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EFSA journal. European Food Safety Authority2024; 22(4); e8733; doi: 10.2903/j.efsa.2024.8733

Safety and efficacy of a feed additive consisting of a dry extract obtained from the leaves of Ginkgo biloba L. (ginkgo extract) for horses, dogs, cats, rabbits and guinea pigs (FEFANA asbl).

Abstract: Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the safety and efficacy of a feed additive obtained from the dried leaves of L. (ginkgo extract) when used as a sensory additive in feed for horses, dogs, cats, rabbits and guinea pigs. Ginkgo extract contains ≥ 24% total flavonoids, ≥ 6% total terpene lactones and ≤ 1 mg/kg ginkgolic acids. The EFSA Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) concluded that ginkgo extract is safe for the target species at the following concentrations in complete feed: 2.8 mg/kg for horses and cats, 1.1 mg/kg for rabbits and guinea pigs, and 3.3 mg/kg for dogs. No safety concern would arise for the consumers from the use of ginkgo extract up to the highest level in feed which is considered safe for food-producing species (horses and rabbits). The additive should be considered as irritant to skin and eyes, and as a dermal and respiratory sensitiser. The use of the additive at the proposed level in feed for the target species is not considered to be a risk to the environment. While the available data indicate that preparations have a distinctive flavour profile, there is no evidence that the ginkgo extract would impart flavour to a food or feed matrix. Therefore, the FEEDAP Panel cannot conclude on the efficacy of the additive.
© 2024 European Food Safety Authority. EFSA Journal published by Wiley‐VCH GmbH on behalf of European Food Safety Authority.
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Publication Date: 2024-04-10 PubMed ID: 38601873PubMed Central: PMC11004906DOI: 10.2903/j.efsa.2024.8733Google Scholar: Lookup
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Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The European Food Safety Authority (EFSA) has concluded research on the safety and effectiveness of using a feed additive derived from Ginkgo biloba leaves for animals such as horses, dogs, cats, rabbits, and guinea pigs. The research finds that the feed additive is safe and does not pose any environmental risks, but there is no evidence that the additive would enhance the flavor of the food or feed.

Research Methodology

  • The EFSA was asked by the European Commission to investigate a sensory additive derived from the leaves of Ginkgo biloba.
  • For this investigation, the additives were evaluated for their total flavonoids, total terpene lactones, and ginkgolic acid content.
  • The EFSA Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) then reviewed these substances and their impact on the target species.

Findings

  • The FEEDAP panel discovered that Ginkgo extract is safe for animals at the following concentrations in complete feed: horses and cats at 2.8 mg/kg, rabbits and guinea pigs at 1.1 mg/kg, and dogs at 3.3 mg/kg.
  • There was found to be no safety concern for consumers from the use of ginkgo extract up to the highest level considered safe for food-producing species such as horses and rabbits.
  • The extract was, however, found to be irritating to the skin and eyes and could potentially cause dermal and respiratory sensitization.

Environmental Impact and Efficacy

  • The research suggested that using the additive in feed does not pose a risk to the environment.
  • Despite available data indicating that Ginkgo preparations provide a distinctive flavor profile, there wasn’t any evidence suggesting that the extract would influence the flavor of the food or feed matrix.
  • Consequently, the FEEDAP Panel could not definitively conclude on the efficacy of the additive. This means that while the ginkgo extract is safe for use, the researchers did not find any evidence that it improves the taste of the feed.

Cite This Article

APA
Bampidis V, Azimonti G, Bastos ML, Christensen H, Durjava M, Kouba M, López-Alonso M, López Puente S, Marcon F, Mayo B, Pechová A, Petkova M, Ramos F, Villa RE, Woutersen R, Brantom P, Chesson A, Schlatter J, Westendorf J, Dirven Y, Manini P, Dusemund B. (2024). Safety and efficacy of a feed additive consisting of a dry extract obtained from the leaves of Ginkgo biloba L. (ginkgo extract) for horses, dogs, cats, rabbits and guinea pigs (FEFANA asbl). EFSA J, 22(4), e8733. https://doi.org/10.2903/j.efsa.2024.8733

