title: Toxicity and carcinogenicity studies of Ginkgo biloba extract in rat and mouse: liver, thyroid, and nose are targets.
abstract: Ginkgo biloba extract (GBE) is a popular herbal supplement that is used to improve circulation and brain function. In spite of widespread human exposure to relatively high doses over potentially long periods of time, there is a paucity of data from animal studies regarding the toxicity and carcinogenicity associated with GBE. In order to fill this knowledge gap, 3-month and 2-year toxicity and carcinogenicity studies with GBE administered by oral gavage to B6C3F1/N mice and F344/N rats were performed as part of the National Toxicology Program's Dietary Supplements and Herbal Medicines Initiative. The targets of GBE treatment were the liver, thyroid, and nose. These targets were consistent across exposure period, sex, and species, albeit with varying degrees of effect observed among studies. Key findings included a notably high incidence of hepatoblastomas in male and female mice and evidence of carcinogenic potential in the thyroid gland of both mice and rats. Various nonneoplastic lesions were observed beyond control levels in the liver, thyroid gland, and nose of rats and mice administered GBE. Although these results cannot be directly extrapolated to humans, the findings fill an important data gap in assessing risk associated with GBE use.
authors: National Institute of Environmental Health Sciences, Research Triangle Park, Durham, North Carolina, USA ridercv@niehs.nih.gov.
authors: Cynthia V
authors: CV
authors: Rider
authors: Integrated Laboratory Systems Incorporated, Research Triangle Park, Durham, North Carolina, USA.
authors: Abraham
authors: A
authors: Nyska
authors: National Institute of Environmental Health Sciences, Research Triangle Park, Durham, North Carolina, USA.
authors: Michelle C
authors: MC
authors: Cora
authors: National Institute of Environmental Health Sciences, Research Triangle Park, Durham, North Carolina, USA.
authors: Grace E
authors: GE
authors: Kissling
authors: National Institute of Environmental Health Sciences, Research Triangle Park, Durham, North Carolina, USA.
authors: Cynthia
authors: C
authors: Smith
authors: National Institute of Environmental Health Sciences, Research Triangle Park, Durham, North Carolina, USA.
authors: Gregory S
authors: GS
authors: Travlos
authors: Battelle, Columbus, Ohio, USA.
authors: Milton R
authors: MR
authors: Hejtmancik
authors: Battelle, Columbus, Ohio, USA.
authors: Laurene M
authors: LM
authors: Fomby
authors: Battelle, Columbus, Ohio, USA.
authors: Curtis A
authors: CA
authors: Colleton
authors: Battelle, Columbus, Ohio, USA.
authors: Michael J
authors: MJ
authors: Ryan
authors: Charles River Laboratories, Pathology Associates, Durham, North Carolina, USA.
authors: Linda
authors: L
authors: Kooistra
authors: Charles River Laboratories, Pathology Associates, Durham, North Carolina, USA.
authors: James P
authors: JP
authors: Morrison
authors: National Institute of Environmental Health Sciences, Research Triangle Park, Durham, North Carolina, USA.
authors: Po C
authors: PC
authors: Chan
mesh_terms: D000818:Animals; D015197:Carcinogenicity Tests; D002273:Carcinogens / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D005260:Female; D020441:Ginkgo biloba / Q000737:chemistry / Q000633:toxicity*; D008099:Liver / Q000187:drug effects* / Q000473:pathology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009666:Nose / Q000187:drug effects* / Q000473:pathology; D009929:Organ Size / Q000187:drug effects; D010936:Plant Extracts / Q000737:chemistry / Q000633:toxicity*; D051381:Rats; D011916:Rats, Inbred F344; D013961:Thyroid Gland / Q000187:drug effects* / Q000473:pathology
chemical_list: D002273:Carcinogens; D010936:Plant Extracts
keywords: hepatocarcinogenicity; herbal; nasal lesions; natural medicine; thyroid tumors
references: Eur J Pharmacol. 2004 Jun 28;494(2-3):131-8
references: 15212966
references: Cancer Lett. 1995 Feb 10;89(1):29-35
references: 7882299
references: Food Nutr Res. 2010 Sep 30;54:
references: 20927202
references: OMICS. 2010 Feb;14(1):75-90
references: 20141330
references: Pharmacoepidemiol Drug Saf. 2010 Jul;19(7):694-8
references: 20582906
references: J Chromatogr A. 2009 Mar 13;1216(11):2204-10
references: 18814876
references: Clin Ther. 2011 Nov;33(11):1749-58
references: 22030445
references: Circ Cardiovasc Qual Outcomes. 2010 Jan;3(1):41-7
references: 20123670
references: PLoS One. 2008 Jun 18;3(6):e2493
references: 18560566
references: Natl Toxicol Program Tech Rep Ser. 1992 Sep;409:1-171
references: 12621521
references: Toxicol Pathol. 2007 Jan;35(1):170-7
references: 17325986
references: J Neurochem. 2008 May;105(4):1418-27
references: 18221374
references: Neurochem Int. 2002 Jun;40(7):647-53
references: 11900860
references: Pharmazie. 2000 Nov;55(11):864-5
references: 11126011
references: Toxicol Pathol. 2007 Jan;35(1):163-9
references: 17325985
references: Drug Metab Dispos. 2012 Jun;40(6):1113-21
references: 22393123
references: Toxicol Pathol. 2011 Feb;39(2):348-60
references: 21422261
references: Drug Metab Dispos. 2012 Jan;40(1):178-86
references: 22019630
references: J Gen Intern Med. 2005 Jul;20(7):657-61
references: 16050865
references: Toxicol Pathol. 2002 Sep-Oct;30(5):580-91
references: 12371667
references: J Food Sci. 2008 Jan;73(1):R14-9
references: 18211362
references: Acta Pol Pharm. 2010 Jul-Aug;67(4):335-43
references: 20635528
references: Int J Immunopharmacol. 2000 Mar;22(3):229-36
references: 10685005
references: Natl Toxicol Program Tech Rep Ser. 2000 Sep;476:1-290
references: 12571687
references: JAMA. 2009 Dec 23;302(24):2663-70
references: 20040554
references: Drug Metab Rev. 1993;25(1-2):173-205
references: 8449146
references: JAMA. 2008 Nov 19;300(19):2253-62
references: 19017911
references: Fundam Appl Toxicol. 1989 May;12(4):731-7
references: 2744275
references: J Pharmacol Exp Ther. 2010 Dec;335(3):771-80
references: 20739453
references: Biometrics. 1988 Jun;44(2):417-31
references: 3390507
references: Endocr Rev. 1991 May;12(2):135-50
references: 2070777
references: Toxicol Pathol. 1998 Nov-Dec;26(6):717-23
references: 9864087
references: J Pharm Pharmacol. 2002 May;54(5):661-9
references: 12005361
references: Toxicol Pathol. 2013 Aug;41(6):826-41
references: 23262642
references: Toxicol Pathol. 2010 Aug;38(5):776-95
references: 20585142
references: Pharm Res. 2009 Apr;26(4):872-82
references: 19034627
references: Toxicol Pathol. 1997 Jan-Feb;25(1):39-48
references: 9061850
references: Fundam Appl Toxicol. 1994 Aug;23(2):280-97
references: 7982536
references: Am J Hypertens. 2010 May;23(5):528-33
references: 20168306
references: J Chromatogr A. 2009 Mar 13;1216(11):2002-32
references: 19195661
references: Toxicol Pathol. 2004 Jul-Aug;32(4):393-401
references: 15307212
references: Toxicology. 2002 Aug 15;177(2-3):167-77
references: 12135620