<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>      Hexachloronaphthalene
      (CAS reg. nr: 1335-87-1)
      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/007, The Hague, 14 December 2000
007-1
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<pre>      Preferred citation:
      Health Council of the Netherlands: Committee on Updating of Occupational
      Exposure Limits. Hexachloronaphthalene; Health-based Reassessment of
      Administrative Occupational Exposure Limits. The Hague: Health Council of
      the Netherlands, 2000; 2000/15OSH/007.
      all rights reserved
007-2
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<pre>1     Introduction
      The present document contains the assessment of the health hazard of
      hexachloronaphthalene 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: hexachloronaphthalene, 1335-87-1, Halowax, Nibren,
      naphthalene or hexachloro- (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                              :    hexachloronaphthalene
       synonyms                          :    -
       CAS reg nr                        :    1335-87-1
       molecular formula                 :    C10H2Cl4
       structural formula                :
      Data from How92.
007-3 Hexachloronaphthalene
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<pre>      The technical product Halowax 1014 can often erroneously be found under the
      same CAS reg nr as the original mixture. The theoretical chlorination degree is
      63.5%, the actual degree varies from 62 to 64% (Aho80, Bel53). Halowax 1014
      (CAS reg nr 12616-36-3) is said to be a mixture of penta- and
      hexachloronaphthalenes (Ham57) or of tetra- to octachloronaphthalenes
      (Asp86).
3     Physical and chemical properties
       molecular weight                 :     334.8
       melting point                    :     137°C
       boiling point                    :     343 - 388°C
       vapour pressure                  :     20°C: < 133 Pa
       solubility in water              :     insoluble
       log Poct/water                   :     7.59
       conversion factors               :     not applicable
       (20°C, 101.3 kPa)
      Data from ACG91, DFG97.
      Hexachloronaphthalene is a white or yellow wax-like compound, with a typical
      odour. The compound decomposes upon heating and combustion, forming
      corrosive and very toxic fumes, e.g. hydrochloric acid (NIA98).
4     Uses
      Hexachloronaphthalene has been used in the manufacture of electric wire
      insulation and also as an additive to special lubricants (ACG91). The
      manufacturing of chlorinated naphthalenes (Halowax) has been discontinued in
      the USA since 1977 (Ben94).
5     Biotransformation and kinetics
      After a single oral dose of Halowax 1014 (containing mainly penta- and
      hexachloronaphthalene) at 20 mg/kg bw to rats, one component
      (hexachloronaphthalene) concentrated in the liver. The concentration ratio
      between the liver and adipose tissue was about 140 after 10 days, and 5 after 4
      months. The component was characterised by comparison with GC/MS data of
007-4 Health-based Reassessment of Administrative Occupational Exposure Limits
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<pre>      all available chloronaphthalenes. It was shown that the bioaccumulating
      compound was 1,2,3,5,6,7-hexachloronaphthalene (Asp86). Later it was shown
      that the retained compound actually was a mixture of two
      hexachloronaphthalenes: the 1,2,3,4,6,7- and 1,2,3,5,6,7-isomers (Asp94).
      Also when rats were orally dosed with a mixture of the identified isomers of
      hexachloronaphthalene, the isomers were strongly retained in the liver. The
      half lives were calculated to be 41 days in adipose tissue and 36 days in the
      liver (Asp94).
           After a single intra peritoneal injection with Halowax 1014 in rats, the
      activity of several drug metabolizing enzymes in the liver was increased: aryl
      hydrocarbon hydroxylase, ethoxycoumarine deethylase and UDP
      glucuronosyltransferase (Aho80).
6     Effects and mechanism of action
      Human data
      A quantity of 2 ml of a 3% solution of either Halowax 1014 or
      hexachloronaphthalene was applied on the skin of six Caucasian and four
      Negro male volunteers, daily for a minimum of 6 weeks to a maximum of 12
      weeks. With both compounds dermal effects developed, from increase in
      number of epidermal cells (day 5), follicular involvement without erythema
      (day 10), follicular accentuation (day 14), small comedones (week 3 - 5), to
      large comedones (week 6 - 12). Pretreatment with vitamin A did not result in
      any amelioration of the effect (Ham57).
