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At least 253 records · Page 14Linked to original sources
PubMed1975

Toxicology of octabromobiphenyl and decabromodiphenyl oxide.

Decabromodiphenyl oxide (DBDPO) and octabromobiphenyl (OBBP) perform well as fire-retardant additives for thermoplastics. Both compounds have low acute oral toxicity and low skin absorption toxicity. They are neither primary skin irritants or skin sensitizers and are only mildly irritating to the eyes. A 30-day dietary feeding study in rats established 8 mg DBDPO/kg-day as an unequivocal no-effect level and 80 mg/kg-day as a marginal effect level. A no-effect level was not established for OBBP in a comparative study. A 2-yr rat study providing 0.1 mg DBDPO/kg-day in the diet revealed the bromine concentration reached a plateau in the liver within 30 days, while the concentration in adipose tissue slowly increased. A comparable OBBP study revealed bromine concentration in the liver and adipose tissue increased steadily and rapidly with no attainment of a plateau during 180 days of the study. Neither compound produced an accumulation of bromine in other tissues. After administration of 14C DBDPO, all 14C activity was eliminated via the feces within 2 days. After administration of 14C OBBP, 62% was eliminated with a half-life of less than 24 hr; the half-life for the remainder was greater than 16 days. In a teratology study, 10, 100, or 1000 mg DBDPO/kg-day had no effect in rats. Reproductive capacity of rats was not effected at 3, 30, or 100 mg DBDPO/kg-day. No effects were observed on cytogenetic examination of bone marrow cells of parents and weanlings from the reproduction study.

Abnormalities, Drug-Induced↗
PubMed2005

Total body burden arising from a week's repeated dermal exposure to N,N-dimethylformamide.

BACKGROUND: Hazardous chemicals and their metabolites may accumulate in the body following repeated airborne exposures and skin contact. AIMS: To estimate the contribution of skin absorption to total body burden of N,N-dimethylformamide (DMF) across a working week in two groups with similar levels of respiratory exposure but dissimilar skin contact. METHODS: Twenty five workers in a synthetic leather (SL) factory, 20 in a copper laminate circuit board (CLCB) factory, and 20 age and sex matched non-DMF exposed subjects, were recruited. Environmental monitoring of DMF exposure via respiratory and dermal routes, as well as biological monitoring of pre-shift urinary N-methylformamide (U-NMF), were performed for five consecutive working days. RESULTS: Environmental and biological monitoring showed no detectable exposure in controls. The average airborne DMF concentration (geometric mean (GM) 3.98 ppm, geometric standard deviation (GSD) 1.91 ppm), was insignificantly lower for SL workers than for CLCB workers (GM 4.49, GSD 1.84 ppm). Dermal DMF exposure and U-NMF values, however, were significantly higher for SL workers. A significant pattern of linear accumulation was found across a five day work cycle for SL workers but not for CLCB workers. CONCLUSIONS: Dermal exposure to DMF over five consecutive days of occupational exposure can result in the accumulation of a significant DMF body burden. The long term exposure response under both repeated and intermittent conditions of substantial skin exposure is worthy of note.

Adult↗
PubMedDate not supplied

The pig as an experimental animal model of percutaneous permeation in man: qualitative and quantitative observations--an overview.

The pig has been a well-recognized experimental animal in biomedical research for many centuries. Physiological and anatomical similarities between man and pig made this animal a good model for man in many research areas. Pharmacological and toxicological research on the skin is often based on knowledge of skin absorption and percutaneous permeation. Anatomical, physiological and biochemical similarities are cited and various uses of the pig as a model for man in the investigation of skin permeation are reviewed. Further, several isolated organ models are reviewed. The importance of full details of the experimental animal, namely its age, sex, breed, size (weight) and body region, is emphasized.

Animals↗
PubMedDate not supplied

Dermal absorption of neat liquid solvents on brief exposures in volunteers.

The dermal absorption of liquid 1,1,1-trichloroethane (111TRI), trichloroethene (TRI), tetrachloroethene (TETRA), toluene (TOL), and m-xylene (XYL) was studied in volunteers. The solvents were applied for 3 min on the volar forearm over an area of 27 cm2. An inhalation exposure with a known input rate served as a reference exposure. Using the linear system dynamics method, permeation rates were calculated from exhaled air concentration courses measured after both inhalation and dermal exposure. The permeation time courses of the solvents showed two different patterns. TRI, TOL, and 111TRI in three subjects showed fast increase in permeation, reaching maximal permeation rates a few minutes after initiation of exposure. Slower permeation was seen in the other three subjects exposed to 111TRI and in all subjects exposed to TETRA and XYL with the time of maximal permeation rates of 15-25 min. These differences in the permeation may partly be explained by the irritation of the skin observed in all subjects showing fast permeation kinetics. The flux into the skin averaged over the exposure period amounted to 56, 430, 69, 223, and 46 nmol/cm2/min for 111TRI, TRI, TETRA, TOL, and XYL, respectively. Comparing the dermal uptake with the respiratory uptake at the TLV, all solvents showed substantial skin absorption, although at present only TOL has a skin indication in the American Conference of Governmental Industrial Hygienists threshold limit value list.

