In vitro kinetics of styrene and styrene oxide metabolism in rat, mouse, and human.

Styrene oxide (SO), a labile metabolite of styrene, is generally accepted as being responsible for any genotoxicity associated with styrene. To better define the hazard associated with styrene, the activity of the enzymes involved in the formation (monooxygenase) and destruction of SO (epoxide hydrolase and glutathione-S-transferase) were measured in the liver and lungs from naive and styrene-exposed male Sprague-Dawley rats and B6C3F1 mice (three daily 6-h inhalation exposures at up to 600 ppm styrene) and Fischer 344 rats (four daily 6-h inhalation exposures at up to 1000 ppm styrene), and in samples of human liver tissue. Additionally, the time course of styrene and SO in the blood was measured following oral administration of 500 mg styrene/kg body weight to naive Fischer rats and rats previously exposed to 1000 ppm styrene.

Determination of styrene-7,8-oxide in whole rat blood by gas chromatography-mass spectrometry.

A rapid and selective method for the determination of styrene-7,8-oxide (SO) in whole blood has been developed. Blood samples as small as 0.1 ml are extracted once with benzene containing phenyl propylene oxide as an internal standard.

Determination of the effect of tridiphane on the pharmacokinetics of [14C]-atrazine following oral administration to male Fischer 344 rats.

The absorption, distribution, metabolism and excretion of [14C]-atrazine was studied in male Fischer 344 rats administered a 30 mg [14C]-atrazine/kg of body weight oral dose with or without pretreatment with a non-radiolabeled oral dose of 60 mg tridiphane/kg of body weight. The objective of this study was to determine whether tridiphane had any meaningful effect on the pharmacokinetics and/or metabolism of atrazine in the rat. The 14C plasma time-course exhibited a mono-exponential decrease with an absorption and elimination half-life of approximately 3 h and 11 h, respectively for both treatment groups.

Metabolism and disposition of ethylene carbonate in male Fischer 344 rats.

Ethylene carbonate (EC) has a toxicity profile which resembles that of ethylene glycol (EG). To determine whether the toxicity of EC could be explained on the basis of its metabolism to EG, male Fischer 344 rats were given 200 mg/kg of uniformly labeled [14C]EC in water by gavage and the disposition of the radiolabel was then followed for 72 hr. EC was rapidly metabolized, with approximately 57 and 27% of the administered dose eliminated in the expired air as 14CO2 and in the urine, respectively; the remainder was found in the carcass.

Metabolism and disposition of propylene glycol monomethyl ether (PGME) beta isomer in male rats.

Male Fischer 344 rats were given a single po dose of approximately 1 or 8.7 mmol/kg of radiolabelled propylene glycol monomethyl ether (PGME) beta isomer (2-methoxy-1-propanol). After dosing, expired air, excreta, and tissues were analyzed for 14C activity and metabolites in urine were isolated and identified.