Evidence map›Paper›PMID 30321397›Full record

ArticleToxicological sciences : an official journal of the Society of Toxicology2019

Application of Benchmark Concentration (BMC) Analysis on Zebrafish Data: A New Perspective for Quantifying Toxicity in Alternative Animal Models.

Jui-Hua Hsieh, Kristen Ryan, Alexander Sedykh, Ja-An Lin, Andrew J Shapiro, Frederick Parham, Mamta Behl

Abstract read
In one paragraph

Article in Toxicological sciences : an official journal of the Society of Toxicology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing 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

22 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Rapid behavioral screening in the planarianFrontiers in toxicology · 2026
    Article
  5. Article
  6. Statistical analysis of multi-endpoint phenotypic screening increases sensitivity of planarian neurotoxicity testing.Toxicological sciences : an official journal of the Society of Toxicology · 2025
    Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Review
  13. Article
  14. Article
  15. Article
  16. Exploring the Influence of Experimental Design on Toxicity Outcomes in Zebrafish Embryo Tests.Toxicological sciences : an official journal of the Society of Toxicology · 2022
    Article
  17. Article
  18. Article
  19. Accounting for Artifacts in High-Throughput Toxicity Assays.Methods in molecular biology (Clifton, N.J.) · 2022
    Article
  20. Use of Zebrafish in Drug Discovery Toxicology.Chemical research in toxicology · 2020
    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

7 authors.

Jui-Hua HsiehKelly Government Solutions, Durham, North Carolina, 27709, USA.
Kristen RyanDivision of the National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, 27709, USA.
Alexander SedykhSciome, Durham, North Carolina, 27709, USA.
Ja-An LinDepartment of Biostatistics, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, 27516, USA.
Andrew J ShapiroDivision of the National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, 27709, USA.
Frederick ParhamDivision of the National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, 27709, USA.
Mamta BehlDivision of the National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, 27709, USA.

Funding

Toxicological Assessments for the National Toxicology ProgramZIAES103316 · NIEHS · NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES · PI WALKER, NIGEL J · 2016 to 2019
$31.9M
Biomolecular Screening and Alternative Approaches for the National Toxicology ProgramZIAES103318 · NIEHS · NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES · PI CASEY, WARREN · 2016 to 2021
$25.0M
NIEHS NIH HHS HHSN273201700005C
6 · The paper itself

Abstract

Over the past decade, the zebrafish is increasingly being used as a model to screen for chemical-mediated toxicities including developmental toxicity (DT) and neurotoxicity (NT). One of the major challenges is lack of harmonization in data analysis approaches, thereby posing difficulty in comparing findings across laboratories. To address this, we sought to establish a unified data analysis strategy for both DT and NT data, by adopting the benchmark concentration (BMC) analysis. There are two critical aspects in the BMC analysis: having a toxicity endpoint amenable for BMC and selecting a proper benchmark response (BMR) for the endpoint. For the former, in addition to the typical endpoints in NT assay (eg, hyper/hypo- response quantified by distance moved), we also used endpoints that assess the differences in movement patterns between chemical-treated embryos and control embryos. For the latter, we standardized the selection of BMR, which is analogous to minimum activity threshold, based on intrinsic response variations in the endpoint. When comparing our BMC results with a traditionally used LOAEL method (lowest-observed-adverse-effect level), we found high active compound concordance (100% for DT vs 74% for NT); generally, the BMC was more sensitive than LOAEL (no. of BMC more sensitive/no. of concordant active compounds, 43/50 for DT vs 16/26 for NT). Using the BMC with standardized toxicity endpoints and an appropriate BMR, we may now have a unified data-analysis approach to comparing results across different zebrafish datasets, for a better understanding of strengths and challenges when using the zebrafish as a screening tool.

Indexed as

Animal Testing AlternativesBenchmarkingZebrafishAnimalsEmbryonic DevelopmentEmbryo, NonmammalianEndpoint DeterminationEnvironmental PollutantsNervous SystemToxicity TestsEnvironmental Pollutants

Identifiers

PMID30321397
PMCPMC6317423

What OpenQuestion holds

Textmetadata
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.