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<pre>      Pentacarbonyliron
      (CAS reg no: 13463-40-6)
      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/036, The Hague, 7 March 2002
036-1
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<pre>      Preferred citation:
      Health Council of the Netherlands: Committee on Updating of Occupational
      Exposure Limits. Pentacarbonyliron; Health-based Reassessment of
      Administrative Occupational Exposure Limits. The Hague: Health Council of the
      Netherlands, 2002; 2000/15OSH/036.
      all rights reserved
036-2
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<pre>1     Introduction
      The present document contains the assessment of the health hazard of
      pentacarbonyliron 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, Wageningen, the Netherlands).
          The evaluation of the toxicity of pentacarbonyliron has been based on the
      review by the American Conference of Governmental Industrial Hygienists
      (ACG99). Where relevant, the original publications were reviewed and evaluated
      as will be indicated in the text. In addition, literature was retrieved from the data
      bases Toxline, Medline, and Chemical Abstracts, covering the periods of 1981 to
      July 1999, 1966 to November 1999, and 1937 to September 1999, respectively, and
      using the following key words: iron pentacarbonyl, iron carbonyl, carbonyls,
      iron, Fe(CO)5, and 13463-40-6. The final literature search has been carried out in
      November 1999.
          In July 2001, the President of the Health Council released a draft of the
      document for public review. The committee received no comments.
2     Identity
       name                        :     pentacarbonyliron
       synonyms                    :     iron pentacarbonyl; iron carbonyl
       molecular formula:          :     Fe(CO)5
       CAS reg no                  :     13463-40-6
      Data from How 92.
      Pentacarbonyliron is a viscous, colourless to yellow, oily liquid (ACG99).
036-3 Pentacarbonyliron
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<pre>3     Physical and chemical properties
       molecular weight              :    195.9
       melting point                 :    -20 oC
       boiling point                 :    103 oC
       flash point                   :    -15 oC (closed cup)
       vapour pressure               :    at 20 oC: 3.5 kPa
       solubility in water           :    insoluble
       log P octanol/water           :    not found
       conversion factors            :    1 mg/m 3 = 0.123 ppm
       (20 oC, 101.3 kPa)                 1 ppm = 8.15 mg/m 3
      Data from ACG99, Che99, Lid96.
      Pentacarbonyliron is a highly flammable, viscous, colourless to yellow, oily
      liquid. It is decomposed by light to iron monocarbonyl and carbon monoxide. It
      is pyrophoric in air and in an acetic acid solution; it burns to ferric oxide
      (ACG99).
            The vapour is heavier than air and spreads over the floor, where it can be
      ignited from a distance. It reacts vigorously with oxidants, acids, and halogens
      (Che99).
4     Uses
      Pentacarbonyliron has been used as an antiknock agent in gasoline in Europe. It
      may also be encountered in situations where finely divided iron comes into
      contact with carbon monoxide. It is a strong reducing agent (ACG99).
5     Biotransformation and kinetics
      No data have been found.
036-4 Health-based Reassessment of Administrative Occupational Exposure Limits
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<pre>6     Effects and mechanism of action
      Human data
      The committee did not find information on the health effects of exposure of
      humans to pentacarbonyliron
      According to ACGIH, the clinical picture of acute exposure to high
      concentrations ot pentacarbonyliron is expected to resemble that of nickel
      carbonyl: immediate symptoms of headache and dizziness are followed within 12
      to 36 hours by fever, cyanosis, cough, and dyspnoea; the primary effects are on
      the lungs, but degenerative central nervous system changes have been also
      reported (ACG99).
      Animal data
       acute toxicity data:
       LClo inhalation 5.5 h rat          :      270 mg/m 3
       LClo inhalation 45 min rabbit      :      2040 mg/m 3
       LC50 inhalation 30 min rat         :      910 mg/m 3
       LC50 inhalation 30 min mouse       :      2190 mg/m 3
       LC50 inhalation 10 min mouse       :      7000 mg/m 3
       LD50 intravenous rabbit            :      11 mg/kg
       LD50 oral rabbit                   :      12 mg/kg
       LD50 oral guinea pig               :      22 mg/kg
       LD50 dermal rabbit                 :      240 mg/kg
      Data from Lew92, Sun59.
      Rats (Alderley park; n=4/sex/group) were exposed to pentacarbonyliron
      concentrations of 270, 122, and 57 mg/m3 (33, 15, 7 ppm, resp), 5.5 hours/day, for
      1, 2, and 18 days, respectively. In the high-concentration group, animals showed
      lethargy, respiratory difficulty, 4% COHb, and 3 animals were dead the next day.
