Tox and Hound – 1080

by Chris Holstege

Early in my career, I received a call from my emergency department (ED) that a local pest remover had an M44 cyanide device discharge in his face. He was hyperventilating while insufflating amyl nitrite. I began to look further into it and I was rather stunned at the number of markedly toxic substances “licensed” pest removers had access to. Clinicians are certainly well aware of the toxicity of sodium cyanide, but few have heard of the pesticide sodium monofluoroacetate (SMFA).

SMFA is both chemically and toxicologically identical to the fluoroacetate found in certain poisonous plants found in Australia, South Africa, and South America.¹ SMFA is also known as “1080”, referring to an invoice number assigned in US government labs. SMFA was discovered by a Belgian chemist and patented in Germany as a mothproofing agent. Used in the 40’s as a predacide (something that kills mammals larger than rodents) and a rodenticide, President Nixon banned the poison from being used in 1972. In 1981, the Environmental Protection Agency (EPA) was petitioned by the livestock owners to revisit the 1972 predacide cancellation decision with respect to SMFA. EPA held informal hearings in 1981 and formal administrative hearings in 1982 resulting in a final decision to permit EPA to consider applications for registration of SMFA in toxic collars and single-dose baits. In 1985, the EPA granted a registration of a toxic collar product which was transferred in 1986 to the Animal and Plant Health Inspection Service (APHIS) of the U.S. Department of Agriculture (USDA).

SMFA is an acute toxicant predacide which is used against coyotes which prey on sheep and goats. Registered end-use products are injected into the rubber reservoirs of the Livestock Protection collars, also referred to as the “toxic collar” (not to be confused with this toxic collar), which are strapped to the throats of sheep or goats. Coyotes attempting to kill collared livestock are likely to puncture the collars and to be fatally poisoned by SMFA as a result of the attack. SMFA is a restricted use pesticide in the U.S. which may be used only by trained, certified applicators and which is only registered for use in livestock protection collars. SMFA is manufactured by one U.S. Company: Tull Chemical Co. in Oxford, Alabama, which has been manufacturing the poison since 1956.

In November 2004, Rep. Peter DeFazio (D-OR) asked the Department of Homeland Security to halt production and use of SMFA due to its potential use as a terrorist agent.² In December 2005, Rep. DeFazio introduced a bill “to prohibit the manufacture, processing, possession, or distribution in commerce of the poison sodium fluoroacetate”, as well as to destroy existing stores of the poison. This bill failed. However, on March 30 of 2017, Rep. DeFazio (D-OR) reintroduced a bill in the House of Representatives “to prohibit the use of the poisons sodium fluoroacetate and sodium cyanide for predator control.” So why is Rep. DeFazio looking to ban substances that are used to protect docile sheep and other livestock from the ravages of predators, such as coyotes?

Properties

Let’s first discuss the properties of the compound, which actually make it an effective poison to kill predators as well as effective for use by suicidal applicators and potential terrorists. The synthetic form of the SMFA (CAS # 62-74-8) exists as a white powder (similar in appearance to flour or powdered sugar) that remains stable for long periods of time. It is odorless, tasteless, and readily dissolves into water. When present in natural water sources it degrades within seven days due to its metabolism by microorganisms within those environments. In water devoid of microorganisms, SMFA appears to remain stable. It is relatively insoluble in organic solvents such as ethanol or vegetable oils. The only reported distinguishing characteristic is that it has a weak vinegar taste when mixed with water. It is heat stable; it does not decompose until temperatures approach 200º C. SMFA is highly toxic to vertebrates, although the sensitivity of different species varies dramatically. In man, the estimated lethal poisoning dose (LD50) ranges from 2 to 5 mg/kg body weight, making it one of the more deadly toxins based on weight need to kill.³

Routes of Exposure

SMFA is well absorbed from the gastrointestinal tract, the respiratory tract, open wounds, mucous membranes, and ocular exposure, so universal contact precautions should be followed for all unknown intentional overdoses. The majority of human exposures reported in the medical literature have been through ingestion. Toxicity has been reported to be the same whether it is administered orally, subcutaneously, intramuscularly, or intravenously. Dusts containing SMFA are effectively toxic by inhalation.

