Vertebrate Pesticide Toxicology Manual (Poisons)

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2.2 Flocoumafen (Storm®)


Chemical Name: 4-hydroxy-3-[1,2,3,4-tetrahydro-3-[4-

(4-trifluoromethylbenzyloxy) phenyl]-1-naphthyl) coumarin
Synonyms: Flocoumafen is the approved name, Storm® is the trade name.

Flocoumafen and brodifacoum are extremely similar in terms of their chemistry, biological activity, potency, persistence, and risk of secondary poisoning. For further details on the toxicology, mode of action, etc. of flocoumafen see the previous section on brodifacoum.

2.2.1 Physical and chemical properties

Flocoumafen is an off-white solid with a melting point cis-isomer of 181–191C and a vaporisation point at 133 pPa (25ºC). Flocoumafen’s solubility is 1.1 mg/L in water and >10 g/L in acetone, alcohols, chloroform, and dichloromethane. It is stable to hydrolysis and does not undergo any detectable degradation when stored at pH7–9 for 28 days at 50ºC.

2.2.2 Historical development and use

Flocoumafen is a second-generation anticoagulant that was developed by Shell Research in the early 1980s. Flocoumafen has been used against a wide range of rodent pests including the principal commensal species. It is also effective against rodents that have become resistant to other anticoagulant rodenticides. It is currently registered for use in New Zealand as a rodenticide under the trade name ‘Storm’. Flocoumafen is not extensively used in the field in New Zealand.


2.2.3 Fate in the environment

Flocoumafen is not readily soluble in water. In physico-chemical terms flocoumafen is extremely similar to brodifacoum. Hence if flocoumafen-containing baits were to be used in the field, when these baits disintegrate flocoumafen is likely to remain in the soil where it will be slowly degraded by soil micro-organisms. Microbial degradation will be dependent on climatic factors such as temperature, and the presence of species able to degrade flocoumafen.


      1. Toxicology and pathology

Onset of symptoms

Flocoumafen is a potent second-generation anticoagulent similar to brodifacoum. Its symptoms, time to onset of poisoning, mode of action, and toxicity to birds and mammals are like those of brodifacoum (Table 14). For practical considerations, species such as dogs, cats, and pigs, the risk of poisoning from baits or secondary poisoning from eating contaminated rodents will be similar to that for brodifacoum.

Table 14. Acute oral toxicity (LD50mg/kg) of flocoumafen (Hone & Mulligan 1982)

Species LD50 (mg/kg)

Dog 0.075–0.25

Gerbil 0.18

Rat 0.25

Rabbit 0.70

Sheep >5.0

Cat >10.0


Goat >10.0

Pig 60.0

Mode of action

Like other anticoagulant toxins, flocoumafen acts by interfering with the normal synthesis of vitamin K-dependent clotting factors in the liver of vertebrates (Hadler & Shadbolt 1975). In the liver cells the biologically inactive vitamin K1-2,3 epoxide is reduced by a microsomal enzyme into biologically active vitamin K, which is essential for the synthesis of prothrombin and other clotting factors. Flocoumafen antagonism of the enzyme vitamin K1-epoxide reductase in the liver causes a gradual depletion of the vitamin and consequently of vitamin K-dependent factors, which results in an increase in blood-clotting time until the point where no clotting occurs.

Pathology and regulatory toxicology

Pathological lesions in animals poisoned with flocoumafen are similar to those for brodifacoum and other anticoagulants. In regulatory studies flocoumafen has been shown to lack genetoxicity in a range of in vitro and in vivo regulatory toxicology studies evaluating the potential of this toxicant to induce chromosomal damage or genetic mutation.
In a teratogenicity study in rats some deaths or signs of haemorrhaging were reported at 0.4 mg/kg/day in females, but there were no reports of teratogenicity in foetuses. Hence regulatory studies indicate that flocoumafen lacks mutagenic or teratogenic effects at the doses tested (WHO 1995).
Fate in animals (see section 2.1.4)

Absorption, metabolism, and excretion


The persistence of flocoumafen in sub-lethally exposed animals is as great, if not greater, than that of brodifacoum (see Table 11). In rats, absorption of flocoumafen is also rapid reaching a maximum concentration in blood after 4 hours (Huckle et al. 1989) (see Table 15). Similar rapid absorption occurs for other anticoagulants (Kamil 1987) (Table 15).

