In vitro models for liver toxicity testing

— There are several hundred industrial chemicals with neurotoxic potential. The neurotoxic risks of most of these chemicals are unknown. Additional methods are needed to assess the risks more effectively and to elucidate the mechanisms of neurotoxicity more accurately than is possible with the conventional methods. This paper deals with general tasks concerning the use of in vitro models in the evaluation of neurotoxic risks. It is based on our previous studies with various in vitro models and on recent literature. The induction of glial fibrillary acidic protein in astrocyte cultures after treatment with known neurotoxicants (mercury compounds and aluminium) is discussed in more detail as an important response which can be detected in vitro. When used appropriately with in vivo tests and with previous toxicological data, in vitro neurotoxicity testing considerably improves risk assessment. The incorporation of in vitro tests into the early stages of risk evaluation can reduce the number of animals used in routine toxicity testing, by identifying chemicals with high neurotoxic potential.

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Ingested Engineered Nanomaterials Affect the Expression of Mucin Genes—An In Vitro-In Vivo Comparison

Nanomaterials ◽

10.3390/nano11102621 ◽

2021 ◽

Vol 11 (10) ◽

pp. 2621

Author(s):

Gerrit Bredeck ◽

Angela A. M. Kämpfer ◽

Adriana Sofranko ◽

Tina Wahle ◽

Veronika Büttner ◽

...

Keyword(s):

Toxicity Testing ◽

In Vitro Models ◽

Engineered Nanomaterials ◽

Intestinal Mucus ◽

Specific Effects ◽

Intestinal Infections ◽

Mucin Expression ◽

Mucin Genes

The increasing use of engineered nanomaterials (ENM) in food has fueled the development of intestinal in vitro models for toxicity testing. However, ENM effects on intestinal mucus have barely been addressed, although its crucial role for intestinal health is evident. We investigated the effects of ENM on mucin expression and aimed to evaluate the suitability of four in vitro models of increasing complexity compared to a mouse model exposed through feed pellets. We assessed the gene expression of the mucins MUC1, MUC2, MUC5AC, MUC13 and MUC20 and the chemokine interleukin-8 in pre-confluent and confluent HT29-MTX-E12 cells, in stable and inflamed triple cultures of Caco-2, HT29-MTX-E12 and THP-1 cells, and in the ileum of mice following exposure to TiO2, Ag, CeO2 or SiO2. All ENM had shared and specific effects. CeO2 downregulated MUC1 in confluent E12 cells and in mice. Ag induced downregulation of Muc2 in mice. Overall, the in vivo data were consistent with the findings in the stable triple cultures and the confluent HT29-MTX-E12 cells but not in pre-confluent cells, indicating the higher relevance of advanced models for hazard assessment. The effects on MUC1 and MUC2 suggest that specific ENM may lead to an elevated susceptibility towards intestinal infections and inflammations.

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In Vitro Models for Acute Toxicity Testing

The Contribution of Acute Toxicity Testing to the Evaluation of Pharmaceuticals ◽

10.1007/978-3-642-70390-4_7 ◽

1986 ◽

pp. 46-52

Author(s):

J. M. Frazier

Keyword(s):

Acute Toxicity ◽

Toxicity Testing ◽

In Vitro Models ◽

Acute Toxicity Testing

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Human-Derived In Vitro Models Used for Skin Toxicity Testing Under REACh

10.1007/164_2020_368 ◽

2020 ◽

Author(s):

Susanne N. Kolle ◽

Robert Landsiedel

Keyword(s):

Toxicity Testing ◽

Skin Toxicity ◽

In Vitro Models

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Barriers, Nephrotoxicology and Chronic Testing In Vitro

Alternatives to Laboratory Animals ◽

10.1177/026119290203002s15 ◽

2002 ◽

Vol 30 (2_suppl) ◽

pp. 101-105 ◽

Cited By ~ 7

Author(s):

Pilar Prieto

Keyword(s):

Chronic Exposure ◽

Cellular Response ◽

Chronic Toxicity ◽

Intestinal Barrier ◽

Toxicity Testing ◽

In Vitro Models ◽

Renal Epithelium ◽

Acute And Chronic Exposure

In many organs of the human body, there are effective physiological barriers which contribute to regulation of the uptake, transport and secretion of endogenous and exogenous materials. ECVAM is involved in the development of several in vitro models for detecting damage to various barriers, including, the renal epithelium, the intestinal barrier, and the blood–brain barrier, after acute and chronic exposure to chemicals and products of various kinds. Long-term toxicity testing is an important issue in toxicology. At present, there are no generally accepted in vitro models available for replacing chronic testing in animals. Under chronic exposure conditions, the cellular response is greater than that which can be predicted in the standard cytotoxicity models. Therefore, the approach to predicting chronic toxicity will need to involve more-complex in vitro models. Several currently available in vitro long-term toxicity systems are under evaluation.

