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OXYGEN DIFLUORIDE

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Classification   |    Detailed evidence-based information

Substances Included Synonyms

Therapeutic Toxic Class

    A) Oxygen difluoride is a very strong oxidizing agent used in the preparation of complex fluorides.

Specific Substances

    A) No Synonyms were found in group or single elements
    1.2.1) MOLECULAR FORMULA
    1) F2-O

Available Forms Sources

    A) FORMS
    1) Oxygen difluoride is an unstable, colorless gas with a foul odor; it is yellowish-brown when a liquid (Sax & Lewis, 1987; Sax & Lewis, 1989; Budavari, 1989; ACGIH, 1986).
    B) SOURCES
    1) Oxygen difluoride is prepared by passing fluorine slowly through an aqueous NaOH solution (Budavari, 1989).
    C) USES
    1) It reacts explosively with even mild reducing agents, and is used as an oxidizer for rocket propellants (ACGIH, 1986; HSDB , 1991).
    2) Oxygen difluoride is a very strong oxidizing agent used in the preparation of complex fluorides (Raffle, 1987).

Overview

Life Support

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

Clinical Effects

    0.2.1) SUMMARY OF EXPOSURE
    A) The toxicity of oxygen difluoride resembles that of ozone, with additional fluoride gas effects. The primary acute effects seen will be irritation of the eyes and lungs with mild CNS depression.
    B) Delayed signs seen may include pulmonary edema and pulmonary hemorrhages.
    0.2.4) HEENT
    A) Lacrimation may occur. Although no cases have been reported, the gas would be expected to cause serious burns to the eyes.
    0.2.6) RESPIRATORY
    A) Oxygen difluoride is highly irritating to the respiratory tract. Pulmonary edema, congestion, or lung tissue damage may occur.
    0.2.7) NEUROLOGIC
    A) Drowsiness, muscular weakness, and headache have been reported.
    0.2.8) GASTROINTESTINAL
    A) Vomiting may occur.
    0.2.10) GENITOURINARY
    A) Oxygen difluoride is highly irritating to the kidneys and may cause distension and edema of the organs of the internal genitalia.
    0.2.14) DERMATOLOGIC
    A) It is a corrosive skin irritant. Although there are no human case reports, it is expected that this gas, under pressure, would cause serious burns.
    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) At the time of this review, no data were available to assess the carcinogenic potential of this agent.

Laboratory Monitoring

    A) No toxic levels have been established for oxygen difluoride.
    B) If respiratory tract irritation is present, monitor arterial blood gases and chest x-ray.

Treatment Overview

    0.4.2) ORAL/PARENTERAL EXPOSURE
    A) Because oxygen difluoride is a GAS, there is little to no risk of ingestion exposure.
    B) Treatment should include recommendations listed in the INHALATION EXPOSURE section when appropriate.
    0.4.3) INHALATION EXPOSURE
    A) INHALATION: Move patient to fresh air. Monitor for respiratory distress. If cough or difficulty breathing develops, evaluate for respiratory tract irritation, bronchitis, or pneumonitis. Administer oxygen and assist ventilation as required. Treat bronchospasm with an inhaled beta2-adrenergic agonist. Consider systemic corticosteroids in patients with significant bronchospasm.
    B) Administer humidified oxygen to patients in respiratory distress. Consider PEEP if pulmonary edema ensues.
    C) ACUTE LUNG INJURY: Maintain ventilation and oxygenation and evaluate with frequent arterial blood gases and/or pulse oximetry monitoring. Early use of PEEP and mechanical ventilation may be needed.
    D) Carefully observe patients for development of any systemic signs or symptoms and administer treatment as necessary.
    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).
    2) Treat dermal irritation or burns with standard topical therapy. Patients developing dermal hypersensitivity reactions may require treatment with systemic or topical corticosteroids or antihistamines.
    3) Treatment should include recommendations listed in the INHALATION EXPOSURE section when appropriate.

Range Of Toxicity

    A) Animals exposed 7 hours per day for 30 days to 0.1 ppm showed no detectable effects.
    B) This agent is highly toxic to a variety of species in concentrations as low as 0.5 ppm, but below this there is a sharp toxicity cut-off.

Clinical Effects

Summary Of Exposure

    A) The toxicity of oxygen difluoride resembles that of ozone, with additional fluoride gas effects. The primary acute effects seen will be irritation of the eyes and lungs with mild CNS depression.
    B) Delayed signs seen may include pulmonary edema and pulmonary hemorrhages.

Heent

    3.4.1) SUMMARY
    A) Lacrimation may occur. Although no cases have been reported, the gas would be expected to cause serious burns to the eyes.
    3.4.3) EYES
    A) BURNS - Although no cases have been reported, the gas, especially if under pressure, would be expected to cause serious burns of the eyes.
    B) LACRIMATION has been seen in experimental animals exposed to 26 ppm (Hathaway et al, 1991).