Publication

EFSA journal. European Food Safety Authority
ISSN: 1831-4732
NlmUniqueID: 101642076
Country: United States
Language: English
Volume: 22
Issue: 4
Pages: e8733
PII: e8733

Researcher Affiliations

Bampidis, Vasileios
    Azimonti, Giovanna
      Bastos, Maria de Lourdes
        Christensen, Henrik
          Durjava, Mojca
            Kouba, Maryline
              López-Alonso, Marta
                López Puente, Secundino
                  Marcon, Francesca
                    Mayo, Baltasar
                      Pechová, Alena
                        Petkova, Mariana
                          Ramos, Fernando
                            Villa, Roberto Edoardo
                              Woutersen, Ruud
                                Brantom, Paul
                                  Chesson, Andrew
                                    Schlatter, Josef
                                      Westendorf, Johannes
                                        Dirven, Yvette
                                          Manini, Paola
                                            Dusemund, Birgit

                                              Conflict of Interest Statement

                                              If you wish to access the declaration of interests of any expert contributing to an EFSA scientific assessment, please contact interestmanagement@efsa.europa.eu.

                                              References

                                              This article includes 63 references
                                              1. Aa L, Fei F, Tan Z, Aa J, Wang G, Liu C. The pharmacokinetics study of ginkgolide A, B and the effect of food on bioavailability after oral administration of ginkgolide extracts in beagle dogs. Biomed Chromatography 32(6), e4212.
                                                doi: 10.1002/bmc.4212google scholar: lookup
                                              2. Abdellah NZ, George SM, Reneah Bushra R. The potential toxic effects of ginkgo biloba extract on thyroid gland of adult male and female albino rats: light and electron microscopic study. Ain Shams Journal of Forensic Medicine and Clinical Toxicology 29, 26–35.
                                                doi: 10.21608/AJFM.2017.18207google scholar: lookup
                                              3. Ahlemeyer B, Selke D, Schaper C, Klumpp S, Krieglstein J. Ginkgolic acids induce neuronal death and activate protein phosphatase type‐2C. European Journal of Pharmacology 430, 1–7.
                                                doi: 10.1016/s0014-2999(01)01237-7pubmed: 11698056google scholar: lookup
                                              4. Baron‐Ruppert G, Luepke NP. Evidence for toxic effects of alkylphenols from Ginkgo biloba in the hen's egg test (HET). Phytomedicine 8, 133–138.
                                                doi: 10.1078/0944-7113-00022pubmed: 11315756google scholar: lookup
                                              5. Berg K, Braun C, Krug I, Schrenk D. Evaluation of the cytotoxic and mutagenic potential of three ginkgolic acids. Toxicology 327, 47–52.
                                                doi: 10.1016/j.tox.2014.10.001pubmed: 25448085google scholar: lookup
                                              6. Biber A, Koch E. Bioavailability of ginkgolides and bilobalide from extracts of Ginkgo biloba using GC/MS. Planta Medica 65, 192–193.
                                                pubmed: 10193211
                                              7. Biernacka P, Felisiak K, Adamska I, Śnieg M, Podsiadło C. Effect of brewing conditions on antioxidant properties of Ginkgo biloba leaves infusion. Antioxidants 12, 1455.
                                                doi: 10.3390/antiox12071455pmc: PMC10376522pubmed: 37507994google scholar: lookup
                                              8. Bu S, Xiong A, Yang Z, Aissa‐Brahim F, Chen Y, Zhang Y, Zhou X, Cao F. Bilobalide induces apoptosis in 3T3‐L1 mature adipocytes through ROS‐mediated mitochondria pathway. Molecules 2023(28), 6410.
                                                doi: 10.3390/molecules28176410google scholar: lookup
                                              9. Burdock GA. Fenaroli's handbook of flavor ingredients (6th ed.). .
