A friend of mine is worried that carbon monoxide levels taken 6 days after death show a higher reading in comparisum to oxygen taken 6 days after death than would have been, if taken at the time of death. This figure is paramount to a court case and him loosing his job. Can anyone comment? The O2 reading was taken with an oximeter before death, disguising the carbon monoxide poisoning CARBON MONOXIDE
See Occupational Exposure Standards
Human Health Effects:
Toxicity Summary:
It is a product of the incomplete combustion of carbon-containing fuels and is also produced by natural processes or by biotransformation of halomethanes within the human body. With external exposures to additional carbon monoxide, subtle effects can begin to occur, and exposure to higher levels can result in death. The health effects of carbon monoxide are largely the result of the formation of carboxyhemoglobin (COHb), which impairs the oxygen carrying capacity of the blood. ... During typical daily activities, people encounter carbon monoxide in a variety of microenvironments - while travelling in motor vehicles, working at their jobs, visiting urban locations associated with combustion sources, or cooking or heating with domestic gas, charcoal or wood fires - as well as in tobacco smoke. ... Studies of human exposure have shown that motor vehicle exhaust is the most important source for regularly encountered elevated carbon monoxide levels. ... The workplace is another important setting for carbon monoxide exposures ... Certain industrial processes can expose workers to carbon monoxide produced directly or as a byproduct ... Carbon monoxide is absorbed through the lungs, and the concentration of carboxyhemoglobin will depend ... mainly on the concentrations of inspired carbon monoxide and oxygen ... and will also depend on the duration of exposure, pulmonary ventilation, and the concentration of carboxyhemoglobin originally present ... In addition to its reaction with hemoglobin, carbon monoxide combines with myoglobin, cytochromes, and metalloenzymes such as cytochromoe c oxidase and cytochrome P-450. ... The binding of carbon monoxide to hemoglobin, producing carboxyhemoglobin and decreasing the oxygen carrying capacity of blood, appears to be the principal mechanism of action underlying the induction of toxic effects of low-level carbon monoxide exposures. The precise mechanisms by which toxic effects are induced ... are not understood fully but likely include the induction of a hypoxic state in many tissues of diverse organ systems. ... A unique feature of carbon monoxide exposure, therefore, is that the blood carboxyhemoglobin level represents a useful biological marker of the dose that the individual has received. ... The formation of carboxyhemoglobin is a reversible process; however, because of the tight binding of carbon monoxide to hemoglobin, the elimination half-time is quite long, ranging from 2 to 6.5 hr ... The level of carboxyhemoglobin in the blood may be determined directly by blood analysis or indirectly by measuring carbon monoxide in exhaled breath. ... Decreased oxygen uptake and the resultant decreased work capacity under maximal exercise conditions have clearly been shown to occur ... However, of greater concern at more typical ambient carbon monoxide exposure levels are certain cardiovascular effects (i.e., aggravation of angina symptoms during exercise) likely to occur in a smaller, but sizeable, segment of the general population. This group, chronic angina patients, is currently viewed as the most sensitive risk group for carbon monoxide exposure effects ... The adverse health consequences of low level carbon monoxide exposure to patients with ischemic heart disease are very difficult to predict in the at-risk population of individuals with heart disease. ... At high carbon monoxide concentrations, excessive increases in hemoglobin and hematocrit may impose an additional workload on the heart and compromise blood flow to the tissues. ... It is unlikely that carbon monoxide has any direct effects on lung tissue except for extremely high concentrations associated with carbon monoxide poisoning. ... Occupational or accidental exposure to the products of combustion and pyrolysis, particularly indoors, may lead to acute decrements in lung function if the carboxyhemoglobin levels are high. It is difficult, however, to separate the potential effects of carbon monoxide from those due to other respiratory irritants in the smoke and exhaust. ... Of special note are those individuals who are taking drugs with primary or secondary depressant effects that would be expected to exacerbate carbon monoxide-related neurobehavorial decrements. Other groups at possible increased risk for carbon monoxide-induced neurobehavorial effects are the aged and ill ... Under normal circumstances, the brain can increase blood flow or tissue oxygen extraction to compensate for the hypoxia caused by exposure to carbon monoxide. ...
[Environmental Health Criteria 213: Carbon Monoxide pp. 1-12 (1999) by the International Programme on Chemical Safety (IPCS) under the joint sponsorship of the United Nations Environment Programme, the International Labour Organisation and the World Health Organization.]**QC REVIEWED**
... Studies in several laboratory animal species provide strong evidence that maternal carbon monoxide exposures ... produce reductions of birth weight, cardiomegaly, delays in behavorial development and disruptions in cognitive function. ... Laboratory animal studies suggest that enzyme metabolism of xenobiotic compounds may be affected by carbon monoxide exposure. ... The decreases in xenobiotic metabolism shown with carbon monoxide exposure might be important to individuals receiving treatment with drugs. ... Tissues of highly active oxygen metabolism, such as heart, brain, liver, kidney, and muscle, may be particularly sensitive to carbon monoxide poisoning. There are reports ... of effects on liver, kidney, bone and the immune capacity of the lung and spleen. It is generally agreed that the severe tissue damage occurring during acute carbon monoxide poisoning is due to one of more of the following: (1) ischemia resulting from the formation of carboxyhemoglogin, (2) inhibition of oxygen release from oxyhemoglobin, (3) inhibition of oxygen release from oxyhemoglobin, (3) inhibition of cellular cytochrome function (e.g., cytochrome oxidases) and (4) metabolic acidosis. ... Whereas certain data also suggest that perinatal effects (e.g., reduced birth weight, slowed post-natal developments, sudden infant death syndrome) are associated with carbon monoxide exposure, insufficient evidence exists by which to either qualitatively confirm such an association in humans or establish any pertinent exposure-effect relationships. ... There remains little direct information on the possible enhancement of carbon monoxide toxicity by concomitant drug use or abuse ... The greatest evidence for a potentially important interaction of carbon monoxide comes from studies with alcohol in both laboratory animals and humans, where at least additive effects have been obtained. The significance of this is augmented by the high probable incidence of combined alcohol use and carbon monoxide exposure. ... Besides being a source of carbon monoxide for smokers as well as non-smokers, tobacco smoke is also a source of other chemicals with which environmental carbon monoxide could interact. ... On the basis of known effects described, patients with reproducible exercise-induced ischemia appear to be the best established as a sensitive group within the general population that is at increased risk for experiencing health effects of concern (i.e., decreased exercise duration due to exacerbation of cardiovascular symptoms) at ambient or near-ambient carbon monoxide concentrations ... Decrements in exercise duration in the healthy population would therefore be of concern mainly to competing athletes, rather than to ordinary people carrying out the common activities of daily life. It can be hypothesized, however, from both clinical and theoretical work and from experimental research on laboratory animals, that certain other groups in the population may be at probable risk from exposure to carbon monoxide. Identifiable probable risk groups can be categorized by gender differences; by age ...; by genetic variations...; by pre-existing diseases...; or by the use of medications, recreational drugs or alterations in environment ... Unfortunately, little empirical evidence is currently available by which to specify health effects associated with ambient or near-ambient carbon monoxide exposure to these probable risk groups. ...
[Environmental Health Criteria 213: Carbon Monoxide pp. 12-18 (1999) by the International Programme on Chemical Safety (IPCS) under the joint sponsorship of the United Nations Environment Programme, the International Labour Organisation and the World Health Organization.]**QC REVIEWED**
... Carbon monoxide is responsible for a large percentage of the accidental poisonings and deaths reported throughout the world each year. ... Outdoors, concentrations of carbon monoxide are highest near street intersections, in congested traffic, near exhaust gases from internal combustion engines and from industrial sources, and in poorly ventilated areas such as parking garages and tunnels. Indoors, carbon monoxide concentrations are highest in workplaces or in homes that have faulty or poorly vented combustion appliances or downdrafts or backdrafts. The symptoms and signs of acute carbon monoxide poisoning correlate poorly with the level of carboxyhemoglobin measured at the time of arrival at the hospital. ... Neurological symptoms of carbon monoxide poisoning can ocur, such as headache, dizziness, weakness, nausea, confusion, disorientation and visual disturbances. Exertional dyspnea, increases in pulse and respiratory rates and syncope are observed with continuous exposure ... When carboxyhemoglobin levels are higher than 50%, convulsions and cardiopulmonary arrest may occur. Complications occur frequently in carbon monoxide poisoning (immediate death, myocardial impairment, hypotension, arrhythmias, pulmonary edema). Perhaps the most insidious effect of carbon monoxide poisoning is the delayed development of neuropyschiatric impairment ... and the neurobehavioral consequences, especially in children. Carbon monoxide poisoning during pregnancy results in high risk for the mother, by increasing the short-term complications rate and for the fetus by causing fetal death, developmental disorders, and cerebral anoxic lesions. Furthermore, the severity of fetal intoxication cannot be assessed by the maternal rate. Carbon monoxide poisoning occurs frequently, has severe consequences, including immediate death, involves complications and late sequelae and is often overlooked. ...
[Environmental Health Criteria 213: Carbon Monoxide pp. 18-19 (1999) by the International Programme on Chemical Safety (IPCS) under the joint sponsorship of the United Nations Environment Programme, the International Labour Organisation and the World Health Organization.]**QC REVIEWED**
Human Toxicity Excerpts:
SYMPTOMATOLOGY: 1. NO SYMPTOMS OR SHORTNESS OF BREATH DURING VIGOROUS MUSCULAR EXERCISE (0 TO 10% COHB (CARBOXYHEMOGLOBIN). 2. A MILD HEADACHE ...AND BREATHLESSNESS ON MODERATE EXERCISE (10-20% COHB). 3. THROBBING HEADACHE, IRRITABILITY, EMOTIONAL INSTABILITY, IMPAIRED JUDGEMENT, DEFECTIVE MEMORY, AND RAPID FATIGUE (20-30% COHB).
[Gosselin, R.E., R.P. Smith, H.C. Hodge. Clinical Toxicology of Commercial Products. 5th ed. Baltimore: Williams and Wilkins, 1984.,p. III-98]**PEER REVIEWED**
SYMPTOMATOLOGY: 4. SEVERE HEADACHE, WEAKNESS, NAUSEA & VOMITING, DIZZINESS, DIMNESS OF VISION, CONFUSION (30-40% COHB). 5. INCREASING CONFUSION, SOMETIMES HALLUCINATIONS, SEVERE ATAXIA, ACCELERATED RESPIRATIONS...(40-50% COHB). 6. SYNCOPE OR COMA WITH INTERMITTENT CONVULSIONS, TACHYCARDIA WITH A WEAK PULSE...(50-60% COHB)... PALLOR OR CYANOSIS.7. INCREASING DEPTH OF COMA WITH INCONTINENCE OF URINE & FECES (60-70% COHB). 8. PROFOUND COMA WITH DEPRESSED OR ABSENT REFLEXES, A WEAK THREADY PULSE, SHALLOW AND IRREGULAR RESPIRATIONS AND COMPLETE QUIESCENCE (70-80% COHB). 9. RAPID DEATH FROM RESPIRATORY ARREST (ABOVE 80% COHB). 10. MISCELLANEOUS & ATYPICAL REACTIONS INCLUDE VARIOUS SKIN LESIONS, SWEATING, HEPATOMEGALY, HYPERPYREXIA, ALBUMINURIA, OLIGURIA, ANGINAL PAIN, & CONGESTIVE HEART FAILURE...
[Gosselin, R.E., R.P. Smith, H.C. Hodge. Clinical Toxicology of Commercial Products. 5th ed. Baltimore: Williams and Wilkins, 1984.,p. III-98]**PEER REVIEWED**
SYMPTOMATOLOGY: 11. DURING CONVALESCENCE A BRONCHOPNEUMONIA MAY DEVELOP BECAUSE OF THE ASPIRATION OF SALIVA OR VOMITUS... 12. MYOCARDIAL INFARCTION, WITH OR WITHOUT CORONARY THROMBOSIS, MAY APPEAR AT ANY TIME UP TO ONE WEEK FOLLOWING AN ACUTE POISONING. 13. AFTER AN UNEVENTFUL CONVALESCENCE, SIGNS OF NERVE OR BRAIN INJURY MAY APPEAR AT ANY TIME WITHIN THREE WEEKS FOLLOWING AN ACUTE EXPOSURE. AMONG PERMANENT SEQUELAE ARE NEUROPATHIES, VARIOUS MOTOR AND MENTAL DEFECTS, SOME OF WHICH MIMIC MULTIPLE SCLEROSIS OR PARKINSONISM, AND DEATH.
[Gosselin, R.E., R.P. Smith, H.C. Hodge. Clinical Toxicology of Commercial Products. 5th ed. Baltimore: Williams and Wilkins, 1984.,p. III-98]**PEER REVIEWED**
Rapidly fatal cases of carbon monoxide poisoning are characterized by congestion and hemorrhages in all organs. In longer-term, eventually fatal cases, the hypoxic lesions observed are related to the duration of posthypoxic unconsciousness. ... The maximal period of carbon monoxide induced posthypoxic unconsciousness compatible with complete neurological recovery is 21 hr in patients under 48 years of age and 11 hours in older patients. Complete recovery of mental functon was not observed when the carbon monoxide induced unconsciousness exceeded 15 hours in the older or 64 hours in the younger group.
[Gilman, A.G., T.W. Rall, A.S. Nies and P. Taylor (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 8th ed. New York, NY. Pergamon Press, 1990. 1620]**PEER REVIEWED**
THE FETUS MAY BE EXTREMELY SUSCEPTIBLE TO EFFECTS OF CARBON MONOXIDE, AND THE GAS READILY CROSSES THE PLACENTA. INFANTS BORN TO WOMEN WHO HAVE SURVIVED SHORT TERM EXPOSURE TO A HIGH CONCENTRATION OF THE GAS WHILE PREGNANT OFTEN DISPLAY NEUROLOGICAL SEQUELAE, AND THERE MAY BE GROSS DAMAGE TO THE BRAIN.
[Gilman, A.G., T.W. Rall, A.S. Nies and P. Taylor (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 8th ed. New York, NY. Pergamon Press, 1990. 1620]**PEER REVIEWED**
Persistent low levels of COHb in the fetus of a woman who has smoked during pregnancy may also have effects on the development of the CNS.
[Gilman, A.G., T.W. Rall, A.S. Nies and P. Taylor (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 8th ed. New York, NY. Pergamon Press, 1990. 1620]**PEER REVIEWED**
Carbon monoxide at levels encountered in tobacco smoke has been suspected to impair night-time vision. In rats, chronic prenatal exposure to similar concn has been shown to affect visual evoked cortical potentials.
[Grant, W.M. Toxicology of the Eye. 3rd ed. Springfield, IL: Charles C. Thomas Publisher, 1986. 183]**PEER REVIEWED**
A CARBON MONOXIDE-INTOXICATED PATIENT DEVELOPED INCR PERMEABILITY-TYPE PULMONARY EDEMA DEMONSTRATED BY A NORMAL CAPILLARY WEDGE PRESSURE AND PRODUCTION OF PROTEIN-RICH EDEMA FLUID.
