Safety of a feed additive consisting of a tincture derived from the roots of Gentiana lutea L. (gentian tincture) for all animal species (FEFANA asbl).
Abstract: Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the safety of a tincture derived from L. (gentian tincture). It is intended to be used as a sensory additive for all animal species. The product is a water/ethanol solution, with a dry matter content of approximately 4.3% and it contains on average 0.0836% polyphenols (of which 0.0463% are flavonoids and 0.0027% xanthones) and 0.0022% gentiopicroside. The additive is intended for use in complete feed or drinking water up to a maximum level of 50 mg tincture/kg for all animal species, except horses, for which the proposed use is 200 mg/kg in complete feed. In a previous assessment, due to the genotoxic potential identified in vitro for xanthones (gentisin and isogentisin) and gentiopicroside the Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) could not conclude on the safety of the additive for long-living animals and on risks of genotoxicity and carcinogenicity for dermal exposure of unprotected users. The additive did not raise safety concern for short-living animals, consumers and the environment. The applicant has provided information in the form of literature to address the previously identified genotoxic activity of xanthones and gentiopicroside and the risk for the user. Considering that the literature identified provided no new evidence, the FEEDAP Panel reiterated that it is not in a position to conclude on the safety of the additive for long-living and reproductive animals. No conclusions could be drawn on the potential of the additive to be a dermal/eye irritant or a skin sensitiser. When handling the tincture, exposure of unprotected users to xanthones (gentisin and isogentisin) and gentiopicroside cannot be excluded. Therefore, to reduce the risk, the exposure of the users should be minimised.
© 2023 European Food Safety Authority. EFSA Journal published by Wiley‐VCH GmbH on behalf of European Food Safety Authority.
Publication Date: 2023-02-24 PubMed ID: 36846385PubMed Central: PMC9950874DOI: 10.2903/j.efsa.2023.7869Google Scholar: Lookup
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Summary
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The research evaluated the safety of a feed additive – a tincture derived from the roots of Gentiana lutea L, also known as gentian tincture. The scientists were unable to conclusively establish the product’s safety for long-living and reproductive animals due to potential genotoxic effects.
What is the Research About?
- The research specifically interrogates the safety of a tincture derived from the roots of Gentiana lutea L. (gentian tincture), intended to be used as a sensory additive for all animal species. The product is a water/ethanol solution notable for its dry matter content of about 4.3%. It contains on average about 0.0836% polyphenols, which are subdivided into 0.0463% flavonoids and 0.0027% xanthones, and 0.0022% gentiopicroside.
- The EFSA received this request from the European Commission to provide a scientific opinion on the safety of this tincture. The additive’s proposed use was up to 50 mg per kg of feed for all species, except horses, where 200 mg/kg in complete feed was the proposed usage.
Previous Assessment
- In an earlier assessment, the Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) was unable to arrive at a conclusion on the safety of the additive for longer-living animals and risks associated with genotoxicity and carcinogenicity that could affect dermal exposure in unprotected users.
- This was due to identified in vitro genotoxic potential for xanthones (gentisin and isogentisin) and gentiopicroside. The additive was not deemed a safety concern for short-living animals, consumers, and the environment in this former assessment.
Further Assessment
- To address the previous findings concerning the genotoxic effects, the applicant provided additional literature for consideration. However, this new literature did not present fresh evidence that would allow the FEEDAP Panel to conclusively determine the safety of the additive for long-living and reproductive animals.
- The FEEDAP Panel also could not finalize the safety risks associated with dermal/eye irritation or skin sensitization from the additive. Their study inferred that exposure of unprotected users to the xanthones (gentisin and isogentisin), and gentiopicroside in the tincture could not be excluded. They recommended minimization of user exposure to lower the risk.
Cite This Article
APA
Bampidis V, Azimonti G, Bastos ML, Christensen H, Durjava M, Kouba M, López-Alonso M, Puente SL, Marcon F, Mayo B, Pechová A, Petkova M, Ramos F, Sanz Y, Villa RE, Woutersen R, Brantom P, Chesson A, Westendorf J, Manini P, Pizzo F, Dusemund B.
(2023).
Safety of a feed additive consisting of a tincture derived from the roots of Gentiana lutea L. (gentian tincture) for all animal species (FEFANA asbl).