                                                doi: 10.1201/9781439847503google scholar: lookup
                                              10. Caria H, Chaveca T, Laires Aand Rueff J. Genotoxicity of quercetin in the micronucleus assay in mouse bone marrow erythrocytes, human lymphocytes, V79 cell line and identification of kinetochore‐containing (CREST staining) micronuclei in human lymphocytes. Mutation Research 343, 85–94.
                                                doi: 10.1016/0165-1218(95)90075-6pubmed: 7791812google scholar: lookup
                                              11. Carver JH, Carrano AV, MacGregor JT. Genetic effects of the flavonols quercetin, kaempferol, and galangin on Chinese hamster ovary cells in vitro. Mutation Research 113, 45–60.
                                                doi: 10.1016/0165-1161(83)90240-6pubmed: 6828043google scholar: lookup
                                              12. Chen F, Li L, Xu F, Sun Y, Du F, Ma X, Zhong C, Li X, Wang F, Zhang N, Li C. Systemic and cerebral exposure to and pharmacokinetics of flavonols and terpene lactones after dosing standardized Ginkgo biloba leaf extracts to rats via different routes of administration. British Journal of Pharmacology 170, 440–457.
                                                doi: 10.1111/bph.12285pmc: PMC3834766pubmed: 23808355google scholar: lookup
                                              13. Court MH, Greenblatt DJ. Molecular basis for deficient acetaminophen glucuronidation in cats. An interspecies comparison of enzyme kinetics in liver Microsomes. Biochemical Pharmacology 53, 1041–1047.
                                                doi: 10.1016/s0006-2952(97)00072-5pubmed: 9174118google scholar: lookup
                                              14. Crebelli R, Aquilina G, Falcone E, Carere A. Urinary and faecal mutagenicity in Sprague–Dawley rats dosed with the food mutagens quercetin and rutin. Food and Chemical Toxicology 25, 9–15.
                                                doi: 10.1016/0278-6915(87)90301-2pubmed: 3817665google scholar: lookup
                                              15. da Silva J, Herrmann SM, Heuser V, Peres W, Possa Marroni N, González‐Gallego J, Erdtmann B. Evaluation of the genotoxic effect of rutin and quercetin by comet assay and micronucleus test. Food and Chemical Toxicology 40, 941–947.
                                                doi: 10.1016/s0278-6915(02)00015-7pubmed: 12065216google scholar: lookup
                                              16. EFSA (European Food Safety Authority). Compendium of botanicals reported to contain naturally occurring substances of possible concern for human health when used in food and food supplements. EFSA Journal 10(5), 2663.
                                                doi: 10.2903/j.efsa.2012.2663google scholar: lookup
                                              17. EFSA FEEDAP Panel (EFSA Panel on Additives and Products or Substances used in Animal Feed). Guidance for the preparation of dossiers for sensory additives. EFSA Journal 10(1), 2534.
                                                doi: 10.2903/j.efsa.2012.2534google scholar: lookup
                                              18. EFSA FEEDAP Panel (EFSA Panel on Additives and Products or Substances used in Animal Feed), Rychen G, Aquilina G, Azimonti G, Bampidis V, Bastos ML, Bories G, Chesson A, Cocconcelli PS, Flachowsky G, Gropp J, Kolar B, Kouba M, López‐Alonso M, López Puente S, Mantovani A, Mayo B, Ramos F, Saarela M, Innocenti ML. Guidance on the identity, characterisation and conditions of use of feed additives. EFSA Journal 15(10), 5023.
                                                doi: 10.2903/j.efsa.2017.5023google scholar: lookup
                                              19. EFSA FEEDAP Panel (EFSA Panel on Additives and Products or Substances used in Animal Feed), Rychen G, Aquilina G, Azimonti G, Bampidis V, Bastos ML, Bories G, Chesson A, Cocconcelli PS, Flachowsky G, Gropp J, Kolar B, Kouba M, López‐Alonso M, López Puente S, Mantovani A, Mayo B, Ramos F, Saarela M, Martino L. Guidance on the assessment of the safety of feed additives for the target species. EFSA Journal 15(10), 5021.
