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Biomedical subjects

R C Wester

Publications and source records attributed to R C Wester.

At least 19 recordsLinked to original sources
PubMed1992

In vitro percutaneous absorption of cadmium from water and soil into human skin.

The objective was to determine percutaneous absorption of cadmium as the chloride salt from water and soil into and through human skin. 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 cadmium-109 at 13 ppb. Water solutions of cadmium-109 at 116 ppb were prepared for comparative analysis. Human cadaver skin was dermatomed to 500-microns, and used in glass diffusion cells with human plasma as the receptor fluid (3 ml/hr flow rate) for a 16-hr skin application time. Cadmium in water (5 microliters/cm2) penetrated skin to concentrations of 8.8 +/- 0.6 and 12.7 +/- 11.7% of the applied dose from two human skin sources. Percentage doses absorbed into plasma were 0.5 +/- 0.2 and 0.6 +/- 0.6%, respectively. Cadmium from soil (0.04 g soil/cm2) penetrated skin at concentrations of 0.06 +/- 0.02 and 0.13 +/- 0.05% for the two human skin sources. Amounts absorbed into plasma were 0.01 +/- 0.01 and 0.07 +/- 0.03%. Most of the nonabsorbed cadmium was recovered in the soap and water skin surface wash. Binding of cadmium from water to soil was greater than binding from water to powdered human stratum corneum, supporting the lower absorption from soil than from water. Short-term exposure of cadmium in water to human skin for 30 min (bath or swim) resulted in skin uptake, which upon further perfusion (48 hr), absorbed into the plasma receptor fluid (systemic). Cadmium in soil was increased from 6.5 to 65 ppb.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Cutaneous↗
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↗
PubMed1992

In vivo percutaneous absorption of hydrocortisone: multiple-application dosing in man.

Percutaneous absorption of hydrocortisone was measured in six healthy adult men from whom informed consent had been obtained. The study compared a single topical dose to multiple-topical dose treatments (one vs three applications) on the same day. 14C-Labeled hydrocortisone in acetone was applied to 2.5 cm2 of ventral forearm skin and protected with a nonocclusive polypropylene chamber. The amount of 14C measured in urine collected over 7 days was used to determine hydrocortisone absorption. The treatments, performed 2 to 3 weeks apart, each utilized adjacent sites on the same individuals. A single dose of 13.33 micrograms/cm2 delivered 0.056 microgram/cm2 of hydrocortisone through the skin. When the single dose was tripled to 40 micrograms/cm2, the amount delivered through the skin increased by nearly three times, from 0.056 to 0.140 micrograms/cm2; the expected delivery was 3 x 0.056 micrograms/cm2 = 0.168 microgram/cm2. Three serial doses of 13.33 micrograms/cm2 (total, 40 micrograms/cm2) were also expected to deliver 0.168 micrograms/cm2 with or without soap and water washing between doses, but the observed amount of hydrocortisone delivered through the skin significantly exceeded our expectations. This indicates that multiple-dosing treatments resulted in a significant increase in bioavailability. It is postulated that increased vehicle application and washing dissolved and mobilized previously dosed hydrocortisone and increased bioavailability.

Administration, Cutaneous↗
PubMed1992

Percutaneous absorption of [14C]chlordane from soil.

The objective was to determine percutaneous absorption of chlordane in vitro and in vivo from soil into and through skin. The data are needed to calculate the absorbed dose of chlordane from soil, which is then used to assess the toxicity risk. Chlordane, an insecticide for which residues exist in soil, is restricted currently to use for termite control. Chlordane is highly lipophilic with little or no movement out of soil. Soil (Yolo County 65-California-57-8; 26% sand, 26% clay, 48% silt, 0.9% organic) was passed through 10-, 20-, and 48-mesh sieves. Soil then retained by 80-mesh was mixed with 14C-labeled chemical at 67 ppm. Acetone solutions were prepared for comparative analysis. Human cadaver skin was dermatomed to 500 microns and used in glass diffusion cells with human plasma as the receptor fluid (3 ml/h flow rate) for a 24-h skin application time. Chlordane concentration within skin from in vitro studies was 0.34 +/- 0.31% from soil and 10.8 +/- 8.2% from acetone vehicle (p less than .01). Individual variation from human skin sources was evident (p less than .008). Chlordane accumulation in human plasma receptor fluid was the same for soil (0.04 +/- 0.05%) and acetone (0.07% +/- 0.06%) formulations. Most of the remaining chlordane was recovered in the soap and water skin surface wash. In contrast, in vivo percutaneous absorption of chlordane in the rhesus monkey was the same for soil (4.2 +/- 1.8%) and acetone (6.0 +/- 2.8%) formulations (p = .29, nonsignificant). Multiple soap and water washings were necessary to remove chlordane from skin, suggesting that a single wash may not adequately remove all the chlordane.

