Agriculture Reference
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substituents at position 2 in these nitroheterocyclic compounds has been
studied over a wide range of molecules, and the active compounds have been
classified into the azomethine (-CH=N-), vinyl (-CH=CH-), and heterocyclic
groups [13].
As previously mentioned, the main compounds of this group, FZD, FTD,
NFT, NFS and NFZ, are rapidly metabolized in vivo, leading to a significant
decrease of their parent compounds levels in plasma. Studies have been shown
that the metabolites of nitrofurans establish covalent bonds with cellular
macromolecules, particularly with proteins.
The toxicological significance of bound residues depends on a number of
factors, including the release of the residue in a biologically active form during
digestion of tissue (e.g. liver, meat), the bioavailability of the released residue
which is determined by its absorption from the gastrointestinal tract, and any
particular toxicity arising from the binding of the metabolites to amino acids or
peptides [34].
For furazolidone it was shown that the detection of the parent drug is not
feasible [19] because the respective residues are highly unstable in vitro and
exhibit a very short half-life in vivo and in post-mortem tissues. The drug is
therefore not found as a residue or only at very low concentrations at zero
withdrawal time. It has been proved that tissue bound metabolites are formed
but, however, the free side chain of furazolidone, the molecule AOZ, is more
stable. It can be detected and measured in tissues of pigs for up to 7 weeks
after withdrawal of drug [20] thus being a more suitable marker residue for
furazolidone. By analogy, side-chain moieties of other metabolites of
furaltadone, nitrofurantoin, nifursol and nitrofurazone are the molecules
AMOZ, AHD, DNSH and SEM respectively and serve as marker residues for
these drugs. See Figure 1 for a summary of the main nitrofurans and
respective metabolites [10].
The total residue and metabolism study provides the necessary
information to determine the appropriate marker residue (the compound used
to monitor the depletion of total residue in a food animal tissue) and to
determine the target tissue (generally, the edible tissue from which residue
deplete most slowly). Additional information derived from these studies
includes 1) establishing the marker residue to total residue ratio that will
ultimately be used to calculate the tolerance (maximum residue limit) in the
target tissue; and 2), a metabolism profile in the food-producing animal for
comparison with the metabolism profile of the toxicological species. Residue
depletion studies using non-radiolabelled drug provide additional information
necessary for developing tolerances and withdrawal times [35].
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