      Histological examination revealed lung oedema and congestion. In the 15-ppm
      group, similar effects (mortality in 4 animals 3-4 days later, lethargy, respiratory
      difficulty, lung oedema and congestion) were observed. Exposure to 7 ppm did
036-5 Pentacarbonyliron
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<pre>      not result in signs of toxicity or in macroscopic changes in lungs, liver, kidneys,
      spleen, and adrenals (no more data/details presented) (Gag70).
           In a more recent study, rats (SPF-Wistar; n=5/sex/group) were exposed
      (whole body) to 81.5, 24, and 8.15 mg/m3 (10, 3, 1 ppm, resp) pentacarbonyliron, 6
      hours/day, 5 days/week, for 28 days. Because of severe toxicity (mortality) in the
      10- and 3-ppm group, treatment was discontinued after 1 and 2 exposures,
      respectively. Two additional test groups were included and exposed to 2.4, and
      0.82 mg/m3 (0.3, 0.1 ppm, resp). In the 10-ppm group, animals showed abdominal
      respiration, piloerection, reddish crusts on the edges of the nose, deteriorated
      general state, and squatting posture. All animals were dead or sacrificed
      moribund by study day 4. Upon postmortem macroscopic and microscopic
      examination, there were minimal irritation of the upper respiratory tract
      (inflammatory changes in the submucosa of the nasal cavities and the trachea in
      6/10 and 4/10 animals, resp), and effects on the lungs (intensive discolouration in
      10/10, minimal to marked interstitial pneumonia in 10/10, minimal to marked
      regenerative proliferation in 8/10), spleen (strongly reduced size and lymphocyte
      depletion in 3/10 and 4/10, resp), mediastinal lymph nodes (2/5 females), and liver
      (yellowish, grey, or green-brown foci in 4/10). In the 3-ppm group, 50% of the
      animals were dead or sacrificed moribund by study day 4, showing signs similar
      to those seen in the 10-ppm group. In the surviving animals (2 males, 3 females),
      observed without further exposure for about 4 weeks, piloerection and
      accelerated respiration lasted up to study day 5 and 9, respectively. The absolute
      and relative lung weights of these animals were increased. Postmortem
      macroscopic and microscopic examinations revealed some minimal upper
      respiratory tract irritation (inflammatory changes in the submucosa of the nasal
      cavities and trachea in 1/10 and 3/10 animals, resp) and effects on the lungs
      (intensive discolouration in 5/10, minimal to marked interstitial pneumonia in 7/10,
      minimal to marked regenerative proliferation in 6/10), spleen (lymphocyte
      depletion in 2/5 females, resp) and liver (foci in 1/5 females). There were no
      effects on body weight development or on haematological, clinical chemical, and
      urinalysis parameters. In the animals exposed to 8.15 mg/m3, 2.4 mg/m3, and 0.82
      mg/m3 (1, 0.3, 0.1 ppm, resp), no substance-related clinical signs and findings or
      influence on body weight development were seen. There was a dose-related
      increase in carboxyhaemoglobin (COHb), measured after 17 days on test, which
      was statistically significant in male animals exposed to 1, 0.3, and 0.1 ppm and in
      female animals exposed to 1 and 0.3 ppm. The highest percentage of COHb was
      2.1. Further, increases in absolute and relative lung weight were found (see Table
036-6 Health-based Reassessment of Administrative Occupational Exposure Limits
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<pre>Tabel 1 Absolute and relative lung weights of rats (n=5/sex/group) exposed to pentacarbonyliron, 6 hours/day, 5
days/week, 28 days.
                                            males                                        females
                         0          0.82       2.4 (0.3) 8.15 (1)      0           0.82       2.4 (0.3) 8.15 (1)
                                    (0.1) a                                        (0.1)
absolute lung wt (g)     1.1        1.2 b      1.09       1.312 b      0.96        0.93       0.94       0.94
relative lung wt (%)     0.29       0.31       0.29       0.336 b      0.43        0.41       0.43       0.42
a                            3
      concentrations in mg/m and ppm (between brackets)
b
      p ≤ 0.05
             1). Postmortem macroscopic and microscopic examination did not reveal
             compound-related changes (Kli95).