EFSA J, 21(2), e07869.
https://doi.org/10.2903/j.efsa.2023.7869 Publication
Researcher Affiliations
References
This article includes 26 references
- Anour R, Leinker S, van den Hoven R. Improvement of the lung function of horses with heaves by treatment with a botanical preparation for 14 days.. Vet Rec 2005 Dec 3;157(23):733-6.
- Chang-Liao WL, Chien CF, Lin LC, Tsai TH. Isolation of gentiopicroside from Gentianae Radix and its pharmacokinetics on liver ischemia/reperfusion rats.. J Ethnopharmacol 2012 Jun 1;141(2):668-73.
- Cvetković S, Todorović S, Nastasijević B, Mitić‐Ćulafić D, Đukanović S, Knežević‐Vukčević J, Nikolić B. Assessment of genoprotective effects of Gentiana lutea extracts prepared from plants grown in field and in vitro. Industrial Crops and Products 154, 112690.
- Cvetković S, Nastasijević B, Mitić-Ćulafić D, Đukanović S, Tenji D, Knežević-Vukčević J, Nikolić B. New insight into the antigenotoxic activity of Gentiana lutea extracts - Protective effect against food borne mutagens.. Mutat Res Genet Toxicol Environ Mutagen 2020 Oct-Dec;858-860:503251.
- Cvetković S, Vuletić S, Vunduk J, Klaus A, Mitić-Ćulafić D, Nikolić B. The role of Gentiana lutea extracts in reducing UV-induced DNA damage.. Mutagenesis 2023 Feb 3;38(1):71-80.
- Djukanovic S, Cvetkovic S, Mitic‐Culafic D, Knezevic‐Vukcevic J, Nikolic B. Anti‐genotoxic potential of Gentiana lutea extracts against the food sweetener saccharin. IOP Conference Series Earth Environmental Sciences 333, 012059.
- EFSA FEEDAP Panel (EFSA Panel on Additives and Products or Substances used in Animal Feed). Guidance on studies concerning the safety of use of the additive for users/workers. EFSA Journal 2012;10(1):2539, 5 pp.
- 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, Villa RE, Wallace RJ, Wester P, Anguita M, Galobart J, Innocenti ML, Martino L. Guidance on the assessment of the safety of feed additives for the target species.. EFSA J 2017 Oct;15(10):e05021.
- EFSA FEEDAP Panel (EFSA Panel on Additives and Products or Substances used in Animal Feed). General approach to assess the safety for the target species of botanical preparations which contain compounds that are genotoxic and/or carcinogenic. .
- EFSA SC (EFSA Scientific Committee). Scientific Opinion on genotoxicity testing strategies applicable to food and feed safety assessment. EFSA Journal 2011;9(9):2379, 69 pp.
- Hardy A, Benford D, Halldorsson T, Jeger M, Knutsen HK, More S, Naegeli H, Noteborn H, Ockleford C, Ricci A, Rychen G, Silano V, Solecki R, Turck D, Younes M, Aquilina G, Crebelli R, Gürtler R, Hirsch-Ernst KI, Mosesso P, Nielsen E, van Benthem J, Carfì M, Georgiadis N, Maurici D, Parra Morte J, Schlatter J. Clarification of some aspects related to genotoxicity assessment.. EFSA J 2017 Dec;15(12):e05113.
- Hardy A, Benford D, Halldorsson T, Jeger MJ, Knutsen HK, More S, Naegeli H, Noteborn H, Ockleford C, Ricci A, Rychen G, Schlatter JR, Silano V, Solecki R, Turck D, Younes M, Bresson JL, Griffin J, Hougaard Benekou S, van Loveren H, Luttik R, Messean A, Penninks A, Ru G, Stegeman JA, van der Werf W, Westendorf J, Woutersen RA, Barizzone F, Bottex B, Lanzoni A, Georgiadis N, Alexander J. Guidance on the assessment of the biological relevance of data in scientific assessments.. EFSA J 2017 Aug;15(8):e04970.
- More SJ, Bampidis V, Benford D, Bennekou SH, Bragard C, Halldorsson TI, Hernández-Jerez AF, Koutsoumanis K, Naegeli H, Schlatter JR, Silano V, Nielsen SS, Schrenk D, Turck D, Younes M, Benfenati E, Castle L, Cedergreen N, Hardy A, Laskowski R, Leblanc JC, Kortenkamp A, Ragas A, Posthuma L, Svendsen C, Solecki R, Testai E, Dujardin B, Kass GE, Manini P, Jeddi MZ, Dorne JC, Hogstrand C. Guidance on harmonised methodologies for human health, animal health and ecological risk assessment of combined exposure to multiple chemicals.. EFSA J 2019 Mar;17(3):e05634.
