National Toxicology Program

National Toxicology Program
http://ntp.niehs.nih.gov/go/ts-m000058

Testing Status of Black Cohosh - M000058

 

CASRN: 84776-26-1

Synonyms/Common Names

  • Black snake root
  • Cimicifuga racemosa
  • Remifemin

Known Uses

Dietary supplement used for the treatment of menstrual and menopausal symptoms.

Chemical Properties

Toxicity Effects (HSDB)

Nomination Background

Short-Term Toxicity

  • 14 days (Gavage)  (C00058B)  Completed 
    • Rats: Harlan Sprague-Dawley
    • Dose: 38 dams/dose group; 0, 100, 300, or 1000 mg/kg/day.
  • 90 days (Gavage)  (C00058C)  Completed 
    • Subchronic Macrocytic Non-regenerative Anemia (megaloblastic disorder)
    • Mice: B6C3F1
    • Dose: 0, 1000 mg/kg; 32/per dose.
  • 90 days (Gavage)  (C00058)  Completed 
    • Citation: Mercado-Feliciano M, Cora MC, Witt KL, Granville CA, Hejtmancik MR, Fomby L, Knostman KA, Ryan MJ, Newbold R, Smith C, Foster PM, Vallant MK, Stout MD. Anethanolic extract of black cohosh causes hematological changes but not estrogenic effects in female rodents. Toxicol Appl Pharmacol. 2012 Sep 1;263(2):138-47. doi:10.1016/j.taap.2012.05.022. Epub 2012 Jun 9.Pubmed Abstract
    • Mice: B6C3F1
    • Dose: Females: 0, 62.5, 125, 250, 500 or 1000 mg/kg.
  • 13 weeks (Gavage)  (C20112)  Completed 
    • Citation: Mercado-Feliciano M, Cora MC, Witt KL, Granville CA, Hejtmancik MR, Fomby L, Knostman KA, Ryan MJ, Newbold R, Smith C, Foster PM, Vallant MK, Stout MD. Anethanolic extract of black cohosh causes hematological changes but not estrogenic effects in female rodents. Toxicol Appl Pharmacol. 2012 Sep 1;263(2):138-47. doi:10.1016/j.taap.2012.05.022. Epub 2012 Jun 9.Pubmed Abstract
    • Rats: Wistar Han
    • Dose: 0, 15, 125, 250, 500, or 1000 mg/kg.

Long-Term Carcinogenicity

  • 2 years (Gavage)  (C00058B)  Histopath in progress 
    • Rats: Harlan Sprague-Dawley; Mice: B6C3F1
    • Dose: Rats: 0, 75, 250, or 750 mg/kg/day; 50/sex/dose Female mice: 0, 30, 100, 300, or 1000 mg/kg/day; 70/dose.

Genetic Toxicology

  • Micronucleus  (G00058B)  Completed 
    • Citation: Mercado-Feliciano M, Cora MC, Witt KL, Granville CA, Hejtmancik MR, Fomby L, Knostman KA, Ryan MJ, Newbold R, Smith C, Foster PM, Vallant MK, Stout MD. Anethanolic extract of black cohosh causes hematological changes but not estrogenic effects in female rodents. Toxicol Appl Pharmacol. 2012 Sep 1;263(2):138-47. doi:10.1016/j.taap.2012.05.022. Epub 2012 Jun 9.Pubmed Abstract
    • Mice: B6C3F1
    • Female Positive 
  • Micronucleus  (G00058C)  Completed 
    • Mice: B6C3F1
    • Female Positive 
  • Micronucleus  (G00058)  Completed 
    • Citation: Mercado-Feliciano M, Cora MC, Witt KL, Granville CA, Hejtmancik MR, Fomby L, Knostman KA, Ryan MJ, Newbold R, Smith C, Foster PM, Vallant MK, Stout MD. Anethanolic extract of black cohosh causes hematological changes but not estrogenic effects in female rodents. Toxicol Appl Pharmacol. 2012 Sep 1;263(2):138-47. doi:10.1016/j.taap.2012.05.022. Epub 2012 Jun 9.Pubmed Abstract
    • Rats: Wistar Han
    • Female Positive 
  • 365 days Micronucleus  (G00058E)  Completed 
    • Mice: B6C3F1
    • Female Positive 
  • Micronucleus  (G00058F)  On Test 
    • In vitro
  • Micronucleus  (G00058G)  On Test 
    • In vitro
  • Micronucleus  (G00058H)  On Test 
    • In vitro
  • Micronucleus  (G00058I)  On Test 
    • In vitro
  • Micronucleus  (G00058J)  On Test 
    • In vitro
  • Micronucleus  (G00058K)  On Test 
    • In vitro
  • Micronucleus  (G00058L)  On Test 
    • In vitro
  • Micronucleus  (G00058M)  On Test 
    • In vitro
  • Micronucleus  (G00058N)  On Test 
    • In vitro
  • Micronucleus  (G00058O)  On Test 
    • In vitro
  • Micronucleus  (G00058P)  On Test 
    • In vitro
  • Micronucleus  (G00058Q)  On Test 
    • In vitro
  • Micronucleus  (G00058R)  On Test 
    • In vitro
  • Micronucleus  (G00058S)  On Test 
    • In vitro
  • Micronucleus  (G00058T)  On Test 
    • In vitro
  • Micronucleus  (G00058U)  On Test 
    • In vitro
  • Salmonella  (A13815)  Completed 
    •  Negative 
  • Salmonella  (G00058D)  Completed 
    •  Equivocal 
  • Salmonella  (G00058V)  On Test 
    • Salmonella  (G00058W)  On Test 
      • Salmonella  (G00058X)  On Test 
        • Salmonella  (G00058Y)  On Test 
          • Salmonella  (G00058Z)  On Test 

            Organ Systems Toxicity

            • 28 days Immunotoxicity (Gavage)  (I00058)  Completed 
              • Citation: Smith MJ, Germolec DR, Frawley RP, White KL Jr. Immunomodulatory effects of black cohosh (Actaea racemosa) extract in female B6C3F1/N mice. Toxicology. 2013 Jun 7;308:146-57. doi: 10.1016/j.tox.2013.03.017. Epub 2013 Apr 6.Pubmed Abstract
              • Female Mice: B6C3F1
              • Dose: 0, 62.5, 125, 250, 500 or 1000 mg/kg.
            • Continuous Breeding (Gavage)  (R00058B)  Completed 
              • Male and Female Rats: Harlan Sprague-Dawley
              • Dose: 0, 250, 500, or 100 mg/kg/day.
            • Continuous Breeding (Gavage)  (R00058)  Completed 
              • Dose range finding
              • Male and Female Rats: Harlan Sprague-Dawley
              • Dose: 0, 100, 300, or 1000 mg/kg.

            Toxicogenomics

            • 13 weeks Microarray Analysis (Gavage)  (T00058)  Assigned 
              • Subchronic Macrocytic Non-regenerative Anemia (megaloblastic disorder)
              • Mice: B6C3F1
              • Dose: 0 or 1000 mg/kg; 32 mice/group.
            NTP is located at the National Institute of Environmental Health Sciences, part of the National Institutes of Health.