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

[5] The FDA has previously set a threshold of 14% COHb in certain clinical trials evaluating the therapeutic potential of carbon monoxide.

[4][10][11] In humans, the Hb-Kirklareli mutation has a relative 80,000 times greater affinity for carbon monoxide than oxygen resulting in systemic carboxyhemoglobin reaching a sustained level of 16% COHb.

[4] Some deep-diving marine mammal species are known to contain concentrations of carbon monoxide in their blood that resembles levels seen in chronic cigarette smokers, which may provide benefits against hypoxia.

Trace evidence for an endogenous presence of carbon monoxide dates back to Marcellus Donato circa 1570 who noted an unusually red complexion upon conducting an autopsy of victims who died from charcoal fumes in Mantua.

[4] Similar findings pertaining to red complexion later emerged as documented by Johann Jakob Wepfer in the 1600s, and M. Antoine Portal in the late 1700s.

[4] The mechanism for carbon monoxide poisoning in the context of carboxyhemoglobin formation is widely credited to Claude Bernard whose memoirs beginning in 1846 and published in 1857 notably phrased, "prevents arterials blood from becoming venous".

Hoppe-Seyler likewise coined the name Kohlenoxydhämoglobin[22] which may have similarly been directly translated back into English as "carbonic oxide hæmoglobin".

[23] The term carboxyhæmoglobin appeared as early as 1895 in works by John Haldane while the name for CO was still widely regarded as carbonic oxide.

As carboxy is now firmly associated with the CO2 carboxyl group, and carbon monoxide is generally regarded as a carbonyl, IUPAC has recommended "carbonylhemoglobin" as the preferred COHb nomenclature.

[26][27] Most methods require laboratory equipment, skilled technicians, or expensive electronics therefore rapid and economical detection technologies remain in development.

While inhaling air is critical to supply cells with oxygen for aerobic respiration via the Bohr effect and Haldane effect (and perhaps local low oxygen partial pressure e.g. active muscles),[32] exhaling the cellular waste product carbon dioxide is arguably the more critical aspect of respiration.

Whereas the body can tolerate brief periods of hypoxia (as commonly occurs in anaerobic exercise, although the brain, heart, liver and kidney are significantly less tolerant than skeletal muscle), failure to expel carbon dioxide may cause respiratory acidosis (meaning bodily fluids and blood become too acidic thereby affecting homeostasis).

[33] In absence of oxygen, cells switch to anaerobic respiration which if prolonged may significantly increase lactic acid leading to metabolic acidosis.

[4] Additionally, treatment in a hyperbaric chamber is a more effective manner of reducing the half-life of carboxyhemoglobin to 30 minutes[4] and allows oxygen to dissolve in biological fluids for delivery to tissues.

[citation needed] Supplemental oxygen takes advantage of Le Chatelier's principle to quicken the decomposition of carboxyhemoglobin back to hemoglobin:[39] As carbon monoxide is now understood to have a therapeutic potential, pharmaceutical efforts have focused on development of carbon monoxide-releasing molecules and selective heme oxygenase inducers.

[40] An alternative method for drug delivery consists of carbon monoxide immobilized on polyethylene glycol (PEG)-lyated bovine carboxyhemoglobin which is currently in late clinical development.