Suzanne D. E. Held

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Furan is a volatile solvent and chemical intermediate that is hepatotoxic and hepatocarcinogenic in rats and mice but is not mutagenic or DNA-reactive. Furan hepatotoxicity requires cytochrome P450 2E1 bioactivation to cis-2-butene-1,4-dial. We have previously shown that furan biotransformation kinetics determined with freshly isolated rat hepatocytes in(More)
Furan is both hepatotoxic and hepatocarcinogenic in rats. The kinetics of furan biotransformation by male F-344 rats were studied in vivo and in vitro in order to understand target tissue dosimetry. A physiologically based pharmacokinetic (PBPK) model for furan in rats was developed from gas uptake studies using initial furan concentrations of 100, 500,(More)
Furan, a rodent hepatotoxicant and hepatocarcinogen, produced incubation time- and concentration-dependent decreases in the glutathione (GSH) content and viability of freshly isolated F-344 rat hepatocytes in vitro. Since furan itself did not significantly react with GSH, these data indicate the formation of a reactive metabolite of furan in hepatocyte(More)
The metabolism of radiolabeled monochloronitrobenzene isomers was compared in isolated hepatocytes and hepatic subcellular fractions from male Fischer-344 rats. 2-Chloronitrobenezene was converted by isolated hepatocytes to 2-chloroaniline, 2-chloroaniline-N-glucuronide, and S-(2-nitrophenyl)glutathione in approximately equal quantities (13-19% of the added(More)
The dose dependence of the urinary excretion of acrylonitrile (ACN) metabolites was studied after oral administration of [2,3-14C]ACN to male F-344 rats (0.09 to 28.8 mg/kg) and male B6C3F1 mice (0.09 to 10.0 mg/kg). Urine was the major route of excretion of ACN metabolites (77 to 104% of the dose), with less than 8% of the dose excreted in the feces.(More)
Maternal undernutrition during pregnancy alters the physiology, behaviour and cognitive abilities of the offspring in sheep. Undernutrition restricted to the time around conception alters the physiology of the offspring, but effects on the behaviour and cognitive abilities are unknown. We studied the effects of mild periconceptional undernutrition in sheep(More)
The direct acting mutagen 2-cyanoethylene oxide (CEO), formed in the liver by oxidation of acrylonitrile (ACN), is thought to mediate the extrahepatic carcinogenic effects of ACN in rats. This study determined the tissue distribution of CEO (3 mg/kg p.o.) in F-344 rats and B6C3F1 mice. Radioactivity from [2,3-14C]CEO was widely distributed in the major(More)
The physiologically based dosimetry description for acrylonitrile (ACN) and its mutagenic epoxide metabolite 2-cyanoethylene oxide (CEO) in F-344 rats (M. L. Gargas, M. E. Anderson, S.K.O. Teo, R. Batra, T. R. Fennell, and G. L. Kedderis, 1995, Toxicol. Appl. Pharmacol. 134, 185-194) has been refined to include a physiological stomach compartment and the(More)
Laboratory rabbits kept in barren 'traditional' cages tend to develop stereotypic behaviours and bone deformities. We have used an alternative regime, housing adult does as groups of four or five in floor pens (2.5-3 m2) supplied with hiding places and bedding. High- and low-ranking members of each group were identified, and their immunological status(More)