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At least 145 records · Page 8Linked to original sources
PubMed1992

Percutaneous absorption and skin distribution of [14C]flutrimazole in mini-pigs.

The percutaneous absorption and skin distribution of a skin cream containing 1% 14C-labelled 1-[(fluorophenyl) (4-fluorophenyl) phenylmethyl]-1H-imidazole (flutrimazole, UR-4056, CAS 119006-77-8) was studied in minipigs. The same dose of flutrimazole was administered i.v. and topically (as a cream) on scarified skin according to a crossover protocol. Samples of urine and faeces were taken at various intervals after administration, and radioactivity was measured. The percentage of radioactivity accumulated in urine after topical and intravenous administration were 1.46% and 41.7%, respectively. In faeces, the percentage of radioactivity observed was 6.0% after intravenous administration, and none was detected after topical application. In order to study the distribution and penetration of [14C]flutrimazole, the cream was applied to intact and scarified skin. At various intervals after administration, skin samples were taken. The samples for the autoradiographic studies were cut transversely, and for the measurement of the levels of radioactivity at different skin depths, slices were cut parallel to the cutaneous layers. The results obtained indicate that [14C]flutrimazole penetrates quickly into the different epidermic layers and is retained mainly in the strata spinosum, granulosum and basale. The stratum basale possibly acts as a selective barrier preventing the penetration of the compound into the dermis. The percentage of radioactivity in the stratum corneum is lower than that detected in all the other epidermic layers taken together. The stratum corneum offers low resistance to penetration by the flutrimazole, which very probably crosses the epidermic strata by a transcellular route.

Animals↗
PubMed1990

[Absorption of chromium through the skin and urinary excretion in rats].

The aim of the experiment was to evaluate the diffusion rate in vitro and the skin absorption rate of trivalent and hexavalent chromium from aqueous solution. Excretion of chromium in urine was also measured. The experiment was carried out on 47 Wistar male rats, 4-5 months old. The solutions of chromium sulfate or potassium dichromate contained 2.5, 5.0 and 10.0 mg Cr per milliliter. Exposure time was 4 hrs. It was found that diffusion rate of Cr3+ was seven-time less than of Cr2O7(2-). Absorption rates of both ions through the skin were similar. Excretion rates of chromium in urine were not different in case exposure to both xenobiotics. It can be concluded that diffusion does not play an important role in absorption of chromium through the skin. It seems that oxidation grade of chromium has no influence on the excretion rate of this metal from the organism.

Animals↗
PubMed2001

Evaluation of percutaneous absorption and skin irritation of ketoprofen through rat skin: in vitro and in vivo study.

The influences of different mechanisms of penetration enhancers (such as menthol, azone, ethanol and nonivarnide) regarding the percutaneous absorption and skin irritation of ketoprofen formulations through rat skin were investigated by in vitro and in vivo study. The skin irritation degree at the end of the experiment (10 h) was deterinined by pathologic biopsy and colorimetry methods. In vitro, the menthol showed the most potent enhancing effect. Furthermore, the enhancement effect of a combination of menthol and nonivamide was higher than that of their individual use alone. In vivo the formulation containing 0.05% nonivantide, 5% menthol and 20% ethanol showed a higher penetration rate and an acceptable degree of skin irritation compared to a commercial product (Formax plus gel containing 3% ketoprofen), indicating that it could be used in the clinical situation.

Animals↗
PubMedDate not supplied

Evaluation of barrier creams against sulphur mustard. I. In vitro studies using human skin.

The purpose of this study was to assess the effectiveness of a range of passive and reactive barrier cream formulations against the chemical warfare agent sulphur mustard (SM) using an in vitro diffusion cell system containing human skin. In general, proprietary formulations were relatively effective under occluded conditions, but ineffective under unoccluded conditions. For example, SM skin absorption rates through occluded control and Stokoderm pre-treated skin were 538 +/- 193 and 200 +/- 51 microg x cm(-2) x h(-1), respectively (p < 0.05). Under unoccluded conditions, control and Stokoderm pre-treated skin absorption rates were 4.41 +/- 1.90 and 36.84 +/- 15.19 microg x cm(-2) x h(-1) (p < 0.05). Novel (perfluorinated) barrier creams were generally more effective under unoccluded conditions; pre-treatment with one formulation led to an 18-fold reduction in skin absorption rate and reduced the total amount of SM penetrated by 95% of the applied dose. Several proprietary formulations also had adverse effects on the effectiveness of the skin decontaminant fuller's earth. The rate (Jss) and total amount (percentage of dose) of SM absorbed through the skin were deemed to be independent parameters of barrier cream performance. These data indicate that (1) perceived conditions of use, (2) compatibility with existing protective equipment and (3) the rate and extent of SM skin absorption must all be taken into account when evaluating barrier creams in vitro.

