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PERFLUOROISOBUTYLENE

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Classification   |    Detailed evidence-based information

Substances Included Synonyms

Therapeutic Toxic Class

    A) Perfluoroisobutylene is an organofluorine (fluoroalkene) gas produced as a by-product of the manufacture and pyrolysis (thermal decomposition) of polytetrafluoroethylene (Teflon) and perfluoroethylpropylene (Halon 1301). It is a potent edematogenic gas, causing marked pulmonary edema, and is part of a potential new generation of chemical warfare weapons.

Specific Substances

    1) Perfluoroisobutene
    2) Perfluoroisobutylene
    3) Isobutene, octafluoro
    4) Octafluoroisobutylene
    5) Octafluoro-sec-butene
    6) Pentafluoro-(2-trifluoromethyl)-propene
    7) PFIB
    8) 1-Propene, 1,1,3,3,3-pentafluoro-2-trifluoromethyl-
    9) Molecular Formula: C4-F8
    10) CAS 382-21-8
    1.2.1) MOLECULAR FORMULA
    1) C4-F8

Available Forms Sources

    A) FORMS
    1) Perfluoroisobutene (PFIB) is an organofluorine (fluoroalkene) and edematogenic gas which is a thermal decomposition product of polytetrafluoroethylene (Teflon) and perfluoroethylpropylene (Halon 1301) (Hathaway et al, 1991; p 169; Onyefuru et al, 1996). The gas is colorless and toxic, causing marked lung injury, in particular, permeability pulmonary edema (Lehnert et al, 1995; Smith et al, 1982).
    2) Perfluoroisobutylene, a Teflon decomposition product, is the most toxic of the known fluoroalkene compounds, and has a toxicity 10 times greater than that of phosgene in experimental animals. It is colorless and a potent irritant of the eyes, skin, and mucous membranes.
    B) SOURCES
    1) Perfluoroisobutylene is evolved as a thermal decomposition product from Teflon and Halon 1301 at temperatures of 315 to 500 degrees C or greater (Hathaway et al, 1991). It is also a by-product of tetrafluoroethylene production (Lehnert et al, 1995).
    2) At temperatures above 400 degrees C, the principle toxic decomposition products of Teflon are PERFLUOROISOBUTYLENE and CARBONYL FLUORIDE (Okawa & Polakoff, 1974).
    3) Teflon itself, is a highly stable thermoplastic homopolymer of tetrafluoroethylene, composed of at least 20,000 C2F4 monomer units linked into quite long unbranched chains, with a molecular weight that may be in the millions. Teflon is inert under ordinary conditions (Budavari, 1996; ILO, 1983).
    a) The fumes are more toxic when Teflon is heated to 800 degrees C than when it is heated to 625 degrees C (Clayton & Clayton, 1994). In one occupational setting, cases of polymer fume fever were noted in either smokers or employees who worked in areas where the temperature of thermal processing was 480 degrees C instead of the prescribed 360 degrees C (Clayton & Clayton, 1994).
    b) Filtering the particulate material produced at temperatures of 450 degrees C prevented the development of clinical signs in subsequently exposed experimental animals, indicating that the particulates themselves contain the toxic agent (Clayton & Clayton, 1994; Waritz & Kwon, 1968).
    C) USES
    1) Perfluoroisobutylene (PFIB) is reported to be under development as a new generation of chemical warfare agents. Short exposures may be disabling and smaller concentrations may cause a delayed death. It will cause pulmonary edema when used as an inhalant. Most existing protection equipment and activated charcoal offer no protection against its use.
    a) PFIB has been synthesized at 99+% purity and stored in Class 1A cylinders at concentrations of 10,000 ppm in nitrogen (Smith et al, 1982).

Overview

Life Support

    A) This overview assumes that basic life support measures have been instituted.

Clinical Effects

    0.2.1) SUMMARY OF EXPOSURE
    A) Perfluoroisobutylene (PFIB), a Teflon decomposition product, is the most toxic of the known fluoroalkene compounds, and has a toxicity 10 times greater than that of phosgene in experimental animals. It is colorless and a potent irritant of the eyes, skin, and mucous membranes.
    1) Acute human exposures have produced headache, cough, substernal chest pain, dyspnea and fever, followed by pneumonitis and pulmonary edema within several hours. Short exposures to high inhalational concentrations may result in death due to pulmonary edema within 24 hours. No cumulative toxicity is apparent following subacute exposures.
    2) Although polytetrafluoroethylene (Teflon) is inert under ordinary circumstances, when the polymer is heated under conditions of inadequate ventilation, polymer fume fever may result.
    3) Polymer fume fever is an influenza-like syndrome. When Teflon is heated to between 315 and 375 degrees C, inhalation exposure to the fumes can cause chills, fever, profuse sweating, cough, dyspnea, flu-like symptoms, and chest tightness, which are generally self-limited and last for 24 to 48 hours. Respiratory discomfort may persist for several weeks after an acute attack.
    4) If smoking tobacco is contaminated with even very small amounts of Teflon, polymer fume fever may result.
    5) Polymer fume fever is similar to metal fume fever, and occurs after inhalation exposure to the pyrolysis products of fluorocarbon polymers, especially polytetrafluoroethylene (Teflon). Pulmonary infiltrates are often seen in patients with polymer fume fever.
    B) PFIB is an edematogenic toxin, producing pulmonary edema, with symptoms of chest discomfort and shortness of breath.
    C) Teflon decomposition products are temperature dependent.
    1) At temperatures of 315 to 375 degrees C and up to 500 degrees C, Teflon decomposition products are primarily the monomer, tetrafluoroethylene, perfluoroisopropylene, other C4-C5 perfluoro-compounds, and an unidentified waxy particulate fume (which may be the etiologic agent for polymer fume fever).
    2) At decomposition temperatures of 500 to 800 degrees C, the principal decomposition product is CARBONYL FLUORIDE, which is hydrolyzable to CARBON DIOXIDE and HYDROGEN FLUORIDE.
    a) If exposure to these decomposition products is a possibility, refer to the CARBONYL FLUORIDE and HYDROFLUORIC ACID HAZARDTEXT Hazard Managements and the FLUORINATED HYDROCARBONS and HYDROFLUORIC ACID MEDITEXT Medical Managements for further information.
    D) It is possible that PFIB may be under development as a new generation of chemical warfare agents.
    0.2.3) VITAL SIGNS
    A) Hyperpyrexia, mild sinus tachycardia, and reversible mild hypertension have been seen in patients with polymer fume fever.
    0.2.4) HEENT
    A) Perfluoroisobutylene is an irritant of the eyes and mucous membranes. A pungent or metallic smell and a metallic taste occur in patients with polymer fume fever.
    0.2.5) CARDIOVASCULAR
    A) Mild sinus tachycardia and reversible mild hypertension may occur in patients with polymer fume fever.
    0.2.6) RESPIRATORY
    A) Respiratory tract irritation, pneumonitis, and noncardiogenic pulmonary edema may occur. Mild hypoxia has been reported in patients with polymer fume fever. Sequelae have included prolonged decreases in diffusing capacity, reversible obstructive changes, and, possibly, pulmonary fibrosis following multiple episodes of polymer fume fever.
    0.2.7) NEUROLOGIC
    A) Headache, weakness, malaise, and paresthesias have been reported in patients with polymer fume fever.
    0.2.8) GASTROINTESTINAL
    A) Nausea and vomiting may occur with polymer fume fever.
    0.2.10) GENITOURINARY
    A) Workers exposed to Teflon decomposition products may have increased levels of urinary fluoride.
    0.2.13) HEMATOLOGIC
    A) Leukocytosis with a left shift in the differential count has been reported in patients with polymer fume fever.
    B) Disseminated intravascular coagulopathy was noted in one animal experiment. This effect has not been reported in exposed humans.
    0.2.14) DERMATOLOGIC
    A) Skin irritation may occur with perfluoroisobutylene exposure.
    0.2.15) MUSCULOSKELETAL
    A) Myalgia may occur in patients with polymer fume fever.
    0.2.20) REPRODUCTIVE
    A) At the time of this review, no data were available to assess the teratogenic potential of this agent.
    B) At the time of this review, no data were available to assess the potential effects of exposure to this agent during pregnancy or lactation.
    0.2.21) CARCINOGENICITY
    A) No data were available on the possible carcinogenicity of Teflon decomposition products, including perfluoroisobutylene, in humans at the time of this review.

