Abstract
As data on food contamination with the mycotoxin citrinin (CIT) are scarce, a recently developed method for biomarker analysis (Blaszkewicz et al. in Arch Toxicol 87:1087–1094, 2013) was applied to investigate CIT exposure of German adults. CIT and its human metabolite dihydrocitrinone (HO-CIT) were determined in urine samples from a group of 50 healthy adults (n = 27 females and n = 23 males). After cleanup by immunoaffinity (CitriTest®) columns, extracts were analyzed by LC–MS/MS. The mycotoxin and its major metabolite HO-CIT were detected in 82 and 84 % of all urine samples, at concentrations ranging from 0.02 (limit of detection, LOD) to 0.08 ng/mL for CIT, and 0.05 (LOD) to 0.51 ng/mL for HO-CIT. Median urine analyte levels in the cohort were 0.03 (CIT) and 0.06 ng/mL (OH-CIT) or adjusted to creatinine 20.2 ng/g crea (CIT) and 60.9 ng/g crea (HO-CIT), respectively. Except for higher urinary CIT levels in males, differences between subgroups were not significant. This first biomarker analysis indicates widespread and variable exposure to CIT in German adults, and conversion of ingested mycotoxin to its less toxic metabolite HO-CIT, which may serve as biomarker of exposure in addition to the parent compound.
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References
Ali N, Blaszkewicz M, Hossain K, Degen GH (2014) Biomonitoring of the mycotoxin citrinin in urine samples from Bangladesh. Naunyn-Schmiedeberg’s Arch Pharmacol 387(Suppl. 1):S25
Blaszkewicz M, Liesenhoff-Henze K (2012) Creatinine in urine [Biomonitoring Methods, 2010]. The MAK collection for occupational health and safety, pp 169–184. Wiley VCH. doi:10.1002/3527600418.bi6027urie0012
Blaszkewicz M, Muñoz K, Degen GH (2013) Methods for analysis of citrinin in human blood and urine. Arch Toxicol 87(6):1087–1094
Castegnaro M, Canadas D, Vrabcheva T, Petkova-Bocharova T, Chernozemsky IN, Pfohl-Leszkowicz A (2006) Balkan endemic nephropathy: role of ochratoxin A through biomarkers. Mol Nutr Food Res 50:519–529
Commission Regulation (EU) No 212/2014 of 6 March 2014 amending Regulation (EC) No 1881/2006 as regards maximum levels of the contaminant citrinin in food supplements based on rice fermented with red yeast Monascus purpureus. http://faolex.fao.org/docs/pdf/eur131703.pdf
Degen GH (2011) Tools for investigating workplace related risks from mycotoxin exposure. World Mycotoxin J 4:315–327
Degen GH, Ali N, Blaszkewicz M (2014) Individual profiles of ochratoxin A and citrinin and their metabolites in human blood and urine. In: 36th mycotoxin workshop 16–18 June 2014, Göttingen, Germany, conference abstracts, p 107
Duarte SC, Pena A, Lino CM (2011) Human ochratoxin A biomarkers: from exposure to effect. Crit Rev Toxicol 41(3):187–212
Dunn BB, Stack ME, Park DL, Joshi A, Friedman L, King RL (1983) Isolation and identification of dihydrocitrinone, a urinary metabolite of citrinin in rats. J Toxicol Environ Health 12:283–289
EC/SCOOP (2002) Assessment of dietary intake of ochratoxin A by the population of EU member states. Report of the scientific cooperation (SCOOP), task 3.2.7. Directorate General Health and Consumer Protection, European Commission. http://ec.europa.eu/food/fs/scoop/index_en.html
European Food Safety Authority (EFSA) (2006) Opinion of the Scientific Panel on contaminants in the food chain on a request from the commission related to ochratoxin A in food. EFSA J 365:1–56
European Food Safety Authority (EFSA), Panel on Contaminants in the Food Chain (2012) Scientific Opinion on the risks for public and animal health related to the presence of citrinin in food and feed. EFSA J 10:2605
Flajs D, Peraica M (2009) Toxicological properties of citrinin. Arh Hig Rada Toksikol 60:457–464
