<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>      Cyclopentane
      (CAS reg. nr: 287-92-3)
      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/002, The Hague, 14 December 2000
002-1
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<pre>      Preferred citation:
      Health Council of the Netherlands: Committee on Updating of Occupational
      Exposure Limits. Cyclopentane; Health-based Reassessment of Administrative
      Occupational Exposure Limits. The Hague: Health Council of the Netherlands,
      2000; 2000/15OSH/002.
      all rights reserved
002-2
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<pre>1     Introduction
      The present document contains the assessment of the health hazard of
      cyclopentane 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. (Coronel Institute of the
      Academic Medical Centre, Amsterdam, the Netherlands).
           Literature was retrieved from the data bases Medline and Chemical
      Abstracts, starting from 1966 and 1970, respectively, and using the following
      key words: cyclopentane, pentamethylene or 287-92-3. Also the CD-roms
      Poltox (from 1994 backwards), HSEline, Cisdoc, Mhidas and NIOSHtic (from
      1997 backwards) were consulted. Data considered to be critical were evaluated
      by reviewing the original publications. The final literature search has been
      carried out in December 1997.
           In March 2000, the President of the Health Council released a draft of the
      document for public review. The committee received no comments.
2     Identity
       name                                 :    cyclopentane
       synonyms                             :    pentamethylene
       molecular/structural formula         :    C5H10
       CAS reg nr                           :    287 - 92 - 3
3     Physical and chemical properties
       molecular weight                     :    70.2
       boiling point                        :    490C
       melting point                        :    -940C
       vapour pressure                      :    45 kPa
       solubility in water                  :    none
       log Poct/water                       :    7 (calculated)
       conversion factors                   :    1 ppm = 2.92 mg/m3
       (20oC, 101.3 kPa)                         1 mg/m3 = 0.34 ppm
      Data from IPC91.
002-3 Cyclopentane
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<pre>      Cyclopentane is a flammable colourless liquid with a mild sweet odour. The
      odour threshold is not known. The vapour is heavier than air and may travel
      along the ground, distant ignation is possible. As a result from flow, agitation,
      etc. electrostatic charges can be generated (IPC91).
4     Uses
      Cyclopentane is used mainly as a reagent in the laboratory. It is found in
      petroleum ether and other commercial solvents that are used as a fuel, in fat
      and wax extraction, in paints and in the shoe industry.
5     Biotransformation and kinetics
      Cyclopentane vapour can be absorbed into the body by inhalation (IPC91,
      Hat91, NIO94) and the fluid can be taken up by ingestion (NIO94). No
      quantitative data on the uptake is available. There is no information on the
      distribution, biotransformation, excretion and biological monitoring of
      cyclopentane.
          Pan et al. (Pan91) determined the levels of aliphatic hydrocarbons in blood
      of 85 chemically sensitive patients in the Department of Allergy in the Peking
      Union Medical College Hospital in Beijin, China, by using a purging trap
      method with gas chromatography/mass spectrometry. Thirteen patients had
      levels below the detection limit of less than 1 ppb and 72 were above the
      detection limit. The average level of cyclopentane was 9.0 ppb (0.026 mg/m3).
6     Effects and mechanism of action
      Human data
      There is no human data available on effects induced by exposure to
      cyclopentane exclusively. Most exposure incidents usually involved a mixture
      of hydrocarbons.
      Animal data
      There are very few animal data available. Brown et al. (Bro71) studied the
      influence of some alicyclic hydrocarbons on guinea pig skin. Applications were
      done on both flanks of each guinea pig with a volume of 2 ml per animal. After
002-4 Health-based Reassessment of Administrative Occupational Exposure Limits
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<pre>      exposure to cyclopentane the skin showed slight erythema and dry appearance
      by gross observation. The epidermis/dermis dry weight ratio between treated
      skin and control skin was 2.1. There were no changes in the activity of
      arginase on the skin. From this experiment the authors concluded that the
      effect on the skin due to cyclopentane exposure was minor relative to other
      alicyclic hydrocarbons with a higher number of C atoms.
