirmed that human skin appendages, hair follicles and sebaceous glands, constitute a route of penetration for steroids and thus probably for other chemicals of similar molecular weight and properties.

Adult↗

Transdermal delivery of mixnoxidil with block copolymer nanoparticles.

We evaluated the effect of hydrodynamic size of self-assembled nanoparticles on skin penetration of minoxidil in vitro and in vivo. Self-assembled 40- and 130-nm nanoparticles, both containing minoxidil, were prepared by solvent evaporation of poly(-caprolactone)-block-poly(ethyleneglycol) and were applied onto the skin of both hairy and hairless guinea pigs in the Franz diffusion cell. In hairy guinea pig skin, the permeation of the minoxidil that incorporated in 40-nm nanoparticles was 1.5-fold higher in the epidermal layer and 1.7-fold higher in the receptor solution than that of 130-nm nanoparticles. Nanoparticle size dependence on the permeation behavior of minoxidil was not observed for hairless guinea pig skin in either the epidermal layer or the receptor solution. Phospholipid liposomes and ethanol-water admixture, on the other hand, containing the same amount of minoxidil did not show differences in the amount of permeation irrespective of the existence of hair follicles. Confocal microscopy coupled with in vivo and in vitro skin permeation results demonstrated that nanoparticles containing solutes penetrated mainly via shunt routes like hair follicles, resulting in skin absorption of solutes.

Administration, Cutaneous↗

In vitro and in vivo evaluation of caffeic and ferulic acids as topical photoprotective agents.

Topically-applied antioxidant drugs represent a successful strategy for protecting the skin against UV-mediated oxidative damage. However, they can afford to the skin a satisfactory photoprotection only if able to permeate through the stratum corneum and thus to reach deeper cutaneous layers. Caffeic and ferulic acids, dissolved in saturated aqueous solutions at pH 3 or 7.2, have been tested for their capability to permeate through excised human skin mounted in Franz cells. At both pH values, ferulic and, at a lower degree, caffeic acids appeared able to permeate through the stratum corneum. The known higher lipophilicity of ferulic acid may explain the fact that it permeates through the stratum corneum better than caffeic acid. However, vehicle pH values proved to have no influence on biophenol skin permeation profile; this observed lack of pH effect may reflect the drug higher concentration attainable in saturated solutions at high pH. On the basis of the findings obtained in these in vitro experiments, we designed the schedule of a series of in vivo experiments, carried out to evaluate the ability of caffeic and ferulic acids to reduce, in healthy human volunteers, UVB-induced skin erythema, monitored by means of reflectance spectrophotometry. Caffeic and ferulic acids, dissolved in saturated aqueous solution pH 7.2, proved to afford a significant protection to the skin against UVB-induced erythema. To conclude, we have confirmed, by means of in vitro and in vivo experiments, that caffeic and ferulic acids may be successfully employed as topical protective agents against UV radiation-induced skin damage; however their skin absorption is not influenced by the pH of the formulation.

Administration, Topical↗

Applications of liquid chromatography-mass spectrometry in metabolic studies of explosives.

Liquid chromatography-mass spectrometry was used for the detection and identification of metabolites of 2,4,6-trinitrotoluene (TNT) in urine and blood. The metabolites were found in the urine of rats and in the blood of rabbits fed with TNT, in the urine of rats exposed to TNT by skin absorption and in the urine of TNT munition workers. The detected metabolites, formed by reduction processes, included 2-amino-4,6-dinitrotoluene, 4-amino-2,6-dinitrotoluene, 2,4-diamino-6-nitrotoluene and 2,6-diamino-4-nitrotoluene, in addition to untransformed TNT.

Animals↗

Analysis, interpretation, and extrapolation of dermal permeation data using diffusion-based mathematical models.

