A Highly toxic gas that has been used as a chemical warfare agent. It is an
insidious poison as it is not irritating immediately, even when fatal
concentrations are inhaled.
(From The Merck Index, 11th ed, p7304)
PHOSGENE GENERATION FROM CHLOROFORM.
Phosgene # 75-44-5 COCl2 (used as a war gas in WWI) is a
breakdown product of chloroform. Phosgene exposure can cause damage to the
central nervous system in concentrations at only a small fraction of the
permissible exposure limit of chloroform. Chloroform, stabilized with alcohol,
should be purchased in the future whenever possible. If non-stabilized
chloroform is necessary for the work, it needs to be treated like peroxide
forming compounds and be used up in a short amount of time. Amylene is also used
as a stabilizer, but there is evidence that it may not prevent phosgene
generation.
PHOSGENE
CASRN: 75-44-5
Human Toxicity Excerpts:
AT CONCN ... OF 1 PPM IN AIR IT CAUSES LITTLE OR NO IMMEDIATE
IRRITATION, BUT AFTER A LATENT PERIOD OF SOME HR MAY CAUSE SEVERE PULMONARY
EDEMA. AT CONCN OF 4 TO 10 PPM IN AIR IT CAUSES IRRITATION OF RESP TRACT &
EYES.
... EXPOSURE TO GAS MAY CAUSE CONJUNCTIVAL HYPEREMIA, BUT @
IRRITATING CONCN THERE IS AUTOMATIC PROTECTION THROUGH BLEPHAROSPASM, & BY
FAR THE GREATEST DANGER IS TO THE LUNG.
/IN 1968/ ... A MAN WHO HAD A SEVERE ACUTE EXPOSURE ...
EXPERIENCED SEVERE BURNING SENSATION IN THE EYES & IRRITATION OF RESP TRACT
WITH COUGHING, BUT WITHIN THREE TO FIVE MINUTES AFTER BEING REMOVED TO FRESH AIR
THE SYMPTOMS CEASED. AFTER ... SEVERAL HR ... PT DEVELOPED SEVERE PULMONARY
EDEMA, BUT NO OCULAR COMPLICATIONS.
LIQ PHOSGENE SPLASHED IN THE EYES ... CAUSED COMPLETE
OPACIFICATION OF BOTH CORNEAS IN ONE PT, LEADING ULTIMATELY TO PERFORATION &
FORMATION OF SYMBLEPHARON.
INSIDIOUS POISON AS IT IS NOT IRRITATING IMMEDIATELY, EVEN
WHEN FATAL CONCN ARE INHALED. MAY CAUSE SEVERE PULMONARY EDEMA (MAY BE QUICKLY
FATAL) OR PNEUMONIA. INHALATION OF HIGH CONCN CAUSES CHOKING, CONSTRICTED
FEELING IN CHEST, COUGHING, PAINFUL BREATHING, BLOODY SPUTUM.
PATHOLOGIC FINDINGS INCLUDE EXTENSIVE DEGENERATIVE CHANGES IN
EPITHELIUM OF TRACHEA, BRONCHI, & BRONCHIOLI, & HEMORRHAGIC EDEMATOUS
FOCAL PNEUMONIA. CLINICAL FINDINGS: THE PRINCIPAL MANIFESTATIONS IN ACUTE
POISONING WITH PHOSGENE ARE RESPIRATORY AND CIRCULATORY FAILURE. CHRONIC
POISONING DOES NOT OCCUR. AFTER INHALATION OR SKIN ABSORPTION, SYMPTOMS AND
SIGNS MAY BEGIN ANY TIME UP TO 24 HR AFTER EXPOSURE. THESE INCLUDE A BURNING
SENSATION IN THROAT, TIGHTNESS IN CHEST, FEELING OF OPPRESSION, DYSPNEA, &
CYANOSIS, WITH RAPID PROGRESSION TO SEVERE PULMONARY EDEMA & DEATH FROM RESP
& CIRCULATORY FAILURE. LABORATORY FINDINGS: RADIOLOGIC EXAMINATION OF THE
CHEST SHOWS DIFFUSE OPACITIES RESULTING FROM PULMONARY EDEMA.