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↗
PubMed1992

Dermal absorption of the phenoxy herbicide 2,4-D dimethylamine in humans: effect of DEET and anatomic site.

Percutaneous absorption of the 14C-ring-labeled phenoxy herbicide 2,4-D-amine (2,4-dichlorophenoxyacetic acid dimethylamine) was examined following topical applications of the herbicide to the palm and forearm of human volunteers. The effect of two vehicles (water and acetone) and the mosquito repellent DEET (N,N-diethyl-m-toluamide) on dermal absorption of 2,4-D-amine also was investigated. The total percent dermal absorption was calculated from the mean percent urinary recoveries and was not corrected for nonurinary excretion. The data revealed 14 +/- 4.5% (standard deviation) and 10 +/- 11.5% palmar absorption of 2,4-D-amine applied in water, with and without DEET, respectively, and 7 +/- 6.2% and 13 +/- 5.0% forearm absorption of the herbicide applied in water or acetone, respectively. Soap-and-water skin washes conducted at 24 h posttreatment removed up to 34% of the applied dose. Successive tape strips of skin taken at 24 h posttreatment demonstrated generally decreasing herbicide levels in the outer layers. The data bring into question the complete validity of the rhesus monkey model to predict human dermal absorption.

2,4-Dichlorophenoxyacetic Acid↗
PubMed1992

Cutaneous metabolism of theophylline by the human skin.

Percutaneous absorption of theophylline in human skin from five sources was examined by use of a flow-through in vitro diffusion system. The metabolites and unchanged drug were estimated by thin-layer chromatography. Correlation was evident in the percentage of the applied dose that diffused through the five skin samples (range 2.8 +/- 0.5%-7.7 +/- 0.8%); however, the percentage of applied dose absorbed varied between different skin samples (range 3.6 +/- 0.9%-33.4 +/- 2.4%). Between 0.2 +/- 0.1%-4.6 +/- 0.2% of the doses applied were metabolized, and over 60% of the total metabolites formed diffused through the skin. The uptake and metabolism of theophylline by microsomes obtained from four of the human skin samples were measured. All preparations showed detectable activities for the metabolism of theophylline. Microsomal preparations from skin sources A, B, and E, and B, C, and E biotransformed theophylline to 1,3,7-trimethyluric acid and 1,3-dimethyluric acid, respectively. The activities of microsomes from skin samples C and E on the drug produced the pharmacologically active metabolite 3-methylxanthine. The specific activities of the microsomes from skin sources A-E for the formation of 1,3-dimethyluric acid and 3-methylxanthine varied fivefold. However, the variation in specific activities of the microsomes for the formation of 1,3,7-trimethyluric acid was twofold (range 2.8 +/- 0.1-6.2 +/- 0.5 pmol/min per mg protein). These metabolic data may be of value in the development of transdermal theophylline systems. The results indicate that a high level of absorption enhancement will be required before transdermal theophylline preparations could produce therapeutic plasma concentrations.

Adult↗
PubMed1992

Issues in measuring percutaneous absorption of topical corticosteroids.

Studies that examine the pharmacokinetics of topical drugs at their site of action in the skin have been difficult to perform and, therefore, limited in number. In the early years of topical drug pharmacokinetic research, investigators had to rely on the measurement of less direct indicators of drug throughput such as blood levels and urinary excretion. Today, advances in theory are impelling pharmacokinetic research in new directions, including the measurement of drug availability in tissue compartments within the skin. This research will lead to greater precision in pharmacokinetic measurement and greater relevance of these measurements to the therapeutic efficacy of topical corticosteroids in cutaneous disease states.

Administration, Topical↗
PubMed1992

Percutaneous absorption of drugs.

The skin is an evolutionary masterpiece of living tissue which is the final control unit for determining the local and systemic availability of any drug which must pass into and through it. In vivo in humans, many factors will affect the absorption of drugs. These include individual biological variation and may be influenced by race. The skin site of the body will also influence percutaneous absorption. Generally, those body parts exposed to the open environment (and to cosmetics, drugs and hazardous toxic substances) are most affected. Treating patients may involve single daily drug treatment or multiple daily administration. Finally, the body will be washed (normal daily process or when there is concern about skin decontamination) and this will influence percutaneous absorption. The vehicle of a drug will affect release of drug to skin. On skin, the interrelationships of this form of administration involve drug concentration, surface area exposed, frequency and time of exposure. These interrelationships determine percutaneous absorption. Accounting for all the drug administered is desirable in controlled studies. The bioavailability of the drug then is assessed in relationship to its efficacy and toxicity in drug development. There are methods, both quantitative and qualitative, in vitro and in vivo, for studying percutaneous absorption of drugs. Animal models are substituted for humans to determine percutaneous absorption. Each of these methods thus becomes a factor in determining percutaneous absorption because they predict absorption in humans. The relevance of these predictions to humans in vivo is of intense research interest. The most relevant determination of percutaneous absorption of a drug in humans is when the drug in its approved formulation is applied in vivo to humans in the intended clinical situation. Deviation from this scenario involves the introduction of variables which may alter percutaneous absorption.

