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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. ...
... 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. ... ... 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. ...
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). 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... 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. 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. 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.
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.
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. 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.
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. 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. ...CHRONIC EXPOSURE TO LOW CONCENTRATIONS MAY EVOKE AN INSIDIOUS TOXICITY.
...SIGNIFICANTLY, ACTIVE CIGARETTE SMOKERS EXHIBITED PRONOUNCED ELEVATIONS /OF
CARBOXYHEMOGLOBIN/ IN BLOOD LEVELS. 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.
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. 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. 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. /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.
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. 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. 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. 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.
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. 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. 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.
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. 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. 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. 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.
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. ... 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. 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. 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.
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. 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. 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. 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. 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. 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.
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.
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.
THE FETUS MAY BE EXTREMELY SUSCEPTIBLE TO EFFECTS OF CARBON MONOXIDE, AND THE GAS READILY CROSSES
THE PLACENTA. 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.
Pregnant women are more susceptible to the effects of carbon monoxide exposure.
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. 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%. ... 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. ... 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 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. ...
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. CAR EXHAUST CONTAINS 1 TO 7% CARBON MONOXIDE.
THIS IS WELL INTO...TOXIC RANGE... 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.
Emergency Medical Treatment:
Emergency Medical Treatment:
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.
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.
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. ...
... 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. ... ... 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. ...
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.
...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. ...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.
...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. DATA SUGGESTED NO ASSOCIATION BETWEEN PERIODIC CARBON
MONOXIDE EXPOSURE & DEVELOPMENT OF ATHEROSCLEROSIS IN
MONKEYS. 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.
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. ...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. 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). 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). 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.
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. 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.
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.
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. In dead animals, the blood is bright red and mucous membranes are a healthy
pink ... There are no significant lesions in acute cases.
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.
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.
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.
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. 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. 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%.
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. 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.
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.
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.
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. 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. 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.
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.
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. 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.
... 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. 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-naphthalenethamine 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-naphthalenethamine 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-naphthalenethamine in
vitro. 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.
... 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. 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. 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.
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. 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. 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%. Methylene chloride, a constituent of paint and varnish removers, is converted
in vivo to carbon monoxide.
Absorption, Distribution & Excretion: CARBON MONOXIDE IS ELIMINATED THROUGH
THE LUNGS WHEN AIR FREE OF CARBON MONOXIDE
IS INHALED. ... /CARBON MONOXIDE/ READILY CROSSES
PLACENTA. 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. The absorption of carbon monoxide is
said not to occur, but its absorption followed by oxidation within the epidermis
has not been excluded. After continuous exposure to carbon monoxide
for 49 hr, 50% was eliminated in 30-180 min and 90% within
180-420 min. 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.
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%. 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. ...
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.
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.
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. 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. 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.
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. ...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.
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. 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. 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.
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.
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. ...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.
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. 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. 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.
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. CAR EXHAUST CONTAINS 1 TO 7% CARBON MONOXIDE.
THIS IS WELL INTO...TOXIC RANGE... 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.
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%. 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
Artificial Pollution Sources: WATER HEATERS ARE A COMMON SOURCE OF CARBON MONOXIDE.
MOTOR VEHICLES ACCOUNT FOR ABOUT 55 TO 60% OF GLOBAL MAN-MADE EMISSIONS OF
CARBON MONOXIDE.
SINCE MOST...POLYMERIC MATERIALS CONTAIN CARBON, CARBON MONOXIDE IS ONE OF THE PRIMARY GASES
GENERATED FROM THE HEATING AND BURNING OF THESE MATERIALS /PLASTICS/.
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) An unusual emission source is represented by propane-fueled ice-surfacing
machines in indoor skating rinks 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 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 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.
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.
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
extract, hexane extract, nicotine, or potassium. The highest was with potassium
(-0.95). The rate of formation of CO was mainly dependent on the potassium
content of the tobacco and could be estimated from the amounts of potassium,
total carbon, and lignin. The rates of formation of CO increased with a rise in
combustion temperature, which in turn rose as the potassium content of the
tobacco decr. Environmental tobacco smoke was analyzed after smoking of research cigarettes
by a machine in an experimental chamber 13.6 cu m in volume. The ventilation
rate was 3.55 air changes per hour. Air removed for sampling added about 0.5 air
changes per hour. One cigarette was lit every 30 min and was smoked with a 35 ml
puff of 2 sec every minute until extinguished after about 12 min. Mainstream
smoke was vented to the outside of the chamber. Additional tests were performed
with one cigarette smoked every 15 min and with several commercial cigarette
brands. Carbon monoxide concentrations
averaged 2.48 + or - 0.2 mg/cu m in the first series of 9 tests and 1.79 + or -
0.81 mg/cu m in a similar series. With one cigarette every 15 min the carbon monoxide concentrations averaged 4.76 +
or - 0.21 mg/cu m. The airborne yield per cigarette was 67 mg of carbon monoxide. Concentrations of carbon monoxide varied in a saw toothed form
with the pattern of smoking one cigarette every 30 min. The ratio of the average
maximum to the minimum concentration was about 3. The average concentration of
carbon monoxide was about 65 to 70% of
the maximum concentration. The ventilation time of carbon monoxide corresponded to the
predetermined air exchange rate of about 4 per hour. Concentrations of carbon monoxide using commercial brands of
cigarettes in the chamber and in a tavern setting were similar to those produced
by the research cigarettes.