Administration, Cutaneous↗
PubMed1978

Absorption of 8-hydroxyquinolines through the human skin.

The skin absorption of clioquinol and chloroquinaldol in ointment or cream base was studied in fourteen patients with widespread dermatoses. A serum concentration in the range of 0.3--1.3 microgram/ml using clioquinol and 0.05--0.1 microgram/ml with chloroquinaldol was reached by the second day and persisted throughout the topical treatment. The mean serum half-life of clioquinol and of chloroquinaldol was estimated to 25 and 6 hours, respectively. Local application of zinc oxide ointment after the end of the treatment chelate-bound the skin deposits of clioquinol and lowered the serum half-life to 11 hours. The mean daily urinary excretion of the applied amount of clioquinol and chloroquinaldol was 4.5 and 6%, respectively.

Administration, Topical↗
PubMed1992

In vivo percutaneous absorption and skin decontamination of alachlor in rhesus monkey.

The objectives of this study were to determine the percutaneous absorption of alachlor relative to formulation dilution with water, and to determine the ability of soap and water, and of water only, to remove alachlor from skin, relative to time. Alachlor is a preemergence herbicide. The in vivo percutaneous absorption of alachlor in rhesus monkeys was 17.3 +/- 3.3, 15.3 +/- 3.9, and 21.4 +/- 14.2% for 24-h skin exposure to Lasso formulation diluted 1:20, 1:40, and 1:80, respectively. In vivo, there was no support for increased alachlor skin absorption with water dilution, as previously reported for in vitro absorption. The average in vivo absorption of 18% applied dose over 24 h (0.75%/h) was similar to the maximum in vitro rate of 0.8%/h using human skin and human plasma as receptor fluid. Dose accountability in vivo was 80.6-95.2%. [14C]Alachlor in Lasso diluted 1:20 with water was placed on rhesus monkeys at concentrations of 23 micrograms/10 microliters/cm2. Skin decontamination at 0 h with soap and water (50% Ivory liquid 1:1 v/v with water) removed 73 +/- 15.8% (n = 4) of the applied dose with the first wash; this increased to a total of 82.3 +/- 14.8% with two additional washes. Decontamination after 1 h removed 87.5 +/- 12.4% with three successive washes. After 3 h decontamination ability decreased, and after 24 h only 51.9 +/- 12.2% could be recovered with three successive washes. Using water only, at 0 h 36.6 +/- 12.3% alachlor was removed with the first wash and the total increased to 56.0 +/- 14.0% with two additional washes. At 24 h the total amount decreased to 28.7 +/- 12.2% for three successive washes. Alachlor as Lasso in field-use rate (11 micrograms/cm2) and undiluted (217 and 300 micrograms/cm2) proportions were left on rhesus monkey skin for 12 h and decontaminated with soap and water (10% Ivory liquid v/v with water). Continual successive washes (6-8 in sequence) recovered 80-90% of the skin-applied alachlor. These results suggest that simple washing with soap and water is appropriate for removing some chemicals from skin. Decontamination with only water was less effective than with soap and water.

Acetamides↗
PubMed1995

Percutaneous absorption of organic solvents during intermittent exposure in guinea pigs.

Skin absorption under intermittent exposure of guinea pigs to n-butanol, toluene, 1,1,1-trichloroethane was studied. Groups of guinea pigs were exposed to test organic solvents for 1 min at 30-min intervals during 4 h, in all 8 exposures. Skin absorption of solvent was assessed by following the concentration of solvent in the blood. This intermittent exposure was compared to continuous exposure over 4 h. Absorption of toluene and 1,1,1-trichloroethane was low, but a considerable amount of butanol was absorbed through the skin on intermittent exposure. A typical serrated absorption profile was seen for butanol that was less pronounced for toluene and 1,1,1-trichloroethane. The absorption of butanol was highest at the end of the exposure period. The differences in absorption profiles may be due to the differences in vapour pressure in the solvents in association with the animal method used. The amount absorbed varied inversely with vapour pressure. Hair stubble may act as a trap for solvents with low vapour pressure. Adequate ventilation reduces unoccluded skin absorption of volatile organic solvents.

