Silver nanoparticles (AgNPs) are currently one of the most manufactured nanomaterials. A wide range of toxicity studies have been performed on various AgNPs, but these studies report a high variation in toxicity and often lack proper particle characterization. The aim of this study was to investigate size- and coating-dependent toxicity of thoroughly characterized AgNPs following exposure of human lung cells and to explore the mechanisms of toxicity. BEAS-2B cells were exposed to citrate coated AgNPs of different primary particle sizes (10, 40 and 75 nm) as well as to 10 nm PVP coated and 50 nm uncoated AgNPs. The particle agglomeration in cell medium was investigated by photon cross correlation spectroscopy (PCCS); cell viability by LDH and Alamar Blue assay; ROS induction by DCFH-DA assay; genotoxicity by alkaline comet assay and γH2AX foci formation; uptake and intracellular localization by transmission electron microscopy (TEM); and cellular dose as well as Ag release by atomic absorption spectroscopy (AAS). The results showed cytotoxicity only of the 10 nm particles independent of surface coating. In contrast, all AgNPs tested caused an increase in overall DNA damage after 24 h assessed by the comet assay, suggesting independent mechanisms for cytotoxicity and DNA damage. However, there was no γH2AX foci formation and no increased production of intracellular reactive oxygen species (ROS). The reasons for the higher toxicity of the 10 nm particles were explored by investigating particle agglomeration in cell medium, cellular uptake, intracellular localization and Ag release. Despite different agglomeration patterns, there was no evident difference in the uptake or intracellular localization of the citrate and PVP coated AgNPs. However, the 10 nm particles released significantly more Ag compared with all other AgNPs (approx. 24 wt% vs. 4–7 wt%) following 24 h in cell medium. The released fraction in cell medium did not induce any cytotoxicity, thus implying that intracellular Ag release was responsible for the toxicity. This study shows that small AgNPs (10 nm) are cytotoxic for human lung cells and that the toxicity observed is associated with the rate of intracellular Ag release, a ‘Trojan horse’ effect.

https://link.springer.com/content/pdf/10.1186%2F1743-8977-11-11.pdf

Size-dependent cytotoxicity of silver nanoparticles in human lung cells: the role of cellular uptake, agglomeration and Ag release

A critical review of approaches and limitations of inhalation bioavailability and bioaccessibility of metal(loid)s from ambient particulate matter or dust.

Man-made vitreous fibres has a solubility at pH 4.5 of at least 20 nm per day and a melt viscosity of 10-70 poise at 1,400 °C and are formed from a composition which includes 18 to 30 % by weight Al2O3.

Man-made vitreous fibres

Testing of metal compounds for solubility in artificial fluids has been used for many years to assist determining human health risk from exposure to specific compounds of concern. In lieu of obtaining bioavailability data from samples of urine, blood, or other tissues, these studies measured solubility of compounds in various artificial fluids as a surrogate for bioavailability. In this context, the measurement of metal “bioaccessibility” can be used as an in vitro substitute for measuring metal bioavailability. Bioaccessibility can be defined as a value representing the availability of metal for absorption when dissolved in in vitro surrogates of body fluids or juices. The aim of this study was to measure and compare the bioaccessibility of selected cobalt compounds in artificial human tissue fluids and human serum. A second aim was to initiate studies to experimentally validate an in vitro methodology that would provide a conservative estimate of cobalt bioavailability in the assessment of dose from human exposure to various species of cobalt compounds. This study evaluated the bioaccessibility of cobalt(II) from 11 selected cobalt compounds and an alloy in 2 physical forms in 5 surrogate human tissue fluids and human serum. Four (4) separate extraction times were used up to 72 hours. The effect of variables such as pH, dissolution time, and mass-ion effect on cobalt bioaccessibility were assessed as well. We found that the species of cobalt compound as well as the physico-chemical properties of the surrogate fluids, especially pH, had a major impact on cobalt solubility. Cobalt salts such as cobalt(II) sulfate heptahydrate were highly soluble, whereas cobalt alloys used in medical implants and cobalt aluminate spinels used as pigments, showed minimal dissolution over the period of the assay.

Bioaccessibility testing of cobalt compounds

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.