[FEIN A ET AL; CHEST 78 (5): 726 (1980)]**PEER REVIEWED**
PATIENT WITH POSSIBLE RESIDUAL NEUROLOGIC EFFECTS FROM CARBON MONOXIDE AND RETROSPECTIVE STUDY OF PEDIATRIC PATIENTS WITH ACUTE DIAGNOSIS OF CARBON MONOXIDE POISONING ARE PRESENTED. EVIDENCE FOR CONCLUSION THAT CARBON MONOXIDE CAN PRODUCE RESIDUAL NEUROLOGICAL INJURY IS INCLUDED.
[BINDER JW, ROBERTS RJ; CLIN TOXICOL 16 (3): 287 (1980)]**PEER REVIEWED**
The tissues most affected are those most sensitive to oxygen deprivation, such as the brain and the heart, and the lesions are predominantly hemorrhagic. The severe headache following exposure to carbon monoxide is believed to be caused by cerebral edema and increased intracranial pressure resulting from excessive transudation across hypoxic capillaries.
[Gilman, A.G., T.W. Rall, A.S. Nies and P. Taylor (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 8th ed. New York, NY. Pergamon Press, 1990. 1619]**PEER REVIEWED**
...CHRONIC EXPOSURE TO LOW CONCENTRATIONS MAY EVOKE AN INSIDIOUS TOXICITY. ...SIGNIFICANTLY, ACTIVE CIGARETTE SMOKERS EXHIBITED PRONOUNCED ELEVATIONS /OF CARBOXYHEMOGLOBIN/ IN BLOOD LEVELS.
[Fuscaldo, A., B. J. Erlick, and B. Hindman. (eds.). Laboratory Safety-Theory and Practice. New York: Academic Press, 1980. 272]**PEER REVIEWED**
The effects of carbon monoxide induced acute elevation of carboxyhemoglobin concentrations on resting and exercise-induced ventricular arrhythmias were evaluated in 10 patients who had ischemic heart disease and in whom no ectopy during baseline monitoring was noted. Patients were exposed to air, 100 ppm carbon monoxide, or 200 ppm carbon monoxide on successive days in a randomized, double-blind, cross-over fashion. After exposure to 100 and 200 ppm carbon monoxide, venous carboxyhemoglobin levels averaged 4% and 6%, respectively. Symptom-limited supine exercise was performed after exposure. Eight of the 10 patients had evidence of exercise-induced ischemia, either angina, 1.0 mm ST depression, or abnormal ejection fraction response, during 1 or more exposure days. Ambulatory electrocardiograms were obtained on each day and analyzed for arrhythmia frequency and severity. On air and carbon monoxide exposure days, each patient had only 0-1 ventricular premature beat/hr in the 2 hr prior to exposure, during the exposure period, during the subsequent exercise test, and in the 5 hr following exercise.
[Hinderliter AL et al; Arch Environ Health 44 (2): 89-93 (1989)]**PEER REVIEWED**
Correlation between carboxyhemoglobin as determined by venous sample and arterial blood pH were studied retrospectively in 49 cases of carbon monoxide intoxication. Three cases of smoke inhalation were later excluded. The only therapeutic intervention relating to acidosis or ventilatory status was 100% oxygen administration. The range of carboxyhemoglobin levels was 10 to 64%. Of 18 arterial blood gas samples (pH = 7.37 to 7.54 with a mean of 7.43 + or - 0.04, none showed a correlation between carboxyhemoglobin level and pH. A review of records from 104 additional cases of carbon monoxide poisoning showed no significant correlation between these parameters.
[Lebby TI et al; Vet Hum Toxicol 31 (2): 138-40 (1989)]**PEER REVIEWED**
A prospective study of the association between carbon monoxide poisoning and rhabdomyolysis (myonecrosis) was studied prospectively by obtaining serum creatinine levels on 65 patients (20 to 1315 IU/l) who presented with carbon monoxide levels greater than 5.0% (range, 5 to 63.9%). No statistically significant correlation by linear regression analysis between carbon monoxide level and creatinine level was found in these patients. The 4 patients who complained of muscle weakness did not have elevated serum creatinine levels.
[Shapiro AB et al; Vet Hum Toxicol 31 (2): 136-7 (1989)]**PEER REVIEWED**
The simple and interactive effects of carbon monoxide exposure and prior physical work on cognitive performance were evaluated in 16 subjects (healthy males aged 18-29 yr) in 2 hot (WBGT = 30 deg C) environments. Three levels of carboxyhemoglobin (0, 7, and 10%) and three workloads (rest, 35% and 60% of a maximum exercise test) were crossed resulting in nine repeated measured conditions per subject. A bolus + ambient air maintenance technique was used to achieve the targeted carboxyhemoglobin levels. Following administration of carbon monoxide by bolus, subjects either exercised or rested for 50 min, then performed five cognitive tasks: Manikin spatial processing, Sternberg memory, Stroop word color, visual search, and visual tracking, with and without a secondary mathematics task. The only cognitive impairment associated with an elevated carboxyhemoglobin was seen in performance of the second of two sequentially presented Stroop test versions using the same stimuli but with competing instructions. Heat exposure per se had no significant effects on cognitive performance based on comparisons with other subjects who underwent the same protocol in a thermoneutral environment. Elevated carboxyhemoglobin was associated with greater reporting of exertion and eye, ear, nose and throat symptoms during heavy exercise concomitant with greater minute ventilation and heart rate. Except for the latter, these effects were not seen in thermoneutral conditions.
[Bunnell DE, Horvath SM; Aviat Space Environ Med 60 (5): 428-32 (1989)]**PEER REVIEWED**
/Carbon monoxide/ exposure is actually more dangerous for the pregnant woman, who produces nearly twice as much carbon monoxide endogenously each day, and particularly for the pregnant smoker. The increased minute ventilation of gestation also tends to enhance the severity of exposure. Carbon monoxide diffuses readily across placental membranes or uses carrier-mediated facilitate transfer. While the mother is treated and recovers, the infant may show neurologic or behavioral effects of the prenatal exposure. Fetal CNS damage following nonfatal maternal exposures has been seen in humans and reproduced in animals.
[Haddad, L.M., Clinical Management of Poisoning and Drug Overdose. 2nd ed. Philadelphia, PA: W.B. Saunders Co., 1990. 427]**PEER REVIEWED**
The threshold time or carbon monoxide content for fetal damage is not known. Normal infant outcome has been reported after maternal coal furnace and smoking exposure produced carbon monoxide concentrations of at least 24.5% over a number of hours prior to 8 weeks' gestation. The infant was of low birth weight (1950 g at 38 weeks' gestation), but normal development through 6 months of age at the time of the report was found.
[Haddad, L.M., Clinical Management of Poisoning and Drug Overdose. 2nd ed. Philadelphia, PA: W.B. Saunders Co., 1990. 427]**PEER REVIEWED**
In second- and third-trimester exposures, stillbirth has occurred shortly after exposure or has been delayed by several weeks. Cerebral palsy and behavioral disturbances have been observed in surviving fetuses, in addition to normal developmental outcomes.
[Haddad, L.M., Clinical Management of Poisoning and Drug Overdose. 2nd ed. Philadelphia, PA: W.B. Saunders Co., 1990. 427]**PEER REVIEWED**
Acute carbon monoxide poisoning can cause myocardial injury or aggravate underlying vascular disease. High level chronic exposures (carboxyhemoglobin 20-30%) have been reported to produce a severalfold increase in the incidence of coronary artery disease in tatami may makers in Northern Japan. These workers heated their buildings with charcoal braziers while tightly sealing windows and doors to conserve heat during cold winter weather.
[Sullivan, J.B. Jr., G.R. Krieger (eds.). Hazardous Materials Toxicology-Clinical Principles of Environmental Health. Baltimore, MD: Williams and Wilkins, 1992. 170]**PEER REVIEWED**
Peripheral neuropathy following carbon monoxide intoxication has been reported infrequently and appears to occur only after severe acute exposure. The peripheral neuropathy seen in these cases is associated with demyelination with axonal preservation. Symmetric distal motor weakness and numbness are characteristic findings in case reports. One patient manifested characteristic findings of bilateral ulnar nerve lesions. Some impairment in perceptual discrimination has been associated with long-term exposure to low levels of carbon monoxide.
[Sullivan, J.B. Jr., G.R. Krieger (eds.). Hazardous Materials Toxicology-Clinical Principles of Environmental Health. Baltimore, MD: Williams and Wilkins, 1992. 565]**PEER REVIEWED**
Severe carbon monoxide poisoning produces anatomic changes (eg, cerebral edema, hemorrhagic focal necrosis, venodilation, petechiae, perivascular infarct). Bilateral necrosis of the globus pallidus is the characteristic lesion of carbon monoxide toxicity. Other vulnerable areas of the cerebral gray matter include the substantia nigra, hippocampus, cerebral cortex, and cerebellum. These histopathological changes are indistinguishable from other causes such as hypoxia, cardiorespiratory arrest, hypoglycemia, and cyanide poisoning. Rarely, a postanoxic demyelination occurs that follows an initial recovery and progresses to irritability, confusion, coma and death. A 'moth-eaten' appearance characterizes this anoxic leukoencephalopathy in which most of the damage appears in the gray matter of the cerebral cortex, pallidum, thalamus, and cerebellar cortex.
[Ellenhorn, M.J. and D.G. Barceloux. Medical Toxicology - Diagnosis and Treatment of Human Poisoning. New York, NY: Elsevier Science Publishing Co., Inc. 1988. 823]**PEER REVIEWED**
Neurologic sequelae include visual loss, dementia, retardation, constructional apraxia, temporospacial disorientation, memory loss, dysphasia, personality changes, concentration deficits, and frank psychosis. Parkinson's disease does occur after acute carbon monoxide exposures but is very rare. After initial recovery from carbon monoxide exposure patients may develop neurologic symptoms (apathy, mutism, amnesia, urinary incontinence, headache, irritability, personality changes, confusion, memory loss, visual changes) within 2 to 4 weeks of exposure.
[Ellenhorn, M.J. and D.G. Barceloux. Medical Toxicology - Diagnosis and Treatment of Human Poisoning. New York, NY: Elsevier Science Publishing Co., Inc. 1988. 824]**PEER REVIEWED**
Retinal venous engorgement and peripupillary hemorrhage occur occasionally in both acute and subacute carbon monoxide exposures. Their presence should alert the physician to the possibility of carbon monoxide poisoning. In one series of 12 poisonings, all patients exposed to carbon monoxide over 12 hours had hemorrhages in the nerve fiber layer of the retina. Carbon monoxide decreases light sensitivity and dark adaptation. Cochlear and brain stem hypoxia leads to a central hearing loss and vestibular dysfunction (nausea, vomiting, vertigo), with vestibular symptoms usually more prominent than auditory loss.
[Ellenhorn, M.J. and D.G. Barceloux. Medical Toxicology - Diagnosis and Treatment of Human Poisoning. New York, NY: Elsevier Science Publishing Co., Inc. 1988. 824]**PEER REVIEWED**
Bullae occur, especially over pressure areas, and alopecia and sweat gland necrosis are reported rarely. The appearance of bullae appears to be related to the severity of toxicity. Cherry red skin (lips, mucous membranes) is characteristic of nonsurvivors, because the high carboxyhemoglobin levels required to produce this appearance usually are not compatible with life. Carboxyhemoglobin levels can rise after death because of the continuing extraction of oxyhemoglobin. Hence, cherry red skin is an autopsy finding and uncommon in live patients.
[Ellenhorn, M.J. and D.G. Barceloux. Medical Toxicology - Diagnosis and Treatment of Human Poisoning. New York, NY: Elsevier Science Publishing Co., Inc. 1988. 825]**PEER REVIEWED**
Several cases of hemolytic anemia have been reported after severe carbon monoxide poisoning. Thrombocytopenic purpura with respiratory dysfunction occurred in a patient who had a 20% carboxyhemoglobin level 12 hours post-exposure.
[Ellenhorn, M.J. and D.G. Barceloux. Medical Toxicology - Diagnosis and Treatment of Human Poisoning. New York, NY: Elsevier Science Publishing Co., Inc. 1988. 825]**PEER REVIEWED**
Rhabdomyolysis, acute renal failure, and peripheral neuropathies (eg, ulnar palsy) occur rarely. Myonecrosis may be massive, leading to edema, compartment syndrome, and acute renal failure.
[Ellenhorn, M.J. and D.G. Barceloux. Medical Toxicology - Diagnosis and Treatment of Human Poisoning. New York, NY: Elsevier Science Publishing Co., Inc. 1988. 825]**PEER REVIEWED**
Severe visual disturbances occur as a consequence of acute poisoning in which there has been a period of unconsciousness. ... The types of visual disturbance which have been reported may be grouped symptomatically as follows: (a) amaurosis or hemianopsia, (b) constriction of visual fields, and (c) visual abnormalities associated with optic nerve disturbances.
[Grant, W.M. Toxicology of the Eye. 3rd ed. Springfield, IL: Charles C. Thomas Publisher, 1986. 183]**PEER REVIEWED**
A crew of workers in the Holland Tunnel worked 2 hours in an average tunnel concn of 70 ppm carbon monoxide, alternating with 2 hours out of the tunnel, for 8 hour swing shifts. These workers had an average of 5% carboxyhemoglobin with no one above 10%. The average exposure was approximately 35 ppm, and no symptoms or adverse health effects were observed.
[American Conference of Governmental Industrial Hygienists, Inc. Documentation of the Threshold Limit Values and Biological Exposure Indices. 6th ed. Volumes I,II, III. Cincinnati, OH: ACGIH, 1991. 228]**PEER REVIEWED**
... A retrospective study of 1212 tunnel officers exposed to carbon monoxide, resulting in less than 5% carboxyhemoglobin, were found to have a significantly elevated risk of dying from arteriosclerotic heart disease.
[American Conference of Governmental Industrial Hygienists, Inc. Documentation of the Threshold Limit Values and Biological Exposure Indices. 6th ed. Volumes I,II, III. Cincinnati, OH: ACGIH, 1991. 229]**PEER REVIEWED**
Two workers with pre-existing coronary artery disease died after exposure to carbon monoxide sufficient to produce approximately 25% carboxyhemoglobin. This level could be reached after exposure to approximately 2000 ppm carbon monoxide for 15 minutes of light work.
[American Conference of Governmental Industrial Hygienists, Inc. Documentation of the Threshold Limit Values and Biological Exposure Indices. 6th ed. Volumes I,II, III. Cincinnati, OH: ACGIH, 1991. 229]**PEER REVIEWED**
A study was made to determine the type, incidence, and timing of complications that occur in patients who have a carbon monoxide exposure serious enough to require hyperbaric oxygen therapy. Complication data were retrospectively collected from ten year period for 297 consecutive carbon monoxide poisoned emergency department patients who received hyperbaric oxygen therapy. Hyperbaric oxygen therapy was indicated for 41% of the patients because of an elevated carboxyhemoglobin level alone. Central nervous system dysfunction, including loss of consciousness and/or cardiovascular dysfunction, was the criteria for hyperbaric oxygen therapy in 59% of patients regardless of their carboxyhemoglobin level. The mean peak carboxyhemoglobin level was 38 mg%, with 88% of patients having a peak carboxyhemoglobin level greater than 25 mg%. The mortality rate was 6% in this case series. Cardiac arrest occurred in 8% of patients: all experienced their first arrest prior to hyperbaric oxygen therapy. The 3% of patients who sustained an isolated respiratory arrest and those who had a myocardial infarction did so prior to hyperbaric oxygen therapy.
