Skin absorption and penetration.
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Animals↗
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Possible efficacy of a Creek folk medicine through skin absorption: an object lesson in ethnopharmacology.
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Ethnobotany↗
Absorption of lead through the skin.
Absorption of lead through the skin was studied by comparing the effect produced by lead naphthenate or lead acetate solution, when coated on the skin of rats, with data obtained from subcutaneous injections of these solutions. Body weight and liver size and weight decreased in the case of rats receiving the subcutaneous dose. delta-Aminolevulinic acid dehydratase (ALA-D) in liver was decreased in all rats having been treated with lead compounds. The distribution of absorbed lead has been evaluated by assay of the lead content in brain, liver, kidney, spleen and muscle in the rats. The results of this study seem to verify that absorption of lead through the skin does occur and the findings confirm lead naphthenate to be more toxic than lead acetate.
Animals↗
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↗
4,4'-methylene-bis-ortho-chloro-aniline (MBOCA): absorption and excretion after skin application and gavage.
4,4'-methylene-bis-ortho-chloro-aniline ( MBOCA ) is an aromatic amine and industrial chemical that has been shown to cause cancer of several different organs in rats and mice and bladder cancer in dogs. The purpose of this study was to determine the efficacy of using urinary concentrations of MBOCA as a means for evaluating extent of exposure. Male Sprague-Dawley rats were given MBOCA and [14C] MBOCA by either gavage or skin application. Concentrations and amounts of 14C were measured in urine, feces, skin and total carcasses, and parent MBOCA in urine at several intervals after application. The percentages of administered doses excreted and retained in the animals were calculated and comparisons made. Within 72 hr after gavage 16.5% of the administered compound was excreted in urine as 14C but only 0.25% as parent MBOCA . In the same interval after skin application a maximum of 2.54% of administered MBOCA was excreted as 14C but only 0.008% as parent MBOCA . Seventy-two hours after gavage 13.7% of the administered dose was retained in the tissues, and after skin absorption 5-13% was retained. With gavage the rate of excretion of 14C in urine and feces was very high in the first 24 hr (68.3%) but fell off rapidly (2.07%) by the third day. After skin absorption the rates of excretion of 14C were fairly constant over a 3-day period. Less MBOCA was absorbed from the skin if the skin was washed within 8 hr after application, as compared to waiting 24 hr or not washing at all. The amount of parent MBOCA detected in urine is a very small amount of that applied or absorbed. The percentage detected and the rates of excretion depend upon the route of administration, and the interval between exposure and sampling. For these reasons urinary analysis for MBOCA can be used only as very imprecise indicators of extent of recent exposure.
Administration, Oral↗
Assessment and clinical implications of absorption of sunscreens across skin.
Topical sunscreen products are widely used for protection of the skin against the harmful effects of exposure to ultraviolet radiation. Sunscreen agents are incorporated into many everyday-use cosmetics as well as so called 'beach' products. An ideal sunscreen product will provide effective protection against UV radiation with minimal skin absorption of the active ingredients. There is now clear evidence that a common sunscreen chemical, benzophenone-3, is absorbed systemically following topical application to the skin. Other more lipophilic sunscreens are absorbed into the skin, but penetration to deeper tissues and the cutaneous circulation appears to be limited. However, the extent to which sunscreens that are absorbed into the stratum corneum are absorbed to deeper tissues and the systemic circulation over time is currently unknown. The formulation vehicle in which the sunscreen is presented to the skin has a significant effect on absorption into and through the skin. Alcohol-based formulations appear to increase sunscreen absorption. In addition, some sunscreen chemicals may enhance the skin absorption of other sunscreens when applied in combination. Clearly, further research into the influence of sunscreen and formulation properties on skin absorption could lead to optimal design of sunscreen products with respect to efficacy and minimizing absorption. Despite the extensive use of sunscreen products, there have been few reports of adverse effects, and these tend to be limited to acute dermatitis and allergies. Some recent reports have raised concerns that sunscreen chemicals may damage tissues, particularly in the presence of UV radiation. Further research into the toxicity of sunscreens is urgently required. Given the information currently available and the importance of protecting the skin against sun damage, there is no clear justification for restricting the use of sunscreen products at this time.
