When a toast becomes fatal, the story of two children and sodium fluoroacetate

Abstract

Sodium fluoroacetate (FAA) or “1080” is an organic fluorine poison used as rodenticide or pest control in USA, New Zealand or Israel. In Europe, this product has been banned because of its toxicity. The LD50 after ingestion have been estimated to be 2–5 mg/kg in humans. The main symptoms of intoxication include nausea, vomiting, ataxia, convulsion and unconsciousness. Toxicity occurs mainly through a metabolite fluorocitrate by inhibition of aconitase an enzyme implicated in krebs cycle. We describe two fatal cases of FAA poisoning in two children who ate a toast. Quantitative analysis for FAA was carried out by liquid chromatography coupled with mass spectrometry (LC-MS/MS). The sample preparation consisted in protein precipitation. Calibrators ranging from 0.25 to 100 μg/mL were used for quantification with ethylglucuronide-d5 (ETG-d5) as internal standard. The chromatographic column used was a Uptisphere strategy silica 5 μm (Interchim). Ionization was carried out in negative electrospray with MRM transitions of 77–57 and 226–75 for FAA and ETG-d5, respectively. The method has been validated under laboratory conditions and according to international guidelines: intra- and inter-day accuracy < 15% (< 20% at the LOQ), determination coefficients exceeded 0.99 and imprecision was < 15% (< 20% at the LOQ). Two 1-year-old children were admitted to the emergency department for vomiting and seizure. Two hours before, they were seen eating a piece of toast onto which 15 mL of a rat-killing solution was poured. A box with Chinese ideograms and a 10 mL plastic bottle was received at the laboratory. After medical treatment in the pediatric intensive care unit, child A suffered cardiorespiratory arrest 9 hours after ingestion and he died 1h30 after. Child B suffered cardiac decompensation 11 hours after ingestion and was then transferred to another hospital but died a few weeks after. Exhaustive toxicological investigations were requested by the police. For both children, testing of alcohol, narcotics and cyanide were negative in peripheral blood. Large unknown screening in blood and urine showed only medications prescribed in the pediatric intensive care unit (benzodiazepines, ketamine, amiodarone and barbituric were in therapeutic concentrations). After analyzing the product ingested by the children by a specific screening in negative mode (pesticides, rat-killing), a dedicated sodium fluoroacetate assay was used to determine the biological sample concentration for both children. The concentrations of sodium fluoroacetate for the child A were 2.5 μg/mL in peripheral blood, 8.9 μg/mL in urine and 3 μg/mL in gastric contents. For child B concentrations were 3.1 μg/mL in peripheral blood and 10.8 μg/mL in urine. The concentration in the rat-killing solution was about 13.5 g/L. FAA lethal dose in adult humans have been estimated to be 2–10 mg/kg. In the present case, the children shared a toast with 15 mL of rat-killing solution or about 202 mg of sodium fluoroacetate. They were weighing about 10 kg, so they ate 20 to 100 times the lethal dose for an adult. The blood concentrations for both children are similar and rather low. Liu et al. (2020) published a case series of 68 adults intoxicated with FAA, survivors (62) exhibited mean concentration of 35.6 μg/mL and dead patients (6) had a mean concentration of 163.8 μg/mL. However, no lethal concentrations have been reported in children so the concentrations found here can be considered as lethal for children. FAA is a molecule analytically challenging that can be easily missed by large unknown screening methods. Even if FAA is unauthorized in Europe it can still be bought abroad and taken back. Intoxications are rarely seen in France but can still be dramatic.