Bromethalin exposure in a free-ranging American black bear (Ursus americanus)

Sherri L. Cox, Brian Stevens, Felipe Reggeti

National Wildlife Centre and Integrative Biology, University of Guelph (Cox); Canadian Wildlife Health Cooperative (Stevens); Animal Health Laboratory, University of Guelph (Reggeti)

AHL Newsletter 2022;26(2):17. 

A black bear cub (Ursus americanus) from Ontario was found minimally responsive and weak.  After presentation at a veterinary clinic, blood work results were within reference limits except for a mildly elevated ALT (550 U/L; RI: 11-309 U/L); radiographs were unremarkable.  The cub was then transferred to a wildlife rehabilitation center for supportive care, where it developed moderate to severe cerebellar ataxia, inability to control its head movements and self-mutilation of its hind limb.  Occasional unilateral epistaxis was reported.  Analgesics, anti-inflammatories and antibiotics (for possible Toxoplasma infection and the contaminated wound) were prescribed.  The ataxia resolved after a week and the bear was doing well; however, unilateral epistaxis worsened and mucous membranes became pale.  Blood was collected for follow-up testing but the bear’s condition deteriorated and it died soon afterwards.  On the antemortem blood sample, coagulation profile was within normal limits, but the CBC showed pancytopenia and mild hypoalbuminemia (23 g/L; RI: 30-51 g/L).

On postmortem examination, the mucous membranes were markedly pale and no abnormalities were noted in the nasal cavity.  On histopathology, rare perivascular lymphoplasmacytic cuffs and rare focal gliosis were noted in the cerebral cortex. The bone marrow was hypoplastic (cellularity <10%). Fluorescent antibody testing for rabies virus was negative.  Liver samples submitted to the AHL toxicology section tested negative for anticoagulant rodenticides (LC-MS/MS), and no toxins were detected with a comprehensive toxin screen (GC-MS and LC-MS/MS); however, adipose tissue was positive for desmethylbromethalin (LC-MS/MS).

Bromethalin is a potent neurotoxicant with no anticoagulant activity nor known antidote.  It is rapidly absorbed in the gastrointestinal tract and widely distributed throughout body due to its high lipophilicity.  Clinical signs associated with acute toxicity may occur 4 hours to 7 days after ingestion.  Two clinical forms have been described: the initial form consisting of tremors, hyperesthesia, seizures and death; and the paralytic form characterized by depression and disorientation progressing to ataxia and rear limb weakness within 7 days, progressively worsening over 1 to 2 weeks. The mechanism of action consists of uncoupling the oxidative phosphorylation in the mitochondria, resulting in impaired energy metabolism primarily affecting the central nervous system.

The histopathological lesions in this bear were subtle and inconsistent with bromethalin toxicosis (i.e. “spongy degeneration” of the white matter); however, identification of desmethylbromethalin (a highly toxic metabolite of bromethalin) confirmed exposure, absorption and metabolism of the substance.  Since the bear recovered from the neurological signs one week after presentation, it was assumed to be exposed to a low (sub-lethal) dose.  Considering other significant findings including bone marrow hypoplasia leading to pancytopenia and epistaxis, the cause of death was probably multifactorial.

To reduce the risk of accidental exposure to rodenticides, Canadian regulatory agencies prohibited domestic class products containing second-generation anticoagulants, leading to increased popularity of rodenticides with other active ingredients, such as bromethalin.  Since bromethalin-containing rodenticides are easily available (e.g., hardware stores), these products are registered for indoor use only and must be inaccessible to children, pets, livestock and non-target wildlife, in order to ensure consumers’ safety.  Unfortunately, accidental exposures do occur.   AHL

Reference

1. Cox S, et al. Bromethalin exposure in a free-ranging American black bear (Ursus americanus). J Wildl Dis 2022;58(1):235-237.