<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>Tin(IV) oxide, tin(II) oxide
(CAS No: 18282-10-5, 21651-19-4)
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/091, The Hague, 22 October 2003
</pre>

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<pre>Preferred citation:
Health Council of the Netherlands: Committee on Updating of Occupational
Exposure Limits. Tin(IV) oxide, tin(II) oxide; Health-based Reassessment of
Administrative Occupational Exposure Limits. The Hague: Health Council of the
Netherlands, 2003; 2000/15OSH/091.
all rights reserved
</pre>

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<pre>1     Introduction
      The present document contains the assessment of the health hazard of tin oxide
      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 AAE Wibowo, Ph.D., and MM Verberk, Ph.D. (Coronel Institute,
      Academic Medical Centre, Amsterdam, the Netherlands).
           The evaluation of the toxicity of tin oxide has been based on the reviews
      published by the American Conference of Governmental Industrial Hygienists
      (ACG96) and the World Health Organization (WHO80) and in ‘The handbook
      on the toxicology of metals’ (Mag86). Where relevant, the original publications
      were reviewed and evaluated as will be indicated in the text. In addition, in May
      1998, literature was searched in the databases Medline, Embase, and Chemical
      Abstracts starting from 1996, 1998, and 1970, respectively. HSELINE, CISDOC,
      MHIDAS, and NIOSHTIC (covering the period 1985/1987 until 1998) as well as
      Poltox (Toxline, Cambridge Scient. Abstr., FSTA; covering the period 1990 until
      1995), databases available from CD-ROM, were also consulted. The following
      key words were used: tin oxide, stannic oxide, stannous oxide, 18282-10-5, and
      21651-19-4. The final literature search was carried out in Toxline and Medline in
      January 2003.
           In April 2003, the President of the Health Council released a draft of the
      document for public review. The committee received no comments.
2     Identity
      name                    :  tin (IV) oxide                      tin (II) oxide
      synonyms                :  tin dioxide; stannic oxide; stannic tin monoxide; tin protoxide; stannous
                                 anhydride; stannic dioxide; white   oxide
                                 tin oxide
      molecular formula       :  SnO2                                SnO
      structural formula      :  -                                   -
      CAS number              :  18282-10-5                          21651-19-4
091-3 Tin(IV) oxide, tin(II) oxide
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<pre>3     Physical and chemical properties
                              tin(IV) oxide               tin(II) oxide
      molecular weight        150.70                       134.70
                                         o
      boiling point           1800-1900 C (sublimes)       -
      melting point           1630oC                      at 60 kPa: 1080oC (decomposes)
      flash point             not available               not available
      vapour pressure         not available               not available
      solubility              insoluble                   insoluble
      log Poctanol/water      1.29 (estimated)            1.29 (estimated)
      conversion factors      not applicable              not applicable
      Data from Wea87; http://esc.syrres.com.
      Tin(IV) and tin(II) oxide are white or slightly grey and brown to black powders,
      respectively. Tin(IV) oxide occurs naturally as the mineral cassiterite.
      Commercial grades of tin(IV) oxide are also known as polishing powder, putty
      powder, or tin ash (Bud89).
4     Uses
      Tin(IV) oxide is used for polishing glass and metals, in manufacturing milk-
      coloured, ruby, and alabaster glass, enamels, pottery, and putty, as a mordant in
      printing and dyeing fabrics, and in fingernail polishes. Tin(II) oxide is used as a
      reducing agent and in the preparation of stannous salts (Bud89).
5     Biotransformation and kinetics
      There is very little data on the absorption of inhaled tin oxide dust particles, but
      tin levels in the lungs are reported to be elevated by exposure to tin oxide
      (Rob61). Inorganic tin is very poorly absorbed through the digestive tract; it is
      estimated to be less than 5% (WHO80). WHO estimated the mean total daily
      intake of tin by man to range from 0.2 to 17 mg. A diet consisting of fresh foods
      probably provided about 1 to 4 mg/day. The likely daily intake from water was
091-4 Health-based Reassessment of Administrative Occupational Exposure Limits
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<pre>      estimated to be less than 30 g/day, and the daily amount entering the body from
      air, less than 1 g (WHO80).
