<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>

====================================================================== Einde pagina 1 =================================================================

<br><br>====================================================================== Pagina 2 ======================================================================

<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>

====================================================================== Einde pagina 2 =================================================================

<br><br>====================================================================== Pagina 3 ======================================================================

<pre>      Tetrachloronaphthalene
      (CAS Reg. nr: 1335-88-2)
      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/016, The Hague, 14 December 2000
016-1
</pre>

====================================================================== Einde pagina 3 =================================================================

<br><br>====================================================================== Pagina 4 ======================================================================

<pre>      Preferred citation:
      Health Council of the Netherlands: Committee on Updating of Occupational
      Exposure Limits. Tetrachloronaphthalene; Health-based Reassessment of
      Administrative Occupational Exposure Limits. The Hague: Health Council of
      the Netherlands, 2000; 2000/15OSH/016.
      all rights reserved
016-2
</pre>

====================================================================== Einde pagina 4 =================================================================

<br><br>====================================================================== Pagina 5 ======================================================================

<pre>1     Introduction
      The present document contains the assessment of the health hazard of
      tetrachloronaphthalene 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 March 1998, 1981 until
      October 1997 and 1937 until December 1997, respectively, and using the
      following key words: tetrachloronaphthalene, 1335-88-2, Halowax, Nibren,
      naphthalene or tetrachloro- (all isomers). Data considered to be critical were
      evaluated by reviewing the original publications. The final literature search has
      been carried out in March 1998, followed by an additional search in May 1999.
           In February 1999, 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                              :    tetrachloronaphthalene
       synonyms                          :    -
       CAS reg nr                        :    1335-88-2
       molecular formula                 :    C10H4Cl4
       structural formula                :
      Data from How92.
016-3 Tetrachloronaphthalene
</pre>

====================================================================== Einde pagina 5 =================================================================

<br><br>====================================================================== Pagina 6 ======================================================================

<pre>      The technical product Halowax can often erroneously be found under the same
      CAS reg nr as the original mixture. The theoretical chlorination degree of the
      technical product is 53.3%, generally, the actual degree is 53.5%. Halowax
      1001 (CAS reg nr 58718-67-5) has a chlorination degree of 50%; Halowax
      1099 (CAS reg nr 39450-05-5) has a chlorination degree of 52%; Halowax
      1013 (CAS reg nr 12616-35-2) has a chlorination degree of 56%.
3     Physical and chemical properties
       molecular weight                    :    265.96
       melting point:                      :    depending on the isomer: 120 - 198°C
                                                unspecified: 182°C; 115 - 200°C
       boiling point                       :    312 - 360°C
       flash point                         :    210°C (open cup)
       vapour pressure                     :    20°C: <<1Pa
       solubility in water                 :    insoluble
       log Poct/water                      :    depending on the isomer: 5.75 - 6.38
       conversion factors                  :    not applicable
       (20°C, 101.3 kPa)
      Data from ACG91, Ban91, Dre79, Lew92, NIA98, Opp85, Opp87.
      The product is a mixture of isomers. It consists of colourless to light yellow
      crystals with a typical odour, decomposes upon heating or combustion, forming
      corrosive and toxic fumes, e.g. phosgene and hydrochloric acid, and reacts
      vigorously with oxidants (NIA98).
4     Uses
      Tetrachloronaphthalene is used in electrical insulating materials, as a
      component of resins or polymers for coating or impregnating textiles, wood,
      and paper, and as an additive in cutting oils and lubricants (ACG91).
           The manufacturing of chlorinated naphthalenes (Halowax) has been
      discontinued in the USA since 1977 (Ben94).
016-4 Health-based Reassessment of Administrative Occupational Exposure Limits
</pre>

====================================================================== Einde pagina 6 =================================================================

<br><br>====================================================================== Pagina 7 ======================================================================

