Bromethalin causes toxicity by which mechanism?

• A. Inhibiting acetylcholinesterase
• B. Uncoupling oxidative phosphorylation, leading to low ATP and intracellular edema
• C. Blocking voltage-gated sodium channels
• D. Activating GABA receptors

Answer: (D)

Bromethalin toxicity stems from uncoupling oxidative phosphorylation in mitochondria, especially in nervous tissue. By dissipating the proton gradient across the inner mitochondrial membrane, it prevents ATP synthase from making ATP. The resulting ATP depletion impairs energy-dependent processes, notably the Na+/K+ pumps, leading to cellular swelling and cytotoxic edema in the brain. This energy failure in neurons explains the central nervous system signs seen with bromethalin exposure, such as tremors and seizures.

This mechanism is different from inhibiting acetylcholinesterase (which would cause cholinergic overstimulation), blocking voltage-gated sodium channels (which would disrupt action potentials directly), or activating GABA receptors (which would enhance inhibitory signaling).