Environmental Standards & Regulations:
Chemical/Physical Properties:
Molecular Formula: C-O
Molecular Weight: 28.01
Color/Form: COLORLESS GAS Colorless gas [Note: Shipped as a nonliquefied or liquefied compressed gas].
Odor: ODORLESS Odorless.
Taste: TASTELESS
Boiling Point: -191.5 DEG C
Melting Point: -205 DEG C
Critical Temperature & Pressure: CRITICAL PRESSURE: 35 ATMOSPHERES; CRITICAL TEMPERATURE: -139 DEG C
Density/Specific Gravity: 1.250 G/L AT 0 DEG C/4 DEG C
Heat of Combustion: -4.343 BTU/LB= -2,412 CAL/G= -101X10+5 JOULES/KG
Heat of Vaporization: LATENT: 92.8 BTU/LB= 51.6 CAL/G= 2.16X10+5 JOULES/KG
Solubilities: SOL IN BENZENE Appreciably sol in ethyl acetate, chloroform, acetic acid; freely absorbed by
a concentrated soln of cuprous chloride in hydrochloric acid or ammonium
hydroxide; solubility in methanol and ethanol about 7 times as great as in
water; in water 3.3 ml/100 cc at 0 deg C, 2.3 ml at 20 deg C
Spectral Properties: Refractive index of gas = 1.0003364 at 273 K and 546.1 nm
Surface Tension: 9.8 mN/m (of the liquid at 80 K)
Vapor Density: 0.968 (AIR= 1)
Vapor Pressure: GREATER THAN 1 ATM @ 20 DEG C (68 DEG F)
Viscosity: Viscosity gas at 273 K = 16.62 uN s/sq m
Other Chemical/Physical Properties: DECOMP INTO CARBON & CARBON DIOXIDE AT 400-700 DEG C, @ LOWER TEMP WHEN
IN CONTACT WITH CATALYTIC SURFACES Burns in air with bright blue flame; top pressure: 1500 psi; heat capacity @
20 deg C: 6.95 Cal/mole/deg C; heat value/cu m: 3033 kcal; heat of formation:
-26.39 Kcal/mol; above 800 deg c equil reaction favors carbon monoxide formation; decomp the
catalyzer hopcalite (a mixture of the oxides of manganese and copper) @ room
temp, as does palladium on silica gel SPECIFIC VOL: 13.8 CU FT/LB @ 70 DEG F Triple point temp = 68.15 K at 15.35 kPa Phase transition point = 61.55 K at 3.75 kPa Density at critical point = 301.0 kg/m3 Density of liquid = 788.6 kg/m3 at 81.63 K Density of solid, hexagonal = 929 kg/m3 at 65 K Heat capacity of gas at 298 K and 101.33 kPa; Cp = 29.142 J/mol-K, Cv =
20.769 J/mol-K Heat capacity of the liquid = 60.351 J/mol-K at 76 K
Heat of vaporization = 6.042 kJ/mol at 81.63 K Heat of fusion at triple point = 837.3 J/mol Heat of sublimation at triple point = 7.366 kJ/mol
Heat of transition = 632.11 J/mol Free energy of formation of gas at 298 K = -137.381 kJ/mol
Enthalpy of formation of gas = -110.63 kJ/mol Entropy of gas = 197.89 J/mol-K at 298 K and 101.33 kPa
Thermal conductivity of gas (STP) = 23.15 mW/m-K
Thermal conductivity of liquid = 0.1428 W/m-K at 80 K
Dielectric constant of gas = 1.000634 at 298 K and 101.33 kPa
Electric conductivity of liquid = 9.43x10-19 S/m at 85 K
Chemical Safety & Handling:
DOT Emergency Guidelines: Health: TOXIC; may be fatal if inhaled or absorbed through skin. Contact with
gas or liquefied gas may cause burns, severe injury and/or frostbite. Fire will
produce irritating, corrosive and/or toxic gases. Runoff from fire control may
cause pollution. /Carbon monoxide; Carbon monoxide, compressed; Carbon monoxide and hydrogen mixture; carbon monoxide and hydrogen mixture,
compressed/ Fire or explosion: Flammable; may be ignited by heat, sparks or flames. May
form explosive mixtures with air. Those substances designated with a "P" may
polymerize explosively when heated or involved in a fire. Vapors from liquefied
gas are initially heavier than air and spread along ground. Vapors may travel to
source of ignition and flash back. Some of these materials may react violently
with water. Containers may explode when heated. Ruptured cylinders may rocket.
