Incomplete absorption/rapid excretion |
Yes |
Cr(VI) is reduced to Cr(III) in GI tract; Cr(III) is poorly absorbed and excreted in the feces |
Binding to extracellular molecules |
Yes |
Cr(VI) reduction to Cr(III) is mediated by binding to organic molecules |
Dilution upon systemic absorption |
Not applicable |
Point of contact effect, systemic absorption is not applicable |
Low probability of reaching target stem cells |
Yes |
Cr(VI) may be partially or entirely reduced to Cr(III) before reaching the small intestine |
|
Unknown |
Cr(VI) might not directly contact or be absorbed by proliferative crypt cells of the small intestine |
Limited cellular uptake/efficient elimination at target site |
Yes |
Extracellular reduction of Cr(VI) to Cr(III) limits cellular uptake |
|
Unknown |
Crypt cells might not express necessary transporters for absorption |
Limited bioactivation or/efficient detoxification in target cells |
Unknown |
Intracellular reduction of Cr(VI) to Cr(III) might generate free radicals as well as Cr(III)-L species capable of interacting with DNA |
Reaction with non-DNA nucleophiles |
Unknown |
(See previous) |
Reaction with nonutilized regions of DNA |
Yes |
General phenomenon |
Efficient DNA repair |
Unknown |
Cr(VI) might induce epigenetic changes that inhibit DNA repair |
Low probability of producing transforming mutations in multiple critical genes |
Unknown |
Potential epigenetic factors |
Infrequency of neoplastic development from preneoplastic lesion |
Unknown |
Persistent diffuse hyperplasia might increase the chance of neoplastic development |