<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>Gezondheidsraad                               Voorzitter
Health Council of the Netherlands
Aan de Staatssecretaris van Sociale Zaken en Werkgelegenheid
Onderwerp            : Aanbieding adviezen herevaluatie bestuurlijke MAC-waarden
Uw kenmerk           : ARBO/AMIL/97/00648
Ons kenmerk          : U 2706/CB/MP/563-O3
Bijlagen             : 18
Datum                : 14 december 2000
Mijnheer de staatssecretaris,
Op verzoek van uw ambtsvoorganger bied ik u hierbij de eerste adviezen aan van een
reeks over de gezondheidskundige basis van uit het buitenland overgenomen
grenswaarden voor beroepsmatige blootstelling aan stoffen. Het verzoek om deze
adviezen is in algemene zin vervat in brief nr ARBO/AMIL/97/00648 en in latere stadia
door uw departement toegespitst op afzonderlijke stoffen. De adviezen zijn opgesteld
door een daartoe door mij geformeerde internationale commissie van de Gezondheidsraad
en beoordeeld door de Beraadsgroep Gezondheid en Omgeving.
     De beoogde reeks van in het Engels gestelde adviezen zal losbladig worden
gepubliceerd onder ons publicatienummer 2000/15OSH en, conform de aan de
Gezondheidsraad voorgelegde toespitsingen van de adviesaanvraag, betrekking hebben
op 168 stoffen. Het u thans aangeboden eerste pakket bestaat uit een Algemene Inleiding
(publicatienummer 2000/15OSH/000) en uit de adviezen genummerd 2000/15OSH/001
tot en met 2000/15OSH/017, respectievelijk betrekking hebbend op:
cesiumhydroxide, cyclopentaan, diboraan, dimethoxymethaan, dipropylketon,
fenylfosfine, germaniumtetrahydride, hexachloornaftaleen, methaanthiol,
methylcyclohexanol, methylisopropylketon, mica, natriumhydroxide,
octachloornaftaleen, silaan, tetrachloornaftaleen, en yttrium en yttriumverbindingen.
     Bij afronding van de werkzaamheden van de hierboven bedoelde commissie ontvangt
u een Nederlandstalige samenvatting van de in de gehele reeks van adviezen neergelegde
bevindingen.
Bezoekadres                                                                  Postadres
Parnassusplein 5                                                             Postbus 16052
2511 VX Den Haag                                                             2500 BB Den Haag
Telefoon (070) 340 75 20                                                     Telefax (070) 340 75 23
email: GR@gr.nl
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<pre>Gezondheidsraad
Health Council of the Netherlands
Onderwerp            : Herevaluatie uit het buitenland overgenomen grenswaarden
Ons kenmerk          :U
Pagina               :2
Datum                : 14 december 2000
    De u thans aangeboden adviezen heb ik vandaag ter informatie doen toekomen aan
de Minister van Volksgezondheid, Welzijn en Sport en aan de Minister van
Volkshuisvesting, Ruimtelijke Ordening en Milieubeheer.
Hoogachtend,
prof. dr JJ Sixma
Bezoekadres                                                                   Postadres
Parnassusplein 5                                                              Postbus 16052
2511 VX Den Haag                                                              2500 BB Den Haag
Telefoon (070) 340 75 20                                                      Telefax (070) 340 75 23
email: GR@gr.nl
</pre>

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<pre>      Silane
      (CAS Reg. nr: 7803-62-5)
      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/014, The Hague, 14 December 2000
014-1
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<pre>      Preferred citation:
      Health Council of the Netherlands: Committee on Updating of Occupational
      Exposure Limits. Silane; Health-based Reassessment of Administrative
      Occupational Exposure Limits. The Hague: Health Council of the Netherlands,
      2000; 2000/15OSH/014.
      all rights reserved
014-2
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<pre>1     Introduction
      The present document contains the assessment of the health hazard of silane 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 mrs S Bosman-Hoefakker, Ph.D. and H Stouten, M.Sc. (TNO
      Nutrition and Food Research Institute, Zeist, the Netherlands).