          Cavender (Cav94) reported that inhalation exposure to 110 mg/m3 (38
      ppm) cyclopentane vapour induced minimal narcosis, loss of reflexes and
      lethality in mice. He cited this data from a study from Von Oetingen from 1940
      and commented on the low safety margin. On the other hand, Lazarew and
      Kremnewa in 1930 reported that cyclopentane vapour caused immediate
      anaesthesia in a concentration of 110,000 mg/m3, and mortality due to
      respiratory paralysis occurred much later (Laz30). Fang et al. (Fan96) recently
      studied the anaesthetic and convulsant properties of some compounds,
      including cyclopentane, in rats after inhalation. They reported that
      cyclopentane induced excitation (twitching, jerking and hyperactivity) at the
      level of 0.0026 atm blood partial pressure of the test compound. The MIC (the
      minimum inspired concentration required to suppress movement in response to
      stimulation) for cyclopentane was found to be 0.058 atm, and the MAC (the
      minimum alveolar anaesthetic concentration) was 0.053 atm. This study
      showed that the effects after inhalation exposure were excitation followed by
      anaesthesia.
          When ingested, cyclopentane presented a low to moderate aspiration hazard
      in mice (Ger63). It should be noted that the tendency of a substance to
      constitute an aspiration hazard to the lung depends primarily on its physical
      properties. The combination of two physical properties, low viscosity and low
      surface tension, increases the aspiration hazard of light hydrocarbons.
          Effects on the kidneys in rats have been reported by Bernard et al. (Ber89).
      They exposed female SD rats to cyclopentane by giving the animals 5
      intraperitoneal injections of 500 mg/kg bw per week for two weeks. The results
      showed an increase of ß2-microglobulin (geom. mean of 6.67 compared to 2.69
      g/24 h in the control group) and albumin concentrations (geom. mean of 556
      compared to 363 g/24 h in the control group) in the urine.
      No data on long-term exposure, mutagenicity, genotoxicity, carcinogenicity and
      reproduction toxicity have been found.
002-5 Cyclopentane
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<pre>7     Existing guidelines
      The current administrative occupational exposure limit (MAC) for
      cyclopentane in the Netherlands is 1720 mg/m3 (600 ppm), 8 h TWA.
          Existing occupational exposure limits for cyclopentane in some European
      countries and in the USA are summarized in the annex.
8     Assessment of health hazard
      From the available data the committee concludes that the target organs in the
      toxicity of cyclopentane are the central nervous system (CNS) and the kidneys.
          Different concentrations of exposure were reported in animal experiments
      with effects on the CNS. One study reported minimal narcosis, loss of reflexes
      and lethality in mice at a concentration of 110 mg/m3 (Cav94 cited from a
      study in 1940), on the other hand a study from 1930 reported anaesthesia and
      mortality in mice occurring at a level of 110,000 mg cyclopentane per m3
      (Laz30). Intraperitoneal injections of cyclopentane in rats at a dose of 1500
      mg/kg bw induced aberrations of the kidney function (Ber89). From these
      studies a no observed adverse effect level (NOAEL) can not be determined.
          No data on long-term exposure, genotoxicity, mutagenicity, carcinogenicity
      and reproduction toxicity have been found.
      The committee considers the toxicological data base on cyclopentane 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
ACG96 American Conference of Governmental Industrial Hygienists (ACGIH). TLVs and other occupational
      exposure values - 1996 (CD ROM, version 1.7-s4 02/01/95). Cincinnati OH, USA: ACGIH 1996.
ACG00 American Conference of Governmental Industrial Hygienists (ACGIH). 2000 TLVs and BEIs.
      Threshold limit values for chemical and physical agents. Biological Exposure Indices. Cincinnati OH,
      USA: ACGIH, 2000.
Arb96 Arbejdstilsynet. Exposure limit values for substances and materials. Copenhagen, Denmark: The
      Working Environment Service: Instruction no. 3.1.0.2. 1996.
