The NAs are relatively stable compounds but are activatedmetabolically,
via hydroxylation catalyzed by enzymes of the cytochrome
P450 family, and thereby they become carcinogenic. NDMA and
NDEA are the most studied NA with regard to toxicity. Both NDMA
and NDEA are carcinogenic in all of the animals they have been
tested. The target organs are liver, respiratory tract and kidney (IARC,
1978). Because the NA needs to be metabolically activated to become
carcinogenic the target organs are those with activity of the P450
enzyme with affinity for the relevant NA. E.g. NDMA is readily metabolized
in the rat liver, less in rat kidney and lung, and consequently
liver tumors are the primary endpoint in rats (Shank, 1975). Total
liver tumors were found to be the most sensitive endpoint for rats
exposed to NDMA (Zeilmaker et al., 2010).