Overview of the Final MEIC Results: II. The In Vitro--In Vivo Evaluation, Including the Selection of a Practical Battery of Cell Tests for Prediction of Acute Lethal Blood Concentrations in Humans

Toxicology in Vitro : an International Journal Published in Association with BIBRA
B Ekwall

Abstract

In MEIC, all 50 reference chemicals were tested in 61 in vitro assays. To provide a background to the in vitro/in vivo evaluation, mouse LD(50) values were compared with human lethal doses, resulting in a good correlation (R(2) 0.65). To study the relevance of in vitro results, IC(50) values were compared with human lethal blood concentrations (LCs) by linear regression. An average IC(50) for the ten 24-hour human cell line tests predicted peak LCs better (R(2) 0.74) than other groups of tests. When IC(50) values for 32 chemicals which rapidly enter brain were divided by a factor of 3.2 and 48-hour IC(50) values were compared with 48-hour human LCs for 10 slow-acting chemicals, the prediction improved considerably. Human toxicity was clearly underpredicted for only four chemicals, namely digoxin, malathion, nicotine and atropine, indicating a high relevance of the human cell line toxicity. All chemicals entering the brain induced a CNS depression, explaining this syndrome as a cytotoxic effect. Multivariate analysis was used to select an optimal combination of assays, resulting in a battery of three 24-hour human cell line tests (endpoints: protein, ATP and morphology/pH) with good direct prediction of human peak LCs (R(2) 0.77).

References

Jan 1, 1983·Annals of the New York Academy of Sciences·B Ekwall
Aug 1, 1999·Toxicology in Vitro : an International Journal Published in Association with BIBRA·C Clemedson, B Ekwall

❮ Previous
Next ❯

Citations

Jan 13, 2011·Archives of Toxicology·Anna M Wobus, Peter Löser
May 17, 2005·Toxicology in Vitro : an International Journal Published in Association with BIBRA·F LestariB Markovic
May 9, 2001·Toxicology in Vitro : an International Journal Published in Association with BIBRA·E Walum
Nov 9, 2002·Toxicology in Vitro : an International Journal Published in Association with BIBRA·P J Dierickx
Nov 6, 2003·Toxicology in Vitro : an International Journal Published in Association with BIBRA·Paul J Dierickx
Feb 6, 2004·Toxicology in Vitro : an International Journal Published in Association with BIBRA·P A Botham
Aug 1, 1999·Toxicology in Vitro : an International Journal Published in Association with BIBRA·C Clemedson, B Ekwall
Aug 6, 2002·Comparative Biochemistry and Physiology. Part A, Molecular & Integrative Physiology·E-M FröjdöB Isomaa
Oct 16, 2003·Comparative Biochemistry and Physiology. Toxicology & Pharmacology : CBP·Arturo Villegas-NavarroJosé L Reyes
Jul 8, 2009·Critical Reviews in Food Science and Nutrition·Ulf HammerlingNils-Gunnar Ilbäck
May 10, 2008·Toxicology in Vitro : an International Journal Published in Association with BIBRA·C SuñolI Vendrell
Jan 24, 2007·Toxicology and Applied Pharmacology·Catherine McDermottJames J A Heffron
Jan 17, 2014·Basic & Clinical Pharmacology & Toxicology·Erik Walum
Aug 8, 2006·Toxicology in Vitro : an International Journal Published in Association with BIBRA·Kenjiro KogaKazuhiro Shintani
Aug 2, 2005·Toxicology in Vitro : an International Journal Published in Association with BIBRA·Paul J Dierickx
Apr 25, 2015·Drug Discovery Today·David J BraydenJeremy C Simpson
May 1, 2012·Toxicology in Vitro : an International Journal Published in Association with BIBRA·Jessica LundqvistAnna Forsby
Aug 28, 2012·Toxicology in Vitro : an International Journal Published in Association with BIBRA·P PrietoA Kopp-Schneider
Aug 6, 2005·Toxicology in Vitro : an International Journal Published in Association with BIBRA·Helga Tuschl, Christina E Schwab
Mar 23, 2007·Toxicology in Vitro : an International Journal Published in Association with BIBRA·Lijuan ZhangZongcan Zhou
Feb 17, 2006·Toxicology in Vitro : an International Journal Published in Association with BIBRA·James Z XingLi Xie
Jan 17, 2012·Chemical Research in Toxicology·Nynke I KramerJoop L M Hermens
Jan 25, 2002·Journal of Applied Toxicology : JAT·Paul J Dierickx, Ellen M Scheers
Jun 16, 2016·Genetics and Molecular Biology·Leonardo Campos ZanelattoMário Sérgio Mantovani
Jun 13, 2017·Sensors·Cindy SchaudeGerhard J Mohr
May 4, 2018·Journal of Biomaterials Applications·Kanwal IlyasAbdul S Khan
Jul 10, 2012·BMC Medical Ethics·Ray GreekLawrence A Hansen
Sep 27, 2013·Journal of Materials Science. Materials in Medicine·V LorberSandra Utzschneider
Mar 19, 2014·Academic Emergency Medicine : Official Journal of the Society for Academic Emergency Medicine·Jeremiah D SchuurPeter C Hou
Aug 21, 2014·American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics : the Official Publication of the International Society of Psychiatric Genetics·Avinash M VeerappaNallur B Ramachandra
Feb 19, 2020·Current Pharmaceutical Design·Eleonore Fröhlich
Jun 2, 2001·Alternatives to Laboratory Animals : ATLA·P J DierickxE M Scheers
Jun 2, 2001·Alternatives to Laboratory Animals : ATLA·A NovilloA Castaño

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.