Laboratory Monitoring

    A) Monitor CBC with differential count, pulse oximetry or arterial blood gases, and chest x-ray in patients with polymer fume fever, significant respiratory tract irritation, or pulmonary edema.
    B) Monitoring pulmonary function tests may be useful to detect the development of sequelae in patients with one or more episodes of polymer fume fever.
    C) Measuring urinary fluoride levels may give an indication of exposure, but such levels are not well correlated with the degree of exposure or severity of clinical effects in polymer fume fever.

Treatment Overview

    0.4.3) INHALATION EXPOSURE
    A) DECONTAMINATION - Move patient to fresh air. Monitor for respiratory distress; if cough or difficulty in breathing develops, evaluate for respiratory tract irritation, bronchitis, or pneumonitis. Administer 100% humidified supplemental oxygen with assisted ventilation as required.
    B) Rescuers should wear Self-Contained Breathing Apparatus (SCBA) to avoid self-contamination in areas with high concentrations of fumes.
    C) There are no specific treatments. Symptomatic and supportive therapy should be administered.
    D) Respiratory tract irritation, if severe, can progress to pulmonary edema which may be delayed in onset up to 24 to 72 hours after exposure in some cases.
    E) Administer supplemental oxygen to patients with chest discomfort, cough, or dyspnea.
    F) Administration of antipyretic medications (aspirin, acetaminophen, etc) may be useful for symptomatic relief of fever and flu-like symptoms. The history of possible allergy or intolerance should be obtained before these medications are prescribed.
    G) MONITORING PARAMETERS -
    1) If respiratory tract irritation is present, monitor arterial blood gases, chest x-ray, and pulmonary function tests.
    2) Measuring urinary fluoride levels may provide an indication of exposure, but have not been well correlated with the extent of exposure or severity of clinical effects in polymer fume fever.
    3) Elevated white blood cell counts may occur. Monitor CBC in patients with significant exposure.
    H) PULMONARY EDEMA - Maintain ventilation and oxygenation with close arterial blood gas monitoring. If PO2 remains less than 50 mmHg, PEEP or CPAP may be necessary. Avoid net positive fluid balance; monitor through central line or Swan Ganz catheter.
    I) Short-term administration of steroids has been suggested for use in the treatment of polymer fume fever, but their actual utility in this setting is unknown.
    J) Patients with multiple episodes of polymer fume fever might be at risk for the development of chronic pulmonary complications and should have periodic surveillance with chest x-rays and pulmonary function tests.
    K) SEIZURES: Administer a benzodiazepine; DIAZEPAM (ADULT: 5 to 10 mg IV initially; repeat every 5 to 20 minutes as needed. CHILD: 0.1 to 0.5 mg/kg IV over 2 to 5 minutes; up to a maximum of 10 mg/dose. May repeat dose every 5 to 10 minutes as needed) or LORAZEPAM (ADULT: 2 to 4 mg IV initially; repeat every 5 to 10 minutes as needed, if seizures persist. CHILD: 0.05 to 0.1 mg/kg IV over 2 to 5 minutes, up to a maximum of 4 mg/dose; may repeat in 5 to 15 minutes as needed, if seizures continue).
    1) Consider phenobarbital or propofol if seizures recur after diazepam 30 mg (adults) or 10 mg (children greater than 5 years).
    2) Monitor for hypotension, dysrhythmias, respiratory depression, and need for endotracheal intubation. Evaluate for hypoglycemia, electrolyte disturbances, and hypoxia.
    0.4.4) EYE EXPOSURE
    A) DECONTAMINATION: Remove contact lenses and irrigate exposed eyes with copious amounts of room temperature 0.9% saline or water for at least 15 minutes. If irritation, pain, swelling, lacrimation, or photophobia persist after 15 minutes of irrigation, the patient should be seen in a healthcare facility.
    0.4.5) DERMAL EXPOSURE
    A) OVERVIEW
    1) DECONTAMINATION: Remove contaminated clothing and jewelry and place them in plastic bags. Wash exposed areas with soap and water for 10 to 15 minutes with gentle sponging to avoid skin breakdown. A physician may need to examine the area if irritation or pain persists (Burgess et al, 1999).

Range Of Toxicity

    A) The LC50 in rats for a 4-hour inhalation exposure to perfluoroisobutylene is 0.76 ppm.
    B) Perfluoroisobutylene is approximately 10 times more toxic to rats than phosgene, with a 6-hour inhalation exposure to 0.5 ppm being lethal.
    C) LC50's for perfluoroisobutylene in rats were 361 ppm for a 0.25-minute exposure and 17 ppm for a 10-minute exposure.
    D) Rats and mice were killed by a 2-hour inhalation exposure of 0.018 or 0.015 mg/L of perfluoroisobutylene.

Clinical Effects

Summary Of Exposure

    A) Perfluoroisobutylene (PFIB), a Teflon decomposition product, is the most toxic of the known fluoroalkene compounds, and has a toxicity 10 times greater than that of phosgene in experimental animals. It is colorless and a potent irritant of the eyes, skin, and mucous membranes.
    1) Acute human exposures have produced headache, cough, substernal chest pain, dyspnea and fever, followed by pneumonitis and pulmonary edema within several hours. Short exposures to high inhalational concentrations may result in death due to pulmonary edema within 24 hours. No cumulative toxicity is apparent following subacute exposures.
    2) Although polytetrafluoroethylene (Teflon) is inert under ordinary circumstances, when the polymer is heated under conditions of inadequate ventilation, polymer fume fever may result.
    3) Polymer fume fever is an influenza-like syndrome. When Teflon is heated to between 315 and 375 degrees C, inhalation exposure to the fumes can cause chills, fever, profuse sweating, cough, dyspnea, flu-like symptoms, and chest tightness, which are generally self-limited and last for 24 to 48 hours. Respiratory discomfort may persist for several weeks after an acute attack.
    4) If smoking tobacco is contaminated with even very small amounts of Teflon, polymer fume fever may result.
    5) Polymer fume fever is similar to metal fume fever, and occurs after inhalation exposure to the pyrolysis products of fluorocarbon polymers, especially polytetrafluoroethylene (Teflon). Pulmonary infiltrates are often seen in patients with polymer fume fever.
    B) PFIB is an edematogenic toxin, producing pulmonary edema, with symptoms of chest discomfort and shortness of breath.
    C) Teflon decomposition products are temperature dependent.
    1) At temperatures of 315 to 375 degrees C and up to 500 degrees C, Teflon decomposition products are primarily the monomer, tetrafluoroethylene, perfluoroisopropylene, other C4-C5 perfluoro-compounds, and an unidentified waxy particulate fume (which may be the etiologic agent for polymer fume fever).
    2) At decomposition temperatures of 500 to 800 degrees C, the principal decomposition product is CARBONYL FLUORIDE, which is hydrolyzable to CARBON DIOXIDE and HYDROGEN FLUORIDE.
    a) If exposure to these decomposition products is a possibility, refer to the CARBONYL FLUORIDE and HYDROFLUORIC ACID HAZARDTEXT Hazard Managements and the FLUORINATED HYDROCARBONS and HYDROFLUORIC ACID MEDITEXT Medical Managements for further information.
    D) It is possible that PFIB may be under development as a new generation of chemical warfare agents.

Vital Signs

    3.3.1) SUMMARY
    A) Hyperpyrexia, mild sinus tachycardia, and reversible mild hypertension have been seen in patients with polymer fume fever.
    3.3.2) RESPIRATIONS
    A) Tachypnea has been reported in workers with polymer fume fever (Goldstein et al, 1987).
    3.3.3) TEMPERATURE
    A) An elevated temperature is commonly seen in patients with polymer fume fever from exposure to perfluoroisobutylene fumes (ILO, 1983; Hathaway et al, 1991; Rosenstock & Cullen, 1986).
    1) The fever usually clears within 24 hours (ILO, 1983; Hathaway et al, 1991; Reinl, 1964), but has lasted for as long as 50 hours in some cases (Shusterman & Neal, 1986).
    3.3.4) BLOOD PRESSURE
    A) Mild reversible hypertension was seen in workers with polymer fume fever (Shusterman & Neal, 1986; Reinl, 1964).
    3.3.5) PULSE
    A) Mild sinus tachycardia has been reported in workers with polymer fume fever (Goldstein et al, 1987; Shusterman & Neal, 1986; Reinl, 1964).