Adult↗
PubMed2004

Percutaneous absorption of flavan-3-ol conjugates from plant procyanidins.

Catechins (flavanols) are strong antioxidants, free radical scavengers and inhibitors of lipid peroxidation. New bio-based antioxidant compounds obtained by depolymerization of plant polymeric flavanols (procyanidins) in the presence of cysteine or cysteamine, as well as their underivatized counterpart, (-)-epicatechin, were evaluated in terms of their percutaneous absorption profiles taking into account their free radical scavenging efficiency. The evaluation of the percutaneous absorption of flavanols was carried out by an in vitro methodology using both pig and human skin. A good correlation was obtained using both skins in the evaluation of the skin absorption profiles. It can be deduced that 4beta-(S-cysteinyl)epicatechin (Cys-Ec) has a tendency to be located mainly in the outermost layers of the skin, whereas 4beta-(2-aminoethylthio)epicatechin (Cya-Ec) has a pronounced percutaneous absorption capacity. Their antioxidant properties and their skin penetration profiles support their potential cosmetic or pharmacological applications.

Animals↗
PubMed1999

[Tridimensional skin models recording percutaneous absorption]

Today there is a lack of generally accepted alternatives to animal experiments for the evaluation of percutaneous absorption or skin penetration. To evaluate the potential of commercially available reconstructed epidermis we compared the barrier function of the three dimensional human skin equivalents Episkintrade mark, EpiDermtrade mark, and Skinethictrade mark to those of excised human skin. Moreover the batch-to-batch variation of skin equivalents was determined. Methods for evaluation included the determination of transepidermal water loss (TEWL) and of the prednisolone (PD) penetration. Whereas TEWL values of Skinethictrade mark and EpiDermtrade mark were very close (15 g·m-2·h-1), PD-penetration showed a clearly superior barrier function with the Skinethictrade mark model. Drug penetration was only 50% of the EpiDermtrade mark model and PD concentrations in the acceptor medium amounted to 150 ng/ml as compared to 300 ng/ml. The highest values were obtained with the Episkintrade mark model (20 g·m-2·h-1, 500 ng/ml). Therefore this model has the poorest barrier function. The TEWL value for human skin was 9 g·m-2·h-1 and PD concentrations in the acceptor medium were below the limit of detection (10.1 ng/ml). Because of the superior barrier function of the Skinethictrade mark the following evaluation was only performed using this model. Batch-to-batch variation was less than with human skin (interindividual variation of 2 h TEWL 12% and > 19%). Despite of the slightly less well-developed barrier, this skin model clearly appears superior with respect to the reproducibility of data. Therefore future investigations on the potential of human skin equivalents for the determination of percutaneous absorption appear very promising.

Journal Article↗
PubMed2006

In vitro studies on release and human skin permeation of Australian tea tree oil (TTO) from topical formulations.

Essential oils are widely used in pharmaceutical and cosmetic preparations e.g. as fragrance, active ingredient or penetration enhancer. However, reports on skin absorption are rare. Therefore, the aim of our study was to investigate the capability of terpinen-4-ol, the main compound of Australian tea tree oil (TTO), to permeate human skin. In static Franz diffusion cells permeation experiments with heat separated human epidermis were carried out using infinite dosing conditions and compared to liberation experiments. The flux values of three different semisolid preparations with 5% TTO showed the rank order semisolid O/W emulsion (0.067 microl/cm2 h) > white petrolatum (0.051 microl/cm2 h) > ambiphilic cream (0.022 microl/cm2 h). In comparison to the flux value obtained with the native TTO (0.26 microl/cm2 h), the flux values are remarkably reduced due to the lower amount of terpinen-4-ol. P(app) values for cream (2.74+/-0.06 x 10(-7) cm/s) and native TTO (1.62+/-0.12 x 10(-7) cm/s) are comparable whereas white petrolatum (6.36+/-0.21 x 10(-7) cm/s) and semisolid O/W emulsion (8.41+/-0.15 x 10(-7) cm/s) demonstrated higher values indicating a penetration enhancement. No relationship between permeation and liberation was found.

Administration, Cutaneous↗
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↗
PubMed2002

Evaluation of respiratory and cutaneous doses of chlorothalonil during re-entry in greenhouses.