Animals↗
PubMed1991

Controlled release of benzoyl peroxide from a porous microsphere polymeric system can reduce topical irritancy.

Skin absorption of benzoyl peroxide from a topical lotion containing freely dispersed drug was compared with that from the same lotion in which the drug was entrapped in a controlled-release styrene-divinylbenzene polymer system. In an in vitro diffusion system, statistically significant (p = 0.01) differences were found in the content of benzoyl peroxide in excised human skin and in percutaneous absorption. In vivo, significantly (p = 0.002) less benzoyl peroxide was absorbed through rhesus monkey skin from the polymeric system. This controlled release of benzoyl peroxide to skin can alter the dose relation that exists between efficacy and skin irritation. Corresponding studies showed reduced skin irritation in cumulative irritancy studies in rabbits and human beings, whereas in vivo human antimicrobial efficacy studies showed that application of the formulations containing entrapped benzoyl peroxide significantly reduced counts of Propionibacterium acnes (p less than 0.001) and aerobic bacteria (p less than 0.001) and the free fatty acid/triglyceride ratio in skin lipids. These findings support the hypothesis that, at least for this drug, controlled topical delivery can enhance safety without sacrificing efficacy.

Administration, Cutaneous↗
PubMed1991

Glyphosate skin binding, absorption, residual tissue distribution, and skin decontamination.

Glyphosate is a broad-spectrum postemergence translocated herbicide. Its interactions with skin and potential systemic availability through percutaneous absorption was studied by skin binding, skin absorption, residual tissue distribution, and skin decontamination. Glyphosate in a final formulation (Roundup) undiluted and diluted with water 1:20 and 1:32, would not partition into powdered human stratum corneum (less than 1%). In vitro percutaneous absorption through human skin into human plasma as receptor fluid was no more than 2% over a concentration range of 0.5-154 micrograms/cm2 and a topical volume range of 0.014-0.14 ml/cm2. Disposition of glyphosate following iv administration of 93 and 9 micrograms doses to rhesus monkeys was mainly through urine excretion, 95 +/- 8 and 99 +/- 4% in 7 days, respectively. Percutaneous absorption in vivo in rhesus monkey was 0.8 +/- 0.6% for the low dose (25 micrograms/cm2) and 2.2 +/- 0.8% for the high dose (270 micrograms/cm2). No residual 14C was found in organs of the monkeys euthanized 7 days after the topical application. Washing the skin application site with soap and water removed 90 +/- 4% of applied dose, and washing with water only removed 84 +/- 3% of applied dose. Both soap and water and water only were equal in ability to remove glyphosate from skin over a 24 hr skin application period. About 50% of the initially applied dose could be recovered after 24 hr. Glyphosate is very soluble in water and insoluble in most organics (octanol/water log P = -1.70) and therefore not compatible with the lipid-laden stratum corneum.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Topical↗
PubMed1990

In vivo percutaneous absorption of fragrance ingredients in rhesus monkeys and humans.

The percutaneous absorption of the fragrance diethyl maleate was measured in vivo in human and monkey studies. With the application sites occluded, 54% of the applied dose of the volatile fragrance penetrated human skin in 24 hr compared with 69% absorption in the monkey skin. It was concluded that the monkey is a good model for human skin with regard to the penetration of this fragrance material since no significant difference in the absorption of diethyl maleate was observed. The percutaneous absorption of the fragrances benzyl acetate and five other benzyl derivatives (benzyl alcohol, benzyl benzoate, benzamide, benzoin and benzophenone) was determined in vivo in monkeys. Absorption through occluded skin was high for all compounds (approximately 70% of the applied dose in 24 hr) and no significant differences between the values for the different compounds were observed. No correlations were seen between skin penetration of these compounds and their octanol-water partition coefficients. Under unoccluded conditions skin penetration of the fragrances was reduced and there was great variability between compounds, presumably because of variations in the rates of evaporation from the site of application. The data suggest that humans may have significant systemic exposure to these fragrance materials.

