<b>Bijsluiter</b>. De hyperlink naar het originele document werkt niet meer. Daarom laat Woogle de tekst zien die in dat document stond. Deze tekst kan vreemde foutieve woorden of zinnen bevatten en de opmaak kan verdwenen of veranderd zijn. Dit komt door het zwartlakken van vertrouwelijke informatie of doordat de tekst niet digitaal beschikbaar was en dus ingescand en vervolgens via OCR weer ingelezen is. Voor het originele document, neem contact op met de Woo-contactpersoon van het bestuursorgaan.<br><br>====================================================================== Pagina 1 ======================================================================

<pre>Osmium tetraoxide
(CAS No: 20816-12-0)
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/051, The Hague, 31 October 2002
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<pre>Preferred citation:
Health Council of the Netherlands: Committee on Updating of Occupational
Exposure Limits. Osmium tetraoxide; Health-based Reassessment of
Administrative Occupational Exposure Limits. The Hague: Health Council of
the Netherlands, 2002; 2000/15OSH/051.
all rights reserved
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<pre>1     Introduction
      The present document contains the assessment of the health hazard of osmium
      tetraoxide 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 KJ van den Berg, Ph.D. (TNO Nutrition and Food
      Research, Zeist, the Netherlands).
           The evaluation of the toxicity of osmium tetraoxide has been based on the
      review by American Conference of Governmental Industrial Hygienists
      (ACG98). Where relevant, the original publications were reviewed and
      evaluated as will be indicated in the text. In addition, literature was retrieved
      from the on-line databases Medline, Toxline, and Chemical Abstracts, covering
      the period 1966 to 26 April 1999 (19990426/UP), 1965 to 29 January 1999
      (19990129/ED), and 1967 to 24 April 1999 (19990424/ED; vol. 130, iss. 18),
      respectively, and using the following key words: osmium oxide, osmium
      tetraoxide, osmium tetroxide, osmium IV oxide, tetraoxoosmium, and
      20816-12-0. HSDB and RTECS, data bases available from CD-ROM, were
      consulted as well (NIO99, NLM99). The final literature search was carried out
      in April 1999.
           In September 2001, the President of the Health Council released a draft of
      the document for public review. The committee received no comments.
2     Identity
       name                  :    osmium tetraoxide
       synonyms              :    osmium tetroxide; osmic acid (anhydride); osmium oxide;
                                  perosmic acid anhydride; osmium IV oxide; tetraoxoosmium
       molecular formula     :    OsO4
       structural formula    :    -
       CAS number            :    20816-12-0
      Data from ACG98, NLM99.
051-3 Osmium tetraoxide
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<pre>3     Physical and chemical properties
       molecular weight         :      254.2
       boiling point            :      130oC
       melting point            :      39.5-41oC
       flash point              :      not known
       vapour pressure          :      at 27oC: 1.5 kPa
       solubility in water      :      at 25oC: 6.23 g/100 mL
       Log Poctanol/water       :      2.23 (estimated)
       conversion factors       :      1 ppm = 11 mg/m3
       (20oC, 101.3 kPa)               1 mg/m3 = 0.09 ppm
      Data from ACG98, NLM99, Ric94, http://esc.syrres.com.
      Osmium tetraoxide is a colourless to pale yellow solid with a disagreeable
      chlorine-like odour.
4     Uses
      Osmium tetraoxide is mainly used as a biological stain for adipose tissues in
      histopathological laboratories. It is also applied in photography and as a catalyst
      in organic synthesis (ACG98, Ric94)
5     Biotransformation and kinetics
      The committee did not find data on biotransformation and kinetics of osmium
      tetraoxide.