1-Butanol↗
PubMed1992

In vivo and in vitro percutaneous absorption and skin evaporation of isofenphos in man.

Studies were done to determine the percutaneous absorption of isofenphos in human volunteers from whom informed consent had been obtained. In vivo absorption in man was 3.6 +/- 3.6% of applied dose for 24-hr exposure and 3.6 +/- 0.5% for 72-hr exposure. Skin wash recovery data show that isofenphos evaporates from in vivo skin during the absorption process; the surface dose is minimal (< 1%) by 24 hr. Skin stripping showed no residual isofenphos in stratum corneum. This explains the similar absorption for 24 and 72-hr dose prewash exposures. Skin surface recovery in vivo with soap and water was 61.4 +/- 10.4 for the first dosing time (15 min). Time-recovery response declined with time to 0.5 +/- 0.2% at 24 hr. In vitro absorption utilizing flow-through diffusion methodology with human cadaver skin and human plasma receptor fluid gave 2.5 +/- 2.0% dose absorbed, an amount similar to in vivo studies. An additional 6.5 +/- 24% was recovered in the skin samples (total of 9%). Skin surface wash at 24 hr recovered 79.7 +/- 2.2% and skin content was 6.5 +/- 2.4% (total dose accountability of 88.7 +/- 4.6%). Thus, isofenphos was available for absorption during the whole dosing period. Neither in vitro absorption nor in vitro evaporation studies predicted the potential skin evaporation of isofenphos. Published dermal studies in the rat had predicted isofenphos absorption at 47% of applied dose (12-fold greater than actual in man). Subsequent toxicokinetic modeling predicted possible concern with the use of isofenphos.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1987

Urinary chlorophenols in sawmill workers.

The concentration of urinary chlorophenol was assayed for 230 sawmill workers. Information on the work tasks was obtained through questionnaires from occupational health centres. The workers were divided into three groups on the basis of the type of exposure: (1) those with skin absorption as the main route, (2) those with skin and respiratory route of equal importance and (3) those with respiratory tract as the main route. The concentrations of urinary chlorophenol were higher in workers with skin absorption as the main route (median concentration: 7.8 mumol l-1; range 0.1 to 210.9 mumol l-1) than in those with both routes of equal importance (1.4 mumol l-1; range 0.1 to 47.8 mumol l-1, P less than 0.001) or in those with mainly respiratory route (0.9 mumol l-1; range 0.1 to 13.3 mumol l-1, P less than 0.001). The urinary chlorophenol concentration was below 15 mumol l-1 in all workers with the lungs as the main absorption route. In nine out of 112 workers whose main absorption route was the skin, the urinary chlorophenol values were above 50 mumol l-1. Six were loaders when the through-dipping method was used. In two of them urinary chlorophenol concentrations were as high as 170.8 and 210.9 mumol l-1. These results emphasize the need to develop and use simple methods of protection against skin contact with chlorophenols.

Administration, Inhalation↗
PubMed1992

Accidental death caused by the absorption of 2,4-dichlorophenol through the skin.

A case involving an accidental fatality resulting from skin absorption of 2,4-dichlorophenol in a factory is presented. The compound was quantified using gas chromatography after separation on a SP-1240 DA column and detection with flame ionization. Confirmation was obtained with mass spectrometry. Blood concentration was 24.3 mg/l. Other drugs, including ethanol, were not detected.

Accidents, Occupational↗
PubMed1997

The percutaneous absorption and skin distribution of lindane in man. II. In vitro studies.