Respiratory

    3.6.1) SUMMARY
    A) Oxygen difluoride is highly irritating to the respiratory tract. Pulmonary edema, congestion, or lung tissue damage may occur.
    3.6.2) CLINICAL EFFECTS
    A) IRRITATION SYMPTOM
    1) This gas is highly irritating to the respiratory tract (ACGIH, 1986).
    B) ACUTE LUNG INJURY
    1) Systemic effects, including pulmonary edema or congestion, may occur following chronic inhalation of oxygen difluoride (Lewis, 1992).
    C) DISORDER OF RESPIRATORY SYSTEM
    1) LUNG TISSUE DAMAGE - In experimental animals exposed to an average of 4.5 ppm, progressive lung tissue destruction, which did not cease when exposure ceased, was noted (Harrison & Mackenzie, 1973).

Neurologic

    3.7.1) SUMMARY
    A) Drowsiness, muscular weakness, and headache have been reported.
    3.7.2) CLINICAL EFFECTS
    A) DROWSY
    1) Experimental animals exposed to 0.5 ppm for a few hours duration became soporific (ACGIH, 1986). Technicians operating the exposure chambers developed drowsiness at fractions of a ppm (Clayton & Clayton, 1982).
    B) MUSCLE WEAKNESS
    1) Muscular weakness was reported in dogs and monkeys exposed to 26 ppm for 1 hour (Hathaway et al, 1991).
    C) HEADACHE
    1) Inhalation of concentrations less than 1 ppm will cause intractable headache in humans (Hathaway et al, 1991).

Gastrointestinal

    3.8.1) SUMMARY
    A) Vomiting may occur.
    3.8.2) CLINICAL EFFECTS
    A) VOMITING
    1) Vomiting was seen in dogs and monkeys exposed to 26 ppm for 1 hour (Hathaway et al, 1991).

Genitourinary

    3.10.1) SUMMARY
    A) Oxygen difluoride is highly irritating to the kidneys and may cause distension and edema of the organs of the internal genitalia.
    3.10.2) CLINICAL EFFECTS
    A) NEPHRITIS
    1) Oxygen difluoride is highly irritating to the kidneys, especially the cortical medullary zone. These effects are similar to those of fluorine gas (Clayton & Clayton, 1982; ACGIH, 1986).
    3.10.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) EDEMA GENITAL
    a) Exposed experimental animals developed distension and edema of the organs of the internal genitalia (ACGIH, 1986).

Dermatologic

    3.14.1) SUMMARY
    A) It is a corrosive skin irritant. Although there are no human case reports, it is expected that this gas, under pressure, would cause serious burns.
    3.14.2) CLINICAL EFFECTS
    A) SKIN IRRITATION
    1) Oxygen difluoride is irritating or corrosive to the skin (Lewis, 1992).
    B) CHEMICAL BURN
    1) Although there are no human case reports, it is expected that this gas, under pressure and directed at the skin, would cause serious burns (Hathaway et al, 1991).

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 CAS7783-41-7 (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) At the time of this review, no data were available to assess the carcinogenic potential of this agent.
    3.21.3) HUMAN STUDIES
    A) LACK OF INFORMATION
    1) At the time of this review, no data were available to assess the carcinogenic potential of this agent.

Genotoxicity

    A) At the time of this review, no data were available to assess the mutagenic or genotoxic potential of this agent.

Laboratory Monitoring

Monitoring Parameters Levels

    4.1.1) SUMMARY
    A) No toxic levels have been established for oxygen difluoride.
    B) If respiratory tract irritation is present, monitor arterial blood gases and chest x-ray.
    4.1.2) SERUM/BLOOD
    A) TOXICITY
    1) No toxic levels have been established for oxygen difluoride.
    4.1.4) OTHER
    A) OTHER
    1) MONITORING
    a) If respiratory tract irritation is present, monitor arterial blood gases and chest x-ray.

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) Carefully observe patients with inhalation exposure for the development of any systemic signs or symptoms and administer symptomatic treatment as necessary.

Monitoring

    A) No toxic levels have been established for oxygen difluoride.
    B) If respiratory tract irritation is present, monitor arterial blood gases and chest x-ray.

Oral Exposure

    6.5.2) PREVENTION OF ABSORPTION
    A) SUMMARY
    1) Because oxygen difluoride is a GAS, there is little or no risk of ingestion exposure.
    6.5.3) TREATMENT
    A) PROCEDURE EDUCATION
    1) Because oxygen difluoride is a GAS, there is little or no risk of ingestion exposure.
    2) Treatment should include recommendations listed in the INHALATION EXPOSURE section when appropriate.