                                                doi: 10.2903/j.efsa.2017.5021google scholar: lookup
                                              20. EFSA FEEDAP Panel (EFSA Panel on Additives and Products or Substances used in Animal Feed), Rychen G, Aquilina G, Azimonti G, Bampidis V, Bastos ML, Bories G, Chesson A, Cocconcelli PS, Flachowsky G, Gropp J, Kolar B, Kouba M, López‐Alonso M, López Puente S, Mantovani A, Mayo B, Ramos F, Saarela M, Martino L. Guidance on the assessment of the efficacy of feed additives. EFSA Journal 16(5), 5274.
                                                doi: 10.2903/j.efsa.2018.5274google scholar: lookup
                                              21. EFSA FEEDAP Panel (EFSA Panel on Additives and Products or Substances used in Animal Feed), Rychen G, Aquilina G, Azimonti G, Bampidis V, Bastos ML, Bories G, Chesson A, Cocconcelli PS, Flachowsky G, Gropp J, Kolar B, Kouba M, López‐Alonso M, López Puente S, Mantovani A, Mayo B, Ramos F, Saarela M, Innocenti ML. Guidance on the assessment of the safety of feed additives for the consumer. EFSA Journal 15(10), 5022.
                                                doi: 10.2903/j.efsa.2017.5022google scholar: lookup
                                              22. EFSA FEEDAP Panel (EFSA Panel on Additives and Products or Substances used in Animal Feed), Bampidis V, Bastos M, Christensen H, Dusemund B, Kouba M, Kos Durjava M, López‐Alonso M, López Puente S, Marcon F, Mayo B, Pechová A, Petkova M, Ramos F, Sanz Y, Villa RE, Woutersen R, Brock T, de Knecht J, Azimonti G. Guidance on the assessment of the safety of feed additives for the environment. EFSA Journal 17(4), 5648.
                                                doi: 10.2903/j.efsa.2019.5648google scholar: lookup
                                              23. EFSA FEEDAP Panel (EFSA Panel on Additives and Products or Substances used in Animal Feed), Bampidis V, Azimonti G, Bastos ML, Christensen H, Durjava M, Dusemund B, Kouba M, López‐Alonso M, López Puente S, Marcon F, Mayo B, Pechová A, Petkova M, Ramos F, Villa RE, Woutersen R, Brantom P, Chesson A, Galobart J. Guidance on the assessment of the safety of feed additives for the users. EFSA Journal 21(12), e8469.
                                                pmc: PMC10698700pubmed: 38075627
                                              24. EFSA Scientific Committee. Guidance on safety assessment of botanicals and botanical preparations intended for use as ingredients in food supplements, on request of EFSA. EFSA Journal 7(9), 1249.
                                              25. EFSA Scientific Committee, More SJ, Hardy A, Bampidis V, Benford D, Bennekou SH, Bragard C, Boesten J, Halldorsson TI, Hernandez‐Jerez AF, Jeger MJ, Knutsen HK, Koutsoumanis KP, Naegeli H, Noteborn H, Ockleford C, Ricci A, Rychen G, Schlatter JR, Hogstrand C. Guidance on harmonised methodologies for human health, animal health and ecological risk assessment of combined exposure to multiple chemicals. EFSA Journal 17(3), 5634.
                                                doi: 10.2903/j.efsa.2019.5634google scholar: lookup
                                              26. EFSA Scientific Committee, More S, Bampidis V, Benford D, Boesten J, Bragard C, Halldorsson T, Hernandez‐Jerez A, Hougaard‐Bennekou S, Koutsoumanis K, Naegeli H, Nielsen SS, Schrenk D, Silano V, Turck D, Younes M, Aquilina G, Crebelli R, Gürtler R, Schlatter J. Statement on the genotoxicity assessment of chemical mixtures. EFSA Journal 17(1), 5519.
                                                doi: 10.2903/j.efsa.2019.5519google scholar: lookup
                                              27. EFSA Scientific Committee, More SJ, Bampidis V, Benford D, Bragard C, Halldorsson TI, Hernandez‐Jerez AF, Hougaard BS, Koutsoumanis KP, Machera K, Naegeli H, Nielsen SS, Schlatter JR, Schrenk D, Silano V, Turck D, Younes M, Gundert‐Remy U, Kass GE N, Wallace HM. Guidance on the use of the threshold of toxicological concern approach in food safety assessment. EFSA Journal 17(6), 5708.
                                                doi: 10.2903/j.efsa.2019.5708google scholar: lookup