Heent

    3.4.1) SUMMARY
    A) Perfluoroisobutylene is an irritant of the eyes and mucous membranes. A pungent or metallic smell and a metallic taste occur in patients with polymer fume fever.
    3.4.3) EYES
    A) CONJUNCTIVITIS - Eye irritation may occur (Lewis, 1992; Reinl, 1964).
    B) ANIMALS - Perfluoroisobutylene fumes cause eye irritation, with etching of the cornea, and lacrimation in animals (Grant & Schuman, 1993).
    3.4.5) NOSE
    A) IRRITATION - Inhalation of fumes can cause irritation of the mucosa of the nose and throat (Lewis, 1992) HSDB, 1996).
    B) METALLIC SMELL - A pungent or metallic smell may occur in polymer fume fever (Goldstein et al, 1987).
    3.4.6) THROAT
    A) IRRITATION - Inhalation of fumes can cause irritation of the mucosa of the nose and throat (Lewis, 1992) HSDB, 1996).
    B) METALLIC TASTE - Workers with polymer fume fever may experience a metallic taste (Goldstein et al, 1987).

Cardiovascular

    3.5.1) SUMMARY
    A) Mild sinus tachycardia and reversible mild hypertension may occur in patients with polymer fume fever.
    3.5.2) CLINICAL EFFECTS
    A) TACHYARRHYTHMIA
    1) Mild sinus tachycardia has been reported in workers with polymer fume fever (Goldstein et al, 1987; Shusterman & Neal, 1986; Reinl, 1964).
    B) HYPERTENSIVE EPISODE
    1) Mild reversible hypertension has been reported in workers with polymer fume fever (Shusterman & Neal, 1986; Reinl, 1964).
    3.5.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) CIRCULATORY FAILURE
    a) Circulatory collapse occurred in dying rats within 6 hours following a 1.5 minute inhalation exposure of 638 mg/m(3) (78 ppm) (Brown & Rice, 1991).
    2) CYANOSIS
    a) Rats exposed to 0.1 ppm of PFIB for 6 hours/day for 10 days experienced respiratory impairment, proceeding to cyanosis in some cases (Anon, 1192a).

Respiratory

    3.6.1) SUMMARY
    A) Respiratory tract irritation, pneumonitis, and noncardiogenic pulmonary edema may occur. Mild hypoxia has been reported in patients with polymer fume fever. Sequelae have included prolonged decreases in diffusing capacity, reversible obstructive changes, and, possibly, pulmonary fibrosis following multiple episodes of polymer fume fever.
    3.6.2) CLINICAL EFFECTS
    A) DYSPNEA
    1) Dyspnea, cough, and shortness of breath occur in patients with polymer fume fever (Rosenstock & Cullen, 1986; Hathaway et al, 1991; Makulova, 1965; Reinl, 1964). Tracheitis and bronchitis may occur (Reinl, 1964).
    B) CHEST PAIN
    1) Chest discomfort is commonly described in patients with polymer fume fever (Hathaway et al, 1991; Goldstein et al, 1987; Reinl, 1964).
    C) ACUTE LUNG INJURY
    1) PFIB inhalation is known to damage the alveolar-capillary membrane barrier. Plasma leaks extravascularly and produces a fulminating pulmonary edema, thought to be the cause of death (Onyefuru et al, 1996).
    2) Noncardiogenic pulmonary edema and rales may occur in patients inhaling Teflon decomposition products (Ellenhorn & Barceloux, 1988; Hathaway et al, 1991; Brubaker, 1977) HSDB, 1996).
    3) At least two deaths have been reported in workers who developed pulmonary edema from exposure to Teflon decomposition products, including PFIB (Auclair et al, 1983; Makulova, 1965).
    D) PNEUMONITIS
    1) Cough and difficulty breathing occurred in 5 workers exposed to perfluoroisobutylene for less than one minute (Makulova, 1965). Pneumonitis developed 4 to 6 hours following exposure, and only improved by the 5th to 6th postexposure days (Makulova, 1965).
    2) One of these workers developed an exudative pleuritis and another died on the 2nd postexposure day (Makulova, 1965).
    E) HYPOXEMIA
    1) Mild hypoxia with pO2's of 64 to 77 mmHg (FiO2 = room air) was noted in a group of workers with polymer fume fever (Goldstein et al, 1987).
    F) IRRITATION SYMPTOM
    1) Inhalation of Teflon pyrolysis products causes irritation of the mucous membranes (HSDB, 1996).
    G) SEQUELA
    1) Reversible airways obstruction and reduced diffusing capacity lasted for weeks to months in one individual who developed pulmonary edema following inhalation of Teflon decomposition products (Brubaker, 1977).
    2) Another worker had more than 40 episodes of polymer fume fever over a 9 month period, but never developed pulmonary edema (HSDB, 1996; (Goldstein et al, 1987). Eighteen months later, this worker developed shortness of breath on exertion and had an alveolar-capillary block on pulmonary function testing (HSDB, 1996). At autopsy, interstitial pulmonary fibrosis was noted (Goldstein et al, 1987).
    3.6.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) PULMONARY EDEMA
    a) Pulmonary edema was exacerbated by exercise following inhalation exposure to perfluoroisobutylene in rats (Moore et al, 1991; p 169). Overt pulmonary edema occurred approximately 8 hours after exposure to 100 mg/m(3)/10 min. Exercise during the latent period after a lower-level exposure had no effect, however (Lehnert et al, 1995).
    1) Lehnert et al (1991) found the severity of PFIB-induced lung injury to be directly proportional to inhaled PFIB mass concentration. The post-exposure kinetics of lung injury development was inversely proportional to the mass concentration of PFIB.
    b) Rats exposed to 0.5 ppm for 6 hours died due to anoxia produced by accumulation of fluid in the lungs (Smith et al, 1982).
    2) EMPHYSEMA
    a) Toxic inhalational effects in mouse studies have included emphysema at LCLo doses of 10 mg/m(3)/2 hr (RTECS , 2000).

Neurologic

    3.7.1) SUMMARY
    A) Headache, weakness, malaise, and paresthesias have been reported in patients with polymer fume fever.
    3.7.2) CLINICAL EFFECTS
    A) HEADACHE
    1) Headache, dizziness, weakness, and malaise may occur with polymer fume fever (Shusterman & Neal, 1986). The headache has lasted up to 4 days in some cases (Shusterman & Neal, 1986).
    B) PARESTHESIA
    1) Numbness and tingling in the fingertips have been described in patients with polymer fume fever (Albrecht & Bryant, 1987).
    3.7.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) SOMNOLENCE
    a) Somnolence, or general depressed activity, and ataxia has been reported in cat, rabbit, and guinea pig inhalational toxicity studies (RTECS , 2000)
    2) SEIZURES
    a) Seizures occurred in dying rats within 6 hours following a 1.5 minute inhalation exposure of 638 mg/m(3) (78 ppm) (Brown & Rice, 1991) Anon, 1992; Anon, 1992a).

Gastrointestinal

    3.8.1) SUMMARY
    A) Nausea and vomiting may occur with polymer fume fever.
    3.8.2) CLINICAL EFFECTS
    A) NAUSEA AND VOMITING
    1) Nausea and vomiting have been described in workers with polymer fume fever (Albrecht & Bryant, 1987; Goldstein et al, 1987; Reinl, 1964).

Hepatic

    3.9.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) LIVER FATTY
    a) Fatty dystrophy was noted in the livers of rats exposed to perfluoroisobutylene (Danishevskii & Kochanov, 1961).
    2) HEPATIC ENZYMES INCREASED
    a) Inhalational toxicity studies in rats showed changes in conditioned reflexes accompanied by serum hepatic enzyme changes (Smith et al, 1982).

