Abstract
The short-term oral toxicity of the food and cosmetics additive citral was studied in Wistar albino and Long Evans hooded rats with special emphasis on the effects upon blood coagulation and hepatic enzymes. The maximum tolerated, non-lethal dose was found to be 2.4 g/kg by the dietary and the gastric intubation routes of administration. Citral was found to produce a slight prolongation of the thrombotest clotting time in hooded but not albino rats. Citral also produced dose-related hepatomegaly by initial hyperplasia followed by hypertrophy. Histopathologically, citral caused periportal accumulation of lipid and centrilobular depletion of glycogen. Co-administration of citral and warfarin produced 30% mortality in the hooded rats with no effect in the albino rats. Pretreatment with citral increased the metabolism of warfarin, especially in albino rats. It is suggested that albino rats have a higher control level of cytochrome P-450 than hooded rats, but that it is more inducible in hooded rats. Due to structural analogy to fatty acids and the hepatic lipid accumulation, proliferation of hepatic peroxisomes and mitochondria with induction of β-oxidation was studied in both strains of rat following citral administration. Citral did indeed induce peroxisomal β-oxidation with proliferation of peroxisomes, smooth endoplasmic reticulum and mitochondria; however, there was no hypolipidaemic activity. It is thought that citral may be unique in this respect. It is suggested that the β-oxidation is important in the metabolism of citral and other peroxisome-proliferating compounds. Citral also caused induction of ω and ω-1 -oxidation; this may also be important with regard to citral metabolism.