Vertebrate Pesticide Toxicology Manual (Poisons)


Coumatetralyl (Racumin®, No rats & mice®)

:)


Download 0.79 Mb.
Page9/17
Date conversion17.07.2018
Size0.79 Mb.
1   ...   5   6   7   8   9   10   11   12   ...   17

2.4 Coumatetralyl (Racumin®, No rats & mice®)

Chemical Name: 4-hydroxy-3-(1,2,3,4-tetrahydro-1-naphthyl) coumarin

Synonyms: Coumatetralyl is the approved common name

Coumatetralyl is classified as a first-generation anticoagulant. It is less potent than brodifacoum, flocoumafen, or bromadiolone, but more potent than warfarin and pindone. Internationally it is sold under the trade name Racumin®, No rats & mice®.

2.4.1 Physical and chemical properties

The empirical formula for coumatetralyl is C19H16O3 and the molecular weight is 292.6. It is practically insoluble in water, slightly soluble in ether and benzene, soluble in alcohol and acetone, and readily soluble in dimethyl formamide.

2.4.2 Historical development and use

This rodenticide was developed in 1957 by scientists at Bayer, and is marketed worldwide. It is used as a tracking powder or as a cereal bait, wax block, and paste for rodent control.

2.4.3 Fate in the environment

No published information is available on the fate of this rodenticide in soil. It would be likely to be broken down slowly in soil by micro-organisms.

2.4.4 Toxicology and pathology

Onset of signs

Coumatetralyl baits containing 1 mg/kg will kill rats in 5–8 days. In general, the symptoms of poisoning do not appear suddenly.

Mode of action

As for other anticoagulant rodenticides (see brodifacoum), post-mortem examinations reveal extensive multiple haemorrhages throughout the body with considerable quantities of unclotted blood in the chest and abdominal cavities. Rats can withstand single doses of 50 mg/kg of this toxicant, but are unable to survive doses of 1 mg/kg when that dose is ingested over 5 successive days.

Pathology and regulatory toxicology

We could not find any regulatory toxicology studies in the published literature.

Fate in animals

Coumatetralyl is markedly less persistent (in sub-lethally poisoned animals) than brodifacoum (see Table 11). The hepatic half-life of sub-lethally exposed rats is 55 days (Parmar et al. 1987).

Species variation in response to coumatetralyl:

There are comparatively few acute toxicity data for coumatetralyl (Table 17).

Table 17. Acute oral toxicity (LD50 mg/kg) of coumatetralyl (Hone & Mulligan 1982; Worthing & Hance 1991)

Species LD50 mg/kg

Rat 16.5 (single dose)

0.3 (5 days)

Pig 1.0–2.0 (1–7 days)

Hen 50.0 (8 days)

Fish 1000.0 (96 hours)

2.4.5 Diagnosis and treatment of poisoning


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

2.4.6 Non-target effects


    Other than pets gaining access to bait, there are few references to non-target deaths in other species. In recent studies coumatetralyl-poisoned rat carcasses were fed to weka and ferrets. One out of 10 ferrets died, but no weka were killed (O’Connor & Eason 1999).

2.4.7 Summary

Advantages

Disadvantages

No licence required

Not as potent as brodifacoum or other second-generation anticoagulants

Effective for rodent control




Antidote




Less persistent than brodifacoum, flocoumafen, and bromadiolone





  • This compound was first introduced in 1957 and is sold as Racumin®, and is used as a tracking powder or as a cereal bait for rodent control.


  • This bait needs to be ingested over several consecutive days to be most effective.

  • As for other anticoagulants, rodents die within 5–7 days after ingesting a lethal dose of the toxin.

  • As for other anticoagulants, coumatetralyl interferes with the synthesis of vitamin K-dependent clotting factors. If ingested in large enough quantities, it is toxic to mammals, birds, and reptiles.


2.5 Diphacinone (Ditrac®, Liquatox®, Pestoff® (for ferrets))


Chemical Name: 2-(diphenylacetyl-1,3-indandione

Synonyms: Diphacinone is the approved common name
Like coumatetralyl, diphacinone is classified as a first-generation anticoagulant.