Genitourinary

    3.10.1) SUMMARY
    A) Workers exposed to Teflon decomposition products may have increased levels of urinary fluoride.
    3.10.2) CLINICAL EFFECTS
    A) FLUOROSIS
    1) Elevated levels of urinary fluoride have been seen in experimental animals and humans exposed to Teflon decomposition products (Clayton & Clayton, 1994) HSDB, 1996).
    2) One worker who was sintering granular Teflon had urinary fluoride levels of 5 milligrams per liter (Clayton & Clayton, 1994).
    3) A group of workers with a high incidence of prior episodes of polymer fume fever from inhalation of Teflon decomposition products did not have elevated urinary fluoride levels (Okawa & Polakoff, 1974).
    3.10.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) FLUOROSIS
    a) Rats developed a urinary fluoride excretion 4 times that of normal when exposed to Teflon decomposition products for 1 hour (Clayton & Clayton, 1994; Scheel et al, 1968a).
    2) RENAL FUNCTION ABNORMAL
    a) Dystrophic changes were seen in the kidneys of rats exposed to perfluoroisobutylene (Danishevskii & Kochanov, 1961).

Hematologic

    3.13.1) SUMMARY
    A) Leukocytosis with a left shift in the differential count has been reported in patients with polymer fume fever.
    B) Disseminated intravascular coagulopathy was noted in one animal experiment. This effect has not been reported in exposed humans.
    3.13.2) CLINICAL EFFECTS
    A) LEUKOCYTOSIS
    1) White blood cell counts of 12,700 to 20,000 per cubic millimeter with left-shifted differential counts have been observed in workers with polymer fume fever (Goldstein et al, 1987; Shusterman & Neal, 1986; Reinl, 1964).
    3.13.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) DISSEMINATED INTRAVASCULAR COAGULATION
    a) Disseminated intravascular coagulopathy (DIC) has been reported in rats fatally poisoned with pyrolysis products of Teflon evolved during a 30-minute exposure at 595 degrees C (Zook et al, 1983). This effect has not been reported in exposed humans.

Dermatologic

    3.14.1) SUMMARY
    A) Skin irritation may occur with perfluoroisobutylene exposure.
    3.14.2) CLINICAL EFFECTS
    A) SKIN IRRITATION
    1) Perfluoroisobutylene is a skin irritant (Lewis, 1992).

Musculoskeletal

    3.15.1) SUMMARY
    A) Myalgia may occur in patients with polymer fume fever.
    3.15.2) CLINICAL EFFECTS
    A) MUSCLE PAIN
    1) Myalgia may be part of the flu-like symptoms of polymer fume fever (Albrecht & Bryant, 1987).

Reproductive

    3.20.1) SUMMARY
    A) At the time of this review, no data were available to assess the teratogenic potential of this agent.
    B) At the time of this review, no data were available to assess the potential effects of exposure to this agent during pregnancy or lactation.
    3.20.2) TERATOGENICITY
    A) LACK OF INFORMATION
    1) At the time of this review, no data were available to assess the teratogenic potential of this agent.
    3.20.3) EFFECTS IN PREGNANCY
    A) LACK OF INFORMATION
    1) At the time of this review, no data were available to assess the potential effects of exposure to this agent during pregnancy or lactation.

Carcinogenicity

    3.21.1) IARC CATEGORY
    A) IARC Carcinogenicity Ratings for CAS382-21-8 (International Agency for Research on Cancer (IARC), 2016; International Agency for Research on Cancer, 2015; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010a; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2008; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2007; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2006; IARC, 2004):
    1) Not Listed
    3.21.2) SUMMARY/HUMAN
    A) No data were available on the possible carcinogenicity of Teflon decomposition products, including perfluoroisobutylene, in humans at the time of this review.
    3.21.3) HUMAN STUDIES
    A) LACK OF INFORMATION
    1) PERFLUOROISOBUTYLENE - No data were available on the possible carcinogenicity of Teflon decomposition products, including perfluoroisobutylene, at the time of this review.
    B) SARCOMA
    1) TEFLON - One human with a Teflon surgical implant has been reported who developed a local sarcoma (HSDB, 1996).
    3.21.4) ANIMAL STUDIES
    A) SARCOMA
    1) TEFLON - Experimental animals implanted subcutaneously with Teflon have developed local sarcomas (Hathaway et al, 1991).

Genotoxicity

    A) At the time of this review, no data were available on the potential genotoxicity of perfluoroisobutylene.

Laboratory Monitoring

Monitoring Parameters Levels

    4.1.1) SUMMARY
    A) Monitor CBC with differential count, pulse oximetry or arterial blood gases, and chest x-ray in patients with polymer fume fever, significant respiratory tract irritation, or pulmonary edema.
    B) Monitoring pulmonary function tests may be useful to detect the development of sequelae in patients with one or more episodes of polymer fume fever.
    C) Measuring urinary fluoride levels may give an indication of exposure, but such levels are not well correlated with the degree of exposure or severity of clinical effects in polymer fume fever.
    4.1.2) SERUM/BLOOD
    A) HEMATOLOGIC
    1) Monitor the white blood cell count in patients with polymer fume fever, as leukocytosis with a left shift may occur (Goldstein et al, 1987; Shusterman & Neal, 1986; Reinl, 1964).
    B) ACID/BASE
    1) Monitor arterial blood gases in patients with more severe polymer fume fever, pulmonary edema, or respiratory tract irritation.
    4.1.3) URINE
    A) URINARY LEVELS
    1) Monitoring urinary fluoride levels might be useful as an indication of exposure, but have not been well correlated with the extent of exposure or severity of clinical effects in polymer fume fever (Clayton & Clayton, 1994; Okawa & Polakoff, 1974).
    2) Elevated levels of fluoride have been found in the urine of experimental animals and humans exposed to fluoride-containing thermal decomposition products of Teflon (Clayton & Clayton, 1994; Scheel et al, 1968a) HSDB, 1996).
    3) One worker who was sintering granular Teflon had urinary fluoride levels of 5 milligrams per liter (Clayton & Clayton, 1994).
    4) A good indication of exposure to toxic amounts of fluoride compounds is a urinary fluoride level of 3.0 milligrams per liter or greater (Okawa & Polakoff, 1974).
    4.1.4) OTHER
    A) OTHER
    1) PULMONARY FUNCTION TESTS
    a) Monitor pulmonary function tests in patients with more severe polymer fume fever or pulmonary edema. Diffusing capacity abnormalities and reversible obstructive changes may occur.

Radiographic Studies

    A) CHEST RADIOGRAPH
    1) If respiratory tract irritation is present, monitor chest x-ray.

Methods

    A) MULTIPLE ANALYTICAL METHODS
    1) Teflon decomposition products are decomposed in part by hydrolysis in alkaline solutions, and can thus be determined in the air as fluoride to provide some index of exposure (Sittig, 1985) ACGIH, 1992).
    2) Perfluoroisobutylene can be measured by reacting it in methanol with a mixture of pyridine and piperidine, which produces a stable yellow color that can either be read spectrophotometrically at 412 mu or visually compared with a permanent secondary standard. This method will detect 0.1 ppm of perfluoroisobutylene at 25 degrees C with a sample of 0.1 cubic foot (Marcali & Linch, 1966).
    a) A light weight portable kit with an aspirator for collecting samples has been described for field use (Marcali & Linch, 1966).
    3) A wafer permeation device has also been described for use as a primary standard for perfluoroisobutylene, which may be useful at the part per billion level (Menichelli, 1982).

Treatment

Life Support

    A) Support respiratory and cardiovascular function.

Patient Disposition

    6.3.3) DISPOSITION/INHALATION EXPOSURE
    6.3.3.5) OBSERVATION CRITERIA/INHALATION
    A) Symptomatic patients should be observed in a controlled setting for 24 to 36 hours for delayed respiratory effects.
    1) Patients that have been observed for several hours following an exposure, and remain asymptomatic, may be treated as outpatients. The patient should be instructed to return to a health care facility if any symptoms develop.
    2) Patients that were initially symptomatic who become asymptomatic after 24 to 36 hours of observation may be released with arrangement of follow-up appointment to assess pulmonary status.
    3) Close outpatient follow-up should be continued in patients who develop adult respiratory distress syndrome since these patients are at high risk to develop bronchiolitis obliterans within several weeks.