Runoff may create fire or explosion hazard. /Carbon
monoxide; Carbon monoxide,
compressed; Carbon monoxide
and hydrogen mixture; carbon monoxide
and hydrogen mixture, compressed/ Public safety: CALL Emergency Response Telephone Number. ... Isolate spill or
leak area immediately for at least 100 to 200 meters (330 to 660 feet) in all
directions. Keep unauthorized personnel away. Stay upwind. Many gases are
heavier than air and will spread along ground and collect in low or confined
areas (sewers, basements, tanks). Keep out of low areas. Ventilate closed spaces
before entering. /Carbon monoxide; Carbon monoxide, compressed; Carbon monoxide and hydrogen mixture; carbon monoxide and hydrogen mixture,
compressed/ Protective clothing: Wear positive pressure self-contained breathing
apparatus (SCBA). Wear chemical protective clothing which is specifically
recommended by the manufacturer. It may provide little or no thermal protection.
Structural firefighters' protective clothing provides limited protection in fire
situations ONLY; it is not effective in spill situations. /Carbon monoxide; Carbon monoxide, compressed; Carbon monoxide and hydrogen mixture; carbon monoxide and hydrogen mixture,
compressed/ Evacuation: ... Fire: If tank, rail car or tank truck is involved in a fire,
ISOLATE for 1600 meters (1 mile) in all directions; also, consider initial
evacuation for 1600 meters (1 mile) in all directions. /Carbon monoxide; Carbon monoxide, compressed; Carbon monoxide and hydrogen mixture; carbon monoxide and hydrogen mixture,
compressed/ Fire: DO NOT EXTINGUISH A LEAKING GAS FIRE UNLESS LEAK CAN BE STOPPED. Small
fires: Dry chemical, CO2, water spray or alcohol-resistant foam. Large fires:
Water spray, fog or alcohol-resistant foam. FOR CHLOROSILANES, DO NOT USE WATER;
use AFFF alcohol-resistant medium expansion foam. Move containers from fire area
if you can do it without risk. Damaged cylinders should be handled only by
specialists. Fire involving tanks: Fight fire from maximum distance or use
unmanned hose holders or monitor nozzles. Cool containers with flooding
quantities of water until well after fire is out. Do not direct water at source
of leak or safety devices; icing may occur. Withdraw immediately in case of
rising sound from venting safety devices or discoloration of tank. ALWAYS stay
away from tanks engulfed in fire. /Carbon monoxide;
Carbon monoxide,
compressed; Carbon monoxide
and hydrogen mixture; carbon monoxide
and hydrogen mixture, compressed/ Spill or leak: ELIMINATE all ignition sources (no smoking, flares, sparks or
flames in immediate area). All equipment used when handling the product must be
grounded. Fully encapsulating, vapor protective clothing should be worn for
spills and leaks with no fire. Do not touch or walk through spilled material.
Stop leak if you can do it without risk. Do not direct water at spill or source
of leak. Use water spray to reduce vapors or divert vapor cloud drift. Avoid
allowing water runoff to contact spilled material. FOR CHLOROSILANES, use AFFF
alcohol-resistant medium expansion foam to reduce vapors. If possible, turn
leaking containers so that gas escapes rather than liquid. Prevent entry into
waterways, sewers, basements or confined areas. Isolate area until gas has
dispersed. /Carbon monoxide; Carbon monoxide, compressed; Carbon monoxide and hydrogen mixture; carbon monoxide and hydrogen mixture,
compressed/ First aid: Move victim to fresh air. Call 911 or emergency medical service.
Apply artificial respiration if victim is not breathing. Do not use
mouth-to-mouth method if victim ingested or inhaled the substance; induce
artificial respiration with the aid of a pocket mask equipped with a one-way
valve or other proper respiratory medical device. Administer oxygen if breathing
is difficult. Remove and isolate contaminated clothing and shoes. In case of
contact with substance, immediately flush skin or eyes with running water for at
least 20 minutes. In case of contact with liquefied gas, thaw frosted parts with
lukewarm water. Keep victim warm and quiet. Keep victim under observation.