           The absorption through the digestive tract depends on the oxidation state of
      tin: tin (II) is more readily absorbed than tin (IV). The anion complement may
      also influence the rate of absorption (WHO80). When absorbed through the
      digestive tract, tin leaves the vascular system rapidly. Baselt and Cravey reported
      that the average concentration of tin in the blood of normal subjects is 0.14 mg/L,
      that it resides primarily in the erythrocytes, and that it is believed to originate
      from the diet (Bas89). According to the WHO, bone is the main site of
      deposition, and the highest concentrations of tin are found in the lungs, kidneys,
      liver, and bone (levels not reported) (WHO80). Schroeder et al. reported that tin
      was found in almost every tissue they analysed in American adults, the intestinal
      tract containing the highest concentrations. Median concentrations (in dry ash)
      found were 18 mg/kg in the oesophagus, 16 mg/kg in the stomach, 28 mg/kg in
      the duodenum, 36 mg/kg in the jejunum, 79 mg/kg in the ileum, 130 mg/kg in the
      caecum, 45 mg/kg in the sigmoid colon, and 57 mg/kg in the rectum. In lungs,
      adrenals, and liver, median concentrations were 37, 23, and 23 mg/kg,
      respectively. Tin was seldom detected in the brain or muscle (Sch64). Magos
      stated that the biological half-life of inorganic tin in bone is about 400 days, both
      in man and in animals. Penetration of the blood-brain barrier and placenta
      appears to be very slight. With the exception of the lungs, inorganic tin does not
      accumulate in the soft organs with increasing age (Mag86).
           Inorganic tin is mainly excreted in the urine. The fraction excreted with the
      bile varies with the type of compound and is probably below 15% (WHO80).
      The tin concentrations in the urine of Americans have been estimated to average
      0.023 mg/L, with a range from 0-0.040 mg/L (Bas89).
           The committee concludes that respirable tin oxide dusts is very poorly
      absorbed through the lungs, most probably due to its insolubility in water.
6     Effects and mechanism of action
      Human data
      There is no epidemiological data available. Various case-reports on effects due to
      occupational exposure to tin oxide have been published. Long-term occupational
      exposure by inhalation to tin oxide aerosols results in accumulation of the
      compound in the lung tissues, since it is poorly absorbed. This means that the
      lungs are the target organ.
091-5 Tin(IV) oxide, tin(II) oxide
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<pre>          The clinical picture in the lungs has been called benign pneumoconiosis
      (Cut49, Dun50, Pen48, Rob49, Rob61, Spen54, Zor66). The diagnosis was
      mostly based on chest X-rays. In some cases, the patients were asymptomatic
      with normal lung functions (Cut49, Zor66). Dundon and Hughes described a
      case of a 72-year-old man who complained of constant lower abdominal pain
      during 2 weeks, nocturia, and a rapid loss of body weight. Occupational history
      of the patient showed that he had been working for 18 years near a de-tinning
      furnace, in which tin oxide was recovered from tin scrap by a calcining process.
      He did not have any symptoms of respiratory disease during his working life.
      Nine years after his last exposure, he was admitted to a hospital because of
      epigastric pain and vomiting. A chest roentgenogram showed a ‘peculiar
      widespread mottling of both lung fields by discrete shadows’. There were no
      respiratory complains. The vital capacity of the lungs was 85% of normal value
      (Dun50).
