Carbon monoxide carboxyhemoglobin

A deterrnination that carbon monoxide might be a metaboUte of methylene chloride in humans (33) suggests that unacceptable levels of carboxyhemoglobin would exist in the blood of persons exposed to methylene chloride vapors at concentrations greater than 500 ppm for extended periods of time. These conditions are rarely encountered in most industrial appHcations. However, as with any organic solvent, adequate ventilation should be provided to ensure compliance with all industrial and governmental regulations. 

One of the most carefully worked out dose-response relationships is that for carbon monoxide poisoning. Based on controlled studies of exposure in humans at low levels and on observations in humans who have suffered high level exposures because of their occupation or because of accidents or suicide attempts, the relationship between blood levels of carboxyhemoglobin (COHb) and toxicity is understood as follows ... 

Carboxyhemoglobin carbon monoxide Blood 4-6 h No Traffic, body formation... 

Carboxyhemoglobin Concentration [HbCO] This can be estimated with the method of Jones and co workers. The subject holds a deep breath for 20 s to allow equilibration of carbon monoxide between alveolar air and blood and then expires a sample of that air into a container. The air carbon monoxide concentration may be directly related to carboxyhemoglobin concentration [HbCO]. The test can be performed before exposure in an environmental chamber to help to verify that the subject has not received inordinate ambient pollutant exposure. 

Adult male volunteers were exposed to purified air,2 -2 - to ozone alone, or to ozone in combination with nitrogen dioxide and carbon monoxide. No additional effects were detected when nitrogen dioxide at 0.3 ppm was added to ozone. The addition of carbon monoxide at 30 ppm to the ozone-nitrogen dioxide mixture produced no additional effects, other than a slight increase in blood carboxyhemoglobin content and small decreases in psychomotor performance, which were not consistent in different subject groups. 

Carbon monoxide also bonds to hemoglobin to form a compound known as carboxyhemoglobin ... 

The bond between iron and carbon monoxide, however, is at least 300 times stronger than that between iron and oxygen. When carbon monoxide is present in the lungs, therefore, it displaces oxygen from oxyhemoglobin, forming carboxyhemoglobin instead ... 

Monoxide for Carboxyhemoglobin Determination in Evaluating Carbon Monoxide Exposures Resulting from the Operation of Gasoline Fork Lift Trucks in Holds of Ships, Am. Ind. Hyg. Assoc. J., 1979, 30, 477-483. 

However, the mathematics describes an idealized situation, and the real situation in vivo may not be so straightforward. For example, with carbon monoxide, as already indicated, the toxicity involves a reversible interaction with a receptor, the protein molecule hemoglobin (see chap. 7 for further details of this example). This interaction will certainly be proportional to the concentration of carbon monoxide in the red blood cell. However, in vivo about 50% occupancy or 50% carboxyhemoglobin may be sufficient for the final toxic effect, which is cellular hypoxia and lethality. Duration of exposure is also a factor here because hypoxic cell death is not an instantaneous response. This time-exposure index is also very important in considerations of chemical carcinogenesis. 

The number of receptor sites and the position of the equilibrium (Eq. 1) as reflected in KT, will clearly influence the nature of the dose response, although the curve will always be of the familiar sigmoid type (Fig. 2.4). If the equilibrium lies far to the right (Eq. 1), the initial part of the curve may be short and steep. Thus, the shape of the dose-response curve depends on the type of toxic effect measured and the mechanism underlying it. For example, as already mentioned, cyanide binds very strongly to cytochrome a3 and curtails the function of the electron transport chain in the mitochondria and hence stops cellular respiration. As this is a function vital to the life of the cell, the dose-response curve for lethality is very steep for cyanide. The intensity of the response may also depend on the number of receptors available. In some cases, a proportion of receptors may have to be occupied before a response occurs. Thus, there is a threshold for toxicity. With carbon monoxide, for example, there are no toxic effects below a carboxyhemoglobin concentration of about 20%, although there may be... 

The mechanism underlying carbon monoxide poisoning is well understood at the biochemical level. Carbon monoxide binds to the iron atom in hemoglobin at the same binding site as oxygen, but it binds more avidly, indeed about 240 times more strongly. The product is carboxyhemoglobin, which may contain one or more carbon monoxide molecules. 

Figure 7.67 The dissociation of carboxyhemoglobin in the blood of a patient poisoned with carbon monoxide. The graph shows the effects of (A) breathing air (B), oxygen, or (C) oxygen at increased pressure (2.5 atmospheres) on the rate of dissociation. Source From Ref. 19.

Andersen, M.E., Clewell, H.J., Gargas, M.L., MacNaughton, M.G., Reitz, R.H., Nolan, R.J. McKenna, M.J. (1991) Physiologically based pharmacokinetic modelling with dichloromethane, its metabolite, carbon monoxide, and blood carboxyhemoglobin in rats and humans. Toxicol, appl. Pharmacol.. 108, 14-27... 

Carbon monoxide Motor vehicle emissions Burning fossil fuels Incomplete combustion Combines with hemoglobin to form carboxyhemoglobin, poisonous Asphyxia and death... 

One hemoglobin adduct, carboxyhemoglobin, is a special case in that it is both an indicator of exposure and an effect. Carboxyhemoglobin is the key biochemical derangement caused by carbon monoxide, so its concentration is directly related to health risk. For other biomarkers that utilize hemoglobin adducts, hemoglobin is not the biochemical target. 

The blood of an individual exposed to carbon monoxide shows elevated levels of carboxyhemoglobin. 

Carbon monoxide enters the bloodstream through the lungs and reacts with oxyhemoglobin (02Hb) to produce carboxyhemoglobin (COHb) ... 

Their injuries were inhalation bums, presumably caused by breathing in the hot smoke produced by the burning of the toy fireworks. In view of the observed increase of carboxyhemoglobin observed in their blood, inhalation of carbon monoxide also probably occurred. The appearance of soot on forcibly exhaling suggested the inhalation of a considerable amount of smoke as well. 

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