<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
</pre>

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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>      Methanethiol
      (CAS reg. nr 74-93-1)
      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/008, The Hague, 14 December 2000
008-1
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<pre>      Preferred citation:
      Health Council of the Netherlands: Committee on Updating of Occupational
      Exposure Limits. Methanethiol; Health-based Reassessment of Administrative
      Occupational Exposure Limits. The Hague: Health Council of the Netherlands,
      2000; 2000/15OSH/008.
      all rights reserved
008-2
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<pre>1     Introduction
      The present document contains the assessment of the health hazard of
      methanethiol 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 MA Maclaine Pont, M.Sc. (Wageningen
      University, the Netherlands).
            Literature was retrieved from the data bases Medline, Toxline and
      Chemical Abstracts covering the periods 1966 until February 1998, 1981 until
      October 1997 and 1937 until December 1997, respectively, and using the
      following key words: methanethiol (and isotopic compounds), methyl
      mercaptan or 74-93-1. Data considered to be critical were evaluated by
      reviewing the original publications. The final literature search has been carried
      out in February 1998, followed by an additional search in May 1999.
           In December 1998, the President of the Health Council released a draft of
      the document for public review. Comments were received by the following
      individuals and organizations: dr P Wardenbach (Bundesanstalt für
      Arbeitsschutz und Arbeitsmedizin, Dortmund, Germany). These comments
      were taken into account in deciding on the final version of the document.
2     Identity
       name                              :    methanethiol
       synonyms                          :    mercaptomethane
                                              methylmercaptan
                                              methyl mercaptan
                                              methyl sulfhydrate
                                              thiomethanol
                                              thiomethyl alcohol
       CAS reg nr                        :    74-93-1
       molecular formula                 :    CH3SH
      Data from ACG91, How92.
008-3 Methanethiol
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<pre>3     Physical and chemical properties
       molecular weight                   :     48.11
       melting point                      :     -123°C
       boiling point                      :     5.9°C
       vapour pressure                    :     20°C: > 1 kPa
       odour threshold                    :     0.0032 mg/m3
                                                0.00004 - 0.082 mg/m3
       flash point (open cup)             :     -17.8 °C
       explosive limits                   :     3.9 - 21.8 vol% in air
       solubility in water                :     20°C: 23.3 g/l
       log Poct/water                     :     not found
       conversion factors                 :     1 mg/m3 = 0.50 ppm
       (20 °C, 101.3 kPa)                       1 ppm = 2.00 mg/m3
      Data from Amo83, Lid96, Rut86.
      Methanethiol is a colourless gas with a very disagreeable odour, described as
      that of rotten cabbage. The gas is heavier than air and spreads over the floor
      with a chance of ignition from a distance. Combustion of the product results in
      toxic gases. It reacts vigorously with oxidants, with a chance of fire and
      explosion. It reacts with acids, forming toxic and flammable gas (hydrogen
      sulphide). It reacts with light metals (NIA98).
4     Uses
      Methanethiol is used to give odour to natural gas and in the synthesis of
      methionine. It is also employed as an intermediate in the production of
      pesticides, fungicides, jet fuel, and plastics. In addition, it may be encountered
      as a by-product in the operations of paper and pulp mills (ACG86, ACG91).
5     Biotransformation and kinetics
      Metabolic studies have been performed with radiolabeled methanethiol
      intraperitoneally injected in the rat. Both the carbon (14C) and the sulphur (35S)
      of the methanethiol were rapidly oxidized to carbon dioxide and sulphate,
      respectively. In the first hour after the injection 29.2% of the dose was exhaled
008-4 Health-based Reassessment of Administrative Occupational Exposure Limits
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<pre>      as CO2. In the first eight hours after the injection 32% of the dose was found in
      the urine as sulphur compounds. Further the methyl moiety was incorporated in
      the methyl groups of methionine, choline and creatine. The sulphur moiety was
      not incorporated in methionine or cysteine (Can53).
          Other investigators established the half-life time for the metabolism of
      methanethiol into sulphate. After a single intra peritoneal injection into rats the
      t½ was 1.21 hour. The t½ for the elimination of sulphate in the urine was 8.47
      hour (Der84).
          Methanethiol could be detected in exhaled air (0.04 to 0.10 mg/m3) of
      persons exposed to high concentrations of methanethiol (concentration is not
      reported; probably more than 20 mg/m3). After exposure to lower
      concentrations of a combination of methanethiol, hydrogen sulphide and
      dimethylsulphide, dimethylsulphide is detected in exhaled air. After exposure
      to 11.3 ppm sulphides the concentration of dimethylsulphide in exhaled air was
      0.62 ppm. The authors suggest that the method can be used to assess recent
      exposure to a mixture of sulphide compounds (Jäp93).
