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PubMed1984

Skin typing for assessment of skin cancer risk and acute response to UV-B and oral methoxsalen photochemotherapy.

Skin typing is a clinical classification system based on a patient's historical reporting of the acute skin response to sunlight. It is advocated as a means of determining an individual's relative risk of skin tumors and has been used to determine the initial therapeutic dose of UV radiation for UV-B phototherapy or oral methoxsalen photochemotherapy (PUVA) for psoriasis. Among PUVA-treated patients, the relative risk of cutaneous carcinoma was significantly higher among patients with skin types I and II compared with patients with skin type IV (3.2 and 2.3, respectively). Skin type was a better predictor of this risk than eye or hair color. The minimal erythemal dose ( MErD ) and minimal phototoxic dose (MPD) increased with increasing skin type number, but within a given skin type each varied as much as sixfold. Skin type was a good clinical predictor of skin cancer risk, but lacked specificity as a predictor of an individual's MErD or MPD.

Administration, Oral↗
PubMed1986

Skin blood flow changes in anaesthetized humans: comparison between skin thermal clearance and finger pulse amplitude measurement.

The effect of general anaesthesia on skin blood flow in the left hand, measured by a new non-invasive probe using the thermal clearance method was examined. A mercury silastic gauge was placed around the third left finger and the plethysmographic wave amplitude was recorded to measure changes in finger pulse amplitude. Heart rate (HR), mean arterial blood pressure (MABP) and skin temperature were also recorded. General anaesthesia was induced by droperidol and phenoperidine injection and propanidid infusion in eight female patients. Skin thermal clearance, plethysmographic wave amplitude, HR, MABP and skin temperature were 0.40 +/- 0.02 w X m-1 degree C-1, 9 +/- 1 mm, 98 +/- 5 beats X min-1, 12.50 +/- 0.93 kPa and 33.3 +/- 3.4 degrees C respectively. The minimal value of MABP was 9.58 +/- 1.06 kPa, whereas skin thermal clearance, plethysmographic wave amplitude, HR and skin temperature increased to 0.45 +/- 0.02 w X m-1 degree C-1, 29 +/- 3 mm, 110 +/- 4 beats X min-1 and 34.4 +/- 0.4 degrees C. Changes in skin thermal clearance correlated well with plethysmographic wave amplitude. Statistically significant changes in these two parameters occurred before significant change in HR, MABP or skin temperature. The results show that the new non-invasive probe using the thermal clearance method appears to be a useful device for measuring cutaneous microcirculation in anaesthetized humans, and responds more quickly than change in skin temperature, which is a delayed effect of skin blood flow change. Our results also show that the intensity of cutaneous vasodilatation induced by general anaesthesia did not relate to the vascular tone before anaesthesia.

Adult↗
PubMed2003

Skin cleansers for occupational use: testing the skin compatibility of different formulations.

OBJECTIVES: Skin-compatible hand cleansing is crucial for the prevention of occupational dermatitis. In this article we give an overview of skin-cleansing products and their ingredients and investigate whether solvents or abrasives could be avoided in cleansers for severely soiled skin. METHODS: Comparison of skin compatibility, cleansing power and effectiveness of different formulations of skin cleansers was performed via Duhring chamber tests [visual score, trans-epidermal water loss (TEWL)] and standard hand-wash tests. RESULTS: The results show that, dependent on the grade of contamination, a range of skin cleansers that allow adequate skin cleansing, is necessary. Solvents could be avoided, by the use of powerful cleansing systems based on tenside/oil mixtures. Only for special contaminations may solvents be useful. Powerful cleansing activity could be performed without abrasives. CONCLUSIONS: The worker must be able to choose the skin cleanser that is adequate for the contamination that is present. Therefore, information and education of the workers are crucial for skin-compatible skin cleansing.

Anti-Infective Agents, Local↗
PubMed1985

Treatment of skin, skin structure, bone, and joint infections with ceftazidime.