[Sloan EP et al; Ann Emerg Med 18 (6): 629-34 (1989)]**PEER REVIEWED**
This paper reports a fetal death due to accidental nonlethal maternal carbon monoxide intoxication in which both maternal and fetal carboxyhemoglobin concentrations were obtained. The corrected carboxyhemoglobin concentration was 61% at the time of death in utero, while the maternal carboxyhemoglobin was measured at 7% after one hour of supplemental oxygen. The mechanisms of fetal death were reviewed and it was emphasized the different carbon monoxide kinetics in the fetal circulation.
[Farrow JR et al; J Forensic Sci 35 (6): 1448-52 (1990)]**PEER REVIEWED**
The results of the first prospective, multicenter study of acute carbon monoxide poisoning in pregnancy were collected and followed. We collected and followed cases of carbon monoxide poisoning occurring during pregnancy between December 1985 and March 1989. The sources of carbon monoxide were malfunctioning furnaces (n = 16), hot water heaters (n = 7), car fumes In = 63, and methylene chloride inhalation (n = 3). Pregnancy outcome was adversely affected in 3 of 5 pregnancies with severe toxicity; two stillbirths, and one cerebral palsy with tomographic findings consistent with ischemic damage. All adverse outcome occurred in cases treated with high flow oxygen, whereas the 2 cases of severe toxicity with normal outcomes followed hyperbaric oxygen therapy. All 31 babies exposed in utero to mild or moderate carbon monoxide poisoning exhibited normal physical and neurobehavioral development. Severe maternal carbon monoxide toxicity was associated with significantly more adverse fetal cases when compared to mild maternal toxicity (P less than 0.001). It is concluded that while severe carbon monoxide poisoning poses serious short- and long-term fetal risk, mild accidental exposure Is likely to result in normal fetal outcome. Because fetal accumulation of carbon monoxide is higher and its elimination slower than in the maternal circulation, hyperbaric oxygen may decrease fetal hypoxia and improve outcome.
[Koren G et al; Reprod Toxicol 5 (5): 397-403 (1991)]**PEER REVIEWED**
A longitudinal study of one hundred consecutive admissions to the Royal Adelaide Hospital for carbon monoxide poisoning was conducted from 1986 to 1989. Twenty-five patients left hospital with persistent symptoms and signs of this poisoning. Five subsequently recovered. Twenty-four other patients, who were well when they left hospital, did not attend for a review one month after discharge. Extensive neuropsychiatric testing at this time showed 32% (24 of 76) had obvious sequelae of their exposure. Overall, the frequency of neuropsychiatric sequelae in the patients who only received oxygen at atmospheric pressure was 63 (N = 8) on discharge and 67% (N = 6) on one month follow-up. The frequency of sequelae among those who were given one hyperbaric oxygen treatment only was 46% (N = 24) on discharge and 50% (N = 20) on one month follow-up. In contrast, the frequency of sequelae in patients who had two or more hyperbaric oxygen treatments was only 13% (N = 68) on discharge (P less than 0.005) and 18% (N = 50) on follow-up (P less than 0.0051 the frequency of sequelae was also significantly greater if hyperbaric oxygen was delayed (P less than 0.05). No markers of severe poisoning could be identified.
[Gorman DF et al; Anaesth Intensive Care 20 (3): P311-6 (1992)]**PEER REVIEWED**
Single photon emission computed tomography (SPECT) with technetium-99 (99mTc) hexamethylprophylene amine oxime (HM-PAO) were repeatedly performed in a 55 year old woman with carbon monoxide poisoning. The initial brain single photon emission computed tomography 10 days after anoxic insult showed focal hypoperfusion which appeared 20 days prior to the onset of delayed neurologic sequelae, and the findings of follow-up single photon emission computed tomography correlated with the clinical course of carbon monoxide poisoning. The possibilities of early hypoperfusion on single photon emission computed tomography of acute carbon monoxide poisoning were discussed.
[Choi IS, Lee MS; Eur Neurol 33 (6): 461-4 (1993)]**PEER REVIEWED**
Carbon monoxide is the most frequent cause of immediate fire deaths, and carbon monoxide poisoning should be suspected in every fire victim. Carbon monoxide levels at fires may reach 10%, which can raise carboxyhemoglobin levels in active firefighters without respiratory protection to 75% within 1 minute.
[Ellenhorn, M.J. and D.G. Barceloux. Medical Toxicology - Diagnosis and Treatment of Human Poisoning. New York, NY: Elsevier Science Publishing Co., Inc. 1988. 820]**PEER REVIEWED**
Two patients, a brother and sister experienced carbon monoxide poisoning simultaneously. Both /exhibited/ deficits in frontal lobe/executive functioning along with mild disturbances in memory and visual spatial information processing. A review of the literature indicates that frontal lobe deficits are commonly found following carbon monoxide poisoning along with the /established/ known deficits in memory and visual spatial information processing.
[Deckel AW; Brain Injury 8 (4): 345-56 (1994)]**PEER REVIEWED**
Medical Surveillance:
The following medical procedures should be made available to each employee who is exposed to carbon monoxide at potentially hazardous levels: A complete history and physical examination. ... Examination of the cardiovascular system, the pulmonary system, the blood, and the central nervous system should be stressed. A complete blood count should be performed including a red cell count, a white cell count, a differential count of a stained smear, as well as hemoglobin and hematocrit. ... The aforementioned medical examinations should be repeated on an annual basis, with the exception that a carboxyhemoglobin determination should be performed at any time overexposure is suspected or signs or symptoms of toxicity occur.
[Mackison, F. W., R. S. Stricoff, and L. J. Partridge, Jr. (eds.). NIOSH/OSHA - Occupational Health Guidelines for Chemical Hazards. DHHS(NIOSH) PublicationNo. 81-123 (3 VOLS). Washington, DC: U.S. Government Printing Office, Jan. 1981. 1]**PEER REVIEWED**
Populations at Special Risk:
MEN WITH CHRONIC BRONCHITIS OR ASTHMA RESIST EFFECT OF CARBON MONOXIDE VERY BADLY AND COURSE OF CARBON MONOXIDE POISONING IS UNFAVORABLY INFLUENCED BY ALCOHOLISM, OBESITY, AND CHRONIC DISEASE OF HEART. CHRONIC VASCULAR DISEASE INCREASES THE DAMAGE DONE TO BASAL GANGLIA.
[Hamilton, A., and H. L. Hardy. Industrial Toxicology. 3rd ed. Acton, Mass.: Publishing Sciences Group, Inc., 1974. 243]**PEER REVIEWED**
THE FETUS MAY BE EXTREMELY SUSCEPTIBLE TO EFFECTS OF CARBON MONOXIDE, AND THE GAS READILY CROSSES THE PLACENTA.
[Gilman, A.G., T.W. Rall, A.S. Nies and P. Taylor (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 8th ed. New York, NY. Pergamon Press, 1990. 1620]**PEER REVIEWED**
ANEMIC PERSONS ARE MORE SUSCEPTIBLE TO CARBON MONOXIDE THAN ARE INDIVIDUALS WITH NORMAL AMT OF HEMOGLOBIN. INCR METABOLIC RATE ENHANCES THE SEVERITY OF SYMPTOMS IN CARBON MONOXIDE POISONING; THIS IS WHY CHILDREN SUCCUMB EARLIER THAN ADULTS WHEN EXPOSED TO A GIVEN CONCN OF THE GAS.
[Gilman, A.G., T.W. Rall, A.S. Nies and P. Taylor (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 8th ed. New York, NY. Pergamon Press, 1990. 1619]**PEER REVIEWED**
Pregnant women are more susceptible to the effects of carbon monoxide exposure.
[Mackison, F. W., R. S. Stricoff, and L. J. Partridge, Jr. (eds.). NIOSH/OSHA - Occupational Health Guidelines for Chemical Hazards. DHHS(NIOSH) PublicationNo. 81-123 (3 VOLS). Washington, DC: U.S. Government Printing Office, Jan. 1981. 1]**PEER REVIEWED**
Persons with a history of coronary heart disease, anemia, pulmonary heart disease, cerebrovascular disease, thyrotoxicosis, and smokers would be expected to be at increased risk from exposure.
[Mackison, F. W., R. S. Stricoff, and L. J. Partridge, Jr. (eds.). NIOSH/OSHA - Occupational Health Guidelines for Chemical Hazards. DHHS(NIOSH) PublicationNo. 81-123 (3 VOLS). Washington, DC: U.S. Government Printing Office, Jan. 1981. 1]**PEER REVIEWED**
Smoking cigarettes resulted in higher carboxyhemoglobin levels than exposure to carbon monoxide levels present in street air. ... Heavy cigarette smokers may have carboxyhemoglobin levels as high as 15-17%.
[WHO; Environ Health Criteria 13: Carbon Monoxide p.74 (1979)]**PEER REVIEWED**
... Fetal carboxyhemoglobin half-lives are expected to decease from 6 to 7 hours to 2 to 4 hours by the use of maternal oxygen therapy. The fetal rate of elimination remains slower than that of the mother.
[Haddad, L.M., Clinical Management of Poisoning and Drug Overdose. 2nd ed. Philadelphia, PA: W.B. Saunders Co., 1990.,p. 427-8]**PEER REVIEWED**
... On the basis of known effects described, patients with reproducible exercise-induced ischemia appear to be the best established as a sensitive group within the general population that is at increased risk for experiencing health effects of concern (i.e., decreased exercise duration due to exacerbation of cardiovascular symptoms) at ambient or near-ambient carbon monoxide concentrations ... Decrements in exercise duration in the healthy population would therefore be of concern mainly to competing athletes, rather than to ordinary people carrying out the common activities of daily life.
[Environmental Health Criteria 213: Carbon Monoxide pp. 17 (1999) by the International Programme on Chemical Safety (IPCS) under the joint sponsorship of the United Nations Environment Programme, the International Labour Organisation and the World Health Organization.]**QC REVIEWED**
... It can be hypothesized, however, from both clinical and theoretical work and from experimental research on laboratoy animals, that certain other groups in the population may be at probable risk from exposure to carbon monoxide. Identifiable probable risk groups can be categorized by gender differences; by age (e.g., fetuses, young infants and the elderly); by genetic variations (i.e., hemoglobin abnormalities); by pre-existing diseases, either known or unknown, that already decrease the availablity of oxygen to critical tissues; or by the use of medications, recreational drugs or alterations in environment (e.g., exposure to other air pollutants or to high altitude). Unfortunately, little empirical evidence is currently available by which to specify health effects associated with ambient or near-ambient carbon monoxide exposure to these probable risk groups. ...
[Environmental Health Criteria 213: Carbon Monoxide pp. 17-18 (1999) by the International Programme on Chemical Safety (IPCS) under the joint sponsorship of the United Nations Environment Programme, the International Labour Organisation and the World Health Organization.]**QC REVIEWED**
Probable Routes of Human Exposure:
...LARGE QUANTITIES OF CARBON MONOXIDE GAS RELEASED BY BURNING CHARCOAL CAN RESULT IN SEVERE POISONING OR DEATH. HIBACHIS SHOULD NEVER BE USED AS A SOURCE OF HEAT IN SLEEPING QUARTERS.
[Arena, J. M. Poisoning: Toxicology, Symptoms, Treatments. Fourth Edition. Springfield, Illinois: Charles C. Thomas, Publisher, 1979. 240]**PEER REVIEWED**
CAR EXHAUST CONTAINS 1 TO 7% CARBON MONOXIDE. THIS IS WELL INTO...TOXIC RANGE...
[Arena, J. M. Poisoning: Toxicology, Symptoms, Treatments. Fourth Edition. Springfield, Illinois: Charles C. Thomas, Publisher, 1979. 240]**PEER REVIEWED**
Occupational exposure to increased ambient carbon monoxide has been a major menace to firefighters, traffic police, coal miners, coke oven and smelter workers, caisson workers, toll both attendants, and transportation mechanics. As commuting distances increase, workers driving to and from work are exposed to more ambient carbon monoxide.
[Sullivan, J.B. Jr., G.R. Krieger (eds.). Hazardous Materials Toxicology-Clinical Principles of Environmental Health. Baltimore, MD: Williams and Wilkins, 1992. 540]**PEER REVIEWED**
Emergency Medical Treatment:
Emergency Medical Treatment:
EMT Copyright Disclaimer:
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The following Overview, *** CARBON MONOXIDE ***, is relevant for this HSDB record chemical.
Life Support:
o This overview assumes that basic life support measures
have been instituted.
Clinical Effects:
SUMMARY OF EXPOSURE
0.2.1.1 ACUTE EXPOSURE
o Carbon monoxide poisoning causes a multitude of effects
due to inhibition of cellular oxidation, resulting in
tissue hypoxia and cellular poisoning. Clinical
symptoms of mild poisoning are nonspecific and may
mimic those of a nonspecific viral illness, with
vomiting, headache, malaise, weakness, fatigue and
shortness of breath.
o The main manifestations of carbon monoxide poisoning
develop in the organ systems most dependent on oxygen
use: the central nervous system and the myocardium.
o MILD TOXICITY - Minor exposures result in a throbbing
temporal or frontal headache, fatigue, dyspnea on
exertion, lightheadedness and dizziness. Patients with
cardio- or cerebrovascular disease may experience
exacerbation, such as myocardial ischemia or
infarction, or stroke.
o MODERATE TOXICITY - Moderate exposures may produce
severe headache, weakness, dizziness, nausea, vomiting,
syncope, tachycardia and tachypnea followed by
bradycardia and bradypnea, flushing, cyanosis,
perspiration, decreased vigilance, diminished manual
dexterity, impaired sensorimotor task performance,
prolonged reaction time, difficulty thinking, impaired
judgement, blurred or darkened vision, ataxia, loss of
muscular control, tinnitus or roaring in the ears,
sleepiness, hallucinations and cardiovascular toxicity.
o SEVERE TOXICITY - Severe exposures produce syncope,
seizures, confusion, disorientation, convulsions,
involuntary evacuations, skin bullae, cardiovascular
toxicity, ventricular dysrhythmias, cardiorespiratory
depression, pulmonary edema, respiratory failure,
stupor, loss of consciousness, coma, collapse and
death.
o DELAYED EFFECTS - Neuropsychiatric effects can appear
several days after exposure. These include vegetative
state, akinetic mutism, parkinsonism, apraxia, agnosia,
visual impairment, amnestic/confabulatory state,
depression, dementia, psychosis, paralysis, chorea,
cortical blindness, peripheral neuropathy and
incontinence. Personality changes may also occur, with
increased irritability, verbal aggression, violence,
impulsivity and moodiness.
o Carboxyhemoglobin levels correlate poorly with signs
and symptoms of toxicity and with prognosis, and
interpretation may be confounded by delays in
obtaining blood samples and therapeutic interventions
(oxygen administration). The classic 'cherry-red
skin' of carbon monoxide poisoning is rare.
o Contact with liquid carbon monoxide or its container
can cause freezing and freezing burns of skin and
eyes.
HEENT
0.2.4.1 ACUTE EXPOSURE
o Visual field deficits, retinopathy, or retrobulbar
neuritis are late findings.
CARDIOVASCULAR
0.2.5.1 ACUTE EXPOSURE
o Atrial and ventricular dysrhythmias, heart block,
hypotension, and ECG changes suggestive of cardiac
ischemia, may occur with severe poisoning.