6     Effects and mechanism of action
      Human data
      Low level symptoms of exposure to methanethiol are eye and mucous
      membrane irritation, dizziness, staggering gait, nausea, and vomiting.
      Respiratory tract irritation may lead to pulmonary oedema and hepatic and
      renal damage (ACG91).
          Workers (n=29) in the digest area of a pulpmill, where woodchips are
      'digested' into carbohydrates, had a higher incidence of chest illness than a
      control group of 310 railroad workers (missed work at least 1 week during the
      past three years, 36.3% vs. 14.8% in the control group, p < 0.05). The exposure
      was mainly to methanethiol, with a maximum concentration of 15.0 ppm (30
      mg/m3) and a mean of 1.4 ppm (2.8 mg/m3), calculated as an 8 h time weighted
      average (TWA). Lower concentrations of SO2 were present (mean 0.5 ppm) in
      less sites than methanethiol. The measuring time is not given. Spirometric
      values of these workers were not different from those of the control group, nor
      after correction for smoking (Ena84). However, the committee considers that
      the parameter studied (absenteeism because of alleged disease) did not really
      reflect chest illness, further chest illness was not well defined, and thirdly, the
      effects cannot be unequivocally ascribed to methanethiol.
008-5 Methanethiol
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<pre>          Another group of workers (n=17) in a pulpmill was exposed to a mixture of
      methanethiol (0.07 - 2.0 ppm, 0.14 - 4.0 mg/m3), hydrogen sulphide (0.05 - 5.2
      ppm), and dimethylsulphide (0.03 - 3.2 ppm, calculated as a 8 h TWA). There
      are no further data as to how the measurements were performed. The number
      of complaints (subjective symptoms) among the workers was comparable to
      that of a control group (n=50). However, the average annual number of days on
      sick leave of the workers tended to be higher (12.9 against 7.1 days, no
      statistical calculation). The activity of delta-aminolaevulinic acid synthase and
      haem synthase in blood was decreased in 8 and 6 cases, respectively (in the
      table the investigators presented only 5 cases instead of 6, who are below the
      range of the control values). No statistical calculation was performed (Ten83).
      Since the workers were exposed to a mixture of compounds, the committee
      concludes that the effects found cannot be ascribed to methanethiol alone.
          A 53-year old Negro labourer was hospitalized because of coma appearing
      shortly after exposure to methanethiol. There are no data on the exposure
      concentration and duration. Acute, severe haemolytic anaemia and
      methaemoglobinaemia developed: both were brief in duration. The likely
      mechanism of the haemolysis was an oxidant effect of methanethiol in a person
      deficient in erythrocyte glucose-6-phosphate dehydrogenase. Deep coma
      persisted until death 28 days after exposure to the chemical agents. The
      immediate cause of death was pulmonary embolism (Shu70).
          Inhabitants of areas in the neighbourhood of paper mills were studied for
      respiratory and other symptoms. The highly polluted areas had concentrations
      of 2 - 5 µg/m 3 methanethiol as an annual mean; the highest daily average
      concentration was 50 µg/m 3. The concentrations were estimated from a
      computer simulation model, no measurement data were reported. The residents
      were also exposed to hydrogen sulphide (respectively 8 and 100 µg/m 3) and to
      low concentrations of sulphur dioxide. The complaints of the residents from
      severely polluted areas were compared with those from moderately polluted and
      nonpolluted areas. The Odds Ratio for eye and nasal symptoms and for cough
      during the previous 12 months were significantly increased in the severely
      polluted areas, compared with the control group. For these symptoms and for
      breathlessness or wheezing and for headache, there was a dose-related increase
      in Odds Ratio for having experienced symptoms often or constantly. Only for
      eye symptoms in residents from moderately polluted areas the increase was
      statstically significant (Jaa90). It can be concluded that adverse health effects
      occur after exposure to malodorous sulphur compounds at levels considerably
      lower than reported previously by other authors, and also at levels lower than
008-6 Health-based Reassessment of Administrative Occupational Exposure Limits
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<pre>      the current Dutch MAC values (for methanethiol 1 mg/m3, for hydrogen
      sulphide 15 mg/m3). The observed exposure to hydrogen sulphide was
      considerably lower than the current WHO standard (150 µg/m 3 for 24 h mean).
