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<pre>Oxygen difluoride
(CAS No: 7783-41-7)
Health-based Reassessment of Administrative Occupational Exposure Limits
Committee on Updating of Occupational Exposure Limits,
a committee of the Health Council of the Netherlands
No. 2000/15OSH/126, The Hague, June 8, 2004
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<pre>Preferred citation:
Health Council of the Netherlands: Committee on Updating of Occupational
Exposure Limits. Oxygen difluoride; Health-based Reassessment of
Administrative Occupational Exposure Limits. The Hague: Health Council of the
Netherlands, 2004; 2000/15OSH/126.
all rights reserved
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<pre>1     Introduction
      The present document contains the assessment of the health hazard of oxygen
      difluoride by the Committee on Updating of Occupational Exposure Limits, a
      committee of the Health Council of the Netherlands. The first draft of this
      document was prepared by MA Maclaine Pont, M.Sc. (Wageningen University
      and Research Centre, Wageningen, the Netherlands).
           The evaluation of the toxicity of oxygen difluoride has been based on the
      review by the American Conference of Governmental Industrial Hygienists
      (ACGIH) (ACG91). Where relevant, the original publications were reviewed and
      evaluated as will be indicated in the text. In addition, in December 1999,
      literature was searched in the databases Toxline, Medline, and Chemical
      Abstracts, starting from 1981, 1966, and 1937, respectively, and using the
      following key words: oxygen difluoride, fluorine monoxide, oxygen fluoride,
      fluorine oxide, and 7783-41-7.
           In February 2001, the President of the Health Council released a draft of the
      document for public review. No comments were received.
           An additional search in Toxline and Medline in January 2004 did not result in
      information changing the committee’s conclusions.
2     Identity
      name                   :    oxygen difluoride
      synonyms               :    difluorine monoxide; fluorine monoxide; fluorine oxide; oxygen
                                  fluoride
      molecular formula      :    F2O
      CAS number             :    7783-41-7
126-3 Oxygen difluoride
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<pre>3     Physical and chemical properties
      molecular weight        :   54
      boiling point           :   -145°C
      melting point           :   -224°C
      flash point             :   -
      vapour pressure          :  at 20oC: >> 100 kPa
      solubility in water     :   slightly soluble
      log Poctanol/water      :   -1.03 (estimated)
      conversion factors      :   at 20oC, 101.3 kPa: 1 mg/m3 = 0.44 ppm
                                                      1 ppm = 2.25 mg/m3
      Data from ACG91, NLM04, http://esc.syrres.com.
      Oxygen difluoride is an unstable, colourless gas, yellowish-brown when liquid,
      with a foul odour (ACG91). Odour thresholds of 0.2-1.0 mg/m3 (0.1-4 ppm) have
      been reported (Amo83, Rut86).
           It reacts explosively with even mild reducing agents. Upon decomposition, it
      forms HF and CO (ACG91).
4     Uses
      Oxygen difluoride has been used as an oxidiser for rocket propellants (ACG91).
5     Biotransformation and kinetics
      The committee did not find data on the biotransformation and kinetics of oxygen
      difluoride.
6     Effects and mechanism of action
      Human data
      Personnel inadvertently exposed to oxygen difluoride during experiments in
      which animals were exposed to concentrations of 0.2-22 mg/m3 (0.1-10 ppm)
      suffered from severe headache (no details presented) (ACG91).
126-4 Health-based Reassessment of Administrative Occupational Exposure Limits
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<pre>      Animal data
      The committee did not find data from studies on the eye and skin irritation or
      sensitisation of oxygen difluoride.
          One-hour LC50 values were 3.4, 5.9, 58.5, and 58.5 mg/m3 (1.5, 2.6, 26, and
      26 ppm) in male rats, male mice, male and female dogs, and male and female
      monkeys, respectively (Dar72, Dav70, Ver77). Signs of toxicity observed were
      tachypnoea and muscular weakness in rats and mice and gagging, lachrymation,
      salivation, dyspnoea, muscular weakness, vomiting, and tetany in dogs and
      monkeys. Macroscopic changes included massive pulmonary oedema and
      haemorrhage, as the most characteristic changes, as well as liver, spleen, and
      kidney congestion at lethal concentrations and slight to moderate lung
      congestion and oedema at sublethal levels (Dav70). All 10 rats survived
      exposures to 22.5 mg/m3 (10 ppm) for 5 minutes and to 11.3 mg/m3 (5 ppm) for
      15 minutes. Five-minute exposures to 45, 67.5, and 90 mg/m3 (20, 30, and 40
      ppm) were lethal to 7/10, 9/10, and 10/10 rats, respectively, while 7/10 and 7/10
      rats died following 15-minute exposures to 22.5 and 33.8 mg/m3 (10 and 15
      ppm), respectively. Animals generally died within about 10 to 60 hours after
      exposure. Apart from overt respiratory distress immediately prior to death,
      Lester and Adams did not observed any evidence of irritation of the external
      mucosa or any indication of respiratory embarrassment. Gross and microscopic
      examination only revealed lung injury, mainly concerning the alveolar rather
      than the bronchiolar or bronchial epithelium. In animals killed 5 minutes to 29
      hours after being exposed to 45 mg/m3 (20 ppm) for 5 minutes, lesions of some
      severity were observed after 7 hours, were distinctive at 14 hours, and included
      severe diffuse acute pneumonia by 29 hours (Les65).