                                              28. EFSA FEEDAP Panel (EFSA Panel on Additives and Products or Substances used in Animal Feed), Rychen G, Aquilina G, Azimonti G, Bampidis V, Bastos ML, Bories G, Chesson A, Cocconcelli PS, Flachowsky G, Gropp J, Kolar B, Kouba M, López‐Alonso M, López Puente S, Mantovani A, Mayo B, Ramos F, Saarela M, Innocenti ML. Guidance on the assessment of the safety of feed additives for the consumer. EFSA Journal 15(10), 5022.
                                                doi: 10.2903/j.efsa.2017.5022google scholar: lookup
                                              29. EMA (European Medicines Agency). Assessment report on Ginkgo biloba L., folium. EMA/HMPC/321095/2012.
                                              30. EMA (European Medicines Agency). European Union herbal monograph on Ginkgo biloba L., folium. EMA/HMPC/321097/2012.
                                              31. Hernandez JP, Mota LC, Huang W, Moore DD, Baldwin WS. Sexually dimorphic regulation and induction of P450s by the constitutive androstane receptor (CAR). Toxicology 256, 53–64.
                                                doi: 10.1016/j.tox.2008.11.002pmc: PMC2798732pubmed: 19041682google scholar: lookup
                                              32. Hori Y, Fujisawa M, Shimada K, Oda A, Katsuyama S, Wada K. Rapid analysis of 4‐O‐methylpyridoxine in the serum of patients with Ginkgo biloba seed poisoning by ion‐pair high‐performance liquid chromatography. Biological and Pharmaceutical Bulletin 27, 486–491.
                                                doi: 10.1248/bpb.27.486pubmed: 15056852google scholar: lookup
                                              33. Huang P, Zhang L, Chai C, Qian XC, Li W, Li JS, Di LQ, Cai BC. Effects of food and gender on the pharmacokinetics of ginkgolides A, B, C and bilobalide in rats after oral dosing with ginkgo terpene lactones extract. Journal of Pharmaceutical and Biomedial Analysis 100, 138–144.
                                                doi: 10.1016/j.jpba.2014.07.030google scholar: lookup
                                              34. Ito N, Hagiwara A, Tamano S, Kagawa M, Shibata M, Kurata Y, Fukushima S. Lack of carcinogenicity of quercetin in F344/DuCrj rats. Japanese Journal of Cancer Research 80, 317–325.
                                                doi: 10.1111/j.1349-7006.1989.tb02313.xpmc: PMC5917733pubmed: 2501248google scholar: lookup
                                              35. Lautz LS, Jeddi MZ, Girolami F, Nebbia C, Dorne JLCM. Metabolism and pharmacokinetics of pharmaceuticals in cats (Felix sylvestris catus) and implications for the risk assessment of feed additives and contaminants. Toxicology Letters 338, 114–127.
                                                doi: 10.1016/j.toxlet.2020.11.014pubmed: 33253781google scholar: lookup
                                              36. Li H, Chen T, Cottrell J, Wang H. Nuclear translocation of adenoviral‐enhanced yellow fluorescent protein‐tagged‐human constitutive androstane receptor (hCAR): A novel tool for screening hCAR activators in human primary hepatocytes. Drug and Metaboilsm Disposition 37, 1098–1106.
                                                doi: 10.1124/dmd.108.026005google scholar: lookup
                                              37. Lin H, Guo X, Zhang S, Dial SL, Guo L, Manjanatha MG, Moore MM, Mei N. Mechanistic evaluation of Ginkgo biloba leaf extract‐induced genotoxicity in L5178Y cells. Toxicological Sciences 139, 338–349.
                                                doi: 10.1093/toxsci/kfu037pmc: PMC8142259pubmed: 24595819google scholar: lookup
                                              38. MacGregor JT, Wehr CM, Manners GD, Jurd L, Minkler JL, Carrano AV. In vivo exposure to plant flavonols. Influence on frequencies of micronuclei in mouse erythrocytes and sister‐chromatid exchange in rabbit lymphocytes. Mutation Research 124, 255–270.
                                                doi: 10.1016/0165-1218(83)90197-0pubmed: 6656827google scholar: lookup
                                              39. Maeda J, Inoue K, Ichimura R, Takahashi M, Kodama Y, Saito N, Yoshida M. Essential role of constitutive androstane receptor in Ginkgo biloba extract induced liver hypertrophy and hepatocarcinogenesis. Food and Chemical Toxicology 83, 201–209.
