Spectral Reflectance Measurement of Evaporating Chemical Films: Initial Results and Application to Skin Permeation.

The present study has 2 aims. First, the method of spectral reflectance was used to measure evaporation rates of thin (∼25-300 μm) films of neat liquid volatile organic chemicals exposed to a well-regulated wind speed u. Gas-phase evaporation mass transfer coefficient (k) measurements of 10 chemicals, 9 of which were measured at similar u, are predicted (slope of log-log data = 1.

In vitro human skin permeation of benzene in gasoline: Effects of concentration, multiple dosing and skin preparation.

In vitro human skin benzene permeation was measured from gasoline formulations with benzene concentrations ranging from 0.8 to 10 vol% and from neat benzene. Steady-state fluxes (J), permeability coefficients (k) and lag times (t) were calculated from infinite dose exposures.

Molecular and biochemical characteristics of the inulosucrase HugO from Streptomyces viridochromogenes DSM40736 (Tü494).

Polyfructans are synthesized from sucrose by plants (mostly inulin) and by both Gram-negative and Gram-positive bacteria (mostly levan). In the phylum Actinobacteria only levan synthesis by Actinomyces species has been reported. We have identified a putative fructansucrase gene (hugO) in Streptomyces viridochromogenes DSM40736 (Tü494).

Effect of stratum corneum heterogeneity, anisotropy, asymmetry and follicular pathway on transdermal penetration.

The impact of the complex structure of the stratum corneum on transdermal penetration is not yet fully described by existing models. A quantitative and thorough study of skin permeation is essential for chemical exposure assessment and transdermal delivery of drugs. The objective of this study is to analyze the effects of heterogeneity, anisotropy, asymmetry, follicular diffusion, and location of the main barrier of diffusion on percutaneous permeation.

In vitro human epidermal permeation of nicotine from electronic cigarette refill liquids and implications for dermal exposure assessment.

Nicotine plus flavorings in a propylene glycol (PG) vehicle are the components of electronic cigarette liquids (e-liquids), which are vaporized and inhaled by the user. Dermal exposure to nicotine and e-liquids may occur among workers in mixing and filling of e-cigarettes in the manufacturing process. Inadvertent skin contact among consumers is also a concern.

The VanRS Homologous Two-Component System VnlRSAb of the Glycopeptide Producer Amycolatopsis balhimycina Activates Transcription of the vanHAXSc Genes in Streptomyces coelicolor, but not in A. balhimycina.

In enterococci and in Streptomyces coelicolor, a glycopeptide nonproducer, the glycopeptide resistance genes vanHAX are colocalized with vanRS. The two-component system (TCS) VanRS activates vanHAX transcription upon sensing the presence of glycopeptides. Amycolatopsis balhimycina, the producer of the vancomycin-like glycopeptide balhimycin, also possesses vanHAXAb genes.

Effect of Frozen Human Epidermis Storage Duration and Cryoprotectant on Barrier Function Using Two Model Compounds.

Skin is commonly stored frozen and then thawed prior to use for in vitro permeation experiments. Does frozen storage of skin alter its barrier property? Numerous studies have found contradictory answers to this question. In this study, the steady-state flux and lag time of diethyl phthalate (DEP) were measured for fresh human skin and skin frozen at -85°C for 1, 2, 3, 6, 9, 12, and 18 months with 10% glycerol as a cryoprotective agent.

Alternative Pathway to a Glycopeptide-Resistant Cell Wall in the Balhimycin Producer Amycolatopsis balhimycina.

Balhimycin, a vancomycin-type glycopeptide, is a lipid II targeting antibiotic produced by Amycolatopsis balhimycina. A. balhimycina has developed a self-resistance mechanism based on the synergistic action of different enzymes resulting in modified peptidoglycan.

The transient dermal exposure II: post-exposure absorption and evaporation of volatile compounds.

The transient dermal exposure is one where the skin is exposed to chemical for a finite duration, after which the chemical is removed and no residue remains on the skin's surface. Chemical within the skin at the end of the exposure period can still enter the systemic circulation. If it has some volatility, a portion of it will evaporate from the surface before it has a chance to be absorbed by the body.

Self-resistance mechanisms of actinomycetes producing lipid II-targeting antibiotics.

Glycopeptides and several lantibiotics are lipid II-targeting antibiotics produced by actinomycetes. To protect themselves from their own product, antibiotic producers developed self-resistance mechanisms. Inspection of different producer strains revealed that their resistance is not only based on a single determinant but on the synergistic action of different factors.

Dermal permeation of 2-hydroxypropyl acrylate, a model water-miscible compound: effects of concentration, thermodynamic activity and skin hydration.

Unlabelled: The goal of these studies was to measure and interpret the skin permeability characteristics of 2-hydroxypropyl acrylate (HPA) as a model compound that is completely miscible with water.

Methods: In vitro permeation from HPA-H2O binary mixtures through human epidermis and silicone membranes was measured. Thermodynamic activities of HPA and H2O in these mixtures were determined.

Analysis of finite dose dermal absorption data: implications for dermal exposure assessment.

A common dermal exposure assessment strategy estimates the systemic uptake of chemical in contact with skin using the fixed fractional absorption approach: the dermal absorbed dose is estimated as the product of exposure and the fraction of applied chemical that is absorbed, assumed constant for a given chemical. Despite the prominence of this approach there is little guidance regarding the evaluation of experiments from which fractional absorption data are measured. An analysis of these experiments is presented herein, and limitations to the fixed fractional absorption approach are discussed.

Design-based re-engineering of biosynthetic gene clusters: plug-and-play in practice.

