Evidence map›Paper›PMID 37566783›Full record

ArticleEnvironmental science & technology2023

Integrating Concentration-Dependent Toxicity Data and Toxicokinetics To Inform Hepatotoxicity Response Pathways.

Daniel P Russo, Lauren M Aleksunes, Katy Goyak, Hua Qian, Hao Zhu

Abstract read
In one paragraph

Article in Environmental science & technology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
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

4 citing papers in PubMed.

  1. Article
  2. Review
  3. Article
  4. Review
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

5 authors.

Daniel P RussoDepartment of Chemistry and Biochemistry, Rowan University, Glassboro, New Jersey 08028, United States.
Lauren M AleksunesDepartment of Pharmacology and Toxicology, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, New Jersey 08854, United States.
Katy GoyakExxonMobil Biomedical Sciences, Inc., Annandale, New Jersey 08801, United States.
Hua QianExxonMobil Biomedical Sciences, Inc., Annandale, New Jersey 08801, United States.
Hao ZhuDepartment of Chemistry and Biochemistry, Rowan University, Glassboro, New Jersey 08028, United States.ORCID 0000-0002-3559-6129

Funding

Translational Research Support CoreP30ES005022 · NIEHS · UNIV OF MED/DENT NJ-R W JOHNSON MED SCH · PI BRIAN T BUCKLEY · 1988 to 2026
$47.4M
New Jersey Alliance for Clinical Translational Science: NJ ACTSUL1TR003017 · NCATS · RUTGERS BIOMEDICAL/HEALTH SCIENCES-RBHS · PI PANETTIERI, REYNOLD ALEXANDER · 2019 to 2023
$28.9M
Discovering Chemical Activity Networks-Predicting Bioactivity Based on StructureR35ES031709 · NIEHS · OREGON STATE UNIVERSITY · PI Robyn L Tanguay · 2021 to 2026
$5.2M
Mechanism-Driven Virtual Adverse Outcome Pathway Modeling for HepatotoxicityR01ES031080 · NIEHS · TULANE UNIVERSITY OF LOUISIANA · PI ZHU, HAO · 2020 to 2024
$2.3M
Virtual nanostructure simulation (VINAS) portalR01GM148743 · NIGMS · TULANE UNIVERSITY OF LOUISIANA · PI Hao Zhu · 2023 to 2026
$1.1M
NCATS NIH HHS UL1 TR003017NIEHS NIH HHS P30 ES005022NIEHS NIH HHS R01 ES031080NIEHS NIH HHS R35 ES031709NIGMS NIH HHS R01 GM148743
6 · The paper itself

Abstract

Failure of animal models to predict hepatotoxicity in humans has created a push to develop biological pathway-based alternatives, such as those that use in vitro assays. Public screening programs (e.g., ToxCast/Tox21 programs) have tested thousands of chemicals using in vitro high-throughput screening (HTS) assays. Developing pathway-based models for simple biological pathways, such as endocrine disruption, has proven successful, but development remains a challenge for complex toxicities like hepatotoxicity, due to the many biological events involved. To this goal, we aimed to develop a computational strategy for developing pathway-based models for complex toxicities. Using a database of 2171 chemicals with human hepatotoxicity classifications, we identified 157 out of 1600+ ToxCast/Tox21 HTS assays to be associated with human hepatotoxicity. Then, a computational framework was used to group these assays by biological target or mechanisms into 52 key event (KE) models of hepatotoxicity. KE model output is a KE score summarizing chemical potency against a hepatotoxicity-relevant biological target or mechanism. Grouping hepatotoxic chemicals based on the chemical structure revealed chemical classes with high KE scores plausibly informing their hepatotoxicity mechanisms. Using KE scores and supervised learning to predict in vivo hepatotoxicity, including toxicokinetic information, improved the predictive performance. This new approach can be a universal computational toxicology strategy for various chemical toxicity evaluations.

Indexed as

Chemical and Drug Induced Liver InjuryHigh-Throughput Screening AssaysAnimalsBiological AssayDatabases, FactualHumansToxicokineticsadverse outcome pathway modelingbig databiological pathway modelingdata miningsupervised learning

Identifiers

PMID37566783
PMCPMC10448720

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Registered trials

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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.