           The evaluation of the toxicity of silane has been based on the review by the
      American Conference of Governmental Industrial Hygienists (ACG91). Where
      relevant, the original publications were reviewed and evaluated as will be
      indicated in the text. In addition, literature was retrieved from the online data
      bases Medline, Toxline, and Chemical Abstracts covering the period 1966 to 2
      June 1997 (19970602/UP), 1965 to 21 March 1997 (970321/ED), and 1967 to
      29 April 1997 (970429/ED; vol 126, iss 18), respectively. Medline was
      searched with the CAS Registry Number 7803-62-5 and the names monosilane,
      SiH4, silicon hydride, silicon tetrahydride, silanes/CT(L)(AE OR PO OR
      TO)/CT, silanes/CT(L)(ME OR PK)/CT, and silanes/CT(L)(PD/CT AND (CI
      OR DE)/CT, Toxline with the CAS Registry Number 7803-62-5, and Chemical
      Abstracts with 7803-62-5 in the Sections “Toxicology” and “Air Pollution and
      Industrial Hygiene”. HSDB and RTECS, data bases available from CD-ROM,
      were consulted as well (NIO97, NLM97). The final literature search has been
      carried out in June 1997.
           In February 1999, the President of the Health Council released a draft of the
      document for public review. The committee received no comments.
2     Identity
       name                               :     silane
       synonyms                           :     monosilane
                                                silicane
                                                silicon hydride
                                                silicon tetrahydride
       molecular formula                  :     SiH4
       CAS reg nr                         :     7803-62-5
      Data from ACG91a, NLM97.
014-3 Silane
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<pre>3     Physical and chemical properties
       molecular weight         :    32.12
       boiling point            :    -111.5°C
       melting poin             :    -185°C
       flash point              :    extremely flammable; may ignite spontaneously in air
       vapour pressure          :    -
       solubility               :    decomposes slowly in water
                                     decomposes in potassium hydroxide solutions
                                     practically insoluble in alcohol, ether, benzene, chloroform,
                                     silicochloroform and silicon tetrachloride
       log Poct/water           :    -
       conversion factors       :    1 ppm = 1.3 mg/m3
       (20°C, 101.3 kPa)             1 mg/m3 = 0.75 ppm
      Data from ACG91a, NLM97.
      Silane is a colourless gas with a repulsive odour. At temperatures above 400°C,
      it decomposes into silicon and hydrogen.
4     Uses
      Silane finds use in the doping of solid-state devices and as a source of
      hyperpure silicon for semiconductors (ACG91a).
5     Biotransformation and kinetics
      No data on the biotransformation and kinetics of silane were found.
6     Effects and mechanism of action
      Human data
      The concentration of silane causing toxic effects in humans has not been
      determined. It will be mildly toxic by inhalation and silanes are irritating to the
      skin, eyes, and mucous membranes (ACG91a). It was stated that its vapours
      may cause dizziness and suffocation (NLM97).
014-4 Health-based Reassessment of Administrative Occupational Exposure Limits
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<pre>      Animal data
      In rats, the 4-hour LC50 is 9600 ppm (approximately 13,345 mg/m3). No effects
      were seen in rats exposed up to 126 ppm (approx. 175 mg/m3) for 1 hour. In
      mice, 4 out of 10 animals died following exposure to 9600 ppm (approx.
      13,345 mg/m3) for 4 hours (ACG91a).
           When male ICR mice were exposed to 2500, 5000, 7500, or 10,000 ppm
      (approx. 3475, 6950, 10,425, 13,900 mg/m3) for 30 minutes, 1 hour, or 4
      hours*, only in the animals exposed to 10,000 ppm for 4 hours, mortality (i.e.,
      9/12; all within 24 h) was observed. At autopsy of these animals, increased
      relative kidney weights, renal tubular necrosis, splenic atrophy, appearance of
      macrophages with debris of degenerated cells in bone marrow and thymus, and
      inflammatory changes of the nasal mucosa was seen. In the groups exposed for
      30 minutes or 1 hour and sacrificed at week 2, mainly effects on the kidneys
      were found (tubular interstitial nephrosis in 6/8 and 7/8 animals, respectively).
      Following exposure to 7500 ppm (only 30-min exposure), tubular nephrosis
      was seen in 4/8 animals. The 1- and 4-hour exposures to 5000 ppm caused
      tubular interstitial nephritis in 1/8 and 2/8 animals sacrificed at week 2,
      respectively, and acute renal tubular necrosis in 0/4 and 1/4 animals sacrificed
      after 2 days, respectively. Concerning the 2500 ppm groups, the only effect
      observed was acute renal tubular necrosis in 1/4 animals exposed for 4 hours
      (Tak93).
           In a separate (earlier conducted) study, male ICR mice (n=10/group) were
      exposed to approximately 1000 ppm (approx. 1390 mg/m3) of silane for 1 hour
      or 2, 4, or 8 hours. After sacrifice 3 days postexposure, the organs were
      examined grossly, and histoogically (all exposed and non-exposed mice: nasal
      cavity, lung, liver, kidney, spleen, thymus, bone marrow, and testis; some of
      the mice: cornea, trachea, thyroid, salivary glands, and oesophagus).
