Abstract
The mechanism of sulfhemoglobin (SHb) formation and species differences in the formation of SHb and methemoglobin (MHb) were investigated. Erythrocytes or hemolysates were incubated with phenylhydroxylamine (PHA), aniline or its monochloro derivatives in the presence or absence of liver microsomes from various species (mouse, rat, guinea pig, rabbit, cat, dog and monkey). It was confirmed that SHb was produced by the N-hydroxy metabolites of aniline and its derivatives and was not induced via MHb. There was a relationship in SHb or MHb formation between the chemical structure of aniline derivatives and their N-hydroxy metabolite production activities in the animals (in vivo and in vitro). Species differences in the production rates of N-hydroxy metabolites from aniline and its derivatives by liver microsomes (as well as in the susceptibility of erythrocytes to N-hydroxy compounds) in vitro were not reflected in species differences in MHb and SHb formation in vivo.