             In concordance with the Dutch Expert Committee on Occupational Standards
             (DECOS), another committee of the Health Council of the Netherlands (DEC92),
             the committee considers COHb levels <5% not to be toxicologically relevant, i.e.,
             there will be only a small or neglectible risk of effects on behaviour and mental
             capacities at these levels. Based on the relative lung weight effects in male
             animals, the committee concludes that the no-observed-adverse-effect level in
             this 28-day inhalation study is 2.4 mg/m3 (0.3 ppm).
             The committee did not find data on the potential mutagenicity/genotoxicity,
             carcinogenicity, and reproduction toxicity of pentacarbonyliron.
7            Existing guidelines
             The current administrative occupational exposure limit (MAC) for
             pentacarbonyliron in the Netherlands is 0.08 mg/m3 (0.01 ppm), 8-hour TWA,
             expressed as iron.
                 Existing occupational exposure limits for pentacarbonyliron in some
             European countries and in the USA are summarised in the annex.
8            Assessment of health hazard
             The committee did not find human data on effects of pentacarbonyliron but
             effects due to inhalation exposure to pentacarbonyliron may resemble those of
             nickel carbonyl, being effects on the lungs and the central nervous system in
             humans.
036-7        Pentacarbonyliron
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<pre>          The committee did not find experimental animal data on the toxicokinetics or
      on the potential irritation and sensitisation of pentacarbonyliron.
          Acute inhalation experiments in which 3 out of 4 (3/4) rats died following a
      5.5-hour exposure to 270 mg/m3 (33 ppm) and 4/4 rats following two 5.5-hour
      exposures to 122 mg/m3 (15 ppm) showed pentacarbonyl to be a very toxic
      compound. Acute oral and dermal lethality data in rabbits (LD 50-values: 12 and
      240 mg/kg bw, resp) demonstrated a similar potential following other routes.
          In a 4-week inhalation study with intermittent exposure in rats (Kli95),
      exposure to 24 mg/m3 (3 ppm) caused mortality in 50% of the animals, lung
      effects (increased absolute and relative lung weights, intensive discolouration,
      minimal to marked interstitial pneumonia, minimal to marked regenerative
      proliferation) in 50% or more of the animals, and occasional minimal upper
      respiratory tract irritation. At exposure to 8.15 mg/m3 (1 ppm), there was only an
      increase in relative lung weights in male animals without accompanying
      histological changes while no effects were seen following exposure to 2.4 mg/m3
      (0.3 ppm).
          The committee takes the NOAEL of 2.4 mg/m3 of this study (Kli95) as a
      starting point in deriving a health-based recommended occupational exposure
      limit (HBROEL). For the extrapolation to a HBROEL, an overall assessment factor
      of 12 is established. This factor covers the following aspects: the type of effect,
      intra- and interspecies variation, and differences between experimental
      conditions and the exposure pattern of the worker. Thus, applying this factor -
      assuming that the dose inhaled by rats is equivalent to the dose inhaled by
      humans - and the preferred value approach, a health-based occupational
      exposure limit of 0.2 mg/m3 is recommended for pentacarbonyliron, or of 0.05
      mg/m3, measured as Fe.
      The committee recommends a health-based occupational exposure limit for
      pentacarbonyliron of 0.05 mg/m3, measured as Fe, as an 8-hour time-weighted
      average (TWA).
036-8 Health-based Reassessment of Administrative Occupational Exposure Limits
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<pre>       References
ACG99  American Conference of Governmental Industrial Hygienists (ACGIH). Iron pentacarbonyl.
       In: TLVs ® and other occupational exposure values - 1999. [CD-ROM]. Cincinnati OH, USA:
       ACGIH® , Inc, 1999.
ACG00  American Conference of Governmental Industrial Hygienists (ACGIH). Guide to occupational
       exposure values - 2000. Cincinnati OH, USA: ACGIH® , Inc, 2000: 67.
ACG01  American Conference of Governmental Industrial Hygienists (ACGIH). 2001 TLVs ® and
       BEIs® . Threshold Limit Values for chemical substances and physical agents. Biological
       Exposure Indices. Cincinnati OH, USA: ACGIH® , Inc, 2001: 36.
Arb00a Arbejdstilsynet. Grænseværdier for stoffer og materialer. Copenhagen, Denmark:
       Arbejdstilsynet, 2000; (At-vejledning C.0.1).
Arb00b Arbetarskyddstyrelsen. Hygieniska gränsvärden och åtgärder mot luftföroreningar. Solna,
       Sweden: National Board of Occupational Safety and Health, 2000; (Ordinance AFS 2000/3).
