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Journal of Venomous Animals and Toxins

Print version ISSN 0104-7930On-line version ISSN 1678-4936

J. Venom. Anim. Toxins vol.6 n.1 Botucatu  2000 

Review article



Toad envenoming in dogs: effects and treatment



1 Department of Veterinary Clinics of the School of Veterinary Medicine and Animal Science of Botucatu - UNESP, State of São Paulo, Brazil; 2 Center for the Study of Venoms and Venomous Animals - CEVAP-UNESP, State of São Paulo, Brazil; 3 Veterinary Hospital of the School of Veterinary Medicine of Presidente Prudente - UNOESTE, State of São Paulo, Brazil.



ABSTRACT: Toads (order: Anura; family: Bufonidae; genus: Bufo) are distributed throughout the world, but more species are found in areas of tropical and humid temperate climates. Although toads do not have a venom inoculation system, they are venomous animals because the glands covering the whole surface of their bodies secrete a milk-like venom of which composition is not yet completely known. Some of these glands are the bilateral glands located in post-orbital position. These glands, which are somewhat diamond-shaped and can be seen by the naked eye, are known as parotids. Toad envenoming in dogs may cause local and systemic alterations and may cause death by cardiac ventricular fibrillation. The electrocardiographic alterations observed consist of gradual deterioration of the normal standards with progressive appearance of negative ventricular deflections that can result in ventricular fibrillation and death if the envenomed dog is not promptly treated. Traditional therapy consists mainly of administration of atropine and propranolol; the latter used to prevent ventricular fibrillation.
KEY WORDS: toad, Bufo, venom, dogs, envenoming.




Toads (order: Anura; family: Bufonidae; genus: Bufo) are distributed throughout the world, but are found mainly in areas of tropical and humid temperate climates (9,10,25). Each region is characterized by the presence of some species of these amphibians. In Brazil, the most commonly found species are Bufo marinus, B. typhonius, B. crucifer, B. ictericus, B. granulosus, B. ocellatus, B. rufus and B. paracnemis (5). However, not all of these species cause death to envenomed dogs (2).

Although toads do not have a venom inoculation system, they are considered venomous animals, as the glands covering the whole surface of their skin secrete a highly toxic venom (33). Some of these glands are the bilateral glands located in post-orbital position. These glands, which are somewhat diamond-shaped and can be seen by the naked eye (7), are known as parotid glands. The parotid glands are composed of a large concentration of granular glands responsible for the production and storage of a thick and creamy secretion. There are also the mucous glands that produce a less viscous secretion. (2,7,11,24,26). These secretions help protect against predators, and thus, are considered a kind of defensive mechanism of these animals that lack spines, nails, or sharp teeth (25). In addition. walking, hopping, inflation of the lungs, and vocalizing are also defensive mechanisms. Habermehl (12) stated that 50 million years ago, amphibians already had venomous characteristics, while their predators were not yet on earth. The skin secretion of these amphibians is important for their protection against microorganisms that can grow in the mucous. This covers the skin allowing respiration (25,33), hydric and electrolytic changes, and thermoregulation (5).

Some predators, including some species of snakes, are immune to toad venom (11).

Dogs may be envenomed by biting or eating toads. The toad venom is secreted into the predator’s mouth, and it can be absorbed by the mucosa of the upper gastrointestinal tract or by skin injuries (18,24,25). Toad venom is mainly cardiotoxic and causes envenomation similar to that caused by digitalis (2,4,8,17,26,29,32,36,39). Envenomed animals show a false positive result in tests that evaluate the plasmatic concentration of digoxin (19).

Knowledge about the toxicity of toad venom comes from the past when the venom was used by different people for various purposes. Roman women used toad secretion to poison their husbands (8). South American Indians, especially from the Amazon region, used venoms of anurans from the Dendrobatidae family and species of B. blombergi on the tip of their arrows for hunting and fighting (2,8,21,33,36). In Japan, under the called of "Senso", and in China, under the name of "Ch’an’Su", dried toad venom was used as an expectorant, anti-hemorrhagic, diuretic, and cardiac stimulant (7,8,38). In Hawaii, a child died after having eaten a toad killed by his father in a sugarcane field. This report shows that toad envenoming is also a problem in humans (29).

The chemical composition of toad venom is very complex and varies depending on species (7). The venom composition is generally considered the best information for the taxonomic classification of this group of amphibians (6). Amphibian venom is an important source of information for biopharmacology, and knowledge of these venoms may contribute to the synthesis of chemically active substances with possible use in humans (25).

