Bundeswehr Institute of Pharmacology and Toxicology, Neuherbergstrasse 11, 80937 Munich, Germany.
Bundeswehr Institute of Pharmacology and Toxicology, Neuherbergstrasse 11, 80937 Munich, Germany.
Toxicol Lett. 2023 Oct 1;388:24-29. doi: 10.1016/j.toxlet.2023.10.007. Epub 2023 Oct 10.
Organ-on-a-chip platforms are an emerging technology in experimental and regulatory toxicology (species-specific differences, ethical considerations). They address gaps between in vivo and in vitro models. However, there are still certain limitations considering material, setup and applicability. The current study examined the suitability of a commercially available polydimethylsiloxane-based (PDMS) organ-chip for the toxicokinetic characterization of the highly toxic nerve agent VX and the organophosphate pesticide parathion. The respective concentrations of 1000 µmol/L and 100 µmol/L VX and parathion were chosen deliberately high in order to study concentrations even if high compound absorption by PDMS might occur. Neuronal and liver spheroids, totaling 2 × 10 cells were used to study concentration changes of VX and parathion. In addition, VX enantiomers were quantified. The current study suggests a significant absorption of VX, respectively parathion by PDMS. This might require future investigation of alternative materials or coatings to limit absorption for organophosphorus compounds in toxicokinetic studies.
器官芯片平台是实验毒理学和监管毒理学中的一项新兴技术（物种特异性差异，伦理考虑）。它们解决了体内和体外模型之间的差距。然而，考虑到材料、设置和适用性，仍然存在某些局限性。本研究考察了一种市售的基于聚二甲基硅氧烷（PDMS）的器官芯片用于研究高度毒性神经毒剂 VX 和有机磷农药对硫磷的毒代动力学特征的适用性。选择 1000µmol/L 和 100µmol/L 的 VX 和对硫磷浓度故意设得很高，以便即使 PDMS 可能会发生高化合物吸收，也能研究浓度。总共使用 2×10 个神经元和肝球体来研究 VX 和对硫磷的浓度变化。此外，还对 VX 对映体进行了定量分析。本研究表明 PDMS 对 VX 和对硫磷有明显的吸收。这可能需要进一步研究替代材料或涂层来限制毒代动力学研究中有机磷化合物的吸收。
