Abstract  Current guidance for the estimation of dermal absorption (DA) of pesticides recommends the use of default values, read-across of information between formulations and in vitro testing. While QSARs exist to estimate percutaneous absorption, their use is currently not encouraged. Therefore, the potential of publicly available models for DA estimation was investigated based on data from 564 human in vitro DA experiments on pesticides. The classic Potts Guy model, the correction of Cleek Bunge for highly lipophilic chemicals, the mechanistic model of Mitragotri, and the COSMOS model were used to estimate the permeability coefficient kp. Different approaches were explored to calculate the percentage of external dose absorbed. IH SkinPerm was examined as stand-alone model. The models generally failed to accurately predict experimental values. For 30-40% of the predictions, there was overestimation by one order of magnitude. Three models underpredicted >10% of the cases, the remaining models <5%. DA of hydrophilic substances was typically underpredicted. Overprediction was more prominent for solid preparations and suspensions. The molecular weight, irritation potential and skin thickness did not correlate with the models' predictivity. Of the models investigated, IH SkinPerm performed best with 38% of the predictions within one order of magnitude and 2% underpredicted cases.

Abstract  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. The analysis provides a set of simple algebraic expressions that may be used in the evaluation of finite dose dermal absorption experiments, affording a more data-driven approach to dermal exposure assessment. Case studies are presented that demonstrate the application of these tools to the assessment of dermal absorption data.

Abstract  Printing in three dimensions (3-D printing) constitutes an emergent technology for producing objects made of metals, biologicals and polymers. Already used in several industries, the process holds promise for larger-scale commercialization and, thereby, elevated worker exposures to process hazards. This article examines some of those hazards specifically. This article frames the present state of 3-D printing and examines the literature about related hazards. The authors also report original findings from a preliminary hazard assessment of the process and chemicals associated with a commercial-grade photopolymerization 3-D printer. Exposures to organic polymers, particulate matter, the corrosive cleaning agent sodium hydroxide and noise were assessed. With 3-D printing stories seemingly appearing weekly, one could get the impression that it is a recent technological advance. Indeed, the increase in personal 3-D printers alone reportedly averaged almost 350% per year from 2008 to 2011 (Wohlers Associates, 2013). However, the essential technique, also known as additive manufacturing (AM), has existed for several decades. It is only because of recent advances in CAD/CAM software, in conjunction with important lapsed patents, that the technology has seen such intensive attention and explosive growth (IPO, 2013). OSH professionals encounter AM in the aerospace, architecture, automotive, medical and dental fabrication, defense, and commercial and consumer product manufacturing industries (Stratasys, 2016). Key areas of interest for newer or emerging development are biomedical applications, electrodes and circuits, but the technology has potential uses in a nearly limitless number of applications. A sampling of these include medical prosthetics (Photo 1), miniature Li-ion microbatteries only 200 μm long (Sun, Wei, Ahn, et al., 2013), embedded inventory control tags and shoes. In an amusing case of life imitating art, NASA has even demonstrated an interest in 3-D printing to create food for astronauts while in flight, much like the food replicators of the Starship Enterprise in the 1966 television show Star Trek (NASA, 2013). As it is most often seen commercially, 3-D printing, or AM, employs the use of premixed resins sold in proprietary cartridge containers for use in a manufacturer’s printer carcass. Two major categories of materials are utilized: inks and supports. Inks are most often plastic monomers thin-layered atop each other to create an object, and support materials are simultaneously layered in and around the inks to provide structure during the build-up (i.e., printing) process. A vendor-supplied makeup for representative types of such inks and supports is shown in Tables 1 and 2 (p. 58), respectively. When exposed to UV light, these organic polymers polymerize, or cure, to a solid, finished state. During the jetting process of the inks and support materials, and/or under the UV polymerization step, hazardous airborne decomposition materials may be produced (CMU).

Abstract  An initial study of processing biodegradable Polycaprolactone (PCL) through 3D printing technology was conducted using Fujifilm Dimatix DMP-2800 material printer. The aim of this work was to investigate a potential method of preparing and processing biodegradable polycaprolactone through 3D printing. PCL inks with a concentration of 5wt% and 10wt% were prepared to investigate their processability. The influences of waveform peak height, time gap, printing voltage, droplet velocity, substrate temperature and droplet spacing on PCL ink droplet formation as well as final deposition quality were investigated. Multi-layer PCL structures were printed and characterized with the geometric quality of deposited PCL measured using a Talysurf 2000 and Bruker ContourGT-I. It was found that PCL solvent ink can reach relative stable droplet formation and deposition when plate temperature was 30 ºC and droplet velocity was 6m/s. Printed PCL solvent ink showed ‘coffee ring’ effect after solidification. When deposition droplet spacing equals to 40µm, printed PCL film showed the lowest surface roughness.