Absorption↗
Investigation of the absorption of hypericin into the skin of hairless mice.
The skin absorption of hypericin was evaluated in hairless mice to develop an optimised hypericin topical formulation that could be used in the clinical study of psoriasis. Hypericin (0.01-1.0%) in Beeler basis, polyethylene glycol ointment, carbopol gel, cetomacrogol cream, petrolatum or emulsifying ointment, with and without skin-absorption enhancers (isopropylidene glycerol and diethylene glycol monoethyl ether), was tested in-vivo on hairless mice skin. Using a skin-stripping technique and the intrinsic fluorescence of hypericin under standardised UV365 irradiation, it was demonstrated that the absorption of hypericin very much depended on the vehicle used. The concentrations of hypericin in the skin were then estimated by HPLC analysis. For this purpose, two vehicles were employed, with which hypericin penetrated the skin of hairless mice well (emulsifying ointment with isopropylidene glycerol) or very poorly (polyethylene glycol ointment). In the case of emulsifying ointment with isopropylidene glycerol (0.05% hypericin), a substantial concentration of hypericin (8.6+/-3.2 microg g(-1)) (mean +/- s.d., n = 5) was found in the skin. With polyethylene glycol ointment, however, only a limited hypericin skin concentration (0.38+/-0-34 microg g(-1), n = 5) was achieved. These results show that emulsifying ointment with polyethylene glycol holds promise as an effective topical vehicle for the treatment of skin diseases, such as psoriasis, with hypericin.
Administration, Cutaneous↗
Percutaneous absorption in preterm infants.
The skin of preterm infants varies considerably in its level of maturity. To understand skin absorption in premature infants better, we report a technique for the assessment of percutaneous absorption at various gestational and postnatal ages using stable, isotope-labeled (13C6) benzoic acid. Our results indicate that in the preterm infant, this method detects enhanced skin absorption in the first postnatal days, which declines over three weeks to that expected of a full-term infant. This approach also indicates an inverse relationship between gestational age and skin absorption, as well as postnatal age and skin absorption. The reported technique is a safe and noninvasive method using a model skin penetrant for the study of percutaneous absorption in preterm infants from which basic data may be derived to add to our understanding of skin barrier function.
Benzoates↗
Effect of heat on the percutaneous absorption and skin retention of three model penetrants.
The effect of heat on the transdermal delivery of model penetrants of differing lipophilicity through artificial membranes (non-rate limiting) and human epidermis was investigated in vitro. Saturated suspensions of the model penetrants; methyl paraben (MP), butyl paraben (BP) and caffeine (CF) in deionised water (vehicle) were used to attain maximal thermodynamic activity. Franz cell experiments were performed at temperatures ranging from 23 to 45 degrees C using the infinite dose method. Artificial membrane studies showed the penetrant diffusivity (diffusion coefficient) in the vehicle to be totally dependent on temperature and not changes in donor solubility. Epidermal flux and retention of all penetrants was found to be affected by temperature. The amount of penetrant retained in the epidermis was found to be in the order BP>CF>MP whilst the transdermal fluxes increased in the order MP>BP>CF with increasing receptor temperature. Estimated epidermal diffusivity of MP was found to be significantly affected by temperature (P< or =0.05) compared to BP and CF. Using Arrhenius plots, a lower activation energy was recorded for CF and may suggest a difference in permeation kinetics compared to the other penetrants.
Adjuvants, Pharmaceutic↗
Effect of methyl substitution of benzene on the percutaneous absorption and skin irritation in hairless rats.
