• Aldose reductase inhibitor
• Cancer preventive

• Metabolism: The major urinary metabolite of CTN is dihydrocitrinone. (A2982)
• Uses/Sources: Citrinin is a mycotoxin originally isolated from Penicillium citrinum. It has since been found to be produced by a variety of other fungi which are used in the production of human foods such as grain, cheese, sake and red pigments. Citrinin is also produced by a variety of other fungi including Aspergillus niveus, Aspergillus ochraceus, Aspergillus oryzae, Aspergillus terreus, Monascus ruber, Monascus purpureus, and Penicillium camemberti. (L1958)
• Health Effects: Citrinin acts as a nephrotoxin. It causes mycotoxic nephropathy in livestock and has been implicated as a cause of Balkan nephropathy and yellow rice fever in humans. Though the kidney is the major target organ of citrinin toxicity, other target organs such as liver and bone marrow have also been reported. (L1958, A2982)
• Symptoms: Irritation of the eyes, skin, or respiratory tract, depending on the route of exposure. May produce an allergic hypersensitivity dermatitis or asthma with bronchospasm and wheezing with chronic exposure. (A704)
• Treatment: In case of oral exposure, consider gastric lavage and/or activated charcoal. Immediate dilution with milk or water may be of benefit in caustic or irritant chemical ingestions. In case of inhalation, consider moving patient to frsh air. Maintain ventilation, and oxygenation. In case of eye or skin contact, consider decontamination of the exposed region. (A704)
• Route of Exposure: Oral, dermal, inhalation, and parenteral (contaminated drugs). (A3101)

• Carcinogenicity: 3, not classifiable as to its carcinogenicity to humans. (L135)
• Toxicity: LD50: 112 mg/kg (Oral, Mouse) (A709) LD50: 50 mg/kg (Oral, Rat) (A2982) LD50: 67 mg/kg (Subcutaneous, Rat) (A2982)

Citrinin produces proximal tubular necrosis, but only after transport into proximal tubular cells. It utilizes the organic anion transporter for entry into the cells, a transporter probably important physiologically for moving metabolic substrates into cells. Citrinin is also cytotoxic and increases formation of reactive oxygen species by stimulating the production of superoxide anion in the respiratory chain. It further potentiates this oxidative stress by modifying antioxidative enzymatic defences by inhibiting GSSG-reductase and transhydrogenase. Citrinin also alters mitochondrial function and permeability, decreasing Ca2+ accumulation in the matrix by inhibiting its influx and increasing its efflux. This is thought to induce apoptosis through the release of cytochrome c from the mitochondria, which is known to activate apoptosis-regulating caspases 3, 6, 7, and 9. Citrinin inhibits respiration by interfering with the NADH oxidase and NADH cytochrome c reductase involved with complex I of the respiratory chain. Mycotoxins are often able to enter the liver and kidney by human organic anion transporters (hOATs) and human organic cation transporters (hOCTs). They can also inhibit uptake of anions and cations by these transporters, interefering with the secretion of endogenous metabolites, drugs, and xenobiotics including themselves. This results in increased cellular accumulation of toxic compounds causing nephro- and hepatotoxicity. (A707, A2860, A2982, A3014)