Administration, Topical↗
PubMed1990

Percutaneous absorption and skin decontamination of PCBs: in vitro studies with human skin and in vivo studies in the rhesus monkey.

Knowledge of the entry of polychlorinated biphenyls through the skin into the body and subsequent disposition aids estimation of potential for human health hazard. [14C]Aroclor 1242 and [14C]Aroclor 1254 were separately administered intravenously and topically to rhesus monkeys. Following iv administration, 30-d excretion was 39.4 +/- 5.9% urine and 16.1 +/- 0.8% feces (total 55.5 +/- 5.1%) for Aroclor 1242, and 7.0 +/- 2.2% urine and 19.7 +/- 5.8% feces (total 26.7 +/- 7.5%) for Aroclor 1254. Mineral oil and trichlorobenzene are common PCB cosolvents in transformers. Skin absorption of Aroclor 1242 was 20.4 +/- 8.5% formulated in mineral oil and 18.0 +/- 3.8% in trichlorobenzene (p greater than .05). Absorption of Aroclor 1254 was 20.8 +/- 8.3% in mineral oil and 14.6 +/- 3.6% in trichlorobenzene (p greater than .05). PCBs are thus absorbed through skin, and excretion from the body is slow. Vehicle (trichlorobenzene or mineral oil) did not affect percutaneous absorption. In vitro skin absorption in human cadaver skin did not correlate with in vivo findings. This was due to lack of PCB partition from skin into the water receptor fluid, even with addition of 6% Oleth 20 (Volpo 20) solubilizer. Skin decontamination of PCBs showed soap and water to be as effective as or better than the solvent ethanol, mineral oil, and trichlorobenzene in removing PCBs from skin. There is a dynamic time lapse for PCBs between initial skin contact and skin absorption (irreversible removal). Thus initially most PCBs could be removed from skin, but this ability decreased with time to the point where at 24 h only about 25% of the initial PCB skin dose could be recovered with skin washing.

Administration, Topical↗
PubMed1990

Diseased skin models in the hairless guinea pig: in vivo percutaneous absorption.

We observed hydrocortisone and benzoic acid absorption in relation to experimentally induced in vivo damaged skin models in the hairless guinea pig. Radioactivity of the drugs in urine was calculated as absorbed dose. Both drugs have different patterns of excretion in urine. Damaging the skin abolished some barrier function and increased the absorption of both model drugs. With cellophane-tape-stripped skin, the absorption was increased 3 times and 2 times for each drug, respectively. Irritation with 2% sodium lauryl sulfate increased absorption by a ratio of 2-4 times. Defatting with chloroform/methanol (2:1) mixture increased absorption to the greatest extent (5- and 2.7-fold). The possible mechanism of a delipidization effect was considered in view of a visible skin lesion and inflammatory reaction. Precautions are proposed for those with damaged/diseased skin in dealing with topical medications or handling solvents.

Administration, Topical↗
PubMed1990

Percutaneous absorption of [14C]DDT and [14C]benzo[a]pyrene from soil.

The objective was to determine percutaneous absorption of DDT and benzo[a]pyrene in vitro and in vivo from soil into and through skin. Soil (Yolo County 65-California-57-8; 26% sand, 26% clay, 48% silt) was passed through 10-, 20-, and 48-mesh sieves. Soil then retained by 80-mesh was mixed with [14C]-labeled chemical at 10 ppm. Acetone solutions at 10 ppm were prepared for comparative analysis. Human cadaver skin was dermatomed to 500 microns and used in glass diffusion cells with human plasma as the receptor fluid (3 ml/hr flow rate) for a 24-hr skin application time. With acetone vehicle, DDT (18.1 +/- 13.4%) readily penetrated into human skin. Significantly less DDT (1.0 +/- 0.7%) penetrated into human skin from soil. DDT would not partition from human skin into human plasma in the receptor phase (less than 0.1%). With acetone vehicle, benzo[a]pyrene (23.7 +/- 9.7%) readily penetrated into human skin. Significantly less benzo[a]pyrene (1.4 +/- 0.9%) penetrated into human skin from soil. Benzo[a]pyrene would not partition from human skin into human plasma in the receptor phase (less than 0.1%). Substantivity (skin retention) was investigated by applying 14C-labeled chemical to human skin in vitro for only 25 min. After soap and water wash, 16.7 +/- 13.2% of DDT applied in acetone remained absorbed to skin. With soil only 0.25 +/- 0.11% of DDT remained absorbed to skin. After soap and water wash 5.1 +/- 2.1% of benzo[a]pyrene applied in acetone remained absorbed to skin. With soil only 0.14 +/- 0.13% of benzo[a]pyrene remained absorbed to skin.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorption↗