<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>      Octachloronaphthalene
      (CAS Reg. nr: 2234-13-1)
      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/012, The Hague, 14 December 2000
012-1
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<pre>      Preferred citation:
      Health Council of the Netherlands: Committee on Updating of Occupational
      Exposure Limits. Octachloronaphthalene; Health-based Reassessment of
      Administrative Occupational Exposure Limits. The Hague: Health Council of
      the Netherlands, 2000; 2000/15OSH/012.
      all rights reserved
012-2
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<pre>1     Introduction
      The present document contains the assessment of the health hazard of
      octachloronaphthalene 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 October 1997, respectively, and using the
      following key words: octachloronaphthalene, 2234-13-1, Halowax, Nibren,
      naphthalene or octachloro- (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                              :    octachloronaphthalene
       synonyms                          :    -
       CAS reg nr                        :    2234-13-1
       molecular formula                 :    C10Cl8
       structural formula                :
      Data from How92.
      The technical product Halowax 1051 can often erroneously be found under the
      same CAS reg nr as that for octachloronaphthalene. Halowax 1051 is a mixture
      of octa- and heptachloronaphthalenes (Asp84). The chlorination degree is
      approximately 70%. The theoretical chlorination degree of
      octachloronaphthalene is 70.3% (Aho80, Bel53).
012-3 Octachloronaphthalene
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<pre>3     Physical and chemical properties
       molecular weight:                   :   403.74
       melting point:                      :   185 - 200 °C
       boiling point:                      :   410°C
       vapour pressure:                    :   20°C: < 133 Pa
       solubility in water:                :   insoluble
       log Poct/water:                     :   calculated: 7.9
                                               measured: 6.4 - 8.4
       conversion factors:                 :   not applicable
       (20°C, 101.3 kPa)
      Data from ACG91, Ban91, Opp85, Opp87.
      Octachloronaphthalene is a non-flammable, pale yellow, wax-like solid
      (ACG91).
4     Uses
      Octachloronaphthalene has been utilized as a fireproof and waterproof additive
      in cable insulation and in other protective coating materials.
      Octachloronaphthalene has also found use as an additive to lubricants
      (ACG91).
           The manufacturing of chlorinated naphthalenes (Halowax) has been
      discontinued in the USA since 1977 (Ben94).
5     Biotransformation and kinetics
      When rabbits were given a single oral dose of 1000 mg octachloronaphthalene
      no increase in urinary metabolites was measured. The faeces and urine were
      not investigated for unmetabolized products (Cor58).
           One day after a single intra peritoneal injection in mice of 1 mg per animal
      the highest concentration of octachloronaphthalene was found in the adipose
      tissue: 2.1% of the dose. Lower concentrations were found in the liver (1.9%),
      spleen (0.80%), and kidneys (0.32%). The concentration in adipose tissue
      increased gradually up to day 7. Several biological half-life times were
      calculated during the exponential elimination phase: 3.72 days for the adipose
012-4 Health-based Reassessment of Administrative Occupational Exposure Limits
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<pre>      tissue, 3.39 days for the testes, 2.25 days for the spleen, 2.20 for the kidneys
      and as the fastest: 1.51 days for the lungs (Ois83). The investigators did not
      recover 100% of the amount injected, probably a part remained at the site of
      injection.
          After a single intra peritoneal injection of Halowax 1051 into rats the
      activity of several drug-metabolizing enzymes was increased: the
      arylhydrocarbon hydroxylase activity was increased 4.3-fold in the liver and
      6.1-fold in the kidneys. The ethoxycoumarin deethylase activity was increased
      9.6-fold in the liver and 53-fold in the kidneys. The
      UDP-glucuronosyltransferase activity was increased 4.5-fold in the liver. The
      enzyme activities in the small intestines were not increased (Aho82). An earlier
      study by the same authors gave comparable results (Aho80).
6     Effects and mechanism of action
      Human data
      Halowax 1051 was tested on the skin of the ear of 3 volunteers in a 50%
      mineral oil suspension for 30 days. No acne or any other skin effect was
      observed (She57).
      Animal data
      A quantity of 20 mg, applied 5 times per week for two weeks on the skin of
      hairless mice, did not induce gross or histological changes (Puh82).
          Four calves received quantities of octachloronaphthalene in the range of 4.0
      - 10.0 mg/lb (8.8 - 22 mg/kg body weight) as a total oral dose, given in small
      portions for 7 - 11 days. Only one calf developed hyperkeratosis (not the high
      dose animal); it was moribund in 21 days. The top dose animal and one low
      dose animal remained unaffected; the dosage was repeated from the 23rd to the
      27th day without any symptoms; neither did these two calves show any
      symptoms during the 150-day period of observation. The fourth animal
      received 11 mg/kg, and developed symptoms like lacrimation, salivation and
      nasal discharge by the eighth day; the symptoms disappeared after
      approximately 50 days (Bel53).
          The addition of 0.05% to 0.30% of
      octachloronaphthalene/heptachloronaphthalene (9:1) to the diet of rats
      (approximately 25 to 150 mg/kg body weight) greatly accelerated the loss of
012-5 Octachloronaphthalene
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<pre>      vitamin A from the liver. There was no effect on the vitamin A or vitamin E
      concentration in the blood, nor did the vitamin E in the liver change
      significantly (Dea55).