1. The absorption of lindane through human skin was assessed in vitro using static diffusion cells with 50% aqueous ethanol as the receptor fluid. Four formulations of lindane were applied, three of which were commercial preparations. The dermal distribution of lindane within the skin was also examined, focusing particularly on any association of lindane to the stratum corneum. The results were then compared with a parellel in vivo study. 2. Two of the formulations contained white spirit as the predominant solvent, and lindane absorption was greatest from these preparations in terms of the percentage of the applied dose (15-25% by 24 h). Absorption was less from an aqueous spray dilution (3% by 24 h), with absorption from acetone being the least (< 1% by 24 h). Similar amounts of lindane penetrated by 24 h for the acetone and white spirit-based applications (approx. 8 micrograms). This supported the in vivo observation that similar plasma lindane levels were recorded following exposure to the acetone solution and the white spirit-based formulation A, although the lindane concentration in acetone was 40-fold higher. 3. For the acetone and water-based preparations, a soap/water swab of the skin surface at 6 h contained the majority of the applied dose (around 75%). Substantial amounts of lindane were recovered in tape-strippings taken at 6 h (representative of stratum corneum content) which were significantly greater than lindane in the remainder of the skin, for the acetone solution and formulation A. This provided a strong indication that lindane had accumulated in the stratum corneum, a property that has been linked with other lipophilic chemicals.

Acetone↗
PubMed1995

In vitro percutaneous absorption of arildone, a highly lipophilic drug, and the apparent no-effect of the penetration enhancer Azone in excised human skin.

PURPOSE: Arildone, a novel lipophilic antiviral drug when evaluated in Clinical Trials showed limited skin absorption and antiviral efficacy. These studies were conducted to explain the apparent poor absorption characteristics and attempt to promote skin absorption by using Azone, a penetration enhancer. METHODS: Standard in vitro skin permeation methods using excised human skin were employed to characterise the absorption of Arildone. 14C-Arildone was used to estimate the distribution in skin layers by scintigraphic and autoradiographic procedures. RESULTS: The aqueous solubility and distribution constant values for Arildone were 2 micrograms ml-1 and 5 x 10(5) (isopropyl myristate/water), respectively. Absorption through full thickness skin or stratum corneum-viable epidermal membranes (diffusional resistant dermis removed), from a propylene glycol vehicle, was slow and the addition of Azone had no effect on the permeation rate. Distribution studies showed accumulation of Arildone in the stratum corneum. The concentration of Arildone in the viable epidermis was estimated from sectioning the skin and was found to be in sufficient amounts (400 micrograms cm-3) to have potential antiviral activity. CONCLUSIONS: The apparent accumulation of Arildone in the stratum corneum suggested that the hydrophilic skin region presented the main barrier to permeation. Azone which affected the permeability of the stratum corneum was therefore not effective at enhancing Arildone absorption. Vehicles which readily permeate and enhance the transfer of lipophilic drugs from the stratum corneum into the viable epidermis were recommended.

Aged↗
PubMed1985

Pattern of neurotoxicity of n-hexane, methyl n-butyl ketone, 2,5-hexanediol, and 2,5-hexanedione alone and in combination with O-ethyl O-4-nitrophenyl phenylphosphonothioate in hens.

This investigation was designed to study the neurotoxicity produced in hens by the aliphatic hexacarbons n-hexane, methyl n-butyl ketone (MnBK), 2,5-hexanediol (2,5-HDOH), and 2,5-hexanedione (2,5-HD) following daily dermal application of each chemical alone and in combination with O-ethyl O-4-nitrophenyl phenylphosphonothioate (EPN). Dermal application was carried out on the unprotected back of the neck. To assess whether the joint neurotoxic action of various chemicals is caused by the enhancement of absorption through the skin or by interaction at the molecular level, two additional experiments were performed. In the first experiment, EPN was dissolved in each of the aliphatic hydrocarbons prior to their topical application. In the second experiment, EPN was dissolved in acetone and applied at a different location from that of the aliphatic hexacarbons. Dermal application was carried out for 90 d followed by a 30-d observation period. The results show that hens treated with EPN developed severe ataxia followed by improvement during the observation period; n-hexane produced leg weakness with subsequent recovery, whereas the same dose of MnBK, 2,5-HDOH, or 2,5-HD produced clinical signs of neurotoxicity characterized by gross ataxia; concurrent dermal application of EPN with n-hexane or 2,5-HDOH at the same site or at different sites produced an additive neurotoxic action; simultaneous dermal application of EPN and MnBK at different sites resulted in an additive effect, whereas it caused potentiation when applied at the same site; and concurrent topical application of EPN and 2,5-HD produced a potentiating neurotoxic effect. While no histopathologic lesion was produced at the end of the observation period when any test chemical was applied alone, binary treatments of EPN and aliphatic hexacarbons resulted in histopathologic changes in some hens, with morphology and distribution characteristic of EPN neurotoxicity. The joint potentiating or additive action of aliphatic hexacarbons on EPN neurotoxicity was: 2,5-HD greater than MnBK greater than 2,5-HDOH greater than n-hexane. The mechanism of this joint action seems to be related both to enhancing skin absorption of EPN and/or its metabolic activation by n-hexane and its related chemicals.