The collective experience with ceftazidime in the treatment of skin, soft tissue, bone, and joint infections is presented. Patients were treated with dosages ranging between 25 and 150 mg/kg per day for between five and 42 days. A total of 570 patients with skin and skin structure infections were treated with ceftazidime. Comparative studies, using either cefamandole or tobramycin plus ticarcillin as control drugs, included 239 patients. There were 600 evaluable patients in five categories of skin or skin structure infection: 252 patients had cellulitis, 107 had wound infections, 103 had abscesses, 90 had skin ulcers, and 48 had other miscellaneous infections. Bacteriologic etiologies were gram-negative rods in 303 episodes, gram-positive cocci in 241, anaerobes in 14 episodes, and miscellaneous other organisms in 48 episodes. Overall bacteriologic efficacy was 90 percent in ceftazidime-treated infections and 76 percent in control-treated infections. The clinical efficacy of ceftazidime against infections caused by the gram-positive cocci, particularly Staphylococcus species, was surprisingly good (85 percent) and similar to the efficacy achieved in the cefamandole-treated patients (85 percent). The overall clinical efficacy for ceftazidime was 93 percent. One hundred thirty-four patients with bone or joint infections received ceftazidime. The dosages were similar, but the duration of treatment was the longest in this group. Ceftazidime treatment was compared with standard dosages of tobramycin and ticarcillin in 11 patients. Osteomyelitis was cured in 58 of the 101 patients who received ceftazidime. In five patients, osteomyelitis failed to respond: in two, a resistant Pseudomonas strain emerged; the other three failures were due to persistent bone sequestra. Thirty-eight patients showed improvement. Of those in the tobramycin and ticarcillin group, nine of 10 evaluable patients (90 percent) showed either cure or improvement. The one failure was due to a persistent sequestrum. Thirteen patients with septic arthritis and seven with bursitis were also treated with ceftazidime; the overall cure rate was 75 percent. Adverse reactions to ceftazidime were severe, and the drug was discontinued in 13 of 570 (2.3 percent) patients with skin or skin structure infections and in five of 134 (3.7 percent) patients with bone and joint infections. These data suggest that ceftazidime is effective as monotherapy in the treatment of skin, skin structure, bone, and joint infections, and that it may be more efficacious against staphylococcal infections than predicted from in vitro data.

Abscess↗
PubMed2002

Non-animal testing strategies for assessment of the skin corrosion and skin irritation potential of ingredients and finished products.

The dermatotoxicologist today is faced with a dilemma. Protection of workers and consumers from skin toxicities (irritation and allergy) associated with exposure to products, and the ingredients they contain, requires toxicological skin testing prior to manufacture, transport, or marketing. Testing for skin corrosion or irritation has traditionally been conducted in animals, particularly in rabbits via the long established Draize test method. However, this procedure, among others, has been subject to criticism, both for its limited predictive capacity for human toxicity, as well as for its use of animals. In fact, legislation is pending in the European Union which would ban the sale of cosmetic products, the ingredients of which have been tested in animals. These considerations, and advancements in both in vitro skin biology and clinical testing, have helped drive an intensive effort among skin scientists to develop alternative test methods based either on in vitro test systems (e.g. using rat, pig or human skin ex vivo, or reconstructed human skin models) or ethical clinical approaches (human volunteer studies). Tools are now in place today to enable a thorough skin corrosion and irritation assessment of new ingredients and products without the need to test in animals. Herein, we describe general testing strategies and new test methods for the assessment of skin corrosion and irritation. The methods described, and utilized within industry today, provide a framework for the practicing toxicologist to support new product development initiatives through the use of reliable skin safety testing and risk assessment tools and strategies.

Animal Testing Alternatives↗
PubMed2003

Comparison of skin permeation enhancement by 3-l-menthoxypropane-1,2-diol and l-menthol: the permeation of indomethacin and antipyrine through Yucatan micropig skin and changes in infrared spectra and X-ray diffraction patterns of stratum corneum.

