Distribution and Metabolism of Citrinin: A Review

  • Bonnie B. Dunn
  • Leonard Friedman
Part of the Biodeterioration Research book series (BIOR, volume 4)


Citrinin was first isolated by Hetherington and Raistrick in 1931 from a culture filtrate of Penicillium Thom. Other species of Penicillium as well as several species of Aspergillius also produce citrinin (Timonin and Rouatt, 1944; Krogh et al., 1970; Mislivec and Tuite, 1970; Ito et al., 1973; Pohland and Mislivec, 1976; Stoloff, 1976; Nelson et al., 1980; Mislivec, 1981). It is a potentially important mycotoxin; it had been found as a natural contaminant of peanuts (Diener, 1960), corn (Mislivec and Tuite, 1970), rice (Saito et al., 1971); wheat, rye, barley, and oats in Canada (Scott et al., 1972); barley and oats in Denmark (Krogh et al., 1973); naturally rotted apples containing Penicillium expansum (Harwig et al., 1973); and Indian groundnuts infected with A. flavus. P. citrinum and A. terreus (Subrahmanyam and Rao, 1974).


High Performance Liquid Chromatographic Urinary Metabolite Aspergillus Terreus Penicillic Acid Penicillium Expansum 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Ambrose, A.M. and DeEds, F. (1945). Some toxicological and pharmacological properties of citrinin. Abstract. Proc. Soc. Exp. Biol. Med. 59, 289.Google Scholar
  2. Ambrose, A.M. and DeEds, F. (1946). Some toxicological and pharmacological properties of citrinin. J. Pharmacol. Exp. Ther. 88, 173–186.Google Scholar
  3. Berndt, W.O. (1983). Transport of citrinin by rat renal cortex. Arch. Toxicol. 54(1), 35–40.Google Scholar
  4. Berndt, W.O. and Hayes, A.W. (1982). The effect of probenecid on citrinin-induced nephrotoxicity. Toxicol. Appl. Pharmacol. 64, 118–124.Google Scholar
  5. Carlton, W.W., Sansing, G., Szczech, G.M., and Tuite, J. (1974). Citrinin mycotoxicosis in beagle dogs. Food Cosmet. Toxicol. 12, 479–490.Google Scholar
  6. Carlton, W.W. and Tuite, J. (1977). Metabolites of P. viridicatum toxicology. In: Mycotoxins in Human and Animal Health (J. Rodricks, C. Hesseltine, und M. Mehlman, eds.), Pathotox Publishers, Inc., Park Forest South, IL.Google Scholar
  7. Chu, W.C. (1946). Miscellaneous pharmacologic actions of citrinin. J. Lab. Clin. Med. 31, 72.Google Scholar
  8. Ciegler, M.M., Detroy, R.W., and Lillihoj, E.B. (1971). Patulin, Penicillic Acid and Other Carcinogenic Lactones. Academic Press, New York.Google Scholar
  9. Dailey, R.E., Blaschka, A.M., and Brouwer, E.A. (1977). Adsorption, distribution and excretion of 14C-patulin by rats. J. Toxicol. Environ. Health 3, 479–489.Google Scholar
  10. Damodaran, C. and Shanmugasundaram, E.R.B. (1978). Distribution of radioactive citrinin in tissues and serum proteins. J. Radioanal. Chem. 46, 373–377.Google Scholar
  11. Diener, U.L. (1960). The mycoflora of peanuts in storage. Phvtopatholopy 50, 220–223.Google Scholar
  12. Dunn, B.B. (1982). Adsorption, Distribution and Excretion of 14 C-Citrinin. Google Scholar
  13. Doctoral Dissertation, University of Maryland, College Park, MD.Google Scholar
  14. Dunn, B.B., Stack, M.E., Park, D.L., Joshi, A., Friedman, L., and King, R.L. (1983). Isolation and identification of dihydrocitrinone, a urinary metabolite of citrinin in rats. J. Toxicol. Environ. Health 12, 283–289.Google Scholar
  15. Durackova, Z., Betina, V., and Nemec, P. (1976). Systematic analysis of mycotoxins by thin layer chromatography. J. Chromatogr. 116, 141.Google Scholar
  16. Friis, P., Hasselager, E., and Krogh, P. (1969). Isolation of citrinin and oxalic acid from Penicillium viridicatum Westling and their nephrotoxicity in rats and pigs. Acta Pathol. Microbiol. Scand. 77, 559–560.Google Scholar
  17. Galtier, P. (1978). Contribution of pharmacokinetic studies to mycology-Ochratoxin A. Vet. Sci. Commun. 1, 349–358.Google Scholar