Effects of contact or inhalation may be delayed. Ensure that medical personnel
are aware of the material(s) involved, and take precautions to protect
themselves. /Carbon monoxide; Carbon monoxide, compressed; Carbon monoxide and hydrogen mixture; carbon monoxide and hydrogen mixture,
compressed/ Health: TOXIC; Extremely hazardous. Inhalation extremely dangerous; may be
fatal. Contact with gas or liquefied gas may cause burns, severe injury and/or
frostbite. Odorless, will not be detected by sense of smell. /Carbon monoxide, refrigerated liquid
(cryogenic liquid)/ Fire or explosion: EXTREMELY FLAMMABLE. May be ignited by heat, sparks or
flames. Flame may be invisible. Containers may explode when heated. Vapor
explosion and poison hazard indoors, outdoors or in sewers. Vapors from
liquefied gas are initially heavier than air and spread along ground. Vapors may
travel to source of ignition and flash back. Runoff may create fire or explosion
hazard. /Carbon monoxide, refrigerated
liquid (cryogenic liquid)/ Public safety: CALL Emergency Response Telephone Number. ... Isolate spill or
leak area immediately for at least 100 to 200 meters (330 to 660 feet) in all
directions. Keep unauthorized personnel away. Stay upwind. Many gases are
heavier than air and will spread along ground and collect in low or confined
areas (sewers, basements, tanks). Keep out of low areas. Ventilate closed spaces
before entering. /Carbon monoxide,
refrigerated liquid (cryogenic liquid)/ Protective clothing: Wear positive pressure self-contained breathing
apparatus (SCBA). Wear chemical protective clothing which is specifically
recommended by the manufacturer. It may provide little or no thermal protection.
Structural firefighters' protective clothing provides limited protection in fire
situations ONLY; it is not effective in spill situations. Always wear thermal
protective clothing when handling refrigerated/cryogenic liquids. /Carbon monoxide, refrigerated liquid
(cryogenic liquid)/ Evacuation: ... Fire: If tank, rail car or tank truck is involved in a fire,
ISOLATE for 800 meters (1/2 mile) in all directions; also, consider initial
evacuation for 800 meters 1//2 mile) in all directions. /Carbon monoxide, refrigerated liquid
(cryogenic liquid)/ Fire: DO NOT EXTINGUISH A LEAKING GAS FIRE UNLESS LEAK CAN BE STOPPED. Small
fires: Dry chemical, CO2 or water spray. Large fires: Water spray, fog or
regular foam. Move containers from fire area if you can do it without risk. Fire
involving tanks: Fight fire from maximum distance or use unmanned hose holders
or monitor nozzles. Cool containers with flooding quantities of water until well
after fire is out. Do not direct water at source of leak or safety devices;
icing may occur. Withdraw immediately in case of rising sound from venting
safety devices or discoloration of tank. ALWAYS stay away from tanks engulfed in
fire. /Carbon monoxide, refrigerated
liquid (cryogenic liquid)/ Spill or leak: ELIMINATE all ignition sources (no smoking, flares, sparks or
flames in immediate area). All equipment used when handling the product must be
grounded. Fully encapsulating, vapor protective clothing should be worn for
spills and leaks with no fire. Do not touch or walk through spilled material.
Stop leak if you can do it without risk. Use water spray to reduce vapors or
divert vapor cloud drift. Do not direct water at spill or source of leak. If
possible, turn leaking containers so that gas escapes rather than liquid.
Prevent entry into waterways, sewers, basements or confined areas. Isolate area
until gas has dispersed. /Carbon monoxide,
refrigerated liquid (cryogenic liquid)/ First aid: Move victim to fresh air. Call 911 or emergency medical service.
Apply artificial respiration if victim is not breathing. Administer oxygen if
breathing is difficult. Remove and isolate contaminated clothing and shoes. In
case of contact with substance, immediately flush skin or eyes with running
water for at least 20 minutes. In case of contact with liquefied gas, thaw
frosted parts with lukewarm water. Keep victim warm and quiet. Keep victim under
observation. Effects of contact or inhalation may be delayed. Ensure that
medical personnel are aware of the material(s) involved, and take precautions to
protect themselves. /Carbon monoxide,
refrigerated liquid (cryogenic liquid)/ Initial Isolation and Protective Action Distances: Small Spills (from a small
package or small leak from a large package): First, ISOLATE in all Directions 30
meters (100 feet); then, PROTECT persons Downwind during DAY 0.2 kilometers (0.1
miles) and NIGHT 0.2 kilometers (0.1 miles). LARGE SPILLS (from a large package
or from many small packages): First, ISOLATE in all Directions 125 meters (400
feet); then, PROTECT persons Downwind during DAY 0.6 kilometers (0.4 miles) and
NIGHT 1.8 kilometers (1.1 miles). /Carbon monoxide;
Carbon monoxide,
compressed/
Fire Potential: Flammable gas.