3-l-Menthoxypropane-1,2-diol (MPD) is a derivative of l-menthol, which has an enhancement effect on drug permeation through skin. In this study, the effect of MPD on drug permeation through skin was compared with that of l-menthol. MPD or l-menthol at final concentrations of 3% in 40% ethanol was added to the drugs indomethacin or antipyrine and each mix then applied to Yucatan micropig skin in vitro. Drug concentrations in the skin were higher in the presence of either MPD or l-menthol, however, only l-menthol shortened the lag time of permeation. MPD enhanced the skin permeation of the drugs only by increasing the skin concentration of the drugs. In contrast, l-menthol enhanced the skin permeation of the drugs by increasing both the skin concentration and the diffusion rate in skin. The infrared (IR) spectra and X-ray diffraction patterns of stratum corneum after treatment with MPD did not differ from those of intact stratum corneum. A change in the IR spectra of stratum corneum after treatment with l-menthol was observed at the CH band, and the peaks representative of the lipid structure in the X-ray diffraction patterns decreased in intensity. These results suggest that l-menthol, but not MPD, disrupts the intercellular lipid structure of stratum corneum. Thus, MPD is expected to be a moderate skin permeation enhancer.

Administration, Topical↗
PubMed2001

Hyaluronic acid skin fillers: adverse reactions and skin testing.

BACKGROUND: Hyaluronic acid (HA) fillers have been proposed as alternatives to other temporary skin fillers, such as bovine collagen, for treating facial skin lines and for providing lip augmentation. Several types of commercial HA fillers are now available in many countries. They include Restylane, which is produced by microbiologic engineering techniques, and Hylaform, which is HA extract derived from rooster combs. They have been approved for use in several countries, but not currently in the United States. There are no recommendations to perform pretreatment skin testing by the manufacturers. OBJECTIVE: Our purpose is to describe and comment on our experiences with Hylaform and Restylane fillers. Observation of any side effects and skin testing results were documented. METHODS: Between September 1996 and September 2000, 709 patients were treated with Hylaform and Restylane and were followed up clinically for at least 1 year. Three of these patients (0.42%) developed delayed skin reactions. Three other patients were referred for evaluation of their skin reactions from other practitioners. Five of these 6 patients agreed to skin testing of their forearms. RESULTS: In the 5 patients tested, challenge intradermal skin testing was positive in 4 patients; the reactions started approximately 8 weeks after injection. CONCLUSIONS: There was a slight incidence of delayed inflammatory skin reactions to two HA fillers. Both of these reactions occurred after the first and repeat injections. Challenge skin testing was positive in 4 of 5 tested patients.

Biocompatible Materials↗
PubMed1990

General considerations of the choice of dose limits, averaging areas and weighting factors for the skin in the light of revised skin cancer risk figures and experimental data on non-stochastic effects.

In recent years considerable clinical and experimental data have become available which can form the basis of a better understanding of the response of skin to radiation exposure and should lead to improved radiological protection criteria. Recent biological data from man and pig on the non-stochastic effects following exposure with a range of beta-emitters are combined with recent epidemiological analyses of skin cancer risks in man to form a basis for suggested improved protection criteria for the skin following whole- or partial-body skin exposures. Specific consideration is given to the choice of an organ weighting factor for the evaluation of effective dose-equivalent. Since the stochastic and non-stochastic end-points involve different cell types, which reside at different depths in the skin, the design of an ideal physical dosemeter may depend on the proportion of the body skin that is exposed and the penetrating power of the radiation. Possible choices of design parameters for skin dosemeters are discussed. The limitation of skin exposure from small radioactive sources ('hot particles') is an important practical problem, which is addressed for the first time using animal data. Dose limitation on the basis of an average dose to an area of skin in the vicinity of the particle or on the basis of number of beta-particles emitted could be used. Animal data, for several energies and sizes of beta-emitting sources, indicate that limitation of the average dose to 1 Gy (average dose to 1 cm2 of skin at a depth between 100 and 150 microns) should prevent the occurrence of transient acute ulceration from small sources with dimensions of less than about 1 mm.

