Aleksandr B. Stefaniak

Formulation and stability of a novel artificial human sweat under conditions of storage and use

A limitation of most artificial sweat formulations used for in vitro assessment of chemical release from materials in contact with skin have little biological relevance to human sweat. The purposes of this paper are to provide guidance for preparation of a novel artificial sweat with chemical constituents at concentrations that match human sweat and to characterize chemical stability. The artificial sweat was characterized under conditions of use (with and without sebum at 36 degrees C) and storage (without sebum at -4, 4, and 23 degrees C) over 28 days by gas chromatography-mass spectroscopy, high-performance liquid chromatography, enzymatic assay kits, and ion-selective electrodes. Seven indicator constituents were tracked: sodium, chloride, glucose, lactic acid, urea, pantothenic acid, and alanine. With or without sebum at 36 degrees C, the sweat solvent was chemically stable for 14 days. Storage by refrigeration at 4 degrees C retained the chemical integrity of the solvent longest. Based on these results, the solvent should be used within 14 days of preparation. The artificial sweat model presented herein is most similar to human sweat and has applications as a dissolution solvent, donor solution in diffusion cells, or vehicle for patch testing. This sweat model may aid researchers in understanding potential release and percutaneous absorption of chemicals in contact with human skin surface liquids.

Nanoscale reference materials for environmental, health and safety measurements: needs, gaps and opportunities

Abstract The authors critically reviewed published lists of nano-objects and their physico-chemical properties deemed important for risk assessment and discussed metrological challenges associated with the development of nanoscale reference materials (RMs). Five lists were identified that contained 25 (classes of) nano-objects; only four (gold, silicon dioxide, silver, titanium dioxide) appeared on all lists. Twenty-three properties were identified for characterisation; only (specific) surface area appeared on all lists. The key themes that emerged from this review were: 1) various groups have prioritised nano-objects for development as “candidate RMs” with limited consensus; 2) a lack of harmonised terminology hinders accurate description of many nano-object properties; 3) many properties identified for characterisation are ill-defined or qualitative and hence are not metrologically traceable; 4) standardised protocols are critically needed for characterisation of nano-objects as delivered in relevant media and as administered to toxicological models; 5) the measurement processes being used to characterise a nano-object must be understood because instruments may measure a given sample in a different way; 6) appropriate RMs should be used for both accurate instrument calibration and for more general testing purposes (e.g., protocol validation); 7) there is a need to clarify that where RMs are not available, if “(representative) test materials” that lack reference or certified values may be useful for toxicology testing and 8) there is a need for consensus building within the nanotechnology and environmental, health and safety communities to prioritise RM needs and better define the required properties and (physical or chemical) forms of the candidate materials.

International guidelines for the in vivo assessment of skin properties in non-clinical settings: Part 2. transepidermal water loss and skin hydration

There is an emerging perspective that it is not sufficient to just assess skin exposure to physical and chemical stressors in workplaces, but that it is also important to assess the condition, i.e. skin barrier function of the exposed skin at the time of exposure. The workplace environment, representing a non‐clinical environment, can be highly variable and difficult to control, thereby presenting unique measurement challenges not typically encountered in clinical settings.

Dissolution and biodurability: Important parameters needed for risk assessment of nanomaterials.