2.5.1 Physical and chemical properties

The empirical formula for diphacinone sodium salt is C23H15O3 Na and the molecular weight is 362.4. It is soluble in water; more soluble in ethyl alcohol, acetone and hot water; insoluble in benzene and toluene.

2.5.2 Historical development and use

Diphacinone is a first-generation anticoagulant, of the indandione class, produced and primarily used in the USA where it is used to control mice, rats, prairie dogs (Cynomys spp.), ground squirrels, voles and other rodents (Hayes & Laws 1991); and in South America where cattle are treated with diphacinone to provide live baits for vampire bats (Mitchell 1986).

Diphacinone is more toxic than warfarin or pindone to most rodents. In New Zealand it is registered primarily for rodent control, and more recently it has been incorporated into a fish-based bait for ferret control (Ogilvie et al. 1995).

This anticoagulant was first introduced for use in New Zealand in the 1950s as a rodenticide. It is available in both a liquid concentrate (Liquatox®) on a limited-sale basis in 50-ml plastic envelopes that are mixed with a litre of water for use as a liquid rodent bait, and a Ditrac® All Weather Block.

2.5.3 Fate in the environment

Comparative soil absorption and mobility studies have shown diphacinone to be relatively immobile. When tested in the laboratory, the half-life of diphacinone in soil under aerobic conditions is about 30 days and under anaerobic conditions is about 60 days (WHO 1995).

2.5.4 Toxicology and pathology

Onset of signs

Diphacinone baits at 3 mg/kg will kill rodents in 5–8 days. Rats can withstand relatively high single doses of this toxicant, but are unable to survive doses of <1 mg/kg when that dose is ingested over 5 successive days.

Mode of action

Diphacinone, like other anticoagulants, inhibits the formation of vitamin K-dependent clotting factors. This inhibition is prolonged when compared with the relatively short effect of warfarin. This is consistent with its prolonged persistence (90 days) in the liver (Bullard et al. 1976).

Pathology and regulatory toxicology


Clinical and post-mortem signs of toxicosis are as for other anticoagulants. Post-mortem examinations have revealed extensive multiple haemorrhages throughout the body with considerable quantities of unclotted blood in the chest and abdominal cavities.

Multidose studies with diphacinone in rats have demonstrated the difficulty in establishing a clear NOEL with persistent bioaccumulative compounds (like most anticoagulant rodenticides). No clear NOELs were obtained in a 90-day study spanning doses of 1.7–27.0 µg/kg/day (Elias & Johns 1981).

Fate in animals

See brodifacoum (section 2.1.4) and Table 11.

Absorption, metabolism, and persistence:

When diphacinone was administered (orally) to rodents, as with other anticoagulants concentrations reached their highest levels in the liver. Eight days after the administration of the compound in rats and 4 days in mice, the liver had the highest level of residues, but kidneys and lungs also contained significant concentrations of diphacinone; brain, fat, and muscles had the lowest levels (Yu et al. 1982). This is the typical pattern observed in tissue distribution studies with all anticoagulant poisons (see Table 18).

Table 18. Radioactivity in the tissue of female rats 8 days after oral administration of a single dose of 14C-diphacinone (0.4 mg/kg). Results are ppm equivalent expressed as a mean  SE (Adapted from Yu et al. 1982)

Tissue

Concentration


Liver

Kidney

Lung

Gonad

Spleen

Blood

Heart

Fat

Muscle

1.394  0.072

0.239  0.050

0.110  0.011

0.081  0.018

0.075  0.002

0.051  0.007

0.031  0.005

0.026  0.009

0.017  0.004

Few data exist on the changing patterns of tissue distribution over time. However, by comparing two different publications on diphacinone distribution (in rats after 8 days: Yu et al. 1982 and cows after 90 days Bullard et al. 1976), it would appear that residue can readily be detected in a range of tissues within a week of ingestion (Table 18), but after 3 months the liver and kidney are the only organs containing significant concentrations (Table 19).