New dermal penetration data have been measured in both "infinite" and finite dose experiments on a range of compounds of varying lipophilicities. The data are analyzed, using parameter fitting, to determine the values of parameters governing the overall skin absorption processes. Two one-dimensional diffusion models are used. The first is novel, and well suited to the modeling of dermal uptake in occupational exposure scenarios. The second is an implementation of a model taken from the literature. The models are compared in a variety of exposure scenarios, and exhibit good mutual agreement. Both successfully reproduce expected features of the absorption process. Penetration parameters are determined by analyzing both infinite and finite dose data. Prediction of dermal absorption with finite dose scenarios is carried out and compared with experimental data obtained under these conditions. Parameters determined may also have an important role in improving the reliability of predictive QSARs used to estimate the extent of penetration of untested molecules.

Administration, Cutaneous↗

Fatal systemic poisoning after skin exposure to monochloroacetic acid.

Little information is available on the toxicity of monochloroacetic acid. We report the case of a 38 year-old man who was splashed with an 80% monochloroacetic acid solution on 25-30% of his body surface. In addition to epidermal and superficial dermal burns, features of systemic poisoning occurred within a few hours including disorientation, agitation, cardiac failure and coma. He later developed severe metabolic acidosis, rhabdomyolysis, renal insufficiency and cerebral edema, and died due to uncal herniation on d 8. The 4 h post exposure plasma monochloroacetic acid concentration was 33 mg/L confirming skin absorption. In addition to its corrosive action, monochloroacetic acid probably blocks the tricarboxylic acid cycle (Kreb's cycle) and may also react with sulfhydryl groups in enzymes, causing severe tissue damage in energy-rich organs.

Accidents↗

Erbium:YAG laser-mediated oligonucleotide and DNA delivery via the skin: an animal study.

Topical delivery of antisense oligonucleotides (ASOs) and DNA is attractive for treatment of skin disorders. However, this delivery method is limited by the low permeability of the stratum corneum (SC). The objective of this study was to enhance and optimize the skin absorption of gene-based drugs by an erbium:yttrium-aluminum-garnet (Er:YAG) laser. The animal model utilized nude mice. In the in vitro permeation study, the Er:YAG laser treatment produced a 3-30-fold increase in ASO permeation which was dependent on the laser fluence and ASO molecular mass used. The fluorescence microscopic images showed a more-significant localization of a 15-mer ASO in the epidermis and hair follicles after laser application as compared with the control. The expressions of reporter genes coding for beta-galactosidase and green fluorescent protein (GFP) in skin were assessed by X-gal staining and confocal laser scanning microscopy. The SC ablation effect and photomechanical waves produced by the Er:YAG laser resulted in DNA expression being extensively distributed from the epidermis to the subcutis. The GFP expression in 1.4 J/cm2-treated skin was 160-fold higher than that in intact skin. This non-invasive, well-controlled technique of using an Er:YAG laser for gene therapy provides an efficient strategy to deliver ASOs and DNA via the skin.

Administration, Topical↗

[The toxicity of N,N-dimethylformamide (DMF)].

Industrial use of N, N-dimethylformamide (DMF) is increasing in recent years. The toxic properties of this substance are reviewed from the standpoint of industrial hygiene. Hepatotoxicity has been emphasized by many authors. Care should be taken against the skin absorption of DMF. N-methylformamide (MF) was identified as the major urinary metabolite of DMF. Measurements of MF in urine have been found effective as a means of biological monitoring of DMF exposure.

Abnormalities, Drug-Induced↗

Toxicological evaluations of some brominated biphenyls.

Extensive toxicological studies were carried out to define the probable hazard of octabromobiphenyl (OBB) to workers, users, and the environment. OBB had low acute toxicity in mammals and birds by various routes of administration. It was essentially non-irritating to rabbit eyes, non-irritating to human skin and caused only mild skin irritation and no sensitization in the guinea pig. OBB caused equivocal effects in the rat fetus. OBB was stored in the body fat of rats and caused liver enlargement at high single doses or low repeated doses. The studies indicate probable low safety factors in application and use and probable bioaccumulation. Hexabromobiphenyl (HBB) was more acutely toxic than OBB by skin absorption in the rabbit and caused liver enlargement at lower single doses.