Abstract  A microscopic model of passive transverse mass transport of small solutes in the viable epidermal layer of human skin is formulated on the basis of a hexagonal array of cells (i.e., keratinocytes) bounded by 4-nm-thick, anisotropic lipid bilayers and separated by 1-μm layers of extracellular fluid. Gap junctions and tight junctions with adjustable permeabilities are included to modulate the transport of solutes with low membrane permeabilities. Two keratinocyte aspect ratios are considered to represent basal and spinous cells (longer) and granular cells (more flattened). The diffusion problem is solved in a unit cell using a coordinate system conforming to the hexagonal cross section, and an efficient two-dimensional treatment is applied to describe transport in both the cell membranes and intercellular spaces, given their thinness. Results are presented in terms of an effective diffusion coefficient, D¯¯¯epi, and partition coefficient, K¯¯¯epi/w, for a homogenized representation of the microtransport problem. Representative calculations are carried out for three small solutes—water, l-glucose, and hydrocortisone—covering a wide range of membrane permeability. The effective transport parameters and their microscopic interpretation can be employed within the context of existing three-layer models of skin transport to provide more realistic estimates of the epidermal concentrations of topically applied solutes.

Abstract  1,4-Dioxane is a potentially carcinogenic solvent. It is a problematic groundwater contaminant because of its unique physical-chemical properties. It is found in a wide range of consumer products as a by-product contaminant. This research aimed to investigate contaminant properties and behavior of dioxane in the environment and also in the human body. The dioxane ability to decontamination by adsorption processes was evaluated with four adsorbents. The adsorption efficiencies of activated carbon (AC), metal oxide nanomaterials (TiO[subscript]2 and MgO), and diatomaceous earth (DE) were assessed in aqueous and vapor phases using infrared spectroscopy. AC showed the highest adsorptive capacity for dioxane at equilibrium in both phases. The rate and extent of dermal absorption are important in the analysis of risk from dermal exposure to dioxane. For this purpose, a new flow through diffusion system (FTDS) was developed by modifying a Bronaugh flow through diffusion cell with flow capacity in both the donor and receptor compartments and using attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR) as the analytical technique. FTDS can provide ‘real time’ quantitative high-density permeation data over time and is characterized by the simplicity of its use and the low cost of test samples. The in vitro dermal absorption study of dioxane across human skin showed that the absorption parameters of dioxane were 1.16 ± 0.22 hr, 5.7 X 10[superscript]-4 ± (0.62) cm/hr, 0.286 ± 0.035 mg/cm2/hr, 4.8 X 10-5 (± 0.32) cm[superscript]2/hr, and 1.99 ± 0.086 mg for lag time, permeability, steady-state flux, diffusivity, and total amount absorbed over 8 hr, respectively. The study of the effect of the surfactant sodium lauryl sulphate and solvent systems water, ethanol, propylene glycol, and ethyl acetate on permeation profiles revealed that these solvents and surfactants increased the permeation of dioxane significantly. The FT-IR spectra of stratum corneum treated with solvents showed that there was broadening of the CH[subscript]2 asymmetric stretching vibration of the CH[subscript]2 peak near 2920 cm[superscript]-1 only in samples treated with ethanol. The lipid extract precipitates were detected and were mostly composed of the stratum corneum lipid part.

Abstract  The overall goal of this research was to further develop and improve an existing skin diffusion model by experimentally confirming the predicted absorption rates of topically-applied volatile organic compounds (VOCs) based on their physicochemical properties, the skin surface temperature, and the wind velocity. In vitro human skin permeation of two hydrophilic solvents (acetone and ethanol) and two lipophilic solvents (benzene and 1,2-dichloroethane) was studied in Franz cells placed in a fume hood. Four doses of each (14)C-radiolabed compound were tested - 5, 10, 20, and 40μLcm(-2), corresponding to specific doses ranging in mass from 5.0 to 63mgcm(-2). The maximum percentage of radiolabel absorbed into the receptor solutions for all test conditions was 0.3%. Although the absolute absorption of each solvent increased with dose, percentage absorption decreased. This decrease was consistent with the concept of a stratum corneum deposition region, which traps small amounts of solvent in the upper skin layers, decreasing the evaporation rate. The diffusion model satisfactorily described the cumulative absorption of ethanol; however, values for the other VOCs were underpredicted in a manner related to their ability to disrupt or solubilize skin lipids. In order to more closely describe the permeation data, significant increases in the stratum corneum/water partition coefficients, Ksc, and modest changes to the diffusion coefficients, Dsc, were required. The analysis provided strong evidence for both skin swelling and barrier disruption by VOCs, even by the minute amounts absorbed under these in vitro test conditions.

