Literature review on the genotoxicity, reproductive toxicity, and carcinogenicity of ethyl methanesulfonate

Toxicology Letters
Elmar GockeThomas Pfister

Abstract

In order to assess the risk of patients being exposed to an anti-AIDS medication contaminated with EMS we have performed in depth genotoxicity, general toxicity and DMPK investigations. The results of these studies are reported in the accompanying papers of this issue. Prior to starting our investigations we searched the literature for toxicity data on this well established mutagen with specific attention to dose-response relations in in vivo genotoxicity studies, since, obviously, in vivo data are pivotal for risk assessment. There are numerous published in vivo genotoxicity studies on EMS, with generally 50mg/kg - or higher - being the minimal dose used. The dose of 50mg/kg induced effects in some, but not all studies, while the dose of 100mg/kg was clearly positive in most studies, except for heritable mutations where a single dose of 100mg/kg was not observed to induce measurable effects in post-meiotic stages and even the maximal dose of 250 mg/kg was negative in pre-meiotic stages of male germ cell development. For somatic cells, NOEL values could not be derived for any of the endpoints studied. Although a large number of genotoxicity studies are available, none of the studies was sufficiently detailed to allow unambiguou...Continue Reading

References

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Citations

Jul 20, 2010·Oncogene·M M Lovric, C J Hawkins
Dec 18, 2010·Mutagenesis·Azeddine ElhajoujiMicheline Kirsch-Volders
Jan 15, 2016·Environmental and Molecular Mutagenesis·Steven M BryceStephen D Dertinger
Feb 23, 2013·Toxicology in Vitro : an International Journal Published in Association with BIBRA·Maja ŠrutGöran I V Klobučar
Jan 1, 2013·Toxicology in Vitro : an International Journal Published in Association with BIBRA·S SwitallaK Sewald
Mar 18, 2017·Journal of Toxicology and Environmental Health. Part a·Erico R CarmonaClaudio Inostroza-Blancheteau
Feb 9, 2016·AIDS·David C BoettigerUNKNOWN Data collection on Adverse events of Anti-HIV Drugs (D:A:D) study group
May 17, 2017·Critical Reviews in Toxicology·Alan BoobisHeli Miriam Hollnagel
Sep 4, 2014·Environmental Science & Technology·Yukako KomakiMichael J Plewa
Feb 19, 2014·Environmental and Molecular Mutagenesis·Xuefei CaoRobert H Heflich
Oct 27, 2016·AIDS·Mira HleyhelUNKNOWN on behalf the ANRS French Perinatal Cohort study Group
Apr 4, 2017·Environmental and Molecular Mutagenesis·Steven M BryceStephen D Dertinger
Aug 31, 2019·Oxidative Medicine and Cellular Longevity·Serena GalatiAnnamaria Buschini

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