Cancer risk assessment for 1,3-butadiene: data integration opportunities

Chemico-biological Interactions
R Julian Preston

Abstract

The US Environmental Protection Agency recently released its new guidelines for carcinogen risk assessment together with supplemental guidance for assessing susceptibility from early-life exposure to carcinogens. In particular, these guidelines encourage the use of mechanistic data in support of dose-response characterization at doses below those at which an increase in tumor frequency over background levels might be detected. In this context of the utility of mechanistic data for human cancer risk assessment, the International Life Sciences Institute (ILSI) has developed a human relevance framework (HRF) that can be used to assess the plausibility of a mode of action (MoA) described for animal models operating in humans. The MoA is described as a sequence of key events and processes that result in an adverse outcome. A key event is a measurable precursor step that is in itself a necessary element of the MoA or is a bioindicator for such an element. A number of cellular and molecular perturbations have been identified as key events whereby DNA-reactive chemicals can produce tumors. These include DNA adducts in target tissues, gene mutations and/or chromosomal alterations in target tissues and enhanced cell proliferation in targ...Continue Reading

References

Jan 20, 2004·Critical Reviews in Toxicology·M E Bette MeekDorothy E Patton
Jan 19, 2006·Critical Reviews in Toxicology·R Julian Preston, Gary M Williams

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Citations

Feb 24, 2010·Toxicological Sciences : an Official Journal of the Society of Toxicology·Nadia I GeorgievaJames A Swenberg
Oct 18, 2011·Toxicological Sciences : an Official Journal of the Society of Toxicology·Gunnar BoysenJames A Swenberg
Jun 11, 2009·Risk Analysis : an Official Publication of the Society for Risk Analysis·Alexandre Roger Raymond Péry, Frederic Yves Bois
Nov 3, 2009·Risk Analysis : an Official Publication of the Society for Risk Analysis·Roberta L GrantMichael Honeycutt
Mar 6, 2007·Chemico-biological Interactions·Matthew W HimmelsteinR Jeffrey Lewis
Sep 28, 2010·Critical Reviews in Toxicology·Richard J AlbertiniMichael L Gargas
Sep 28, 2010·Critical Reviews in Toxicology·Christopher R KirmanMichael L Gargas
Jun 27, 2019·Rapid Communications in Mass Spectrometry : RCM·Gunnar BoysenArnon Nagler

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