The in vitro assessment of the toxicity of volatile, oxidisable, redox-cycling compounds: phenols as an example.
The in vitro assessment of the toxicity of volatile, oxidisable, redox-cycling compounds: phenols as an example.
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DOI：
10.1007/s00204-021-03036-w
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发表时间：
2021-06
影响因子：
6.1
通讯作者：
Castell JV
中科院分区：
文献类型：
--
作者：
Tolosa L;Martínez-Sena T;Schimming JP;Moro E;Escher SE;Ter Braak B;van der Water B;Miranda MA;van Vugt-Lussenburg BMA;Castell JV
苯酚被认为是剧毒化学品。由于其命运不明确（降解、自动氧化和挥发性），难以在体外系统中研究其影响。在一系列氧化还原循环酚的体外研究过程中，我们发现了几种体外高通量测试系统中交叉污染的证据，特别是三甲基苯-1，4-二醇/三甲基氢醌（TMHQ）和2，6-二叔丁基-4-乙基苯酚（DTBEP），TMHQ具有快速降解动力学，降解速率快。所得醌向相邻威尔斯孔的扩散速率，其它降解产物也能够空气扩散。DTBEP表现出较低的降解动力学，但较高的扩散速率。在这两种情况下，由于浓度降低以及与相邻威尔斯孔的交叉污染，体外毒性被低估。我们确定了TMHQ的四种降解产物和DTBEP的五种降解产物，这表明目前对细胞的影响不仅归因于母体酚类化合物。为了克服这些缺点，我们详细研究了在孵育过程中发生的物理化学变化，并使用透气和不透气的塑料密封件来防止它。通过使用两种塑料密封件，极大地防止了扩散，如GC-MS分析所示。不透气的塑料密封件，将化合物扩散以及氧化减少到最低限度，并且不影响培养细胞的生物学性能。因此，在相邻的威尔斯孔中未观察到毒理学交叉污染，从而可以更可靠地对苯酚诱导的毒性进行体外评估。在线版本包含补充材料，可通过10.1007/s 00204 -021-03036-w获得。
Phenols are regarded as highly toxic chemicals. Their effects are difficult to study in in vitro systems because of their ambiguous fate (degradation, auto-oxidation and volatility). In the course of in vitro studies of a series of redox-cycling phenols, we found evidences of cross-contamination in several in vitro high-throughput test systems, in particular by trimethylbenzene-1, 4-diol/trimethylhydroquinone (TMHQ) and 2,6-di-tertbutyl-4-ethylphenol (DTBEP), and investigated in detail the physicochemical basis for such phenomenon and how to prevent it. TMHQ has fast degradation kinetics followed by significant diffusion rates of the resulting quinone to adjacent wells, other degradation products being able to air-diffuse as well. DTBEP showed lower degradation kinetics, but a higher diffusion rate. In both cases the in vitro toxicity was underestimated because of a decrease in concentration, in addition to cross-contamination to neighbouring wells. We identified four degradation products for TMHQ and five for DTBEP indicating that the current effects measured on cells are not only attributable to the parent phenolic compound. To overcome these drawbacks, we investigated in detail the physicochemical changes occurring in the course of the incubation and made use of gas-permeable and non-permeable plastic seals to prevent it. Diffusion was greatly prevented by the use of both plastic seals, as revealed by GC–MS analysis. Gas non-permeable plastic seals, reduced to a minimum compounds diffusion as well oxidation and did not affect the biological performance of cultured cells. Hence, no toxicological cross-contamination was observed in neighbouring wells, thus allowing a more reliable in vitro assessment of phenol-induced toxicity. The online version contains supplementary material available at 10.1007/s00204-021-03036-w.
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影响因子：
3.3
作者：
Piersma, A. H.;Bosgra, S.;van der Burg, B.
通讯作者：
van der Burg, B.
影响因子：
2.2
作者：
BLEIN, O;RONOT, X;ADOLPHE, M
通讯作者：
ADOLPHE, M
影响因子：
4.5
作者：
Campbell, Jerry L.;Yoon, Miyoung;Clewell, Harvey J.
通讯作者：
Clewell, Harvey J.
DOI：
10.1016/j.comtox.2017.09.001
发表时间：
2017-11-01
期刊：
Computational toxicology (Amsterdam, Netherlands)
影响因子：
--
作者：
Pradeep, Prachi;Mansouri, Kamel;Judson, Richard
通讯作者：
Judson, Richard
DOI：
10.1007/978-1-4939-9420-5_13
发表时间：
2019-01-01
期刊：
EXPERIMENTAL CHOLESTASIS RESEARCH
影响因子：
--
作者：
Schimming, Johannes P.;ter Braak, Bas;van de Water, Bob
通讯作者：
van de Water, Bob