          Referring to a report from 1945, it was stated that exposure to 1.1 mg/m3 (0.5
      ppm), 7 hours/day, for 2 days, was lethal to a wide variety of experimental
      animals (see also below). Besides effects on the respiratory tract, kidney, and
      internal genitalia injury were reported (no more data presented) (ACG91). Citing
      the same report, repeated exposure of mice, rats, guinea pigs, rabbits, and dog to
      0.23 mg/m3 (0.1 ppm), 7 hours/day, for 30 days, was said to produce no evidence
      of toxicity. At higher concentrations (4.5-11.3 mg/m3 or 2-5 ppm), there was
      some variability in toxicity with species and age with older mice being more
      resistant (no further data presented) (Ano67) [the committee noted that these data
      were not quoted in ACG91].
          Davis studied the induction of oxygen difluoride tolerance in mice by 1-hour
      pre-exposures to 0.7, 1.1, and 2.3 mg/m3 (0.25, 0.5, and 1.0 ppm) and 1-hour re-
      exposures to multilethal concentrations at various periods up to 24 days post-
126-5 Oxygen difluoride
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<pre>      exposure. No significant tolerance was observed at the lower induction
      concentrations. In mice exposed to 7.9-9.6 mg/m3 (3.5-4.3 ppm) 24 hours, 8
      days, or 24 days after exposure to 2.3 mg/m3 (1 ppm), mortality was 60, 10, and
      50%, respectively, compared to 100% in animals not pre-exposed, suggesting
      that tolerance can be produced when the induction concentration is near lethal
      levels (Dav70).
           There are indications that oxygen difluoride does not induce
      methaemoglobinaemia in rats (Dos68).
      The committee did not find data on long-term exposure, mutagenicity,
      genotoxicity, carcinogenicity, and reproduction toxicity of oxygen difluoride.
7     Existing guidelines
      The current administrative occupational exposure limit (MAC) for oxygen
      difluoride in the Netherlands is 0.1 mg/m3, which is a ceiling value.
           Existing occupational exposure limits for oxygen difluoride in some
      European countries and in the USA are summarised in the annex.
8     Assessment of health hazard
      Oxygen difluoride is a hazard from a chemical and a toxicological point of view.
      It reacts explosively with even mild reducing agents.
           The committee did not find data on the biotransformation and kinetics of
      oxygen difluoride.
           In man, exposure to concentrations of 0.2-22 mg/m3 (0.1-10 ppm) caused
      severe headache.
           In experimental animals, 1-hour LC50 values were 3.4, 5.9, 58.5, and 58.5
      mg/m3 (1.5, 2.6, 26, and 26 ppm) in rats, mice, dogs, and monkeys, respectively,
      death being due to severe pulmonary oedema and haemorrhage.
           Exposure to 1.1 mg/m3 (0.5 ppm), 7 hours/day, for 2 days, was lethal to mice,
      rats, guinea pigs, rabbits, and dog while no effects were seen after exposure to
      0.23 mg/m3 (0.1 ppm), for 30 days. However, the committee considers that these
      very limitedly reported data from a study performed in 1945 cannot be used in
      deriving a health-based occupational exposure limit.
           The committee did not find data on long-term exposure, mutagenicity,
      genotoxicity, carcinogenicity, and reproduction toxicity of oxygen difluoride.
126-6 Health-based Reassessment of Administrative Occupational Exposure Limits
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<pre>      The committee considers the toxicological database on oxygen difluoride too
      poor to justify recommendation of a health-based occupational exposure limit.
      Since serious pulmonary effects have been found at a 10-fold higher
      concentration, the committee concludes that the present MAC-value of 0.1
      mg/m3, as a ceiling value, is too high.
      References
ACG91 American Conference of Governmental Industrial Hygienists (ACGIH). Oxygen difluoride. In:
      Documentation of the threshold limit values and biological exposure indices. 6th ed. Cincinnati,
      Ohio, USA: ACGIH®, 1991: 1153-4.
ACG03 American Conference of Governmental Industrial Hygienists (ACGIH). Guide to occupational
      exposure values - 2003. Cincinnati OH, USA: ACGIH®, 2003: 102.
ACG04 American Conference of Governmental Industrial Hygienists (ACGIH). 2004 TLVs® and BEIs®
      based on the documentation of the Threshold Limit Values for chemical substances and physical
      agents & Biological Exposure Indices. Cincinnati OH, USA: ACGIH®, 2004: 43.