      Biochemical and haematological parameters examined included alkaline
      phosphatase, aspartate and alanine aminotransferase, cholinesterase, blood urea
      nitrogen, sodium, potassium, red blood cell count, and total and differential
      white blood cell counts. Neither mortality nor exposure-related changes in any
      of the organs were observed. Biochemical or haematological parameters
      affected included an increase in red blood cell counts in mice exposed for 8
      hours, an increase in blood urea nitrogen in mice exposed for 1 hour and a
*     Number of animals exposed: 8 per concentration when exposed for 30 min, all sacrificed 2 weeks postexposure; 12
      per concentration when exposed for 1 or 4 h, 4 sacrificed 2 days and 8 animals 2 weeks postexposure.
014-5 Silane
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<pre>      decrease in the 8-hour exposure group, and a decreased white blood cell count
      after 1-hour exposure (Oma92).
           The latter mentioned study included a subacute experiment in which mice
      (n=10/group) were exposed to 6 hours/day, 5 day/week 1000 ppm (approx.
      1390 mg/m3), for 2 or 4 weeks (parameters examined: see above; time of
      sacrifice: on the day after the final exposure). These treatments did not induce
      mortality, nor exposure-related haematological, biochemical, or histological
      changes in the mice exposed for 2 weeks. In mice exposed for 4 weeks, mild
      irritation, manifested in the form of a small amount of exudate (in 8/10
      animals), and inflammatory cells and/or necrotic cells of the nasal mucosa (in
      6/10) was observed. As to haematology/biochemical parameters, there was a
      statistically significant increase in white blood cell counts (lymphocytes and
      neutrophils) only (Oma92).
      Mutagenicity and genotoxicity
      Mutagenicity tests with silane showed positive results in the S. typhimurium
      strains TA98, TA100, TA1535, and TA1537, and in E. Coli WP2 uvrA when
      tested with and without metabolic activation (Ara94).
      No data on carcinogenicity or reproduction toxicity of silane have been found.
7     Existing guidelines
      The current administrative occupational exposure limit (MAC) for silane in the
      Netherlands is 0.7 mg/m3 (5 ppm), 8 h TWA.
           Existing occupational exposure limits for silane in some European
      countries and in the USA are summarized in the annex.
8     Assessment of health hazard
      The toxicological data base of silane is poor. No human data were available.
      Animal data were limited to acute mortality studies in rats and mice, one acute
      study in mice, and one (sub)acute study in mice with only one exposure level.
           From mortality data in rats and mice (4-h LC50s of 9600 and between 5000
      and 10,000 ppm, respectively), it can be seen that silane is not toxic, i.e. no
      classification or labelling is warranted. Acute inhalation experiments in mice
      with relatively high exposure concentrations have shown that the target organ
014-6 Health-based Reassessment of Administrative Occupational Exposure Limits
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<pre>      is the kidney. Exposure to silane causes acute renal tubular necrosis and tubular
      interstitial nephritis. No observed effect levels (NOEL) of 2500 and 5000 ppm
      (approx. 3475, 6950 mg/m3) can be established for 1-hour and 30-minutes
      exposures, respectively. After exposure for 4 hours to 2500 ppm (approx. 3475
      mg/m3), the lowest level tested, acute renal tubular necrosis was found in one
      out of four animals. No effects on histological, biochemical, and
      haematological parameters were seen in mice exposed to 1000 ppm (approx.
      1390 mg/m3) for up to 8 hours.
           In a well conducted, subacute inhalation experiment in mice, the target
      organ was the nasal cavity. Exposure to 1000 ppm (approx. 1390 mg/m3), the
      only level tested, for 4 weeks (6 hours/day, 5 days/week), resulted in
      inflammation of the nasal cavity as indicated by histological and
      haematological changes; these effects were not observed in mice exposed for 2
      weeks. These treatment regimes did not cause other histological, biochemical,
      or haematological changes.
           Silane was mutagenic in in vitro bacterial test systems. No other tests were
      available. Considering the positive results, the committee recommends to have
      more mutagenicity testing.
           The current occupational exposure limit of silicon tetrahydride has been
      based on the acute toxicity of germanium tetrahydride (which was based on
      comparisons with antimony hydride and arsenic hydride), viz, haemolyse in
      guinea pigs following 1-hour exposure (ACG91a, ACG91b). However, no such
      effects were found in mice singly or repeatedly exposed to silane vapours which
      makes the use of and comparison with the toxicity data of germanium
      tetrahydride questionable.
