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<pre>Nitrogen trifluoride
(CAS No: 7783-54-2)
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/125, The Hague, June 8, 2004
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<pre>Preferred citation:
Health Council of the Netherlands: Committee on Updating of Occupational
Exposure Limits. Nitrogen trifluoride; Health-based Reassessment of
Administrative Occupational Exposure Limits. The Hague: Health Council of the
Netherlands, 2004; 2000/15OSH/125.
all rights reserved
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<pre>1     Introduction
      The present document contains the assessment of the health hazard of nitrogen
      trifluoride 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).
           In November 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: nitrogen trifluoride, nitrogen
      fluoride (NF3), and 7783-54-2.
           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                    :     nitrogen trifluoride
      synonyms                :     nitrogen fluoride; trifluoroamine; trifluoroammonia;
                                    perfluoroammonia
      molecular formula       :     NF3
      CAS number              :     7783-54-2
3     Physical and chemical properties
      molecular weight        :   71.0
      boiling point           :   -129oC
      melting point           :   -208.5oC
      flash point             :   -
      vapour pressure         :   at 20°C: >100 kPa
      solubility in water     :   very slightly soluble
      log Poctanol/water      :   -1.60
      conversion factors      :   at 20°C, 101.3 kPa: 1 mg/m3 = 0.34 ppm
                                                       1 ppm = 2.96 mg/m3
      Data from ACG91, NLM04, http://esc.syrres.com.
      Nitrogen trifluoride is a colourless, stable gas with a mouldy odour (ACG91).
125-3 Nitrogen trifluoride
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<pre>          The gas is heavier than air. It decomposes upon combustion or after contact
      with a hot surface, forming toxic vapours (i.e., hydrogen fluoride). The
      compound is a strong oxidiser and reacts vigorously with flammable and
      reducing agents. In the presence of water, it corrodes many metals. It reacts
      vigorously with many compounds, upon heating and electric discharge, with a
      chance for fire and explosion (NIA98).
          None out of 5 volunteers could detect any odour at 100 ppm (2960 mg/m3)
      and one of them thought he could detect the odour at 500 ppm (14,800 mg/m3)
      (Tor62).
4     Uses
      Nitrogen trifluoride is an oxidiser for high-energy fuels and is used in chemical
      synthesis (ACG91). It is used as a fluorine source for the hydrogen fluoride and
      deuterium fluoride (HF/DF) high-energy chemical lasers (Woy80).
5     Biotransformation and kinetics
      A generalised moderate increase in rat tissue fluoride levels appeared at the end
      of a 50-minute exposure to NF3 concentrations of 14,750 mg/m3 (5000 ppm) and
      disappeared in one day. However, in erythrocytes, high concentrations of
      fluoride persisted up to 48 hours after exposure (no statistical calculation).
      Appreciable amounts of fluoride appeared in the spleens of some animals during
      48 hours after exposure, possibly reflecting high concentrations in erythrocytes.
      There was no accumulation of fluorine in the adrenals and thyroid gland or in the
      testes (no quantitative data) (Dos70b).
6     Effects and mechanism of action
      Human data
      The committee did not find data on effects in humans following (occupational)
      exposure to nitrogen trifluoride.
      Animal data
      The committee did not find data on local effects, e.g., on skin, eyes, and mucous
      membranes, of nitrogen trifluoride.
125-4 Health-based Reassessment of Administrative Occupational Exposure Limits
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<pre>           Using groups of 10 male rats and mice, 15-minute LC50 values of 26,700 and
      19,300 ppm (79,000 and 57,128 mg/m3) were calculated for rats and mice,
      respectively, while 1-hour LC50 values were 6,700 and 7,500 ppm (19,832 and
      22200 mg/m3), respectively. Using groups of 2-3 dogs and monkeys,
      approximate 15-minute LC50 values were 38,000 and 24,000 ppm (112,480 and
      70140 mg/m3) for dogs and monkeys, respectively, and 1-hour LC50s 9,600 and
      10,000 ppm (28,416 and 29,600 mg/m3), respectively. All animals died because
      of extensive methaemoglobin formation and resulting anoxia. Although the dog
      was the most resistant species tested to the lethal effects of NF3, dog blood
      exhibited much more severe decreases in haematology parameters after exposure
      to this material. Dogs surviving exposure to 9600 ppm (28,416 mg/m3) for 60
      min exhibited Heinz-body anaemia with red blood cell count, haemoglobin, and
      haematocrit decreasing 33% to minimum values by the end of the second week
      post-exposure. Recovery of haematological values to pre-exposure levels was
      attained in 40 days (Ver73). For mice, a 4-hour LC50 value of 2000 ppm (5920
      mg/m3) was listed (NIO04). All male rats (n=4-8/group) survived exposures to
      20,000, 10,000, 5000, 2500, and 1000 ppm (59,200-9600 mg/m3) for 0.2, 0.5, 1,
      2, and 7 hours, respectively. Concentrations of 20,000 and 10,000 ppm were
      lethal to all rats within 0.5 and 1 hour, respectively, while exposure to 5000 and
      2500 ppm resulted in the death of 75% of the animals within 2 and 7 hours,
      respectively. The cause of death was excessive methaemoglobinaemia (Tor62).
