Preliminary evaluation of the human relevance of respiratory tumors observed in rodents exposed to naphthalene

Regulatory Toxicology and Pharmacology : RTP
Vincent J PiccirilloW James Bover

Abstract

Inhalation bioassays in mice and rats exposed to naphthalene (NA) show incidences of lung and nasal cancer, respectively. This paper describes a preliminary mode of action (MOA)/human relevance (HR) framework for NA. Species differences in both carcinogenic and cytotoxic responses between the rodent and human have been noted based on qualitative and quantitative differences in metabolism. Some occur at the initial oxidation of NA in the rat through CYP2F, versus CYP2A13 metabolism in the human respiratory system and which results in a difference in the specific naphthoquinone formed. Normally, subsequent reactive metabolites are then conjugated through glutathione, but high dose exposures, as in the rat bioassay, result in glutathione depletion, and the availability of 1,2-naphthoquinone for other conjugation. In the rat nose, it is proposed that a naphthoquinone imine is formed via a species and site-specific aryl amidase acting on an amino acid conjugate of the quinone. Such a quinone imine is believed to be the active agent in Alachlor and phenacetin, resulting in the same profile of respiratory tumors in the rat as NA. Based on the MOA and the limited epidemiological data indicating no human evidence of nasal or lung tumor ...Continue Reading

References

Jul 1, 1973·Journal of Comparative and Physiological Psychology·J Le MagnenS Tallon
Jul 1, 1982·Chemico-biological Interactions·D L WarrenA R Buckpitt
Jul 21, 1999·Human & Experimental Toxicology·W F HeydensM A Martens
Jul 23, 1999·Toxicological Sciences : an Official Journal of the Society of Toxicology·B A WetmoreM B Genter
Oct 13, 2000·Regulatory Toxicology and Pharmacology : RTP·T GreenM J Clapp
Jun 9, 2001·Chemico-biological Interactions·T GreenR Moore
Dec 18, 2002·Drug Metabolism and Disposition : the Biological Fate of Chemicals·John-Michael SauerKarl A Desante
Dec 19, 2002·Drug Metabolism Reviews·A BuckpittC Plopper
Oct 23, 2003·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Jill S WarringtonDavid J Greenblatt
Jan 16, 2004·The Journal of Pharmacology and Experimental Therapeutics·R Michael BaldwinAlan R Buckpitt
Jan 20, 2004·Critical Reviews in Toxicology·Samuel M CohenPenelope A Fenner-Crisp
Jan 20, 2004·Critical Reviews in Toxicology·M E Bette MeekDorothy E Patton
Jan 23, 2004·Toxicological Sciences : an Official Journal of the Society of Toxicology·Samuel M CohenDorothy Patton
Aug 21, 2004·Toxicological Sciences : an Official Journal of the Society of Toxicology·A J PhimisterC G Plopper
Oct 26, 2005·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Taehyeon M ChoErnest Hodgson
Nov 23, 2006·Critical Reviews in Toxicology·Alan R BoobisWilliam Farland
Nov 28, 2006·Expert Opinion on Drug Metabolism & Toxicology·Marcella MartignoniRuben de Kanter
Dec 21, 2006·Toxicologic Pathology·Alan M JeffreyGary M Williams
Nov 6, 2007·Regulatory Toxicology and Pharmacology : RTP·David Brusick
Jan 15, 2008·Regulatory Toxicology and Pharmacology : RTP·Kenneth T BogenCurtis J Omiecinski
Jan 16, 2008·Regulatory Toxicology and Pharmacology : RTP·David BrusickJames A Swenberg
Jun 21, 2008·Risk Analysis : an Official Publication of the Society for Risk Analysis·Kenneth T Bogen
Jan 19, 2010·Veterinary Pathology·D L BrownJ M Cullen
Feb 17, 2010·Regulatory Toxicology and Pharmacology : RTP·Brian MageeJohn Hinz
Dec 21, 2011·Inhalation Toxicology·Darol E DoddRodney A Miller
Jan 19, 2012·Toxicological Sciences : an Official Journal of the Society of Toxicology·Leslie RecioGregory L Kedderis
Jul 26, 2012·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Liang LiDafang Zhong

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Citations

Feb 25, 2014·Toxicological Sciences : an Official Journal of the Society of Toxicology·Joseph A CichockiJohn B Morris
Jul 24, 2015·Critical Reviews in Toxicology·Lisa A BaileyLorenz R Rhomberg
Apr 15, 2015·Critical Reviews in Toxicology·Richard H MckeeJuan-Carlos Carrillo
Dec 24, 2013·Chemico-biological Interactions·Gregory L KedderisLeslie Recio
Aug 14, 2019·Toxicological Sciences : an Official Journal of the Society of Toxicology·Thomas Hill Iii, Rory B Conolly
Jan 27, 2019·Toxicology Letters·Sarah A CarrattLaura S Van Winkle

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