          Robertson et al. examined the lungs of 7 deceased subjects who had been
      employed in the tin-melting industry using chemical and X-ray-diffraction
      analysis and X-ray-emission spectroscopy. They found evidence of
      pneumoconiosis with nodular opacities, each about 3 to 5 mm in size, in 6 of the
      subjects. Macroscopic examination of the lung tissues showed black or dark dust
      foci, 2 to 5 mm in size and distributed uniformly. No silicotic or fibrous nodules
      were seen. Microscopically, the dust foci consisted of dense aggregates of dust-
      laden macrophages surrounding the respiratory bronchioles. Sometimes, the dust
      deposition was more extensive and it surrounded the entire length of the terminal
      non-respiratory bronchiole. A few dust-laden cells were seen lying free in the
      alveoli. Chemical analysis and X-ray-diffraction analysis showed that the lungs
      contained tin oxide. X-ray-emission microanalysis identified the tin in the lung
      phagocyte (Rob61).
          More recently, Sluis-Cremer et al. argued whether this form of abnormality
      could be called pneumoconiosis at all, since no tissue reaction of any kind was
      found. They reported 2 cases in which both subjects showed moderately profused
      small nodules on radiographic examination of the chest. One subject had been
      employed in a tin mine for 26 years. He was free of symptoms and credited as
      clinically normal. The other subject had been employed in a de-tinning plant for
      15 years with minor complaints of productive cough, and basal crackles were
      present on auscultation. The forced expired vital capacity (FVC) of the lungs was
      90% and the one-second forced expiratory volume (FEV1) 96% of predicted
      values. Lung biopsy of this patient showed focal aggregations of macrophages
      containing blackish dust particles in some of the air spaces and in the
      perivascular and peribronchial connective tissue. There was a slight increase of
091-6 Health-based Reassessment of Administrative Occupational Exposure Limits
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<pre>      perivascular and peribronchial connective tissue, but the dust deposits in the air
      spaces were not associated with reticulin or collagen deposition. Electron
      microscopy analysis displayed tin to be present in the dust. Exposure levels were
      not reported (Slu89).
      Animal data
      The committee did not find experimental animal data on the potential irritation or
      sensitisation of the tin oxides.
           Schafer and Bowles reported an oral LD50 of 775 mg/kg bw for tin(II) oxide
      in deer mice (Sch85).
           De Groot et al. claimed that there were marked differences in the toxicity of
      various oxides and salts of tin in rats when given by oral administration. In their
      experiments, groups of rats (Wistar; n=10/sex/group) were fed diets containing 0,
      0.03, 0.10, 0.30, or 1.00% of various tin salts or oxides for periods of either 4 or
      13 weeks. Animals received tin(II) and tin(IV) oxide for 13 and 4 weeks,
      respectively. Effects on behaviour, mortality, body weights, food consumption,
      blood, urine, and biochemical parameters, and organ weights were examined and
      gross and microscopic examinations were performed. No adverse effects were
      noted at any dose of both tin oxides, as well as stannous sulphide and oleate.
      However, severe growth retardation, decreased food efficiency, slight anaemia,
      and slight histological changes in the liver were observed with 0.3% or more of
      stannous chloride, orthophosphate, sulphate, oxalate, and tartrate. The authors
      concluded that the differences in response to different tin compounds suggested
      that insoluble tin compounds are relatively harmless substances whereas cationic
      tin compounds soluble in water or dilute acid may be toxic at dietary levels
      above 0.1% (Gro73). From these studies, the committee concludes that dietary
      exposure to levels of tin(II) and tin(IV) oxide up to 1% for 13 and 4 weeks,
      respectively, did not induce any effect in rats. From data on initial body weight,
      body weight gain, and total food intake of animals exposed to tin(IV) oxide in
      the 4-week experiment with tin(IV) oxide and from data on body weight and
      food intake of control animals during the several time points in the 13-week
      study with tin(II) oxide*, the committee estimates that the daily intakes may have
      been about 700-850 mg tin per kg bw.
      The committee did not find data on long-term exposure by inhalation or on
      carcinogenicity, mutagenicity/genotoxicity, and reproduction toxicity.
*     For the 13-week study, only data on animals exposed to tin(II) chloride and control animals were presented.
091-7 Tin(IV) oxide, tin(II) oxide
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<pre>7     Existing guidelines
      The current administrative occupational exposure limit (MAC) for tin oxide in
      the Netherlands is 2 mg/m3, 8-hour TWA .
