Date of this Version
The reported LD50 for technical grade bromethalin ranges from 1.8 mg/kg in the cat, 4.7 mg/kg in the dog, and 13 mg/kg in rabbits, and up to >1000 mg/kg in guinea pigs (VanLier and Ottosen 1981, VanLier and Cherry 1988). Mitochondrial electron transport studies using purified rat brain and liver mitochondria have been performed, and have established that bromethalin is an effective uncoupler of oxidative phosphorylation (VanLier and Ottosen 1981, Cherry et al. 1982, VanLier and Cherry 1988). Mitochondrial oxidative phosphorylation is the major mechanism for production of ATP in the brain. Uncoupling of this reaction in bromethalin-poisoned animals may result in a lack of adequate ATP formation and diminished Na+ - K+ ion channel pump activity. We are currently investigating alternate mechanisms of action for bromethalin toxicosis in the rat. Regardless of mechanism of action, cerebral edema and elevated cerebrospinal fluid pressure (CSFP) develops. Microscopic examination of neurologic tissues (brain and spinal cord) from lethally dosed animals revealed diffuse spongy degeneration of the white matter and intramyelinic edema (VanLier and Cherry 1988, Dorman et al. 1990).