• An across-species comparison of the sensitivity of different organisms to Pb-based perovskites used in solar cells.

      Wang, Guiyin; Zhai, Yujia; Zhang, Shirong; Diomede, Luisa; Bigini, Paolo; Romeo, Margherita; Cambier, Sebastien; Contal, Servane; Nguyen, Nhung H A; Rosická, Petra; et al. (2020-03-15)
      Organic-inorganic perovskite solar cells (PSCs) are promising candidates as photovoltaic cells. Recently, they have attracted significant attention due to certified power conversion efficiencies exceeding 23%, low-cost engineering, and superior electrical/optical characteristics. These PSCs extensively utilize a perovskite-structured composite with a hybrid of Pb-based nanomaterials. Operation of them may cause the release of Pb-based nanoparticles. However, limited information is available regarding the potential toxicity of Pb-based PSCs on various organisms. This study conducted a battery of in vitro and in vivo toxicity bioassays for three quintessential Pb-based PSCs (CH3NH3PbI3, NHCHNH3PbBr3, and CH3NH3PbBr3) using progressively more complex forms of life. For all species tested, the three different perovskites had comparable toxicities. The viability of Caco-2/TC7 cells was lower than that of A549 cells in response to Pb-based PSC exposure. Concentration-dependent toxicity was observed for the bioluminescent bacterium Vibrio fischeri, for soil bacterial communities, and for the nematode Caenorhabditis elegans. Neither of the tested Pb-based PSCs particles had apparent toxicity to Pseudomonas putida. Among all tested organisms, V. fischeri showed the highest sensitivity with EC50 values (30 min of exposure) ranging from 1.45 to 2.91 mg L-1. Therefore, this study recommends that V. fischeri should be preferably utilized to assess. PSC toxicity due to its increased sensitivity, low costs, and relatively high throughput in a 96-well format, compared with the other tested organisms. These results highlight that the developed assay can easily predict the toxic potency of PSCs. Consequently, this approach has the potential to promote the implementation of the 3Rs (Replacement, Reduction, and Refinement) principle in toxicology and decrease the dependence on animal testing when determining the safety of novel PSCs.
    • A comprehensive view on mechanistic approaches for cancer risk assessment of non-genotoxic agrochemicals.

      Luijten, Mirjam; Corvi, Raffaella; Mehta, Jyotigna; Corvaro, Marco; Delrue, Nathalie; Felter, Susan; Haas, Bodo; Hewitt, Nicola J; Hilton, Gina; Holmes, Thomas; et al. (2020-10-07)
    • Differential effects of fluoxetine and venlafaxine in the neural embryonic stem cell test (ESTn) revealed by a cell lineage map.

      de Leeuw, Victoria C; Hessel, Ellen V S; Pennings, Jeroen L A; Hodemaekers, Hennie M; Wackers, Paul F K; van Oostrom, Conny T M; Piersma, Aldert H (2019-10-05)
    • An efficient neuron-astrocyte differentiation protocol from human embryonic stem cell-derived neural progenitors to assess chemical-induced developmental neurotoxicity.

      de Leeuw, Victoria C; van Oostrom, Conny T M; Westerink, Remco H S; Piersma, Aldert H; Heusinkveld, Harm J; Hessel, Ellen V S (2020-09-12)
    • Look-alikes may not act alike: Gene expression regulation and cell-type-specific responses of three valproic acid analogues in the neural embryonic stem cell test (ESTn).

      de Leeuw, Victoria C; Hessel, Ellen V S; Piersma, Aldert H (2019-03-15)
      In vitro assays to assess developmental neurotoxicity of chemicals are highly desirable. The murine neural embryonic stem cell test (ESTn) can mimic parts of early differentiation of embryonic brain and may therefore be useful for this purpose. The aim of this study was to investigate whether this test is able to rank the toxic potencies of three valproic acid analogues and to study their mode of action by investigating their individual effects on four cell types: stem cells, neurons, astrocytes and neural crest cells. Using immunocytochemical read-outs and qPCR for cell type-specific genes, the effects of valproic acid (VPA), 2-ethylhexanoic acid (EHA) and 2-ethyl-4-methylpentanoic (EMPA) were assessed. VPA and EHA but not EMPA downregulated cell type-specific differentiation makers and upregulated stem cell related markers (Fut4, Cdh1) at different time points during differentiation. Expression of Gfap, a marker for astrocytes, was dramatically downregulated by VPA and EHA, but not by EMPA. This finding was verified using immunostainings. Based on the number and extent of genes regulated by the three compounds, relative potencies were determined as VPA > EHA > EMPA, which is consistent with in vivo developmental toxicity potency ranking of these compounds. Thus, ESTn using a combination of morphology, gene and protein expression readouts, may provide a medium-throughput system for monitoring the effects of compounds on differentiation of cell types in early brain development.
    • A next-generation sequencing based method for determining genetic stability in Clostridium tetani vaccine strains.

      Pennings, Jeroen L A; Abachin, Eric; Uhlrich, Sylvie; Esson, Raphaël; Mallet, Laurent; Vandebriel, Rob J (2020-03-01)
    • Use of the kinetically-derived maximum dose concept in selection of top doses for toxicity studies hampers proper hazard assessment and risk management.

      Heringa, Minne B; Cnubben, Nicole H P; Slob, Wout; Pronk, Marja E J; Muller, Andre; Woutersen, Marjolijn; Hakkert, Betty C (2020-07-01)