Figure 1: Metabolism of Benzo (a) pyrene
To establish the validity of a test system, it is critical to
demonstrate target tissue exposure. This is especially true in cases
where there is an adverse outcome in the in vitro mammalian cell
bases assay (ICH S2(R1), 2012). This evidence of target tissue exposure
can be demonstrated either by showing cytotoxicity to the target tissue
or by directly measuring a drug or related toxic metabolite in the
target tissue.
In vivo , assessment of cytotoxicity can be conducted by
histopathological evaluation of the target tissue or by analyzing
changes in the blood biochemistry values.
The direct measurement of drug-related substances can be performed in
blood, plasma, or target tissues. Autoradiographic techniques can be
used to assess tissue exposure to these substances. ((ICH S2(R1), 2012;
Kirkland et al., 2019). Demonstration of target tissue exposure is
critical in validating a NAM that can be used as a follow-up to anin vitro assay. Therefore, the goal of this study was to verify
that in CEGA tested chemicals can reach the fetal chicken liver (target
organ) following administration into the air sac of the fertilized egg
at sufficient levels to produce genotoxic effect(s), and to form of
sufficient amounts of reactive metabolite(s) from a parent compound upon
reaching the target tissue.