Synthetic biology is revolutionizing the way in which the biosphere is explored for natural products. Through computational genome mining, thousands of biosynthetic gene clusters are being identified in microbial genomes, which constitute a rich source of potential novel pharmaceuticals. New methods are currently being devised to prioritize these gene clusters in terms of their potential for yielding biochemical novelty.

Dermal absorption of finite doses of volatile compounds.

Laplace domain solutions to a previously published finite dose skin diffusion model are presented. The purpose of the current analysis is to derive a simple algebraic expression quantifying the total mass that is systemically absorbed at infinite time after exposure, relative to the applied mass. The resulting expression is a function of two dimensionless parameters: f, the fractional depth within the skin surface through which the permeant is initially deposited, and χ, the ratio of maximum evaporation flux to maximum dermal flux.

Application of numerical methods for diffusion-based modeling of skin permeation.

The application of numerical methods for mechanistic, diffusion-based modeling of skin permeation is reviewed. Methods considered here are finite difference, method of lines, finite element, finite volume, random walk, cellular automata, and smoothed particle hydrodynamics. First the methods are briefly explained with rudimentary mathematical underpinnings.

Dermal penetration potential of perfluorooctanoic acid (PFOA) in human and mouse skin.

Recent data, using a murine model, have indicated that dermal exposure to perfluorooctanoic acid (PFOA) induces immune modulation, suggesting that this may be an important route of PFOA exposure. To investigate the dermal penetration potential of PFOA, serum concentrations were analyzed in mice following topical application. Statistically significant and dose-responsive increases in serum PFOA concentrations were identified.

In vitro human epidermal penetration of 1-bromopropane.

1-Bromopropane (1-BP; CAS number 106-94-5), also known as n-propyl bromide, is a halogenated short-chain alkane used as an organic solvent with numerous commercial and industrial applications, including garment dry cleaning and vapor degreasing of metals. The purpose of this study was to determine the dermal absorption characteristics and corrosivity of 1-BP. Heat-separated human epidermal membranes were mounted on static diffusion cells.

Self-resistance and cell wall composition in the glycopeptide producer Amycolatopsis balhimycina.

The prevailing resistance mechanism against glycopeptides in Gram-positive pathogens involves reprogramming the biosynthesis of peptidoglycan precursors, resulting in d-alanyl-d-lactate depsipeptide termini. Amycolatopsis balhimycina produces the vancomycin-like glycopeptide balhimycin and therefore has to protect itself from the action of the glycopeptide. We studied the roles of the accessory resistance gene orthologs vanY(b), vnlR(b), and vnlS(b), which are part of the balhimycin biosynthetic gene cluster (represented by the subscript "b").

Mathematical models of skin permeability: an overview.

Mathematical models of skin permeability play an important role in various fields including prediction of transdermal drug delivery and assessment of dermal exposure to industrial chemicals. Extensive research has been performed over the last several decades to yield predictions of skin permeability to various molecules. These efforts include the development of empirical approaches such as quantitative structure-permeability relationships and porous pathway theories as well as the establishment of rigorous structure-based models.

Tissue binding affects the kinetics of theophylline diffusion through the stratum corneum barrier layer of skin.

New data sets on both (i) equilibrium theophylline (TH) partitioning/binding in stratum corneum and (ii) transient TH diffusion through human epidermis are explained by an extended partition-diffusion model with reversible binding. Data conform to a linear binding isotherm within the tested concentration range (0-2000 μg/mL) with an equilibrium ratio of bound-to-free solute of approximately 1.4.

Glycopeptide biosynthesis in the context of basic cellular functions.

Using molecular genetics, biochemistry and organic chemistry the biosynthesis of glycopeptides has been elucidated in detail. It can be categorised in three parts: precursor supply, linking of the peptide backbone and modification reactions. The important steps of the biosynthesis are carried out at a multi-enzyme complex consisting of three non-ribosomal peptide synthetases (NRPS), three oxygenases and one halogenase.

In vitro dermal penetration of 4-chloro-3-methylphenol from commercial metal working fluid and aqueous vehicles.

The biocide 4-chloro-3-methylphenol (CMP, CAS number 59-50-7) is a common additive to metal-working fluids (MWF) and building materials. National Institute for Occupational Safety and Health (NIOSH) researchers previously identified and quantified CMP in a commercial water-soluble MWF, TRIM VX, and demonstrated irritancy and sensitization potential of both TRIM VX and CMP alone after dermal exposure in a murine model. In the current study, the in vitro human epidermal permeability of CMP contained in a working dilution of TRIM VX (20% in water) was evaluated and, for comparison, permeability from an aqueous buffer was also assessed.

A paired comparison between human skin and hairless guinea pig skin in vitro permeability and lag time measurements for 6 industrial chemicals.

The purpose of the present study was to measure and compare permeability coefficients (k(p)) and lag times (tau) in human skin and hairless guinea pig (HGP) skin. Paired experiments employed heat-separated epidermal membranes from human and HGP sources mounted on static in vitro diffusion cells. Infinite-dose, saturated aqueous solutions of 6 industrial chemicals were used as donors: aniline, benzene, 1,2- dichloroethane, diethyl phthalate, naphthalene, and tetrachloroethylene.

Evaluation of irritancy and sensitization potential of metalworking fluid mixtures and components.

There are approximately 1.2 million workers exposed to metalworking fluids (MWF), which are used to reduce the heat and friction associated with industrial machining and grinding operations. Irritancy and sensitization potential of 9 National Toxicology Program (NTP) nominated MWFs (TRIM 229, TRIM VX, TRIM SC210, CIMTECH 310, CIMPERIAL 1070, CIMSTAR 3800, SYNTILO 1023, SUPEREDGE 6768, and CLEAREDGE 6584) were examined in a combined local lymph node assay (LLNA).