Monitoring

    A) Monitor CBC with differential count, pulse oximetry or arterial blood gases, and chest x-ray in patients with polymer fume fever, significant respiratory tract irritation, or pulmonary edema.
    B) Monitoring pulmonary function tests may be useful to detect the development of sequelae in patients with one or more episodes of polymer fume fever.
    C) Measuring urinary fluoride levels may give an indication of exposure, but such levels are not well correlated with the degree of exposure or severity of clinical effects in polymer fume fever.

Inhalation Exposure

    6.7.1) DECONTAMINATION
    1) Move patient from the toxic environment to fresh air. Monitor for respiratory distress. If cough or difficulty in breathing develops, evaluate for hypoxia, respiratory tract irritation, bronchitis, or pneumonitis.
    2) OBSERVATION: Carefully observe patients with inhalation exposure for the development of any systemic signs or symptoms and administer symptomatic treatment as necessary.
    3) INITIAL TREATMENT: Administer 100% humidified supplemental oxygen, perform endotracheal intubation and provide assisted ventilation as required. Administer inhaled beta-2 adrenergic agonists, if bronchospasm develops. Consider systemic corticosteroids in patients with significant bronchospasm (National Heart,Lung,and Blood Institute, 2007). Exposed skin and eyes should be flushed with copious amounts of water.
    6.7.2) TREATMENT
    A) IRRITATION SYMPTOM
    1) Respiratory tract irritation, if severe, can progress to pulmonary edema which may be delayed in onset up to 24 to 72 hours after exposure in some cases.
    B) OXYGEN
    1) Administer supplemental oxygen to patients with chest discomfort, cough, or dyspnea. Positive pressure ventilation and positive end expiratory pressure may be administered in cases of pulmonary edema to maintain peripheral tissue oxygenation until underlying alveolar-capillary damage has resolved.
    C) SUPPORT
    1) ANTIPYRETICS - Administration of antipyretic medications (aspirin, acetaminophen, etc) may be useful for symptomatic relief of fever and flu-like symptoms. The history of possible allergy or intolerance should be obtained before these medications are prescribed.
    D) MONITORING OF PATIENT
    1) If respiratory tract irritation is present, monitor pulse oximetry or arterial blood gases, chest x-ray, and pulmonary function tests.
    2) Measuring urinary fluoride levels may provide an indication of exposure, but have not been well correlated with the extent of exposure or severity of clinical effects in polymer fume fever (Clayton & Clayton, 1982; Okawa & Polakoff, 1974).
    3) Elevated white blood cell counts may occur. Monitor CBC in patients with significant exposure.
    E) ACUTE LUNG INJURY
    1) ONSET: Onset of acute lung injury after toxic exposure may be delayed up to 24 to 72 hours after exposure in some cases.
    2) NON-PHARMACOLOGIC TREATMENT: The treatment of acute lung injury is primarily supportive (Cataletto, 2012). Maintain adequate ventilation and oxygenation with frequent monitoring of arterial blood gases and/or pulse oximetry. If a high FIO2 is required to maintain adequate oxygenation, mechanical ventilation and positive-end-expiratory pressure (PEEP) may be required; ventilation with small tidal volumes (6 mL/kg) is preferred if ARDS develops (Haas, 2011; Stolbach & Hoffman, 2011).
    a) To minimize barotrauma and other complications, use the lowest amount of PEEP possible while maintaining adequate oxygenation. Use of smaller tidal volumes (6 mL/kg) and lower plateau pressures (30 cm water or less) has been associated with decreased mortality and more rapid weaning from mechanical ventilation in patients with ARDS (Brower et al, 2000). More treatment information may be obtained from ARDS Clinical Network website, NIH NHLBI ARDS Clinical Network Mechanical Ventilation Protocol Summary, http://www.ardsnet.org/node/77791 (NHLBI ARDS Network, 2008)
    3) FLUIDS: Crystalloid solutions must be administered judiciously. Pulmonary artery monitoring may help. In general the pulmonary artery wedge pressure should be kept relatively low while still maintaining adequate cardiac output, blood pressure and urine output (Stolbach & Hoffman, 2011).
    4) ANTIBIOTICS: Indicated only when there is evidence of infection (Artigas et al, 1998).
    5) EXPERIMENTAL THERAPY: Partial liquid ventilation has shown promise in preliminary studies (Kollef & Schuster, 1995).
    6) CALFACTANT: In a multicenter, randomized, blinded trial, endotracheal instillation of 2 doses of 80 mL/m(2) calfactant (35 mg/mL of phospholipid suspension in saline) in infants, children, and adolescents with acute lung injury resulted in acute improvement in oxygenation and lower mortality; however, no significant decrease in the course of respiratory failure measured by duration of ventilator therapy, intensive care unit, or hospital stay was noted. Adverse effects (transient hypoxia and hypotension) were more frequent in calfactant patients, but these effects were mild and did not require withdrawal from the study (Wilson et al, 2005).
    7) However, in a multicenter, randomized, controlled, and masked trial, endotracheal instillation of up to 3 doses of calfactant (30 mg) in adults only with acute lung injury/ARDS due to direct lung injury was not associated with improved oxygenation and longer term benefits compared to the placebo group. It was also associated with significant increases in hypoxia and hypotension (Willson et al, 2015).
    8) Loop diuretics, such as furosemide or torsemide, and controlled fluid intake have been shown to reduce the extracellular fluid volume in PFIB induced pulmonary edema in animal studies (Onyefuru et al, 1996).
    F) CORTICOSTEROID
    1) Short-term administration of steroids has been suggested for use in the treatment of polymer fume fever (Brubaker, 1977), but their actual utility in this setting is unknown.
    G) SEIZURE