The permeation rate and skin retention of benzene and methylbenzenes were assessed in vitro using hairless rat skin. The effects of unocclusive dermal exposures of these chemicals (15 microl every 2h for 8h a day for 4 days) on the transepidermal water loss (TEWL), erythema and skin histopathology were measured in CD hairless rats. The expression of IL-1 alpha and TNF-alpha in the skin and blood were measured at the end of dermal exposures. The flux of benzene was about 1.5-, 2.5- and 80-fold higher than toluene, xylene and tetramethyl benzene isomers (TMB), respectively, and the values were inversely correlated with molecular weight (r(2)=0.7455) and logoctanol-water partition coefficient (r(2)=0.7831). The retention of chemicals in stratum corneum (SC) was in the order of TMB>xylene>toluene approximately benzene. The TEWL and erythema data demonstrated that the irritation was in the following order: TMB>xylene>benzene. The histo-pathological examination showed that xylene and TMB induced granulocyte infiltration, swelling of the epidermis, and extensive disruption and damage of stratum corneum. Likewise, the expression of IL-1 alpha in the blood and TNF-alpha in the skin after dermal exposures was higher for TMB followed by xylene and benzene compared to control. In conclusion, the aromatic hydrocarbon chemicals induced cumulative irritation upon low-level repeat exposures for a 4-day period and the irritation increased with the number of methyl groups of benzene. The affinity of the chemical to SC and their gradual accumulation in the skin in the present study is the reason for the differences in the skin irritation profiles of different aromatic chemicals. Our ultimate goal is to develop a biologically based model that connects skin retention of chemical to the skin irritation response. The findings of the present study will be helpful in understanding the role of these chemicals in the jet fuel and various petroleum based fuels in inducing skin irritation response.
Animals↗
Zinc absorption through skin: correction of zinc deficiency in the rat.
The therapeutic effect of topical administration of zinc was tested in pregnant rats consuming a diet deficient in the element. Four groups of rats were fed a zinc-deficient diet for 24 hr. Half of the animals were treated during this period with a topical application of oil saturated with zinc chloride, for the full 24 hr in one group, and for the last 8 hr in the other. In the two remaining groups, oil without zinc chloride was applied under the same conditions as described above, and in all cases oral ingestion of the supplement was prevented. At the end of the 24-hr period, the animals were killed and plasma zinc was determined. An additional group of animals consuming a diet adequate in zinc was killed without any treatment to provide control values of normal plasma zinc. Rats consuming the deficient diet and without topical zinc supplementation had plasma zinc values significantly lower than all other groups after 24 hr. Animals receiving zinc supplementation for 8 hr had plasma levels similar to those of the control group fed an adequate zinc diet and significantly higher than those of rats that received no zinc application to the skin. In animals in which zinc was applied for 24 hr, plasma zinc values were significantly higher than in any other group, including normal controls. The results indicate that percutaneous transport of zinc may be of sufficient magnitude to be clinically significant and that topical application of this element may be useful in cases of dietary zinc deficiency or diseases producing a zinc deficiency state.
Animals↗
Percutaneous absorption and skin irritation upon low-level prolonged dermal exposure to nonane, dodecane and tetradecane in hairless rats.
Even though the dermal toxicity of hydrocarbon fuels has been well established in the literature, there is little information available on the dermal penetration kinetics and irritation potential of the individual hydrocarbons. The penetration and skin retention of nonane, dodecane and tetradecane was assessed in vitro using hairless rats' skin. The effects of unocclusive dermal exposures of these chemicals (15 microL every 2 h for 8 h a day for four days) on the transepidermal water loss (TEWL) and erythema were measured in CD hairless rats. The expression of interleukin 1alpha (IL- 1alpha) and TNF-alpha in the skin and blood were measured at the end of dermal exposures. The flux of dodecane was 3- and 77-fold higher than nonane and tetradecane. The retention of chemicals in stratum corneum (SC) was in the order of tetradecane > dodecane > nonane, and directly correlated to the log Kp (r2 = 0.9900) and molecular weight of the chemicals (r2 = 0.8782). The TEWL and erythema data indicate that irritation was in the following order: tetradecane > dodecane > nonane. Likewise, the expression of IL-lalpha in the blood and TNF-alpha in the skin after dermal exposures was higher for tetradecane followed by dodecane and nonane compared to control. In conclusion, the aliphatic hydrocarbon chemicals of the present study induced cumulative irritation upon low-level repeat exposures for a four-day period. The affinity of the chemicals to SC and their gradual accumulation in the skin in the present study is the probable cause for the differences in the skin irritation profiles of different aliphatic chemicals. The findings of the present study will be helpful in understanding the skin irritation response of the chemicals in humans; indeed the reality check arises from dermal exposures in humans and human experience in occupational handling of these chemicals.
