Scandinavian Society for Cell Toxicology – Thirty Years of Scientific Pioneering

Walum, Erik

doi:10.1111/bcpt.12194

Cited by 4 publications

(3 citation statements)

References 20 publications

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“…In the 1980s, progress in understanding of cell biology and culture methods, and increasing interest in animal alternatives for toxicity assessment, led to a large growth in research and publications on cytotoxicity assessment. 6 Previously, interest had focused on immune-mediated cytotoxicity and on anticancer therapy. Using the web browser PubMed and the search term "cytotoxic", nine publications were retrievable by a worldwide web search for up to the year 1940, 24 up to 1955, 1,856 up to 1970, 17,249 up to 1985, 67,898 up to 2000, and 157,069 up to May 21, 2016.…”

Section: Introduction and Literature Reviewmentioning

confidence: 99%

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Validation of a Multiparametric, High-Content-Screening Assay for Predictive/Investigative Cytotoxicity: Evidence from Technology Transfer Studies and Literature Review

O’Brien

Edvardsson

2017

Chem. Res. Toxicol.

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A multiparametric, live-cell, high-content-screening (HCS) cytotoxicity assay was first demonstrated in 2006 ( Arch. Toxicol. 2006 , 80 , 580 - 604 ) to be highly concordant with human hepatotoxicity, including idiosyncratic hepatotoxicities and other target organ toxicities in contrast to historical assays. The success of the assay was attributed to its simultaneous measurement of multiple appropriate "cytobiomarkers": use of human cells with xenometabolic competence for toxicities mediated by metabolites, 72 h exposure to enable expression of slower-acting toxicants, exposure to a wide-range of concentrations from 30- to 100-fold the efficacious concentration, and normalizing the in vitro cytotoxic concentration to an estimate of the in vivo concentration of exposure. An overwhelming volume of evidence has accumulated over the last 10 years to support this approach as necessary in predictive toxicology. Equivalent assays have now been successfully applied in ∼50 studies across a wide variety of toxicants, toxicities, cell types, and disciplines. Review herein of the wider literature on cytotoxicity since the first assay was reported 100 years ago supports the selection of key cytobiomarkers along a final common pathway of cell injury, including cell proliferation, mitochondrial activity, apoptosis, lysosomal mass, oxidative stress, and cell membrane permeability. HCS studies without inclusion of such key cytobiomarkers or without testing to sufficiently high concentration have not been as successful. Furthermore, a subset of the original toxicants has been reanalyzed herein using the original HCS assay and has confirmed their high sensitivities and specificities across locations, HCS technologies, staff, laboratories, and time. A protocol is demonstrated for operational validation of the assay within laboratories to demonstrate proficiency and quality management.

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Section: Introduction and Literature Reviewmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Validation of a Multiparametric, High-Content-Screening Assay for Predictive/Investigative Cytotoxicity: Evidence from Technology Transfer Studies and Literature Review

O’Brien

Edvardsson

2017

Chem. Res. Toxicol.

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“…The number of participants was 71, from 9 countries and with many young scientists. With this workshop, SSCT celebrated its 30-year anniversary.Professor Erik Walum, the first president of SSCT, gave a lecture about the history of SSCT [1]. After the establishment in October 1983, the first SSCT meeting was held on the initiative of Bj€ orn Ekwall, Uppsala.…”

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confidence: 99%

Workshop of Scandinavian Society for Cell Toxicology 25‐27 September 2013 in Denmark

Knudsen

Mathiesen

Nielsen

et al. 2014

Basic Clin Pharma Tox

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The workshop 'Frontiers in Cell Toxicity Testing' consisted of 5 sessions and a poster exhibition. Together, there were 28 oral presentations and 12 poster presentations. The number of participants was 71, from 9 countries and with many young scientists. With this workshop, SSCT celebrated its 30-year anniversary.Professor Erik Walum, the first president of SSCT, gave a lecture about the history of SSCT [1]. After the establishment in October 1983, the first SSCT meeting was held on the initiative of Bj€ orn Ekwall, Uppsala. The annual SSCT workshop has been organized every year since 1983 with exception of 2010 and 2012. The important mission of SSCT has been to promote the study of effects of chemicals in cellular models. This mission was concretized in the Multicentre Evaluation of In Vitro Cytotoxicity (MEIC) programme (1989)(1990)(1991)(1992)(1993)(1994)(1995)(1996)(1997)(1998)(1999), initiated and guided by Dr. Bj€ orn Ekwall. The main goal of this project was the evaluation of the predictive value of in vitro cytotoxicity tests for human toxicity.The Bj€ orn Ekwall Memorial Lecture held in 2013 was given by Professor Per Artursson (Uppsala University, Sweden) who received this year's Bj€ orn Ekwall Memorial Award. In his presentation 'Towards quantitative predictions of ADMET properties in vitro', Per Artursson told about the failure in previous times of 40% of drug candidates during the clinical trials due to unpredictable pharmacokinetic events. He told that today the application of new methods based on advanced cell and molecular biology in early drug discovery has resulted in almost complete elimination of clinical failure due to unpredictable pharmaceutical events. In some cases, these new methods have now been accepted by regulatory agencies as surrogates for in vivo studies. Per Artursson also presented weaknesses of the current in vitro methodologies. To overcome these challenges, he presented recent approaches towards more quantitative predictions of drug exposure: for example, models for estimation of free drug concentration, proteomics-informed quantification of drug transport and metabolism, and in vitro predictions of drug-induced liver injury.The scientific programme included presentations of new technologies in cell toxicity testing including efficient and sensitive techniques of high-content screening (HCS) based on in vitro monitoring of biochemical and morphological responses of individual live cells to chemical stress in microtitre plates [2][3][4]. This technique can be further refined and developed for use in preclinical testing, diagnostic and prognostic testing as well as monitoring.Attention was also given to the new paradigm in human toxicology focusing on adverse outcome pathways (AOP) to further qualify and quantify the mechanisms involved in human toxicology by use of human biological material [5] and exemplified with fluorochemicals by Taxvig et al. [6].In the section on risk assessment, an update on the REACH regulation was provided, and new technologies of epigenetics and tr...

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Contributions of the Scandinavian Countries to the Development of Non-Animal Alternatives in Toxicology

Forsby

Knudsen

Tähti

2019

The History of Alternative Test Methods in Toxicology

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Scandinavian Society for Cell Toxicology – Thirty Years of Scientific Pioneering

Cited by 4 publications

References 20 publications

Validation of a Multiparametric, High-Content-Screening Assay for Predictive/Investigative Cytotoxicity: Evidence from Technology Transfer Studies and Literature Review

Validation of a Multiparametric, High-Content-Screening Assay for Predictive/Investigative Cytotoxicity: Evidence from Technology Transfer Studies and Literature Review

Workshop of Scandinavian Society for Cell Toxicology 25‐27 September 2013 in Denmark

Contributions of the Scandinavian Countries to the Development of Non-Animal Alternatives in Toxicology

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