RESPIRATORY
0.2.6.1 ACUTE EXPOSURE
o Tachypnea is common. Respiratory failure, dyspnea, or
pulmonary edema may occur.
NEUROLOGIC
0.2.7.1 ACUTE EXPOSURE
o Acute effects include headache, syncope, seizures,
dizziness, confusion and coma.
o Delayed effects may occur days to weeks after exposure;
advanced age and neurologic anomalies during the acute
event appear to be risk factors.
1. Severe effects may include mental deterioration,
disorientation, hypokinesia, mutism, confusion, severe
memory loss, coma, gait disturbances, incontinence,
speech disturbance, tremor, visual loss, movement
disorders, and Parkinsonian syndrome.
2. Subtle effects may include headache, anorexia, nausea,
apathy, lethargy, forgetfulness, personality changes,
memory problems, irritability and dizziness.
GASTROINTESTINAL
0.2.8.1 ACUTE EXPOSURE
o Nausea and vomiting are common; may mimic acute
gastroenteritis or food poisoning.
GENITOURINARY
0.2.10.1 ACUTE EXPOSURE
o Hematuria, albuminuria, renal failure, myoglobinuria,
and acute tubular necrosis have developed with severe
poisoning.
HEMATOLOGIC
0.2.13.1 ACUTE EXPOSURE
o Carboxyhemoglobin level may be elevated initially, but
diminishes rapidly following removal from exposure and
institution of oxygen therapy, which greatly reduces
the half life of COHb.
o COHb level correlates poorly with symptoms, especially
if measured after oxygen initiated.
DERMATOLOGIC
0.2.14.1 ACUTE EXPOSURE
o Bullous lesions associated with carbon monoxide
poisoning generally appear within 24 hours of exposure
and are usually located on the palms and soles.
MUSCULOSKELETAL
0.2.15.1 ACUTE EXPOSURE
o Muscle necrosis, rhabdomyolysis, compartment syndrome
and elevated CPK have been reported following toxic
exposures. Elevated CPK and myoglobinuria are
characteristic. Delayed movement disorders have been
reported following CO poisoning.
REPRODUCTIVE HAZARDS
o CO exposure during pregnancy is teratogenic, depending
upon the stage of pregnancy. The fetus is more
vulnerable to CO poisoning than the mother.
OTHER
0.2.23.1 ACUTE EXPOSURE
o High-risk groups include infants, pregnant women, the
elderly, and patients with a history of ischemic heart
disease or chronic obstructive lung disease.
o Sudden infant death syndrome (SIDS) may be a
misdiagnosis of carbon monoxide toxicity in some cases.
Laboratory:
o Determine COHb level when the patient is first seen and
repeat every 2 to 4 hours until patient is asymptomatic or
level is within the normal range.
o Monitor ECG, electrolytes, CPK, urinalysis, arterial blood
gases if symptomatic or if the COHb level is greater than
20%. Pulse oximetry is NOT a reliable estimate of
oxyhemoglobin saturation.
o Monitor cardiac function.
o CT scan or MRI should be considered if neurologic symptoms
persist.
Treatment Overview:
INHALATION EXPOSURE
o DECONTAMINATION - Move patient to fresh air to protect
both the patient and first-responders. Monitor for
respiratory distress. Administer 100 percent
humidified supplemental oxygen with assisted ventilation
as required. Giving mouth-to-mouth resuscitation does
not place the provider at risk of CO poisoning.
o ADMINISTER 100% OXYGEN by tight-fitting face mask to
reduce the biological half-life of CO.
o CARBOXYHEMOGLOBIN (COHb) LEVEL -
1. Determine when the patient is first seen and repeat at
2 to 4 hourly intervals until patient is asymptomatic.
2. A COHb level should be obtained prior to oxygen therapy
as long as this does not delay the initiation of this
treatment.
3. COHb concentrations frequently do not correlate well
with the severity of the poisoning. In an appropriate
setting, any patient found unconscious, seizing, or
with ECG changes or metabolic acidosis should be
treated as a severe carbon monoxide poisoning,
regardless of the COHb concentration.
o CONSIDER HYPERBARIC OXYGEN therapy for severely poisoned
patients (coma, seizures, other neurologic
abnormalities, myocardial ischemia). Also consider in
pregnant patients. Institute hyperbaric therapy as
quickly as possible, ideally within 6 to 8 hours.
o SEIZURES: Administer a benzodiazepine IV; DIAZEPAM
(ADULT: 5 to 10 mg, repeat every 10 to 15 min as
needed. CHILD: 0.2 to 0.5 mg/kg, repeat every 5 min
as needed) or LORAZEPAM (ADULT: 2 to 4 mg; CHILD: 0.05
to 0.1 mg/kg).
1. Consider phenobarbital if seizures recur after diazepam
30 mg (adults) or 10 mg (children > 5 years).
2. Monitor for hypotension, dysrhythmias, respiratory
depression, and need for endotracheal intubation.
Evaluate for hypoglycemia, electrolyte disturbances,
hypoxia.
o ECG - Indicated in adult patients found unconscious,
with chest pain or other significant symptoms, or with
COHb level greater than 20%, to detect signs of
myocardial damage.
o Patients with signs of increased intracranial pressure
should be hyperventilated with 100% oxygen via an
endotracheal tube to keep the arterial pCO2 level at 25
to 30 mmHg.
1. Parenteral fluids should be limited to 2/3 to 3/4 of
normal maintenance. Osmotic diuretics (e.g.,
mannitol), or other methods to reduce intracranial
pressure may be used but are unlikely to affect
outcome.
o ADMISSION CRITERIA - Neurological symptoms or signs,
abnormal ECG, and metabolic acidosis.
Range of Toxicity:
o COHb levels above 25 percent (0.25) are usually considered
toxic, although COHb levels do not correlate well with
clinical severity; patients may have significant toxicity
with mildly elevated or even normal COHb levels,
particularly if they were obtained after oxygen therapy
was initiated.
o Toxicity is best determined by the patient's
cardiovascular and mental status, arterial pH, and
bicarbonate levels.
[Rumack BH: POISINDEX(R) Information System. Micromedex, Inc., Englewood, CO, 2003; CCIS Volume 116, edition exp May, 2003. Hall AH & Rumack BH (Eds):TOMES(R) Information System. Micromedex, Inc., Englewood, CO, 2003; CCIS Volume 116, edition exp May, 2003.] **PEER REVIEWED**
Antidote and Emergency Treatment:
Treatment includes 100% oxygen and, in severe cases, hyperbaric oxygen. The half-life of carboxyhemoglobin is 6 hours at room air, 1.5 hours with 100% oxygen, and 23 minutes at three atmospheres of pressure.
[Haddad, L.M., Clinical Management of Poisoning and Drug Overdose. 2nd ed. Philadelphia, PA: W.B. Saunders Co., 1990. 303]**PEER REVIEWED**
The prompt administration of oxygen is critical to maternal and fetal survival. In gestationally appropriate pregnancies, it is reasonable to use indicators of adequate fetal oxygenation central nervous system responsiveness (heart rate and variability), in addition to responses of the mother and her laboratory findings, in adjusting or terminating oxygen therapy. To ensure adequate treatment of the fetus, it has been recommended that the mother receive oxygen therapy for five times as long as it is expected to require to return her carbon monoxide concentrations to normal; this is how long it may take for fetal levels to normalize. The maternal carboxyhemoglobin elimination rate can be increased from a half-life of 2 to 3 hours to 3/4 of an hour by breathing 100% oxygen; fetal carboxyhemoglobin half-lives are expected to decease from 6 to 7 hours to 2 to 4 hours by the use of maternal oxygen therapy. The fetal rate of elimination remains slower than that of the mother.
[Haddad, L.M., Clinical Management of Poisoning and Drug Overdose. 2nd ed. Philadelphia, PA: W.B. Saunders Co., 1990.,p. 427-8]**PEER REVIEWED**
Animal Toxicity Studies:
Toxicity Summary:
It is a product of the incomplete combustion of carbon-containing fuels and is also produced by natural processes or by biotransformation of halomethanes within the human body. With external exposures to additional carbon monoxide, subtle effects can begin to occur, and exposure to higher levels can result in death. The health effects of carbon monoxide are largely the result of the formation of carboxyhemoglobin (COHb), which impairs the oxygen carrying capacity of the blood. ... During typical daily activities, people encounter carbon monoxide in a variety of microenvironments - while travelling in motor vehicles, working at their jobs, visiting urban locations associated with combustion sources, or cooking or heating with domestic gas, charcoal or wood fires - as well as in tobacco smoke. ... Studies of human exposure have shown that motor vehicle exhaust is the most important source for regularly encountered elevated carbon monoxide levels. ... The workplace is another important setting for carbon monoxide exposures ... Certain industrial processes can expose workers to carbon monoxide produced directly or as a byproduct ... Carbon monoxide is absorbed through the lungs, and the concentration of carboxyhemoglobin will depend ... mainly on the concentrations of inspired carbon monoxide and oxygen ... and will also depend on the duration of exposure, pulmonary ventilation, and the concentration of carboxyhemoglobin originally present ... In addition to its reaction with hemoglobin, carbon monoxide combines with myoglobin, cytochromes, and metalloenzymes such as cytochromoe c oxidase and cytochrome P-450. ... The binding of carbon monoxide to hemoglobin, producing carboxyhemoglobin and decreasing the oxygen carrying capacity of blood, appears to be the principal mechanism of action underlying the induction of toxic effects of low-level carbon monoxide exposures. The precise mechanisms by which toxic effects are induced ... are not understood fully but likely include the induction of a hypoxic state in many tissues of diverse organ systems. ... A unique feature of carbon monoxide exposure, therefore, is that the blood carboxyhemoglobin level represents a useful biological marker of the dose that the individual has received. ... The formation of carboxyhemoglobin is a reversible process; however, because of the tight binding of carbon monoxide to hemoglobin, the elimination half-time is quite long, ranging from 2 to 6.5 hr ... The level of carboxyhemoglobin in the blood may be determined directly by blood analysis or indirectly by measuring carbon monoxide in exhaled breath. ... Decreased oxygen uptake and the resultant decreased work capacity under maximal exercise conditions have clearly been shown to occur ... However, of greater concern at more typical ambient carbon monoxide exposure levels are certain cardiovascular effects (i.e., aggravation of angina symptoms during exercise) likely to occur in a smaller, but sizeable, segment of the general population. This group, chronic angina patients, is currently viewed as the most sensitive risk group for carbon monoxide exposure effects ... The adverse health consequences of low level carbon monoxide exposure to patients with ischemic heart disease are very difficult to predict in the at-risk population of individuals with heart disease. ... At high carbon monoxide concentrations, excessive increases in hemoglobin and hematocrit may impose an additional workload on the heart and compromise blood flow to the tissues. ... It is unlikely that carbon monoxide has any direct effects on lung tissue except for extremely high concentrations associated with carbon monoxide poisoning. ... Occupational or accidental exposure to the products of combustion and pyrolysis, particularly indoors, may lead to acute decrements in lung function if the carboxyhemoglobin levels are high. It is difficult, however, to separate the potential effects of carbon monoxide from those due to other respiratory irritants in the smoke and exhaust. ... Of special note are those individuals who are taking drugs with primary or secondary depressant effects that would be expected to exacerbate carbon monoxide-related neurobehavorial decrements. Other groups at possible increased risk for carbon monoxide-induced neurobehavorial effects are the aged and ill ... Under normal circumstances, the brain can increase blood flow or tissue oxygen extraction to compensate for the hypoxia caused by exposure to carbon monoxide. ...
[Environmental Health Criteria 213: Carbon Monoxide pp. 1-12 (1999) by the International Programme on Chemical Safety (IPCS) under the joint sponsorship of the United Nations Environment Programme, the International Labour Organisation and the World Health Organization.]**QC REVIEWED**
... Studies in several laboratory animal species provide strong evidence that maternal carbon monoxide exposures ... produce reductions of birth weight, cardiomegaly, delays in behavorial development and disruptions in cognitive function. ... Laboratory animal studies suggest that enzyme metabolism of xenobiotic compounds may be affected by carbon monoxide exposure. ... The decreases in xenobiotic metabolism shown with carbon monoxide exposure might be important to individuals receiving treatment with drugs. ... Tissues of highly active oxygen metabolism, such as heart, brain, liver, kidney, and muscle, may be particularly sensitive to carbon monoxide poisoning. There are reports ... of effects on liver, kidney, bone and the immune capacity of the lung and spleen. It is generally agreed that the severe tissue damage occurring during acute carbon monoxide poisoning is due to one of more of the following: (1) ischemia resulting from the formation of carboxyhemoglogin, (2) inhibition of oxygen release from oxyhemoglobin, (3) inhibition of oxygen release from oxyhemoglobin, (3) inhibition of cellular cytochrome function (e.g., cytochrome oxidases) and (4) metabolic acidosis. ... Whereas certain data also suggest that perinatal effects (e.g., reduced birth weight, slowed post-natal developments, sudden infant death syndrome) are associated with carbon monoxide exposure, insufficient evidence exists by which to either qualitatively confirm such an association in humans or establish any pertinent exposure-effect relationships. ... There remains little direct information on the possible enhancement of carbon monoxide toxicity by concomitant drug use or abuse ... The greatest evidence for a potentially important interaction of carbon monoxide comes from studies with alcohol in both laboratory animals and humans, where at least additive effects have been obtained. The significance of this is augmented by the high probable incidence of combined alcohol use and carbon monoxide exposure. ... Besides being a source of carbon monoxide for smokers as well as non-smokers, tobacco smoke is also a source of other chemicals with which environmental carbon monoxide could interact. ... On the basis of known effects described, patients with reproducible exercise-induced ischemia appear to be the best established as a sensitive group within the general population that is at increased risk for experiencing health effects of concern (i.e., decreased exercise duration due to exacerbation of cardiovascular symptoms) at ambient or near-ambient carbon monoxide concentrations ... Decrements in exercise duration in the healthy population would therefore be of concern mainly to competing athletes, rather than to ordinary people carrying out the common activities of daily life. It can be hypothesized, however, from both clinical and theoretical work and from experimental research on laboratory animals, that certain other groups in the population may be at probable risk from exposure to carbon monoxide. Identifiable probable risk groups can be categorized by gender differences; by age ...; by genetic variations...; by pre-existing diseases...; or by the use of medications, recreational drugs or alterations in environment ... Unfortunately, little empirical evidence is currently available by which to specify health effects associated with ambient or near-ambient carbon monoxide exposure to these probable risk groups. ...