Five female workers were monitored for 5 consecutive days during re-entry into a greenhouse containing ornamental plants. Skin contamination (excluding hands) was evaluated with nine pads of filter paper placed on the skin. Hand contamination was assessed by washing with 95% ethanol. Respiratory exposure was evaluated by personal air sampling. The respiratory dose was based on a lung ventilation of 15 l/min. The doses absorbed were estimated assuming 10% skin absorption and 100% lung retention. Dislodgeable foliar residue was determined on days of re-entry to evaluate the decay of chlorothalonil. Chlorothalonil was analysed in the different matrices by GC-MS. Respiratory exposure was less than skin contamination, being 11.4+/-5.1% (mean+/-SD) of total exposure. The estimated total absorbed dose did not exceed the acceptable daily intake of 0.03 mg/kg body mass. The hands and unexposed skin of all workers were always found to be contaminated. Greater precautions are therefore needed to reduce skin exposure (clean gloves and suitable clean clothing every day).

Calibration↗
PubMed2005

Transdermal delivery of tea catechins by electrically assisted methods.

Tea polyphenols, including (+)-catechin, (-)-epicatechin, and (-)-epigallocatechin-3-gallate (EGCG), have been shown to possess potent antioxidant and chemopreventive activities. The aim of this study was to assess the effects of electroporation, iontophoresis, and their combination on the transdermal delivery of tea catechins across porcine skin. The permeation characteristics were investigated using various analogues of catechins, pH values, and modes of electroporation and iontophoresis. The mechanisms by which these catechins were transported via the skin were elucidated by examining the electric conductivity, transepidermal water loss (TEWL), and fusion of stratum corneum lipid liposomes (SCLL). The isomers, (+)-catechin and (-)-epicatechin, showed different behaviors of skin permeation and local skin deposition with the electrically assisted methods. The results suggest evidence of selective skin absorption of (-)-epicatechin over (+)-catechin. A synergistic effect was detected for (+)-catechin but not for (-)-epicatechin after application of electroporation followed by iontophoresis. The presence of a gallic acid ester in the structure of EGCG significantly increased the skin uptake of catechins. However, a negligible amount of or no EGCG molecules permeated across the skin. The mechanisms involved in the enhancement of electroporation may be the skin reservoir effect and an increase in skin permeability. The TEWL profiles suggest that in addition to the force of electrorepulsion, the skin hydration effect and structural alterations may also have contributed to the enhancement by iontophoresis. Electroporation did not influence the skin barrier function, although the skin permeability increased according to the SCLL fusion study.

Administration, Cutaneous↗
PubMed2005

Design of a phytosphingosine-containing, positively-charged nanoemulsion as a colloidal carrier system for dermal application of ceramides.

Positively charged oil/water (o/w) nanoemulsions (PN) are effective vehicles to change the permeability of the skin. This study focused on the preparation and characterisation of phytosphingosine (PS) containing PN (PPN) which serve as colloidal carriers for the dermal application of ceramide IIIB (CIIIB) and the stratum corneum (SC) lipids (PPNSC) such as ceramide III (CIII), cholesterol, and palmitic acid. The investigations were conducted using appropriate emulsification and homogenisation processing conditions to optimise PPNSC with regard to droplet size, physical stability, and solubility of PS, CIII and CIIIB. A decrease in droplet size was observed through eight homogenisation cycles at a pressure of 500 bar and a temperature of 50 degrees C. Above these optimal values, an increase in droplet size was observed. PS and ceramides have low solubilities in oil and water. When Lipoid E-80 (LE80) was added to the oil phase, the solubility of PS and ceramides increased, indicating some interactions shown by DSC measurements. SC lipids and CIIIB could be successfully incorporated in PPN without producing any physical instability. The high stability of PPNSC is probably due to the presence of a hydrophilic (Tween 80) and a lipophilic surfactant (LE80), supported by the lipophilic cosurfactant PS, at the o/w interface. It was shown that PS was responsible for the positive charge and thus supported the high physical stability of PPNSC. This optimised emulsion was selected for further skin absorption evaluation.

Calorimetry, Differential Scanning↗
PubMed1984

Percutaneous absorption, disposition, and excretion of 4,4'-methylenebis(2-chloroaniline) in dogs.

Percutaneous (pc) absorption, disposition, and excretion of 14C-MBOCA (4,4'-methylenebis(2-chloroaniline) ) were investigated in male beagle-type dogs by HPLC and compared to intravenously (iv) administered controls. Following application of 115 muCi MBOCA to a 25 cm2 area of the skin, no measurable radioactivity was detected in blood for the subsequent 24-hr period, but 14C-MBOCA and metabolites were excreted in urine and bile. During the 24-hr collection period, a total of 1.3% of the administered dose was recovered in the urine (0.4% of which was unchanged MBOCA). At 24 hr 0.62% of the dose was recovered in gallbladder bile. Approximately 90% of the administered dose was recovered in skin at the application site. Liver, kidney, and fat were the tissues with highest radioactivity. After a bolus iv injection, MBOCA disappeared rapidly from blood (t 1/2 beta = 0.70 hr). In the 24 hr following iv injection, 46% of the administered dose was excreted in urine (0.54% of which was unchanged MBOCA). At 24 hr 32% of the dose was recovered in gallbladder bile. Tissue radioactivity was 10-20 X higher after iv than pc administration and highest in liver, kidney, fat, and lung. The results demonstrated in a canine model that skin absorption was a viable route of entry for MBOCA and that unmetabolized MBOCA was a small percentage (0.4-0.5%) of the total urinary excretion. MBOCA was rapidly and extensively metabolized and excreted in urine and bile following both iv and pc administration.