<pre>5     Biotransformation and kinetics
      When rats were given a single oral dose of 1 g of tetrachloronaphthalene, 45%
      was recovered in the urine in the next four days. The compound was partly
      metabolized into sulphate (4%), mercapturic acid (3%), and glucuronic acid
      (38%). The rest of the dose was not accounted for. Further analysis of the
      metabolites was not performed (Cor58).
          After a single intra peritoneal injection of 100 mg/kg body weight of Nibren
      D130 (chlorination degree 50 - 60%) into rats the activity of several
      drug-metabolizing enzymes was increased: the aryl hydrocarbon hydroxylase
      activity was increased 4.4-fold in the liver, and 7.1-fold in the kidneys; the
      ethoxycoumarin deethylase activity was increased 12-fold in the liver and
      24-fold in the kidneys; the UDP-glucuronyltransferase was increased 3.6-fold
      in the liver. The enzyme activities in the small intestines were not increased
      (Aho82). A similar study with Halowax 1099 (chlorination degree 52%) using
      the same dosing regimen, also showed the induction of several
      drug-metabolizing enzymes in rat liver (Aho80).
6     Effects and mechanism of action
      Human data
      Halowax 1001 (tri- and tetrachloronaphthalenes) was tested on the skin of ears
      of 3 volunteers in a 50% mineral oil suspension for 30 days. No acne or any
      other skin effect was observed (She57).
          Halowax-induced hepatic dysfunctioning was described in wire cable
      workers, assemblers and labourers, including the description of nine deaths due
      to occupational Halowax exposure (study from 1944, cited in ACG91).
      Animal data
      A very old study reports that after exposure to 1 mg/m3 of tetrachloro-
      naphthalene for 16 hours/day, for 6 weeks, rats only showed damage of the
      liver. No further data are available (Dri37).
          After feeding 10 rats daily with 500 mg of a mixture of tetra- and
      pentachloronaphthalene, all animals fell ill and either died or were sacrificed
016-5 Tetrachloronaphthalene
</pre>

====================================================================== Einde pagina 7 =================================================================

<br><br>====================================================================== Pagina 8 ======================================================================

<pre>      by the 63rd day. The livers showed fatty infiltration and fatty degeneration
      (Ben38).
          Two of three calves developed mild symptoms associated with
      hyperkeratosis after receiving 7.4 or 12.1 mg/lb via the feed for 10 days
      (respectively 16 and 27 mg/kg body weight as a total dose, given in small
      portions in 10 - 13 days). Both calves showed some lacrimation, slight nasal
      discharge and some depression that persisted for several days. The dosing was
      repeated during the 23rd to 30th day. Slight symptoms that lasted several days
      again appeared. At the end of 150 days of observation there were no symptoms
      of hyperkeratosis or any other effects (Bel53).
          1,2,3,4-Tetrachloronaphthalene was intra peritoneal injected into immature
      male rats (n=4) on day 1 and day 3 at a dose of 150 µmol/kg bw (39.9 mg/kg).
      A control group (n=10) was injected with corn oil. On day 6 no effects were
      found on the relative liver weight and the activity of several liver enzymes
      (Cam83).
      Mutagenicity and genotoxicity
      1,2,3,4-Tetrachloronaphthalene was negative in the Ames assay, using
      Salmonella typhimurium strains TA98, TA100, TA1535, and TA1537, with
      and without rat and hamster liver metabolic activation (Haw83).
      No data on carcinogenicity or reproduction toxicity of tetrachloronaphthalene
      have been found.
7     Existing guidelines
      The current administrative occupational exposure limit (MAC) for
      tetrachloronaphthalene in the Netherlands is 2 mg/m3, 8 h TWA.
          Existing occupational exposure limits for tetrachloronaphthalene in some
      European countries and in the USA are summarized in the annex.
8     Assessment of health hazard
      Very few data are available on the toxicity of tetrachloronaphthalene. Limited
      data in humans indicate that the compound is not acnegenic after dermal
      application (She57). It did induce hyperkeratosis, some lacrimation, slight
      nasal discharge and some depression in calves after oral administration
016-6 Health-based Reassessment of Administrative Occupational Exposure Limits
</pre>

====================================================================== Einde pagina 8 =================================================================

<br><br>====================================================================== Pagina 9 ======================================================================

