Toxicity assessment of air-delivered particle-bound polybrominated diphenyl ethers

Kim, Jong Sung; Klösener, Johannes; Flor, Susanne; Peters, Thomas M.; Ludewig, Gabriele; Thorne, Peter S.; Robertson, Larry W.; Luthe, Gregor

doi:10.1016/j.tox.2014.01.005

Cited by 18 publications

(11 citation statements)

References 55 publications

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“…2). These findings confirm observations reporting that PBDE-99 within the same concentration range used in the present study did not produce cell damage in A549 cells (Kim et al 2014). Another report assessed DOPO toxicity in PC12 and B35 neuroblastoma cell models and also observed no damage using a concentration range comparable to that applied in the present study, further confirming the low cytotoxic potential of DOPO (Hendriks et al 2014).…”

Section: Resultssupporting

confidence: 94%

Multiparameter toxicity assessment of novel DOPO-derived organophosphorus flame retardants

Hirsch

Striegl²,

Mathes

et al. 2016

Arch Toxicol

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Halogen-free organophosphorus flame retardants are considered as replacements for the phased-out class of polybrominated diphenyl ethers (PBDEs). However, toxicological information on new flame retardants is still limited. Based on their excellent flame retardation potential, we have selected three novel 9,10-dihydro-9-oxa-10-phosphaphenanthrene-10-oxide (DOPO) derivatives and assessed their toxicological profile using a battery of in vitro test systems in order to provide toxicological information before their large-scale production and use. PBDE-99, applied as a reference compound, exhibited distinct neuro-selective cytotoxicity at concentrations ≥10 µM. 6-(2-((6-oxido-6H-dibenzo[c,e][1,2]oxaphosphinin-6-yl)amino)ethoxy)-6H-dibenzo[c,e][1,2]oxaphosphinine 6-oxide (ETA-DOPO) and 6,6′-(ethane-1,2-diylbis(oxy))bis(6H-dibenzo[c,e][1,2]oxaphosphinine-6-oxide) (EG-DOPO) displayed adverse effects at concentrations >10 µM in test systems reflecting the properties of human central and peripheral nervous system neurons, as well as in a set of non-neuronal cell types. DOPO and its derivative 6,6′-(ethane-1,2-diylbis(azanediyl))bis(6H-dibenzo[c,e][1,2]oxaphosphinine-6-oxide) (EDA-DOPO) were neither neurotoxic, nor did they exhibit an influence on neural crest cell migration, or on the integrity of human skin equivalents. The two compounds furthermore displayed no inflammatory activation potential, nor did they affect algae growth or daphnia viability at concentrations ≤400 µM. Based on the superior flame retardation properties, biophysical features suited for use in polyurethane foams, and low cytotoxicity of EDA-DOPO, our results suggest that it is a candidate for the replacement of currently applied flame retardants.Electronic supplementary materialThe online version of this article (doi:10.1007/s00204-016-1680-4) contains supplementary material, which is available to authorized users.

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Section: Resultssupporting

confidence: 94%

Multiparameter toxicity assessment of novel DOPO-derived organophosphorus flame retardants

Hirsch

Striegl²,

Mathes

et al. 2016

Arch Toxicol

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“…MicroSprayer® IA-1C aerosolizer for liquid aerosols and DP-4 Dry Powder Insufflator™ for powder aerosols have been used for intratracheal delivery of nanoparticles and occupational and environmental toxicants to mice and rats [63][64][65][66]. Both devices have also been used in cellular studies [35,61,[67][68][69][70][71][72][73][74]. Particle sizes produced by DP-4 Dry Powder Insufflator™ were linked to the respective sizes of the formulated or of the not-formulated powders [75] and are roughly similar before and after aerosolization [76].…”