Animals↗
PubMed1996

Influence of dibutyl phthalate on dermal sensitization to fluorescein isothiocyanate.

What limited evidence there is indicates that the formulation in which a chemical allergen is encountered on the skin can have a marked impact upon the induction of cutaneous immune responses and the subsequent development of contact sensitization. The purpose of the present investigations was to examine further this phenomenon by analysis of the influence of dibutyl phthalate (DBP) on dermal sensitization to fluorescein isothiocyanate (FITC), a skin sensitizing fluorochrome. Addition of DBP augmented very substantially, in a dose-dependent fashion, the ability of topically applied FITC to stimulate proliferative responses in mice by draining lymph node cells (LNC), a correlate of skin sensitizing potential. Under these conditions, exposure of mice to DBP alone failed to elicit significant LNC responses. The influence of DBP on the accumulation of dendritic cells (DC) induced by FITC was examined also. Although 10% DBP had little effect on the numbers of DC found within draining nodes 18 hr following exposure of mice to FITC, the phthalate did result in a very substantial increase in the frequency of lymph node DC bearing detectable antigen (FITC+ DC). Furthermore, in the presence of DBP the median amount of FITC associated with antigen-bearing DC was higher. In vitro skin absorption studies indicated that DBP was associated with a small increase in percutaneous absorption of FITC. Collectively these data demonstrate that the vehicle formulation can exert a marked influence on dermal sensitization and that one mechanism which may be relevant is the increased acquisition of antigen by DC, associated possibly with altered penetration of the allergen into or through the skin.

Administration, Topical↗
PubMedDate not supplied

The dermal bioavailability of radiolabelled benzo[a]pyrene from acetone or from oils of differing viscosity, assessed by DNA and protein binding.

Tritium-labelled benzo[a]pyrene ([3H]BaP) was applied to mouse skin in acetone or mineral oils of differing viscosity. Epidermal DNA and protein were extracted after 24 or 48 h and the degree of adduct formation determined by the radioactivity present. When [3H]BaP was applied in acetone, the degree of DNA and protein binding was around 15-20 times greater than that observed when a low-viscosity oil was used as a vehicle. When applied in oils of differing viscosity, however, only a twofold difference was seen across the whole viscosity range (13.5 cSt* at 40 degrees C to 1665 cSt at 60 degrees C). From measurements made of urine and faecal radioactivity and from small-scale investigations using other routes of administration, it was clear that the grooming activity of the animals had a marked effect on skin absorption and macromolecular binding. It is possible that greater grooming activity with low-viscosity oils may explain why oil viscosity did not have a greater effect on binding levels, but further studies are needed to investigate this. These findings may have important implications in the interpretation of long-term skin painting studies and may assist in the interpretation of analytical data and short-term biological assays.

Acetone↗
PubMed1993

Metabolism of propranolol during percutaneous absorption in human skin.

This in vitro study evaluated the extent of the absorption and metabolism of propranolol in human skin from four sources. Between 10.4 +/- 3.1 and 36.6 +/- 2.6% of the applied dose was absorbed; however, only a small portion (between 4.1 +/- 0.9 and 16.1 +/- 1.3%) of the dose permeated through the skin. Naphthoxyacetic acid formed during percutaneous absorption was located in the skin supernate. 4'-Hydroxypropranol was formed during percutaneous absorption and by skin microsomes. In addition, the microsomes biotransformed propranolol to norpropranolol. The retention of some of the absorbed drug and metabolites in the skin could explain the low plasma concentration and irritation observed following topical application of propranolol.

Adult↗
PubMedDate not supplied

Percutaneous absorption of 5-iodo-2' deoxycytidine in the hairless rat and in man.

A study of percutaneous absorption of the anti-herpetic agent 5-iodo-2' deoxycytidine (IDC) was performed in vitro on the rat and on man and in vivo on the rat, using samples of normal skin and skin stripped of its stratum corneum. With normal skin, absorption was 1.84 cm.h1 10(-4) for the rat and 0.33 cm.h1 10(-4) for human skin; when the stratum corneum was absent, absorption was approximately 15 times higher. The results are discussed in terms of efficacy and toxicity of the drug.

Animals↗