6     Effects and mechanism of action
      Human data
      In a very brief summary report, osmium tetraoxide in small (not further
      specified) amounts is reported to be irritating for the respiratory system and the
      eyes. In the eyes, moderate to severe conjunctivitis was observed, but also cases
      of blindness have been reported. Black discolourations of the skin may occur,
      caused by reduced osmium dioxide or metallic osmium. Also rashes on the face,
051-4 Health-based Recommended Occupational Exposure Limits
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<pre>      arms, and hands were observed. Prolonged inhalation of small amounts of
      osmium tetraoxide may lead to headache, insomnia, nausea, gastrointestinal
      complaints, diarrhoea, persisting irritation of the respiratory system with little
      secretion, and, under certain conditions, to pulmonitis. The highest
      concentration that could be tolerated for 6 hours without harmful effects was
      reported to be 0.001 mg/m3 (Flu31). Because of lack of detailed information, the
      committee considers this report to be inadequate for use as a basis in standard
      setting.
          Workers exposed to osmium tetraoxide have experienced irritation of the
      nose and throat that persisted for at least 12 hours after cessation of exposure
      (no data on concentration were given). Following a brief exposure to osmium
      tetraoxide vapour (concentration unknown), workers experienced delayed
      lachrymation and ‘halo’ effects (ACG98). At concentrations of osmium
      tetraoxide ranging from 0.1-0.6 mg/m3, workers suffered from lachrymation and
      disturbances of vision, conjunctivitis, and complained of headache and cough.
      In most cases, recovery occurred within a few days (McL46).
          In 2 cases of osmium tetraoxide poisoning in medical staff, altered
      respiratory functions indicative for a bronchitis with a tendency to chronicity
      were found (Vio69).
          Osmium tetraoxide is considered a precipitating factor in the occurrence of
      occupational asthma (Whi88).
          Osmium tetraoxide has been found corrosive to the skin and has produced
      dermatitis (ACG98).
      Animal data
      Irritation
      Osmium tetraoxide as a 1 % solution, caused severe corneal damage, permanent
      opacity, and superficial vascularisation to a rabbit’s eye (Bru33).
          In rabbits (n=4) exposed to an initial calculated concentration of 1316
      mg/m3 for 30 minutes, pulmonary oedema was observed and deaths occurred
      after 4 days (Bru33).
          The committee did not find data on the possible sensitising effects of
      osmium tetraoxide.
051-5 Osmium tetraoxide
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<pre>      Acute toxicity
      Acute 4-hour LC (less than 50% mortality) values for osmium tetraoxide of 40
      ppm (400 mg/m3) for rats and mice have been reported (ACG98).
          An oral LD50 of 162 mg/kg bw has been reported for mice. Intraperitoneal
      LD50 values were 13.5 and 14.1 mg/kg bw for mice and rats, respectively
      (Ric94). These data were obtained from an unpublished report; the large
      differences between the LD50s after oral and intraperitoneal administration
      cannot be explained.
          Effects on the bone marrow have been reported after exposure of guinea
      pigs to osmium tetraoxide (concentration unknown) (ACG98).
          No data from subacute, subchronic, chronic, or carcinogenicity studies were
      found.
      Mutagenicity and genotoxicity
      Osmium tetraoxide did not induce sex-linked lethals, visible mutations, or
      changes in fertility in Drosophila (Aue47).
          Osmium tetraoxide was found to cause DNA damage as indicated by a
      positive result in the rec-assay system using recombination-proficient and
      -deficient strains of B. subtilis (Kad80, Kan80).
          Biochemical studies indicate that osmium tetraoxide may bind to specific
      regions in the DNA double helix (Luk84), more specifically to
      thymidine-containing mismatches (Wur91), and may cause DNA damage by
      introduction of methoxyamine-binding sites and the formation of alkali-labile
      sites (Liu88).
      Reproductive toxicity
      In the chick embryo test, osmium tetraoxide had an LD50 of 1.2 mg/egg. No
      teratogenicity or abnormal developments were observed (Rid52).
          The committee did not find other reproduction toxicity data.
7     Existing guidelines
      The current administrative occupational exposure limit (MAC) for osmium
      tetraoxide in the Netherlands is 0.0002 ppm (0.002 mg/m3), 8-hour TWA.
051-6 Health-based Recommended Occupational Exposure Limits
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<pre>          Existing occupational exposure limits for osmium tetraoxide in some
      European countries and in the USA are summarised in the annex.
