Evidence map›Paper›PMID 22687605›Full record

ArticleToxicology and applied pharmacology2012

An ethanolic extract of black cohosh causes hematological changes but not estrogenic effects in female rodents.

Minerva Mercado-Feliciano, Michelle C Cora, Kristine L Witt, Courtney A Granville, Milton R Hejtmancik, Laurene Fomby, Katherine A Knostman, Michael J Ryan, Retha Newbold, Cynthia Smith and 3 more

Abstract readComparative Study
In one paragraph

Article in Toxicology and applied pharmacology, 2012. 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
1.7field-weighted citation impact, top 15% 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

16 citing papers in PubMed, 34 citations in OpenAlex.

  1. Review of black cohosh-induced toxicity and adverse clinical effects.Journal of environmental science and health. Part C, Toxicology and carcinogenesis · 2025
    Review
  2. Article
  3. Article
  4. Article
  5. Article
  6. Mechanistic Evaluation of Black Cohosh Extract-Induced Genotoxicity in Human Cells.Toxicological sciences : an official journal of the Society of Toxicology · 2021
    Article
  7. Article
  8. Evaluating Sufficient Similarity of Botanical Dietary Supplements: Combining Chemical and In Vitro Biological Data.Toxicological sciences : an official journal of the Society of Toxicology · 2019
    Article
  9. How similar is similar enough? A sufficient similarity case study with Ginkgo biloba extract.Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association · 2018
    Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Review
  16. 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

13 authors at 3 institutions in 1 country.

Minerva Mercado-FelicianoNational Toxicology Program, National Institute of Environmental Health Sciences, National Institutes of Health, 111 Alexander Drive, Research Triangle Park, NC, USA.
Michelle C Cora
Kristine L Witt
Courtney A Granville
Milton R Hejtmancik
Laurene Fomby
Katherine A Knostman
Michael J Ryan
Retha Newbold
Cynthia Smith
Paul M Foster
Molly K Vallant
Matthew D Stout
National Institutes of Health · USBattelle · USNational Institute of Environmental Health Sciences · US

Funding

NTP DATABASE SUMMARIZATION AND EVALUATIONZ01ES045004 · NIEHS · NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES · PI KISSLING, GRACE E · 1997 to 2008
$193k
Intramural NIH HHS Z01 ES045004Intramural NIH HHS Z99 ES999999NIEHS NIH HHS N01 ES035514NIEHS NIH HHS N01 ES055536NIEHS NIH HHS N01 ES055551PHS HHS 1 Z01 ESO45004-11
6 · The paper itself

Abstract

Black cohosh rhizome (Actaea racemosa) is used as a remedy for pain and gynecological ailments; modern preparations are commonly sold as ethanolic extracts available as dietary supplements. Black cohosh was nominated to the National Toxicology Program (NTP) for toxicity testing due to its widespread use and lack of safety data. Several commercially available black cohosh extracts (BCE) were characterized by the NTP, and one with chemical composition closest to formulations available to consumers was used for all studies. Female B6C3F1/N mice and Wistar Han rats were given 0, 15 (rats only), 62.5 (mice only), 125, 250, 500, or 1000 mg/kg/day BCE by gavage for 90 days starting at weaning. BCE induced dose-dependent hematological changes consistent with a non-regenerative macrocytic anemia and increased frequencies of peripheral micronucleated red blood cells (RBC) in both species. Effects were more severe in mice, which had decreased RBC counts in all treatment groups and increased micronucleated RBC at doses above 125 mg/kg. Dose-dependent thymus and liver toxicity was observed in rats but not mice. No biologically significant effects were observed in other organs. Puberty was delayed 2.9 days at the highest treatment dose in rats; a similar magnitude delay in mice occurred in the 125 and 250 mg/kg groups but not at the higher doses. An additional uterotrophic assay conducted in mice exposed for 3 days to 0.001, 0.01, 0.1, 1, 10, 100 and 500 mg/kg found no estrogenic or anti-estrogenic activity. These are the first studies to observe adverse effects of BCE in rodents.

Indexed as

Anemia, MacrocyticAnimalsCimicifugaDose-Response Relationship, DrugErythrocytesEstrogensEthanolFemaleHematologic DiseasesLiverMicePlant ExtractsRatsRats, WistarSeverity of Illness IndexSexual MaturationEstrogensEthanolPlant Extracts

Identifiers

PMID22687605
PMCPMC3422379
OpenAlexW2075829893

What OpenQuestion holds

Textmetadata
LicenceTDM
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.