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- W4205720612 endingPage "849" @default.
- W4205720612 startingPage "820" @default.
- W4205720612 abstract "Assessment of genotoxicity is a critical component of mode of action (MOA) analysis and carcinogen risk assessment due to its influence on quantitative risk extrapolation approaches. To date, clear guidance and expert consensus on the determination of a mutagenic MOA remains elusive, resulting in different estimates of carcinogenic risk for the same chemical among different stakeholders. Oral toxicity criteria for hexavalent chromium [Cr(VI)], for example, differ by orders of magnitude due largely to the interpretation of in vivo genotoxicity data. Herein, we review in vivo genotoxicity studies for Cr(VI) to inform the MOA for Cr(VI)-induced tumors observed in a two-year cancer bioassay in mice and rats exposed via drinking water. Overall, genotoxicity results in carcinogenic target tissues (viz., oral cavity and duodenum) are negative. Results in the intestine are consistent with imaging data indicating little to no chromium present in the crypt compartment following oral exposure. Positive genotoxicity results in nontarget tissues have been reported at high doses mostly following nonphysiological routes of exposure. Given the negative genotoxicity results in carcinogenic target organs from oral exposure to Cr(VI), there is scientific justification to support the use of nonlinear low-dose extrapolation methods in the derivation of oral toxicity criteria for Cr(VI). These results highlight important differences between genotoxicity testing for hazard identification purposes and quantitative risk assessment." @default.
- W4205720612 created "2022-01-25" @default.
- W4205720612 creator A5036645180 @default.
- W4205720612 creator A5067929281 @default.
- W4205720612 creator A5077954298 @default.
- W4205720612 creator A5086232184 @default.
- W4205720612 creator A5091600678 @default.
- W4205720612 date "2021-11-26" @default.
- W4205720612 modified "2023-10-01" @default.
- W4205720612 title "A review of mammalian <i>in vivo</i> genotoxicity of hexavalent chromium: implications for oral carcinogenicity risk assessment" @default.
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- W4205720612 doi "https://doi.org/10.1080/10408444.2021.2000934" @default.