NFPA Hazard Classification: Health: 3. 3= Materials that, on short exposure, could cause serious
temporary or residual injury, including those requiring protection from all
bodily contact. Fire fighters may enter the area only if they are protected from
all contact with the material. Full protective clothing, including
self-contained breathing apparatus, coat, pants, gloves, boots, and bands around
legs, arms, and waist, should be provided. No skin surface should be exposed.
Flammability: 4. 4= This degree includes flammable gases, pyrophoric liquids,
and Class IA flammable liquids. The preferred method of fire attack is to stop
the flow of material or to protect exposures while allowing the fire to burn
itself out. Reactivity: 0. 0= This degree includes materials that are normally stable,
even under fire exposure conditions, and that do not react with water. Normal
fire fighting procedures may be used.
Flammable Limits: Lower flammable limit: 12.5% by volume; Upper flammable limit: 74% by volume
Autoignition Temperature: 1292 DEG F (700 DEG C)
Fire Fighting Procedures: Use water spray to keep fire-exposed containers cool. Extinguish fire using
agent suitable for surrounding fire. Use powder or carbon dioxide. If material on fire or involved in fire: Do not extinguish fire unless flow
can be stopped. Use water in flooding quantities as fog. Cool all affected
containers with flooding quantities of water. Apply water from as far a distance
as possible. Let fire burn; shut off flow of gas and cool adjacent exposures with water.
Extinguish (only if wearing self-contained breathing apparatus) with dry
chemicals or carbon dioxide.
Firefighting Hazards: Flame has very little color. Containers may explode in fire.
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. Asphyxiation due to carbon dioxide production may result /from combustion/.
Explosive Limits & Potential: VERY DANGEROUS, WHEN EXPOSED TO HEAT.
Hazardous Reactivities & Incompatibilities: Strong oxidizers, bromine trifluoride, chlorine trifluoride, lithium.
... Explosion /occurred/ during reduction of iron oxide with carbon monoxide /due to/ formation of
pentacarbonyliron at temperatures between 0 and 150 deg C.
Carbon monoxide is exothermically
oxidized over silver oxide, and the temperature may attain 300 deg C.
Synthesis gas (carbon monoxide +
hydrogen) at 40 bar containing a low level of hydrogen sulfide
was to be freed of the latter impurity by adding the theoretical quantity of
oxygen and passing the mixture over a catalyst. Introduction of oxygen (from a
supply at 60 bar) via a simple T-piece ... caused development of an intense
inverse flame in the locally very high oxygen concentration which burned through
the reactor side wall opposite the oxygen inlet and ejected a meter-long
flame-jet. Several explosions occurred during the preparation /of bis(fluoroformyl)
peroxide/, which involves charging carbon monoxide
into a mixture of fluorine and oxygen.
Aluminum powder burns when heated in carbon dioxide, and presence of aluminum
chloride or aluminum iodide vapor in carbon monoxide
or carbon dioxide accelerated the reaction to incandescence.
At temperatures ... above 30 deg C, explosions occurred /with bromine
trifluoride and carbon monoxide/.
Immediately Dangerous to Life or Health: 1200 ppm
Protective Equipment & Clothing: Wear appropriate personal protective clothing to prevent the skin from
becoming frozen from contact with the liquid or from contact with vessels
containing the liquid. Wear appropriate eye protection to prevent eye contact with the liquid that
could result in burns or tissue damage from frostbite.
Quick drench facilities and/or eyewash fountains should be provided within
the immediate work area for emergency use where there is any possibility of
exposure to liquids that are extremely cold or rapidly evaporating.
Recommendations for respirator selection. Max concn for use: 350 ppm.
Respirator Class(es): Any supplied-air respirator. Recommendations for respirator selection. Max concn for use: 875 ppm.
Respirator Class(es): Any supplied-air respirator operated in a continuous flow
mode. Recommendations for respirator selection. Max concn for use: 1200 ppm.
Respirator Class(es): Any air-purifying, full-facepiece respirator (gas mask)
with a chin-style, front- or back-mounted canister providing protection against
the compound of concern. End of service life indicator (ESLI) required. Any
self-contained breathing apparatus with a full facepiece. Any supplied-air
respirator with a full facepiece. Recommendations for respirator selection. Condition: Emergency or planned
entry into unknown concn or IDLH conditions. Respirator Class(es): Any
self-contained breathing apparatus that has a full facepiece and is operated in
a pressure-demand or other positive pressure mode. Any supplied-air respirator
with a full facepiece and operated in pressure-demand or other positive pressure
mode in combination with an auxiliary self-contained breathing apparatus
operated in pressure-demand or other positive pressure mode.
