Carboxyhemoglobin effect

Carboxyhemoglobin effect. Cigarette smoke was administered by inhalation with a modified Walton horizontal smoke exposure machine to mice at intermittent doses. During the first 30 seconds of each 1-minute cycle, the subjects were exposed to smoke diluted either 1 10 or 1 5 with air. This treatment produced carboxyhemoglobin... 

The 8-h no-effect mean geometric concentration of 1 ppm (with excursions up to 6 ppm) from the Leeser et al. (1990) study was used as the basis for time scaling the AEGL-1 values. This study was chosen because it was well conducted all workers had full medical examinations and routine blood tests, including measurements of blood cyanide and carboxyhemoglobin. Atmospheric HCN concentrations were monitored in the plant several times during the year. Because of the extrapolation from a long-term exposure, the... 

A number of compounds act in synergy with cyanide to produce toxic effects. In smoke, hydrogen cyanide may interact with other toxicants (Birky and Clarke 1981). High blood cyanide levels were found in fire victims however, the carboxyhemoglobin levels were also high. Thus, it is difficult to assess the... 

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. 

Villard, B. Lacarelle, J. Catalin, and B. Bruguerolle. Effects of different exposure times to tobacco smoke intoxication on carboxyhemoglobin and hepatic enzymate activities in mice. J Pharmacol Toxicol Methods 1996 35(4) 211-215. 

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... 

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.

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. 

Horvath, S.M., T.E.Dahms, and I.F.O=Hanlon. 1971. Carbon monoxide and human vigilance a deleterious effect of present urban concentrations. Arch. Environ. Health 23(5) 343-347. Horvath, S.M., P.B.Raven, T.E.Dahms, and D.I.Gray. 1975. Maximal aerobic capacity at different levels of carboxyhemoglobin. J. Appl. Physiol. 38(2) 300-303. 

The authors, based on previous reports of the vasogenic effects of marijuana, suggested that this event may have been related to increased concentrations of catecholamine and carboxyhemoglobin, and diminishing cerebral autoregulatory capacity. 

FIGURE 20.2. Effect of carboxyhemoglobin (COHb) upon the shape of the oxyhemoglobin dissociation curve in healthy males. Based on data of Haldane and Priestley (1935) as presented by Shephard (1983). 

A rise in temperature commonly causes a decrease in /S, although the opposite effect is also found. In the case of ovalbumin the solubility has a minimum value at 25°C (S0rensen and H0yrup, 1915-1917). An ammonium sulfate solution saturated with a protein at 0°C may throw out 90 % of this protein if the solution is allowed to warm up to room temperature. For example, carboxyhemoglobin is ten times as soluble in ammonium... 

Fig. 4. Effect of temperature and pH on salting-out curves of carboxyhemoglobin by phosphate. Replotted from Green (1931).

Figure 4 shows the effect of change of pH and temperature on the log s curve for carboxyhemoglobin (in this case for phosphate) (replotted from Green, 1931). It will be seen that the curves are parallel, showing the constancy of Ks. The position of the line in relation to the vertical scale varies because of the variation of /3 since it is straight, the same effect could be produced by a displacement along the horizontal axis. In other words a... 

We start with data on the emission of CO. A dispersion model gives us estimates on the CO-concentrations in the air. An exposure model is used to obtain estimates of the number of persons exposed to different CO-concentrations. Then follows a model relating CO-levels to carboxyhemoglobin (COHb) leveb in the blood. Finally, a dose-response model is required to obtain estimates for the health effects. These estimates should be gjven in terms of a frequency distribution to account for uncertainty. 

Most BEIs are defined as concentrations of determinants or biomarkers anticipated in biological specimens collected from healthy workers whose exposure to certain chemicals by all routes is equivalent to that of workers with inhalation only exposure at the OEL. Others measure reversible effects on the body, and still others are those that are below the concentrations associated with health effects. However, other definitions are common. For example, the German biological tolerance values (BAT) can be defined as rates of excretion of the chemical or its metabolites, or the maximum possible deviation from the norm of biological parameters induced by these substances in exposed humans. BEIs for some chemicals use other criteria, such as direct comparison with a measurable toxic effect, like carboxyhemoglobin in blood for carbon monoxide. 

Carbon monoxide is eliminated via the lungs. Dissociation and excretion of carbon monoxide occur rapidly after cessation of exposure but slow as carboxyhemoglobin levels decrease. Cardiovascular injury can result from carboxymyoglobin formation and vasodilation from cellular effects of carbon monoxide. Clinical neurological effects and any delayed neurological sequelae can be attributed to asphyxia as well as lipid peroxidation, and hypotension, which induce ischemic-reperfusion injury. 

Carbon monoxide binds very strongly to hemoglobin in red blood cells, resulting in the production of carboxyhemoglobin (COHb) this can actually be used as a marker for exposure to carbon monoxide. The presence of COHb impairs the normal transport of oxygen within the blood and can result in adverse effects on tissues, such as those in the cardiovascular and nervous systems, which have high oxygen needs. 

An important physiological effect of CO is its interference with 02 transfer, brought about by the combination of CO gas with hemoglobin (Hb), forming carboxyhemoglobin, HbCO, or COHb ... 

One of the more insidious effects of carbon monoxide poisoning is the delayed development of neuropsychiatric sequelae, which may include personality changes, motor disturbances, and memory impairment. These manifestations do not correlate either with the length of exposure or the maximum blood carboxyhemoglobin concentration but are more likeiy if patients experienced a deep coma. ... 

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