      However, the committee considers it questionable to ascribe the effects to
      methanethiol, because it is not the only compound to which the inhabitants
      were exposed.
      Animal data
      The acute toxicity of methanethiol in animals after short-term exposure is
      moderate: the LC50 for rats is 1350 mg/m3, for mice the LC50 is 6.53 mg/m3
      (Lew92).*
            Observations from one rat, exposed to 20,000 mg/m3 methanethiol, indicate
      that it affected the respiration, and stopped it altogether after 14 min of
      exposure. Autopsy revealed small bleedings in the lungs and alveoli filled with
      erythrocytes (Lju43).
            Groups of 31 male Sprague Dawley rats were exposed to 0, 2, 17 and 57
      ppm (4, 34, and 114 mg/m3), for 7 hours/day, 5 days/week for 3 months. After
      three months there was a concentration-related decrease of the body weight,
      which was significant in the high-dose group. No effects were observed in
      organ weights and clinical chemistry parameters (Tan81). It can be concluded
      that the NOAEL for subchronic exposure in rats is 34 mg/m3. However, the
      nose was not examined for possible local effects.
      No data on long-term exposure, mutagenicity, genotoxicity, carcinogenicity
      and reproduction toxicity have been found.
7     Existing guidelines
      The current administrative occupational exposure limit (MAC) for
      methanethiol in the Netherlands is 0.5 ppm (1 mg/m3), 8 h TWA.
            Existing occupational exposure limits for methanethiol in some European
      countries and in the USA are summarized in the annex.
*     There must be an error in one of these data, then it is not expected that there is a 200-fold species difference between
      rats and mice.
008-7 Methanethiol
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<pre>8     Assessment of health hazard
      At high concentrations methanethiol affects respiration both in humans and
      animals, leading ultimately to death (Shu70, Lju43). At lower concentrations
      respiratory irritation is observed, together with eye and skin irritation
      (ACG91). Local irritation of the respiratory tract seems to be the critical effect.
      However, the human studies available describe effects after exposure to a
      mixture of compounds, and the animal study did not include the local effects.
      The no observed adverse effect level (NOAEL) found in the subchronic animal
      study was 34 mg/m3 and concerned a decrease in body weight (Tan81).
           It is expected that after inhalation of methanethiol the compound is totally
      resorbed and to a large extent metabolized. A small fraction is exhaled
      unchanged (Jäp93).
           No data on long-term exposure, mutagenicity, genotoxicity, carcinogenicity
      and reproduction toxicity have been found.
      The committee considers the toxicological data base on methanethiol too poor
      to justify recommendation of a health-based occupational exposure limit.
      Regarding the available animal data the committee has no reason to suspect
      that the current MAC value of 1 mg/m3 (0.5 ppm), 8 hour time weighted
      average (TWA) is too high. This concentration is also well above the reported
      odour thresholds.
      References
ACG86 American Conference of Governmental Industrial Hygienists (ACGIH). Documentation of the threshold
      limit values and biological exposure indices. 5th ed. Cincinnati, Ohio, USA: ACGIH, 1986; 405.
ACG91 American Conference of Governmental Industrial Hygienists (ACGIH). Documentation of the threshold
      limit values and biological exposure indices. 6th ed. Cincinnati, Ohio, USA: ACGIH, 1991; 1026-8.
ACG00 American Conference of Governmental Industrial Hygienists (ACGIH). Guide to occupational
      exposure values -2000. Cincinnati, Ohio, USA: ACGIH, 2000.
Amo83 Amoore JE, Hautala E. Odor as an aid to chemical safety: odor thresholds compared with Threshold
      Limit Values and volatilities for 214 industrial chemicals in air and water dilution. J Appl Toxicol
      1983; 3: 272-90.
Arb96 Arbejdstilsynet. Exposure limit values for substances and materials. Copenhagen, Denmark: The
      Working Environment Service; Instruction no. 3.1.0.2. 1996.
008-8 Health-based Reassessment of Administrative Occupational Exposure Limits
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<pre>Can53 Canellakis ES, Tarver H. The metabolism of methylmercaptan in the intact animal. Arch Biochem
      Biophys 1953; 42: 446-55.
Der84 Derr RF, Draves K. The time course of methanethiol in the rat. Res Commun Chem Pathol Pharmacol
      1984; 46: 363-9.
