Thallium toxicosis in a dog consequent to ingestion of Mycoplasma agar plates

Abstract

A 1-year-old dog ingested a mixture of blood agar and Mycoplasma agar plates. The Mycoplasma agar plates contained thallium acetate, which resulted in an estimated minimum dose of 5 mg thallium acetate/kg bodyweight. Clinical signs over the course of 2–3 weeks included vomiting, diarrhea, weight loss, alopecia, dysphonia, ataxia, paresthesia, intension tremors, megaesophagus with subsequent aspiration pneumonia, and several seizure episodes. The dog was treated with intravenous fluids and placement of a gastric feeding tube. Thallium concentrations in hair were 8.2 µg/g in samples taken on day 19, 16.4 µg/g in samples taken 3 months after exposure, 13.4 µg/g in samples taken 5 months after exposure, and nondetectable in samples taken 7 months after exposure. The blood thallium concentration was 190 µg/l on day 19 and nondetec table 3 months after exposure. Megaesophagus and dysphonia continued for 10 months after exposure. This case of thallium poisoning following ingestion of mycoplasma agar plates demonstrates that unusual sources of thallium still exist and suggests that thallium toxicosis should be included in the list of differential diagnoses in dogs presented with megaesophagus, especially if alopecia and other unexplained peripheral neuropathies are present. Hair and blood samples are useful specimens to reach an accurate diagnosis even if taken several weeks post exposure. The postexposure blood and hair thallium concentrations reported in this case are useful data for diagnosticians investigating dogs with potential thallium poisoning.

Thallium, especially in salt form, is one of the most toxic heavy metals, with many uses throughout history. ¹⁹ Despite being banned as a rodenticide in the United States in 1972, it is readily available from chemical supply companies, is still available as a restricted use rodenticide in Europe, and can be used without restrictions in many developing countries. Currently, thallium is used by the semiconductor industry, in optical lenses, and for cardiac perfusion imaging. ⁸ Interestingly, the medical databases that prominent animal and human poison control centers rely upon do not list thallium as a potential constituent of growth media used to culture microorganisms.

The course of thallium poisoning is influenced by the amount ingested, the duration of exposure, and the amount of time since exposure.^27,28 Both accidental and intentional thallium poisonings of dogs continue to occur, and as a result, thallium toxicosis should be considered as a differential when an animal is presented with clinical signs of gastroenteritis combined with alopecia and/or peripheral neuropathies of unknown origin.^{7,22,24,27,28} The current report describes in detail the clinical presentation, diagnostic toxicology work-up, and successful management of a dog with thallium poisoning consequent to ingestion of Mycoplasma agar plates. The case of a second dog that developed identical clinical signs after exposure to Mycoplasma agar plates illustrates the unique hazard that thallium-containing growth media can present. This risk should be of concern to veterinarians and other health care professionals who work with and dispose of such media.

A 1-year-old, 30-kg, female spayed shepherd mix ingested approximately 20 agar plates (day 0) that were disposed of in a bag that was left unattended. The plates were a mixture of blood agar and Mycoplasma agar plates. Within 24 hr of ingestion, intense emesis (over 20 episodes) and diarrhea were noted; both resolved after 48 hr. Anorexia and diffuse alopecia became apparent 1 week postingestion. Approximately 10 days after ingestion, the exposure history was investigated further. The owner, a large animal veterinarian, realized that the Mycoplasma agar plates contained 500 mg thallium acetate/liter of prepared media. The minimum number of Mycoplasma agar plates consumed was estimated by the owner to be 15, with each plate containing 20 ml of media. Thus, the dog ingested approximately 150 mg of thallium acetate, or 5 mg thallium acetate/kg bodyweight.