002-6 Health-based Reassessment of Administrative Occupational Exposure Limits
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<pre>Ber89 Bernard AM, de Rusis R, Nordman J-C, Lauwerys RR. Evaluation of the subacute nephrotoxicity of
      cyclohexane and other industrial solvents in the female Sprague-Dawley rat. Toxicol Lett 1989; 45:
      271-80.
Bro71 Brown VKH, Box VL. The influence of some alicyclic hydrocarbons on the arginase activity of guinea
      pig skin. Br J Dermatol 1971; 85: 432-6.
Cav94 Cavender F. Alicyclic hydrocarbons. In:Patty's Industrial Hygiene and Toxicology, Fourth edition, Vol
      II, Part B., Clayton GD, Clayton FE, editors, New York: John Wiley and Sons Inc., 1994: 1267.
Fan96 Fang Z, Sonner J, Laster MJ, Ionescu P, Kandel L, Koblin DD et al. Anesthetic and properties of
      aromatic compounds and cycloalkanes: implications for mechanisms of narcosis. Anest Analg 1996;
      83: 1097-104.
Ger63 Gerarde HW. Toxicological studies on hydrocarbons. Arch Environ Health 1963; 6: 329-41.
Hat91 Hathaway GJ, Proctor NH, Hughes JP, Fischman ML, editors, In: Proctor and Hughes's Chemical
      hazards of the workplace, third edition, 1991, New York: Van Nostrand Reinhold, 1991: 202.
HSE99 Health and Safety Executive (HSE). EH40/99 Occupational Exposure Limits 1999. Sudbury (Suffolk),
      England: HSE Books, 1999.
IPC91 International Programme on Chemical Safety (IPCS)-European Communities. International Chemical
      Safety Cards. Cyclopentane. 1991: ICSC0353.
Laz30 Lazarew NW, Kremnewa SN. Bemerkungen uber die Giftigkeit der Dampfe des Zyklopentans und
      seiner Homologen. Arch Exp Pathol Pharmakol 1930; 149: 116-118.
NBO96 National Board of Occupational Safety and Health. Occupational exposure limit values. Solna,
      Sweden: NBOSH, 1996; Ordinance AFS1996/2.
NIO94 National Institute of Occupational Safety and Health (NIOSH). NIOSH Pocket Guide to Chemical
      Hazards 1994. US Dept Health & Human Services, Washington, 1994.
Pan91 Pan Y, Johnson AR, Rea WJ. Aliphatic hydrocarbon solvents in chemically sensitive patients. Bol Asoc
      Med P R. 1991; 83: 316-320 (abstract, cited from OSH CD-rom).
SZW00 Ministerie van Sociale zaken en Werkgelegenheid (SZW). Nationale MAC-lijst 2000. The Hague, the
      Netherlands: Servicecentrum SDU Uitgevers, 2000.
TRG00 TRGS 900: Grenzwerte in der Luft am Arbeitsplatz; Technische Regeln fur Gefahrstoffe; B Arb Bl
      2000; 2..
002-7 Cyclopentane
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<pre>             Annex
Occupational exposure limits for cyclopentane in various countries.
country                           occupational                     time-weighted   type of exposure   notea      lit refb
-organisation                     exposure limit                   average         limit
                                  ppm            mg/m3
The Netherlands
-Ministry                         600            1720              8h              administrative                SZW00
Germany
-AGS                              -              -                                                               TRG00
-DFG MAK-Kom.                     -              -                                                               DFG99
Great-Britain
-HSE                              -              -                                                               HSE99
Sweden                            -              -                                                               NBO96
Denmark                           300            850               8h                                            Arb96
USA
-ACGIH                            600            1720              8h              TLV                           ACG00
-OSHA                             -              -                 -
-NIOSH                            600            1720              10 h            REL
European Union
-SCOEL
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
002-8        Health-based Reassessment of Administrative Occupational Exposure Limits
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