Anticoagulant Rodenticides - Organic Pollutants: An Ecotoxicological Perspective - page 221

however, that because they possess ionizable hydroxyl groups, water solubility is
pH dependent. With brodifacoum, for example, water solubilities are 3.8 × 10 −3 and
10 mg/L at pH values of 5.2 and 9.3, respectively. An increase in pH encourages
some ionization, and solubility increases accordingly.

11.3 metaBoLISm of antIcoaguLant rodentIcIdeS
Metabolism has been studied in more detail for warfarin than for other related
rodenticides. The metabolism of warfarin appears to be essentially similar to that
of related compounds, and will be taken as a model for the group. Two main types
of primary metabolic attack have been recognized: (1) monooxygenase attack upon
diverse positions on the molecule to yield hydroxy metabolites and (2) conjugation
of the hydroxyl group to yield glucuronides. The hydroxy metabolites formed by
monooxygenase attack are also subject to conjugation in the case of warfarin and
related ARs. More than one form of P450 is involved in warfarin metabolism. Hepatic
cytochrome P450 2 C9 appears to be the most important of them, and is involved
in warfarin hydroxylation in both rats and humans (Aithal et al. 1999; Wadelius
and Pirmohamed 2007). Other forms, including CYP2e1, CYP2c13, CYP2A2, and
CYP3a3, have been implicated in resistance mechanisms to ARs (see Section 11.6).
In a study of metabolism of 14C-flocoumafen by the Japanese quail (Huckle et
al. 1989), biotransformation was extensive and rapid, with eight metabolites detected
in excreta. The elimination of radioactivity from the liver of Japanese quail was
biphasic (Figure 11.2). After an initial period of rapid elimination, there followed a

10

1

10 -1

0 0 0 0 0 0 0
Time (days)

70 80 90 100 110 120

fIgure 11.2 Loss of flocoumafen residues from quail liver. Depletion of radioactivity from
Japanese quail after a single oral dose (14 mg/kg). Data are presented as microgram equiva-
lents of f per gram of tissue and are mean values of two animals. Data collected at day 7 and
day 12 were from four animals and three animals, respectively (from Huckle et al. 1989).