[Environmental Health Criteria 213: Carbon Monoxide pp. 12-18 (1999) by the International Programme on Chemical Safety (IPCS) under the joint sponsorship of the United Nations Environment Programme, the International Labour Organisation and the World Health Organization.]**QC REVIEWED**
... Carbon monoxide is responsible for a large percentage of the accidental poisonings and deaths reported throughout the world each year. ... Outdoors, concentrations of carbon monoxide are highest near street intersections, in congested traffic, near exhaust gases from internal combustion engines and from industrial sources, and in poorly ventilated areas such as parking garages and tunnels. Indoors, carbon monoxide concentrations are highest in workplaces or in homes that have faulty or poorly vented combustion appliances or downdrafts or backdrafts. The symptoms and signs of acute carbon monoxide poisoning correlate poorly with the level of carboxyhemoglobin measured at the time of arrival at the hospital. ... Neurological symptoms of carbon monoxide poisoning can ocur, such as headache, dizziness, weakness, nausea, confusion, disorientation and visual disturbances. Exertional dyspnea, increases in pulse and respiratory rates and syncope are observed with continuous exposure ... When carboxyhemoglobin levels are higher than 50%, convulsions and cardiopulmonary arrest may occur. Complications occur frequently in carbon monoxide poisoning (immediate death, myocardial impairment, hypotension, arrhythmias, pulmonary edema). Perhaps the most insidious effect of carbon monoxide poisoning is the delayed development of neuropyschiatric impairment ... and the neurobehavioral consequences, especially in children. Carbon monoxide poisoning during pregnancy results in high risk for the mother, by increasing the short-term complications rate and for the fetus by causing fetal death, developmental disorders, and cerebral anoxic lesions. Furthermore, the severity of fetal intoxication cannot be assessed by the maternal rate. Carbon monoxide poisoning occurs frequently, has severe consequences, including immediate death, involves complications and late sequelae and is often overlooked. ...
[Environmental Health Criteria 213: Carbon Monoxide pp. 18-19 (1999) by the International Programme on Chemical Safety (IPCS) under the joint sponsorship of the United Nations Environment Programme, the International Labour Organisation and the World Health Organization.]**QC REVIEWED**
Non-Human Toxicity Excerpts:
...WHEN THE CARBON MONOXIDE LEVEL IN THE AIR EXCEEDS 3%, DEATH OCCURS ALMOST AT ONCE. LOWER LEVELS ARE ASSOCIATED WITH VERTIGO, MUSCULAR WEAKNESS, DIFFICULT, RAPID & STERTOROUS RESPIRATION, INTERMITTENT HEART BEAT, LOSS OF POWER OVER SPHINCTERS AND DEATH IN COMA.
[Humphreys, D.J. Veterinary Toxicology. 3rd ed. London, England: Bailliere Tindell, 1988. 82]**PEER REVIEWED**
...EXPOSING /DOGS/...FOR 11 WK, 6 DAYS/WK & 5.5 HR/DAY TO 100 PPM CARBON MONOXIDE. ...AS EARLY AS THE SECOND WK THE EKG SHOWED CHANGES WHICH PERSISTED AND AT NECROPSY THERE WERE SIGNS OF DEGENERATION IN INDIVIDUAL MUSCLE FIBERS IN MYOCARDIUM, HEMORRHAGE & NECROSIS. SOME OF THE DOGS HAD SHOWN DISTURBANCE OF GAIT & OF POSTURAL & POSITION REFLEXES, AND AT NECROPSY THERE WERE FOUND HISTOLOGICAL CHANGES IN CORTEX OF THE HEMISPHERES & IN THE GLOBUS PALLIDUS OF THE BRAIN STEM RESEMBLING...THOSE FOUND AFTER ACUTE POISONING BUT SMALLER, MORE SCATTERED & LESS DESTRUCTIVE.
[Hamilton, A., and H. L. Hardy. Industrial Toxicology. 3rd ed. Acton, Mass.: Publishing Sciences Group, Inc., 1974. 242]**PEER REVIEWED**
...DOGS EXPOSED TO 96 PPM OF CARBON MONOXIDE FOR 11 WK SHOWED SIGNIFICANT RISE IN RED CELL COUNT IN 1ST WEEKS, BUT THEN DROP TO THE ORIGINAL LEVEL OR BELOW. ...INCREASE DUE TO MARROW ACTIVITY /AS/ INCREASED RETICULOCYTES & SOME NORMOBLASTS /WERE FOUND/. ...IN ANIMAL EXPERIMENTS...A RISE IN INTRACRANIAL BLOOD PRESSURE OCCURS UNDER THE INFLUENCE OF CARBON MONOXIDE...ATTRIBUTED TO THE INCR CONGESTION AND EDEMA.
[Hamilton, A., and H. L. Hardy. Industrial Toxicology. 3rd ed. Acton, Mass.: Publishing Sciences Group, Inc., 1974. 247]**PEER REVIEWED**
...EXPOSED RABBITS TO CARBON MONOXIDE FOR 8 WK AND FOUND THAT UPTAKE OF CHOLESTEROL IN THE INTIMA OF BLOOD VESSELS WAS CONSIDERABLY ENHANCED. HISTOLOGICALLY INJURIES TO ARTERIAL WALLS CAUSED BY CARBON MONOXIDE WERE INDISTINGUISHABLE FROM THOSE CAUSED BY SPONTANEOUS ARTERIOSCLEROSIS. /OTHER/ ...ANIMAL STUDIES INDICATED THAT CARBON MONOXIDE HAS A DIRECT TOXIC EFFECT ON LUNG TISSUE BY DISRUPTING THE OXIDATIVE METABOLIC CHAIN AND PROFOUNDLY INHIBITS ALL CELLULAR ACTIVITY ESPECIALLY IN HEART AND BRAIN TISSUE WERE THE CELLS HAVE THE GREATEST NEED FOR OXYGEN.
[Hamilton, A., and H. L. Hardy. Industrial Toxicology. 3rd ed. Acton, Mass.: Publishing Sciences Group, Inc., 1974. 252]**PEER REVIEWED**
DATA SUGGESTED NO ASSOCIATION BETWEEN PERIODIC CARBON MONOXIDE EXPOSURE & DEVELOPMENT OF ATHEROSCLEROSIS IN MONKEYS.
[BING RJ ET AL; J CLIN PHARMACOL 20 (8-9): 487 (1980)]**PEER REVIEWED**
PLASMA LEUCINE AMINOPEPTIDASE (LAP) LEVELS AND RESPIRATION RATES OF ISOLATED LIVER MITOCHONDRIA WERE STUDIED IN CARBON MONOXIDE-POISONED RATS SAMPLED AT RESP ARREST. INCR IN LAP LEVELS PARALLELED A DECR IN RESP CONTROL RATIO & THE ADP/OXYGEN RATIO.
[KATSUMATA Y ET AL; FORENSIC SCI INT 16 (2): 119 (1980)]**PEER REVIEWED**
PREGNANT RATS WERE EXPOSED TO 150 PPM CARBON MONOXIDE IN AIR & EXAMINATION OF OFFSPRING SHOWED OFFSPRING WEIGHED LESS @ BIRTH, SHOWED REDUCED GROWTH RATES, & PERFORMED POORLY ON NEGATIVE GEOTAXIS AND HOMING TESTS.
[FECHTER LD, ANNAU Z; NEUROBEHAV TOXICOL 2 (1): 7 (1980)]**PEER REVIEWED**
...EXPOSED RABBITS DURING PREGNANCY TO 180 PPM CARBON MONOXIDE. PERINATAL DEATH OCCURRED IN 43 OF 123 TREATED OFFSPRING BUT IN ONLY ONE OF A COMPARABLE CONTROL GROUP. THE BIRTH WEIGHT WAS APPROXIMATELY 10 G LESS IN THE TREATED GROUP AND 3 HAD DEFECTS OF THEIR EXTREMITIES.
[Shepard, T. H. Catalog of Teratogenic Agents. 3rd ed. Baltimore, MD.: Johns Hopkins University Press, 1980. 53]**PEER REVIEWED**
The comparative acute toxicity of a branded American cigarette and kreteks (Indonesian cigarettes containing approx 60% tobacco and 40% ground clove buds) was assessed by exposure of groups of 10 male and 10 female rats to 3 different but equivalent (in terms of total particulate matter) concn of smoke (1.15 to 6.00% v/v) from each type of cigarette. The smoke was delivered "nose only" using a rodent smoking machine within a single 1-hr period, with a total delivery of 30 min smoke and a 15 min air-breathing period between the 2 smoke exposures. The only differences observed were more severe signs of smoke intoxication in the American smoke exposed rats which, at least in part, was attributed to the higher concn of carbon monoxide. Carbon monoxide concn in American smoke atmospheres were 2 to 2.5 times higher than that of kretek smoke (peak concn of 3000 ppm and 1500 ppm, respectively).
[Clark GC; Arch Toxicol 63 (1): 1-6 (1989)]**PEER REVIEWED**
Arterial blood gases were measured in 52 unanesthetized Sprague-Dawley rats following 6 wk exposure to either room air at ambient altitude (950 m), room air containing 100 ppm carbon monoxide at ambient altitude, room air at 4575 m simulated high altitude, or room air containing 100 ppm carbon monoxide at 4575 m simulated high altitude. Pa(CO2) was significantly higher in animals exposed to carbon monoxide both at ambient altitude (38.2 vs 34.5 Torr) and simulated high altitude (28.3 vs 23.6 Torr).
[Davies DG, McGrath JJ; Respir Physiol 75 (2): 193-8 (1989)]**PEER REVIEWED**
Male Fischer 344 rats were exposed continuously for 6 wk to: 100 or 500 ppm carbon monoxide; 15,000 feet simulated high altitude; or 100 or 500 ppm carbon monoxide at simulated high altitude. Simulated high altitude decr body wt significantly; carbon monoxide and carbon monoxide/simulated high altitude interaction had no significant effect on body weight. Carbon monoxide and simulated high altitude increased hematocrit ratio significantly; 500 ppm carbon monoxide increased hematocrit ratio to a greater extent than 100 ppm carbon monoxide. There was a significant interaction between 500 ppm carbon monoxide and simulated high altitude on hematocrit ratio. The mean electrical axis was shifted to the right by simulated high altitude, and shifted to the left by carbon monoxide. The effect was dose dependent, with the greater left shift occurring with 500 ppm carbon monoxide.
[Cooper R et al; Physiol Behav 46 (1): 75-9 (1989)]**PEER REVIEWED**
The effects of carbon monoxide were studied in the isolated working rat heart. Hearts removed from male Sprague Dawley rats were perfused via the left atrium with Krebs-Henseleit solution oxygenated with 95% O2/5% CO2 (O2). Heart rate and atrial pressures were measured by a transducer inserted in the aortic outflow line and connected to a data logger. Aortic flow was determined by collecting the effluent from the aortic bubble trap in a graduated cylinder. Coronary flow through the pulmonary cannula was collected and measured in a graduated cylinder. After 30 min, the hearts were challenged with solutions containing either carbon monoxide (5% CO/90% O2/5% CO2) or nitrogen (N2: 5% N2/90% O2/5% CO2) for 10 min. After recovery in O2, hearts were challenged with the alternate test solution. Carbon monoxide increased coronary flow and coronary flow as a percent of cardiac output 13% and 16% respectively (P < 0.05; P < 0.01). N2 had no significant effect on either coronary flow parameter. Carbon monoxide and N2 had no significant effect on heart rate, cardiac output, oxygen consumption or on aortic flow or pressure.
[Lin H, McGrath JJ; Physiol Behav 46 (1): 81-4 (1989)]**PEER REVIEWED**
Newborn Sprague Dawley rats were exposed to 500 ppm carbon monoxide for up to 32 days of age, at which time the remaining exposed rats and ambient air controls continued development in room air to 200 days of age. In the carbon monoxide group, ventricular wt to body wt ratio was 26% greater than controls at 6 days of age, more than double at 15 days, and remained 47% greater at 28 days (6 rats per time period). Although absolute myocyte volumes were not different between the two groups at any time period, the carbon monoxide group did have greater G myocyte vol relative to body wt during the carbon monoxide exposure period. Binucleate myocytes of both ventricles were longer than controls during the exposure, but did not have increased width. By 200 days of age, myocytes from left ventricle plus septum of carbon monoxide exposed rats were significantly shorter and carbon monoxide exposed rats had more total myocytes than controls (36 million vs 32 million for controls, p < 0.05). In this study, cardiomegaly induced by 500 ppm carbon monoxide from birth to 32 days of age was primarily to myocyte hypertrophy with myocytes having increased length to width ratios (ie, alterations consistent with a vol induced model). Following removal from carbon monoxide exposure, there was regression of both cardiomegaly and myocyte hypertrophy. With increasing time after removal from carbon monoxide, myocytes tended to become shorter and smaller compared to age matched controls. This trend was present at 105 days and significant by 200 days of age, resulting in an increased number of myocytes in the myocardium long after removal of rats from carbon monoxide exposure.
[Clubb FJ et al; J Mol Cell Cardiol 21 (9): 945-55 (1989)]**PEER REVIEWED**
Neither the mixed-function oxidase mediated hydroxylation nor the acetylation of aniline was altered by exposure to 7.5% carbon monoxide/20% O2 for 2.5 hr in isolated perfused rabbit lung. p-Nitroanisole O-demethylation by isolated New Zealand rabbit lungs ventilated with 7.5% carbon monoxide/20% O2 for 2.5 hr was significantly decr (approx 37%) in comparison to controls.
[Trela BA et al; J Toxicol Environ Health 27 (3): 331-40 (1989)]**PEER REVIEWED**
Lungs of male New Zealand rabbits were removed and perfused with (14)C-4-ipomeanol for 2 hr starting with an initial concn of 0.1 mM. Lungs were ventilated with either air (control) or 7.5% carbon monoxide/20% O2. 4-Ipomeanol derived (mixed function oxidase mediated) covalent binding was identical in the control and carbon monoxide treatment groups. Lungs perfused with 4-ipomeanol and ventilated with air or 7.5% carbon monoxide/20% O2 both displayed alveolar type II cell hyperplasia and alveolar macrophage infiltration. There was no histological evidence of Clara cell damage in any of the 4-ipomeanol perfused lungs.
[Trela BA et al; J Toxicol Environ Health 27 (3): 341-50 (1989)]**PEER REVIEWED**
In dead animals, the blood is bright red and mucous membranes are a healthy pink ... There are no significant lesions in acute cases.
[Booth, N.H., L.E. McDonald (eds.). Veterinary Pharmacology and Therapeutics. 5th ed. Ames, Iowa: Iowa State University Press, 1982. 947]**PEER REVIEWED**
Carbon monoxide, which increases capillary permeability, accelerates plaque formation in animals on atherogenic, high-cholesterol diets. The effect of carbon monoxide may actually be due, however, to a lack of oxygen, since atheroma formation is also enhanced in animals subjected to hypoxia.
[Amdur, M.O., J. Doull, C.D. Klaasen (eds). Casarett and Doull's Toxicology. 4th ed. New York, NY: Pergamon Press, 1991. 450]**PEER REVIEWED**
Carbon monoxide exposure in rabbits, at 180 ppm exposure for four hours, results in focal intimal damage and edema. This is in the range of carbon monoxide exposure that humans might experience from cigarette smoke.
[Amdur, M.O., J. Doull, C.D. Klaasen (eds). Casarett and Doull's Toxicology. 4th ed. New York, NY: Pergamon Press, 1991. 453]**PEER REVIEWED**
One experimental study on the effects of carbon monoxide on the natural history of heart disease in the cynomolgus monkey has been reported. /Animals were/ exposed ... to carbon monoxide concentration of 137 mg/cu m (120 ppm) for 24 wk. The average carboxyhemoglobin level of 12.4% resulted in a polycythemia with an increase in hematocrit from 35 to 50%. All animals developed increased P-wave amplitude and T-inversion which suggested nonspecific myocardial stress rather than ischemia. Animals in which an experimental myocardial infarction was produced prior to exposure to carbon monoxide had more marked electrocardiographic changes than animals breathing room air.