    1) SUMMARY
    a) Attempt initial control with a benzodiazepine (eg, diazepam, lorazepam). If seizures persist or recur, administer phenobarbital or propofol.
    b) Monitor for respiratory depression, hypotension, and dysrhythmias. Endotracheal intubation should be performed in patients with persistent seizures.
    c) Evaluate for hypoxia, electrolyte disturbances, and hypoglycemia (or, if immediate bedside glucose testing is not available, treat with intravenous dextrose).
    2) DIAZEPAM
    a) ADULT DOSE: Initially 5 to 10 mg IV, OR 0.15 mg/kg IV up to 10 mg per dose up to a rate of 5 mg/minute; may be repeated every 5 to 20 minutes as needed (Brophy et al, 2012; Prod Info diazepam IM, IV injection, 2008; Manno, 2003).
    b) PEDIATRIC DOSE: 0.1 to 0.5 mg/kg IV over 2 to 5 minutes; up to a maximum of 10 mg/dose. May repeat dose every 5 to 10 minutes as needed (Loddenkemper & Goodkin, 2011; Hegenbarth & American Academy of Pediatrics Committee on Drugs, 2008).
    c) Monitor for hypotension, respiratory depression, and the need for endotracheal intubation. Consider a second agent if seizures persist or recur after repeated doses of diazepam .
    3) NO INTRAVENOUS ACCESS
    a) DIAZEPAM may be given rectally or intramuscularly (Manno, 2003). RECTAL DOSE: CHILD: Greater than 12 years: 0.2 mg/kg; 6 to 11 years: 0.3 mg/kg; 2 to 5 years: 0.5 mg/kg (Brophy et al, 2012).
    b) MIDAZOLAM has been used intramuscularly and intranasally, particularly in children when intravenous access has not been established. ADULT DOSE: 0.2 mg/kg IM, up to a maximum dose of 10 mg (Brophy et al, 2012). PEDIATRIC DOSE: INTRAMUSCULAR: 0.2 mg/kg IM, up to a maximum dose of 7 mg (Chamberlain et al, 1997) OR 10 mg IM (weight greater than 40 kg); 5 mg IM (weight 13 to 40 kg); INTRANASAL: 0.2 to 0.5 mg/kg up to a maximum of 10 mg/dose (Loddenkemper & Goodkin, 2011; Brophy et al, 2012). BUCCAL midazolam, 10 mg, has been used in adolescents and older children (5-years-old or more) to control seizures when intravenous access was not established (Scott et al, 1999).
    4) LORAZEPAM
    a) MAXIMUM RATE: The rate of intravenous administration of lorazepam should not exceed 2 mg/min (Brophy et al, 2012; Prod Info lorazepam IM, IV injection, 2008).
    b) ADULT DOSE: 2 to 4 mg IV initially; repeat every 5 to 10 minutes as needed, if seizures persist (Manno, 2003; Brophy et al, 2012).
    c) PEDIATRIC DOSE: 0.05 to 0.1 mg/kg IV over 2 to 5 minutes, up to a maximum of 4 mg/dose; may repeat in 5 to 15 minutes as needed, if seizures continue (Brophy et al, 2012; Loddenkemper & Goodkin, 2011; Hegenbarth & American Academy of Pediatrics Committee on Drugs, 2008; Sreenath et al, 2009; Chin et al, 2008).
    5) PHENOBARBITAL
    a) ADULT LOADING DOSE: 20 mg/kg IV at an infusion rate of 50 to 100 mg/minute IV. An additional 5 to 10 mg/kg dose may be given 10 minutes after loading infusion if seizures persist or recur (Brophy et al, 2012).
    b) Patients receiving high doses will require endotracheal intubation and may require vasopressor support (Brophy et al, 2012).
    c) PEDIATRIC LOADING DOSE: 20 mg/kg may be given as single or divided application (2 mg/kg/minute in children weighing less than 40 kg up to 100 mg/min in children weighing greater than 40 kg). A plasma concentration of about 20 mg/L will be achieved by this dose (Loddenkemper & Goodkin, 2011).
    d) REPEAT PEDIATRIC DOSE: Repeat doses of 5 to 20 mg/kg may be given every 15 to 20 minutes if seizures persist, with cardiorespiratory monitoring (Loddenkemper & Goodkin, 2011).
    e) MONITOR: For hypotension, respiratory depression, and the need for endotracheal intubation (Loddenkemper & Goodkin, 2011; Manno, 2003).
    f) SERUM CONCENTRATION MONITORING: Monitor serum concentrations over the next 12 to 24 hours. Therapeutic serum concentrations of phenobarbital range from 10 to 40 mcg/mL, although the optimal plasma concentration for some individuals may vary outside this range (Hvidberg & Dam, 1976; Choonara & Rane, 1990; AMA Department of Drugs, 1992).
    6) OTHER AGENTS
    a) If seizures persist after phenobarbital, propofol or pentobarbital infusion, or neuromuscular paralysis with general anesthesia (isoflurane) and continuous EEG monitoring should be considered (Manno, 2003). Other anticonvulsants can be considered (eg, valproate sodium, levetiracetam, lacosamide, topiramate) if seizures persist or recur; however, there is very little data regarding their use in toxin induced seizures, controlled trials are not available to define the optimal dosage ranges for these agents in status epilepticus (Brophy et al, 2012):
    1) VALPROATE SODIUM: ADULT DOSE: An initial dose of 20 to 40 mg/kg IV, at a rate of 3 to 6 mg/kg/minute; may give an additional dose of 20 mg/kg 10 minutes after loading infusion. PEDIATRIC DOSE: 1.5 to 3 mg/kg/minute (Brophy et al, 2012).
    2) LEVETIRACETAM: ADULT DOSE: 1000 to 3000 mg IV, at a rate of 2 to 5 mg/kg/min IV. PEDIATRIC DOSE: 20 to 60 mg/kg IV (Brophy et al, 2012; Loddenkemper & Goodkin, 2011).
    3) LACOSAMIDE: ADULT DOSE: 200 to 400 mg IV; 200 mg IV over 15 minutes (Brophy et al, 2012). PEDIATRIC DOSE: In one study, median starting doses of 1.3 mg/kg/day and maintenance doses of 4.7 mg/kg/day were used in children 8 years and older (Loddenkemper & Goodkin, 2011).
    4) TOPIRAMATE: ADULT DOSE: 200 to 400 mg nasogastric/orally OR 300 to 1600 mg/day orally divided in 2 to 4 times daily (Brophy et al, 2012).
    H) FOLLOW-UP VISIT
    1) Patients with multiple episodes of polymer fume fever might be at risk for the development of chronic pulmonary complications and should have periodic surveillance with chest x-rays and pulmonary function tests.
    I) EXPERIMENTAL THERAPY
    1) NAC - Oral administration of N-acetylcysteine prior to gas exposure in rats demonstrated increased survival rates. This has not been established in humans, but could be considered in severe exposures as an attempt to lessen the acute insult (Lailey, 1997).

