The amino sugar galactosamine (galN) induces alterations in the hepatic uridine nucleotide pool and
has been widely used as a model of human viral hepatitis. Histopathological and clinical chemistry
analyses of a cohort of rats following administration of galN revealed extreme interindividual variability
in the extent of the toxic response which enabled classification of ‘responder’ and ‘non-responder’
phenotypes. An integrative metabolic profiling approach was applied to characterize biomarkers of
exposure to galN in urine, serum, feces and liver from responders and non-responders. The presence
of N-acetylglucosamine and galN in the urine correlated with the occurrence and extent of toxic
response. Conversely, the novel identification of galN-pyrazines in the feces of non-responders and
their virtual absence in the feces of responders suggests an alternative means of distribution and
metabolism of galN in non-responders. The absence of the UDP-hexosamines in the liver of
non-responders further supports differential metabolism of galN and suggests an ability of non-
responders to avoid UDP-glucose depletion. An observed disturbance of gut microbial derived
metabolites in the urine and feces of non-responders may suggest a role of the microflora in reducing
the effective dose of galN. This systems level metabonomic approach has provided new mechanistic
insights into differential response to galN and is widely applicable to the study of interindividual variation
in metabolism for any xenobiotic intervention.