           Acne was also produced on the skin of several volunteers: seven areas of
      skin in 3 to 5 white and Negro male adults were investigated by applying a
      50% suspension of Halowax 1014 daily for 35 days. Five subjects were treated
      daily for 2 months with Halowax 1014 on their back and biopsies were taken at
      regular intervals, up to 16 weeks. Fulminant inflammatory acne developed,
      which was not confined to the sites of application, but also appeared on areas to
      which the wax was transferred by the hands or clothing. The disease slowly
      resolved over the next half year. Residual scarring, hyperpigmentation and
      other characteristic symptoms remained evident at one year (She57). Several
      cases are described of persons who died from liver cirrhosis, liver atrophy,
      toxic jaundice or related diseases. All were exposed to Halowax, but its
      composition is not known (Str44).
007-5 Hexachloronaphthalene
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<pre>          A group of 9,028 workers, exposed to a mixture of polychlorinated
      naphthalenes, was investigated for work-related causes of mortality and
      morbidity. In this group 460 individuals were diagnosed with chloracne (5%).
      There was an elevated mortality due to liver cirrhosis. After leaving out the
      cases which could be associated with alcohol abuse, 83 cases with liver
      cirrhosis were observed, resulting in a SMR of 1.67 (no confidence limits were
      given, p<0.01). Although exposure to chlorinated naphthalenes ceased in 1945,
      the elevated mortality from cirrhosis persisted through the 80s. Furthermore,
      the workers were probably also exposed to other chlorinated hydrocarbons
      (War96). Although the authors tried to relate the incidence of chloracne with
      causes of death, no such relationship was found. In the total cohort (not
      corrected for alcohol abuse) an increase in death from ischemic heart disease,
      digestive system diseases, and all cancers, was also found; this increase was not
      found in the subcohort of individuals with chloracne.
          In a group of 16 workers for many years occupationally exposed to a
      mixture of chlorinated naphthalenes, six had liver dysfunctions, especially
      elevated levels of the enzyme gamma-glutamyltransferase (GGT). None of
      them had chloracne. The naphthalene waxes contained in some cases a mixture
      of 40% pentachlorinated and 35% hexachlorinated naphthalenes (Pop97). In
      view of the fact that 10 of the 16 workers were not available for examination,
      that the workers were exposed to a mixture of compounds and that data are
      lacking concerning occupational circumstances, this study gives only weak
      support to the hypothesis that hexachloronaphthalene can induce liver toxicity.
      Animal data
      Halowax 1014 (according to the authors hexachloronaphthalene) was
      investigated for dermal effects. A quantity of 29 mg was topically applied three
      times per week for two weeks on hairless mice. Within 14 days hyperkeratotic
      scaly skin was observed. Histologically hyperkeratosis, epidermal hyperplasia,
      sebaceous gland involution and intraepidermal keratinous cyst formation were
      evident (Puh82).
          Halowax 1014 (according to the authors a mixture of penta- and
      hexachloronaphthalene) and hexachloronaphthalene were applied as a 3%
      solution on the ear canal skin of rabbits daily for 5 days; each time 1 ml was
      applied, the rabbits received thus 5 times 30 mg. In both cases mild dermatitis,
      thickening of the epidermis, and proliferation of the follicles and sebaceous
      gland ducts were observed. The effects gradually receded upon discontinuation
007-6 Health-based Reassessment of Administrative Occupational Exposure Limits
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<pre>      of the applications. Pretreament with vitamin A did not result in any
      amelioration of the effect (Ham57).