                                                doi: 10.1016/j.fct.2015.06.010pubmed: 26115596google scholar: lookup
                                              40. Maeda J, Kijima A, Inoue K, Ishii Y, Ichimura R, Takasu S, Kuroda K, Matsushita K, Kodama Y, Saito N, Umemura T, Yoshida M. In vivo genotoxicity of Ginkgo biloba extract in gpt delta mice and constitutive androstane receptor knockout mice. Toxicological Sciences 140, 298–306.
                                                doi: 10.1093/toxsci/kfu090pubmed: 24824808google scholar: lookup
                                              41. Mauri P, Simonetti P, Gardana C, Minoggio M, Morazzoni P, Bombardelli E, Pietta P. Liquid chromatography/atmospheric pressure chemical ionization mass spectrometry of terpene lactones in plasma of volunteers dosed with Ginkgo biloba L. extracts. Rapid Communications in Mass Spectrometry 15, 929–934.
                                                doi: 10.1002/rcm.316pubmed: 11400198google scholar: lookup
                                              42. Meltz ML, MacGregor JT. Activity of the plant flavanol quercetin in the mouse lymphoma L5178Y TK+/− mutation, DNA single‐strand break, and Balb/c 3T3 chemical transformation assays. Mutation Research 88, 317–324.
                                                doi: 10.1016/0165-1218(81)90043-4pubmed: 7254225google scholar: lookup
                                              43. NTP (National Toxicology Program). Toxicology and carcinogenesis studies of Ginkgo biloba extract in F344/N rats and B6C3F1/N mice (gavage studies). Research Triangle Park, NC: 2013.
                                              44. Papiez MA, Cierniak A, Krzysciak W, Bzowska M, Taha HM, Jozkowicz A, Piskula M. The changes of antioxidant defense system caused by quercetin administration do not lead to DNA damage and apoptosis in the spleen and bone marrow cells of rats. Food and Chemical Toxicology 46, 3053–3058.
                                                doi: 10.1016/j.fct.2008.06.006pubmed: 18602965google scholar: lookup
                                              45. PhEur (European Pharmacopoeia). “Ginkgo dry extract, refined and quantified (Ginkgonis extractum siccum raffinatum et quantificatum)”. European Pharmacopoeia 11th Edition. Monograph 04/2008:1827 (corrected 11.0).
                                              46. PhEur (European Pharmacopoeia). “Ginkgo leaf (Ginkgonis folium)”. European Pharmacopoeia 11th Edition, 2020. Monograph 01/201:1828.
                                              47. Pietta PG, Gardana C, Mauri PL, Maffei‐Fracino R, Carini M. Identification of flavanoid metabolites after oral administration to rats of a Ginkgo biloba extract. Journal of Chromatography B Biomedical Applications 673, 75–80.
                                                pubmed: 8925077
                                              48. Resende FA, Vilegas W, Dos Santos LC, Varanda EA. Mutagenicity of flavonoids assayed by bacterial reverse mutation (Ames) test. Molecules 17, 5255–5268.
                                                doi: 10.3390/molecules17055255pmc: PMC6268182pubmed: 22565478google scholar: lookup
                                              49. Sahu RK, Basu R, Sharma A. Genetic toxicological of some plant flavonoids by the micronucleus test. Mutation Research 89, 69–74.
                                                doi: 10.1016/0165-1218(81)90132-4pubmed: 7242547google scholar: lookup
                                              50. Saito D, Shirai A, Matsushima T, Sugimura T, Hirono I. Test of carcinogenicity of quercetin, a widely distributed mutagen in food. Teratogenesis, Carcinogenesis and Mutagenesis 1, 213–221.
                                                doi: 10.1002/tcm.1770010209pubmed: 6119812google scholar: lookup
                                              51. Schötz K. Quantification of allergenic urushiols in extracts of Ginkgo biloba leaves, in simple one‐step extracts and refined manufactured material (EGb 761). Phytochemical Analysis: An International Journal of Plant Chemical and Biochemical Techniques 15(1), 1–8.
                                                doi: 10.1002/pca.733google scholar: lookup
