In vivo and In vitro Assessment of Particulate Matter Toxicology

Akhtar, Umme S.; Scott, Jeremy A.; Chu, Amanda M. Y.; Evans, Greg J.

doi:10.1007/978-3-642-12278-1_22

Cited by 11 publications

(17 citation statements)

References 82 publications

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“…These inhalation exposure studies have been used to provide insights on the interaction of an airborne substance with a biological model. While animal models for inhalation exposure studies have been considered the “gold standard,” (Akhtar et al, 2011, Paur et al, 2011) there has been a demand to find alternative models. In a 2007 report from the National Academy of Sciences entitled “Toxicity Testing in the 21 st Century: A vision and Strategy” the authors called for eliminating animal usage with a combination of human cell-based tissue models, advanced analytical methods, and computational toxicology (National Research Council, 2007).…”

Section: Introductionmentioning

confidence: 99%

“…It is now widely accepted that the ALI exposure is a more realistic approach than exposing cells under submerged conditions. In ALI conditions, the apical surface of the cells is exposed to the air while the basolateral surface of the cells is fed with culture medium through a porous membrane (Akhtar et al, 2011, Maier et al, 2008), similar to what occurs in vivo . To conduct cell exposures at ALI conditions, new in vitro exposure technologies were developed both at research universities and commercially (Blank et al, 2006, de Bruijne et al, 2009, Aufderheide and Mohr, 1999, Aufderheide and Mohr, 2004, Lenz et al, 2009, Tippe et al, 2002, Cooney and Hickey, 2011, Aufderheide et al, 2013, Savi et al, 2008, Volckens et al, 2009, Ning et al, 2008, Zavala et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

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Assessment of biological responses of EpiAirway 3-D cell constructs versus A549 cells for determining toxicity of ambient air pollution

Zavala

O’Brien

Lichtveld

et al. 2016

Inhalation Toxicology

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Context EpiAirway™ 3-D constructs are human-derived cell cultures of differentiated airway epithelial cells that may represent a more biologically relevant model of the human lung. However, limited information is available of its utility for exposures to air pollutants at the air-liquid interface (ALI). Objective To assess the biological responses of EpiAirway™ cells in comparison to the responses of A549 human alveolar epithelial cells after exposure to air pollutants at ALI. Methods Cells were exposed to filtered air, 400ppb of ozone (O3) or a photochemically-aged Synthetic Urban Mixture (SynUrb54) consisting of hydrocarbons, nitrogen oxides, O3, and other secondary oxidation products for 4 h. Basolateral supernatants and apical washes were collected at 9 and 24 h post-exposure. We assessed cytotoxicity by measuring lactate dehydrogenase (LDH) release into the culture medium and apical surface. Interleukin 6 (IL-6) and interleukin 8 (IL-8) proteins were measured in the culture medium and in the apical washes to determine the inflammatory response after exposure. Results Both O3 and SynUrb54 significantly increased basolateral levels of LDH and IL-8 in A549 cells. No significant changes in LDH and IL-8 levels were observed in the EpiAirway™ cells, however, IL-6 in the apical surface was significantly elevated at 24 h after O3 exposure. Conclusion LDH and IL-8 are robust endpoints for assessing toxicity in A549 cells. The EpiAirway™ cells show minimal adverse effects after exposure suggesting that they are more toxicologically resistant compared to A549 cells. Higher concentrations or longer exposure times are needed to induce effects on EpiAirway™ cells.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Assessment of biological responses of EpiAirway 3-D cell constructs versus A549 cells for determining toxicity of ambient air pollution

Zavala

O’Brien

Lichtveld

et al. 2016

Inhalation Toxicology

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“…Furthermore, the Health Effects Institute (HEI) calls for the development and application of next-generation multi-pollutant approaches to understanding exposure to and health effects of air pollutants [3]. Animal inhalation exposure studies have been conducted in an effort to assess the toxic effects of inhaled aerosols and have been considered the “gold standard,” [4, 5] however, logistical and ethical reasons have led to demand a reduction and replacement of animal testing with alternate methods [5, 6]. For these reasons, there is a need to develop alternative in vitro methods and exposure systems which can provide new insights into the pollutant-cell interactions that lead to the observed adverse health effects in humans [7].…”

Section: Introductionmentioning

confidence: 99%

“…The standard method for traditional in vitro exposures studies relies on submerged culture conditions where the airborne pollutant is added to a culture medium and then directly added to cells [4, 5, 7, 8]. In this exposure method a particle dose is delivered to the cells in a liquid suspension, which alters the particles' physical and chemical characteristics [9, 10].…”

