Anticoagulant Rodenticides - Organic Pollutants: An Ecotoxicological Perspective - page 225

and these links are necessary for the formation of blood clots. Because clotting pro-
teins turn over slowly (half-life of prothrombin in the rat is about 10 h), several days
will elapse after inhibition of the vitamin K cycle before the level of functional clot-
ting proteins is sufficiently low for severe hemorrhaging to occur. Typically, rats and
mice begin to die from hemorrhaging 5 days or more after exposure to ARs. Owing
to the strong affinity of superwarfarins for the reductase, the available binding sites
may be progressively occupied by ARs over a period of weeks or even months of
continuing exposure to low levels of the compounds. Evidently, all the superwarfa-
rins bind to the same site, and it is to be expected that by so doing they will have an
additive toxic effect. What is unclear, and can make interpretation of residue data
difficult, is what degree of occupancy of the reductase binding sites by ARs will lead
to serious hemorrhaging. Some individuals appear perfectly healthy when carrying
liver residues high enough to cause hemorrhaging in others.
Because of the difficulties of interpretation of residue data, it is important to have
other evidence to aid the recognition of toxic effects in the field. Hemorrhaging is usu-
ally easy to identify in a postmortem examination if carcasses are in reasonable condi-
tion. If early toxic effects are to be identified in live vertebrates, however, a biomarker
assay is needed (Fergusson 1994). The detection of undercarboxylated gla proteins in
blood has already been used to monitor human exposure to warfarin and other ARs
(Knapen et al. 1993). The development of such an assay, for example, an ELISA assay,
which could be used in predators and scavengers exposed to rodenticides in the field,
has obvious attractions. It should then be possible to establish when levels of exposure
in the field are high enough to begin to inhibit the vitamin K cycle, and increase the
blood level of undercarboxylated clotting proteins. Toxic effects could be identified at
an early stage before the occurrence of deaths due to hemorrhaging.
Because of the delay in the appearance of hemorrhaging following exposure to
warfarin and related ARs, a suitable interval must elapse between exposure of exper-
imental animals to the chemical and the assessment of mortality in toxicity testing.
Typically, this period is at least 5 days. Some values of acute oral LD50 of rodenti-
cides to vertebrates are given in Table 11.2.
Looking at the data overall, brodifacoum and flocoumafen are more toxic than
warfarin to mammals. However, toxicity of the two former compounds to birds var-
ies considerably between species. On available evidence, the galliform birds chicken
( Gallus domesticus ) and Japanese quail ( Coturnix coturnix japonica ) are much less
sensitive to flocoumafen than are mammals. The chicken is less sensitive to brodi-
facoum than mammals. The mallard duck ( Anas platyrhynchus ), however, is just as
sensitive as mammals to brodifacoum, whereas studies with the barn owl ( Tyto alba )
indicate that this species has comparable sensitivity to the rat or mouse. In toxicity
tests on 13 species of birds native to New Zealand, LD50s for brodifacoum ranged
from 0.95 mg/kg in the pukeko to >20 mg/kg in the Paradise shelduck (Eason et
al. 2002). Thus, it appears that flocoumafen and brodifacoum are generally more
toxic to mammals than to birds, although some birds are of comparable sensitivity
to mammals.
Newton et al. (1990) fed mice containing brodifacoum to barn owls, and estimated
that birds lethally poisoned by the rodenticide ( n = 4) had consumed 0.150-0.182
mg/kg of the compound. The birds died within 6-17 days of receiving a single dose