Section: Exposure With Particlesmentioning

confidence: 99%

In Vitro Assessment of Chronic Nanoparticle Effects on Respiratory Cells

Frőhlich¹,

Meindl²

2015

Nanomaterials - Toxicity and Risk Assessment

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Nanoparticles (NPs) are included in a variety of consumer products including cosmetics, food, and food packaging. They are also used in medical products for dermal and oral application and for inhalation. The thinness of the air-blood barrier, the large absorption area of the lung, and the relatively low inactivation by enzymes provide fast entry to the systemic blood circulation at high drug concentrations. In addition to intended uptake, exposure to airborne particles from the environment and to NPs released during the manufacturing process may occur. Cytotoxicity is routinely studied for 4-48 h of exposure, but NPs may accumulate in cells and can cause cellular effects after longer times. Both extent and consequences of cellular NP accumulation are currently largely unknown. In vitro studies could help estimating the extent and the consequences of cellular accumulation and classify NPs according to their potential to cause adverse effects upon chronic exposure. Furthermore, such information could help to decrease the amount of labor-and cost-intensive and ethically problematic animal studies. Important parameters for representative chronic cytotoxicity testing in vitro include choice of the appropriate cells and of physiological relevant culture and exposure conditions, verification of uptake, and identification of cell damage. Calu-3 bronchial epithelial cells are a suggested cell line for physiologically relevant testing when cultured on membranes, which allows supplying the cells with nutrients only from the basal side (culture at an air-liquid interface). This culturing also enables the exposure to NPs by aerosol. Cytotoxicity can be identified by changes in cell number, membrane integrity, amount of DNA or protein, and metabolic activity.

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“…Emerging contaminants such as the flame retardants (polybromo-diphenil, PBDEs ethers) PBDE-47, -99, and -209 are widespread in indoor and outdoor environmental contamination. These substances are present in fabrics, electrical materials, dust; e.g., they induce pulmonary toxicity by promoting an inflammatory response in lung epithelial cells [ 43 , 44 , 45 ]. The same PBDE profile has been described in southern Europe by Besis et al [ 46 ], while Pozo et al identified, of 26 PBDEs routinely analyzed, the presence of three (PBDE-47, -99 and -100) in the coastal areas of Sicily [ 47 ].…”

Section: Environmental Pollution and Health Of Respiratory Systemmentioning

confidence: 99%

Impact of Air Pollution in Airway Diseases: Role of the Epithelial Cells (Cell Models and Biomarkers)

Albano

Montalbano

Gagliardo

et al. 2022

IJMS

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Biomedical research is multidisciplinary and often uses integrated approaches performing different experimental models with complementary functions. This approach is important to understand the pathogenetic mechanisms concerning the effects of environmental pollution on human health. The biological activity of the substances is investigated at least to three levels using molecular, cellular, and human tissue models. Each of these is able to give specific answers to experimental problems. A scientific approach, using biological methods (wet lab), cell cultures (cell lines or primary), isolated organs (three-dimensional cell cultures of primary epithelial cells), and animal organisms, including the human body, aimed to understand the effects of air pollution on the onset of diseases of the respiratory system. Biological methods are divided into three complementary models: in vitro, ex vivo, and in vivo. In vitro experiments do not require the use of whole organisms (in vivo study), while ex vivo experiments use isolated organs or parts of organs. The concept of complementarity and the informatic support are useful tools to organize, analyze, and interpret experimental data, with the aim of discussing scientific notions with objectivity and rationality in biology and medicine. In this scenario, the integrated and complementary use of different experimental models is important to obtain useful and global information that allows us to identify the effect of inhaled pollutants on the incidence of respiratory diseases in the exposed population. In this review, we focused our attention on the impact of air pollution in airway diseases with a rapid and descriptive analysis on the role of epithelium and on the experimental cell models useful to study the effect of toxicants on epithelial cells.

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Toxicity assessment of air-delivered particle-bound polybrominated diphenyl ethers

Cited by 18 publications

References 55 publications

Multiparameter toxicity assessment of novel DOPO-derived organophosphorus flame retardants

Multiparameter toxicity assessment of novel DOPO-derived organophosphorus flame retardants

In Vitro Assessment of Chronic Nanoparticle Effects on Respiratory Cells

Impact of Air Pollution in Airway Diseases: Role of the Epithelial Cells (Cell Models and Biomarkers)

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