<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>      Dipropyl ketone
      (CAS reg. nr: 123-19-3)
      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/005, The Hague, 14 December 2000
005-1
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<pre>      Preferred citation:
      Health Council of the Netherlands: Committee on Updating of Occupational
      Exposure Limits. Dipropyl ketone; Health-based Reassessment of
      Administrative Occupational Exposure Limits. The Hague: Health Council of
      the Netherlands, 2000; 2000/15OSH/005.
      all rights reserved
005-2
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<pre>1     Introduction
      The present document contains the assessment of the health hazard of dipropyl
      ketone 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, Current Contents,
      Embase and Chemical Abstracts, starting from 1966, 1970, 1988 and 1970,
      respectively, and using the following key words: dipropyl ketone, propyl
      ketone, heptanone, butyrone, or 123-19-3. Also 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. Comments were received by the following
      individuals and organizations: A Aalto (Ministry of Social Affairs and Health,
      Tampere, Finland), 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                              :     dipropyl ketone
       synonyms                          :     propyl ketone
                                               4-heptanone
                                               butyrone
                                               heptan-4-one
       molecular formula                 :     C7H14O
       structural formula                :     CH3CH2CH2COCH2CH2CH3
       CAS reg nr                        :     123 - 19 - 3
005-3 Dipropyl ketone
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<pre>3     Physical and chemical properties
       molecular weight                 :     114.2
       boiling point                    :     143.70C
       melting point                    :     -32.60C
       vapour pressure                  :     0.73 kPa
       solubility in water              :     insoluble
       log Poct/water                   :     not known
       conversion factors               :     1 mg/m3 = 0.21 ppm
       (20oC, 101.3 kPa)                      1 ppm = 4.66 mg/m3
      Data from Top94, CKB00, Wea86.
      Dipropyl ketone is a stable, colourless liquid with a pleasant but penetrating
      odour and a burning taste. The odour threshold is not known.
4     Uses
      Dipropyl ketone is used as a solvent for nitro-cellulose, oils, resins and
      polymers, and in flavourings (ACG96).
5     Biotransformation and kinetics
      No data on biotransformation and kinetics of dipropyl ketone have been found.
      The compound may be absorbed via inhalation, ingestion and through the skin
      (Car74, Hat91).
6     Effects and mechanism of action
      Human data
      No data on human (occupational) exposure to dipropyl ketone have been found.
      Animal data
      Single applications of dipropyl ketone to the skin of guinea pigs or rabbits
      produced slight irritation. Repeated skin applications of 0.5 ml for a 10-day
005-4 Health-based Reassessment of Administrative Occupational Exposure Limits
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<pre>      period produced slight erythema (Top94). When dipropyl ketone was applied to
      the eyes of rabbits, only slight irritation was observed (Top94). There is no
      information whether the compound causes skin sensitization.
      The single oral LD50 in rats was 3047 mg/kg bw and the single skin application
      LD50 in rabbits 4624 mg/kg bw (Car74). An LD100 of 271 mg/kg bw after
      intravenous injection was reported for mice (Jep75).
          From six rats none died after 4 h inhalation exposure to 9320 mg/m3 (2000
      ppm) dipropyl ketone (Car74). The LC50 of a single 6 h exposure of rats was
      12,535 mg/m3 (2690 ppm) (Top94).
          Panson and Winek (Pan80) studied the aspiration hazard of dipropyl ketone
      on SD albino rats. The dosis used was 1 ml/kg bw. They found that six of seven
      animals died within the next 24 hours. The lungs showed from 25 to 50%
      congestion with only a very small amount of focal hemorrhage in the lobes.
      Two out of seven animals had blood clots at the base of their hearts.
          Dipropyl ketone administered by gavage to eight rats at a dose of 2000
      mg/kg bw, 5 days/week produced severe central nervous system (CNS)
      depression and reduced weight gain (it is not mentioned how many weeks this
      effect lasted) (unpublished data, cited in Top94). One rat died after 1 week of
      treatment due to cardiorespiratory failure. Lowering the dose to 1000 mg/kg bw
      resulted in restored weight gain and the absence of deleterious clinical effects
      over a 12-week period. Haematological determinations and serum clinical
      chemistry were unaffected, except for a reduction in glucose level. Relative
      liver and kidney weights were increased, and histological examination of the
      liver revealed hypertrophy of the hepatocytes. Repeated contact with the
      stomach resulted in hyperkeratosis and evidence of chronic irritation of the
      nonglandular gastric epithelium. Inhalation exposure to a concentration of
      1864 mg/m3 (400 ppm) dipropyl ketone decreased respiration and 3845 mg/m3
      (825 ppm) produced CNS depression. Narcosis occurred after exposure to 7456
      mg/m3 (1600 ppm), exposure to 14,912 mg/m3 (3200 ppm) killed three out of
      four rats. The duration of exposure was not reported (Top94).
