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Acute toxicity testing of inhalable/gaseous compounds by cell-based methods in vitro - application to volatile organic compounds

: Ritter, Detlef; Knebel, Jan


Toxicology letters 238 (2015), Nr.2, Supplement, S.S178, Abstract P07-016
ISSN: 0378-4274
ISSN: 1879-3169
European Societies of Toxicology (EUROTOX Congress) <51, 2015, Porto>
Fraunhofer ITEM ()

Cell-based in vitro methods using the “air-lifted interface” culture technique have been applied to test the biological activity of airborne materials from different sources such as environmental, workplace or chemical compounds, also, in their relevant inhalable state. A good predictability for acute toxicity testing could be demonstrated in a pre-validation study using relatively high toxic chemical gases such as nitrogen dioxide and ozone and inert gases. To extend this range of substances, a set of volatile organic compounds (VOCs) was tested for applicability using this short-exposure in vitro test. Therefore, a test matrix of different VOCs was set up from the database of the European Chemicals Agency (ECHA), including VOCs differing in acute inhalation toxicity and hydrophobicity. Cell-based in vitro testing was carried out using vaporized compounds, an improved air-liquid interface in vitro procedure (PRIT ExpoCube) using a human lung cell line (A549cells) and measurement of cytotoxicity (WST-1). In vitro ED50 values were estimated from dose-response curves and correlated to in vivo acute toxicity data. A good correlation of the relative toxicity between in vitro and in vivo results was found in this set of compounds including hydrophobic, low-toxic and hydrophilic low-toxic substances. The results demonstrate that it was possible to study the acute inhalation toxicity of VOCs in their relevant, inhalable gaseous state by cell-based in vitro methods. Therefore, it is concluded that this in vitro approach can be classified as a useful alternative method for acute toxicity screening purposes in the sense of the “3Rs”