Bromethalin is a neurotoxic

rodenticide Rodenticides are chemicals made and sold for the purpose of killing rodents. While commonly referred to as "rat poison", rodenticides are also used to kill mice, squirrels, woodchucks, chipmunks, porcupines, nutria, beavers, and voles. Despi ...

that damages the

central nervous system The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain and spinal cord. The CNS is so named because the brain integrates the received information and coordinates and influences the activity of all p ...

History

Bromethalin was discovered in the early 1980s through an approach to find replacement rodenticides for first-generation anticoagulants, especially to be useful against rodents that had become resistant to Warfarin-type anticoagulant poisons. A structured study was undertaken to develop a substance that would be both poisonous to rodents, but also would be readily eaten by rodents. Bromethalin—N-

methyl In organic chemistry, a methyl group is an alkyl derived from methane, containing one carbon atom bonded to three hydrogen atoms, having chemical formula . In formulas, the group is often abbreviated as Me. This hydrocarbon group occurs in ...

-2,4- dinitro-N ( 2,4,6-tribromophenyl)-6-(

trifluoromethyl The trifluoromethyl group is a functional group that has the formula -CF3. The naming of is group is derived from the methyl group (which has the formula -CH3), by replacing each hydrogen atom by a fluorine atom. Some common examples are trifluoro ...

) benzeneamine— was the outcome of that study, as the specific formulation had both desired rodenticidal properties.

Mechanism of action

Bromethalin works by being metabolised to n-desmethyl-bromethalin and uncoupling

mitochondria A mitochondrion (; ) is an organelle found in the cells of most Eukaryotes, such as animals, plants and fungi. Mitochondria have a double membrane structure and use aerobic respiration to generate adenosine triphosphate (ATP), which is used ...

oxidative phosphorylation Oxidative phosphorylation (UK , US ) or electron transport-linked phosphorylation or terminal oxidation is the metabolic pathway in which cells use enzymes to oxidize nutrients, thereby releasing chemical energy in order to produce adenosine t ...

, which causes a decrease in

adenosine triphosphate Adenosine triphosphate (ATP) is an organic compound that provides energy to drive many processes in living cells, such as muscle contraction, nerve impulse propagation, condensate dissolution, and chemical synthesis. Found in all known forms ...

(ATP) synthesis. The decreased ATP inhibits the activity of the Na/K ATPase enzyme, thereby leading to a subsequent buildup of cerebral spinal fluid (CSF) and vacuolization of

myelin Myelin is a lipid-rich material that surrounds nerve cell axons (the nervous system's "wires") to insulate them and increase the rate at which electrical impulses (called action potentials) are passed along the axon. The myelinated axon can ...

. The excess CSF results in increased

intracranial pressure Intracranial pressure (ICP) is the pressure exerted by fluids such as cerebrospinal fluid (CSF) inside the skull and on the brain tissue. ICP is measured in millimeters of mercury ( mmHg) and at rest, is normally 7–15 mmHg for a supine adul ...

, which in turn permanently damages neuronal

axon An axon (from Greek ἄξων ''áxōn'', axis), or nerve fiber (or nerve fibre: see spelling differences), is a long, slender projection of a nerve cell, or neuron, in vertebrates, that typically conducts electrical impulses known as action p ...

s. This damage to the central nervous system can cause

paralysis Paralysis (also known as plegia) is a loss of motor function in one or more muscles. Paralysis can also be accompanied by a loss of feeling (sensory loss) in the affected area if there is sensory damage. In the United States, roughly 1 in 5 ...

convulsion A convulsion is a medical condition where the body muscles contract and relax rapidly and repeatedly, resulting in uncontrolled shaking. Because epileptic seizures typically include convulsions, the term ''convulsion'' is sometimes used as a ...

s, and

death Death is the irreversible cessation of all biological functions that sustain an organism. For organisms with a brain, death can also be defined as the irreversible cessation of functioning of the whole brain, including brainstem, and brain ...

.Bromethalin
Animal Disease Diagnostic Laboratory, Spring 1997 Newsletter

Risk of poisoning to humans

Despite risk of severe symptoms and death, most unintentional pediatric exploratory exposures (licking or tasting a pellet) have not shown serious effects, and no deaths have been reported at this time in children, though toxicity is possible if significant amounts are ingested. Due to need for active metabolite generation to produce toxicity, fatal toxicity may be delayed by hours to days. All cases should be managed in consultation with a local poison control center. All intentional ingestions for self harm carry significant risk of death or severe neurologic effects and require monitoring in a hospital setting. In humans the most common initial effects of unintentional exposure are nausea, vomiting, abdominal pain, and diarrhea, though delayed seizures have been reported. No antidote for bromethalin is known; care is symptomatic and supportive. In pets, signs to watch for include severe muscle

tremor A tremor is an involuntary, somewhat rhythmic, muscle contraction and relaxation involving oscillations or twitching movements of one or more body parts. It is the most common of all involuntary movements and can affect the hands, arms, eyes, f ...

s, hyperexcitability, fits, extreme sensitivity to being touched ( hyperesthesia) and

seizure An epileptic seizure, informally known as a seizure, is a period of symptoms due to abnormally excessive or synchronous neuronal activity in the brain. Outward effects vary from uncontrolled shaking movements involving much of the body with lo ...

s that appear to be caused by light or noise. Owners of animals that have eaten bromethalin accidentally should seek immediate veterinary attention and be decontaminated. Contacting an animal poison control center can help ensure that timely and appropriate therapy is started.

References

{{Neurotoxins Rodenticides Nitrobenzenes Anilines Bromoarenes Trifluoromethyl compounds Respiratory toxins Neurotoxins