[WHO; Environ Health Criteria 13: Carbon Monoxide p.48 (1979)]**PEER REVIEWED**
When fertilized chicken eggs were continuously exposed to carbon monoxide concentration of 747 mg/cu m (650 ppm) for up to 18 days of incubation, the percentage of eggs hatching decreased to 46% and developmental anomalies of the tibia and metatarsal bones were noted.
[WHO; Environ Health Criteria 13: Carbon Monoxide p.53 (1979)]**PEER REVIEWED**
Pregnant rats were exposed to 1.5% (15,000 ppm) carbon monoxide for five to eight minutes ten times on alternate days during their 21 day pregnancy. This resulted in maternal unconsciousness and abortion or absorption of most fetuses. The surviving newborns did not grow normally. Similar exposure to 5,900 ppm affected only a small percentage of animals.
[Zenz, C. Occupational Medicine-Principles and Practical Applications. 2nd ed. St. Louis, MO: Mosby-Yearbook, Inc, 1988. 866]**PEER REVIEWED**
Quantitative data on fetal weight of two groups of pregnant rabbits exposed to carbon monoxide continually for 30 days /was reported/. Exposure to 90 ppm yielded maternal carboxyhemoglobin concentrations of 9-10% from a control value of 4.5%. Mortality of the young rabbits during the following 21 days increased to 25% from a control value of 13%. Doubling the concentration of carbon monoxide to 180 ppm resulted in maternal carboxyhemoglobin concentrations of 16-18%, birth weights deceased 20% from 53.7 to 44.7 gm. and neonatal mortality was 35% compared with 1% from the controls. Mortality during the following 21 days was the same value as for the controls, 27%.
[Zenz, C. Occupational Medicine-Principles and Practical Applications. 2nd ed. St. Louis, MO: Mosby-Yearbook, Inc, 1988. 866]**PEER REVIEWED**
The effects of carbon monoxide on newborn survival in animals /was studied/. Rats /were exposed/ to mixtures of illuminating gas in air, with inspired carbon monoxide concentration of 0.43%. In 22 newborn rats 12-48 hours old exposed to carbon monoxide, the average survival times was about 196 minutes, in contrast to an average survival of about 36 minutes in mature animals.
[Zenz, C. Occupational Medicine-Principles and Practical Applications. 2nd ed. St. Louis, MO: Mosby-Yearbook, Inc, 1988. 866]**PEER REVIEWED**
By sequestering intracellular myoglobin of cardiac muscle cells in the nonfunctioning carboxymyoglobin form carbon monoxide blocks myoglobin-facilitated diffusion of oxygen as well as myoglobin-mediated oxidative phosphorylation. ... The hypothesis that the carbon monoxide blockade of myoglobin function may be responsible at the cellular level for a component of the cardiotoxicity of carbon monoxide observed during exercise /was studied/. Suspensions of isolated rat cardiac myocytes were held in near steady states of oxygen pressure near the intracellular partial pressure of oxygen of the working heart (2 to 5 torr) and near the end-venous partial pressure of oxygen (20 torr). These suspensions were exposed to carbon monoxide at low pressure (0.07 to 70 torr; 90 to 90,000 ppm). The fraction of intracellular carboxymyoglobin determined spectrophotometrically was in good agreement with the fraction predicted from the ratio of carbon monoxide partial pressure to oxygen partial pressure. The effects observed were related to the fraction of intracellular myoglobin bound to carbon monoxide. At physiological oxygen pressures no greater than 5 torr after sequestration of approximately 50% of the myoglobin steady state oxygen uptake decreased significantly and was significantly less than the respiration of cell groups for which the fraction of carboxymyoglobin was 0% to 40%. When respiration is diminished the rate of aerobic adenosine triphosphate synthesis (oxidative phosphorylation) also decreases. As in the whole heart cytoplasmic adenosine triphosphate concentration in isolated heart cells is controlled at a constant level by the creatine phosphokinase equilibrium. When adenosine triphosphate utilization is unchanged a sensitive monitor of the decreased adenosine triphosphate synthesis is the ratio of phosphocreatine to adenosine triphosphate. When carboxymyoglobin was at least 40% of the total intracellular myoglobin it was found that the ratio of phosphocreatine to adenosine triphosphate in carbon monoxide treated heart cells was significantly lower than that in control cells from the same preparation. Thus, it was concluded that sequestering intracellular myoglobin as carboxymyoglobin significantly decreased the rate of oxidative phosphorylation of isolated cardiac myocytes. It was estimated that intracellular myoglobin-dependent oxidative phosphorylation will be inhibited when approximately 20% to 40% of the arterial hemoglobin in the whole animal is carboxyhemoglobin.
[Wittenberg BA, Wittenberg JB; Res Rep Health Eff Inst 62: 1-12 (1993)]**PEER REVIEWED**
The present experiments investigated alterations of peripheral nervous system activity in male Wistar rats by prenatal exposure (from day 0 to day 20 of pregnancy) to relatively low levels of carbon monoxide (75 and 150 ppm). The voltage clamp analysis of ionic currents recorded from sciatic nerve fibers showed that prenatal exposure to carbon monoxide produced modifications of sodium current properties. In particular, in 40-day-old rats exposed to carbon monoxide (75 and 150 ppm) during gestation the inactivation kinetics of transient sodium current were significantly slowed. Analysis of the potential dependence of steady-state Na inactivation, h infinity (V) showed that the percentage of the maximum number of activable sodium channels at the normal resting potential (-80 mV) was increased to approximately 85% in carbon monoxide exposed rats. Moreover the voltage-current relationship showed a negative shift of sodium equilibrium potential in carbon monoxide treated animals. In 270-day-old carbon monoxide exposed rats parameters of sodium inactivation were not significantly modified; the reversal potential was still lower with respect to controls. The results indicate that prenatal exposure to mild carbon monoxide concentrations produces reversible changes in sodium inactivation kinetics and on irreversible change in sodium equilibrium potential. These alterations could reflect carbon monoxide influence on the rate of ion channel development.
[Carrat'u MR et al; Arch Toxicol 67 (5): 297-301 (1993)]**PEER REVIEWED**
In response to acute maternal hypoxia ornithine decarboxylase activity increased significantly in fetal rat brain peaking at 4 hr. This was associated with increased ornithine decarboxylase mRNA and elevated polyamine concentrations. To correlate this response with development we measured ornithine decarboxylase activity in the rat from gestational day E 17 to postnatal day P 10. We also examined to what extent hypoxia induces increased ornithine decarboxylase activity in adult rat brains and whether the response to chronic hypoxia differed from that to acute hypoxia. To test the hypothesis that this increased activity is due to hypoxic hypoxia per se, we subjected pregnant dams to inspired carbon monoxide concentrations ranging from 150 to 1000 ppm and assayed ornithine decarboxylase activity in the fetal brain 4 hr later. In the fetus ornithine decarboxylase activity was elevated on E 17 in the cerebrum and cerebellum. It declined gradually to about one-tenth E 17 levels by E 21 and remained low thereafter except for a postnatal elevation in the cerebellum on P 3. In response to 10.5% 02, in the 3-day-old rat, ornithine decarboxylase activity peaked between 2 and 3 hr of hypoxia increasing 3-fold in the hippocampus and 2-fold in cerebellum. Similar increases were seen in the hypoxic adult rat brain. In inspired oxygen dose-response studies exposure of P 3 rat pups to 13.25% 02 for 2.5 hr produced a 1.5-fold increase in ornithine decarboxylase activity; 10.5% 02 produced a 2-3-fold increase while in response to 9% 02 ornithine decarboxylase activity remained at baseline levels. With maternal carbon monoxide-hypoxia, ornithine decarboxylase activity increased in the fetal brain at 4 hr, as seen with hypoxic-hypoxia. For example, in hippocampus, ornithine decarboxylase activity doubled at 500 ppm and tripled at 600 ppm. It was concluded: (1) apparently the ability to respond thus is not lost as the animal ages and may represent an important cellular response to acute hypoxia; (2) the increase in hypoxic induced ornithine decarboxylase activity is relative to the already elevated activity seen from E 17 to E 20; a vast reserve for the induction of fetal ornithine decarboxylase activity probably exists and may indicate the importance of this enzyme during this time frame for differentiation and growth promotion: and (3) the carbon monoxide-hypoxia studies suggest that some aspects of the cellular responses to carbon monoxide- and hypoxic-hypoxia are similar.
[Packianathan S et al; Developmental Brain Research 76 (l): 131-40 (1993)]**PEER REVIEWED**
Energy metabolite levels in the brain after a brief exposure to carbon monoxide were investigated using mice. Male ddY-mice were exposed to carbon monoxide in an exposure chamber for 15 minutes and then transferred to room air. Blood was drawn and brain tissue preparation was conducted at 0 min, 30 min, 4 (hr), 1 day, 4 days, or 8 days after exposure. Brain energy charge potential was calculated. There was a decrease of spontaneous activities in all mice during carbon monoxide exposure, with clonic seizures and death occurring in 33%. Blood carboxyhemoglobin was 63% immediately after exposure; it decreased to 29% 30 min later, and returned to normal in 4 hr. Phosphocreatine, ATP, and energy charge potential levels were lower by 24%, 20%, and 13%, respectively, while adenosine-diphosphate, adenosine-monophosphate, and pyruvate, and pyruvate/lactate ratios were higher by 16%, 216%: 108%, and 209%, respectively. At 4 hr, 1 day, 4 days, and 8 days after exposure, the levels of these metabolites did not differ from those of controls. /It was/ concluded that energy metabolism in the whole brain of mice does not appear to be impaired by acute carbon monoxide poisoning.
[Matsuoka M et al; Research Communications in Chemical Pathology and Pharmacology 81 (1): 15-20 (1993)]**PEER REVIEWED**
The kinetics of carbon monoxide binding to cytochrome p450 in rat liver microsomes were examined using the flash photolysis technique. Modulation of the kinetics by p450 form-specific effectors such as anti-p450 monoclonal antibodies and substrates was used to elucidate the kinetic behavior of individual p450s within the endoplasmic reticulum. The problem of attributing a kinetic parameter to a single p450 in the presence of multiple microsomal p450s was overcome with a difference method that employs the difference of the kinetic profiles obtained in the presence and absence of a p450 effector. Applying this approach to study the conformation/dynamics of p450 2Bl in microsomes from phenobarbital-treated rats revealed that the substrate benzphetamine enhances while testosterone inhibits the rate of carbon monoxide binding to this p450. Similar experiments with p450 lAl in microsomes from 3-methylcholanthrene-treated rats showed that the substrate benzo(a)pyrene accelerates carbon monoxide binding. These results show that the access channel between solvent and heme in the p450 interior can be altered in a substrate- and p450-dependent manner to either hinder or facilitate carbon monoxide diffusion to the heme iron. Analytical difference methods may be employed to characterize the conformation of individual p450s in their native membrane environment in the endoplasmic reticulum.
[Koley AP et al; Biochemistry 33 (9): 2484-9 (1994)]**PEER REVIEWED**
A study was conducted to more thoroughly investigate the effects of carbon monoxide and cyanide on the electrocardiographic responses in rats. Female Sprague Dawley rats were exposed to 1,500 or 2,400 ppm carbon monoxide and/or treated with cyanide. Carbon monoxide initially induced hyperglycemia and many fold increases in blood lactate concentration along with rebound increases in blood glucose during recovery. Cyanide produced hyperglycemia, but there was no glucose rebound nor a significant lactate increase. Carbon monoxide exposure at the concn used had a major effect in slowing both AV conduction and ventricular repolarization in the rat. In contrast, cyanide treatment of the rat with 4 mg/kg had little effect on either conduction or repolarization. Falling blood pressure elicited by carbon monoxide exposure appeared to be associated with a slowing of ventricular repolarization.
[Katzman GM, Penney DG; Toxicol Lett 69 (2): 139-53 (1993)]**PEER REVIEWED**
Wistar female rats were exposed to relatively mild concentrations of carbon monoxide (75 and 150 ppm) from day 0 to day 20 of pregnancy. The results show that prenatal exposure to carbon monoxide (150 ppm) produced a significant reduction in the minimum frequency of ultrasonic calls emitted by rat pups removed from their nest. Moreover, a significant decrease in the responsiveness (rate of calling) to a challenge dose of diazepam (0.25 mg/kg) was found in male pups exposed to carbon monoxide (150 ppm) during gestation. Prenatal carbon monoxide (75 and 150 ppm) did not significantly affect locomotor activity or D-amphetamine-induced hyperactivity in both 14 and 21 day old animals. Furthermore, adult male rats exposed to this chemical (150 ppm) during gestation exhibited significant alterations in the acquisition of an active avoidance task. carbon monoxide-induced learning disruption does not seem to be linked to changes in the emotionality of animals. Gestational exposure to carbon monoxide induces in rat offspring both short and long term behavioral changes characterized by altered ontogeny of emotional responsiveness to environmental challenges and by learning impairment.
[Di Giovanni V et al; Brain Res 616 (1-2): 126-31 (1993)]**PEER REVIEWED**
Adult male rats were exposed to 500 ppm carbon monoxide continuously for 30 days, while litter-mate controls remained in room air (AIR). Heart weight-to-body weight ratio and hematocrit were increased significantly. Right ventricle free wall thickness was increased significantly as was right to left heart diameter and average heart diameter. Cross-sectional areas of the left ventricle free wall, interventricular septum (S) and right ventricle midway between the apex and base were increased significantly. Morphometric analysis of the carbon monoxide-exposed and AIR hearts revealed no significant differences in the number of small (27-114 um) or larger (> 114 um) blood vessels in any region; however, there was a trend towards an increased number of the smaller vessels, both arterioles and venules, in the carbon monoxide-exposed rats. The larger arteries in the S and right ventricle were significantly larger in the carbon monoxide-exposed rats. There was a significant overall effect of carbon monoxide on larger artery diameter across all heart regions, consistent with the appearance of heart radiographs taken. There were no differences in the diameter of the small vessels in any region of the heart between the carbon monoxide-exposed and AIR rats. The vessel cross-sectional area of the larger vessels tended to be increased in all regions of the heart. The cross-sectional area of the large arteries in the left ventricle was increased significantly. Arterial wall thickness was decreased significantly in right ventricle and there was a significant overall effect of carbon monoxide in decreasing wall thickness and the ratio of wall thickness-to-vessel luminal diameter in these vessels. No vascular pathology was observed. The results suggest changes in coronary vessel architecture during chronic carbon monoxide-induced cardiac hypertrophy and are consistent with earlier hemodynamic and morphometric studies of carbon monoxide exposed hearts.
[Penney DG et al; J Appl Toxicol 14 (1): 47-54 (1994)]**PEER REVIEWED**
Carbon monoxide intoxication decr systemic blood pressure and peripheral resistance. ... To assess the role of the skin in this process, the perfusion of hind limb shaven skin in anesthetized rats /were measured/ during acute moderate carbon monoxide intoxication. At a steady blood level of 25% carboxyhemoglobin, the red cell flux was measured as an index of tissue perfusion. ... The mean blood pressure decr by 30% during carbon monoxide exposure, but there was no change in mean red blood cell flux of the hind limb skin microvessel bed. ...Rat hind limb perfusion was not affected by acute moderate steady state carbon monoxide intoxication.