Inhalation Exposure

    6.7.1) DECONTAMINATION
    A) 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.
    B) OBSERVATION: Carefully observe patients with inhalation exposure for the development of any systemic signs or symptoms and administer symptomatic treatment as necessary.
    C) 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) OXYGEN
    1) Administer humidified oxygen to patients in respiratory distress. Consider PEEP if pulmonary edema ensues. Signs and symptoms of pulmonary edema may be delayed in onset up to 24 to 72 hours after exposure in some cases.
    B) 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).
    C) GENERAL TREATMENT
    1) FLUORIDE TOXICITY - Case reports of humans exposed to oxygen difluoride developing systemic FLUORIDE TOXICITY are LACKING.
    2) If SYSTEMIC FLUORIDE TOXICITY - is suspected following oxygen difluoride exposure, REFER to the FLUORIDE MEDITEXT(R) Medical Management for more information.
    D) Treatment should include recommendations listed in the ORAL EXPOSURE section when appropriate.

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) 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.
    B) GENERAL TREATMENT
    1) Treatment should include recommendations listed in the INHALATION EXPOSURE section when appropriate.
    C) Treatment should include recommendations listed in the ORAL EXPOSURE section when appropriate.

Range Of Toxicity

Summary

    A) Animals exposed 7 hours per day for 30 days to 0.1 ppm showed no detectable effects.
    B) This agent is highly toxic to a variety of species in concentrations as low as 0.5 ppm, but below this there is a sharp toxicity cut-off.

Minimum Lethal Exposure

    A) GENERAL/SUMMARY
    1) The minimum lethal human dose to this agent has not been delineated.

Maximum Tolerated Exposure

    A) GENERAL/SUMMARY
    1) The maximum tolerated human exposure to this agent has not been delineated.
    B) CONCENTRATION LEVEL
    1) In its resemblance to ozone, inhalation of oxygen difluoride at fractions of a part per million produced an intractable headache in persons performing tests; was soporific and an irritant to the entire respiratory tract, resulting in pulmonary edema and hemorrhage at all concentrations above 0.5 ppm in exposures of animals for a few hour's duration (ACGIH, 1986).
    2) A sharp cut-off in effect was noted below 0.5 ppm. Thirty day, daily repeated exposure to 0.1 ppm oxygen difluoride of 5 species of animals, including 1 non-rodent species showed no detectable effects by any of several tests applied (ACGIH, 1986).

Workplace Standards

    A) ACGIH TLV Values for CAS7783-41-7 (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) Oxygen difluoride
    a) TLV:
    1) TLV-TWA:
    2) TLV-STEL:
    3) TLV-Ceiling: 0.05 ppm
    b) Notations and Endnotes:
    1) Carcinogenicity Category: Not Listed
    2) Codes: Not Listed
    3) Definitions: Not Listed
    c) TLV Basis - Critical Effect(s): Headache; pulm edema; URT irr
    d) Molecular Weight: 54
    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 CAS7783-41-7 (National Institute for Occupational Safety and Health, 2007):
    1) Listed as: Oxygen difluoride
    2) REL:
    a) TWA:
    b) STEL:
    c) Ceiling: 0.05 ppm (0.1 mg/m(3))
    d) Carcinogen Listing: (Not Listed) Not Listed
    e) Skin Designation: Not Listed
    f) Note(s):
    3) IDLH:
    a) IDLH: 0.5 ppm
    b) Note(s): Not Listed

    C) Carcinogenicity Ratings for CAS7783-41-7 :
    1) ACGIH (American Conference of Governmental Industrial Hygienists, 2010): Not Listed ; Listed as: Oxygen difluoride
    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 ; Listed as: Oxygen difluoride
    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 CAS7783-41-7 (U.S. Occupational Safety, and Health Administration (OSHA), 2010):
    1) Listed as: Oxygen difluoride
    2) Table Z-1 for Oxygen difluoride:
    a) 8-hour TWA:
    1) ppm: 0.05
    a) Parts of vapor or gas per million parts of contaminated air by volume at 25 degrees C and 760 torr.
    2) mg/m3: 0.1
    a) Milligrams of substances per cubic meter of air. When entry is in this column only, the value is exact; when listed with a ppm entry, it is approximate.
    3) Ceiling Value:
    4) Skin Designation: No
    5) Notation(s): Not Listed

Toxicity Information

    7.7.1) TOXICITY VALUES
    A) References: Budavari, 1989 HSDB, 1991 Proctor et al, 1988 RTECS, 1991
    1) TCLo- (INHALATION)HUMAN:
    a) 500 ppb

Physicochemical

Physical Characteristics

    A) Oxygen difluoride is a colorless gas. When liquid, it is yellowish-brown (Budavari, 1989).
    B) It is an unstable, colorless gas with a foul odor; it is yellowish-brown when liquid (Sax & Lewis, 1987; Sax & Lewis, 1989; Budavari, 1989; ACGIH, 1986).

Ph

    1) No information found at the time of this review.

Molecular Weight

    A) 54.00 (Budavari, 1989; RTECS , 1991; Sax & Lewis, 1989)

References

General Bibliography

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