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Computational fluid dynamics applied to the ventilation of small-animal laboratory cages

Laboratory Animals ◽

10.1177/0023677220937718 ◽

2020 ◽

pp. 002367722093771

Author(s):

Ira Katz ◽

Kateryna Voronetska ◽

Mickaël Libardi ◽

Matthieu Chalopin ◽

Patricia Privat ◽

...

Keyword(s):

Fluid Dynamics ◽

Computational Fluid Dynamics ◽

Noble Gas ◽

Small Animal ◽

Toxicity Testing ◽

Exposure Period ◽

In Vitro Models ◽

Gas Distribution

Several studies based on in vivo or in vitro models have found promising results for the noble gas argon in neuroprotection against ischaemic pathologies. The development of argon as a medicinal product includes the requirement for toxicity testing through non-clinical studies. The long exposure period of animals (rats) during several days results in technical and logistic challenges related to the gas administration. In particular, a minimum of 10 air changes per hour (ACH) to maintain animal welfare results in extremely large volumes of experimental gas required if the gas is not recirculated. The difficulty with handling the many cylinders prompted the development of such a recirculation-based design. To distribute the recirculating gas to individually ventilated cages and monitor them properly was deemed more difficult than constructing a single large enclosure that will hold several open cages. To address these concerns, a computational fluid dynamics (CFD) analysis of the preliminary design was performed. A purpose-made exposure chamber was designed based on the CFD simulations. Comparisons of the simulation results to measurements of gas concentration at two cage positions while filling show that the CFD results compare well to these limited experiments. Thus, we believe that the CFD results are representative of the gas distribution throughout the enclosure. The CFD shows that the design provides better gas distribution (i.e. a higher effective air change rate) than predicted by 10 ACH.

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In Vitro Models of Liver Toxicity

Handbook of Experimental Pharmacology - Drug-Induced Hepatotoxicity ◽

10.1007/978-3-642-61013-4_5 ◽

1996 ◽

pp. 99-117

Author(s):

R. G. Thurman ◽

P. E. Ganey ◽

S. A. Belinsky ◽

J. G. Conway ◽

M. Z. Badr

Keyword(s):

Liver Toxicity ◽

In Vitro Models

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Microcystin-LR Does Not Alter Cell Survival and Intracellular Signaling in Human Bronchial Epithelial Cells

Toxins ◽

10.3390/toxins12030165 ◽

2020 ◽

Vol 12 (3) ◽

pp. 165 ◽

Cited By ~ 2

Author(s):

Ondřej Brózman ◽

Barbara Kubickova ◽

Pavel Babica ◽

Petra Laboha

Keyword(s):

Human Health ◽

Respiratory System ◽

Intracellular Signaling ◽

Liver Toxicity ◽

Organic Anion ◽

In Vitro Models ◽

Cyanobacterial Blooms ◽

Bronchial Epithelial ◽

Mitogen Activated Protein

Changes in ecological and environmental factors lead to an increased occurrence of cyanobacterial water blooms, while secondary metabolites-producing cyanobacteria pose a threat to both environmental and human health. Apart from oral and dermal exposure, humans may be exposed via inhalation and/or swallowing of contaminated water and aerosols. Although many studies deal with liver toxicity, less information about the effects in the respiratory system is available. We investigated the effects of a prevalent cyanotoxin, microcystin-LR (MC-LR), using respiratory system-relevant human bronchial epithelial (HBE) cells. The expression of specific organic-anion-transporting polypeptides was evaluated, and the western blot analysis revealed the formation and accumulation of MC-LR protein adducts in exposed cells. However, MC-LR up to 20 μM neither caused significant cytotoxic effects according to multiple viability endpoints after 48-h exposure, nor reduced impedance (cell layer integrity) over 96 h. Time-dependent increase of putative MC-LR adducts with protein phosphatases was not associated with activation of mitogen-activated protein kinases ERK1/2 and p38 during 48-h exposure in HBE cells. Future studies addressing human health risks associated with inhalation of toxic cyanobacteria and cyanotoxins should focus on complex environmental samples of cyanobacterial blooms and alterations of additional non-cytotoxic endpoints while adopting more advanced in vitro models.

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