Biopersistence and biodurability have the potential to influence the long-term toxicity and hence pathogenicity of particles that deposit in the body. Therefore, biopersistence and biodurability are considered to be important parameters needed for the risk assessment of particles and fibres. Dissolution, as a measure of biodurability, is dependent on the chemical and physical properties (size, surface area, etc.) of particles and fibres and also of the suspension medium including its ionic strength, pH, and temperature. In vitro dissolution tests can provide useful insights as to how particles and fibres may react in biological environments; particles and fibres that release ions at a higher rate when suspended in vitro in a specific simulated biological fluid will be expected to do so when they exist in a similar biological environment in vivo. Dissolution of particles and fibres can follow different reaction kinetics. For example, the majority of micro-sized particles and fibres follow zero-order reaction kinetics. In this case, although it is possible to calculate the half-time of a particle or fibre, such calculation will be dependent on the initial concentration of the investigated particle or fibre. Such dependence was eliminated in the shrinking sphere and fibre models where it was possible to estimate the lifetimes of particles and fibres as a measure of their biodurability. The latter models can be adapted for the dissolution studies of nanomaterials. However, the models may apply only to nanomaterials where their dissolution follows zero-order kinetics. The dissolution of most nanomaterials follows first-order kinetics where dependence on their initial concentration of the investigated nanomaterials is not required and therefore it is possible to estimate their half-times as a measure of their biodurability. In dissolution kinetics for micro-sized and nano-sized particles and fibres, knowledge of dissolution rate constants is necessary to understand biodurability. Unfortunately, many studies on dissolution of nanoparticles and nanofibres do not determine the dissolution rates and dissolution rate constants. The recommendation is that these parameters should be considered as part of the important descriptors of particle and fibre physicochemical properties, which in turn, will enable the determination of their biodurability.

Characterization of silver nanoparticles in selected consumer products and its relevance for predicting children’s potential exposures

Due to their antifungal, antibacterial, antiviral, and antimicrobial properties, silver nanoparticles (AgNPs) are used in consumer products intended for use by children or in the home. Children may be especially affected by the normal use of consumer products because of their physiological functions, developmental stage, and activities and behaviors. Despite much research to date, childrens potential exposures to AgNPs are not well characterized. Our objectives were to characterize selected consumer products containing AgNPs and to use the data to estimate a childs potential non-dietary ingestion exposure. We identified and cataloged 165 consumer products claiming to contain AgNPs that may be used by or near children or found in the home. Nineteen products (textile, liquid, plastic) were selected for further analysis. We developed a tiered analytical approach to determine silver content, form (particulate or ionic), size, morphology, agglomeration state, and composition. Silver was detected in all products except one sippy cup body. Among products in a given category, silver mass contributions were highly variable and not always uniformly distributed within products, highlighting the need to sample multiple areas of a product. Electron microscopy confirmed the presence of AgNPs. Using this data, a childs potential non-dietary ingestion exposure to AgNPs when drinking milk formula from a sippy cup is 1.53 μg Ag/kg. Additional research is needed to understand the number and types of consumer products containing silver and the concentrations of silver in these products in order to more accurately predict childrens potential aggregate and cumulative exposures to AgNPs.

Particle size distributions by transmission electron microscopy: an interlaboratory comparison case study.

This paper reports an interlaboratory comparison that evaluated a protocol for measuring and analysing the particle size distribution of discrete, metallic, spheroidal nanoparticles using transmission electron microscopy (TEM). The study was focused on automated image capture and automated particle analysis. NIST RM8012 gold nanoparticles (30 nm nominal diameter) were measured for area-equivalent diameter distributions by eight laboratories. Statistical analysis was used to (1) assess the data quality without using size distribution reference models, (2) determine reference model parameters for different size distribution reference models and non-linear regression fitting methods and (3) assess the measurement uncertainty of a size distribution parameter by using its coefficient of variation. The interlaboratory area-equivalent diameter mean, 27.6 nm ± 2.4 nm (computed based on a normal distribution), was quite similar to the area-equivalent diameter, 27.6 nm, assigned to NIST RM8012. The lognormal reference model was the preferred choice for these particle size distributions as, for all laboratories, its parameters had lower relative standard errors (RSEs) than the other size distribution reference models tested (normal, Weibull and Rosin-Rammler-Bennett). The RSEs for the fitted standard deviations were two orders of magnitude higher than those for the fitted means, suggesting that most of the parameter estimate errors were associated with estimating the breadth of the distributions. The coefficients of variation for the interlaboratory statistics also confirmed the lognormal reference model as the preferred choice. From quasi-linear plots, the typical range for good fits between the model and cumulative number-based distributions was 1.9 fitted standard deviations less than the mean to 2.3 fitted standard deviations above the mean. Automated image capture, automated particle analysis and statistical evaluation of the data and fitting coefficients provide a framework for assessing nanoparticle size distributions using TEM for image acquisition.