8     Assessment of health hazard
      In humans, low (not specified) levels of osmium tetraoxide were irritating for
      the eyes, skin, nose, and respiratory system. At higher levels of exposure (not
      specified), it may be corrosive to the eyes and the skin, and also may cause
      systemic effects, pneumonia, and lethality. The highest concentration stated to
      be tolerated for 6 hours without harmful effects is 0.001 mg/m3, but the
      relevance of this finding cannot be evaluated due to limited reporting.
          No data on biotransformation and kinetics of osmium tetraoxide were found.
          In experimental animals, osmium tetraoxide was corrosive to the eyes. No
      data on potential sensitising effects of osmium tetraoxide were found.
          Acute 4-hour LC50 values of 40 ppm (400 mg/m3) for osmium tetraoxide in
      rats and mice were reported. In rabbits, inhalation exposure to an initial
      concentration of 1316 mg/m3 for 30 minutes caused pulmonary oedema and
      deaths after 4 days. An oral LD50 of 162 mg/kg bw for mice, and an
      intraperitoneal LD50 of 13.5 mg/kg bw for mice and of 14.1 mg/kg bw for rats
      have been reported. The large differences in LD50 values cannot be explained.
          No data from subacute, subchronic, chronic, reproduction toxicity, or
      carcinogenicity studies were found.
          Some evidence for a DNA damaging potential has been found in a B.
      subtilis system, but no data from other bacterial or mammalian cell mutagenicity
      or genotoxicity assay systems were found. Osmium tetraoxide is not mutagenic
      or genotoxic in Drosophila.
      The committee considers the toxicological database on osmium tetraoxide is too
      poor to justify recommendation of a health-based occupational exposure limit.
      The committee concludes that there is insufficient information to comment on
      the level of the present MAC-value.
      References
ACG98 American Conference of Governmental Industrial Hygienists (ACGIH). Osmium tetroxide. In:
      TLVs® and other occupational exposure values -1998. [CD-ROM]. Cincinnati OH, USA: ACGIH,
      1998.
051-7 Osmium tetraoxide
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<pre>ACG02a American Conference of Governmental Industrial Hygienists (ACGIH). Guide to occupational
       exposure values - 20002 Cincinnati OH, USA: ACGIH®, 2002: 98.
ACG02b American Conference of Governmental Industrial Hygienists (ACGIH). 2002 TLVs® and BEIs®.
       Threshold Limit Values for chemical substances and fysical agents. Biological Exposure Indices.
       Cincinnati OH, USA: ACGIH®, Inc, 2002: 45.
Arb00a Arbejdstilsynet. Grænseværdier for stoffer og materialer. Copenhagen, Denmark: Arbejdstilsynet,
       2000; At-vejledning C.0.1.
Arb00b Arbetarskyddsstyrelsen. Hygieniska gränsvärden och åtgärder mot luftföroreningar. Solna, Sweden:
       Arbetarskyddsstyrelsen, 2000; Ordinance AFS 2000/3.
Aue47  Auerbach C, Robson JM. Tests of chemical substances for mutagenic action. Proc R Soc Edinburgh
       1947; 62B: 284-91.
Bru33  Brunot FR. The toxicity of osmium tetroxide (osmic acid). J Ind Hyg 1933; 15: 136-43.
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.
DFG02  Deutsche Forschungsgemeinschaft (DFG): Senatskommission zur Prüfung gesundheitsschädlicher
       Arbeitsstoffe. MAK- und BAT-Werte-Liste 2002. Maximale Arbeitsplatzkonzentrationen und
       Biologische Arbeitsstofftoleranzwerte. Weinheim, FRG: Wiley-VCH, 2002: 91 (rep no 38).
Flu31  Flury F, Zernik F. Osmiumtetroxyd. In: Schädliche Gase. Dämpfe, Nebel, Rauch- und Staubarten.
       Berlin, FRG: Julius Springer Verlag, 1931: 253-4.
HSE02  Health and Safety Executive (HSE). EH40/2002. Occupational Exposure Limits 2002. Sudbury
       (Suffolk), England: HSE Books, 2002: 23.
