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• W2034334042 abstract "1. The objectives of the current studies were to evaluate the factors influencing the toxicokinetics of 1-bromopropane (1-BP) in rodents after intravenous (IV) and inhalation exposure.2. F-344 rats were administered 1-BP via IV bolus injection at 5 and 20 mg/kg and blood concentration determined versus time. F-344 rats and B6C3F1 mice were also exposed to starting inhalation concentrations 70, 240, 800 and 2700 ppm 1-BP in a closed gas uptake system and chamber 1-BP levels were monitored for 6 h. Plasma bromide concentrations were determined to estimate total metabolized dose. Rats were pretreated with chemical inhibitors of cytochrome P450 and glutathione (GSH) synthesis, prior to exposure to 1-BP at 800 ppm within inhalation chambers.3. Systemic clearance of 1-BP in rat was rapid and decreased with increasing dose. As inhalation chamber concentration of 1-BP increased, the terminal elimination rates decreased. Half-life of 1-BP in rats following inhibition of P450 (9.6 h) or depletion of GSH (4.1 h) increased relative to controls (2.0 h) at 800 ppm. The percentage of 1-BP metabolized decreased with increasing inhalation exposure. Hepatic levels of GSH were significantly lowered regardless of the exposure level in both rats and mice. Chamber concentration–time curves were fit to a two compartment model which was used to estimate metabolic rate constants.4. These data suggest that in rat, 1-BP clearance is saturable and that elimination is highly dependent on both P450 and GSH-dependent metabolism. This investigation in rodents may provide an understanding of interspecies differences in toxicokinetics and eventually aid translation of animal studies to human risk assessment." @default.
• W2034334042 created "2016-06-24" @default.
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• W2034334042 date "2014-01-17" @default.
• W2034334042 modified "2023-09-24" @default.
• W2034334042 title "Species and sex-dependent toxicokinetics of 1-bromopropane: the role of hepatic cytochrome P450 oxidation and glutathione (GSH)" @default.
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• W2034334042 doi "https://doi.org/10.3109/00498254.2013.879624" @default.
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