Most cited articles in the Archives of Toxicology: the debate about possibilities and limitations of in vitro toxicity tests and replacement of in vivo studies

Highly porous, elastic, and degradable polyurethane and polyurethane/polylactide (PU/PLDL) sponges, in various shapes and sizes, with open interconnected pores, and porosity up to 90% have been manufactured. They have been intended for gap filling in the injured spinal cord. The porosity of the sponges depended on the content of polylactide, i.e., it decreased with the increase of polylactide content. The rise of polylactide content caused an increase of Young modulus and rigidity as well as a more complex morphology of the polyurethane/polylactide blends. The mechanical properties, in vitro toxicity, and degradation in artificial cerebrospinal fluid were tested. Sponges underwent continuous degradation with varying degradation rates depending on the polymer composition. In vitro cell studies with fibroblast cultures proved the biocompatibility of the polymers. Based on the obtained results, the designed PU/PLDL sponges appeared to be promising candidates for bridging gaps within injured spinal cord in further in vitro and in vivo studies.

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Comparison of In Vivo and In Vitro Toxicity Tests from Co-inertia Analysis

ACS Symposium Series - Computer-Aided Molecular Design ◽

10.1021/bk-1995-0589.ch018 ◽

1995 ◽

pp. 250-266 ◽

Cited By ~ 1

Author(s):

James Devillers ◽

Daniel Chessel

Keyword(s):

Toxicity Tests ◽

In Vitro Toxicity

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Toxicity of Zero- and One-Dimensional Carbon Nanomaterials

Nanomaterials ◽

10.3390/nano9091214 ◽

2019 ◽

Vol 9 (9) ◽

pp. 1214 ◽

Cited By ~ 12

Author(s):

Iruthayapandi Selestin Raja ◽

Su-Jin Song ◽

Moon Sung Kang ◽

Yu Bin Lee ◽

Bongju Kim ◽

...

Keyword(s):

Quantum Dot ◽

Carbon Nanomaterials ◽

Volume Ratio ◽

In Vivo Studies ◽

In Vitro Toxicity ◽

One Dimensional ◽

Multi Walled Carbon Nanotubes ◽

Living Organisms

The zero (0-D) and one-dimensional (1-D) carbon nanomaterials have gained attention among researchers because they exhibit a larger surface area to volume ratio, and a smaller size. Furthermore, carbon is ubiquitously present in all living organisms. However, toxicity is a major concern while utilizing carbon nanomaterials for biomedical applications such as drug delivery, biosensing, and tissue regeneration. In the present review, we have summarized some of the recent findings of cellular and animal level toxicity studies of 0-D (carbon quantum dot, graphene quantum dot, nanodiamond, and carbon black) and 1-D (single-walled and multi-walled carbon nanotubes) carbon nanomaterials. The in vitro toxicity of carbon nanomaterials was exemplified in normal and cancer cell lines including fibroblasts, osteoblasts, macrophages, epithelial and endothelial cells of different sources. Similarly, the in vivo studies were illustrated in several animal species such as rats, mice, zebrafish, planktons and, guinea pigs, at various concentrations, route of administrations and exposure of nanoparticles. In addition, we have described the unique properties and commercial usage, as well as the similarities and differences among the nanoparticles. The aim of the current review is not only to signify the importance of studying the toxicity of 0-D and 1-D carbon nanomaterials, but also to emphasize the perspectives, future challenges and possible directions in the field.

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Ancient and Modern Cereals as Ingredients of the Gluten-Free Diet: Are They Safe Enough for Celiac Consumers?

Foods ◽

10.3390/foods10040906 ◽

2021 ◽

Vol 10 (4) ◽

pp. 906

Author(s):

Francesca Colombo ◽

Chiara Di Lorenzo ◽

Simone Biella ◽

Corinne Bani ◽

Patrizia Restani

Keyword(s):

Celiac Disease ◽

Autoimmune Disorder ◽

Gluten Free Diet ◽

In Vivo Studies ◽

In Vitro Toxicity ◽

Gluten Free ◽

Wide Variability

Celiac disease is an autoimmune disorder that occurs in genetically predisposed individuals after consuming prolamins from some cereals. Although the products available for celiac subjects have increased significantly in quality and quantity over the last few decades, research still focuses on identifying new ingredients to improve the nutritional, sensorial and functional qualities of gluten-free products. In terms of toxicity for people with celiac disease, there is a wide variability between ancient and modern grains. The most contradictory results are related to the role of oats in the gluten-free diet. In order to clarify the role of minor cereals (such as oat) and ancient grains in the diets of celiac patients, this review discusses recent in vitro and in vivo studies performed on those cereals for which the toxicity for celiac subjects is still controversial. According to in vivo studies, selected oat varieties could be tolerated by celiac patients. On the other hands, although some wheat-ancient grains (Triticum monococcum, Triticum aestivum ssp. spelta and Kamut®) showed a reduced in vitro toxicity, to date, these grains are still considered toxic for celiac patients. Contradictory results underline the importance of studying the safety of “unusual” cereals in more detail.