<pre>      (Bel53). Hepatic dysfunctioning has been reported after occupational exposure
      to Halowax (ACG91).
           In an inhalation study in rats liver effects were observed after exposure to 1
      mg/m3 tetrachloronaphtahalene during 6 weeks (Dri37).
           The activity of several enzymes was increased in liver and kidneys of rats,
      after intra peritoneal injection of the technical product (Aho80, Aho82).
           The target organs for toxicity are probably the liver and/or the kidneys.
           No carcinogenicity studies have been found, neither any case report or
      epidemiological study of cancer in humans exposed to this chemical.
           No reproduction toxicity studies have been found.
      The committee considers the toxicological data base on tetrachloronaphthalene
      too poor to recommend a health-based occupational exposure limit.
      Given the effects found in the inhalation study in rats, the committee concludes
      that the present MAC-value for tetrachloronaphthalene of 2 mg/m3, as an 8 h
      time weighted average, is too high.
      References
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; 1511-2.
ACG00 American Conference of Governmental Industrial Hygienists (ACGIH). Guide to occupational
      exposure values -2000. Cincinnati, Ohio, USA: ACGIH, 2000.
Aho80 Ahotupa M, Aitio A. Effect of chlorinated naphthalenes and terphenyls on the activities of drug
      metabolizing enzymes in rat liver. Biochem Biophys Res Commun 1980; 93: 250-7.
Aho82 Ahotupa M, Hietanen E, Mäntylä E, et al. Effects of polychlorinated paraffins on hepatic, renal and
      intestinal biotransformation rates in comparison to the effects of polychlorinated biphenyls and
      naphthalenes. J Appl Toxicol 1982; 2: 47-53.
Arb96 Arbejdstilsynet. Exposure limit values for substances and materials. Copenhagen, Denmark: The
      Working Environment Service; Instruction no. 3.1.0.2. 1996.
Bel53 Bell WB. The relative toxicity of the chlorinated naphthalenes in experimentally produced bovine
      hyperkeratosis (X-disease). Vet Med 1953; 48: 135-40, 149.
Ben38 Bennett GA, Drinker DK, Warren MF. Morphological changes in the livers of rats resulting from
      exposure to certain chlorinated hydrocarbons. J. Ind Hyg Toxicol 1938; 20: 97-123.
Ben94 Benya TJ, Leber AP. Halogenated cyclic hydrocarbons. In: Clayton GD, Clayton FE, ed. Patty’s
      Industrial hygiene and toxicology. 4th ed. New York: John Wiley & Sons, Inc 1994; 2D: 2425-583.
016-7 Tetrachloronaphthalene
</pre>

====================================================================== Einde pagina 9 =================================================================

<br><br>====================================================================== Pagina 10 ======================================================================