          Octachloronaphthalene was injected intra peritoneal into immature male
      rats at doses of 0 (n=5), 15 (n=4), 60 (n=4) 150 (n=8) and 600 µmol/kg (n=8)
      (6, 24, 60 and 242 mg/kg body weight respectively) on day 1 and day 3. On day
      6 there was a decrease in relative liver weight (p<0.05) at the highest dose. At
      the other dose levels no effect on the relative liver weight was found. There was
      a dose-related increase in the activity of several liver enzymes (p<0.01 from 24
      mg/kg upward) (Cam81).
      No data on long-term exposure, carcinogenicity, genotoxicity, mutagenicity or
      reproduction toxicity of octachloronaphthalene were found.
7     Existing guidelines
      The current administrative occupational exposure limit (MAC) for
      octachloronaphthalene in the Netherlands is 0.1 mg/m3, 8 h TWA with a skin
      notation.
          Existing occupational exposure limits for octachloronaphthalene 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 octachloronaphthalene. Limited
      data indicate that the compound is not acnegenic after dermal application on
      humans (She57) and on hairless mice (Puh82).
          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.
          Oral dosing of 25 mg/kg body weight depleted the vitamin A content of the
      liver of rats (Dea55). Two intraperitoneal injections of 242 mg/kg body weight
      decreased the relative liver weight of immature rats (Cam81). The target organ
      for toxicity is probably the liver.
          Data on long-term exposure of animals have not been found.
      The committee considers the toxicological data base on octachloronaphthalene
      too poor to recommend a health-based occupational exposure limit.
012-6 Health-based Reassessment of Administrative Occupational Exposure Limits
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<pre>      The committee concludes that there is insufficient information to comment on
      the level of the present MAC value.
      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; 1141-2.
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. 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.
Ban91 Banerjee S, Baughman GL. Bioconcentration factors and lipid solubility. Environ Sci Technol 1991;
      25: 536-9.
Bel53 Bell WB. The relative toxicity of the chlorinated naphthalenes in experimentally produced bovine
      hyperkeratosis (X-disease). Vet Med 1953; 48: 135-40, 149.
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; IID: 2425-583.
Cam81 Campbell MA, Bandeira S, Robertson L, et al. Octachloronaphthalene induction of hepatic microsomal
      aryl hydrocarbon hydroxylase activity in the immature male rat. Toxicology 1981; 22: 123-32.
Cor58 Cornish HH, Block WD. Metabolism of chlorinated naphthalenes. J Biol Chem 1958; 231: 583-8.
Dea55 Deadrick RE, Bieri JG, Cardenas RR jr. Effects of octachloronaphthalene on vitamin A metabolism in
      the rat. J Nutr 1955; 57: 287-95.
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.
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.
NBO96 National Board of Occupational Safety and Health. Occupational exposure limit values. Solna,
      Sweden: NBOSH, 1996: Ordinance AFS 1996/2.
012-7 Octachloronaphthalene
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<pre>Ois83 Oishi H, Oishi S. Tissue distribution and elimination of chlorinated naphthalenes in mice. Toxicol Lett
      1983; 15: 119-22.
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; 249-64.
Puh82 Puhvel SM, Sakamoto M, Ertl DC, et al. Hairless mice as models for chloracne: a study of cutaneous
      changes induced by topical application of established chloracnegens. Toxicol Appl Pharmacol 1982;
      64: 492-503.
She57 Shelley WB, Kligman AM. The experimental production of acne by penta- and
      hexachloronaphthalenes. 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.
TRG00 TRGS 900 [Grenzwerte in der Luft am Arbeitsplatz; Technische Regeln für Gefahrstoffe]. German. B
      Arb Bl. 2000; 2.
012-8 Health-based Reassessment of Administrative Occupational Exposure Limits
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<pre>             Annex
Occupational exposure standards for octachloronaphthalene in various countries.
country                             occupational exposure           time-weighted      type of exposure   notea      lit refb
-organisation                       limit                           average            limit
                                    ppm           mg/m3
the Netherlands
-Ministry                           -             0.1               8h                 administrative     S          SZW00
Germany
-AGS                                              0.1c              8h                 administrative                TRG00
-DFG MAK-Kom.                       -             -d                                                                 DFG99
Great Britain
-HSE                                -             -                                                                  HSE99
                                                  e
Sweden                              -                                                                                NBO96
Denmark                             -             0.1               8h                                    S          Arb96
USA
-ACGIH                              -             0.1               8h                 TLV                S          ACG00
                                    -             0.3               15 min             STEL
-OSHA                               -             0.1               8h                 PEL                S
-NIOSH                              -             0.1               10 h               REL                S
                                    -             0.3               15 min             STEL
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 TWA 8 h and a STEL (10 min) of 0.6 mg/m3
     with a skin notation. However, the CAS reg number assigned to this mixture is the same as that for trichloronaphthalene.
012-9        Octachloronaphthalene
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<pre>012-10 Health-based Reassessment of Administrative Occupational Exposure Limits</pre>

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