Administration, Cutaneous↗
Transdermal absorption and skin metabolism of viprostol, a synthetic prostaglandin E2 analogue.
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Animals↗
Percutaneous absorption and skin sensitization.
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Animals↗
[Therapy of toxin absorption in skin burns. Synthetic skin replacement or tannic acid (author's transl)].
The influence of toxic factors from burned skin on pathogenesis of burn disease has been demonstrated in recent years. For preparation for skin transplantation synthetic material is used. The present study was undertaken to investigate if such material could inhibit the resorption of toxic factors. Specific mitochondrial alterations, which are reproducibly found 5 days after skin burn or application of burn toxin, served as parameter. Rats, which were treated shortly after burn or later with tannic acid were used as controls. Glucose and urea were measured in serum to check the synthetic function. Therapy with Epigard resulted in a better general condition and normal values of glucose and urea, but no reduction of specific mitochondrial alterations. Treatment with tannic acid caused no improvement in general condition, glucose and urea levels were not significantly altered. Only the early application resulted in a reduction of mitochondrial alterations. An otherwise indicated therapy with a synthetic skin material is not suitable for inhibition of the resorption of toxic factors from burnt skin.
Animals↗
Effect of skin pretreatment with fatty acids on percutaneous absorption and skin retention of piroxicam after its topical application.
The enhancing effect of several fatty acids from different subclasses: saturated (lauric acid), mono-unsaturated (oleic acid) and poly-unsaturated (linoleic and linolenic acids) in the percutaneous absorption of piroxicam was investigated. These fatty acids were applied on the skin membrane in three different ways: included in the vehicle, as a pretreatment or both. An increase in piroxicam flux value was found for lauric and oleic acids in the following order: skin pretreatment with 5% fatty acids followed by application of gels containing 5% fatty acids>skin pretreatment with 5% fatty acids followed application of control gel>gel containing 5% fatty acids without skin pretreatment. For linoleic and linolenic acids, the piroxicam flux in the two pretreatment experiments was almost the same, although higher than when fatty acids were included in the formulation. Skin pretreatment with 5% linolenic acid in propylene glycol followed by application of control gel or a gel containing 5% linolenic acid, showed the highest enhancing capacity. After skin pretreatment with fatty acids, the lag time values decreased nearly three times compared to those obtained when the same fatty acids were included in the formulation. The amount of piroxicam retained in the skin after pretreatment with fatty acids was found to be very similar for all fatty acids and 3-fold higher than in the experiments without skin pretreatment.
Administration, Topical↗
In vitro percutaneous absorption models.
In vitro skin absorption studies are commonly used to estimate in vivo skin absorption in topical safety and efficacy evaluations. In vitro studies are more economical and result in minimization or elimination of the use of animals.
Administration, Cutaneous↗
Percutaneous alcohol absorption and skin necrosis in a preterm infant.
A 27-week gestation infant developed severe haemorrhagic skin necrosis on the back and buttocks after umbilical arterial catheterisation. Before catheterisation the skin was cleaned with methylated spirits. A blood alcohol level taken 18 hours after catheterisation showed a blood ethanol level of 259 mg/100 ml and a blood methanol level of 26 mg/100 ml. We conclude that the methylated spirits caused this extensive skin damage and that percutaneous absorption via the readily permeable skin of this immature baby resulted in the dangerously high alcohol levels.
Catheterization↗