Abnormalities, Drug-Induced↗

Iodine supplementation in children receiving long-term parenteral nutrition.

In 18 children receiving long-term total parenteral nutrition (TPN) without iodide supplements, thyroid function test results were normal but serum iodide levels were greater than in control subjects (p less than 0.01). Iodine contamination of TPN solutions and fat emulsions accounted for only half of the recommended parenteral intake. Skin absorption of topical iodinated disinfectant may explain the adequate, if not excessive, iodine intake. We conclude that iodine is an unnecessary supplement in TPN solutions.

Adolescent↗

Urinary 1-hydroxypyrene as biomarker of exposure to polycyclic aromatic hydrocarbons in workers in petrochemical industries: baseline values and dermal uptake.

The suitability of urinary 1-hydroxypyrene as a biomarker for the assessment of exposure to polycyclic aromatic hydrocarbons (PAH) in petrochemical industries was evaluated in 562 workers involved in various operations in petrochemical industries. The median 1-hydroxypyrene concentration in 121 of these workers (both smokers and non-smokers) who had had no recent occupational exposure to PAH was 0.11 mumol/mol creatinine. The upper limit of the 95% confidence interval was 0.51 mumol/mol creatinine. During activities with a low potential exposure to PAH, such as loading bitumen and the handling of clarified slurry oils and furfural extracts, 1-hydroxypyrene concentrations were only marginally increased compared with the values measured in the 121 workers with no recent occupational exposure to PAH. Despite the substantially higher potential exposure to PAH during clean-out operations of various oil refinery installations, the concentrations of 1-hydroxypyrene in the workers involved were in the same range. This suggests that personal protection equipment was generally adequate to prevent excessive exposure. However, in workers digging PAH-contaminated soil and workers engaged in the production of needle coke from ethylene cracker residue, significantly increased urinary 1-hydroxypyrene concentrations were measured. A major decrease in urinary 1-hydroxypyrene following the application of dermal protective equipment in the ground workers suggested that skin absorption plays a major role in occupational exposure to PAH. The excretion of 1-hydroxypyrene by the workers of the needle coke plant was investigated in relation to potential determinants of exposure to PAH. It was indeed found that not only inhalatory but also dermal exposure was a significant determinant of occupational exposure to PAH.

Air Pollutants, Occupational↗

Metabolic conversion of cyoctol during skin passage in humans.

Upon application of 14C-labeled cyoctol to the forearm of healthy volunteers, no parent cyoctol was detectable in ipsilateral blood plasma. The 14C activity was largely accounted for by a component with higher lipophilicity than the parent compound, as justified from their HPLC retention. Thus, this study suggests that human skin is capable of nearly complete cutaneous first-pass metabolism, resulting in negligible systemic availability of cyoctol. In a comparable experiment, rabbits were also able to convert cyoctol during skin absorption to a more lipophilic metabolite, which was identified as the palmitoleic acid ester of O-demethylated cyoctol by GC/MS. However, chromatographic evidence indicates that the human ipsilateral metabolite differs from the rabbit cyoctol metabolite.

Androgen Antagonists↗

Urinary 2-methoxy acetic acid accumulation in response to 2-methoxy ethanol exposure.