Humans↗
PubMed1997

Dietary L-histidine regulates murine skin levels of trans-urocanic acid, an immune-regulating photoreceptor, with an unanticipated modulation: potential relevance to skin cancer.

Solar ultraviolet-B radiation (UVB; 290-320 nm) causes skin cancer and suppresses cell-mediated immunity, preventing the rejection of UV-induced tumors. One mechanism initiating UV suppression involves the trans to cis photoisomerization of urocanic acid (UCA), a histidine derivative found in the stratum corneum. The addition of L-histidine to nonpurified mouse diet has been shown to increase skin trans-UCA levels and sensitivity to UVB immune suppression. Specially formulated L-histidine diets (0.40-64 g/kg) fed to BALB/c mice that were monitored over a 19-wk period resulted in an unexpected modulation of skin trans-UCA. ANOVA revealed a group-time interaction, providing initial evidence that the skin levels of trans-UCA were modulating up and down in all groups except the control group (6.4 g/kg diet). We observed that both high (64 g/kg diet) and low (0.4 g/kg diet) levels of dietary L-histidine resulted in the increase of skin trans-UCA to levels significantly higher than those recorded in the control group. In mice fed these histidine levels, skin trans-UCA increased to between 2.9 and 3.6 nmol/mg skin (64 g/kg diet, over 5 wk; 0.4 g/kg diet, over 8 wk) and then decreased to approximately 1.69 nmol/mg skin, the base-line level (64 g/kg diet, over 11 wk; 0.4 g/kg diet, over 17 wk). The increase in trans-UCA levels in mice with low L-histidine intake may be the result of protein malnutrition, consistent with weight loss observed in those mice. The modulation of trans-UCA levels in skin by dietary L-histidine has not been previously described; its role in skin cancer development is under investigation.

Administration, Oral↗
PubMed2002

Cultured skin substitutes reduce donor skin harvesting for closure of excised, full-thickness burns.

OBJECTIVE: Comparison of cultured skin substitutes (CSS) and split-thickness skin autograft (AG) was performed to assess whether donor-site harvesting can be reduced quantitatively and whether functional and cosmetic outcome is similar qualitatively in the treatment of patients with massive cutaneous burns. SUMMARY BACKGROUND DATA: Cultured skin substitutes consisting of collagen-glycosaminoglycan substrates populated with autologous fibroblasts and keratinocytes have been shown to close full-thickness skin wounds in preclinical and clinical studies with acceptable functional and cosmetic results. METHODS: Qualitative outcome was compared between CSS and AG in 45 patients on an ordinal scale (0, worst; 10, best) with primary analyses at postoperative day 28 and after about 1 year for erythema, pigmentation, pliability, raised scar, epithelial blistering, and surface texture. In the latest 12 of the 45 patients, tracings were performed of donor skin biopsies and wounds treated with CSS at postoperative days 14 and 28 to calculate percentage engraftment, the ratio of closed wound:donor skin areas, and the percentage of total body surface area closed with CSS. RESULTS: Measures of qualitative outcome of CSS or AG were not different statistically at 1 year after grafting. Engraftment at postoperative day 14 exceeded 75% in the 12 patients evaluated. The ratio of closed wound:donor skin areas for CSS at postoperative day 28 was significantly greater than for conventional 4:1 meshed autografts. The percentage of total body surface area closed with CSS at postoperative day 28 was significantly less than with AG. CONCLUSIONS: The requirement for harvesting of donor skin for CSS was less than for conventional skin autografts. These results suggest that acute-phase recovery of patients with extensive burns is facilitated and that complications are reduced by the use of CSS together with conventional skin grafting.

