Toxicokinetic Interaction between Hepatic Disposition and Pulmonary Bioactivation of Inhaled Naphthalene Studied Using Cyp2abfgs-Null and CYP2A13/2F1-Humanized Mice with Deficient Hepatic Cytochrome P450 Activity

Authors: Nataliia Kovalchuk, Qing-Yu Zhang, Jacklyn Kelty, Laura Van Winkle, Xinxin Ding

This study reported several novel findings related to the toxicokinetics of inhaled naphthalene, the ability of which to cause lung carcinogenesis in humans is a current topic for risk assessment. It shows the accumulation of naphthalene in the liver and lung in mice with compromised hepatic cytochrome P450 (P450) activity; the ability of tissue-stored naphthalene to redistribute to the circulation after termination of active inhalation exposure, prolonging exposure of target tissues to naphthalene; and the ability of non-CYP2ABFGS enzymes of the lung to bioactivate naphthalene. These results suggest potentially large effects of deficiencies in hepatic P450 activity on naphthalene tissue burden and bioactivation in human lungs

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