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, woodchucks, chipmunks, porcupines, nutria, beavers, and voles. Some rodenticides ...

that damages the

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

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 (whereas normal methane has the formula ). In formulas, the group is often abbreviated as ...

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

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

) 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 us ...

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

, which causes a decrease in

adenosine triphosphate Adenosine triphosphate (ATP) is a nucleoside triphosphate that provides energy to drive and support many processes in living cell (biology), cells, such as muscle contraction, nerve impulse propagation, and chemical synthesis. Found in all known ...

(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 Vacuolization is the formation of vacuoles or vacuole-like structures, within or adjacent to cells. Perinuclear vacuolization of epidermal keratinocytes is most likely inconsequential when not observed in combination with other pathologic fin ...

myelin Myelin Sheath ( ) is a lipid-rich material that in most vertebrates surrounds the axons of neurons to insulate them and increase the rate at which electrical impulses (called action potentials) pass along the axon. The myelinated axon can be lik ...

. 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 adu ...

, which in turn permanently damages

neuronal A neuron (American English), neurone (British English), or nerve cell, is an excitable cell that fires electric signals called action potentials across a neural network in the nervous system. They are located in the nervous system and help to ...

axon An axon (from Greek ἄξων ''áxōn'', axis) or nerve fiber (or nerve fibre: see American and British English spelling differences#-re, -er, spelling differences) is a long, slender cellular extensions, projection of a nerve cell, or neuron, ...

s. This damage to the central nervous system can cause

paralysis Paralysis (: paralyses; also known as plegia) is a loss of Motor skill, motor function in one or more Skeletal muscle, muscles. Paralysis can also be accompanied by a loss of feeling (sensory loss) in the affected area if there is sensory d ...

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 often used as a synony ...

s, and

death Death is the end of life; the irreversible cessation of all biological functions that sustain a living organism. Death eventually and inevitably occurs in all organisms. The remains of a former organism normally begin to decompose sh ...

.Paul Klausen
Bromethalin
Animal Disease Diagnostic Laboratory, Spring 1997 Newsletter

Risk of poisoning to humans and pets

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 A poison control center is a medical service that is able to provide immediate, free, and expert treatment advice and assistance over the telephone in case of exposure to poisonous or hazardous substances. Poison control centers answer questions ...

. 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 neural oscillations, oscillations or twitching movements of one or more body parts. It is the most common of all involuntary movements and can affect the h ...

s, hyperexcitability, fits, extreme sensitivity to being touched (

hyperesthesia Hyperesthesia is a condition that involves an abnormal increase in sensitivity to stimuli of the senses. Stimuli of the senses can include sound that one hears, foods that one tastes, textures that one feels, and so forth. Increased touch sensi ...

) and

seizure A seizure is a sudden, brief disruption of brain activity caused by abnormal, excessive, or synchronous neuronal firing. Depending on the regions of the brain involved, seizures can lead to changes in movement, sensation, behavior, awareness, o ...

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. The best treatment is decontamination, but this is only effective if started before symptoms appear.

References

{{Neurotoxins Rodenticides Nitrobenzene derivatives Anilines Bromobenzene derivatives Trifluoromethyl compounds Respiratory toxins Neurotoxins