Burns↗
PubMed2004

[Study in functional compensation of skin flap:an experimental of fast prefabricated random skin flap].

OBJECTIVE: To investigate the possibility and the limit in increasing the survival area of the random skin flap by extremely increasing the ratio of its length and width within 24 hours. METHODS: SD rats (n = 20) were chosen for this study. The rats were randomly divided into: subject group and control one. Pre-made skin flap was prepared as design. The subject group was carried out rapid pre-fabricated skin flap formation training. No training was performed in control group. The changes in perfusion value of micro-circulation inside skin flap were monitored during the whole process, and micro-circulation parameters of the skin flap were used to evaluate whether its blood circulation network was mature or not. RESULTS: Training of pre-made skin flap at 18th hour, the perfusion value of its micro-circulation was basically stable, Skin flap formation was finished at 24th hour. Survival area in control group was (68.25 +/- 0.18)% and in subject group was (97.25 +/- 0.24)% (P < 0.01). There was a significant difference between the two groups. CONCLUSIONS: Within short time, it is possible to establish micro-circulation in skin flap which exceeds the limit set by traditional theory. Digitalized judgment can be used to monitor the fast formation of super-big skin flap. This method is reliable and can increase the survival rate of random skin flap.

Animals↗
PubMed2005

Skin debris and micro-organisms on the periwound skin of pressure ulcers and the influence of periwound cleansing on microbial flora.

Many clinicians use the same solution, most often normal saline, to cleanse the periwound skin and the wound bed itself. However, skin debris such as water-insoluble proteins and lipids are not efficiently removed by normal saline solutions. To analyze the skin debris and micro-organisms found on the periwound skin of pressure ulcers and to evaluate the effect of periwound cleansing on the microbial flora, a descriptive study was conducted among 17 long-term care residents with Stage III and IV pressure ulcers. Skin debris from both the periwound area and normal skin was collected from all 17 residents. In addition, micro-organisms from the wound bed, periwound, and normal skin of five residents were collected before, immediately after, and 6 hours and 24 hours after periwound cleansing using a skin cleanser. All microbial species were identified by cultivation. Cholesterol and nitrogen-containing substances were found in greater quantity on the periwound than on normal skin (P = 0.0027 and P = 0.0054, respectively) and the number of isolated micro-organisms from the periwound area was larger than that from normal skin. Protein showed the highest correlation to the microbial count present on the periwound (r = 0.71, P = 0.0014). The microbial counts of all isolated micro-organisms decreased immediately after cleansing but the number of isolates with high microbial counts increased over time. In the wound bed, the number of isolates with decreasing microbial counts was larger than the number of isolates with increasing microbial counts. Both numbers returned to pre-cleansing values after 24 hours, suggesting that periwound cleansing only (without directly cleansing the wound bed) is effective at reducing the microbial counts in the wound bed for up to 24 hours. Further research is needed to evaluate the effects of periwound cleansing on healing time.

Administration, Cutaneous↗
PubMed1984

Quantitative distribution of locally applied lindane in human skin and subcutaneous fat in vitro. Dependence of penetration on the applied concentration, skin state, duration of action and nature and time of washing.

Commercial concentrations of radiolabelled lindane emulsion were applied to human skin specimens. Penetration of the substance into the different layers of the skin was examined quantitatively under the common conditions of therapy, but with variation of the period of action (3, 10 and 24 h), condition of skin specimens (intact, stripped), concentration of the emulsion applied (0.3 and 1%) and washing with water only or water and soap after different periods of action (3 and 10 h) and examination at different times after the washing procedure (7 and 14 h). The flux of lindane in the skin was found to be time-dependent. Generally, the concentration increased with the depth of the layer. An increased availability of lindane (in absence of the stratum corneum, and at long application period) resulted in a preferential accumulation in the epidermis and not in the subcutaneous fat. When the intact skin had been washed with soap and water 3 h after application, the concentration of lindane found in the layer below the stratum corneum 7 h later was higher than the one found when the skin had not been washed. When intact skin had been washed after a short penetration period (3 h), this resulted in an introduction of lindane by the washing process. This effect did not occur with stripped skin. Lindane could be more efficiently removed from the stratum corneum with soap and water than with water alone. A threefold increase of the lindane concentration applied resulted in a threefold increase of the concentration in all layers of intact skin specimens. In stripped skin specimens, an increase could be observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗
PubMed1997

Comparison of bacillary indexes in slit-skin smears, skin and nerve biopsies; a study from Malawi.