          Six-hour exposure to 5592 mg/m3 (1200 ppm) dipropyl ketone, 5
      days/week, for 2 weeks resulted in a slightly decreased response to stimulation
      during exposure (unpublished data, cited in Top94). The species and number of
      animals used in the experiment were not reported. In this study, marginal liver
      enlargement, but no change in haematology, clinical chemistry or pathology
      were seen at the end of the 2-week exposure period.
005-5 Dipropyl ketone
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<pre>      No data on long-term exposure, mutagenicity, genotoxicity, carcinogenicity
      and reproduction toxicity of dipropyl ketone have been found.
7     Existing guidelines
      The current administrative occupational exposure limit (MAC) of dipropyl
      ketone in the Netherlands is 235 mg/m3 (50 ppm), 8 h TWA.
          Existing occupational exposure limits for dipropyl ketone in some
      European countries and the USA are summarized in the annex.
8     Assessment of health hazard
      There are no human data on exposure to dipropyl ketone. In experimental
      animals dipropyl ketone was found to be slightly irritating to the eyes and the
      skin. No information on skin sensitization has been found. Besides some acute
      animal data only unpublished data from repeated dose studies were available.
      Since the original data were not available to the committee, they can not be
      used to establish a health-based occupational exposure limit for dipropyl
      ketone. The committee considers depression of the central nervous system to be
      the critical effect of dipropyl ketone.
      The committee considers the toxicological data base on dipropyl ketone 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.
CKB00 Chemiekaarten. Gegevens voor veilig werken met chemiecalien. 15e editie. 2000. TNO Arbeid. p. 480.
005-6 Health-based Reassessment of Administrative Occupational Exposure Limits
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<pre>Car74 Carpenter CP, Weil CS, Smyth Jr HF. Range-finding toxicity data: List VIII. Toxicol Appl Pharmacol
      1974; 28: 313-9.
DFG99 Deutsche Forschungsgemeinschaft (DFG): Senatskommission zur Prufung gesundheitsschadlicher
      Arbeitsstoffe. MAK- und BAT-Werte-Liste 1999. Maximale Arbeitsplatzkonzentrationen und
      biologische Arbeitsstofftoleranzwerte. Weinheim, FRG: VCH Verlagsgesellschaft MBH, 1999
      (Mitteilung 35).
Hat91 Hathaway GJ, Proctor NH, Hughes JP, Fischman ML, editors. n-Butane, In: Proctor and Hughes'
      Chemical hazards of the workplace, third edition, New York: Van Nostrand Reinhold 1991: 122.
HSE99 Health and Safety Executive (HSE). EH40/99 Occupational exposure limits 1999. Sudbury (Suffolk),
      England: HSE Books, 1999.
Jep75 Jeppsson R. Parabolic relationship between lipophilicity and biological activity of aliphatic
      hydrocarbons, ethers and ketones after intravenous injections of emulsion formulations into mice. Acta
      Pharmacol Toxicol 1975; 37: 56-64.
NBO96 National Board for Occupational Safety and Health. Occupational exposure limit values. Solna,
      Sweden: NBOSH, 1996; Ordinance AFS1996/2.
Pan80 Panson RD, Winek CL. Aspiration toxicity of ketones. Clin Toxicol 1980; 17: 271-317.
SZW00 Ministerie van Sociale Zaken en Werkgelegenheid (SZW). Nationale MAC-lijst 2000. The Hague, the
      Netherlands: Servicecentrum Sdu Uitgevers, 2000.
Top94 Topping DC, Morgott DA, David RM, O'Donoghue JL. Ketones. In: Patty's industrial hygiene and
      toxicology, fourth ed., Vol II, Part C, Toxicology, Clayton GD and Clayton FE (eds),
      Wiley-Interscience Pub, New York, 1994, p.1808-1809.
TRG00 TRG 900: Grenzwerte in der Luft am Arbeitsplatz; Technische Regeln fur Gefahrstoffe; B Arb Bl
      2000; 2.
Wea86 Weast RC, editor. In: CRC Handbook of chemistry and physics. 66th edition, Boca Raton: CRC Press
      Inc., 1986: 299.
005-7 Dipropyl ketone
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<pre>             Annex
Occupational exposure limits for dipropyl ketone in various countries.
country                       occupational                         time-weighted    type of exposure  notea      lit refb
-organisation                 exposure limit                       average          limit
                              ppm               mg/m3
The Netherlands
-Ministry                     50                235                8h               administrative               SZW00
Germany
-AGS                          -                 238                8h                                            TRG00
-DFG MAK-Kom.                 -                 -                                                                DFG99
Great-Britain
-HSE                          -                 -                                                                HSE99
Sweden                        -                 -                                                                NBO96
Denmark                       -                 -                                                                Arb96
USA
-ACGIH                        50                233                8h               TLV                          ACG00
-OSHA                         -                 -
-NIOSH                        50                235                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
005-8        Health-based Reassessment of Administrative Occupational Exposure Limits
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