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Can the In Vivo Maximum Tolerated Dose be Predicted Using In Vitro Techniques? A Working Hypothesis

Alternatives to Laboratory Animals ◽

10.1177/026119299101900403 ◽

1991 ◽

Vol 19 (4) ◽

pp. 393-402

Author(s):

Ravi Shrivastava ◽

Gareth W. John ◽

Ginette Rispat ◽

Annick Chevalier ◽

Roy Massingham

Keyword(s):

Cell Death ◽

Research Effort ◽

Maximum Tolerated Dose ◽

In Vitro Cytotoxicity ◽

Toxicity Tests ◽

In Vitro Toxicity ◽

Working Hypothesis ◽

Wide Range

All new chemical entities synthesised in our laboratories have routinely been subjected to in vitro toxicity tests. Out of curiosity, we established a working hypothesis in which the in vitro data could be empirically transformed to predict the in vivo four-week standard maximum tolerated dose (MTD) studies in rats and dogs. As a first step to verifying this hypothesis, we report here the findings of an in vitro cytotoxicity study of 25 compounds randomly selected from our files, possessing a wide range of pharmacological activities and for which data from standard four-week MTD studies were available. Single blind in vitro toxicity studies in three carefully selected types of primary and cell line cultures were carried out. In vitro CT50 (concentration inducing 50% cell death) and CT100 (concentration inducing 100% cell death) values were obtained for each of the three cell types and, using empirical assumptions, these results were used to predict the MTD in vivo in the rat and dog. The actual in vivo threshold and toxic doses were obtained from the MTD study reports. The in vivo toxicity values predicted from the in vitro toxicity results with this series of 25 compounds showed a better than 80% correlation with the actual in vivo results obtained in the MTD studies. Whether or not in vitro cytotoxicity predictions are ultimately found to be directly and consistently related to the MTD in vivo for all pharmacological classes of compounds will require many additional studies, but it is hoped that these results will stimulate the necessary research effort required to answer this question.

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Biological Evaluation of a New Sodium-Potassium Silico-Phosphate Glass for Bone Regeneration: In Vitro and In Vivo Studies

Materials ◽

10.3390/ma14164546 ◽

2021 ◽

Vol 14 (16) ◽

pp. 4546

Author(s):

Elisa Fiume ◽

Dilshat U. Tulyaganov ◽

Avzal Akbarov ◽

Nigora Ziyadullaeva ◽

Andrea Cochis ◽

...

Keyword(s):

Lethal Dose ◽

Toxic Substance ◽

Biological Response ◽

Human Mesenchymal Stem Cells ◽

Biological Evaluation ◽

In Vivo Studies ◽

Toxicity Tests ◽

Significant Difference

In vitro and in vivo studies are fundamental steps in the characterization of new implantable materials to preliminarily assess their biological response. The present study reports the in vitro and in vivo characterizations of a novel experimental silicate bioactive glass (BG) (47.5 B, 47.5 SiO2-10 Na2O-10 K2O-10 MgO-20 CaO-2.5 P2O5 mol.%). Cytocompatibility tests were performed using human mature osteoblasts (U2OS), human mesenchymal stem cells (hMSCs) and human endothelial cells (EA.hy926). The release of the early osteogenic alkaline phosphatase (ALP) marker suggested strong pro-osteogenic properties, as the amount was comparable between hMSCs cultivated onto BG surface and cells cultivated onto polystyrene control. Similarly, real-time PCR revealed that the osteogenic collagen I gene was overexpressed in cells cultivated onto BG surface without biochemical induction. Acute toxicity tests for the determination of the median lethal dose (LD50) allowed classifying the analyzed material as a slightly toxic substance with LD50 = 4522 ± 248 mg/kg. A statistically significant difference in bone formation was observed in vivo through comparing the control (untreated) group and the experimental one, proving a clear osteogenic effect induced by the implantation at the defect site. Complete resorption of 47.5 B powder was observed after only 3 months in favor of newly formed tissue, thus confirming the high osteostimulatory potential of 47.5 B glass.

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Characterization of Fibrous Wollastonite NYAD G in View of Its Use as Negative Standard for In Vitro Toxicity Tests

Minerals ◽

10.3390/min11121378 ◽

2021 ◽

Vol 11 (12) ◽

pp. 1378

Author(s):

Dario Di Giuseppe ◽

Valentina Scognamiglio ◽

Daniele Malferrari ◽

Luca Nodari ◽

Luca Pasquali ◽

...

Keyword(s):

Biological Response ◽

Toxicity Tests ◽

In Vitro Toxicity ◽

In Vitro Tests ◽

In Vivo Models ◽

Mineral Fibre ◽

In Vivo Testing ◽

Positive Controls

Today, despite considerable efforts undertaken by the scientific community, the mechanisms of carcinogenesis of mineral fibres remain poorly understood. A crucial role in disclosing the mechanisms of action of mineral fibres is played by in vitro and in vivo models. Such models require experimental design based on negative and positive controls. Commonly used positive controls are amosite and crocidolite UICC standards, while negative controls have not been identified so far. The extensive characterisation and assessment of toxicity/pathogenicity potential carried out in this work indicate that the commercial fibrous wollastonite NYAD G may be considered as a negative standard control for biological and biomedical tests involving mineral fibres. Preliminary in vitro tests suggest that wollastonite NYAD G is not genotoxic. This material is nearly pure and is characterized by very long (46.6 µm), thick (3.74 µm) and non-biodurable fibres with a low content of metals. According to the fibre potential toxicity index (FPTI) model, wollastonite NYAD G is an inert mineral fibre that is expected to exert a low biological response during in vitro/in vivo testing.

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