Evidence map›Paper›PMID 31504990›Full record

ArticleToxicological sciences : an official journal of the Society of Toxicology2019

Evaluating Sufficient Similarity of Botanical Dietary Supplements: Combining Chemical and In Vitro Biological Data.

Kristen R Ryan, Madelyn C Huang, Stephen S Ferguson, Suramya Waidyanatha, Sreenivasa Ramaiahgari, Julie R Rice, Paul E Dunlap, Scott S Auerbach, Esra Mutlu, Tim Cristy and 4 more

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 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing 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

16 citing papers in PubMed.

  1. Review
  2. Immune system evaluation of Echinacea Purpurea root extract in female Harlan Sprague Dawley (Hsd:Sprague Dawley SD) rats.Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association · 2026
    Article
  3. Review of black cohosh-induced toxicity and adverse clinical effects.Journal of environmental science and health. Part C, Toxicology and carcinogenesis · 2025
    Review
  4. Article
  5. Advancing botanical safety: A strategy for selecting, sourcing, and characterizing botanicals for developing toxicological tools.Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association · 2024
    Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Working with the natural complexity: Selection and characterization of black cohosh root extract for use in toxicology testing.Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association · 2022
    Article
  12. Article
  13. Article
  14. Review
  15. A strategy for test article selection and phytochemical characterization of Echinacea purpurea extract for safety testing.Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association · 2020
    Article
  16. 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

14 authors.

Kristen R RyanDivision of the National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709.
Madelyn C HuangDivision of the National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709.
Stephen S FergusonDivision of the National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709.
Suramya WaidyanathaDivision of the National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709.
Sreenivasa RamaiahgariDivision of the National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709.
Julie R RiceDivision of the National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709.
Paul E DunlapDivision of the National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709.
Scott S AuerbachDivision of the National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709.
Esra MutluDivision of the National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709.
Tim CristyBattelle, Columbus, Ohio 43201.
Jessica PeirfeliceBattelle, Columbus, Ohio 43201.
Michael J DeVitoDivision of the National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709.
Stephanie L Smith-RoeDivision of the National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709.
Cynthia V RiderDivision of the National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709.

Funding

Toxicological Assessments for the National Toxicology ProgramZIAES103316 · NIEHS · NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES · PI WALKER, NIGEL J · 2016 to 2019
$31.9M
Intramural NIH HHS ZIA ES103316NIEHS NIH HHS HHSN273201400027C
6 · The paper itself

Abstract

Botanical dietary supplements are complex mixtures with numerous potential sources of variation along the supply chain from raw plant material to the market. Approaches for determining sufficient similarity (ie, complex mixture read-across) may be required to extrapolate efficacy or safety data from a tested sample to other products containing the botanical ingredient(s) of interest. In this work, screening-level approaches for generating both chemical and biological-response profiles were used to evaluate the similarity of black cohosh (Actaea racemosa) and Echinacea purpurea samples to well-characterized National Toxicology Program (NTP) test articles. Data from nontargeted chemical analyses and gene expression of toxicologically important hepatic receptor pathways (aryl hydrocarbon receptor [AhR], constitutive androstane receptor [CAR], pregnane X receptor [PXR], farnesoid X receptor [FXR], and peroxisome proliferator-activated receptor alpha [PPARα]) in primary human hepatocyte cultures were used to determine similarity through hierarchical clustering. Although there were differences in chemical profiles across black cohosh samples, these differences were not reflected in the biological-response profiles. These findings highlight the complexity of biological-response dynamics that may not be reflected in chemical composition profiles. Thus, biological-response data could be used as the primary basis for determining similarity among black cohosh samples. Samples of E. purpurea displayed better correlation in similarity across chemical and biological-response measures. The general approaches described herein can be applied to complex mixtures with unidentified active constituents to determine when data from a tested mixture (eg, NTP test article) can be used for hazard identification of sufficiently similar mixtures, with the knowledge of toxicological targets informing assay selection when possible.

Indexed as

Dietary SupplementsBasic Helix-Loop-Helix ProteinsCells, CulturedCimicifugaConstitutive Androstane ReceptorEchinaceaGene ExpressionHepatocytesHumansPlant PreparationsPPAR alphaPregnane X ReceptorPrimary Cell CultureReceptors, Aryl HydrocarbonReceptors, Cytoplasmic and NuclearAHR protein, humanBasic Helix-Loop-Helix ProteinsConstitutive Androstane ReceptorNR1I2 protein, humanPlant PreparationsPPAR alphaPregnane X ReceptorReceptors, Aryl HydrocarbonReceptors, Cytoplasmic and Nuclearblack cohoshcomplex mixturesEchinacea purpureaherbal supplementssufficient similarity

Identifiers

PMID31504990
PMCPMC6876258

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.