[Lee KC et al; Int J Microcirc Clin Exptl 14 (1-2): 62-6 (1994)]**PEER REVIEWED**
... Studies were conducted to determine the alterations in white blood cells (WBC), red blood cells (RBC), hematocrit (HCT), and hemoglobin (HGB) of maternal and placental blood in protein deprived mice. Mated dams were placed on diets of 16, 8 or 4% protein throughout gestation. The dams were exposed to 0, 125 or 250 ppm carbon monoxide for 6 hr/day for the first two weeks of pregnancy. ... The amounts of WBC and RBC in the maternal and placental blood were related to carbon monoxide exposure levels; the concn of HGB in the maternal blood was also related to carbon monoxide exposure levels. The amounts of WBC, RBC and HGB in the placental blood were related to dietary protein levels.
[Hill M; Teratol 49 (5): 407 (1994)]**PEER REVIEWED**
It has been shown, using the method of rat post implantation embryo culture, that the rat conceptus metabolizes the lipoxygenase inhibitor N-hydroxy-N-methyl-7-propoxy-2-naphthale... in vitro. The capacity to metabolize /this cmpd/ and accumulate its main metabolites depends on the developmental stage and length of exposure. ... To find further evidence for the involvement if cytochrome p450 enzymes in the conceptal metabolism of /this cmpd/, conceptuses preinduced in utero (3-MC or phenobarbital) were exposed to N-hydroxy-N-methyl-7-propoxy-2-naphthale... in vitro and gassed during the second half of the culture period with a mixture containing 35% carbon monoxide, an inhibitor of cytochrome p450 enzymes. Carbon monoxide treatment lead to an inhibition of conceptal metabolism of /the cmpd/ in comparison with that in conceptuses cultured under normal gassing conditions (without carbon monoxide). These results strongly suggest the involvement of cytochrome p450 dependent monooxygenases in the conceptal metabolism of N-hydroxy-N-methyl-7-propoxy-2-naphthale... in vitro.
[Trelouw GD, Bechter R; Toxicol In Vitro 7 (3): 247-58 (1993)]**PEER REVIEWED**
Hypoglycemia and hyperglycemia were induced in mice by fasting and by injecting with glucose, respectively. These and normally fed (normoglycemic) animals were exposed to 0.5% carbon monoxide for 10 min. This altered concn of energy metabolites in the brain, including decr in phosphocreatine and incr in creatine and lactate. The only difference between normoglycemic and hypoglycemic mice was lower lactate in the latter. In hyperglycemic mice, phosphocreatine and ATP were better preserved during carbon monoxide exposure and lactate was lower than in normoglycemic mice. Blood glucose concn correlated well with glucose but not with lactate in the brain. Thus, moderate hypo or hyperglycemia seems not to exacerbate carbon monoxide alterations of brain energy metabolism.
[Matsuoka M et al; Toxicol Lett 73 (2): 135-43 (1994)]**PEER REVIEWED**
... Pregnant rats were exposed to carbon monoxide daily for a 2 hr period throughout gestation. The concn daily for a 2 hr period was between 1,000 to 1,200 ppm. Appropriate pair fed and ad libitum control animals were included to separate the effect of carbon monoxide on fetal growth from maternal underfeeding. Body weights of fetuses exposed to carbon monoxide were significantly lower than those of pair fed and ad libitum controls. ... The difference in fetal body weight between pair fed and ad libitum controls was not significant. Litter size was not significantly different among the three groups. The carbon monoxide exposed dams had significantly higher hematocrit values than the other two groups.
[Leichter J; Biochem Arch 9: 267-72 (1993)]**PEER REVIEWED**
Wistar female rats were exposed to ... carbon monoxide /concentrations/ at 75 or 150 ppm from day 0 to day 20 of pregnancy. The results show that splenic macrophage phagocytosis of Candida albicans was significantly decr in 15 and 21 day old male rats exposed to carbon monoxide /at 150 ppm/ during pregnancy. ... Splenic macrophage killing was significantly reduced in 15 day old male pups prenatally exposed to 75 and 150 ppm of carbon monoxide. Prenatal carbon monoxide /at 150 ppm/ significantly decr the splenic macrophage O2 release in both 15 and 21 day old pups. Carbon monoxide induced alterations in the immune system were not observed in 60 day old rats. These findings indicate that gestational exposure to ... carbon monoxide induces in rat offspring reversible immunological changes characterized by an altered splenic macrophage function.
[Giustino A et al; Pharmacol Toxicol 73 (5): 274-8 (1993)]**PEER REVIEWED**
The involvement of leukocytes in the conversion of xanthinine dehydrogenase to xanthinine oxidase in the brain after carbon monoxide poisoning was investigated in rats. Studies were made of male Wistar rats treated with monoclonal antibodies directed against activation dependent, B2 integrin adhesion molecules present on leukocytes. Rats were exposed to carbon monoxide at 1000 ppm for 40 min followed by 3000 ppm for up 20 min; rats were removed to room air when they lost consciousness. ... Myeloperoxidase activity was incr ten fold in the brain microvessel segments prepared from rats immediately or 90 min after carbon monoxide exposure. Leukocytes played a central role in the oxidative stress mediated by carbon monoxide poisoning. ... Leukocytes were sequestered in the vasculature. The absence of xanthinine dehydrogenase to xanthinine oxidase and lipid peroxidation in leukopenic rats and in rats treated with anti-CD-18 F(ab')2 fragments indicated that leukocytes were involved in precipitating carbon monoxide mediated biochemical changes. The finds ... were consistent with the theory that carbon monoxide mediated brain injury is a type of postischemic reperfusion injury.
[Thom SR; Tox Appl Pharm 123 (2): 234-47 (1993)]**PEER REVIEWED**
Metabolism/Pharmacokinetics:
Metabolism/Metabolites:
Metabolism of the dihalomethanes leads to dehalogenation, and the end product is carbon monoxide. ... The carbon monoxide appears to arise from a formyl halide intermediate resulting from the loss of one halide atom from the halocarbon. This intermediate as an alternative to losing carbon monoxide can covalently bind to cellular protein or lipid.
[Amdur, M.O., J. Doull, C.D. Klaasen (eds). Casarett and Doull's Toxicology. 4th ed. New York, NY: Pergamon Press, 1991. 692]**PEER REVIEWED**
The primary factors that determine the final level of carboxyhemoglobin are: the amount of inspired carbon monoxide; minute alveolar ventilation at rest and during exercise; endogenous carbon monoxide production; blood volume; barometric pressure; and the relative diffusion capability of the lungs. The rate of diffusion from the alveoli and the binding of carbon monoxide with the blood hemoglobin are the steps limiting the rate of uptake into the blood.
[WHO; Environ Health Criteria 13: Carbon Monoxide p.35 (1979)]**PEER REVIEWED**
Endogenous production of carbon monoxide results from metabolism of the alpha-methane carbon atom in the protoporphyrin ring /by hemeoxygenase/ during hemoglobin catabolism and produces a blood carboxyhemoglobin level of 0.4-0.7%.
[Ellenhorn, M.J. and D.G. Barceloux. Medical Toxicology - Diagnosis and Treatment of Human Poisoning. New York, NY: Elsevier Science Publishing Co., Inc. 1988. 820]**PEER REVIEWED**
Methylene chloride, a constituent of paint and varnish removers, is converted in vivo to carbon monoxide.
[Ellenhorn, M.J. and D.G. Barceloux. Medical Toxicology - Diagnosis and Treatment of Human Poisoning. New York, NY: Elsevier Science Publishing Co., Inc. 1988. 820]**PEER REVIEWED**
Absorption, Distribution & Excretion:
CARBON MONOXIDE IS ELIMINATED THROUGH THE LUNGS WHEN AIR FREE OF CARBON MONOXIDE IS INHALED.
[Sax, N.I. Dangerous Properties of Industrial Materials. 6th ed. New York, NY: Van Nostrand Reinhold, 1984. 643]**PEER REVIEWED**
... /CARBON MONOXIDE/ READILY CROSSES PLACENTA.
[Gilman, A.G., T.W. Rall, A.S. Nies and P. Taylor (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 8th ed. New York, NY. Pergamon Press, 1990. 1620]**PEER REVIEWED**
CARBON MONOXIDE IS NOT A CUMULATIVE POISON IN THE USUAL SENSE. CARBOXYHEMOGLOBIN IS FULLY DISSOCIABLE, AND ONCE EXPOSURE HAS BEEN TERMINATED, THE PIGMENT WILL REVERT TO OXYHEMOGLOBIN. LIBERATED CARBON MONOXIDE IS ELIMINATED VIA THE LUNGS.
[Amdur, M.O., J. Doull, C.D. Klaasen (eds). Casarett and Doull's Toxicology. 4th ed. New York, NY: Pergamon Press, 1991. 268]**PEER REVIEWED**
The absorption of carbon monoxide is said not to occur, but its absorption followed by oxidation within the epidermis has not been excluded.
[Hayes, W.J., Jr., E.R. Laws Jr., (eds.). Handbook of Pesticide Toxicology Volume 1. General Principles. New York, NY: Academic Press, Inc., 1991. 139]**PEER REVIEWED**
After continuous exposure to carbon monoxide for 49 hr, 50% was eliminated in 30-180 min and 90% within 180-420 min.
[WHO; Environ Health Criteria 13: Carbon Monoxide p.43 (1979)]**PEER REVIEWED**
COHb is fully dissociable and, once acute exposure is terminated, the carbon monoxide will be excreted via the lungs. Only a very small amount is oxidized to carbon dioxide.
[Gilman, A.G., T.W. Rall, A.S. Nies and P. Taylor (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 8th ed. New York, NY. Pergamon Press, 1990. 1620]**PEER REVIEWED**
The most influential variables in determining carboxyhemoglobin levels are carbon monoxide concn, duration of exposure, and alveolar ventilation. ... The expected blood carboxyhemoglobin values for an average sized adult under conditions of light work for 6 to 8 hours at 35 ppm carbon monoxide will be approximately 5%. After an exposure of 200 ppm for 15 min, an average adult engaged in heavy work or a smaller adult engaged in light work will have a carboxyhemoglobin level of approximately 5%.
[American Conference of Governmental Industrial Hygienists, Inc. Documentation of the Threshold Limit Values and Biological Exposure Indices. 6th ed. Volumes I,II, III. Cincinnati, OH: ACGIH, 1991. 228]**PEER REVIEWED**
The relationship between carboxyhemoglobin formation and transient carbon monoxide exposure was studied in humans to test the accuracy of the Coburn/Forster/Kane (CFKE) equation for predicting carboxyhemoglobin concn under transient carbon monoxide exposure conditions. The study group consisted of 15 male volunteers, mean age 26.5 yr. They were exposed to 6,683 ppm (18)C labeled carbon monoxide for 5 min. Radial arterial and antecubital venous blood samples were collected starting 5 sec before exposure and continuing up to 10 min after exposure ended, and analyzed for carbon monoxide. Minute ventilation and other appropriate pulmonary function parameters were determined .... to calculate the parameters in CFKE equation. The overall mean arterial and venous carboxyhemoglobin concn were 2.08 and 1.39% higher after exposure ended than before exposure began, respectively. The CFKE equation over predicted carboxyhemoglobin concn in venous blood and under predicted carboxyhemoglobin concn in arterial blood. One min after exposure ended, mean arterial carboxyhemoglobin concn began to decr and approached the venous blood carboxyhemoglobin concn in post exposure period ranged from 2.3 to 12.1%, mean 6.2%, regardless of sampling time. The discrepancies were attributed to delays in the appearance of carboxyhemoglobin, approx 1 min in venous blood and 30 sec or less in arterial blood. ...
[Benignus VA et al; J Appl Phys 76 (4): 1739-45 (1994)]**PEER REVIEWED**
Biological Half-Life:
THE BIOLOGICAL HALF-LIFE OF CARBON MONOXIDE CONCENTRATION IN THE BLOOD OF SEDENTARY ADULTS IS ABOUT 2-5 HOURS. THE ELIMINATION OF CARBON MONOXIDE BECOMES SLOWER WITH TIME & THE LOWER THE INITIAL LEVEL OF CARBOXYHEMOGLOBIN, THE SLOWER THE RATE OF EXCRETION.
[International Labour Office. Encyclopedia of Occupational Health and Safety. Vols. I&II. Geneva, Switzerland: International Labour Office, 1983. 396]**PEER REVIEWED**
Mechanism of Action:
Carbon monoxide ... reacts /in the blood stream/ with hemoglobin to form carboxyhemoglobin, a form which is incapable of combining with oxygen. Exposure to air containing 0.4% of carbon monoxide for 20-30 min results in the conversion of 70% of the hemoglobin in the blood to carboxyhemoglobin.
[Humphreys, D.J. Veterinary Toxicology. 3rd ed. London, England: Bailliere Tindell, 1988. 81]**PEER REVIEWED**
Carbon monoxide binds tightly to the reduced form of iron in hemoglobin, reducing the delivery of oxygen to tissues. Although this has for many years been thought to be the sole mechanism of toxicity of carbon monoxide, there is evidence to suggest that carbon monoxide also binds to cytochrome a + a3.
[Amdur, M.O., J. Doull, C.D. Klaasen (eds). Casarett and Doull's Toxicology. 4th ed. New York, NY: Pergamon Press, 1991. 28]**PEER REVIEWED**
Carbon monoxide and ethylisocyanide act as ligands for the reduced heme moiety and thus compete with the endogenous ligand, molecular oxygen. These are potent inhibitors of oxidative reactions. Carbon monoxide also inhibits p450 mediated reductive reactions.
[Amdur, M.O., J. Doull, C.D. Klaasen (eds). Casarett and Doull's Toxicology. 4th ed. New York, NY: Pergamon Press, 1991. 113]**PEER REVIEWED**
The affinity of hemoglobin for carbon monoxide is between 210 and 300 times greater than its affinity for oxygen, the exact factor depending on pH of the blood and partial pressure of carbon dioxide. ... Furthermore, the presence of carboxyhemoglobin alters the dissociation of oxyhemoglobin so that the remaining oxyhemoglobin is somewhat less efficient in transporting oxygen.
[Hayes, W.J., Jr., E.R. Laws Jr., (eds.). Handbook of Pesticide Toxicology Volume 1. General Principles. New York, NY: Academic Press, Inc., 1991. 172]**PEER REVIEWED**
Interactions:
...ADDITION OF CARBON DIOXIDE CAUSED AN INCREASE IN THE RATE OF ELIMINATION OF CARBON MONOXIDE DUE TO THE INCREASE IN MINUTE-VOLUME IT PRODUCED.
[Hamilton, A., and H. L. Hardy. Industrial Toxicology. 3rd ed. Acton, Mass.: Publishing Sciences Group, Inc., 1974. 244]**PEER REVIEWED**
...IF RABBITS EXPOSED TO CARBON MONOXIDE /FOR 8 WK/ WERE FED CHOLESTEROL, THE ACCUMULATION OF FATS /IN BLOOD VESSELS/ INCREASED 3-4 TIMES THAT FOUND IN ANIMALS FED CHOLESTEROL BUT NOT EXPOSED TO CARBON MONOXIDE.
