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Title: Butylated Hydroxytoluene treatment prior to and during pregnancy in the rat : effects of subsequent exposure on hepatic biochemical and histological parameters in male offspring
Author: McFarlane, Mary
ISNI:       0000 0001 3624 0944
Awarding Body: University of Surrey
Current Institution: University of Surrey
Date of Award: 1994
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Butylated Hydroxytoluene (BHT), an antioxidant used as a food additive, has been reported to increase the incidence of hepatocellular adenomas and carcinomas in rats in a two generation feeding study although no such increases have been found in several one generation studies. BHT was fed to groups of 7 male and 50 female Wistar Albino rats (Fo generation) at doses of 0, 25, 100 or 500mg/kg body weight/ day prior to and throughout mating. Male pups from these matings (F1 generation) were weaned onto diets of 0, 25, 100 or 250mg/kg body weight/day BHT until 22 months post weaning. The effect BHT had on rat liver was examined both histologically and biochemically at various key stages in the animals development in an attempt to identify any changes which could account for the development of tumours. The results showed that pups bom to and suckled by dams fed 500mg/kg body weight/day BHT showed a marked failure to gain weight throughout weaning and there is indirect biochemical evidence which suggests that during this period these animals had significantly lower growth hormone levels than controls. Consistently lighter body weights were noted in high dose BHT fed animals when compared to age-matched controls. Biochemically, there were dose related increases in the induction of phase I and II metabolism enzymes throughout development, a similar spectrum being induced to that of Phenobarbitone. Histologically there was proliferation of smooth endoplasmic reticulum, centrilobular enlargement of the hepatocytes and an increase in the incidence of altered hepatic foci in animals at 22 months post weaning. Biochemical and histological examination of the BHT fed dams indicated that metabolic stress was clearly caused by the dual demands of lactation and BHT metabolism and that good quality milk production was probably sacrificed in preference to maintaining the dams detoxification system. General malnourishment and choline deficiency have been shown to increase the incidence of cancer in laboratory animals. Hence malnourishment of pups receiving high doses of BHT provides one possible explanation for the difference in cancer incidence between one and two generation studies.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Food additive; Carcinogenicity; Antioxidants