THE MOST SERIOUS EFFECT OF PHOSGENE IS LUNG IRRITATION. ONLY A
RELATIVELY SMALL PORTION OF THE INHALED GAS HYDROLYZES IN THE RESPIRATORY
PASSAGES, BUT IN THE MOIST ATMOSPHERE OF THE TERMINAL SPACES OF THE LUNGS
COMPLETE HYDROLYSIS OCCURS WITH IRRITANT EFFECTS UPON THE ALVEOLAR WALLS AND
BLOOD CAPILLARIES. THE RESULT OF THIS ACTION IS A GRADUALLY INCREASING EDEMA,
UNTIL AS MUCH AS 30 TO 50% OF TOTAL BLOOD PLASMA HAS ACCUMULATED IN THE LUNG,
CAUSING "DRY LAND DROWNING." THE AIR SPACES GROW LESS AND LESS; THE
BLOOD IS THICKENED BY LOSS OF PLASMA, WHICH RESULTS IN SLOWED CIRCULATION;
OXYGEN EXCHANGE IS SLOWED; AND THE OVERWORKED HEART, WITH INSUFFICIENT OXYGEN,
WEAKENS. THE END RESULT MAY BE EITHER ASPHYXIATION OR HEART FAILURE AND THIS MAY
BE DELAYED. HIGH CONCENTRATIONS OF PHOSGENE ARE IMMEDIATELY CORROSIVE TO LUNG
TISSUE AND RESULT IN SUDDEN DEATH BY SUFFOCATION.
IN INDUST POISONING, 52/82 WORKERS AFFECTED. SYMPTOMS: RESP
TRACT IRRITATION-94%; MALAISE, NAUSEA & VOMITING-54%; HEADACHE-40%; BURNING
& LACRIMATION OF EYES & OTHER-30%. PULMONARY EDEMA IN 3 PERSONS.
The danger period usually is 6 to 24 hours after exposure with
the development of peribronchial edema, pulmonary congestion, and alveolar
edema, all leading to death from anoxia. The delay is ascribed to slow
intrapulmonary hydrolysis of phosgene to hydrogen chloride and chloride.
In massive exposures immediate death sometimes results from
occlusion of the pulmonary circulation secondary to intravascular hemolysis and
thrombus formation.
CONCN GREATER THAN 0.25 MG/L OF AIR (62 PPM) MAY BE FATAL,
WHEN BREATHED FOR ONE-HALF HOUR OR MORE. THREE TO 5 MG/L CAUSES DEATH WITHIN A
FEW MINUTES.
THERE IS ... NO PROTECTIVE RESP REFLEX TO PREVENT THE DEEP
INSPIRATION OF ... /PHOSGENE/.
... SOLVENTS, PAINT REMOVERS, & NONFLAMMABLE DRY CLEANING
FLUIDS CONTAINING ... /CHLORINATED HYDROCARBONS, ESP CARBON TETRACHLORIDE,
CHLOROFORM, & METHYLENE CHLORIDE/ WILL DECOMP TO PHOSGENE IN PRESENCE OF
FIRE OR HEAT; DEATHS HAVE OCCURRED FROM SUCH DECOMPOSITION.
THE LEAST CONCENTRATION THAT CAN CAUSE IMMEDIATE THROAT
IRRITATION IS 3 PPM; 4 PPM CAUSES IMMEDIATE IRRITATION OF THE EYES; 4.8 PPM
CAUSES COUGH. BRIEF EXPOSURE TO 50 PPM MAY BE RAPIDLY FATAL.
Target organs: Respiratory system, skin and eyes.
A male, age 31, was exposed to phosgene when a pipe conducting
the gas accidentally ruptured. That evening, he reported to the hospital with
signs of acute progressive pulmonary edema and extreme hemoconcentration and
leukocytosis. Despite aggressive therapy, the patient died 3.5 hours after
admission.
A man was admitted to the hospital 11 hours after the phosgene
exposure. He was dyspneic, had bilateral rales, and an X-ray indicated pulmonary
edema. During treatment, the patient's condition deteriorated, with worsening
blood gases. With intubation, the patient produced a large amount of pulmonary
edema fluid. The patient remained in critical condition for the next three days.