Section: Introductionmentioning

confidence: 99%

“…In this exposure method a particle dose is delivered to the cells in a liquid suspension, which alters the particles' physical and chemical characteristics [9, 10]. This method also assumes that all particles deposit over the cells' surface, but the number or mass of particles that actually interact with the cells cannot be determined [4]. What is needed is new in vitro technology that can quantify the dynamic changes in the toxicity of particles while maintaining their size, composition, and interaction with other gasses.…”

Section: Introductionmentioning

confidence: 99%

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The Gillings Sampler – An electrostatic air sampler as an alternative method for aerosol in vitro exposure studies

Zavala

Lichtveld

Ebersviller

et al. 2014

Chemico-Biological Interactions

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There is growing interest in studying the toxicity and health risk of exposure to multi-pollutant mixtures found in ambient air, and the U.S. Environmental Protection Agency (EPA) is moving towards setting standards for these types of mixtures. Additionally, the Health Effects Institute's strategic plan aims to develop and apply next-generation multi-pollutant approaches to understanding the health effects of air pollutants. There's increasing concern that conventional in vitro exposure methods are not adequate to meet EPA's strategic plan to demonstrate a direct link between air pollution and health effects. To meet the demand for new in vitro technology that better represents direct air-to-cell inhalation exposures, a new system that exposes cells at the air-liquid interface was developed. This new system, named the Gillings Sampler, is a modified two-stage electrostatic precipitator that provides a viable environment for cultured cells. Polystyrene latex spheres were used to determine deposition efficiencies (38-45%), while microscopy and imaging techniques were used to confirm uniform particle deposition. Negative control A549 cell exposures indicated the sampler can be operated for up to 4 hours without inducing any significant toxic effects on cells, as measured by lactate dehydrogenase (LDH) and interleukin-8 (IL-8). A novel positive aerosol control exposure method, consisting of a p-tolualdehyde (TOLALD) impregnated mineral oil aerosol (MOA), was developed to test this system. Exposures to the toxic MOA at a 1 ng/cm2 dose of TOLALD yielded a reproducible 1.4 and 2 fold increase in LDH and IL-8 mRNA levels over controls. This new system is intended to be used as an alternative research tool for aerosol in vitro exposure studies. While further testing and optimization is still required to produce a “commercially ready” system, it serves as a stepping-stone in the development of cost-effective in vitro technology that can be made accessible to researchers in the near future.

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Similar polycyclic aromatic hydrocarbon and genotoxicity profiles of atmospheric particulate matter from cities on three different continents

Maselli

Cunha

Lim

et al. 2020

Environ and Mol Mutagen

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The extractable organic material (EOM) from atmospheric total suspended particles (TSP) contains several organic compounds including non‐substituted polycyclic aromatic hydrocarbons (PAHs), alkyl‐PAHs, and nitro‐PAHs. These chemicals seem to be among the key drivers of TSP genotoxicity. We have shown previously that the mutagenic potencies of the EOM from Limeira, Stockholm, and Kyoto, cities with markedly different meteorological conditions and pollution sources are similar. Here we compare the profiles of non‐substituted PAHs (27 congeners), alkyl‐PAHs (15 congeners), and nitro‐PAHs (7 congeners) from the same EOM samples from these cities. We also compared the genotoxicity profiles using comet and micronucleus assays in human bronchial epithelial cells. The profiles of PAHs, as well as the cytotoxic and genotoxic potencies when expressed in EOM, were quite similar among the studied cities. It seems that despite the differences in meteorological conditions and pollution sources of the cities, removal, mixing, and different atmospheric transformation processes may be contributing to the similarity of the PAHs composition and genotoxicity profiles. More studies are required to verify if this would be a general rule applicable to other cities. Although these profiles were similar for all three cities, the EOM concentration in the atmospheres is markedly different. Thus, the population of Limeira (∼10‐fold more EOM/m3 than Stockholm and ∼6‐fold more than Kyoto) is exposed to higher concentrations of genotoxic pollutants, and Kyoto's population is 1.5‐fold more exposed than Stockholm's. Therefore, to reduce the risk of human exposure to TSP genotoxins, the volume of emissions needs to be reduced.

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In vivo and In vitro Assessment of Particulate Matter Toxicology

Cited by 11 publications

References 82 publications

Assessment of biological responses of EpiAirway 3-D cell constructs versus A549 cells for determining toxicity of ambient air pollution

Assessment of biological responses of EpiAirway 3-D cell constructs versus A549 cells for determining toxicity of ambient air pollution

The Gillings Sampler – An electrostatic air sampler as an alternative method for aerosol in vitro exposure studies

Similar polycyclic aromatic hydrocarbon and genotoxicity profiles of atmospheric particulate matter from cities on three different continents

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