Data analyzed in this paper were collected within the framework of the Lepra Evaluation Project, an epidemiological study of leprosy in Karonga District, northern Malawi. For 212 patients information on the number of skin lesions, slit-skin smear and skin biopsy results were available. Among 61 patients with a single lesion none were slit-skin-smear positive and two had bacilli detected in skin biopsies. In contrast, among 119 patients with four or more lesions 34 (28.6%) versus 59 (49.6%) had bacilli detectable in slit-skin smears or skin biopsies, respectively. In a further 47 patients skin biopsy results could be compared with split-nerve biopsy results. In 20 of 47 patients the bacterial indexes (BIs) were identical in skin and nerve biopsies, while in 26 of 47 patients the BIs were higher in nerve than in skin biopsies. This difference, which is consistent with several other studies in the literature, provides an insight into the pathogenesis of leprosy.

Adult↗
PubMed1993

Iontophoresis of hydrocortisone across hairless mouse skin: investigation of skin alteration.

The effects of hydration, sodium dodecyl sulfate (SDS), and electric current on the permeability of hairless mouse skin was examined in vitro with a neutral solute, hydrocortisone, as a permeant. The study was carried out by pretreating the skin with (1) normal saline, (2) 0.06% SDS in 0.3% NaCl, (3) normal saline plus 0.5 mA anodic current, and (4) 0.06% SDS in 0.3% NaCl plus 0.5 mA anodic current for 8 h. The pretreated skin was then immediately used for passive or anodic transport of hydrocortisone. Results show that pretreatment of skin with either normal saline or 0.06% SDS resulted in a slightly increased passive penetration of hydrocortisone with a prolonged lag time, but did not significantly change the anodic transport of hydrocortisone. There was no significant difference between normal saline pretreatment and 0.06% SDS pretreatment, indicating that 0.06% SDS did not irreversibly alter the permeability of skin other than its hydration effect. Pretreatment of skin with current, and especially with current combined with 0.06% SDS, yielded a significant increase in both passive and anodic transport of hydrocortisone with reduced lag time, indicating that alteration of the skin structure had occurred. The reversibility of this alteration depends on the duration of exposure of the skin to the electric field. Short-term exposure (< 2 h) does not appear to change the permeability of skin in any significant way; long-term exposure may lead to slowly reversible or irreversible skin alteration.

Animals↗
PubMed1996

Topical all-trans retinoic acid (RA) induces an early, coordinated increase in RA-inducible skin-specific gene/psoriasin and cellular RA-binding protein II mRNA levels which precedes skin erythema.

