Biliary hyperplasia and carcinogenesis in chronic liver damage induced in rats by phomopsin.

Phomopsin, a hexapeptide mycotoxin contaminant of lupin plant and seed materials, was administered subcutaneously to adult rats at a daily dose rate of 30 micrograms/kg body weight (approximately 0.005 median lethal dose) for 2, 6 or 17 wks and the development of liver damage was observed during treatment and for up to 2 yr after. All rats injected for 17 wks developed permanent liver damage characterized by nodular cirrhosis and extensive biliary hyperplasia. Cholangiomas developed in 60% of these rats and cholangiocarcinomas and hepatocellular carcinomas in 13%. Similar effects were produced in some rats injected for 6 wks, while in others the cessation of treatment was followed by almost complete regression of the liver lesions. Livers damaged by 2 wks of injection had fully recovered within a few wks. The permanence of the liver damage is relevant to the management of stock exposed seasonally to the toxin, while its carcinogenic potential in rats, although not high, indicates the need for monitoring of the phomopsin content of lupin seed or flour prepared for human consumption.