Abstract  According to international guidelines skin penetration experiments can be carried out using freshly excised or frozen stored skin. However, this recommendation refers to data obtained in experiments with human cadaver skin. In our study, the percutaneous penetration of the occupationally relevant chemicals anisole, cyclohexanone and 1,4-dioxane was investigated for freshly excised as well as for 4 and 30 days at -20°C stored human skin using the diffusion cell technique. As indicator for the impairment of skin barrier by freezing cholesterol dissolution was determined in the solvents in exposure chambers of diffusion cells. Considering the percutaneously penetrated amounts, the following ranking was determined: 1,4-dioxane>anisole>cyclohexanone (decline to a factor of 5.9). The differences of fluxes between freshly excised and frozen stored skin (4 and 30 days) were not significant (p>0.05). Cholesterol dissolved from the skin indicates no significant differences between freshly excised and frozen stored skin. This study shows that freezing of human skin for up to 30 days does not alter the skin barrier function and the permeability of chemicals.

Abstract  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. The fate of this post-exposure "skin depot" is the focus of this theoretical study. Laplace domain solutions for concentration distribution, flux, and cumulative mass absorption and evaporation are presented, and time domain results are obtained through numerical inversion. The Final Value Theorem is applied to obtain the analytical solutions for the total fractional absorption by the body and evaporation from skin at infinite time following a transient exposure. The solutions depend on two dimensionless variables: χ, the ratio of evaporation rate to steady-state dermal permeation rate; and the ratio of exposure time to membrane lag time. Simple closed form algebraic equations are presented that closely approximate the complete analytical solutions. Applications of the theory to the dermal risk assessment of pharmaceutical, occupational, and environmental exposures are presented for four example chemicals.

Abstract  Published permeability coefficient (K p) data for the transport of a large group of compounds through mammalian epidermis were analyzed by a simple model based upon permeant size [molecular volume (MV) or molecular weight (MW)] and octanol/water partition coefficient (K oct). The analysis presented is a facile means to predict the percutaneous flux of pharmacological and toxic compounds solely on the basis of their physicochemical properties. Furthermore, the derived parameters of the model have assignable biophysical significance, and they provide insight into the mechanism of molecular transport through the stratum corneum (SC). For the very diverse group of chemicals considered, the results demonstrate that SC intercellular lipid properties alone are sufficient to account for the dependence of K p upon MV (or MW) and K oct. It is found that the existence of an “aqueous-polar (pore) pathway” across the SC is not necessary to explain the K p values of small, polar nonelectrolytes. Rather, their small size, and consequently high diffusivity, accounts for their apparently larger-than-expected K p. Finally, despite the size and breadth of the data set (more than 90 compounds with MW ranging from 18 to >750, and log K oct ranging from −3 to + 6), the postulated upper limiting value of K p for permeants of very high lipophilicity cannot be determined. However, the analysis is able to define the physicochemical characteristics of molecules which should exhibit these maximal K p values. Overall, then, we present a facile interpretation of a considerable body of skin permeability measurements that (a) very adequately describes the dependence of K p upon permeant size and lipophilicity, (b) generates parameters of considerable physicochemical and mechanistic relevance, and (c) implies that the SC lipids alone can fully characterize the barrier properties of mammalian skin.

Abstract  This report describes a revision of the model used in ICRP Publication 30 to calculate radiation doses to the respiratory tract of workers resulting from the intake of airborne radionuclides. This revision was motivated by the availability of increased knowledge of the anatomy and physiology of the respiratory tract and of the deposition, clearance, and biological effects of inhaled radioactive particles, and by greatly expanded dosimetry requirements. To meet fully the needs of radiation protection, a dosimetric model for the respiratory tract should: - provide calculations of doses for individual members of the populations of all ethnic groups, in addition to workers; - be useful for predictive and assessment purposes as well as for deriving limits on intakes; - account for the influence of smoking, air pollutants, and respiratory tract diseases; - provide for estimates of respiratory tract tissue doses from bioassay data; and - be equally applicable to radioactive gases as well as to particles. Addressing all of these requirements has resulted in a dosimetry model that is more complex than previous models.

Abstract  Risk management is especially important for military forces deployed in hostile and/or chemically contaminated environments, and on-line or rapid turn-around capabilities for assessing exposures can create viable options for preventing or minimizing incapaciting exposures or latent disease or disability in the years after the deployment. With military support for the development, testing, and validation of state-of-the-art personal and area sensors, telecommunications, and data management resources, the DOD can enhance its capabilities for meeting its novel and challenging tasks and create technologies that will find widespread civilian uses. Strategies to Protect the Health of Deployed U.S. Forces assesses currently available options and technologies for productive pre-deployment environmental surveillance, exposure surveillance during deployments, and retrospective exposure surveillance post-deployment. This report also considers some opportunities for technological and operational advancements in technology for more effective exposure surveillance and effects management options for force deployments in future years.