  18. Haese, G. (1963). Uber Antimycin. Arch. Pharmacol. (Weinheim) 296, 227–232.Google Scholar
  19. Hald, B. and Krogh, P. (1973). Analysis and chemical confirmation of citrinin in barley. J. Assoc. Off. Anal. Chem. 56, 1440–1443.Google Scholar
  20. Harwig, J., Chen, Y.K., Kennedy, B.P.C., and Scott, P.M. (1973). Occurrence of patulin and patulin-producing strains of Penicillium expansum in natural rots of apple in Canada. Can. Inst. Food Sci. Technol. J. 6, 22–25.Google Scholar
  21. Hassall, C.H. and Jones, D.W. (1962). The biosynthesis of phenols. Part 5. A new metabolic product of Aspergillus terreus Thom. J. Chem. Soc. 4189–4191.Google Scholar
  22. Hetherington, A.C. and Raistrick, H. (1931). Studies in the biochemistry of microorganisms. Part XIV. On the production and chemical constitution of a new yellow coloring matter, citrinin, produced from glucose by Penicillium citrinum Thom. Philos. Trans. R. Soc. (London) Ser. B., 220 269–295.Google Scholar
  23. Ito, Y., Kawai, K., and Nozawa, Y. (1973). Biochemical studies of pigments from the pathogenic fungus Microsporum cookei. J. Biochem. 74, 805.Google Scholar
  24. Kawashiro, I., Yanabe, H., Takenchi, H., and Nishimura, C. (1955). Determination of citrinin contained in rice by fluorometry. Bull. Natl. Hyg. Lab. (Tokyo) 73, 191–196.Google Scholar
  25. Krogh, P. (1972). Mycotoxic porcine nephropathy: A possible model for Balkan nephropathy in endemic nephropathy. In: 2nd International Symposium on Endemic Nephropathy pp. 266–270. Bulgarian Academy of Science, Sofia.Google Scholar
  26. Krogh, P., Hald, B., and Pederson, E.J. (1973). Occurrence of ochratoxin A and citrinin in cereals associated with mycotoxic porcine nephropathy. Acta Pathol. Microbiol. Scand. 81, 689–695.Google Scholar
  27. Krogh, P., Hasselager, E., and Friis, P. (1970). Studies on fungal nephrotoxicity isolation of two nephrotoxic compounds from Penicillium viridicatum Westling: Citrinin and oxalic acid. Acta Pathol. Microbiol. Scand. 78, 401–413.Google Scholar
  28. Lepom, P. (1986). Simultaneous determination of the mycotoxins citrinin and ochratoxin A in wheat and barley by high-performance liquid chromatography. J. Chromatogr. 352, 335.Google Scholar
  29. Marti, L.R., Wilson, D.M., and Evans, B.D. (1978). Determination of citrinin in corn and barley. J. Assoc. Off. Anal. Chem. 61, 1353.Google Scholar
  30. Mislivec, P.B. (1981). Toxic species of Penicillium common in food. J. Food Prot. 44, 723–726.Google Scholar
  31. Mislivec, P.B. and Tuite, J. (1970). Species of Penicillium occurring in freshly harvested and stored Dent corn kernals. Mvcologia 62, 67–74.Google Scholar
  32. Neely, W.C., Ellis, S.P., Davis, N.D., and Diener, V.L. (1972). Spectroanalytical parameters of fungal metabolites. I. Citrinin. J. Assoc. Off. Anal. Chem. 55, 1122–1127.Google Scholar
  33. Nelson, T.S., Blasley, J.N., Kirby, L.K., Johnson, Z.B., and Ballam, G.C. (1980). Isolation and identification of citrinin produced by Penicillium lanosum. Poultry Sci. 59, 2055–2059.Google Scholar
  34. Park, D., Dailey, R., Friedman, L., and Heath, J. (1977). The adsorption, distribution and excretion of 14C-penicillic acid by rats. Ann. Nutr. 31, 919–934.Google Scholar
  35. Phillips, R.D., Berndt, W.O., and Hayes, A.W. (1978). Distribution and excretion of [14C]-citrinin in Rats. Abstract. Toxicol. Appl. Pharmacol. 45, 276.Google Scholar
  36. Phillips, R.D., Berndt, W.O., and Hayes, A.W. (1979a). Distribution and excretion Of [14C]-citrinin in rats. Toxicology 12 (3), 285–298.Google Scholar
  37. Phillips, R.D., Berndt, W.O., and Hayes, A.W. (1979b). Renal and hepatic clearance studies of citrinin in rats. Abstract. Toxicol. Appl. Pharmacol. 48(11), A14.Google Scholar
  38. Phillips, R.D., Berndt, W.O., and Hayes, A.W. (1980). Urinary excretion of two metabolites of the mycotoxin 14C-citrinin in rats. Abstract. Toxicol. Appl. Pharmacol. 45, A114.Google Scholar
