Evidence map›Paper›PMID 31158489›Full record

ArticleToxicology in vitro : an international journal published in association with BIBRA2019

Validation of in vitro methods for human cytochrome P450 enzyme induction: Outcome of a multi-laboratory study.

Camilla Bernasconi, Olavi Pelkonen, Tommy B Andersson, Judy Strickland, Iwona Wilk-Zasadna, David Asturiol, Thomas Cole, Roman Liska, Andrew Worth, Ursula Müller-Vieira and 3 more

Open access · hybridAbstract readValidation Study
In one paragraph

Article in Toxicology in vitro : an international journal published in association with BIBRA, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
31citing papers in PubMed, 1 pooled it
6.4field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

31 citing papers in PubMed, 1 synthesis or guideline pooled it, 57 citations in OpenAlex.

  1. Guideline
  2. Article
  3. Review
  4. Review
  5. Transferability and Reproducibility of the HepaRG CometChip Assay.Environmental and molecular mutagenesis · 2025
    Article
  6. Review
  7. HepaRGNAM journal · 2025
    Article
  8. Article
  9. Article
  10. Review
  11. Article
  12. Article
  13. Review
  14. Review
  15. Review
  16. Article
  17. Article
  18. Review
  19. Review
  20. Use of computational toxicology tools to predictCurrent research in toxicology · 2022
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors at 5 institutions in 5 countries.

Camilla BernasconiEuropean Commission, Joint Research Centre (JRC), Ispra, Italy.
Olavi PelkonenResearch Unit of Biomedicine/Pharmacology and Toxicology, Faculty of Medicine, Aapistie 5B, University of Oulu, FIN-90014, Finland; Clinical Research Center, Oulu University Hospital, Finland.
Tommy B AnderssonDrug Metabolism and Pharmacokinetics, Cardiovascular, Renal and Metabolism, IMED Biotech Unit, AstraZeneca, Gothenburg, Sweden; Department of Physiology and Pharmacology, Section of Pharmacogenetics, Karolinska Institutet, SE-171 77 Stockholm, Sweden.
Judy StricklandIntegrated Laboratory Systems (contractor supporting NICEATM), Research Triangle Park, North, Carolina, 27709, USA.
Iwona Wilk-ZasadnaEuropean Commission, Joint Research Centre (JRC), Ispra, Italy.
David AsturiolEuropean Commission, Joint Research Centre (JRC), Ispra, Italy.
Thomas ColeEuropean Commission, Joint Research Centre (JRC), Ispra, Italy.
Roman LiskaEuropean Commission, Joint Research Centre (JRC), Ispra, Italy.
Andrew WorthEuropean Commission, Joint Research Centre (JRC), Ispra, Italy.
Ursula Müller-VieiraBoehringer Ingelheim, Germany. Department of Drug Discovery Sciences, Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach, an der Riss, Germany.
Lysiane RichertKaLy-Cell, 20A, rue du Général Leclerc, 67115 Plobsheim, France(g) Biopredic International, Parc d'activité de la Bretèche Bâtiment A4, 35760 Saint Grégoire, France.
Christophe ChesneBiopredic International, Parc d'activité de la Bretèche Bâtiment A4, 35760 Saint Grégoire, France.
Sandra CoeckeEuropean Commission, Joint Research Centre (JRC), Ispra, Italy. Electronic address: sandra.coecke@ec.europa.eu.
Joint Research Centre · ITAstraZeneca (Sweden) · SEBiopredic (France) · FRBoehringer Ingelheim (Germany) · DEUniversity of Oulu · FI

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

CYP enzyme induction is a sensitive biomarker for phenotypic metabolic competence of in vitro test systems; it is a key event associated with thyroid disruption, and a biomarker for toxicologically relevant nuclear receptor-mediated pathways. This paper summarises the results of a multi-laboratory validation study of two in vitro methods that assess the potential of chemicals to induce cytochrome P450 (CYP) enzyme activity, in particular CYP1A2, CYP2B6, and CYP3A4. The methods are based on the use of cryopreserved primary human hepatocytes (PHH) and human HepaRG cells. The validation study was coordinated by the European Union Reference Laboratory for Alternatives to Animal Testing of the European Commission's Joint Research Centre and involved a ring trial among six laboratories. The reproducibility was assessed within and between laboratories using a validation set of 13 selected chemicals (known human inducers and non-inducers) tested under blind conditions. The ability of the two methods to predict human CYP induction potential was assessed. Chemical space analysis confirmed that the selected chemicals are broadly representative of a diverse range of chemicals. The two methods were found to be reliable and relevant in vitro tools for the assessment of human CYP induction, with the HepaRG method being better suited for routine testing. Recommendations for the practical application of the two methods are proposed.

Indexed as

Animal Testing AlternativesCells, CulturedCell SurvivalCytochrome P-450 Enzyme InducersCytochrome P-450 Enzyme SystemEnzyme InductionHepatocytesHumansLaboratoriesReproducibility of ResultsSolubilityCytochrome P-450 Enzyme InducersCytochrome P-450 Enzyme SystemCYP inductionHepaRGhuman hepatocytesin vitro hepatic systemmetabolismvalidation

Identifiers

PMID31158489
PMCPMC6718736
OpenAlexW2947052349

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.