CEC00  Commission of the European Communities (CEC). Commission Directive 2000/39/EC of 8
       June 2000 establishing a first list of indicative occupational exposure limit values in
       implementation of Council Directive 98/24/EC on the protection of the health and safety of
       workers from the risks related to chemical agents at work. Official Journal of the European
       Communities 2000; L142 (16/06/2000): 47-50.
Che99  Samenwerkingsverband-Chemiekaarten (TNO Arbeid, VNCI). Chemiekaarten: gegevens voor
       het veilig werken met chemicaliën/. (15th ed). The Hague, the Netherlands: ten Hagen &
       Stam, 1999.
DEC92  Dutch Expert Committee on Occupational Standards (DECOS). Health-based recommended
       occupational exposure limit for carbon monoxide. The Hague, the Netherlands: SDU,
       Servicecentrum Uitgevers, 1992; (rep no RA 7/92).
DFG01  Deutsche Forschungsgemeinschaft (DFG): Commission for the Investigation of Health
       Hazards of Chemical Compounds in the Work Area. List of MAK and BAT values 2001.
       Maximum concentrations and biological tolerance values at the workplace. Weinheim, FRG:
       Wiley-VCH, 2001: 68; (rep no 37).
Gag70  Gage JC. The subacute inhalation toxicity of 109 industrial chemicals. Br J Ind Med 1970;
       27: 1-18.
How92  Howard PH, Neil M, eds. Dictionary of chemical names and synonyms. Chelsea MA, USA:
       Lewis Publishers, 1992.
HSE01  Health and Safety Executive (HSE). EH 40/2001. Occupational exposure limits 2001.
       Sudbury (Suffolk), England: HSE Books, 2001: 23.
036-9  Pentacarbonyliron
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<pre>Kli95  Klimisch HJ. Study on the inhalation toxicity of Eisenpentacarbonyl as a vapor in rats;
       28-day test. Ludwigshafen, FRG: BASF, Dept Toxicology, 1995 (available from NTIS,
       Springfield VA, USA; order no: NTIS/OTS 0529732-1).
Lew92  Lewis RJ Sr, ed. Sax's dangerous properties of industrial materials. (8th ed). New York, USA:
       Van Nostrand Reinhold, 1992: 2009.
Lid96  Lide DR, Frederikse HPR, eds. CRC Handbook of chemistry and physics. (77th ed). Boca
       Raton FL, USA: CRC Press, 1996: 3-201.
Sun59  Sunderman FW, West B, Kincaid JF. A toxicity study of iron pentacarbonyl. AMA Arch Ind
       Health 1959; 19: 11-3.
SZW01  Ministerie van Sociale Zaken en Werkgelegenheid (SZW). Nationale MAC-lijst 2001. The
       Hague, the Netherlands: Sdu, Servicecentrum Uitgevers, 2001: 44.
TRG00  TRGS 900. Grenzwerte in der Luft am Arbeitsplatz; Technische Regeln für Gefahrstoffe. B
       ArbBl 2000; 2.
036-10 Health-based Reassessment of Administrative Occupational Exposure Limits
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<pre>             Annex
Occupational exposure limits for pentacarbonyliron in various countries.
country                            occupational               time-weighted   type of          noteb     lit refc
  -organisation                    exposure limit a           average         exposure limit
                                   ppm         mg/m 3
the Netherlands
  - Ministry of Social Affairs     0.01        0.08           8h              administrative             SZW01
and Employment
Germany
  - AGS                            0.1         0.8            8h                                         TRG00
                                   0.2         0.8            15 min
                                                                                               e
  - DFG MAK-Kommission             0.1         0.81           8h                                         DFG01
                                   0.2         1.62           30 min d
Great Britain
  - HSE                            0.01        0.08           8h              OES                        HSE01
Sweden                             -           -                                                         Arb00b
Denmark                            0.1         0.8            8h                                         Arb00a
USA
  - ACGIH                          0.1         0.8            8h              TLV                        ACG01
                                   0.2         1.6            15 min          STEL
  - OSHA                           -           -                                                         ACG00
  - NIOSH                          0.1         0.8            10 h            REL                        ACG00
                                   0.2         1.6            15 min          STEL
European Union
  - SCOEL                          -           -                                                         CEC00
a
      Calculated as iron in all countries, except for Denmark
b
      S = skin notation; which means that skin absorption may contribute considerably to the body burden
c
      sens = substance can cause sensitisation
d
      Reference to the most recent official publication of occupational exposure limits
e
      Maximum frequency per shift : 4
f
      Listed among substances with MAK values but for which no pregnancy risk group classification could be made
036-11       Pentacarbonyliron
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