  39. Phillips, R.D. and Hayes, A.W. (1978). Effect of the mycotoxin citrinin on composition of mouse liver and kidney. Toxicon 16, 351–359.Google Scholar
  40. Phillips, R.D. Hayes, A.W., and Berndt, W.O. (1980). High performance liquid chromatographic analysis of the mycotoxin citrinin and its application to biological fluids. J. Chromatogr. 190, 419–427.Google Scholar
  41. Pohland, A.E. and Mislivec, P.B. (1976). Metabolites of various Penicillium species encountered on foods. In: Mvcotoxins and Other Fungal Related Food Problems. American Chemical Society, Washington, D.C.Google Scholar
  42. Ramadoss, C.S. and Shanmugasundaram, E.R.B. (1973). Effect of citrinin on liver metabolism in rabbits. Indian J. Biochem. Biophys. 10, 296.Google Scholar
  43. Saito, M., Enomota, M., and Tatsuno, T. (1971). Yellowed Rice Toxins. Citrinin. Academic Press, New York.Google Scholar
  44. Sansing, G.A., Lillehój, E.B., Detroy, R.W., and Miller, M.A. (1976). Synergistic toxic effects of citrinin, ochratoxin A and penicillic acid in mice. Toxicon 14, 213–220.Google Scholar
  45. Scott, P.M., van Walbeck, W., Kennedy, B., and Anyeti, D. (1972). Mycotoxins (ochratoxin A, citrinin, and sterigmatocystin) and toxigenic fungi in grains and other agricultural products. J. Agric. Food Chem. 20, 1103–1109.Google Scholar
  46. Stoloff, L. (1976). Occurrence of Mycotoxins in Foods and Feeds. American Chemical Society, Washington, D.C.Google Scholar
  47. Stubblefield, R.D. (1979). Thin layer chromatographic determination of citrinin. J. Assoc. Off. Anal. Chem. 62, 201–202.Google Scholar
  48. Subrahmanyam, P. and Rao, A.S. (1974). Occurrence of aflatoxins and citrinin in groundnut (Arachis hvoogaea L.) at harvest in relation to pod condition and kernel moisture content. Curr. Sci. 43, 707–710.Google Scholar
  49. Tatsuno, T., Tsukioka, M., Sakai, Y., and Asami, Y. (1955). The toxic substance in yellowed rice. Chem. Pharm. Bull. 3, 476.Google Scholar
  50. Thacker, H.L., Carlton, W.W., and Sansing, G.A. (1977). Citrinin mycotoxicosis in the guinea pig. Food Cosmet. Toxicol. 15, 553–561.Google Scholar
  51. Timonin, M.I. (1942). Another mould with anti-bacterial ability. Science 96, 494.Google Scholar
  52. Timonin, M.I. and Rouatt, J.W. (1944). Production of citrinin by Aspergillus species of the Candidus group. Can. J. Publ. Health 35, 80.Google Scholar
  53. Ueno, Y. and Kubota, K. (1976). DNA-attacking ability of carcinogenic mycotoxins in recombination-deficient mutant cells of Bacillis subtilis. Cancer Res. 36, 445–451.Google Scholar
  54. Wang, Y. and Ting, H.S. (1949). Colorimetric determination of citrinin. Chem. Abstr. 43, 4723f.Google Scholar
  55. Wang, Y. and Ting, H.S. (1951). Metabolism of citrinin. II. Adsorption, retention and excretion of citrinin. Chem. Abstr. 45, 3009d.Google Scholar
  56. Wang, Y., Ting, H.S., and Mann, W. (1950). Metabolism of citrinin. I. Determination of free citrinin in blood. Clin. J. Physiol. 17, 259–270.Google Scholar
  57. Wilson, D.M., Tabor, W.H., and Trucksess, M.W. (1976). Screening method for the detection of aflatoxin, ochratoxiri A, zearalenone, penicillic acid, and citrinin. J. Assoc. Off. Anal. Chem. 59, 125–127.Google Scholar
  58. Zimmerli, B., Dick, R., and Banmann, V. (1989). High performance liquid chromatographic determination of citrinin in cereals using an acid buffered silica gel column. J. Chromatogr. 462, 406–410.Google Scholar

Copyright information

© Springer Science+Business Media New York 1994

Authors and Affiliations

  • Bonnie B. Dunn
    • 1
  • Leonard Friedman
    • 2
  1. 1.Positron Emission Tomography DepartmentNational Institutes of HealthBethesdaUSA
  2. 2.Division of Toxicological StudiesCenter for Food Safety and Applied Nutrition, Food and Drug AdministrationBeltsvilleUSA

Personalised recommendations