Recommendations for respirator selection. Condition: Escape from suddenly
occurring respiratory hazards: Respirator Class(es): Any air-purifying,
full-facepiece respirator (gas mask) with a chin-style, front- or back-mounted
canister providing protection against the compound of concern. End of service
life indicator (ESLI) required. Any appropriate escape-type, self-contained
breathing apparatus. Self-contained breathing apparatus; safety glasses and safety shoes; Type D
or Type N canister mask.
Preventive Measures: Work clothing that becomes wet should be immediately removed due to its
flammability hazard. If material not on fire and not involved in fire: Keep sparks, flames, and
other sources of ignition away. Keep material out of water sources and sewers.
Attempt to stop leak if without undue personnel hazard. Use water spray to
knock-down vapors. Personnel protection: Avoid breathing vapors. Keep upwind. ... Do not handle
broken packages unless wearing appropriate personal protective equipment.
Approach fire with caution. Evacuation: If fire becomes uncontrollable or container is exposed to direct
flame consider evacuation of one-third (1/3) mile radius. If material leaking
(not on fire) consider evacuation from downwind area based on amount of material
spilled, location and weather conditions. ... Any individual should be protected from exposure to carbon monoxide that would result in
carboxyhemoglobin levels of 5% for any but transient periods, and that
especially susceptible persons ought not to be subjected to concentrations
giving carboxyhemoglobin levels exceeding 2.5%.
Shipment Methods and Regulations: No person may /transport,/ offer or accept a hazardous material for
transportation in commerce unless that person is registered in conformance ...
and the hazardous material is properly classed, described, packaged, marked,
labeled, and in condition for shipment as required or authorized by ... /the
hazardous materials regulations (49 CFR 171-177)./ The International Air Transport Association (IATA) Dangerous Goods
Regulations are published by the IATA Dangerous Goods Board pursuant to IATA
Resolutions 618 and 619 and constitute a manual of industry carrier regulations
to be followed by all IATA Member airlines when transporting hazardous
materials. The International Maritime Dangerous Goods Code lays down basic principles
for transporting hazardous chemicals. Detailed recommendations for individual
substances and a number of recommendations for good practice are included in the
classes dealing with such substances. A general index of technical names has
also been compiled. This index should always be consulted when attempting to
locate the appropriate procedures to be used when shipping any substance or
article.
Storage Conditions: Store in a cool, dry, well-ventilated location. Separate from alkali metals.
Remove the sources of ignition. Electric installation should be
explosion-proof construction. Protect container against sunlight, and store in
well-ventilated, safe areas.
Cleanup Methods: 1. VENTILATE AREA OF LEAK OR RELEASE TO DISPERSE GAS. 2. STOP FLOW OF GAS. IF
SOURCE OF LEAK IS A CYLINDER AND THE LEAK CANNOT BE STOPPED IN PLACE, REMOVE THE
LEAKING CYLINDER TO A SAFE PLACE IN THE OPEN AIR, AND REPAIR THE LEAK OR ALLOW
THE CYLINDER TO EMPTY. Use water spray to cool and disperse vapors and protect personnel. With
cryogenic liquids, releases may require isolation or evacuation.
Gas leakage: By forced ventilation, maintain concentration of gas below the
range of explosive mixture. Remove the tank or cylinder to an open area. Leave
to bleed off in the atmosphere.
Disposal Methods: SRP: At the time of review, criteria for land treatment or burial (sanitary
landfill) disposal practices are subject to significant revision. Prior to
implementing land disposal of waste residue (including waste sludge), consult
with environmental regulatory agencies for guidance on acceptable disposal
practices. Incineration: Remove leaky cylinders to remote area to empty; then return to
supplier with label indicating that repairs are needed. The waste carbon monoxide can be piped to an approved
incinerator or the cylinder can be placed in a pit to burn carbon monoxide to carbon dioxide under
controlled conditions. Occupational Exposure Standards:
OSHA Standards: Permissible Exposure Limit: Table Z-1 8-hr Time Weighted Avg: 50 ppm (55
mg/cu m). Vacated 1989 OSHA PEL TWA 35 ppm (40 mg/cu m); Ceiling limit 200 ppm (229
mg/cu m) is still enforced in some states.
Threshold Limit Values: 8 hr Time Weighted Avg (TWA): 25 ppm. Excursion Limit Recommendation: Excursions in worker exposure levels may
exceed three times the TLV-TWA for no more than a total of 30 min during a work
day, and under no circumstances should they exceed five times the TLV-TWA,
provided that the TLV-TWA is not exceeded. Biological Exposure Index (BEI): Determinant: carboxyhemoglobin in blood;
Sampling Time: end of shift; BEI: 3.5% of hemoglobin. Determinant: carbon monoxide in end-exhaled air; Sampling
Time: end of shift; BEI: 20 ppm. The determinant may be present in biological
specimens collected from subjects who have not been occupationally exposed, at a
concentration which could affect interpretation of the result. Such background
concentrations are incorporated in the BEI value. The determinant is
nonspecific, since it is also observed after exposure to other chemicals.