Föllmann W, Behm C, Degen GH (2014) Toxicity of citrinin and its metabolite dihydrocitrinone and of mixtures of citrinin and ochratoxin A in vitro. Arch Toxicol 88:1097–1107
Frank KH (1992) Citrinin. Z Ernährungswissenschaften 31:164–177
Frisvad JC, Thrane U, Samson RA, Pitt JI (2006) Important mycotoxins and the fungi which produce them. Adv Exp Med Biol 571:3–31
Huybrechts B, Martins JC, Debongnie Ph, Uhlig S, Callebaut AC (2014). Fast and sensitive LC–MS/MS method measuring human mycotoxin exposure using biomarkers. Arch Toxicol (in press)
Leong YH, Latiff AA, Ahmad NI, Rosma A (2012) Exposure measurement of aflatoxins and aflatoxin metabolites in human body fluids. A short review. Mycotoxin Res 28:79–87
Malir F, Ostry V, Pfohl-Leszkowicz A, Roubal T (2012) Ochratoxin A exposure biomarkers in the Czech Republic and comparison with foreign countries. Biomarkers 17:577–589
Molinié A, Faucet V, Castegnaro M, Pfohl-Leszkowicz A (2005) Analysis of some breakfast cereals on the French market for their contents of ochratoxin A, citrinin and fumonisin B1: development of a method for simultaneous extraction of ochratoxin A and citrinin. Food Chem 92:391–400
Nguyen M, Tozlovanu M, Tran T, Pfohl-Leszkowicz A (2007) Occurrence of aflatoxin B1, citrinin and ochratoxin A in rice in five provinces of the central region of Vietnam. Food Chem 105:42–47
Njumbe Ediage E, Mavungu JD, Song S, Wu A, Van Peteghem C, De Saeger S (2012) A direct assessment of mycotoxin biomarkers in human urine samples by liquid chromatography tandem mass spectrometry. Anal Chim Acta 741:58–69
Ostry V, Malir M, Ruprich J (2013) Producers and important dietary sources of ochratoxin A and citrinin. Toxins 5:1574–1586
Petkova-Bocharova T, Castegnaro M, Michelon J, Maru V (1991) Ochratoxin A and other mycotoxins in cereals from an area of Balkan endemic nephropathy and urinary tract tumours in Bulgaria. IARC Sci Publ 115:83–87
Pfohl-Leszkowicz A, Tozlovanu M, Manderville M, Peraica M, Castegnaro M, Stefanovic V (2007) New molecular and field evidences for the implication of mycotoxins but not aristolochic acid in human nephropathy and urinary tract tumor. Mol Nutr Food Res 51:1131–1146
Schmidt S, Brockmeyer A, Knor K, Thielert G (2003) Vorkommen von Citrinin in Getreide. Mycotoxin Res 19:129–133
Turner PC (2010) Deoxynivalenol and nivalenol occurrence and exposure assessment. World Mycotoxin J 3(4):315–321
Vrabcheva T, Usleber E, Dietrich R, Märtlbauer E (2000a) Co-occurrence of ochratoxin A and citrinin in cereals from Bulgarian villages with a history of Balkan endemic nephropathy. J Agric Food Chem 48:2483–2488
Vrabcheva T, Usleber E, Petkova-Bocharova T, Nikolov I, Chernozemsky I, Dietrich R, Märtlbauer E (2000b) Citrinin in the diet of young and healthy persons living in Balkan endemic nephropathy areas. Mycotoxin Res 16(Suppl. 2):150–153
Xu B, Jia X, Gu L, Sung C (2006) Review on the qualitative and quantitative analysis of the mycotoxin citrinin. Food Control 17:271–285
Acknowledgments
The authors wish to thank Iris Glaeser for excellent technical assistance. We are grateful for a gift of CitriTest® columns (from Vicam, Dr. Stephen Powers). This work was supported by a DAAD scholarship to N.A. and a grant to G.H.D. from the Brigitte und Wolfgang Gedek-Stiftung.
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Ali, N., Blaszkewicz, M. & Degen, G.H. Occurrence of the mycotoxin citrinin and its metabolite dihydrocitrinone in urines of German adults. Arch Toxicol 89, 573–578 (2015). https://doi.org/10.1007/s00204-014-1363-y
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DOI: https://doi.org/10.1007/s00204-014-1363-y