Eye Exposure

    6.8.1) DECONTAMINATION
    A) EYE IRRIGATION, ROUTINE: Remove contact lenses and irrigate exposed eyes with copious amounts of room temperature 0.9% saline or water for at least 15 minutes. If irritation, pain, swelling, lacrimation, or photophobia persist after 15 minutes of irrigation, an ophthalmologic examination should be performed (Peate, 2007; Naradzay & Barish, 2006).

Dermal Exposure

    6.9.1) DECONTAMINATION
    A) DERMAL DECONTAMINATION
    1) DECONTAMINATION: Remove contaminated clothing and wash exposed area thoroughly with soap and water for 10 to 15 minutes. A physician may need to examine the area if irritation or pain persists (Burgess et al, 1999).
    6.9.2) TREATMENT
    A) GENERAL TREATMENT
    1) Treatment should include recommendations listed in the INHALATION EXPOSURE section when appropriate.
    B) IRRITATION SYMPTOM
    1) Treat dermal irritation or burns with standard topical therapy. Patients developing dermal hypersensitivity reactions may require treatment with systemic or topical corticosteroids or antihistamines.

Abstracts

Case Reports

    A) ADULT
    1) Albrecht & Bryant (1987) reported the cases of 3 workers in a rubber and metal stamp company who each developed multiple episodes of polymer fume fever over a 9-month period following the introduction of a polytetrafluoroethylene (Teflon)-based mold release compound into the process. This mold release compound contained less than 1 percent Teflon. All symptoms disappeared when use of the mold release compound was discontinued.
    a) All 3 workers were smokers, and developed multiple episodes of malaise, myalgias, fever, shaking chills, weakness, nausea, numbness and tingling of the fingertips, and dry cough. Temperatures were as high as 103 degrees F in some cases.
    b) Poor industrial hygiene practices contributed to the development of these episodes of polymer fume fever: smoking was allowed in the workplace, hand washing was not routinely done before smoking or eating, and local exhaust ventilation was inadequate. When these deficiencies were corrected, no further symptoms occurred.
    2) Brubaker (1977) reported 9 workers exposed to polytetrafluoroethylene heated to no more than 250 degrees F in a mold spraying and cleaning operation. All 9 workers were smokers, and had one or more episodes of polymer fume fever with symptoms of chills, fever, chest pain, shortness of breath, and cough.
    a) One individual had a documented episode of pulmonary edema. Recurrent chest pain and cough sufficient to prevent return to work were still present at 3 weeks after the acute episode. A moderately severe reversible airway obstructive pattern was seen on pulmonary function testing at 3 weeks, although the chest x-ray had returned to normal. At 2 months, the patient was asymptomatic and the reversible airway obstruction had cleared, although pulmonary function testing showed a reduced diffusing capacity.
    b) The mother of one employee developed an illness similar to polymer fume fever after handling possibly contaminated work clothing and then smoking a cigarette.
    3) One worker had more than 40 episodes of polymer fume fever over a 9 month period, but never developed pulmonary edema (HSDB, 1996; (Goldstein et al, 1987). Eighteen months later, this worker developed shortness of breath on exertion and had an alveolar-capillary block on pulmonary function testing (HSDB, 1996). At autopsy, interstitial pulmonary fibrosis was noted (Goldstein et al, 1987).
    4) In a NIOSH Health Hazard Evaluation of a Teflon product manufacturing facility, 80 percent of workers (60/70) stated on a questionnaire that they had experienced polymer fume fever sometime in the past, and 50 percent had at least one episode in the preceding year (Okawa & Polakoff, 1974).
    a) Fourteen percent of these workers had experienced more than 3 episodes of polymer fume fever in the preceding year, and one-third of the workers had stayed home from work at some time because of polymer fume fever symptoms. Only 10 percent of individuals experiencing symptoms of polymer fume fever had ever consulted a physician for the condition (Okawa & Polakoff, 1974).
    b) At the time of the Health Hazard Evaluation, no workers were complaining of symptomatic polymer fume fever, and urinary fluoride levels collected from 77 employees ranged from 0.098 to 2.19 mg/L (levels of 3.0 mg/L or greater indicate potential exposure to toxic levels of fluoride compounds) (Okawa & Polakoff, 1974).
    5) Goldstein et al (1987) reported 6 workers in an electronics laboratory where Teflon contamination occurred during a cable heating test for electrical conductivity. The onset of symptoms began about 15 minutes after initial exposure, and progressed over the following hour.
    a) Initial complaints were dry throat, cough, and a metallic smell and taste. Dramatic improvement followed symptomatic treatment in an emergency department, but three of these individuals had subsequent worsening of symptoms over the following 4 hours, with cough, dyspnea, weakness, chills, and fever to 38.3 to 39.7 degrees C. Two patients also had nausea and vomiting. Mild tachycardia and tachypnea were noted.
    b) Elevated white blood cell counts and mild hypoxia were initially present. Treatment with supplemental oxygen resulted in improvement over 8 hours, and laboratory abnormalities returned to normal over 2 days. Pulmonary function tests done 3 weeks after exposure showed mild obstructive disease, but these patients were all heavy smokers.
    6) A mechanical engineer developed shaking chills, fever to 38.9 degrees C, headache, dizziness, mild sinus tachycardia (104/minute), and mild hypertension (150/74 mmHg) after being exposed to smoke from Teflon tape inadvertently left in a reaction chamber (Shusterman & Neal, 1986). Leukocytosis with a left shift was present. The fever persisted for 50 hours after exposure, and headaches lasted for 4 days before clearing.
    7) Cough and difficulty breathing occurred in 5 workers exposed to perfluoroisobutylene for less than one minute (Makulova, 1965). Pneumonitis developed 4 to 6 hours following exposure, and only improved by the 5th to 6th postexposure days (Makulova, 1965).
    a) One of these workers developed an exudative pleuritis and another died on the 2nd postexposure day (Makulova, 1965).

Range Of Toxicity

Summary

    A) The LC50 in rats for a 4-hour inhalation exposure to perfluoroisobutylene is 0.76 ppm.
    B) Perfluoroisobutylene is approximately 10 times more toxic to rats than phosgene, with a 6-hour inhalation exposure to 0.5 ppm being lethal.
    C) LC50's for perfluoroisobutylene in rats were 361 ppm for a 0.25-minute exposure and 17 ppm for a 10-minute exposure.
    D) Rats and mice were killed by a 2-hour inhalation exposure of 0.018 or 0.015 mg/L of perfluoroisobutylene.

Minimum Lethal Exposure

    A) ANIMAL DATA
    1) Various Teflon decomposition products vary widely in toxicity in experimental animals (ILO, 1983).
    2) The LC50 in rats for a 4-hour inhalation exposure varies from 40,000 ppm for the tetrafluoroethylene monomer to 0.76 ppm for perfluoroisobutylene (ILO, 1983).
    3) Perfluoroisobutylene is the most toxic of the known fluoroalkene compounds, and has a toxicity 10 times greater than that of phosgene in experimental animals (Ellenhorn & Barceloux, 1988; Waritz & Kwon, 1968), with a 6-hour inhalation exposure to 0.5 ppm being lethal (Waritz & Kwon, 1968).
    4) In inhalation experiments with perfluoroisobutylene, rats were given nose-only exposure to various concentrations for between 0.25 and 10 minutes (Smith et al, 1982). LC50's were calculated for a 0.25-minute exposure (361 ppm) and a 10-minute exposure (17 ppm).
    a) The development of weight loss and pulmonary impairment was seen up to 48 hours after the exposure, and affected animals either died with pulmonary congestion or recovered completely without apparent sequelae (Smith et al, 1982).
    5) Rats and mice were killed by a 2-hour inhalation exposure to 0.018 or 0.015 mg/L of perfluoroisobutylene (Karpov, 1963).
    6) Birds are more susceptible to the toxic effects of Teflon decomposition products than are humans (Griffith et al, 1973).

Maximum Tolerated Exposure

    A) GENERAL/SUMMARY
    1) Although much has been discovered about the toxicity of various Teflon decomposition products, no practical way has ever been developed to express a safe level for exposure, especially for the prevention of polymer fume fever (etiologic agent is unknown) (Okawa & Polakoff, 1974).
    2) Safe use of Teflon products without special engineering controls can generally be done at process temperatures of 275 degrees C (527 degrees F) or lower (Okawa & Polakoff, 1974).
    B) ANIMAL DATA
    1) The minimally TOXIC perfluoroisobutylene dose in rats, mice, cats, and rabbits with a 2-hour inhalation exposure was 0.0026 to 0.0028 mg/L.
    a) This minimally TOXIC dose was based on reversible changes in the blood circulation, pulmonary emphysema, thickening of the alveolar septa, and permeation of the vascular walls with plasma.
    2) Chronic exposure to 0.0002 mg/L of perfluoroisobutylene for 6 hours daily for 9 months had no effects.
    3) Animals who became intoxicated in these studies developed excitation, followed by neural inhibition and immobility. Necropsy studies showed necrotic changes in the brain, heart, lungs, liver, and kidneys.
    4) In chronic exposure studies, rats developed lowered physical endurance, altered formation of conditioned reflexes, decreased oxygen consumption, and decreased CNS excitability. Pathological changes were found at necropsy in the lungs, nervous system, and circulatory system.
    5) (REFERENCE - Karpov, 1963)
    6) No evidence of lung injury was seen in rats exposed to 50 or 83 mg/m(3) of perfluoroisobutylene for 10 minutes; exposure to 90 mg/m(3) produced gravimetric and histopathological changes in the lungs after a latent period of several hours (Lehnert et al, 1993).

Serum Plasma Blood Concentrations

    7.5.2) TOXIC CONCENTRATIONS
    A) TOXIC CONCENTRATION LEVELS
    1) GENERAL
    a) A good indication of exposure to toxic amounts of fluoride compounds is a urinary fluoride level of 3.0 milligrams per Liter or greater (Okawa & Polakoff, 1974).
    2) ANIMAL DATA
    a) Rats developed a urinary fluoride excretion of 4 times normal when exposed to Teflon decomposition products for 1 hour (Clayton & Clayton, 1994).
    3) CASE REPORTS
    a) OCCUPATIONAL
    1) One worker who was sintering granular Teflon had urinary fluoride levels of 5 milligrams per liter (Clayton & Clayton, 1994).