In the beginning of the anorexia, the dog was force-fed small balls of meat and received lactated Ringer solution subcutaneously (3–5 liters of solution daily). Initially, the dog appeared to improve but her clinical condition deteriorated over the next few days, and she developed ataxia, intension tremors, and muscle twitching. She also continued to lose weight (losing a total of 10 kg or 33% of total body weight in 2.5 weeks). Dysphonia became apparent on day 19. At the same time, the dog developed several seizure episodes that were treated successfully with diazepam and phenobarbital intravenously. On day 22, esophageal paralysis was noted, and megaesophagus and aspiration pneumonia were suspected. She began to seizure again and was treated with 2 mg/kg phenobarbital intramuscularly every 12 hr for 3 days and 25 mg/kg ceftiofur every 8 hr subcutaneously for 10 days. The dog had no additional seizures but had hyperesthesia and extensive muscle twitching. A gastric feeding tube (percutaneous endoscopic gastrostomy [PEG] tube) was placed on day 24. The food consisted of a blended mixture of dog food (canned puppy chow, lamb and rice formula), rice, carrots, cottage cheese, water, B-complex vitamins, vitamin E, and omega-3 fatty acids (fish oil). Over the course of 10 months, the PEG tube was replaced 5 times. Despite careful supervision, the dog was able to reach and eat food and other material and developed 2 subsequent aspiration pneumonias approximately 7 and 12 weeks after exposure. The pneumonias were treated with ceftiofur and enrofloxacin, respectively. Chelation therapy was considered but was not initiated due to the fact that the diagnosis of thallium poisoning was not confirmed until approximately 3 weeks after exposure. From week 5 through week 12 after exposure, the dog continued to gain weight and improve her attitude. No further seizures were noted. Three months postexposure, the dog’s hair had returned to normal length and quality, and the hyperesthesia had resolved. The megaesophagus became easier to manage and eventually resolved 10 months postexposure. Additionally, the dysphonia resolved, and the dog began barking approximately 10 months after exposure.

Blood and hair samples were analyzed by graphite furnace atomic absorption spectrometry. ^b On day 19, hair from the withers and a whole blood sample were collected for thallium analysis. The hair contained 8.2 µg/g of thallium (physiological background thallium concentrations in dog hair range from 0.001 to 0.015 µg/g), ¹² and the blood contained 190 µg/l of thallium (physiological background thallium concentrations in blood for human beings and animals are below 2 µg/l). ¹⁸ Three months after exposure, the hair contained 16.4 µg/g thallium, which was twice as high as the concentration on day 19. The blood sample did not contain thallium above the detection limit of 50 µg/l. Five months after exposure, the hair contained 13.4 µg/g thallium, and 7 months after exposure, the thallium concentration in hair was negative at a detection limit of 0.2 µg/g. No significant abnormalities were noted on complete blood cell count and chemistry panels of blood samples collected on days 1 and 19.

The clinical presentation and toxicology results in the dog described herein are consistent with thallium poisoning resulting from ingestion of Mycoplasma agar plates. Thallium acetate has a reported minimum lethal dose in dogs of 10– 20 mg/kg. ¹¹ The mortality of thallium toxicosis in the dog and cat has been reported at 87%. ¹ Although difficult, an exposure assessment was performed in the current case. Assuming ingestion of 15 Mycoplasma agar plates, the dog was exposed to 5 mg/kg of thallium acetate (equivalent to 3.9 mg/kg of thallium ion), which is below the reported minimum lethal dose for dogs and in agreement with a favorable outcome. Interestingly, the estimated exposure level is very similar to a previous report of a dog that developed acute thallium poisoning after exposure to 9.2 mg/kg of thallium sulfate (equivalent to 3.7 mg/kg of thallium ion). ¹⁴ The dog from the 1939 report developed initial vomiting and bloody diarrhea lasting up to 2 days, followed by significant hair loss 7 days post exposure, which is consistent with the clinical presentation in the dog from the present report. The dog’s condition from the 1939 report started to improve on day 12 after exposure, and the dog was released from the clinic 43 days after exposure. Thus, exposure estimates from the current and previous (1939) reports demonstrate that oral doses of approximately 4 mg/kg of thallium ion can cause acute thallium intoxication in dogs, but that full recovery is possible. ¹⁴

Thallium acetate is water soluble, readily absorbed from the gastrointestinal tract, and distributed throughout the body. ²⁷ While thallium is rapidly cleared from the blood under physiological conditions, the half-life of thallium in whole blood of human beings with acute poisoning can be up to 15 days if untreated. ¹⁰ With intensive care, the half-life of thallium in blood can be lowered to 1.4 days. ¹⁰ The dog reported herein had a blood thallium concentration of 190 µg/l at 2.5 weeks post exposure. In human beings poisoned with thallium, blood concentrations varied from 30 to 36,000 µg/l.^2,15 Therefore, while blood thallium has historically been considered an unreliable diagnostic marker when evaluating suspect thallium intoxications, the current report shows that a blood sample taken several weeks after exposure can be of immense diagnostic value to establish an accurate diagnosis. As expected, the blood of the dog in the present report was negative for thallium at 3 months post exposure. Thallium ions do not undergo metabolic reactions and are excreted primarily in feces, but also in urine, especially after toxic exposure. However, in the reported case, urine samples were not available for analysis.