          Existing occupational exposure limits for tin oxide in some European
      countries and in the USA are summarised in the annex.
8     Assessment of health hazard
      The tin oxides are poorly absorbed from the respiratory and intestinal tract
      resulting in little systemic toxicity.
          Numerous cases of workers occupationally exposed to tin oxide dusts,
      aerosols, or fumes have shown that these can produce a benign pneumoconiosis,
      called stannosis, which is characterised by small dense shadows in the
      pulmonary X-ray picture. However, no fibrosis or impairment of lung function is
      observed. The committee did not find human data on exposure-response
      relationships.
          With respect to experimental animal data on tin oxides, the committee only
      found an oral study in which rats were given tin(II) and tin(IV) oxide in their
      diets for 13 and 4 weeks, respectively. At the maximum dose level tested of 1%,
      estimated to be about 700-850 mg tin/kg bw/day, no effects were observed.
      The committee considers the toxicological database on tin (IV) and tin (II) oxide
      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.
091-8 Health-based Reassessment of Administrative Occupational Exposure Limits
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<pre>       References
ACG96  American Conference of Governmental Industrial Hygienists (ACGIH). Tin. In: TLVs® and other
       occupational exposure values - 1996. [CD-ROM]. Cincinnati OH, USA: ACGIH®, Inc, 1996.
ACG03a American Conference of Governmental Industrial Hygienists (ACGIH). Guide to occupational
       exposure values - 2003. Cincinnati OH, USA: ACGIH®, Inc, 2003: 130.
ACG03b American Conference of Governmental Industrial Hygienists (ACGIH). 2003 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®, Inc, 2003: 56.
Arb02  Arbejdstilsynet. Grænseværdier for stoffer og materialer. Copenhagen, Denmark: Arbejdstilsynet,
       2002: 38 (At-vejledning C.0.1).
Bas89  Baselt RC, Cravey RH. Tin. In: Disposition of toxic drugs and chemicals in man. 3rd ed. Chicago IL,
       USA: Year Book Medical Publ, Inc, 1989.
Bud89  Budavari S, O’Neil MJ, Smith A, et al. The Merck index. An encyclopedia of chemicals, drugs, and
       biologicals. 11th ed. Rahway NJ, USA: Merck & Co, Inc, 1989: 1384, 1385.
Cut49  Cutter HC, Faller WW, Stocklen JB, et al. Benign pneumoconiosis in a tin oxide recovery plant. J Ind
       Hyg Toxicol 1949; 31: 139-41.
DFG02  Deutsche Forschungsgemeinschaft (DFG): Commission for the Investigation of Health Hazards of
       Chemical Compounds in the Work Area. List of MAK and BAT values 2002. Maximum
       concentrations and biological tolerance values at the workplace. Weinheim, FRG: Wiley-VCH,
       2002: 104 (rep no 38).
Dun50  Dundon CC, Hughes JP. Stannic oxide pneumoconiosis. Am J Roentgenol Radium Ther Nucl Med
       1950; 63: 797-812.
EC03   European Commission: Directorate General of Employment and Social Affairs. Occupational
       exposure limits (OELs). http://europe.eu.int/comm/employment_social/h&s/areas/oels_en.htm.
Gro73  De Groot AP, Feron VJ, Til HP. Short-term toxicity studies on some salts and oxides of tin in rats.
       Food Cosmet Toxicol 1973; 11: 19-30.
HSE02  Health and Safety Executive (HSE). EH40/2002. Occupational Exposure Limits 2002. Sudbury
       (Suffolk), England: HSE Books, 2002: 27.
Mag86  Magos L. Tin. In: Friberg F, Nordberg GF, Vouk VB, eds. Handbook on the toxicology of metals. 2nd
       ed. Amsterdam, the Netherlands: Elsevier, 1986: 568-93 (Vol II).
Pen48  Pendergrass EP, Pryde AW. Benign pneumoconiosis due to tin oxide. J Ind Hyg Toxicol 1948; 30:
       119-23.
