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International Journal of Toxicology
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Article

In Vitro Rat Hepatic Metabolism of n-Alkanes: Nonane, Decane, and Tetradecane

Sathanandam S. Anand

Department of Pharmaceutical and Biomedical Sciences, College of Pharmacy, University of Georgia, Athens, Georgia, USA

Jerry L. Campbell
Jeffrey W. Fisher

Department of Environmental Health Science, College of Public Health, University of Georgia, Athens, Georgia, USA

Correspondence: Address correspondence to Sathanandam S. Anand, DuPont Haskell Laboratory for Health and Environmental Sciences, P.O. Box 50, 1090 Elkton Road, Newark, DE 19714, USA. E-mail:satheesh.s.anand{at}usa.dupont.com

Jet propellant 8 (JP-8) jet fuel is a complex mixture of aromatic and aliphatic hydrocarbons. The aim of this study was to determine in vitro metabolic rate constants for semivolatile n-alkanes, nonane (C9), decane (C10), and tetradecane (C14), by rat liver microsomal oxidation. The metabolism was assessed by measuring the disappearance of parent compound by gas chromatography. Various concentrations of n-alkanes were incubated with liver microsomes from adult male F-344 rats. Nonlinear kinetic constants for nonane and decane were V max (nmol/mg protein/min) = 7.26 ± 0.20 and 2.80 ± 0.35, respectively, and K M (µM) = 294.83 ± 68.67 and 398.70 ± 42.70, respectively. Metabolic capacity as assessed by intrinsic clearance (V max/K M) was ~four-fold higher for nonane (0.03 ± 0.005) than for decane (0.007 ± 0.001). There was no appreciable metabolism of tetradecane even with higher microsomal protein concentration and longer incubation time. These results show a negative correlation between metabolic clearance and chain length of n-alkanes. These metabolic rate constants will be used to update existing physiologically based pharmacokinetic (PBPK) models for nonane and decane as part of developing a PBPK model for JP-8.

Key Words: n-Alkanes • Decane • In Vitro Metabolism • Nonane • Rat • Tetradecane

International Journal of Toxicology, Vol. 26, No. 4, 325-330 (2007)
DOI: 10.1080/10915810701490075
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