Zelnik (39) reported that the composition of toad venom is complex and has not yet been defined. The substances that make up toad venom may be divided basically into 2 groups, such as the basic compounds (biogenic amines) and steroid derivatives. The basic compounds (biogenic amines) include adrenaline and noradrenaline, bufotenins, dihidrobufotenins, and bufotionin. The steroid derivatives include cholesterol, ergosterol, g-sistosterol, bufotoxins and bufadienolids that are the arenobufogenin, argentinogenin, bufalin, bafarenogin, bufotalin, bufotalinin, cinobufogenin, cinobufotalin, desacetylbufotalin, desacetylcinobufotalin, gamabufotalin, hellebrigenin, jamacobufogenin, marinobufogenin, resibufogenin, telocinobufogenin. Other studies (6,8,20,25,33,35,39) include some substances described above and other substances, such as desacetylbufotalin, cinobufagin, acetylcinobufagin, desacetylcinobufagin, acetylcinobufotalin, desacetylcinobufotalin, marinobufagin, acetylmarinobufagin, 12b-hydroxymarinobufagin, bufotalidin, acetylbufotalidin, acetylresibufogenin, 12b-hydroxyresibufogenin, artebufogenin, vallicepobufagin, quercicobufagin, viridobufagin, regularobufagin, fowlerobufagin; bufotoxins, alvarobufotoxin, arenobufotoxin, cinobufotoxin, fowlerobufotoxin, gamabufotoxin, marinobufotoxin, regularobufotoxin, viridobufotoxin, vulgarobufotoxin, bufagin A, B, and C, bufotalidin, desacetylcinobufagin, desacetylcinobufotalin, serotonin (5-OH triptamin), serotonin, dopamine, epinine, 3-epibufalin, bufalon, bufotalidin, bufotalon, cinobufagin, cinobufaginol, desacetylbufotalin, desacetylcinobufagenin, desacetylcinobufotalin, hellebrigenol, artebufogenin, bufotoxins (cinobufotoxin, gamabufotoxin, marinobufotoxin), bufotenidin, bufoviridin, dopamine, and epinine.

Considering the toxicodynamics of toad venom compounds, these may be classified as shown below.

ADRENALINE. Agonist of the sympathetic autonomic nervous system, which acts on receptors a1, b1 and b2, inducing skin and visceral vasoconstriction (a1), muscle vasodilatation, bronchodilatation (b2), increase in the heart contraction and cardiac frequency (b1) (13).

NORADRENALINE. Agonist of the sympathetic autonomic nervous system, which acts on receptors a1, b1 with the same effects of adrenaline (13).

BUFOTENINS, DIHIDROBUFOTENIN AND BUFOTIONIN. These have hallucinogenic effects on the central nervous system (8,25,39).

CHOLESTEROL, ERGOSTEROL AND GAMA-SISTOSTEROL. They have no action on the venom (39).

BUFODIENOLIDS AND BUFOTOXINS. These have a digitalis-like action (1,4,11). They inhibit the Na+ and K+ pump of cardiac cells, increasing the intracellular concentration of Na+ and, consequently, inhibiting Na+ entrance and stimulating Ca++ elimination. So, Ca++ has its intracellular concentration increased, causing a raise in the heart contraction and a reduction in the heart beat frequency by vagal action (14). However, this latter effect may be controlled by the actions described above for adrenaline and noradrenaline. The effects of the inhibition of the Na+ and K+ pump can be observed in vitro (16).

Some authors believe that no single substance is entirely responsible for the genesis of the clinical signs of toad envenoming. Therefore, Otani et al. (28) reproduced the same symptoms as toad envenoming in rats by administrating a digitalis derived from plants (ouabain) associated with epinephrine.

Signs of toad envenoming may occur almost immediately and may be restricted to local irritation or cause systemic signs. This envenoming may or may not cause death of the envenomed animal within 15 minutes from the onset of the symptoms (17,18,23,26,28). This variety of symptoms is attributed to several factors, as shown below.

TOAD SPECIES. Some species are more venomous than others, for instance, B. marinus is considerably more venomous than B. vulgaris, (6).

REGIONAL VARIATION WITHIN THE SAME TOAD SPECIES. The same species may have more or less venomous communities, probably due to environmental influences, such as diet, climate, and evolutionary adaptations (29). In Hawaii, the mortality rate of untreated animals exposed to Bufo marinus is only 5%, while in Florida untreated exposure to the same species results in nearly 100% mortality. The mortality rate is also low in Texas.

VOMITING AND SALIVATION. The animal eliminates part of the venom, reducing then its toxic effect (3). Clinical signs of toad envenoming are shown in Table 1 (2,17,18,23,28,29).


TABLE 1. Degrees of toad envenoming.

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Other studies have also reported some unusual signs, such as excitation, kyphosis, fecal incontinence, progressive muscle paralysis (31), and blindness (2,32).

