[2] The biological threshold for carboxyhemoglobin tolerance is typically accepted to be 15% COHb, meaning toxicity is consistently observed at levels in excess of this concentration.

[13][9] The discovery that hemoglobin is affected by CO emerged with an investigation by James Watt and Thomas Beddoes into the therapeutic potential of hydrocarbonate in 1793, and later confirmed by Claude Bernard between 1846 and 1857.

Small amounts of carbon monoxide are naturally produced through many enzymatic and non-enzymatic reactions across phylogenetic kingdoms where it can serve as an important neurotransmitter (subcategorized as a gasotransmitter) and a potential therapeutic agent.

[16] The carbon monoxide tolerance level for any person is altered by several factors, including genetics (hemoglobin mutations), behavior such as activity level, rate of ventilation, a pre-existing cerebral or cardiovascular disease, cardiac output, anemia, sickle cell disease and other hematological disorders, geography and barometric pressure, and metabolic rate.

[30] Increasing exposure produces cardiac abnormalities including fast heart rate, low blood pressure, and cardiac arrhythmia;[31][32] central nervous system symptoms include delirium, hallucinations, dizziness, unsteady gait, confusion, seizures, central nervous system depression, unconsciousness, respiratory arrest, and death.

Problems may include difficulty with higher intellectual functions, short-term memory loss, dementia, amnesia, psychosis, irritability, a strange gait, speech disturbances, Parkinson's disease-like syndromes, cortical blindness, and a depressed mood.

[41] Chronic exposure to relatively low levels of carbon monoxide may cause persistent headaches, lightheadedness, depression, confusion, memory loss, nausea, hearing disorders and vomiting.

[42] However, one case noted permanent memory loss and learning problems after a three-year exposure to relatively low levels of carbon monoxide from a faulty furnace.

[28][57] Carbon monoxide detection and poisoning also increases during power outages, when electric heating and cooking appliances become inoperative and residents may temporarily resort to fuel-burning space heaters, stoves, and grills (some of which are safe only for outdoor use but nonetheless are errantly burned indoors).

[11] In the United States, approximately 200 people die each year from carbon monoxide poisoning associated with home fuel-burning heating equipment.

Sources of carbon monoxide include cigarette smoke, house fires, faulty furnaces, heaters, wood-burning stoves,[76] internal combustion vehicle exhaust, electrical generators, propane-fueled equipment such as portable stoves, and gasoline-powered tools such as leaf blowers, lawn mowers, high-pressure washers, concrete cutting saws, power trowels, and welders.

If a relatively high level of carbon monoxide is detected, the device sounds an alarm, giving people the chance to evacuate and ventilate the building.

[107] Carbon monoxide may be quantitated in blood using spectrophotometric methods or chromatographic techniques in order to confirm a diagnosis of poisoning in a person or to assist in the forensic investigation of a case of fatal exposure.

[16][118] Due to the possible severe effects in the baby, pregnant women are treated with oxygen for longer periods of time than non-pregnant people.

[133][134][135][136] A review of all the literature concluded that the role of hyperbaric oxygen is unclear and the available evidence neither confirms nor denies a medically meaningful benefit.

[33] Outcomes are often difficult to predict following poisoning,[141] especially people who have symptoms of cardiac arrest, coma, metabolic acidosis, or have high carboxyhemoglobin levels.

The simplistic understanding for the mechanism of carbon monoxide toxicity is based on excess carboxyhemoglobin decreasing the oxygen-delivery capacity of the blood to tissues throughout the body.

This results following a recurrence of increased carboxyhemoglobin levels; this effect may be due to a late release of carbon monoxide from myoglobin, which subsequently binds to hemoglobin.

[29] The mechanism that is thought to have a significant influence on delayed effects involves formed blood cells and chemical mediators, which cause brain lipid peroxidation (degradation of unsaturated fatty acids).

Carbon monoxide causes endothelial cell and platelet release of nitric oxide, and the formation of oxygen free radicals including peroxynitrite.

[150] The result of these effects is lipid peroxidation, which causes delayed reversible demyelination of white matter in the central nervous system known as Grinker myelinopathy, which can lead to edema and necrosis within the brain.

[150][151] Hallmark pathological changes following poisoning are bilateral necrosis of the white matter, globus pallidus, cerebellum, hippocampus and the cerebral cortex.

The early development of metallurgy and smelting technologies emerging circa 6,000 BC through the Bronze Age likewise plagued humankind with carbon monoxide exposure.

[9] Julian the Apostate, Caelius Aurelianus, and several others similarly documented early knowledge of the toxicity symptoms of carbon monoxide poisoning as caused by coal fumes in the ancient era.

[156] In the fifteenth century, coal miners believed sudden death was caused by evil spirits; carbon monoxide poisoning has been linked to supernatural and paranormal experiences, witchcraft, etc.

Friedrich Hoffmann conducted the first modern scientific investigation into carbon monoxide poisoning from coal in 1716, notably rejecting villagers attributing death to demonic superstition.

John Scott Haldane identified carbon monoxide as the lethal constituent of afterdamp, the gas created by combustion, after examining many bodies of miners killed in pit explosions.

[159] On 14 December 2024 12 individuals died by carbon monoxide poisoning in Gudauri (Georgia) as electric generators using fuel oil were placed in a closed area near their rooms.

[9] In 1884, an article appeared in Scientific American describing the use of a carbon monoxide gas chamber for slaughterhouse operations as well as euthanizing a variety of animals.

[161] As part of the Holocaust during World War II, the Nazis used gas vans at Chelmno extermination camp and elsewhere to murder an estimated 700,000 or more people by carbon monoxide poisoning.