Rob49  Robertson AJ, Whitaker PH. Radiological changes in pneumoconiosis due to tin oxide. J Fac Radiol
       1949; 6: 224-33.
Rob61  Robertson AJ, Rivers D, Nagelschmidt G, et al. Benign pneumoconiosis due to tin oxide. Lancet
       1961; i: 1089-93.
091-9  Tin(IV) oxide, tin(II) oxide
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<pre>Sch85  Schafer EW Jr, Bowles WA Jr. Acute oral toxicity and repellency of 933 chemicals to house and deer
       mice. Arch Environ Contam Toxicol 1985; 14: 111-29.
Sch64  Schroeder HA, Balassa JJ, Tipton IH. Abnormal trace metals in man: tin. J Chronic Dis 1964; 17:
       483-502.
Slu89  Sluis-Cremer GK, Thomas RG, Goldstein B, et al. Stannosis. A report of 2 cases. S Afr Med J 1989;
       75: 124-6.
Spe54  Spencer GE, Wycoff WC. Benign tin oxide pneumoconiosis. AMA Arch Ind Hyg Occup Med 1954;
       10: 295-7.
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, 200; Ordinance AFS 2000:3.
SZW03  Ministerie van Sociale Zaken en Werkgelegenheid (SZW). Nationale MAC-lijst 2003. The
       Hague, the Netherlands: Sdu, Servicecentrum Uitgevers, 2003: 41.
TRG00  TRGS 900. Grenzwerte in der Luft am Arbeitsplatz; Technische Regeln für Gefahrstoffe. BArbBl
       2001; 2.
Wea87  Weast RC, ed. CRC handbook of chemistry and physics. 68th ed. Boca Raton FL, USA: CRC Press,
       Inc, 1987: B-140.
WHO80  World Health Organization: International Programme on Chemical Safety (WHO/IPCS). Tin and
       organotin compounds. A preliminary review. Geneva, Switzerland: WHO, 1980; Environmental
       Health Criteria 15.
Zor66  Zorn O. Barytose und Zinnoxidelunge. Zentralbl Arbeitsmed 1966; 16: 133-5.
091-10 Health-based Reassessment of Administrative Occupational Exposure Limits
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<pre>              Annex
Occupational exposure limits for tin oxides in various countries.
country                              occupational              time-weighted       type of           noteb        referencec
- organisation                       exposure limita           average             exposure limit
                                     ppm           mg/m3
the Netherlands
- Ministry of Social Affairs and     -             2d          8h                  administrative                 SZW03
Employment
Germany
- AGS                                -             2e, f       8h                                                 TRG00
                                     -             8e, f       15 min
- DFG MAK-Kommission                 -             -g                                                             DFG02
Great Britain
- HSE                                -             2e          8h                  OES                            HSE02
                                     -             4e          10 min
Sweden                               -             -                                                              Swe00
Denmark                              -             2e          8h                                                 Arb02
USA
- ACGIH                              -             2h          8h                  TLV                            ACG03b
- OSHA                               -             -                                                              ACG03a
- NIOSH                              -             2           10 h                REL                            ACG03a
European Union
- SCOEL                              -             -                                                              EC03
a
     As tin.
b
     S = skin notation, which means that skin absorption may contribute considerably to body burden; sens = substance can
     cause sensitisation.
c
     Reference to the most recent official publication of occupational exposure limits.
d
     Holds for tin (IV) oxide.
e
     Holds for inorganic tin compounds (except, in most cases, tin hydride (SnH4)).
f
     Inhalable dust.
g
     Listed among substances for which studies of the effects in man or experimental animals had yielded insufficient
     information for the establishment of MAK values.
h
     Holds for oxides and inorganic compounds, except tin hydride (SnH4).
091-11        Tin(IV) oxide, tin(II) oxide
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<pre>091-12 Health-based Reassessment of Administrative Occupational Exposure Limits</pre>

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<br><br>