           In rats, NF3 did not apparently influence the rate at which high concentrations
      of methaemoglobin (MetHb) were reduced, but residual concentrations of
      MetHb or a derivative spectrally similar to MetHb persisted at concentrations of
      as much as 5% for several days (Dos70a).
           Rabbits were much less affected by an intraperitoneal injection of NF3 than
      were rats. Not only did the rabbits survive after much larger doses, moreover,
      they did not develop the cyanotic appearance that was seen in rats. In rabbits,
      slight to moderate cyanosis was observed after an injection of 20.0 mL/kg bw; in
      rats, an injection of 7.95 mL/kg bw induced cyanosis within 20 minutes (Tor62).
           Inhalation of NF3 concentrations of 100 ppm (296 mg/m3), 7 hours/day, 5
      days/week, for 4.5 months, did not induce methaemoglobinaemia in rats
      (n=12/sex; controls: n=6/sex). Organ weights of the female rats were normal but
      the average relative liver, kidney, and spleen weights of the male rats were
      increased (p=0.005, p=0.01, and p=0.06, respectively) compared with a control
      group. Microscopically, degenerative changes were seen in the livers and
      kidneys of both male and female rats. The changes in the livers were described as
      generalised cloudy swelling of the parenchymal cells with some round cell
      filtration and some proliferation of the bile duct epithelium in the portal areas. In
125-5 Nitrogen trifluoride
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<pre>      the kidneys of both sexes, interstitial and slight tubular nephritis were seen. No
      evidence of fluorosis of the teeth or deposition of fluorine in the teeth and bone
      was observed although a very slight increase in total fluorine in the urine was
      detected (Tor62).
           Both in vitro and in vivo data indicate, that 1 mol of NF3 mediates or
      participates in the oxidation of 3 haem equivalents. The in vivo experiments used
      anaesthetised dogs, given an initial concentration of 0.6-1.0% (6000-10,000 ppm
      or 17,760-29,600 mg/m3) endotracheally. The maximum rate of MetHb
      formation under these circumstances was in the order of 1% of total Hb per
      minute (Dos71).
           The committee did not find data on the potential carcinogenicity,
      mutagenicity, genotoxicity, or reproduction toxicity of nitrogen trifluoride.
7     Existing guidelines
      The current administrative occupational exposure limit (MAC) for nitrogen
      trifluoride in the Netherlands of is 29 mg/m3 (10 ppm), 8-hour TWA.
           Existing occupational exposure limits for nitrogen trifluoride in some
      European countries and in the USA are summarised in the annex.
8     Assessment of health hazard
      Nitrogen trifluoride is a strong oxidiser and reacts vigorously with a variety of
      chemicals. In the body, NF3 splits off a fluoride ion and its target is the
      erythrocyte, reacting with haemoglobin to form methaemoglobin (MetHb). At
      high, lethal concentrations, methaemoglobinaemia is the cause of death in rats,
      mice, dogs, and monkeys.
           In a 4.5-month study in rats (Tor62), exposure to NF3 concentrations of 296
      mg/m3, 7 hours/day, 5 days/week, did not induce methaemoglobinaemia.
      However, this concentration induced an increase in relative liver, kidney, and
      spleen weights in male rats and, microscopically, degenerative changes in the
      livers and kidneys of both male and female rats. Since only one concentration
      was used in this study, the committee is of the opinion that this study cannot be
      used as a starting point for deriving a health-based occupational exposure limit.
      The committee considers the liver, kidneys, and spleen to be the target organs for
      toxicity of nitrogen trifluoride.
      The committee considers the toxicological database on nitrogen trifluoride too
      poor to justify recommendation of a health-based occupational exposure limit.
