Skip to main content

Advertisement

SpringerLink
Log in

Highlight Report: Adverse outcome pathways: the need of research on mechanisms of toxicity

  • Letter to the Editor, News and Views
  • Published:
Archives of Toxicology Aims and scope Submit manuscript

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

References

  • Albrecht W, Kappenberg F, Brecklinghaus T et al (2019) Prediction of human drug-induced liver injury (DILI) in relation to oral doses and blood concentrations. Arch Toxicol 93:1609–1637. https://doi.org/10.1007/s00204-019-02492-9

    Article  CAS  PubMed  Google Scholar 

  • Arbo MD, Melega S, Stöber R et al (2016) Hepatotoxicity of piperazine designer drugs: up-regulation of key enzymes of cholesterol and lipid biosynthesis. Arch Toxicol 90(12):3045–3060

    Article  CAS  Google Scholar 

  • Beliaeff B, Burgeot T (2002) Integrated biomarker response: a useful tool for ecological risk assessment. Environ Toxicol Chem 21(6):1316–1322

    Article  CAS  Google Scholar 

  • Chaudhari U, Nemade H, Gaspar JA, Hescheler J, Hengstler JG, Sachinidis A (2016a) MicroRNAs as early toxicity signatures of doxorubicin in human-induced pluripotent stem cell-derived cardiomyocytes. Arch Toxicol 90(12):3087–3098

    Article  CAS  Google Scholar 

  • Chaudhari U, Nemade H, Wagh V et al (2016b) Identification of genomic biomarkers for anthracycline-induced cardiotoxicity in human iPSC-derived cardiomyocytes: an in vitro repeated exposure toxicity approach for safety assessment. Arch Toxicol 90(11):2763–2777

    Article  CAS  Google Scholar 

  • Colaianna M, Ilmjärv S, Peterson H et al (2017) Fingerprinting of neurotoxic compounds using a mouse embryonic stem cell dual luminescence reporter assay. Arch Toxicol 91(1):365–391. https://doi.org/10.1007/s00204-016-1690-2

    Article  CAS  PubMed  Google Scholar 

  • Depledge MH (1994) The rational basis for the use of biomarkers as ecotoxicological tools. In: Fossi MC, Leonzio C (eds) Nondestructive biomarkers in vertebrates. Lewis, Boca Rato, pp 271–295

    Google Scholar 

  • Frey O, Misun PM, Fluri DA, Hengstler JG, Hierlemann A (2014) Reconfigurable microfluidic hanging drop network for multi-tissue interaction and analysis. Nat Commun 5:4250. https://doi.org/10.1038/ncomms5250

    Article  CAS  PubMed  Google Scholar 

  • Ghallab A (2017) Highlight report: metabolomics in hepatotoxicity testing. EXCLI J 21(16):1323–1325. https://doi.org/10.17179/excli2017-1041. (eCollection 2017. No abstract available)

    Article  Google Scholar 

  • Ghallab A, Hofmann U, Sezgin S et al (2019) Bile microinfarcts in cholestasis are initiated by rupture of the apical hepatocyte membrane and cause shunting of bile to sinusoidal blood. Hepatology 69(2):666–683

    Article  CAS  Google Scholar 

  • Godoy P, Hewitt NJ, Albrecht U et al (2013) Recent advances in 2D and 3D in vitro systems using primary hepatocytes, alternative hepatocyte sources and non-parenchymal liver cells and their use in investigating mechanisms of hepatotoxicity, cell signaling and ADME. Arch Toxicol 87(8):1315–1530

    Article  CAS  Google Scholar 

  • Godoy P, Schmidt-Heck W, Natarajan K et al (2016) Gene networks and transcription factor motifs defining the differentiation of stem cells into hepatocyte-lik. J Hepatol 2015 63(4):934–942. https://doi.org/10.1016/j.jhep.2015.05.013. (Epub 2015 May 25. Erratum in: J Hepatol 2016)

    Article  CAS  Google Scholar 

  • Grinberg M, Stöber RM, Edlund K et al (2014) Toxicogenomics directory of chemically exposed human hepatocytes. Arch Toxicol 88(12):2261–2287

    Article  CAS  Google Scholar 

  • Grinberg M, Stöber RM, Albrecht W et al (2018) Toxicogenomics directory of rat hepatotoxicants in vivo and in cultivated hepatocytes. Arch Toxicol 92(12):3517–3533. https://doi.org/10.1007/s00204-018-2352-3