The electrocardiographic alterations consist of gradual deterioration of the normal standards with progressive appearance of negative ventricular deflections, which can result in ventricular fibrillation and death if the animals is not promptly treated (29,30,32).

One has to be careful to estimate the prognosis of dogs envenomed because all the variables that classify the process as light, moderate, or severe have to be considered. These variables are toad species (20), venom potency, amount of venom absorbed (30), size of the affected animal, individual susceptibility, genetic factors, diet, and toad habitat. Some studies report a low mortality rate, although other authors report 100% of mortality of untreated animals in some regions such as Florida (17,29,30,32). Brachycephalic dogs have been reported to be more severely affected (23).

Clinical diagnosis is made by anamnesis to observe if there is contact between the animal and the toad, or if the toad is present in the dog environment (22). Due to the toad’s nightly habits, envenomings usually occur at night (23,31). In addition, clinical examination shows the symptoms and signs described before.

Necropsy can confirm the envenoming if parts of the toad are found in the dog gastrointestinal tract. Another finding that can help characterize toad envenoming at necropsy is a gastrointestinal inflammatory process. This may be hemorrhagic (31) due to toad venom irritating action, lung congestion, edema, and hemorrhage caused by cardiac failure. However, these findings are not specific of toad envenoming (15).

There is no agreement in the literature about the treatment choice (30). However, the following procedures and drugs seem to be good choices.

PROPRANOLOL (non-selective ß-adrenergic antagonist) - Five mg/kg, IV, with repetition after twenty minutes if necessary to control cardiac fibrillation. Palumbo et al. considered (29) Propranolol the most efficient treatment for toad envenoming. These investigators conducted 3 experiments using dogs. The animals were anesthetized using pentobarbital and orally envenomed with B. marinus venom. They were then treated with IV injections of Propranolol when the electrocardiogram showed QRS negative ventricular deflections before ventricular fibrillation. The results obtained by these authors (29) are summarized in Table 2.


TABLE 2. Results obtained by Palumbo et al. (29).

Image286.gif (6420 bytes)


ATROPINE (muscarinic antagonist) administered at dose of 0.04 mg/kg reduces salivation and lung secretions (30).

PENTOBARBITAL SODIUM (barbiturate of short duration) at the dose of 30 mg/kg allows orotracheal intubation and washing of the mouth with water to reduce the venom present in this mucous. Pentobarbital also has an anticonvulsive action (29,30,32). Other options reported by some authors are corticosteroids and antihistamines for the protection of the mucous membranes from the inflammatory process suppression (23,32). Calcium gluconate helps maintain the cellular permeability (17,18,23,26), although it is also considered (an) arrythymogenic (28,29). Potassium aids the recuperation of the Na+ and K+ pump normal operation, reducing the levels of intracellular Ca++ , with consequent return to normal sinusal rhythm (29,32).

In addition, oxytetracycline, chloranphenicol, analgesics, spasmolitic drugs, multivitamins (31), sodium bicarbonate to wash the oral cavity (2), diphenylhydantoin (37), phenoxybenzamine, a-adrenergic antagonist (26), acepromazine, a-adrenergic antagonist (22) are also reported to help in treatment of toad envenoming.

Oliveira and Sakate and Sakate and Oliveira (27,34) have studied other drugs for the treatment of toad envenoming in dogs, and their preliminary results have shown that verapamil seems to be the drug of choice. However, further studies are needed to confirm these results.



Toads (genus Bufo) are very common in Brazil due to the excellent conditions for their survival. In this way, toad envenoming is a health problem for humans and dogs in Brazil. The chemical composition of toad venom is very complex and has not yet been completely defined. Envenomed dogs show mainly cardiotoxic symptoms, such as ventricular fibrillation, arrhythmia, lung edema, and death. Toad envenoming is fatal if the animal is not promptly treated. Today, propranolol and atropine are considered the most efficient drugs for the treatment of toad envenoming. However, the studies of Oliveira and Sakate (27) and Sakate and Oliveira (34) propose other options besides propranolol and atropine.


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FIGURE 1. Transversal cut of the parotid gland of B. ictericus


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FIGURE 2. Electrocardiograph of an experimental dog envenomed by toad venom: A-before envenoming, B- 40 minutes after envenoming. Note the negative ventricular deflections, C- ventricular fibrillation (3). P- wave P = atrial depolarization, Q and R- QRS complex= ventricular depolarization, T- wave T = ventricular repolarization.



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Received 24 March 1998
Accepted 06 October 1998

P. C. LUCAS DE OLIVEIRA - Rua Tuiuti, 119, CEP 19.050-580, Presidente Prudente, São Paulo, Brazil.

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