                                              52. Shizu R, Yoshinari K. Nuclear receptor CAR‐mediated liver cancer and its species differences. Expert Opinion on Drug Metabolism & Toxicology 16, 343–351.
                                                doi: 10.1080/17425255.2020.1746268pubmed: 32202166google scholar: lookup
                                              53. Silva AM, Silva SC, Soares JP, Martins‐Gomes C, Teixeira JP, Leal F, Gaivão I. Ginkgo biloba L. leaf extract protects HepG2 cells against Paraquat‐induced oxidative DNA damage. Plants (Basel) 8, 556.
                                                doi: 10.3390/plants8120556pmc: PMC6963582pubmed: 31795413google scholar: lookup
                                              54. Silva Lima B, Van der Laan JW. Mechanisms of nongenotoxic carcinogenesis and assessment of the human hazard. Regulatory Toxicology and Pharmacology 32, 135–143.
                                                doi: 10.1006/rtph.2000.1427pubmed: 11067770google scholar: lookup
                                              55. Solimani R. Quercetin and DNA in solution: Analysis of the dynamics of their interaction with a linear dichroism study. International Journal of Biological Macromolecules 18, 287–295.
                                                doi: 10.1016/0141-8130(95)01089-0pubmed: 8739133google scholar: lookup
                                              56. Takanashi H, Aiso S, Hirono I, Matsushima T, Sugimura T. Carcinogenicity test of quercetin and kaempferol in rats by oral administration. Journal of Food Safety 5(55), 60.
                                                doi: 10.1111/j.1745-4565.1983.tb00455.xgoogle scholar: lookup
                                              57. Ude C, Schubert‐Zsilavecz M, Wurglics M. Ginkgo biloba extracts: a review of the pharmacokinetics of the active ingredients. Clinical Pharmacokinetics 52(9), 727–749.
                                                doi: 10.1007/s40262-013-0074-5pubmed: 23703577google scholar: lookup
                                              58. Ueda A, Hamadeh HK, Webb HK, Yamamoto Y, Sueyoshi T, Afshari CA, Lehmann JM, Negishi M. Diverse roles of the nuclear orphan receptor CAR in regulating hepatic genes in response to phenobarbital. Molecular Pharmacology 61, 1–6.
                                                doi: 10.1124/mol.61.1.1pubmed: 11752199google scholar: lookup
                                              59. USP (US Pharmacopoieia). Dietray supplements. Powdered Ginkgo Extract Monograph, pp.1156‐1159. .
                                              60. Van den Berg M, Birnbaum LS, Denison M, De Vito M, Farland W, Feeley M, Fiedler H, Hakansson H, Hanberg A, Haws L, Rose M, Safe S, Schrenk D, Tohyama C, Tritscher A, Tuomisto J, Tysklind M, Walker N, Peterson RE. The 2005 World Health Organization reevaluation of human and mammalian toxic equivalency factors for dioxins and dioxin‐like compounds. Toxicological Sciences: An Official Journal of the Society of Toxicology 93, 223–241.
                                                doi: 10.1093/toxsci/kfl055pmc: PMC2290740pubmed: 16829543google scholar: lookup
                                              61. Wang W, Wang M, Ruan Y, Tan J, Wang H, Yang T, Li J, Zhou Q. Ginkgolic acids impair mitochondrial function by decreasing mitochondrial biogenesis and promoting FUNDC1‐dependent mitophagy. Journal of Agrticultural and Food Chemistry 2019(67), 10097–10106.
                                                doi: 10.1021/acs.jafc.9b04178google scholar: lookup
                                              62. Westendorf J, Regan J. Induction of DNA strand‐breaks in primary rat hepatocytes by ginkgolic acids. Pharmazie 55, 864–865.
                                                pubmed: 11126011
                                              63. Zhang Z, Chen S, Mei H, Xuan J, Guo X, Couch L, Dobrovolsky VN, Guo L, Mei N. Ginkgo biloba leaf extract induces DNA damage by inhibiting topoisomerase II activity in human hepatic cells. Scientific Reports 5, 14633.
                                                doi: 10.1038/srep14633pmc: PMC4588569pubmed: 26419945google scholar: lookup

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