NIOSH Recommendations: Recommended Exposure Limit: 10 Hr Time-Weighted Avg: 35 ppm (40 mg/cu m).
Recommended Exposure Limit: Ceiling Value: 200 ppm (229 mg/cu m).
Immediately Dangerous to Life or Health: 1200 ppm
Other Occupational Permissible Levels: Emergency Response Planning Guidelines (ERPG): ERPG(1) 200 ppm (no more than
mild, transient effects) for up to 1 hr exposure; ERPG(2) 350 ppm (without
serious, adverse effects) for up to 1 hr exposure; ERPG(3) 500 ppm (not life
threatening) up to 1 hr exposure.
Manufacturing/Use Information:
Major Uses: REDUCING AGENT IN METALLURGICAL OPERATIONS; FISCHER-TROPSCH PROCESSES FOR
PETROLEUM-TYPE PRODUCTS; MFR OF METAL CARBONYLS IN MFR OF ZINC WHITE PIGMENTS UNISOLATED COMPONENT OF GASEOUS FUELS-EG, WATER GAS; CHEM INT FOR PHOSGENE,
METHANOL, ACETIC ACID, ACRYLIC ACID, SYNTHETIC FUELS (NON-U.S. USE),
DIMETHYLFORMAMIDE, OXO ALCOHOLS VIA ALDEHYDES (EG, BUTYL ALCOHOL), METHYL
FORMATE, ALKYL CARBONATES & SILICON CARBIDE FIBERS; COMONOMER IN
ETHYLENE-CARBON MONOXIDE COPOLYMER;
REDUCING AGENT IN IRON ORE PROCESSING; PURIFICATION AGENT FOR NICKEL VIA NICKEL
CARBONYL; CHEM INT FOR OTHER METAL CARBONYLS-EG, TUNGSTEN CARBONYL; CHEM INT FOR
ETHYLENE GLYCOL (FORMER USE) Carbon monoxide is increasingly being
used on a very large scale for the production of chemical intermediates. It is
used in the production of syngas which can be used in the synthesis of ammonia.
It is used for the synthesis of commodity chemicals and fuels by using syngas as
an alternative to petroleum based feedstocks. It is a reducing agent in blast
furnaces; production of phosgene; purification of metals; production of acetic
acid (consumes more than 500 kt/a), formic acid, methyl formate,
N,N-dimethylformamide, acrylic acid, and propanoic acid. A large variety of
chemicals, ranging from saturated hydrocarbons to oxygenated compounds (i.e.
methanol), are produced using syngas as a feedstock.
MEDICATION (VET)
Manufacturers: Air Products and Chemicals, Inc, Hq, 7201 Hamilton Blvd, Allentown, PA
18195-1501, (610) 481-4911; Industrial Gases Division; Production site: La
Porte, TX 77571; Specialty Gas Department, RD 2, PO Box 351, Tamaqua, PA 18252;
Production site: Hometown, PA 18252 Miles Inc, Hq, One Mellon Center, 500 Grant Street, Pittsburgh, PA
15219-2502, (412) 394-5500; Polymer Division Polyurethane; Production site:
Baytown, TX 77520 Liquid Carbonic Industries Corporation, Hq, 810 Jorie Blvd, Oak Brook, IL
60521 (708) 572-7500; Liquid Carbonic Cylinder Gas Products, PO Box 230;
Production site: Geismer, LA 70734 Dow Chemical USA, Hq, 2020 Dow Center, Midland, MI 48674, (517) 636-1000;
Production site: Freeport, TX 77541 Matheson Gas Products, Inc, Hq, 30 Seaview Dr, Secaucus, NJ 07096, (201)
867-4100; Production sites: Joliet, IL 60434; Newark, CA 94560; Twinsburg, OH
44087 Olin Corporation, Hq, 120 Long Ridge Road, Stamford, CT 06904, (203)
356-2000; Production site: Lake Charles, LA 70602
Methods of Manufacturing: SEPARATION FROM SYNTHESIS GAS-EG, WATER OR COKE OVEN GAS, BY EITHER
ABSORPTION BY SALT SOLUTIONS-EG, CUPROUS AMMONIUM SALTS, OR BY LOW TEMPERATURE
CONDENSATION OR FRACTIONATION; REACTION OF CARBON DIOXIDE & COKE
Produced on industrial scale by partial oxidn of hydrocarbon gases from
natural gas or by gasification of coal & coke. Conveniently prepd in lab by
heating calcium carbonate with zinc dust; by dehydration of formic acid with
H2SO4. Can also be recovered from the off-gas of several industrial processes such
as blast furnace processes or calcium carbide synthesis
Formulations/Preparations: Grade: commercial, 98.0-99.0%; C.P., 99.0-99.5%; ultra-high purity, 99.8%;
research, 99.97-99.99% Available as two-component mixtures in air, argon, helium, hydrogen, nitrogen
and carbon dioxide.
