Physiologically based biokinetic (PBBK) modeling of safrole bioactivation and detoxification in humans as compared with rats

Toxicological Sciences : an Official Journal of the Society of Toxicology
Erryana MartatiAns Punt

Abstract

A physiologically based biokinetic (PBBK) model for the alkenylbenzene safrole in humans was developed based on in vitro- and in silico-derived kinetic parameters. With the model obtained, the time- and dose-dependent formation of the proximate and ultimate carcinogenic metabolites, 1-hydroxysafrole and 1-sulfooxysafrole in human liver were estimated and compared with previously predicted levels of these metabolites in rat liver. In addition, Monte Carlo simulations were performed to predict interindividual variation in the formation of these metabolites in the overall population. For the evaluation of the model performance, a comparison was made between the predicted total amount of urinary metabolites of safrole and the reported total levels of metabolites in the urine of humans exposed to safrole, which adequately matched. The model results revealed no dose-dependent shifts in safrole metabolism and no relative increase in bioactivation at dose levels up to 100mg/kg body weight/day. Species differences were mainly observed in the detoxification pathways of 1-hydroxysafrole, with the formation of 1-oxosafrole being a main detoxification pathway of 1-hydroxysafrole in humans but a minor pathway in rats, and glucuronidation of ...Continue Reading

References

Feb 1, 1977·Toxicology·M S BenedettiA L Broillet
Nov 1, 1987·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·A AnthonyR L Smith
Mar 1, 1983·Acta Pharmacologica Et Toxicologica·J Klungsøyr, R R Scheline
Oct 1, 1981·Food and Cosmetics Toxicology·C IoannidesD V Parke
Oct 1, 1980·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·M DelaforgeJ P Morizot
Nov 1, 1995·Journal of Oral Pathology & Medicine : Official Publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology·Y C KoC C Tsai
Jul 1, 1997·Toxicology and Industrial Health·R P BrownR P Beliles
Mar 26, 2002·Science·UNKNOWN AAAS Committee on Scientific Freedom and Responsibility
Oct 26, 2002·Archives of Environmental Contamination and Toxicology·M J W ChangL L Hsieh
Nov 5, 2003·Critical Reviews in Toxicology·Agneta Falk FilipssonKatarina Victorin
Jan 20, 2004·Critical Reviews in Toxicology·M E Bette MeekDorothy E Patton
Aug 18, 2004·Chemical Research in Toxicology·Yune-Fang UengLi-Kang Ho
Sep 21, 2004·Chemical Research in Toxicology·Suzanne M F JeurissenIvonne M C M Rietjens
Mar 22, 2005·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Yune-Fang UengMing-Jaw Don
Aug 12, 2006·Regulatory Toxicology and Pharmacology : RTP·Tammie R CovingtonHarvey J Clewell
Feb 28, 2007·Chemico-biological Interactions·Robert S DeWoskin
Sep 7, 2007·Toxicological Sciences : an Official Journal of the Society of Toxicology·Xiaofei ZhangCurtis C Dary
Jun 10, 2008·Toxicology and Applied Pharmacology·Ans PuntIvonne M C M Rietjens
Jul 24, 2008·The Journal of Organic Chemistry·Steven R AngleFook S Tham
May 19, 2009·Toxicological Sciences : an Official Journal of the Society of Toxicology·Ans PuntIvonne M C M Rietjens
Sep 11, 2010·Toxicology in Vitro : an International Journal Published in Association with BIBRA·Ala A A Al-SubeihiIvonne M C M Rietjens
Mar 31, 2011·Chemical Research in Toxicology·E MartatiI M C M Rietjens
Apr 27, 2011·Molecular Nutrition & Food Research·Ivonne M C M RietjensAns Punt

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Citations

Sep 21, 2012·Chemical Research in Toxicology·Suzanne J P L van den BergIvonne M C M Rietjens
Jan 31, 2016·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Abdalmajeed M AlajlouniIvonne M C M Rietjens
Feb 11, 2014·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Erryana MartatiIvonne M C M Rietjens
Jun 24, 2016·Archives of Toxicology·Amer J Al-MalahmehIvonne M C M Rietjens
Jun 6, 2017·Food Additives & Contaminants. Part A, Chemistry, Analysis, Control, Exposure & Risk Assessment·Abdalmajeed M AlajlouniIvonne M C M Rietjens
Oct 31, 2017·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·Ai-Hong YangXin He
Mar 14, 2019·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·Linlin HuFei Wu
Jun 17, 2020·Archives of Toxicology·Andrea HartwigGerhard Eisenbrand
Dec 8, 2017·Computational Toxicology·Elisabet BerggrenCatherine Mahony

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