Table 15. Occurrence of peak plasma concentrations in animals after oral ingestion of anticoagulants

Anticoagulant and dose

Species

Tmax hours

Reference

Warfarin 50 mg/kg

Bromadiolone 0.8 mg/kg

Flocoumafen 0.14 mg/kg

Possum

Rat

Rat

6

6–9

4

Eason et al. 1999a

Kamil 1987

Huckle et al. 1989

Following administration of flocoumafen, liver residues in rats consisted mainly of unchanged flocoumafen, although in a repeat-dose study a polar metabolite was also detected, indicating some low level of metabolism is occurring (Warburton & Hutson 1985; Huckle & Warburton 1986).


In rats, eight urinary metabolites have been detected after percutaneous exposure to 14C-flocoumafen (Huckle & Warburton 1986). However, they represented only a small proportion of the total dose, with most excretion occurring in the faeces as unchanged flocoumafen. Unchanged flocoumafen comprised the major proportion of the hepatic radioactivity in rats and was eliminated with a hepatic half-life of 220 days (Huckle et al. 1989). Veenstra et al. (1991) found retention of about 8% of an administered flocoumafen dose of 0.4 mg/kg in the liver of beagle dogs 300 days after dosing.

There are insufficient comparative data in different species to clarify whether or not there is a pattern of species variation in the metabolism of flocoumafen. However, it appears that quail are able to metabolise floucoumafen more effectively than rats (Huckle & Warburton 1989).

The metabolism of flocoumafen by Japanese quail may be partly responsible for the shorter liver retentions of this toxicant in quail (hepatic half-life 155 days; Huckle & Warburton 1989) versus rats (hepatic half-life 220 days; Huckle et al. 1988). Up to 12 radioactive components were detected in the excreta of quail (Huckle & Warburton 1989). Faecal excretion of radio-labelled flocoumafen following an oral dose of 0.14 mg/kg body weight accounted for 23–26% of the dose over the 7-day period; approximately half of this was recovered within the first 24 hours. Less than 0.5% of the dose appeared in the urine within 7 days (Huckle et al. 1989).

When oral14C-flocoumafen doses of 0.02 mg/kg body weight or 0.1 mg/kg body weight were given to rats, once weekly for up to 14 weeks, approximately one-third of each weekly low dose was eliminated through the faeces within 3 days, mostly within the first 24 hours. At the higher dose the faecal excretion ranged from 18% after the first dose to 59% after the 10th dose (Huckle et al. 1988).


Species variation in response to flocoumafen

For a number of species the LD50 is less than 1 mg/kg and this is similar to brodifacoum (see Tables 12 and 14). However, there are several species with surprisingly high LD50 values, e.g. pigs. No aquatic toxicity data was found.

2.2.5 Diagnosis and treatment of poisoning

As for brodificoum, see Section 2.1.5 (pp. 57–60).

2.2.6 Non-target effects

Flocoumafen has the potential to cause both primary and secondary poisoning of non-target species. However, the adverse effects of flocoumafen on wildlife are dependent more on how baits are used and the behaviour of non-target species than the susceptibility of individual species to the toxin. Baits in bait stations are less accessible to non-target species than baits on the ground. Secondary poisoning of birds (e.g. brown skua and harriers) is likely where target species (e.g. rabbits and rats) are a major constituent of the diet. Flocoumafen is extremely persistent in the livers of lethally and sub-lethally poisoned animals, which heightens the potential risk of secondary poisoning in non-target species. As the use of flocoumafen is largely restricted to commensal rodents, the risks of exposure of wildlife are lower, except when it is used around farm buildings.

Livestock must not be allowed access to flocoumafen baits as residues are likely to persist in their livers for up to 9 months or more. There is very little detailed information available on the non-target impacts of this toxin. However, as the properties of this toxin are very similar to those found in brodifacoum, the potential for non-target impacts are likely to be very similar.


2.2.7 Summary

Advantages

Disadvantages

Generally available and no licence required

High risk of secondary poisoning of non-target species if used widely in the field

Effective for rodents

Persistent (>9 months) in liver of vertebrates (can enter food chain and put meat for human consumption at risk) if used in the field

Antidote available

Although an antidote (vitamin K) is available, long-term treatment is needed.

Expensive compared to 1080 or cyanide



  • Flocoumafen has chemical and biological effects that are almost indistinguishable from brodifacoum.

  • Flocoumafen is a synthetic pesticide that was first registered for use approximately 20 years ago.

  • Flocoumafen is not readily soluble, it binds strongly to the soil, and is slowly degraded. It is most unlikely to contaminate waterways as it is used principally for controlling commensal rodents or in bait stations.
  • It is a potent second-generation anticoagulant, which acts by interfering with the synthesis of vitamin K-dependent clotting factors. Flocoumafen is toxic to mammals, birds, and reptiles.

  • When used near farms, livestock must not be allowed access to flocoumafen baits, as residues may persist in the survivors for >9 months.



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