Table 19. Detectable diphacinone residues (mean  S.d.) in tissue of cattle given a single injection of 1 mg/kg (Adapted from Bullard et al. 1976)

Days after treatment

Residues found (ppm  S.D.)


Liver

Kidney

30

60

90

0.15  0.01

0.14  0.1

0.15  0.00

0.08  0.01

0.10  0.02

0.08  0.00

Metabolism of this compound in rats involves mainly hydroxylation and conjugation reactions (Hayes & Laws 1991). The persistence of diphacinone in the liver is more prolonged than of warfarin or pindone (see ection 2.1.4).

Species variation in response to diphacinone

There is a marked species variation in the susceptibility of animals to the toxic effects of diphacinone (Table 20).

Table 20. Acute oral toxicity (LD50mg/kg) of diphacinone

Species Acute oral LD50 (mg/kg)

Rat (unspecified) 0.3–2.3

Dog 3.0–7.5

Cat 14.7

Rabbit 35.0

Pig 150.0

Mouse 340.0

Mallard duck 3158.0


2.5.5 Diagnosis and treatment of poisoning

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

2.5.6 Non-target effects

Other than pets gaining access to bait, there are no references to non-target deaths in other species in New Zealand. Birds have been shown to have been poisoned by eating carcasses. Both great-horned owls and saw-wet owls eating poisoned carcasses were affected, but not barn owls. In the USA golden eagles showed signs of haemorrhages after eating meat from animals poisoned with diphacinone (Savarie et al. 1979).


    Bats have been shown to be susceptible to diphacinone. In Latin America, where paralytic bovine rabies is transmitted by the common vampire bat (Desmodus rotundus), cattle are given sub-lethal intramuscular doses of diphacinone. These cattle effectively act as live baits, and bats that suck blood from treated cattle are killed (Thompson et al. 1972; Mitchell 1986; Said Fernandez & Flores-Crespo 1991). Although information derived in vampire bats cannot be extrapolated to the susceptibility of New Zealand’s short and long-tailed bats, it does suggest that they may be susceptible to anticoagulants via primary or secondary poisoning. Diphacinone is likely to have a slightly lower tendency to cause secondary poisoning when compared with bromadiolone, brodifacoum, or flocoumafen, because it is less potent.

2.5.7 Summary

Advantages

Disadvantages


No licence required

More persistent than coumatetralyl

Effective for rodent control

Less potent than brodifacoum

Antidote




Less persistent than brodifacoum






  • Diphacinone is a first-generation anticoagulant.

  • Diphacinone in bait formulations needs to be ingested over several days before a lethal dose is taken. Rodents will die within 5–8 days of ingesting a lethal dose.

  • Like other anticoagulants diphacinone interferes with the synthesis of vitamin K-dependent clotting factors. If ingested in large enough quantities, it is toxic to mammals, birds, and reptiles.

  • Diphacinone is not readily soluble, it binds strongly to the soil and is slowly degraded.


: Data -> Sites
Data -> T. lobsang rampa the rampa story
Data -> Piergeiron had given him ten days, and that was more than enough time to get everything done
Data -> Kindergarten and Preschool Shared Reading, Guided Reading, Phonemic or Phonological Awareness and Predictable Charts
Data -> Applied Capability Guidechart
Sites -> Thousands Attend International Agricultural Fair Connecting Afghan Farmers to Markets and Technology
Sites -> Get to know your friends better!
Sites -> Watch for a Whole Issue on kc in Current Womens’ Health Reviews 2011 with many authors. It came out Epub aheadof print August 15, 2011 and should be in print inOctober 2011 and available on pubmed one year later. Table of Contents
Sites -> Parish of tangipahoa state of louisiana
Sites -> Young adult funeral service faq’s introduction


1   ...   5   6   7   8   9   10   11   12   ...   17
:)


The database is protected by copyright ©hestories.info 2017
send message

    Main page

:)