125-6 Health-based Reassessment of Administrative Occupational Exposure Limits
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<pre>       Given the effects observed in the inhalation study with rats (Tor62), the
       committee concludes that the current MAC-value of 29 mg/m3 (10 ppm), 8-hour
       TWA, is too high.
       References
ACG91  American Conference of Governmental Industrial Hygienists (ACGIH). Nitrogen trifluoride. In:
       Documentation of the threshold limit values and biological exposure indices. 6th ed. Cincinnati OH,
       USA: ACGIH®, 1991: 1111-2.
ACG03  American Conference of Governmental Industrial Hygienists (ACGIH). Guide to occupational
       exposure values - 2003. Cincinnati OH, USA: ACGIH®, 2003: 97.
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: 42.
Arb02  Arbejdstilsynet. Grænseværdier for stoffer og materialer. Copenhagen, Denmark: Arbejdstilsynet,
       2002: 33 (At-vejledning C.0.1).
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.
Dos70a Dost FN, Reed DJ, Wang CH. Toxicology of nitrogen trifluoride. Toxicol Appl Pharmacol 1970; 17:
       585-96.
Dos70b Dost FN, Reed DJ, Cooper TD, et al. Fluorine distribution in rats following acute intoxication with
       nitrogen and halogen fluorides and with sodium fluoride. Toxicol Appl Pharmacol 1970; 17: 573-84.
Dos71  Dost FN, Reed DJ, Johnson DE, et al. Stoichiometry of the reaction of hemoglobin with nitrogen
       trifluoride in vitro and in vivo. J Pharmacol Exp Ther 1971; 176: 448-54.
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.
HSE02  Health and Safety Executive (HSE). EH40/2002. Occupational Exposure Limits 2002. Sudbury
       (Suffolk), England: HSE Books, 2002: 22.
NIA98  Nederlands Instituut voor Arbeidsomstandigheden (NIA), TNO, VNCI, ed. [Chemiekaarten]. 13th
       ed. 998. Alphen aan den Rijn, the Netherlands: Samsom HD Tjeenk Willink, 1998: 998.
NIO04  US National Institute for Occupational Safety and Health (NIOSH), ed. Nitrogen trifluoride. In: The
       Registry of Toxic Effects of Chemical Substances (RTECS) (last update nitrogen trifluoride file:
       October 2002); http://www.cdc.gov/niosh.
NLM04  US National Library of Medicine (NLM), ed. Nitrogen trifluoride. In: The Hazardous Substances
       Data Bank (HSDB) (last revision data nitrogen trifluoride file: November 2002; last review date:
       September 1994); http://toxnet.nlm.nih.gov.
125-7  Nitrogen trifluoride
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<pre>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: 40.
Tor62 Torkelson TR, Oyen F, Sadek SE, et al. Preliminary toxicologic studies on nitrogen trifluoride.
      Toxicol Appl Pharmacol 1962; 4: 770-81.
TRG03 TRGS 900. Grenzwerte in der Luft am Arbeitsplatz; Technische Regeln für Gefahrstoffe. BArBl
      2003; (9).
Ver73 Vernot EH, Haun CC, MacEwen JD, et al. Acute inhalation toxicology and proposed emergency
      exposure limits of nitrogen trifluoride. Toxicol Appl Pharmacol 1973; 26: 1-13.
Woy80 Woytek AJ. Fluorine compounds, inorganic. In: Mark HF, Othmer DF, Overberger CG, et al ed.
      Ferroelectrics to fluorine compounds, organic. 3rd ed. New York, USA: J Wiley & Sons, Inc, 1980:
      655-772 (Kirk-Othmer encyclopedia of chemical technology; Vol 10).
125-8 Health-based Reassessment of Administrative Occupational Exposure Limits
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<pre>              Annex
Occupational exposure limits for nitrogen trifluoride 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       10            29                                 administrative             SZW04
Employment
Germany
- AGS                                  -             -                                                             TRG03
- DFG MAK-Kommission                   -             -                                                             DFG03
Great Britain
- HSE                                  10            30                8h               OES                        HSE02
                                       15            44                15 min
Sweden                                 -             -                                                             Swe00
Denmark                                10            29                8h                                          Arb02
USA
- ACGIH                                10            -                 8h               TLV                        ACG04
- OSHA                                 10            29                8h               PEL                        ACG03
- NIOSH                                10            29                10 h             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.
125-9         Nitrogen trifluoride
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<pre>125-10 Health-based Reassessment of Administrative Occupational Exposure Limits</pre>

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