- 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, Hirsch-Ernst KI, Mosesso P, Nielsen E, Solecki R, Carfì M, Martino C, Maurici D, Parra Morte J, Schlatter J. Genotoxicity assessment of chemical mixtures.. EFSA J 2019 Jan;17(1):e05519.
- More SJ, Bampidis V, Benford D, Bragard C, Halldorsson TI, Hernández-Jerez AF, Hougaard Bennekou S, Koutsoumanis KP, Machera K, Naegeli H, Nielsen SS, Schlatter JR, Schrenk D, Silano V, Turck D, Younes M, Gundert-Remy U, Kass GEN, Kleiner J, Rossi AM, Serafimova R, Reilly L, Wallace HM. Guidance on the use of the Threshold of Toxicological Concern approach in food safety assessment.. EFSA J 2019 Jun;17(6):e05708.
- Feng B, Zhu H, Guan J, Zhao L, Gu J, Yin L, Fawcett JP, Liu W. A rapid and sensitive UFLC-MS/MS method for the simultaneous determination of gentiopicroside and swertiamarin in rat plasma and its application in pharmacokinetics.. J Pharm Pharmacol 2014 Oct;66(10):1369-76.
- Han H, Xiong AZ, He CY, Liu Q, Yang L, Wang ZT. Combination of UHPLC/Q-TOF-MS, NMR spectroscopy, and ECD calculation for screening and identification of reactive metabolites of gentiopicroside in humans.. Anal Bioanal Chem 2014 Feb;406(6):1781-93.
- Jund R, Mondigler M, Steindl H, Stammer H, Stierna P, Bachert C. Clinical efficacy of a dry extract of five herbal drugs in acute viral rhinosinusitis.. Rhinology 2012 Dec;50(4):417-26.
- Mustafayeva K, Di Giorgio C, Elias R, Kerimov Y, Ollivier E, De Méo M. DNA-damaging, mutagenic, and clastogenic activities of gentiopicroside isolated from Cephalaria kotschyi roots.. J Nat Prod 2010 Feb 26;73(2):99-103.
- Šobot AV, Drakulić D, Joksić G, Vukajlović JM, Savić J, Potočnik J, Tričković JF. Yellow gentian root extract provokes concentration- and time-dependent response in peripheral blood mononuclear cells.. Arh Hig Rada Toksikol 2020 Dec 31;71(4):320-328.
- Wang Z, Wang S, Sun Y, Wang H, Chen G, Wang X, Hattori M, Zhang H. New analytical method for the study of the metabolism of gentiopicroside in rats after oral administration by LC-TOF-MS following picolinoyl derivatization.. J Sep Sci 2014 Feb;37(3):237-43.
- Wang Z, Tang S, Jin Y, Zhang Y, Hattori M, Zhang H, Zhang N. Two main metabolites of gentiopicroside detected in rat plasma by LC-TOF-MS following 2,4-dinitrophenylhydrazine derivatization.. J Pharm Biomed Anal 2015 Mar 25;107:1-6.
- Wang C, Gong X, Bo A, Zhang L, Zhang M, Zang E, Zhang C, Li M. Iridoids: Research Advances in Their Phytochemistry, Biological Activities, and Pharmacokinetics.. Molecules 2020 Jan 10;25(2).
- Wölfle U, Haarhaus B, Seiwerth J, Cawelius A, Schwabe K, Quirin KW, Schempp CM. The Herbal Bitter Drug Gentiana lutea Modulates Lipid Synthesis in Human Keratinocytes In Vitro and In Vivo.. Int J Mol Sci 2017 Aug 22;18(8).
- Xiong K, Gao T, Zhang T, Wang Z, Han H. Simultaneous determination of gentiopicroside and its two active metabolites in rat plasma by LC-MS/MS and its application in pharmacokinetic studies.. J Chromatogr B Analyt Technol Biomed Life Sci 2017 Oct 15;1065-1066:1-7.
- Zeng W, Han H, Tao Y, Yang L, Wang Z, Chen K. Identification of bio-active metabolites of gentiopicroside by UPLC/Q-TOF MS and NMR.. Biomed Chromatogr 2013 Sep;27(9):1129-36.
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