Animals↗
PubMed2001

Kinetics of finite dose absorption through skin 1. Vanillylnonanamide.

Despite the considerable success in predicting the steady-state dermal absorption rates of chemical compounds from large reservoirs applied to skin, correspondingly little progress has been made in predicting the absorption rate and extent for small doses of topically applied compounds. In the latter case, steady-state absorption rates are generally not obtained, and rapid evaporation or penetration of the dose solvent makes application of permeability coefficient models problematic. This report presents a new analysis of the finite dose problem in terms of a diffusion model with three parameters-a characteristic time for diffusion, h2/D; a skin solubility factor, S(m)h; and a capacity factor for absorption of the dose during the dry down period, M*. These parameters can be related to the molecular weight and oil and water solubilities of the permeant in a manner similar to models describing steady-state absorption from saturated solutions. Some variation of the parameter values based on the chemical nature and volume of the dose solvent is anticipated. The applicability of the model is demonstrated by analyzing the in vitro absorption rates of varying doses of vanillylnonamide (VN, synthetic capsaicin) applied to excised human skin from propylene glycol. The analysis shows that a three-parameter model that assigns all of the resistance to transport to diffusion through the stratum corneum is able to explain most of the significant features of VN absorption through skin.

Animals↗
PubMed1997

The percutaneous absorption and skin distribution of lindane in man. I. In vivo studies.

1. The absorption and distribution of lindane through skin was examined using human volunteers. Two different preparations were employed, one with acetone as the vehicle and the other, a commercial product, consisting primarily of white spirit as the solvent base. 2. The mean peak plasma concentrations of lindane following exposure to the acetone and white-spirit based applications were 0.91 and 0.47 ng/ml, respectively. The similarity between these levels did not reflect the 40-fold higher dose of lindane in the acetone vehicle. White spirit enhanced the penetration of lindane with respect to the acetone vehicle, highlighting the influence of vehicle upon percutaneous absorption. Low levels of trichlorophenol glucuronide metabolites, but no lindane, were detected in the urine. 3. The exposure site was washed at 6 h to mimic a decontamination procedure at the end of a working day. The proportion of the applied dose unabsorbed by 6 h was 80% and 10% for the acetone and the white spirit-based formulation, respectively. Small areas of the exposed site were tape stripped at 6 and 24 h to assess any lindane that may be associated with the stratum corneum. High levels were observed in the stratum corneum at 6 h exposure (up to 30% of the applied dose for the white spirit based formulation). However, this level had decreased by 24 h (by at least 90% of the amount found at 6 h). A gauze or gauze/shirt combination covering the application site between 6 and 24 h did account for some of this loss of lindane from the stratum corneum attributed to friction and removal of exfoliated cells. The unaccounted proportion was presumed to have been absorbed through the skin into the systemic circulation. This demonstrates the absorption of chemicals can occur from a depot in the stratum corneum even following a wash procedure.

Acetone↗
PubMed1996

Tritium intake by exposure to plastic case watches.

In recent years tritium has been used in plastic case watches as permanent light sources on watch dials. To measure the release of tritium through the plastic cases, 82 different waterproofed watches were immersed in a water bath for 24 h, and the tritium concentration of the water was measured. The mean tritium release rate was 24,400 Bq d(-1) ranging from 110-162,000 Bq d(-1). Parallel measurements were made to determine the tritium concentration in the urine of 108 wearers of plastic case watches. The mean tritium concentration in urine was 197 Bq L(-1) up to 1,133 Bq L(-1). The whole body dose resulting from exposure to plastic case is negligibly small but given the pathway of skin absorption, the annual skin dose is 3-4 times higher than the dose limit for the public. Plastic case watches are collector's items and are often kept with other watches in glass cabinets or other containers. Storage of a large number of such watches in one container causes tritium to diffuse through the plastic cases and to contaminate watches that did not contain tritium at first. If the container is more or less airtight, the tritium concentration in the container and the tritium release rate from the watches can reach levels up to 4 MBq d(-1).

Humans↗