Characterization of cleaning and disinfecting tasks and product use among hospital occupations

BACKGROUND Healthcare workers have an elevated prevalence of asthma and related symptoms associated with the use of cleaning/disinfecting products. The objective of this study was to identify and characterize cleaning/disinfecting tasks and products used among hospital occupations. METHODS Workers from 14 occupations at five hospitals were monitored for 216 shifts, and work tasks and products used were recorded at five-minute intervals. The major chemical constituents of each product were identified from safety data sheets. RESULTS Cleaning and disinfecting tasks were performed with a high frequency at least once per shift in many occupations. Medical equipment preparers, housekeepers, floor strippers/waxers, and endoscopy technicians spent on average 108-177 min/shift performing cleaning/disinfecting tasks. Many occupations used products containing amines and quaternary ammonium compounds for >100 min/shift. CONCLUSIONS This analysis demonstrates that many occupations besides housekeeping incur exposures to cleaning/disinfecting products, albeit for different durations and using products containing different chemicals.

International guidelines for the in vivo assessment of skin properties in non-clinical settings: part 1. pH

Skin surface pH is known to influence the dissolution and partitioning of chemicals and may influence exposures that lead to skin diseases. Non‐clinical environments (e.g. workplaces) are highly variable, thereby presenting unique measurement challenges that are not typically encountered in clinical settings. Hence, guidelines are needed for consistent measurement of skin surface pH in environments that are difficult to control.

Formulation and stability of a novel artificial sebum under conditions of storage and use

Materials in contact with liquids on the human skin surface may dissolve and permeate into skin. Release and permeation of chemicals in contact with skin is often estimated in vitro using artificial skin liquids, although sebum lipids are generally not included in these models. The purposes of this research were to develop a representative artificial sebum that contains the appropriate types of lipids at levels that match human values and quantitatively characterize the model to understand its utility for in vitro testing. Artificial sebum that consisted of 10 lipids at proportions that closely resembled human sebum was characterized using thin layer chromatography under a variety of storage and use conditions (dry and liquid, 4°C and 32°C, with and without vitamin E) for 28 days. Levels of sebum constituents maintained in solution and dry at 4°C were stable through the duration of the test period. Levels of all sebum lipids maintained dry at 32°C were stable in the presence of vitamin E; however, squalene oxidized rapidly in the absence of vitamin E. Liquids on the human skin surface consist of sebum and sweat with minor amounts of cellular debris and intercellular lipid from the stratum corneum. The relative importance of each component for release of chemicals from materials in contact with skin will depend upon the type of material (metal, organic, etc.). A model artificial sebum was formulated and characterized to aid researchers in understanding potential release of chemicals from materials in contact with skin and subsequent partitioning and absorption.

Emission of particulate matter from a desktop three-dimensional (3D) printer

ABSTRACT Desktop three-dimensional (3D) printers are becoming commonplace in business offices, public libraries, university labs and classrooms, and even private homes; however, these settings are generally not designed for exposure control. Prior experience with a variety of office equipment devices such as laser printers that emit ultrafine particles (UFP) suggests the need to characterize 3D printer emissions to enable reliable risk assessment. The aim of this study was to examine factors that influence particulate emissions from 3D printers and characterize their physical properties to inform risk assessment. Emissions were evaluated in a 0.5-m3 chamber and in a small room (32.7 m3) using real-time instrumentation to measure particle number, size distribution, mass, and surface area. Factors evaluated included filament composition and color, as well as the manufacturer-provided printer emissions control technologies while printing an object. Filament type significantly influenced emissions, with acrylonitrile butadiene styrene (ABS) emitting larger particles than polylactic acid (PLA), which may have been the result of agglomeration. Geometric mean particle sizes and total particle (TP) number and mass emissions differed significantly among colors of a given filament type. Use of a cover on the printer reduced TP emissions by a factor of 2. Lung deposition calculations indicated a threefold higher PLA particle deposition in alveoli compared to ABS. Desktop 3D printers emit high levels of UFP, which are released into indoor environments where adequate ventilation may not be present to control emissions. Emissions in nonindustrial settings need to be reduced through the use of a hierarchy of controls, beginning with device design, followed by engineering controls (ventilation) and administrative controls such as choice of filament composition and color.