Urinary 2-methoxy acetic acid reportedly has a long half-life (77.1 hr) in humans. The authors studied urinary 2-methoxy acetic acid in a group of 18 workers exposed to 2-methoxy ethanol from Monday to Saturday following a 7-d cease in production. The weekly time-weighted average exposure concentration of 2-methoxy ethanol was 4.5 ppm. The urinary 2-methoxy acetic acid of exposed workers was increased significantly, from 18.5 microg/ml (10.6 mg/gm creatinine) on Monday (prior to work) to 48.4 microg/ml (46.5 mg/gm creatinine) on Friday (after work), to 51.2 microg/ml (45.6 mg/gm creatinine) on Saturday after work. These levels occurred, despite that fact that the daily mean time-weighted average 2-methoxy ethanol exposures were very consistent and were close to the current Taiwan Permissible Exposure Limit of 5 ppm. These urinary 2-methoxy acetic acid levels were much higher than levels that occur with inhalation only, and they demonstrate that skin absorption is a significant contributor to 2-methoxy ethanol exposure. The high background concentrations of 2-methoxy acetic acid in the preshift urine samples following a 7-d production halt confirm that there is a long half-life of 2-methoxy acetic acid in humans. The determination of urinary 2-methoxy acetic acid is recommended for exposure assessment of 2-methoxy ethanol.

Acetates↗

Biological monitoring of occupational exposure to toxic chemicals. Collection, processing, and storage of specimens.

Exposure to at least 100 different chemicals may be estimated on an individual basis from their concentrations in blood or urine. The present document reviews sources of error in the collection, processing and storage of specimens for this biological monitoring. Physiological factors cause variation in the concentration of chemicals in the body fluids. Distribution of water depends on posture. Exercise and meals cause changes in blood constituents. The urine output varies and, thus, the concentrations of dissolved chemicals change. Many toxic chemicals show short half times in the blood; thus, their concentrations depend on the timing of the specimen collection. Skin absorption may result in dramatically different chemical concentrations in different parts of the circulation. The stability of chemicals in the collected specimens is generally limited: chemical deterioration, adsorption, precipitation, and evaporation are the main causes of losses. For many chemicals, especially for trace elements, contamination of the specimen is the overwhelmingly most important source of error. As the range of the chemicals measured is wide, the relative importance of the sources of error is different for different chemicals. Information on most chemicals is at present very limited. Thus, before commencing a program on biological exposure monitoring, it is advisable to search the optimal conditions for specimen collection, processing, and storage.

Adsorption↗

Cutaneous bioavailability in hairless rats of tretinoin in liposomes or gel.

Topical bioavailability of drugs incorporated in liposomes is not well known. We compared the skin penetration of tretinoin in liposomes and in a classical alcoholic gel. [3H]Phosphatidylcholine dipalmitoyl (DPPC) and [14C]tretinoin (0.14%) were incorporated in the phospholipidic phase of the liposomes, and [14C]tretinoin was incorporated in a gel for comparison. Skin absorption was studied in vitro with Franz cells. In vivo distribution in cutaneous structures was studied according to Schaefer's method. Liposomes impregnated the stratum corneum, with a partial dissociation between tretinoin and phosphatidyl-choline dipalmitoyl. In dermis, tretinoin diffused alone. Tretinoin release seemed to be controlled, and steady state was reached later with liposomes than with gel. This phenomenon was linked with a significantly reduced absorption (1.60% for liposomes versus 3.09% for the gel) and higher retention in epidermis (mainly stratum corneum) and dermis (41 and 13%, respectively, with liposomal form versus 18 and 8%, respectively, with gel form). This study clearly shows that, compared with the gel, the liposome formulation tends to improve the local effect of tretinoin in the skin and decrease the systemic absorption.

1,2-Dipalmitoylphosphatidylcholine↗

A human exposure study to investigate biological monitoring methods for 2-butoxyethanol.