Pathophysiology

The toxicologic mechanism of SMFA involves disruption of cellular energy production resulting in multisystem organ failure (Figure 1).⁴ The parent compound, fluoroacetate, has very low cellular toxicity. However, once ingested and absorbed, enzymatic reactions within cells convert fluoroacetate to fluoroacetyl-CoA. Fluoroacetyl-CoA, in the presence of oxaloacetate, is converted by citrate synthase to fluorocitrate, a potent inhibitor of the enzyme aconitase. Aconitase catalyzes the reversible Krebs cycle reaction converting citrate to isocitrate. The inhibition of aconitase results in the interruption of the energy-producing Krebs cycle and the buildup of citrate. Fluorocitrate also inhibits the transport of citrate in and out of mitochondria, contributing the buildup of citrate. Elevated citrate levels disrupt energy production via glycolysis by inhibiting the enzyme phosphofructokinase. Elevated citrate levels may also cause life-threatening hypocalcemia. Because it takes time for the metabolic conversion of fluoroacetate to fluorocitrate, there is a delay from the time that the poison is ingested to the initial onset of signs and symptoms.

Clinical Manifestations

Clinical signs and symptoms associated with SMFA poisoning are nonspecific. SMFA poisoning is characterized by a latent period of 30 minutes to 3 hours following the administration of the compound by any route. Even massive doses do not elicit immediate responses, although the latent period may be reduced.

In animal studies, the early stages of poisoning are typically reported as displaying a range of signs including lethargy, vomiting, trembling, excessive salivation, incontinence, muscular weakness, incoordination, hypersensitivity to nervous stimuli, and respiratory distress. Early neurological signs include muscular twitches often affecting the face, such as nystagmus and blepharospasm. These then progress to generalized seizures, initially tonic and then becoming cyclically tonic-clonic with periods of lucidity in between.⁵ Partial paralysis may be seen that lasts for prolonged time periods. Death typically results from depression of the respiratory center, cardiovascular failure, and/or ventricular fibrillation.⁶ On autopsy, there are no characteristic lesions associated with SMFA poisoning.

Numerous human case reports of ingestion exist in the literature with varying presentations depending on the dose.^7–10 Initial symptoms involve the gastrointestinal system with nausea and vomiting reported to occur early – often within the first hour. Patients then can progress rapidly to altered mental status, seizures and multisystem organ failure. However, reports do exist of a latent phase with the resolution of gastrointestinal symptoms followed by a delayed development of altered mental status (e.g., confusion, agitation) and seizures (as late as 20 hours following ingestion in an infant).^3,11 In a retrospective study of 38 human cases of SMFA poisoning, Chi et al noted the most frequent symptom to be nausea and/or vomiting (74%).¹² Electrocardiograph changes were quite variable ranging from mild nonspecific ST and T wave abnormalities (72%) to ventricular tachycardias and asystole. The most common electrolyte abnormalities included hypocalcemia (42%) and hypokalemia (65%). Seven of the 38 patients died in this series. Discriminant analysis identified hypotension, increased serum creatinine, and decreased pH as the most important predictors of mortality, with a sensitivity of 86% and specificity of 96%.

Laboratory Testing

Standard hospital laboratories do not test for SMFA. However, there are laboratories across the country that are able to detect it in biological samples. Chemical detection methods are currently utilized to detect SMFA in human blood specimens. Derivatized extracts are analyzed using gas chromatography/mass spectroscopy (GC/MS) or gas chromatography with electron-capture detection. Since the exact mechanism for SMFA metabolism has not been elucidated, rapid collection of blood specimens should be obtained and immediately stored at 4°C in suspected cases.

Treatment

There is no specific antidote for SMFA toxicity and therapy is primarily focused at supportive care. Even though activated charcoal does appear to bind SMFA, it does not appear to affect either the area under the curve of serum fluoroacetate levels versus time or decrease mortality rates.¹³ A number of different treatments have been explored for SMFA toxicity. Because SMFA induces hypocalcemia, calcium supplementation through the administration of either calcium gluconate or calcium chloride has been shown to be of benefit.¹⁴ In animal models, sodium succinate has been shown to be of benefit as a potential antidote to revive the Krebs cycle.¹⁵ Due to the reported potential for delayed clinical effects, patients with known oral exposure to SMFA should be observed for a minimum of 24 hours following oral exposure.

Coyote by Peter Lloyd