Kad80  Kada T, Hirano K, Shirasu Y. Screening of environmental chemical mutagens by the Rec-assay
       system with Bacillus subtilis. Chem Mutagens 1980; 6: 149-73.
Kan80  Kanematsu N, Hara M, Kada T. Rec assay and mutagenicity studies on metal compounds. Mutat Res
       1980; 77: 109-16.
Liu88  Liuzzi M, Talpaert-Borle M. Characterization of damage in gamma-irradiated and OsO4-treated
       DNA using methoxyamine. Int J Radiat Biol 1988; 54: 709-22.
Luk84  Lukasova E, Vojtiskova M, Jelen F, et al. Osmium-induced alterations in DNA structure. Gen
       Physiol Biophys 1984; 3: 175-91.
McL46  McLaughlin AIG, Milton R, Perry KMA. Toxic manifestations of osmium tetroxide. Br J Ind Med
       1946; 3: 183-6.
NIO99  US National Institute of Occupational Safety and Health (NIOSH). Osmium tetroxide. In: Registry
       of Toxic Effects of Chemical Substances (RTECS). [CD-ROM], issue July 1999. SilverPlatter
       International, 1999 (last update osmium tetraoxide file: July 1999).
051-8  Health-based Recommended Occupational Exposure Limits
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<pre>NLM99 US National Library of Medicine (NLM). Osmium tetroxide. In: Hazardous Substances Data Bank
      (HSDB). [CD-ROM], issue July 1999. SilverPlatter International, 1999 (last update osmium
      tetraoxide file: November 1998).
Ric94 Richardson ML, Gangolli S, eds. O35 Osmium (IV) tetroxide. In: The dictionary of substances and
      their effects. Cambridge, UK: Royal Society of Chemistry, 1994: 351-2 (Vol 6).
Rid52 Ridgway LP, Karnofsky DA. The effects of metals on the chick embryo toxicity and production of
      abnormalities in development. Ann NY Acad Sci 1952; 55: 203-50.
SZW02 Ministerie van Sociale Zaken en Werkgelegenheid (SZW). Nationale MAC-lijst 2002. The Hague,
      the Netherlands: Sdu, Servicecentrum Uitgevers, 2002: 37.
TRG00 TRGS 900. Grenzwerte in der Luft am Arbeitsplatz; Technische Regeln für Gefahrstoffe. BArbBl
      2001; 2.
Vio69 Viotti G, Valbonesi M, Ardoino V. Su tre casi di intossicazione da osmio. Lav Med 1969; 23: 77-82.
Whi88 White RP, Cordasco EM. Occupational asthma. In: Zenz C, ed. Occupational Medicine: Principles
      and practical applications. 2nd ed. Chicago MI, USA: Year Book Med Publ, 1988: 235-42.
Wur91 Wurst H, Pohl FM. Mutant profiles of selectable genetic elements. Proc Natl Acad Sci USA 1991;
      88: 9909-13.
051-9 Osmium tetraoxide
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<pre>             Annex
Occupational exposure limits for osmium tetraoxide 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       0.0002       0.002              8h               administrative             SZW02
and Employment
Germany
- AGS                              -            -                                                             TRG00
- DFG MAK-Kommission               -            -c                                                            DFG02
Great Britain
- HSE                              0.0002       0.002              8h               OES                       HSE02
                                   0.0006       0.006              15 min
Sweden                             -            -                                                             Arb00b
Denmark                            0.0002       0.002              8h                                          Arb00a
USA
- ACGIH                            0.0002       -                  8h               TLV                       ACG02b
                                   0.0006       -                  15 min           STEL
- OSHA                             -            0.002              8h               PEL                       ACG02a
- NIOSH                            0.0002       0.002              10 h             REL                       ACG02a
                                   0.0006       0.006              15 min           STEL
European Union
- SCOEL                            -            -                                                             CEC00
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.
c
       Listed among substances for which studies of the effects in man or in experimental animals have yielded insufficient
      information for the establishment of MAK values.
051-10       Health-based Recommended Occupational Exposure Limits
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