2-Butoxyethanol is a glycol ether widely used in printing inks, varnishes and cleaning fluids. As skin absorption can be significant, biological monitoring is useful in monitoring worker exposure. A number of analytes and matrices have been used previously, including 2-butoxyethanol in blood and free and total 2-butoxyacetic acid in urine. Using a combination of a volunteer study and samples from exposed workers, we compared the applicability of some of the biological monitoring markers available. We conclude that 2-butoxyethanol in blood is not a suitable marker for biological monitoring due to sampling problems. In view of the low-level exposures reported in occupational surveys, 2-butoxyethanol in breath is also unsuitable because of a lack of sensitivity. Measuring 2-butoxyacetic acid in blood is possible, although non-invasive urine samples are preferred. Free 2-butoxyacetic acid in urine has previously been widely used; however, we found that the extent of conjugation of 2-butoxyacetic acid in urine varied from 0 to 100% both within and between individuals and is not related to time, concentration or urine pH. Data from 48 exposed workers suggested that an estimated 57% (95% confidence interval 44-70%) of the total 2-butoxyacetic acid is excreted in the conjugated form, and that conjugation may be activated above a certain exposure level. Using total 2-butoxyacetic acid significantly reduced inter-individual variation. Elimination half-lives for free and total 2-butoxyacetic acid were similar ( approximately 6 h) and there was no delay in excretion of the conjugated metabolite (peak excretion for both free and total was between 6 and 12 h after the end of exposure). In conclusion, we propose that total butoxyacetic acid (after acid hydrolysis) in urine is the biomarker of choice for monitoring exposure to 2-butoxyethanol. Urine samples should be collected post-shift towards the end of the working week.

Adult↗

Reconstruction of benzene exposure for the Pliofilm cohort (1936-1976) using Monte Carlo techniques.

The current cancer slope factor and occupational standards for benzene are based primarily on studies of the rubber hydrochloride (Pliofilm) workers. Previous assessments of this cohort by Rinsky et al. (1981, 1987), Crump and Allen (1984), and Paustenbach et al. (1992) relied on different assumptions about the available industrial hygiene data and workplace practices and processes over time, thereby yielding significantly different estimates of annual benzene exposures for many jobs. Given the inherent limitations and uncertainties involved in estimating historical exposures for this cohort, a probabilistic approach was used to better characterize their likely degree of benzene exposure. Ambient air exposures to benzene were based, in part, on the distribution of air sampling data collected at the Pliofilm facilities and assumptions about how workplace concentrations probably decreased over time as the threshold limit value (TLV) was lowered. The likely uptake of benzene from dermal exposures was estimated based on probability distributions for several exposure factors, including surface area, contact rate and duration, and skin absorption. The assessment also quantitatively accounts for improved engineering controls, extended work hours, incomplete Pliofilm production, and the use and effectiveness of respirators over time. All original data and assumptions are presented in this assessment, as is all new information obtained through additional interviews of former workers. Estimated benzene exposures at the 50th and 95th percentiles are reported as equivalent 8-h time-weighted average (TWA) airborne concentrations for 13 job categories from 1936 to 1965 (Akron I and II facilities) and 1939 to 1976 (St. Mary's facility). Data indicate that estimated equivalent airborne benzene concentrations for St. Mary's workers were highest for four job categories (Neutralizer, Quencher, Knifeman, Spreader), typically ranging from about 50 to 90 ppm during 1939-1946 (lower during 1942-1945), and 10 to 40 ppm during 1947-1976 at the 50th percentile. These estimates are 2-3 times greater than for other jobs in the Pliofilm process, and about 1.5 times less than those estimated at the 95th percentile. Estimates of equivalent airborne benzene concentrations for Akron I and II were about 1.5 times higher than for St. Mary's, but there is less confidence in these estimates, given the lack of industrial hygiene monitoring data for these facilities. Study results suggest that Paustenbach et al. (1992) generally over-estimated exposures for those job categories that had the highest exposure by about a factor of two to four. On the other hand, it was concluded that Rinsky et al. (1981, 1987) under-predicted benzene exposures for most jobs, and Crump and Allen (1984) both under- and overpredicted benzene exposures, depending on the specific job category and time period. The new estimates presented in this analysis incorporate what is considered to be the most likely range of plausible exposure values, and, accordingly, provide a better characterization of the potential workplace exposures for this cohort. These data could be combined with current or future mortality information to calculate a new cancer potency factor or occupational health standard for benzene.

Adult↗