[Hamilton, A., and H. L. Hardy. Industrial Toxicology. 3rd ed. Acton, Mass.: Publishing Sciences Group, Inc., 1974. 252]**PEER REVIEWED**
Male Fischer 344 rats were exposed continuously for 6 wk to: 100 or 500 ppm carbon monoxide (CO); 15,000 feet simulated high altitude; or 100 or 500 ppm CO at simulated high altitude. Simulated high altitude decr body wt significantly; CO and CO/simulated high altitude interaction had no significant effect on body weight. CO and simulated high altitude increased hematocrit ratio significantly; 500 ppm CO increased hematocrit ratio to a greater extent than 100 ppm CO. There was a significant interaction between 500 ppm CO and simulated high altitude on hematocrit ratio. The mean electrical axis was shifted to the right by simulated high altitude, and shifted to the left by CO. The effect was dose dependent, with the greater left shift occurring with 500 ppm CO.
[Cooper R et al; Physiol Behav 46 (1): 75-9 (1989)]**PEER REVIEWED**
Eight pairs of male Wistar rats were continuously infused liquid diet and ethanol (8 g/kg/day) or isocaloric dextrose for 4 mo via gastrostomy cannulas. 4 pairs were also continuously exposed to 200 ppm carbon monoxide (CO), 24 hr/day, 7 days/wk. Mean ethanol intake (g/kg/day) in the ethanol-CO group (13.3 + or - 0.8) was not significantly different from the mean ethanol intake in the ethanol-air group (13.4 + or - 0.7). Blood alcohol levels were 277 + or - 64 and 295 + or - 50 mg/dl, respectively. Body wt gain was significantly higher in control rats (both CO control and corn oil control) at 3 mo. Liver damage was followed monthly by serum alanine aminotransferase and morphologic assessment of liver biopsy. Serum levels of alanine aminotransferase were significantly higher in the CO-ethanol group compared to other groups at 2, 3 and 4 mo. Electron microscopy revealed a greater degree of cell necrosis in the CO-exposed group which explained its significantly higher alanine aminotransferase activity levels. Both exptl groups (CO-ethanol and air-ethanol) had significantly greater liver damage than controls. Rats showed severe steatosis (75% liver cells infiltrated by fat) in 3 mo. Carboxyhemoglobin levels were not different in the ethanol fed and control groups.
[Nanji AA et al; Life Sci 45 (10): 885-90 (1989)]**PEER REVIEWED**
Since the hemoglobin of arterial blood is almost completely saturated with oxygen under normal conditions, the breathing of 100% oxygen by a normal person does not significantly increase the amount of oxygen carried in that way, but it does increase the total oxygen content of the arterial blood by about 10% by increasing the physically dissolved oxygen. Because only part of the hemoglobin of a person poisoned by carbon monoxide can carry oxygen, the same increase in dissolved oxygen constitutes a greater percentage increase in the total oxygen content of the arterial blood ... about a 20% increase in a person half of whose hemoglobin is rendered useless by carbon monoxide. The physically dissolved oxygen is transferred to the tissues with unusual efficiency because of the great difference in its tension in the arterial ... blood as compared with the tissues. At the higher partial pressure, oxygen can compete against carbon monoxide more effectively for hemoglobin and, by mass action, speed the elimination of the poison.
[Hayes, W.J., Jr., E.R. Laws Jr., (eds.). Handbook of Pesticide Toxicology Volume 1. General Principles. New York, NY: Academic Press, Inc., 1991. 398]**PEER REVIEWED**
Pharmacology:
Therapeutic Uses:
MEDICATION (VET): Euthanasia of dogs and cats can be carried out in a carbon monoxide chamber, but there are a number of precautions and guidelines for proper use of such chambers.
[Booth, N.H., L.E. McDonald (eds.). Veterinary Pharmacology and Therapeutics. 5th ed. Ames, Iowa: Iowa State University Press, 1982. 1061]**QC REVIEWED**
Interactions:
...ADDITION OF CARBON DIOXIDE CAUSED AN INCREASE IN THE RATE OF ELIMINATION OF CARBON MONOXIDE DUE TO THE INCREASE IN MINUTE-VOLUME IT PRODUCED.
[Hamilton, A., and H. L. Hardy. Industrial Toxicology. 3rd ed. Acton, Mass.: Publishing Sciences Group, Inc., 1974. 244]**PEER REVIEWED**
...IF RABBITS EXPOSED TO CARBON MONOXIDE /FOR 8 WK/ WERE FED CHOLESTEROL, THE ACCUMULATION OF FATS /IN BLOOD VESSELS/ INCREASED 3-4 TIMES THAT FOUND IN ANIMALS FED CHOLESTEROL BUT NOT EXPOSED TO CARBON MONOXIDE.
[Hamilton, A., and H. L. Hardy. Industrial Toxicology. 3rd ed. Acton, Mass.: Publishing Sciences Group, Inc., 1974. 252]**PEER REVIEWED**
Male Fischer 344 rats were exposed continuously for 6 wk to: 100 or 500 ppm carbon monoxide (CO); 15,000 feet simulated high altitude; or 100 or 500 ppm CO at simulated high altitude. Simulated high altitude decr body wt significantly; CO and CO/simulated high altitude interaction had no significant effect on body weight. CO and simulated high altitude increased hematocrit ratio significantly; 500 ppm CO increased hematocrit ratio to a greater extent than 100 ppm CO. There was a significant interaction between 500 ppm CO and simulated high altitude on hematocrit ratio. The mean electrical axis was shifted to the right by simulated high altitude, and shifted to the left by CO. The effect was dose dependent, with the greater left shift occurring with 500 ppm CO.
[Cooper R et al; Physiol Behav 46 (1): 75-9 (1989)]**PEER REVIEWED**
Eight pairs of male Wistar rats were continuously infused liquid diet and ethanol (8 g/kg/day) or isocaloric dextrose for 4 mo via gastrostomy cannulas. 4 pairs were also continuously exposed to 200 ppm carbon monoxide (CO), 24 hr/day, 7 days/wk. Mean ethanol intake (g/kg/day) in the ethanol-CO group (13.3 + or - 0.8) was not significantly different from the mean ethanol intake in the ethanol-air group (13.4 + or - 0.7). Blood alcohol levels were 277 + or - 64 and 295 + or - 50 mg/dl, respectively. Body wt gain was significantly higher in control rats (both CO control and corn oil control) at 3 mo. Liver damage was followed monthly by serum alanine aminotransferase and morphologic assessment of liver biopsy. Serum levels of alanine aminotransferase were significantly higher in the CO-ethanol group compared to other groups at 2, 3 and 4 mo. Electron microscopy revealed a greater degree of cell necrosis in the CO-exposed group which explained its significantly higher alanine aminotransferase activity levels. Both exptl groups (CO-ethanol and air-ethanol) had significantly greater liver damage than controls. Rats showed severe steatosis (75% liver cells infiltrated by fat) in 3 mo. Carboxyhemoglobin levels were not different in the ethanol fed and control groups.
[Nanji AA et al; Life Sci 45 (10): 885-90 (1989)]**PEER REVIEWED**
Since the hemoglobin of arterial blood is almost completely saturated with oxygen under normal conditions, the breathing of 100% oxygen by a normal person does not significantly increase the amount of oxygen carried in that way, but it does increase the total oxygen content of the arterial blood by about 10% by increasing the physically dissolved oxygen. Because only part of the hemoglobin of a person poisoned by carbon monoxide can carry oxygen, the same increase in dissolved oxygen constitutes a greater percentage increase in the total oxygen content of the arterial blood ... about a 20% increase in a person half of whose hemoglobin is rendered useless by carbon monoxide. The physically dissolved oxygen is transferred to the tissues with unusual efficiency because of the great difference in its tension in the arterial ... blood as compared with the tissues. At the higher partial pressure, oxygen can compete against carbon monoxide more effectively for hemoglobin and, by mass action, speed the elimination of the poison.
[Hayes, W.J., Jr., E.R. Laws Jr., (eds.). Handbook of Pesticide Toxicology Volume 1. General Principles. New York, NY: Academic Press, Inc., 1991. 398]**PEER REVIEWED**
Environmental Fate & Exposure:
Probable Routes of Human Exposure:
...LARGE QUANTITIES OF CARBON MONOXIDE GAS RELEASED BY BURNING CHARCOAL CAN RESULT IN SEVERE POISONING OR DEATH. HIBACHIS SHOULD NEVER BE USED AS A SOURCE OF HEAT IN SLEEPING QUARTERS.
[Arena, J. M. Poisoning: Toxicology, Symptoms, Treatments. Fourth Edition. Springfield, Illinois: Charles C. Thomas, Publisher, 1979. 240]**PEER REVIEWED**
CAR EXHAUST CONTAINS 1 TO 7% CARBON MONOXIDE. THIS IS WELL INTO...TOXIC RANGE...
[Arena, J. M. Poisoning: Toxicology, Symptoms, Treatments. Fourth Edition. Springfield, Illinois: Charles C. Thomas, Publisher, 1979. 240]**PEER REVIEWED**
Occupational exposure to increased ambient carbon monoxide has been a major menace to firefighters, traffic police, coal miners, coke oven and smelter workers, caisson workers, toll both attendants, and transportation mechanics. As commuting distances increase, workers driving to and from work are exposed to more ambient carbon monoxide.
[Sullivan, J.B. Jr., G.R. Krieger (eds.). Hazardous Materials Toxicology-Clinical Principles of Environmental Health. Baltimore, MD: Williams and Wilkins, 1992. 540]**PEER REVIEWED**
Natural Pollution Sources:
NATURAL SOURCES SUCH AS ATMOSPHERIC OXIDN OF METHANE, FOREST FIRES, TERPENE OXIDN & OCEAN (WHERE MICROORGANISMS PRODUCE CARBON MONOXIDE) ARE RESPONSIBLE FOR ABOUT 90% OF ATMOSPHERIC CARBON MONOXIDE; HUMAN ACTIVITY PRODUCES ABOUT 10%.
[Gilman, A. G., L. S. Goodman, and A. Gilman. (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 6th ed. New York: Macmillan Publishing Co., Inc. 1980. 1641]**PEER REVIEWED**
A small amount of carbon monoxide is produced normally in the body. This endogenous carbon monoxide is sufficient in amount to maintain a carbon monoxide hemoglobin saturation of about 0.4 to 0.7 percent. In some persons with blood disease, such as hemolytic anemia, the carbon monoxide saturation may reach 6 percent
[PATTY. INDUS HYG & TOX 3RD ED VOL2A, 2B, 2C, 1981-1982 p.4117]**PEER REVIEWED**
Artificial Pollution Sources:
WATER HEATERS ARE A COMMON SOURCE OF CARBON MONOXIDE.
[Hamilton, A., and H. L. Hardy. Industrial Toxicology. 3rd ed. Acton, Mass.: Publishing Sciences Group, Inc., 1974. 239]**PEER REVIEWED**
MOTOR VEHICLES ACCOUNT FOR ABOUT 55 TO 60% OF GLOBAL MAN-MADE EMISSIONS OF CARBON MONOXIDE.
[International Labour Office. Encyclopedia of Occupational Health and Safety. Vols. I&II. Geneva, Switzerland: International Labour Office, 1983. 396]**PEER REVIEWED**
SINCE MOST...POLYMERIC MATERIALS CONTAIN CARBON, CARBON MONOXIDE IS ONE OF THE PRIMARY GASES GENERATED FROM THE HEATING AND BURNING OF THESE MATERIALS /PLASTICS/.
[Doull, J., C.D. Klaassen, and M. D. Amdur (eds.). Casarett and Doull's Toxicology. 2nd ed. New York: Macmillan Publishing Co., 1980. 551]**PEER REVIEWED**
Concentrations as high as 30% have been measured in automobile exhaust gas, although 7% is more common. Pyrolysis of some vinyl plastics results in the production of appreciable concentrations of carbon monoxide. Natural gas associated with petroleum deposits has no carbon monoxide but in processing natural gas (e.g., cracking), carbon monoxide may be produced. As distributed, manufactured gas commonly has a carbon monoxide content between 2 and 15% (by volume)
[GOSSELIN. CTCP 5TH ED 1984 p.III-94]**PEER REVIEWED**
An unusual emission source is represented by propane-fueled ice-surfacing machines in indoor skating rinks
[GOSSELIN. CTCP 5TH ED 1984 p.III-95]**PEER REVIEWED**
A major source of carbon monoxide for many people is tobacco smoking. Cigarette smoke contains over 2% carbon monoxide, but the average concentration in the smoke that reaches the lungs is about 400 ppm
[PATTY. INDUS HYG & TOX 3RD ED VOL2A, 2B, 2C, 1981-1982 p.4117]**PEER REVIEWED**
Portable stoves, formerly called "salamanders," when used to heat buildings under construction may be dangerous sources of carbon monoxide. Other sources that may give cause for concern are compressed air for respiratory devices such as supplied-air respirators or "scuba" diving equipment, when supplied from reciprocating compressors, in which carbon monoxide may be produced by overheating of lubricating oil
[PATTY. INDUS HYG & TOX 3RD ED VOL2A, 2B, 2C, 1981-1982 p.4115]**PEER REVIEWED**
Estimates have been made of the amounts of carbon monoxide (CO) released into the atmosphere as a result of man's activities and influence. Emissions have generally been calculated from the annual consumption of the various source material and the appropriate emission factors. The combustion of petroleum products remains by far the largest source of CO (81.9% in 1979) and the amounts of this gas generated therefrom are rising steadily (from 345.64 Tg in 1965 to 730.21 Tg in 1979). Refuse incineration also makes a sizable contribution but coal combustion is decreasing in importance (from 3.0% in 1965 to 1.4% in 1979). However, although emissions of CO are still increasing (from 468.08 Tg in 1965 to 891.83 Tg in 1979), the rate of increase is falling. During the periods 1965-70 and 1970-79 the average annual incr of CO emission were 5.4% and 3.6% respectively. Global per capita estimates of man-made emissions of CO increased from 140.0 kg in 1965 to 205.72 kg in 1979.
[Cullis CF, Hirschler MM; Atmos Environ 23 (6): 1195-203 (1989)]**PEER REVIEWED**
Environmental Fate:
ATMOSPHERIC FATE: A photochemical model was used to quantify the sensitivity of the tropospheric oxidants ozone (O3) and OH to changes in methane (CH4), carbon monoxide (CO), and NO emissions and to perturbations in climate and stratospheric chemistry. In most cases, incr CH4 and CO emissions will suppress OH (neg coefficients) in incr O3 (pos coefficients) except in areas where NO and O3 influenced by pollution are sufficient to incr OH. In most regions, NO, CO, and CH4 emission incr will suppress OH and incr O3, but these trends may be opposed by stratospheric O3 depletion and climate change.
[Thompson AM, Stewart RW; Atmos Environ 23 (3): 519-32 (1989)]**PEER REVIEWED**
Other Environmental Concentrations:
Unblended non filter cigarettes were made of the leaf and cutter of 5 kinds of bright tobacco cultivars and smoked to a 30 mm butt length on a smoking machine. Large variations were observed in the rates of formation of CO among the different kinds of tobacco. Leaf cigarette CO values ranged from 15.7 to 22.9 mg/cigarette, while cutter CO values ranged from 13.9 to 19.4 mg/cigarette. The CO formation rate was a more influential factor determining the amount of CO in mainstream smoke than the wt loss of the cigarette during puffs. Correlation coefficients were calculated for rate of CO formation and ethanol benzene e |