Clinical signs included low right side heart pressure, low arterial pressure,
hemoconcentration, and leukocytosis. Twelve days after the accident, the patient
was completely asymptomatic. A pulmonary function study performed about four
weeks after the accident revealed a mild degree of pulmonary obstruction that
/was/ attributed to the patient's smoking.
Recovery from acute phosgene intoxication is usually complete,
however, most victims of severe poisonings complain of chronic symptoms such as
shortness of breath on exertion or reduced physical fitness for several months
to several years after the accident. In patients where phosgene poisoning has
led to chronic disability, the effects are more closely related to smoking
habits, psychological disorders, or existing pulmonary abnormalities than to the
severity of exposure. Pathological effects to organs other than the lung are
rare and are considered to be caused by anoxia, not by a direct action of
phosgene.
The fatal accident involved a 55 year old mason who was
exposed to phosgene released by chipping of brick which had possibly adsorbed
phosgene. In this case, phosgene was a byproduct in the production of aluminum
chloride. ... He was exposed for 30 minutes and first complained of dyspnea
about 2 hours after completing the job. No first aid was given. Five hours after
exposure, he was admitted to the hospital in severe respiratory distress. Chest
films showed pulmonary edema. Despite phlebotomy and treatment with digitalis
and diuretics, the patient died of acute right heart failure about 14 hr after
his initial exposure.
... A case of presumed phosgene exposure due to the breakdown
of trichloroethylene by cigarette smoking /was reported/. The patient had worked
as a drycleaner for 3 mo. Studies indicated that the average concentration of
trichloroethylene in the room was 488 ppm. ... This level would be exceeded when
clothing was removed from the cleaning machine. The patient was known to smoke
40 cigarettes/day. He frequently smoked in the cleaning room. He left work ...
and about 90 minutes later he collapsed and died. An autopsy showed pulmonary
edema. Phosgene was believed to have been generated by the decomposition of
trichloroethylene in contact with the hot tip of a burning cigarette.
... 20 ppm by volume cause lung injuries in 2 min, 25 ppm for
as little as 30 minutes is very dangerous, and 90 ppm is rapidly fatal for
exposures of 30 minutes or less.
PHOSGENE
CASRN: 75-44-5
Metabolism/Metabolites:
... Sensitivity to chloroform correlates with the capacity of
the kidney to metabolize chloroform to the toxic metabolite phosgene. ... Kidney
homogenates of sensitive male DBA/2J mice metabolized chloroform to phosgene
more rapidly than did the less sensitive C57BL/6J mice. Similarly, kidney
homogenates from male mice, which are sensitive to chloroform induced
nephrotoxicity, metabolized chloroform to phosgene at nearly an order of
magnitude more rapidly than did those from female mice. Treatment of female mice
with testosterone, however, reversed this trend. Cytochrome p450 in the
microsomal and mitochondrial fraction of the kidney appeared to catalyze the
metabolism of chloroform to phosgene.
PHOSGENE WAS IDENTIFIED AS A PRODUCT OF CARBON TETRACHLORIDE
METABOLISM IN RAT LIVER.
CYSTEINE INHIBITED IN VITRO COVALENT BINDING OF CHLOROFORM TO
LIVER MICROSOMAL PROTEIN & TRAPPED A REACTIVE METABOLITE, PRESUMABLY
PHOSGENE, AS 2-OXOTHIAZOLIDINE-4-CARBOXYLIC ACID. THIS SUGGESTS THAT THE
CARBON-HYDROGEN BOND OF CHLOROFORM IS OXIDIZED BY A CYTOCHROME p450
MONOOXYGENASE TO PRODUCE TRICHLOROMETHANOL, WHICH SPONTANEOUSLY
DEHYDROCHLORINATES TO YIELD PHOSGENE.
PHOSGENE IS FORMED DURING NADPH AND OXYGEN DEPENDENT
MICROSOMAL OXIDATION OF /CARBON TETRACHLORIDE/.
Phosgene reacts rapidly with water, but more rapidly with
certain chemical groups found in tissue macromolecules, such as free amines and
sulfhydryls. Because of its high reactivity, it is doubtful that any unreacted
phosgene will enter the general circulation even after exposure to high
concentrations of the gas.