The toxicity of thallium is due in part to its similarity to potassium and, therefore, its ability to interfere with potassium-dependent processes such as Na⁺-K⁺ ATPase pumps.^5,13 In fact, thallium has a 10 times higher affinity to Na⁺-K⁺ ATPase than potassium. The most prominent features of thallium poisoning are seen in the skin, and gastrointestinal, nervous, and cardiovascular systems. Acute thallium intoxication presents as severe gastroenteritis within 12 hr to 4 days post exposure.^{1,7,19,22,27,28} This was evidenced by severe vomiting and diarrhea in the presented dog within 24 hr of ingestion of the agar plates. Alopecia is a dominant feature of acute or chronic thallium poisoning and usually develops several days to weeks after initial exposure.^{1,7,19,22,27,28} The dog in the present report developed significant hair loss, losing approximately one-third of her hair coat, within a few weeks. Thallium concentrations in the hair of the affected dog were 8.2 µg/g on day 19, 16.4 µg/g at 3 months, 13.4 µg/g at 5 months, and below 0.2 µg/g at 7 months post exposure. The detected thallium concentrations are consistent with toxic levels determined in human hair. Toxic thallium concentrations in hair of poisoned dogs could not be found in the veterinary literature. The increase in thallium hair concentration between the first and second measurement is possibly a result of the slower uptake of thallium from skin into hair. The series of measurements in the current report demonstrates that hair thallium concentrations can provide useful diagnostic data for several months after exposure.

Neurological signs usually appear from 2 days to 3 weeks post exposure, and are more predominant in human cases of intoxication. ²⁰ A human study showed that thallium concentration in cerebral spinal fluid increased over time despite a decreasing blood thallium concentration, supporting the theory of delayed distribution into the central nervous system. ²³ In dogs with thallium poisoning, neurological signs are rarely reported, but this could be due to the difficulty of assessing pain in companion animals. The paresthesia reported in the current report might have been a sign of pain. The dysphonia and megaesophagus could be manifestations of peripheral neuropathies. ⁴ Dysphonia has been mentioned in previous cases of thallium intoxication in a dog,^1,6 but the development of megaesophagus is of particular interest in the present case. Interestingly, another case of thallium poisoning was identified in the UC Davis Veterinary Teaching Hospital records database (Puschner, personal communication). This dog also ingested Mycoplasma agar plates and developed megaesophagus, which demonstrates that media used to make Mycoplasma agar contains sufficient thallium to cause intoxication of dogs.

Treatment approaches for thallium poisoning have variable results. In contrast to most other metals, decontamination with activated charcoal in recent exposures to thallium is considered beneficial. Various metal chelators such as dimercaprol and D-penicillamine have been used but are no longer recommended due to adverse effects. Hemodialysis and hemoperfusion are effective treatment options in human beings,^9,29 but high costs and availability may prohibit these from being widespread therapies in veterinary medicine. A specific thallium chelator, potassium ferric-cyanoferrate II (Prussian blue), was approved by the FDA in 2003 for the specific treatment of thallium and radiocesium poisoning in human beings. There have been multiple studies in animals showing enhanced elimination and improved survival when soluble Prussian blue is administered.^{3,16,17,21,25,26} Administration within the first 48 hr is most effective, but some human studies have suggested that Prussian blue has effects throughout acute and chronic intoxications. ¹⁹ Due to the amount of time that had passed between the ingestion and identification of the toxin in the reported case, neither activated charcoal nor Prussian blue was administered to the dog. The dog was treated symptomatically, with the primary goal being the successful management of the megaesophagus. However, after placing a PEG tube, Prussian blue therapy could have been considered in the reported case in order to enhance elimination of thallium. In the second thallium poisoning case of a dog with megaesophagus mentioned previously, the dog was euthanized after developing aspiration pneumonia, which was most likely a direct result of the megaesophagus.

The current case of thallium poisoning following ingestion of Mycoplasma agar plates demonstrates that unusual sources of thallium still exist. Thallium toxicosis should be included in the list of differential diagnoses in dogs presented with megaesophagus, especially if alopecia and other unexplained peripheral neuropathies are present. Since clinical signs may be inconclusive, toxicological analysis is needed for confirmation. Hair and blood samples are useful specimens to reach an accurate diagnosis even up to several weeks after the initial exposure. The reported blood and hair thallium concentrations determined at various time points after exposure are useful data to diagnosticians investigating dogs with potential thallium poisoning.