/pdf/dissolution-and-biodurability-important-parameters-needed-2vfrfiztmx.pdf

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

The assessment of biodurability of man-made vitreous fibers is essential to the limitation of health hazards associated with human exposure to environments in which respirable fibers are present. In vitro acellular systems provide effective test methods of measuring fiber solubility provided care is taken to select the most suitable solvent and test conditions for the specific fiber type and dimension.

In vitro assessment of biodurability: acellular systems.

La presente invention concerne une composition de verre pour des fibres susceptibles de se degrader dans un milieu physiologique. The present invention relates to a composition of glass fibers may degrade in a physiological medium. Des compositions de verre avantageuses renferment les constituants suivants pris dans des proportions ponderales ci-apres : Preferred glass compositions contain the following ingredients taken in proportions below: Si0₂ Si0₂ 57 a 70 % 57 70% Al₂0₃ Al₂0₃ 0 a 5 % 0 to 5% Ca0 ca0 5 a 10 % 5 to 10% Mg0 Mg0 0 a 5 % 0 to 5% Na₂0 + K₂0 Na₂0 + K₂0 13 a 18 % 13-18% B₂0₃ B₂0₃ 2 a 12 % 2 to 12% F F 0 a 1,5 % 0 to 1.5% P₂0₅ P₂0₅ 0 a 4 % 0 to 4% Impuretes impurities < 2 % <2%

Glass fibres degradable in physiological medium

The present invention relates to mineral fiber compositions useful for forming fibers which are readily degraded in a physiological medium such as that found within the human body. Advantageous compositions formed according to the present invention comprise the following components in the proportions by weight set forth below: ______________________________________ SiO2 37 to 58 wt. %;Al2 O3 4 to 14 wt. %;CaO 7 to 40 wt. %;MgO 4 to 16 wt. %;P2 O5 1 to 10 wt. %;Fe2 O3 up to about to 15 wt. %:______________________________________ wherein the amount of CaO+MgO+Fe2 O3 is greater than 25% and the total amount of Na2 O+K2 O is less than 7%. The total iron contained within the composition is expressed in the form of ferric oxide (Fe2 O3).

Mineral fibers decomposable in a physiological medium

This article discusses the dissolution of mineral fibers in simulated physiological fluids (SPF), and the parameters that affect the solubility measurement in a dynamic test where an SPF runs through a cell containing fibers (Scholze and Conradt test). Solutions simulate either the extracellular fluid (pH 7.6) or the intracellular fluid (pH 4.5). The fibers have various chemical compositions and are either continuously drawn or processed as wool. The fiber solubility is determined by the amount of SiO2 (and occasionally other ions) released in the solution. Results are stated as percentage of the initial silica content released or as dissolution rate v in nm/day. The reproducibility of the test is higher with the less soluble fibers (10% solubility), than with highly soluble fibers (20% solubility). The influence of test parameters, including SPF, test duration, and surface area/volume (SA/V), has been studied. The pH and the inorganic buffer salts have a major influence: industrial glasswool composition is soluble at pH 7.6 but not at pH 4.5. The opposite is true for rock- (basalt) wool composition. For slightly soluble fibers, the dissolution rate v remains constant with time, whereas for highly soluble fibers, the dissolution rate decreases rapidly. The dissolution rates believed to occur are v1, initial dissolution rate, and v2, dissolution rate of the residual fibers. The SA of fibers varies with the mass of the fibers tested, or with the fiber diameter at equal mass. Volume, V, is the chosen flow rate. An increase in the SA/V ratio leads to a decrease in the dissolution rate.(ABSTRACT TRUNCATED AT 250 WORDS)

In vitro dynamic solubility test: influence of various parameters.

The present invention relates to compositions of mineral fibres capable of being dissolved in a physiological medium. The compositions of said fibres comprise the following constituants, in the weight proportions defined hereafter: SiO2 48 - 67 %; Al2O3 0 - 8 %; Fe2O3 0 - 12 % (total iron expressed in this form); CaO 16 - 35 %; MgO 1 - 16 %; Na2O + K2O 0 - 6,5 %; P2O5 0 - 5 %; considering that these compositions are also defined by the fact that the contents of said constituants respect the following relationships: Na2O + P2O5 » 2 %; Fe2O3 + Al2O3 « 12 %; CaO + MgO + Fe2O3 » 23 %.

Mineral fibres capable of dissolving in a physiological medium

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