          Daily inhalation of a mixture of penta- and hexachloronaphthalene in a
      concentration of 1.16 mg/m3 for 16 hours/day during 134 days (4.5 months)
      induced liver injury in rats: swollen cells, more granules in the cells, and
      hyaline droplets in the cytoplasm. No significant advances of the effects were
      observed between the 72nd and 134th day of exposure. Daily inhalation of the
      same mixture in a concentration of 1.44 mg/m3 for 8 hours/day during 143 days
      (4.8 months) induced similar liver injury as that seen in rats exposed 16 hours
      daily. A higher concentration of 8.88 mg/m3 for 16 hours/day induced weight
      loss in all 80 rats, and 4 died by the end of the first month, 55 within 52 days.
      Liver injury was more marked compared with the lower dosed groups. Rats
      removed from exposure between the 3rd and 5th week continued to die, the
      longest survival time being 35 days. Microscopic examination of the livers of
      these animals revealed no recovery (Ben38). Feeding experiments with the
      same mixture of penta- and hexachloronaphthalene to rats resulted in the same
      liver injury as after inhalation exposure. Daily feeding of 3 g per animal led to
      the death of all 10 animals within 33 days. Daily feeding of 1 g per animal led
      to the death or a moribund state of all 10 animals within 55 days.
          Rats were given 0.02%, 0.0063%, or 0.002% hexachloronaphthalene in the
      diet for 12 weeks. The group size was 39 - 40 animals 39-days old (older rats)
      and 62 - 64 animals 32-days old (younger rats) at the start of the study; interim
      kills were performed at 4 days and at 1, 4, 8, and 12 weeks. Therefore, only 8 -
      16 animals received the diet for 12 weeks. The parameters measured were
      body, liver and kidney weight and the sleeping time after a single intra
      peritoneal injection of hexobarbital or pentylenetetrazol. A treatment- and
      dose-related decrease in food consumption and body weight and an increase in
      relative liver weight was observed within one week of treatment. The treatment
      of half of the number of rats from the top dose was discontinued after 4 weeks.
      A recovery was observed, but after 4 weeks the parameters were not yet
      comparable with those of the control group. At the lowest dose the increase in
      relative liver weight of the combined groups was significant after 1 week
      (0.05>p>0.01) and after 4, 8 and 12 weeks (p<0.001). After 12 weeks the body
      weights of the older and the younger rats were not significantly different from
      the control group, as were the kidney weights and the sleeping times of the
      combined groups (Wei62).
          A technical mixture of hexachloronaphthalene (chlorination degree 62%)
      was given per os to swine and pigs for several days. A total dose of 50 mg/lb
007-7 Hexachloronaphthalene
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<pre>      (110 mg/kg) after 10 days did not induce any effects in swine. After a total dose
      of 90 or 100 mg/lb (198 or 220 mg/kg) after 8 or 9 days pigs became moribund
      or died after 33 to 40 days. Gross lesions were swelling and haemorrhage in the
      liver, mild gastritis, slight thickening of the intestinal wall, oedema of the
      eyelids in some animals and swelling of the epididymis. The plasma vitamin A
      did not remain low after the administration was discontinued. There was a
      temporary drop into the deficiency range 14 days after the initial dose of 70
      mg/lb (145 mg/kg) or more was given to the pigs. However, levels did not
      remain in the deficiency range, and pigs which were severely poisoned later on
      had normal plasma vitamin A values (Lin58).
          After daily oral dosing of 10 mg hexachloronaphthalene/lb body weight (22
      mg/kg) to 6 pigs for 8 or 9 days, they were moribund or had died after 31 to 40
      days. Symptoms before death were depression, anorexia, ataxia, retarded
      weight gain or weight loss. They did not develop other signs characteristic of
      bovine hyperkeratose. Histopathological lesions were observed in liver and
      kidneys. After 14 days the plasma vitamin A levels were decreased (p<0.001).
      No significant differences in the plasma vitamin A levels were observed at
      necropsy (Hub62).