U. S. Production: (1977) AT LEAST 2.8X10+12 G (INCL CAPTIVE MFR) (1982) PROBABLY GREATER THAN 9.08X10+6 G
U. S. Exports: (1984) 1.14X10+13 g /Carbon Dioxide, Nitrous Oxide, and Carbon Monoxide/
Laboratory Methods:
Clinical Laboratory Methods: SPECTROPHOTOMETRIC METHOD COMMONLY USED IN CLINICAL LABORATORIES.
ANALYTE: CARBON MONOXIDE; MATRIX:
BLOOD; PROCEDURE: GAS CHROMATOGRAPHY.
Analytic Laboratory Methods: ANALYTE: CARBON MONOXIDE; MATRIX:
AIR; PROCEDURE: INFRARED ABSORPTION SPECTROPHOTOMETRY. ANALYTE: CARBON MONOXIDE; MATRIX:
AIR; PROCEDURE: COLLECTION IN GAS SAMPLING BAG, ELECTROCHEMICAL ANALYSIS.
AREAL Method Number IP-3A Determination of Carbon
Monoxide (CO) or Carbon Dioxide (CO2) in Indoor Air Using
Nondispersive Infrared (NDIR). Nondispersive IR Detection Limit = 0.60 mg/m3
AREAL Method Number IP-3B Determination of Carbon
Monoxide (CO) or Carbon Dioxide (CO2) in Indoor Air Using Gas
Filter Correlation. GFC Detection Limit = 0.020 ppm
AREAL Method Number IP-3C Determination of Carbon
Monoxide (CO) in Indoor Air Using Electrochemical Oxidation.
Electrochemical oxidation Detection Limit = 1 ppm
ASTM Method Number D3162 Standard Test Method for Carbon Monoxide in the Atmosphere Continuous
Measurement by Nondispersive Infrared Spectrometry. Nondispersive IR Detection
Limit = 0.60 mg/m3 ASTM Method Number D3416 Standard Test Method for Total Hydrocarbons,
Methane, and Carbon Monoxide in the
Atmosphere (Gas Chromatographic Method). GCFID Detection Limit not given
ASTM Method Number D4490 Standard Practice for Measuring the Concentration of
Toxic Gases or Vapors Using Detector Tubes. Toxic gas vapor detector tube
Detection Limit not given EMSLR Method Number 2.6 Reference Method for the Determination of Carbon Monoxide in the Atmosphere
(Nondispersive Infrared Photometry)/ Nondispersive IR Detection Limit 3 ppm
Special References:
Special Reports: Annau X, Fechter LD; The Effects of Prenatal Exposure to Carbon Monoxide. In: Prenatal Exposure to
Toxicants: Developmental Consequences. The Johns Hopkins Series in Environmental
Toxicology 249-67 (1994) Anon; J Occupat Med 36 (6): 595-97 (1994). Occupational Medicine Forum. What
Are the Potential Delayed Health Effects of High-Level Carbon Monoxide Exposure? Seger D, Welch L; Annals Emer Med 24 (2): 242-8 (1994). Carbon Monoxide Controversies:
Neuropsychologic Testing, Mechanisms of Toxicity, and Hyperbaric Oxygen.
Synonyms and Identifiers:
Synonyms: CARBONE (OXYDE DE) (FRENCH) CARBONIC OXIDE CARBONIO (OSSIDO DI) (ITALIAN) CARBON MONOXIDE (DOT)
CARBON OXIDE (CO) FLUE GAS KOHLENMONOXID (GERMAN)
KOOLMONOXYDE (DUTCH) OXYDE DE CARBONE (FRENCH) WEGLA TLENEK (POLISH)
Formulations/Preparations: Grade: commercial, 98.0-99.0%; C.P., 99.0-99.5%; ultra-high purity, 99.8%;
research, 99.97-99.99% Available as two-component mixtures in air, argon, helium, hydrogen, nitrogen
and carbon dioxide.
Shipping Name/ Number DOT/UN/NA/IMO: IMO 2.3; Carbon monoxide UN 1016; Carbon monoxide
Standard Transportation Number: 49 201 90; Carbon monoxide
RTECS Number: NIOSH/FG3500000
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