Amo83 Amoore JE, Hautala E. Odor as an aid to chemical safety: odor thresholds compared with Threshold
      Limit Values and volatilities for 214 industrial chemicals in air and water dilution. J Appl Toxicol
      1983; 3: 272-90.
Ano67 Anonymous. Hygienic guide series. Oxygen difluoride (fluorine monoxide). Am Ind Hyg Assoc J
      1967; 28: 194-6.
Arb02 Arbejdstilsynet. Grænseværdier for stoffer og materialer. Copenhagen, Denmark: Arbejdstilsynet,
      2002: 23 (At-vejledning C.0.1).
Dar72 Darmer KI Jr, Haun CC, MacEwen JD. The acute inhalation toxicology of chlorine pentafluoride.
      Am Ind Hyg Assoc J 1972; 33: 661-8.
Dav70 Davis HV. Acute toxicity of oxygen difluoride. Wright-Patterson Air Force Base OH, USA:
      Aerospace Medical Research Laboratory, 1970; rep no AMRL-TR-70-102, paper no 21 (In:
      Proceedings of the 1st Annual Conference on Environmental Toxicology, Fairborne OH, USA,
      September 9-11, 1970: 329-40).
DFG03 Deutsche Forschungsgemeinschaft (DFG): Commisson for the Investigation of Health Hazards of
      Chemical Compounds in the Work Area. List of MAK and BAT values 2003. Maximum
      concentrations and biological tolerance values at the workplace. Weinheim, FRG: Wiley-VCH
      Verlag & Co. KGaA, 2003; rep no 39.
Dos68 Dost FN, Reed DJ, Wang CH. The mechanism of methemoglobin formation in nitrogen trifluoride
      intoxication (abstract). Fed Proc 1968; 27: 466.
EC04  European Commission: Directorate General of Employment and Social Affairs. Occupational
      exposure limits (OELs); http://europe.eu.int/comm/employment_social/health_safety/areas/
      oels_en.htm.
126-7 Oxygen difluoride
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<pre>HSE02 Health and Safety Executive (HSE). EH40/2002. Occupational Exposure Limits 2002. Sudbury
      (Suffolk), England: HSE Books, 2002.
Les65 Lester D, Adams WR. The inhalational toxicity of oxygen difluoride. Am Ind Hyg Assoc J 1965; 26:
      562-7.
NLM04 US National Library of Medicine (NLM), ed. Fluorine monoxide. In: The Hazardous Substances
      Data Bank (HSDB) (last revision data fluorine monoxide file: January 2003; last review date:
      January 1998); http://toxnet.nlm.nih.gov.
Rut86 Ruth JH. Odor thresholds and irritation levels of several chemical substances: a review. Am Ind Hyg
      Assoc J 1986; 47: A142-51.
Swe00 Swedish National Board of Occupational Safety and Health. Occupational exposure limit values and
      measures against air contaminants. Solna, Sweden: National Board of Occupational Safety and
      Health, 2000; Ordinance AFS 2000:3.
SZW04 Ministerie van Sociale Zaken en Werkgelegenheid (SZW). Nationale MAC-lijst 2004. The Hague,
      the Netherlands: Sdu Uitgevers, 2004: 44.
TRG03 TRGS 900. Grenzwerte in der Luft am Arbeitsplatz; Technische Regeln für Gefahrstoffe. BArBl
      2003; (9).
Ver77 Vernot EH, MacEwen JD, Haun CC, et al. Acute toxicity and skin corrosion data for some organic
      and inorganic compounds and aqueous solutions. Toxicol Appl Pharmacol 1977; 42: 417-23.
126-8 Health-based Reassessment of Administrative Occupational Exposure Limits
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<pre>              Annex
Occupational exposure limits for oxygen difluoride in various countries.
country                               occupational              time-weighted       type of            notea    referenceb
- organisation                        exposure limit            average             exposure limit
                                      ppm        mg/m3
the Netherlands
- Ministry of Social Affairs and      0.05       0.1            ceiling             administrative              SZW04
Employment
Germany
- AGS                                 -          -                                                              TRG03
- DFG MAK-Kommission                  -          -                                                              DFG03
Great Britain
- HSE                                 -          -                                                              HSE00
Sweden                                -          -                                                              Swe00
Denmark                               0.05       0.1            ceiling                                         Arb02
USA
- ACGIH                               0.05       -              ceiling             TLV                         ACG04
- OSHA                                0.05       0.1            8h                  PEL                         ACG03
- NIOSH                               0.05       0.1            ceiling             REL                         ACG03
European Union
- SCOEL                               -          -                                                              EC04
a
     S = skin notation; which means that skin absorption may contribute considerably to body burden; sens = substance can
     cause sensitisation.
b
     Reference to the most recent official publication of occupational exposure limits.
126-9         Oxygen difluoride
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<pre>126-10 Health-based Reassessment of Administrative Occupational Exposure Limits</pre>

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