Workplace Standards

    A) ACGIH TLV Values for CAS382-21-8 (American Conference of Governmental Industrial Hygienists, 2010):
    1) Editor's Note: The listed values are recommendations or guidelines developed by ACGIH(R) to assist in the control of health hazards. They should only be used, interpreted and applied by individuals trained in industrial hygiene. Before applying these values, it is imperative to read the introduction to each section in the current TLVs(R) and BEI(R) Book and become familiar with the constraints and limitations to their use. Always consult the Documentation of the TLVs(R) and BEIs(R) before applying these recommendations and guidelines.
    a) Adopted Value
    1) Perfluoroisobutylene
    a) TLV:
    1) TLV-TWA:
    2) TLV-STEL:
    3) TLV-Ceiling: 0.01 ppm
    b) Notations and Endnotes:
    1) Carcinogenicity Category: Not Listed
    2) Codes: Not Listed
    3) Definitions: Not Listed
    c) TLV Basis - Critical Effect(s): URT irr; hematologic eff
    d) Molecular Weight: 200.04
    1) For gases and vapors, to convert the TLV from ppm to mg/m(3):
    a) [(TLV in ppm)(gram molecular weight of substance)]/24.45
    2) For gases and vapors, to convert the TLV from mg/m(3) to ppm:
    a) [(TLV in mg/m(3))(24.45)]/gram molecular weight of substance
    e) Additional information:

    B) NIOSH REL and IDLH Values for CAS382-21-8 (National Institute for Occupational Safety and Health, 2007):
    1) Not Listed

    C) Carcinogenicity Ratings for CAS382-21-8 :
    1) ACGIH (American Conference of Governmental Industrial Hygienists, 2010): Not Listed ; Listed as: Perfluoroisobutylene
    2) EPA (U.S. Environmental Protection Agency, 2011): Not Listed
    3) IARC (International Agency for Research on Cancer (IARC), 2016; International Agency for Research on Cancer, 2015; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010a; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2008; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2007; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2006; IARC, 2004): Not Listed
    4) NIOSH (National Institute for Occupational Safety and Health, 2007): Not Listed
    5) MAK (DFG, 2002): Not Listed
    6) NTP (U.S. Department of Health and Human Services, Public Health Service, National Toxicology Project ): Not Listed

    D) OSHA PEL Values for CAS382-21-8 (U.S. Occupational Safety, and Health Administration (OSHA), 2010):
    1) Not Listed

Toxicity Information

    7.7.1) TOXICITY VALUES
    A) References: RTECS, 2000; Hathaway et al, 1991; ILO, 1983; Smith et al, 1982; Zook et al, 1983

Pharmacology Toxicology

Toxicologic Mechanism

    A) Many outbreaks of polymer fume fever involve workers who smoked cigarettes contaminated with Teflon particulate matter (Goldstein et al, 1987; Okawa & Polakoff, 1974) HSDB, 1996). The most common source of exposure is smoking cigarettes contaminated with Teflon dust (HSDB, 1996).
    1) Smokers may thus be more susceptible to polymer fume fever than nonsmokers; after exposure, a higher percentage of smokers become symptomatic than do nonsmokers (Goldstein et al, 1987). In one outbreak, all 6 exposed individuals became ill, but the 3 smokers in the group had more serious clinical courses (Goldstein et al, 1987).
    B) The factor involved in the production of polymer fume fever on exposure to heated Teflon has not been identified, but the illness usually occurs when fumes are evolved at temperatures between 300 and 500 degrees C (HSDB, 1996).
    1) Pyrolysis of polytetrafluoroethylene at atmospheric pressure yielded 33 percent perfluoroisobutylene at 750 degrees C (Fokin & Kosyrev, 1960).
    a) Perfluoroisobutylene intoxication in experimental animals characteristically causes pulmonary edema with hyperemia and hemorrhages (Danishevskii & Kochanov, 1961).
    b) Visible effects in experimental animals exposed to Teflon decomposition products include acute upper respiratory tract mucosal irritation, followed by death from pneumonitis and pulmonary edema (Zhemerdey, 1958). Observed hyperemia and irritation may be caused by the presence of various fluorocarbon pyrolysis byproducts, including perfluoroisobutylene (Zhemerdey, 1958).
    2) Brown & Rice (1991) studied the histopathology of rat lung following acute inhalational exposures of 638 mg/m(3) (78 ppm) for 1.5 minutes. Within 5 minutes of exposure, alterations to cilial structure, increased pinocytosis and electron lucency occurred within bronchioles and peribronchial alveoli.
    a) Intercellular leakage in the alveolar spaces, with minimal fluid accumulation was seen. A direct effect of PFIB is suggested by this very rapid action. A gradual development of pulmonary edema, visible histologically 2 to 3 hours after exposure, and followed by death 7+ hours later was reported.
    3) In guinea pigs, mice, rabbits, cats, and rats, the toxicity of evolved Teflon decomposition products was greater at temperatures above 500 degrees C than below 400 degrees C (Treon et al, 1954; Ushakov et al, 1985). In these studies, no animals died following exposure to pyrolysis products evolved at 300 degrees C (Treon et al, 1954; Ushakov et al, 1985).
    a) Observed effects in these animals were oral and nasal discharges, respiratory distress, dyspnea, gasping respirations, corneal injury, and premorbid convulsions (Treon et al, 1954).
    b) It has been concluded that 300 degrees C is the highest safe temperature at which polytetrafluoroethylene can be used (Ushakov et al, 1985).
    4) In rats exposed to Teflon decomposition products evolved at 595 degrees C, respiratory distress was followed by death (Zook et al, 1983). Necropsy findings were focal hemorrhages, fibrin deposition, pulmonary edema, thrombosis of pulmonary capillaries with hypertrophy and hyperplasia of alveolar cells, accumulated macrophages in the alveoli, and disseminated intravascular coagulopathy (Zook et al, 1983).
    5) The underlying toxic mechanism resulting in pulmonary edema is not fully understood (p 209); however, it is known that inhalation of PFIB damages the alveolar-capillary membrane barrier, and plasma leaks extravascularly producing a fulminant pulmonary edema (Onyefuru et al, 1996).
    6) The inhalation toxicity of Teflon decomposition products is related to both the decomposition temperature and a time-dependent atmospheric reaction, with those pyrolysis products produced at 700 degrees C above a methane flame being 850 times more toxic than those produced at a similar temperature in a cup furnace (Williams et al, 1987).
    C) Chronic daily exposure of experimental animals with Teflon pyrolysis products evolved at just above 500 degrees C caused a toxic syndrome consistent with chronic fluoride poisoning (Scheel et al, 1968a). Urinary excretion of fluoride was 4 times normal in these animals after a single inhalation exposure (Scheel et al, 1968a).
    1) In these experiments, the lung and kidneys were the target organs (Scheel et al, 1968a). Inhibition of succinic dehydrogenase was also noted (Scheel et al, 1968a). The observed fluoride toxicity was reversible by about 18 days after cessation of exposure (Scheel et al, 1968a)
    D) When Teflon is pyrolyzed in an electric furnace at 550 degrees C, the principle toxic effects of the evolved fumes in a variety of experimental animal species were due to hydrolyzable fluoride-containing products (Scheel et al, 1968b). Exposure to the particulate matter resulting from Teflon decomposition under these conditions was irritating to the lungs for at least 7 to 10 days following exposure (Scheel et al, 1968b).
    1) The reversible portion of the pulmonary injuries observed in these studies were pulmonary edema and hemorrhage (Scheel et al, 1968b). Irreversible focal emphysema and interstitial fibrosis were also observed in some animals (Scheel et al, 1968b).
    E) When Teflon was heated in an oven to 450 degrees C and the resultant decomposition products were filtered such that the particulate fraction, but not the hydrolyzable fluorocarbons including perfluoroisobutylene, were removed, the toxicity to experimental animals was essentially prevented. This finding suggests that toxicity is due to a particulate-adsorbed toxic agent (Waritz & Kwon, 1968).
    1) However, when the temperature is increased, perfluoroisobutylene is present in lethal concentrations (Waritz & Kwon, 1968). At even higher temperatures, carbonyl fluoride is most likely the principal toxic decomposition product (Waritz & Kwon, 1968).
    F) Perfluoroisobutylene is a direct irritant of the eyes, skin, and mucous membranes (Lewis, 1992).

Physicochemical

Physical Characteristics

    A) Perfluoroisobutylene is a toxic, colorless gas (Smith et al, 1982).
    B) Teflon (polytetrafluoroethylene) is a greyish-white or opaque milk-whitish plastic material that is inert, temperature-resistant, and has a waxy, slippery feel (Hathaway et al, 1991; ILO, 1983; Lewis, 1993) HSDB, 1996).
    1) Teflon can be greyish-white transparent thin sheets, a soft and waxy milk-white solid, or a white powder (HSDB, 1996).

Molecular Weight

    A) PERFLUOROISOBUTYLENE: 200.04 (RTECS , 2000; Lewis, 1992)
    B) TEFLON (POLYTETRAFLUOROETHYLENE): Greater than 1,000,000 (Budavari, 1996; ILO, 1983)

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