DFG99 Deutsche Forschungsgemeinschaft (DFG). List of MAK and BAT values 1999. Commission for the
      investigation of health hazards of chemical compounds in the work area. Weinheim, Germany: VCH
      Verlagsgesellschaft mbH, 1999. Report nr. 35.
Ena84 Enarson DA, Maclean L, Dybuncio A, et al Respiratory health at a pulpmill in British Columbia. Arch
      Environ Health 1984; 39: 325-30.
HSE99 Health and Safety Executive (HSE). Occupational exposure limits 1999. Sudbury, England: HSE
      Books, 1999; Guidance note EH 40/99.
How92 Howard PH, Neil M, ed. Dictionary of chemical names and synonyms. Chelsea, USA: Lewis
      Publishers, 1992.
Hun97 Hunter WJ, Aresini G, Haigh R, et al Occupational exposure limits for chemicals in the European
      Union. Occup Environ Med 1997; 54: 217-22.
Jaa90 Jaakkola JJK, Vilkka V, Marttila O, et al The South Karelia air pollution study; the effects of
      malodorous sulfur compounds from pulp mills on respiratory and other symptoms. Am Rev Respir Dis
      1990; 142: 1344-50.
Jäp93 Jäppinen P, Kangas J, Silakoski L, et al Volatile metabolites in occupational exposure to organic sulfur
      compounds. Arch Toxicol 1993; 67: 104-6.
Lew92 Lewis sr RJ, ed. Sax's dangerous properties of industrial materials. 8th ed. New York, USA: Van
      Nostrand Reinhold, 1992: 2338-9.
Lid96 Lide DR, Frederiks HPR, ed. CRC Handbook of chemistry and physics. 77th ed. Boca Raton, USA:
      CRC Press, 1996; 3-207.
Lju43 Ljunggren G, Norberg B. On the effect and toxicity of dimethyl sulfide, dimethyl disulfide and methyl
      mercaptan. Acta Physiol Scand 1943; 5: 248-55.
NBO96 National Board of Occupational Safety and Health. Occupational exposure limit values. Solna,
      Sweden: NBOSH, 1996; 2: Ordinance AFS 1996/2.
Rut86 Ruth JH. Odor thresholds and irritation levels of several chemical substances: a review. Am Ind Hyg
      Assoc J 1986; 47: A142-51.
Shu70 Shults WT, Fountain EN, Lynch EC. Methanethiol poisoning; irreversible coma and hemolytic anemia
      following inhalation. J Am Med Assoc 1970; 211: 2153-4.
SZW00 Ministerie van Sociale Zaken en Werkgelegenheid (SZW): Arbeidsinspectie. [De nationale MAC-lijst
      2000]. Dutch. The Hague, the Netherlands: Sdu Servicecentrum Uitgeverijen, 2000.
Tan81 Tansy MF, Kendall FM, Fantasia J, e.d. Acute and subchronic toxicity studies of rats exposed to vapors
      of methyl mercaptan and other reduced-sulfur compounds. J Toxicol Environ Health 1981: 8: 71-88.
Ten83 Tenhunen R, Savolainen H, Jäppinen. Changes in haem synthesis associated with occupational
      exposure to organic and inorgani sulphides. Clin Sci 1983; 64: 187-91.
008-9 Methanethiol
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<pre>TRG00  TRGS 900. [Grenzwerte in der Luft am Arbeitsplatz; Technische Regeln für Gefahrstoffe]. German. B
       Arb Bl. 2000; 2.
008-10 Health-based Reassessment of Administrative Occupational Exposure Limits
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<pre>             Annex
Occupational exposure standards for methanethiol 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           1                 8h                  administrative                    SZW00
Germany
-AGS                            0.5           1                 8h                  administrative                    TRG00
-DFG MAK-Kom.                   0.5           1                 8h                  MAK                               DFG99
Great-Britain
-HSE                            0.5           1                 8h                  OES                               HSE99
Sweden                          1c                              8h                  level limit value                 NBO96
Denmark                         0.5           1                 8h                                                    Arb96
USA
-ACGIH                          0.5           0.98              8h                  TLV                               ACG00
-OSHA                           10            20                -                   ceiling
-NIOSH                          0.5           1                 15 min              ceiling; STEL
European Union
-SCOEL                          -             -                                                                       Hun97
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
c
     the limit value 1 ppm applies to the sum total of concentrations of dimethyl disulfide, dimethyl sulfide and methyl
     mercaptan
008-11       Methanethiol
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<pre>008-12 Health-based Reassessment of Administrative Occupational Exposure Limits</pre>

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<br><br>