6029-87-4

Fulvine on reaching the liver is metabolically converted into a cellular toxin. Some of this toxin is retained in the hepatic cells, and produces necrosis and other cellular changes. Some of the toxin escapes to damage the vascular endothelium in the hepatic veins. This may take the form of endothelial proliferation with the later changes characteristic of veno-occlusion. Carried further, the escaping toxic metabolites reach the pulmonary tissues to produce vascular changes with increased capillary permeability and progressive oedema and cellular changes in the lungs, including the development of the big cells and the accumulation of mast cells^[2].

Rat: White SPF and conventional? Male and Female? weighing 50-65 g and 45-60 g^[1]
Administration: 30-45 mg/kg? neutralised aqueous solution by stomach tube? a single dose^[1]
Rat: Male and Female? weighing 40-80 g^[2]
Administration: 50 mg/kg? given by stomach tube? a single dose^[2]

Pathology change: The lungs were congested or oedematous and did not collapse when the chest was opened, showing petechiae or small dark red patches. Large often bloodstained, effusions were present in many rats. The liver appeared enlarged, dark red with a brownish tint, slightly granular and rubbery. The heart seemed enlarged; some rats had gastro-intestinal haemorrhage and prominent red lymph-glands. Varying degrees of ascites were present, and the ventral skin was often oedematous^[1]
.
Behavioral observation: Fulvine induced some developed difficulty in breathing and slowing or cessation of growth in rats^[1]
.
Histological analysis: Fulvine induced moderate ascites, well marked fibrous thickening of the central vein walls, endothelial proliferation and some perivascular centrilobular fibrosis with possibly partial venous occlusion^[2]
.