Fatal Bromethalin Poisoning

Abstract

Bromethalin is a neurotoxin found in some rodenticides. A delusional 21-year-old male presented to a hospital with altered mental status the day after ingesting a bromethalin-based rodenticide. He died 7 days after his self-reported exposure to c. 17 mg bromethalin (equivalent to 0.33 mg bromethalin/kg). His clinicopathologic course was characterized by altered mental status, obtundation, increased cerebrospinal fluid pressure, cerebral edema, death, and diffuse histologic vacuolization of the white matter in the central nervous system seen on microscopic examination at autopsy. The presence of a demethylated form of bromethalin in the patient's liver and brain was confirmed by gas chromatography with mass spectrometry. Clinical signs and lesions observed in this patient are similar to those seen in animals poisoned with bromethalin. This case illustrates the potential for bromethalin ingestion to result in fatal human poisoning.

Medical outcomes of bromethalin rodenticide exposures reported to US poison centers after federal restriction of anticoagulants

“…The EPA's rationale for LAAR's being less toxic than bromethalin was, in part, based on estimates that one 5 g bite of bromethalin is approximately 1/3 as toxic as one 5 g bite of brodifacoum in a 10 kg child based on extrapolation of rat LD50 values [1]. However, death has been reported in a human at a lower limit dose estimate approximately one-tenth of a rat LD50 (human fatal dose case report with analytical substance confirmation, quantity reported by patient 0.33 mg/kg, male rat LD50 3.2 mg/kg) [4]. The EPA asserted that the half-life of bromethalin being significantly shorter compared to LAAR's reduced the risk of adverse outcomes after ingestion [1].…”

“…Animal studies report symptom development up to 14 h after ingestion and death occurring within 2-4 days [7]. In a case report of human exposure that lead to fatality, the patient did not present until the day after the reported ingestion, was medically cleared by the managing team and sent to a psychiatric hospital, where initial symptoms of nausea, vomiting, and agitation progressed to coma by day two and eventually cerebral edema [4]. Within this data set, when the duration of clinical effect was known, 170/179 (94.97%) minor or moderate effects resolved within 24 h. Major effects had longer durations, ranging up to 1 month.…”

“…The proposed mechanism of bromethalin toxicity impacts multiple organ systems and manifests severely in the central nervous system [1,4,7]. Reported effects in animals include paralysis of rear limbs, ataxia, paddling, hyperthermia, muscle tremors, hyper excitability, occasional loss of vocalization, loss of tactile sensation, forelimb extensor rigidity, seizures, and death [7].…”

“…Unlike the LAARs, bromethalin toxicity in humans is poorly characterized and no antidote is available. Death from human ingestion has been reported in a single case report [4]. When an exposed patient enters the health care system, clinicians may be unfamiliar with the substance's effects and range of toxicity.…”

Rodenticides

“…One fatal intentional ingestion of bromethalin-based rodenticide has been published (Pasquale-Styles et al, 2006). A 21-year-old mentally disturbed male was admitted to the hospital the day after ingesting a bromethalincontaining rodenticide (equivalent to approximately 17 mg of active ingredient or 0.33 mg/kg bw).…”