Separation of specific and nonspecific "irritant" effects of topical all-trans retinoic acid (RA) is a key to understanding the mechanism of retinoid action in skin. Cellular RA-binding protein (CRABP) II has been found to be a marker of RA activity in human skin. We have also previously identified a skin-specific gene (RIS-1/psoriasin) which is rapidly induced in human skin treated with RA. Here we compared the kinetics and time-course of RIS-1 and CRABP II gene activation by RA, sodium lauryl sulfate (SLS), a classical irritant, and their vehicle (VH), using a quantitative reverse transcription polymerase chain reaction. RIS-1 and CRABP II were both expressed at very low levels in untreated normal human skin, and in RA-treated skin the kinetics and time course of RIS-1 and CRABP II mRNA induction were similar. Relative to VH-treated skin, RA induced RIS-1 mRNA levels within 6 h, which further increased to 6.4-fold by 24 h (n = 4). Similarly, CRABP II mRNA levels increased from 2.6-fold at 6 h to 7.8-fold after 24 h. At 48 h the relative mRNA levels for both genes decreased towards the steady-state levels. Relative to SLS-treated skin, RIS-1 mRNA increased by 3.2-fold after 6 h and by 5.1-fold after 12 h (n = 3). Also, a 2.6-fold higher CRABP II mRNA observed after 6 h increased to 6-fold after 12 h. After 24 and 48 h RA treatment the relative mRNA levels for both genes decreased towards the steady-state levels. RA-induced skin erythema was not obvious until 24 to 48 h. We conclude, therefore, that induction of RIS-1 and CRABP II mRNA levels by topical RA in human skin are early, coordinated molecular events which precede the clinical cutaneous erythematous response to RA.

Administration, Topical↗
PubMed2000

[Split skin and full-thickness skin grafts].

Skin grafting is one of the earliest described surgical procedures. In the age of microsurgery and free-tissue transfer, it remains a utilitarian means of achieving soft tissue reconstruction. Free skin grafts can be classified into three types: full-thickness skin grafts, split-thickness skin grafts, and composite grafts. The indications, techniques, donor site considerations, postoperative complications, and results of each type are reviewed. The full-thickness skin graft for facial and cervical reconstruction is usually harvested from the upper arm or postauricular region and is applied under a tie-over dressing. When comparing the functional and aesthetic results of full-thickness skin grafts and split-thickness skin grafts in terms of morbidity, skin elasticity, skin sensitivity, matching, and scar recurrence, full-thickness skin grafting seems to be the most adequate technique.

Facial Injuries↗
PubMed1997

Skin absorption of the industrial catalyst dimethylethylamine in vitro in guinea pig and human skin, and of gaseous dimethylethylamine in human volunteers.

OBJECTIVES: The aims of the study were three-fold: to assess the skin uptake of the industrial catalyst dimethylethylamine (DMEA) (a) in vitro from water solutions by fresh guinea-pig and human skin specimens, (b) in gaseous form in vivo in human volunteers, and (c) to estimate the relevance of the uptake as an occupational hazard. METHODS: Specimens from the in vitro and in vivo experiments were analysed by gas chromatography using a nitrogen-sensitive detector. DESIGN: DMEA, diluted with water or isotonic saline solution was applied to fresh human or guinea-pig skin, mounted in Teflon flow-through cells with a perfusion fluid flow rate of 1.5 ml/h, samples being collected at 2-h intervals for 48 h. Three healthy male volunteers each had their right forearm exposed (in a Plexiglass chamber) for 4 h to DMEA at each of three different levels (250, 500 and 1000 mg/m3 air). Urine was collected up to 24 h after the start of each experiment. RESULTS: DMEA penetrated both guinea-pig and human skin. The median steady-state flux and permeability coefficient (Kp) values, were 0.009 mg/cm2 x h and 0.001 cm/h, respectively, for guinea-pig skin, and 0.017 mg/cm2 x h and 0.003 cm/h, respectively, for human skin. The median uptake in the three volunteers at the different DMEA exposure levels (250, 500 or 1000 mg/m3) was 44, 64 and 88 micrograms, respectively. The median Kp for all experiments was 0.037 cm/h. CONCLUSION: Uptake of DMEA through the skin is of far less importance than simultaneous uptake via the airways. Thus, the amount of DMEA excreted in urine is a variable of limited use for the purposes of biological monitoring. Although a wide range of Kp values was obtained in the in vitro experiments, both for guinea-pig and human skin, there was no marked difference in median Kp values between the two types of skin. The Kp values were lower than those obtained for human forearm skin in vivo. However, future studies of other tertiary aliphatic amines may show the in vitro method to yield values predictive of those obtained in in vivo studies.

Adult↗