    Article  CAS  PubMed  Google Scholar 

  • Gu X, Albrecht W, Edlund K et al (2018) Relevance of the incubation period in cytotoxicity testing with primary human hepatocytes. Arch Toxicol. https://doi.org/10.1007/s00204-018-2302-0. (Epub ahead of print)

    Article  PubMed  Google Scholar 

  • Hengstler JG, Bogdanffy MS, Bolt HM, Oesch F (2003) Challenging dogma: thresholds for genotoxic carcinogens? The case of vinyl acetate. Annu Rev Pharmacol Toxicol 43:485–520

    Article  CAS  Google Scholar 

  • Huggett RJ, Kimerle RA, Mehrle PM, Bergman HL (1992) Biomarkers. Biochemical, physiological, and histological markers of anthropogenic stress. Lewis, Boca Raton, p 347

    Google Scholar 

  • Jansen PL, Ghallab A, Vartak N, Reif R, Schaap FG, Hampe J, Hengstler JG (2017) The ascending pathophysiology of cholestatic liver disease. Hepatology 65(2):722–738

    Article  CAS  Google Scholar 

  • Leist M, Ghallab A, Graepel R et al (2017) Adverse outcome pathways: opportunities, limitations and open questions. Arch Toxicol 91(11):3477–3505. https://doi.org/10.1007/s00204-017-2045-3. (Review)

    Article  CAS  PubMed  Google Scholar 

  • McCarty JF, Shugart LR (1990) Biomarkers of environmental contamination. Lewis, CRC, Boca Raton, p 457

    Google Scholar 

  • Rahnenführer J, Leist M, Sachinidis A (2013) Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol 87(1):123–143. https://doi.org/10.1007/s00204-012-0967-3

    Article  CAS  PubMed  Google Scholar 

  • Rempel E, Hoelting L, Waldmann T et al (2015) A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol 89(9):1599–1618

    Article  CAS  Google Scholar 

  • Rodrigues RM, Kollipara L, Chaudhari U et al (2018) Omics-based responses induced by bosentan in human hepatoma HepaRG cell cultures. Arch Toxicol 92(6):1939–1952

    Article  CAS  Google Scholar 

  • Sachinidis A, Albrecht W, Nell P, Cherianidou A, Hewitt NJ, Edlund K, Hengstler JG (2019) Road map for development of stem cell-based alternative test methods. Trends Mol Med 25(6):470–481. https://doi.org/10.1016/j.molmed.2019.04.003. (Review)

    Article  PubMed  Google Scholar 

  • Shinde V, Klima S, Sureshkumar PS et al (2015) Human pluripotent stem cell based developmental toxicity assays for chemical safety screening and systems biology data generation. J Vis Exp 17(100):e52333. https://doi.org/10.3791/52333

    Article  CAS  Google Scholar 

  • Sisnaiske J, Hausherr V, Krug AK, Zimmer B, Hengstler JG, Leist M, van Thriel C (2014) Acrylamide alters neurotransmitter induced calcium responses in murine ESC-derived and primary neurons. Neurotoxicology 43:117–126. https://doi.org/10.1016/j.neuro.2014.03.010

    Article  CAS  PubMed  Google Scholar 

  • Vinken M (2018a) In vitro prediction of drug-induced cholestatic liver injury: a challenge for the toxicologist. Arch Toxicol 92(5):1909–1912. https://doi.org/10.1007/s00204-018-2201-4. (No abstract available)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Vinken M (2018b) Taking adverse outcome pathways to the next level. Toxicol In Vitro 50:A1–A2

    Article  CAS  Google Scholar 

  • Waldmann T, Rempel E, Balmer NV et al (2014) Design principles of concentration-dependent transcriptome deviations in drug-exposed differentiating stem cells. Chem Res Toxicol 27(3):408–420

    Article  CAS  Google Scholar 

  • Waldmann T, Grinberg M, König A et al (2017) Stem cell transcriptome responses and corresponding biomarkers that indicate the transition from adaptive responses to cytotoxicity. Chem Res Toxicol 30(4):905–922

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Leibniz Research Centre for Working Environment and Human Factors, Ardeystr. 67, 44139, Dortmund, Germany

    Hermann M. Bolt

Authors
  1. Hermann M. Bolt
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Hermann M. Bolt.

Ethics declarations

Conflict of interest

The author declares that he has no conflict of interest.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Bolt, H.M. Highlight Report: Adverse outcome pathways: the need of research on mechanisms of toxicity. Arch Toxicol 93, 3385–3386 (2019). https://doi.org/10.1007/s00204-019-02596-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00204-019-02596-2

Search

Navigation