<pre>Cam83 Campbell MA, Bandiera S, Robertson L, et al. Hepta-, hexa-, tetra- and dichloronaphthalene congeners
      as inducers of hepatic microsomal drug-metabolizing enzymes. Toxicology 1983; 26: 193-205.
Cor58 Cornish HH, Block WD. Metabolism of chlorinated naphthalenes. J Biol Chem 1958; 231: 583-8.
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.
Dre79 Dressler H. Chlorinated naphthalenes. In: Chlorocarbons and chlorohydrocarbons. In: Mark HF,
      Othmer DF, Overberger CG, et al. ed. Encyclopedia of Chemical Technology. 3rd ed. New York: J
      Wiley & Sons 1979; 5: 838-43.
Dri37 Drinker CK, Warren MF, Bennett GA. The problem of possible systemic effects from certain
      chlorinated hydrocarbons. J Ind Hyg Toxicol 1937; 19: 283-311. Chem Abstr 31:86813.
Haw83 Haworth S, Lawlor T, Mortelmans K, et al. Salmonella mutagenicity test results for 250 chemicals.
      Environ Mutagen 1983; suppl 1: 3-142.
How92 Howard PH, Neil M, ed. Dictionary of chemical names and synonyms. Chelsea, USA: Lewis
      Publishers, 1992.
HSE99 Health and Safety Executive (HSE). Occupational exposure limits 1999. Sudbury, England: HSE
      Books, 1999; Guidance note EH 40/99.
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.
Lew92 Lewis sr. RJ, ed. Sax’s dangerous properties of industrial materials. 8th ed. New York, USA: Van
      Nostrand Reinhold, 1992; 3210.
Lid96 Lide DR, Frederikse HPR, ed. CRC Handbook of chemistry and physics. 77th ed. Boca Raton, USA:
      CRC Press, 1996;
NBO96 Swedish National Board of Occupational Safety and Health. Occupational exposure limit values. Solna,
      Sweden: NBOSH, 1996: Ordinance AFS 1996/2.
NIA98 Nederlands Instituut voor Arbeidsomstandigheden (NIA), TNO, VNCI, ed. [Chemiekaarten]. Dutch.
      13th ed. Tetrachloornaftaleen. Alphen aan den Rijn, the Netherlands: Samsom HD Tjeenk Willink,
      1998; 1015.
Opp85 Opperhuizen A, Van der Velde EW, Gobas FAPC, et al. Relationship between bioconcentration in fish
      and steric factors of hydrophobic chemicals. Chemosphere 1985; 14: 1871-96.
Opp87 Opperhuizen A. Relationships between octan-1-ol/water partition coefficients, aqueous activity
      coefficients and reversed phase HPLC capacity factors of alkylbenzenes, chlorobenzenes,
      chloronaphthalenes and chlorobiphenyls. Toxicol Environ Chem 1987; 15: 249-64.
She75 Shelley WB, Kligman AM. The experimental production of acne by penta- and
      hexachloro-naphthalenes. AMA Arch Dermatol 1957; 75: 689-95.
SZW00 Ministerie van Sociale Zaken en Werkgelegenheid (SZW): Arbeidsinspectie. [De nationale MAC-lijst
      2000]. Dutch. The Hague, the Netherlands: Sdu Servicecentrum Uitgeverijen, 2000.
016-8 Health-based Reassessment of Administrative Occupational Exposure Limits
</pre>

====================================================================== Einde pagina 10 =================================================================

<br><br>====================================================================== Pagina 11 ======================================================================

<pre>TRG00 TRGS 900. [Grenzwerte in der Luft am Arbeitsplatz; Technische Regeln für Gefahrstoffe; B Arb Bl.
      2000]. German. B Arb Bl 2000; 2.
016-9 Tetrachloronaphthalene
</pre>

====================================================================== Einde pagina 11 =================================================================

<br><br>====================================================================== Pagina 12 ======================================================================

<pre>             Annex
Occupational exposure standards for tetrachloronaphthalene in various countries.
country                      occupational exposure limit       time-weighted        type of exposure    notea      lit refb
-organisation                                      3           average              limit
                             ppm             mg/m
the Netherlands
- Ministry                   -               2                 8h                   administrative      S          SZW00
Germany
- AGS                                        2c                8h                   administrative                 TRG00
- DFG MAK-Kom                -               -d                                                                    DFG99
Great Britain
- HSE                        -               2                 8h                   OES                            HSE99
                             -               4                 15 min               STEL
                                             e
Sweden                       -                                                                                     NBO96
Denmark                      -               2                 8h                                       S          Arb96
USA
- ACGIH                      -               2                 8h                   TLV                            ACG00
- OSHA                       -               2                 8h                   PEL                 S
- NIOSH                      -               2                 10 h                 REL                 S
European Union
- SCOEL                      -               -                                                                     Hun97
a
     S = skin notation; which means that skin absorption may contribute considerably to the body burden
     sens = substance can cause sensitization
b
     reference to the most recent official publication of occupational exposure limits
c
     the inhalable fraction of the aerosol
d
     substance for which no MAK value can be established at present
e
     Sweden has a Level Limit Value for chlorinated naphthalenes of 0.2 mg/m3 8 h TWA and a STEL (10 min) of 0.6 mg/m3
     with a skin notation. However, the CAS reg nr assigned to this mixture is the same as that for trichloronaphthalene
016-10       Health-based Reassessment of Administrative Occupational Exposure Limits
</pre>

====================================================================== Einde pagina 12 =================================================================

<br><br>