      The committee considers the toxicological data base of silane too poor to justify
      the recommendation of a health-based occupational exposure limit.
      The committee concludes that the (sub)acute animal data indicate that the
      present MAC-value of 0.7 mg/m3 (5 ppm), as an 8 h time weighted average
      (TWA), may be too low.
014-7 Silane
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<pre>       References
ACG91a American Conference of Governmental Industrial Hygienists (ACGIH). Silicon tetrahydride. In:
       Documentation of the threshold limit values and biological exposure indices. 6th ed. Cincinnati OH,
       USA: ACGIH, 1991; 1394-5.
ACG91b American Conference of Governmental Industrial Hygienists (ACGIH). Germanium tetrahydride In:
       Documentation of the threshold limit values and biological exposure indices. 6th ed. Cincinnati OH,
       USA: ACGIH, 1991; 702.
ACG00  American Conference of Governmental Industrial Hygienists (ACGIH). 2000 TLVs® and BEIs®.
       Threshold Limit Values for chemical substances and physical agents. Biological Exposure Indices.
       Cincinnati OH, USA: ACGIH, 2000.
Ara94  Araki A, Noguchi T, Kato F, et al. Improved method for mutagenicity testing of gaseous compounds by
       using a gas sampling bag. Mutat Res 1994; 307: 335-44.
Arb96  Arbejdstilsynet. Exposure limit values for substances and materials. Copenhagen, Denmark: The
       Working Environment Service; Instruction no. 3.1.0.2. 1996.
DFG99  Deutsche Forschungsgemeinschaft (DFG): Senatskommission zur Prüfung gesundheitsschädlicher
       Arbeitsstoffe. MAK- und BAT-Werte-Liste 1999. Maximale Arbeitsplatzkonzentrationen und
       biologische Arbeitsstofftoleranzwerte. Weinheim, FRG: VCH Verlagsgesellschaft mbH, 1999;
       Mitteilung 35.
HSE99  Health and Safety Executive (HSE). EH40/99. Occupational Exposure Limits 1999. Sudbury
       (Suffolk), England: HSE Books, 1999.
NBO96  National Board of Occupational Safety and Health. Occupational exposure limit values. Solna,
       Sweden: NBOSH, 1996; Ordinance AFS1996/2.
NIO97  National Institute of Occupational Safety and Health (NIOSH). Registry of Toxic Effects of Chemical
       Substances (RTECS) [CD-ROM], issue April 1997. SilverPlatter International, 1997 (last update
       silane file: January 1997).
NLM97  US National Library of Medicine (NLM). Hazardous Substances Data Bank (HSDB) [CD-ROM],
       issue April 1997. SilverPlatter International, 1997 (last update silane file: February 1997).
Oma92  Omae K, Sakai T, Sakurai H, et al. Acute and subacute inhalation toxicity of silane 1000 ppm in mice.
       Arch Toxicol 1992; 66: 750-3.
SZW00  Ministerie van Sociale Zaken en Werkgelegenheid (SZW). De nationale MAC-lijst 2000. The Hague,
       The Netherlands: Servicecentrum Sdu Uitgevers, 2000.
Tak93  Takebayashi T. Acute inhalation of high concentrations of silane in male ICR mice. Arch Toxicol
       1993; 67: 55-60.
TRG00  TRGS 900. [Grenzwerte in der Luft am Arbeitsplatz; Technische Regeln für Gefahrstoffe]. German. B
       A rb Bl. 2000; 2.
014-8  Health-based Reassessment of Administrative Occupational Exposure Limits
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<pre>             Annex
Occupational exposure standards for silane in various countries.
country                       occupational                   time-weighted        type of exposure notea lit refb
-organisation                 exposure limit                 average              limit
                              ppm           mg/m3
The Netherlands
-Ministry                     0.5           0.7              8h                   administrative         SZW00
Germany
-AGS                          -             -                                                            TRG00
-DFG MAK-Kom.                 -             -                                                            DFG99
Great-Britain
-HSE                          0.5           0.7              8h                   OES                    HSE99
                              1             1.5              15 min               STEL
Sweden                        -             -                                                            NBO96
Denmark                       0.5           0.7              8h                                          Arb96
USA
-ACGIH                        5             6.6              8h                   TLV                    ACG00
-OSHA                         5                              8h                   PEL
-NIOSH                        5             7                10 h                 REL
European Union
-SCOEL
a
     S = skin notation; which mean 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
014-9        Silane
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<pre>014-10 Health-based Reassessment of Administrative Occupational Exposure Limits</pre>

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<br><br>