          Five calves received doses of hexachloronaphthalene in the range of 2.5 -
      11.6 mg/lb (5.6 - 25.6 mg/kg) as a total dose, given in small doses for 5 to 10
      days. Symptoms developed by the fifth day, consisting of hyperkeratosis,
      lacrimation, nasal discharge, salivation, red areas on the oral mucosa,
      anorexia, depression, indentation of horn, and finally extreme weakness or
      prostration. They had to be killed between the 15th and 29th day. Upon autopsy
      the animals had lesions in kidneys, liver, pylorus, gall bladder and small
      intestine (Bel53).
          1,2,3,4,5,6-hexachloronaphthalene was intra peritoneally injected into
      immature male rats (n=4) on day 1 and day 3, with a dose of 30 and 150
      µmol/kg (10 and 50 mg/kg). A control group (n=10) was injected with corn oil.
      On day 6 there was a dose-related increase in the relative liver weight (p<0.05
      in both cases), in the induction of the enzymes B[a]P hydroxylase (p<0.05 at
      the high dose), ethoxyresorufine O-deethylase (p<0.05 in both cases),
      cytochrome b5 (p<0.05 at the high dose) and cytochrome P450 (p<0.05 in both
      cases) (Cam83).
          A very old study reports that after exposure to 1 mg/m3
      hexachloronaphthalene 16 hours/day, for 6 weeks, rats showed only damage to
      the liver (Dri37).
007-8 Health-based Reassessment of Administrative Occupational Exposure Limits
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<pre>      No data on carcinogenicity, genotoxicity or mutagenicity of
      hexachloronaphthalene have been found.
      Reproduction toxicity
      A 1 year old Holstein bull administered 1.8 g of penta- and
      hexachloronaphthalene became aspermatozoal for 6 months, but recovered in
      10 months following treatment (Ben94).
7     Existing guidelines
      The current administrative occupational exposure limit (MAC) for
      hexachloronaphthalene in the Netherlands is 0.2 mg/m3, 8 h TWA.
          Existing occupational exposure limits for hexachloronaphthalene in some
      European countries and in the USA are summarized in the annex.
8     Assessment of health hazard
      Occupational exposure to a mixture of polychlorinated naphthalenes is
      associated with liver dysfunctioning and liver cirrhosis in humans. However,
      the workers were probably also exposed to other chlorinated hydrocarbons
      (Pop97, War96).
          Hexachloronaphthalene and Halowax 1014 are acnegenic in humans
      (Ham57, She57), and in rabbits and hairless mice (Ham57, Puh82) after
      dermal application. The lowest dose applied on humans was 2 ml of a 3%
      solution, that is 60 mg per day.
          After oral dosing calves developed hyperkeratosis, but pigs and swine did
      not, even at doses which were lethal to the animals.
          Inhalation studies in rats to hexachloronaphthalene (1 mg/m3, for 6 weeks)
      or with a mixture of this compound and the pentachloronaphthalene (1.2 - 1.4
      mg/m3, approx. 20 weeks) resulted in effects in the livers (Dri37, Ben38).
          Dosing of 0.002% hexachloronaphthalene via the diet increased the relative
      liver weights in rats after 12 weeks, but not the body weights and the relative
      kidney weights. These were the only parameters measured, histopathology was
      not performed (Wei62). Using default values the consumption of
      hexachloronaphthalene was estimated by the committee to be 1 mg/kg body
      weight per day.
007-9 Hexachloronaphthalene
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<pre>            No data on carcinogenicity, genotoxicity, mutagenicity and reproduction
       toxicity studies have been found.
            The activity of several enzymes was increased in the liver of rats after intra
       peritoneal injection of the technical product (Aho80).
            The 1,2,3,5,6,7- and 1,2,3,4,6,7-isomer can accumulate in the liver of rats
       after oral dosing the technical product (Asp94).
            The limited data available indicate that the target organ for toxicity is
       probably the liver.
       The committee considers the toxicological data base on hexachloronaphthalene
       too poor to recommend a health-based occupational exposure limit.
       Considering the effects found in the inhalation studies in rats, the committee
       concludes that the present MAC value for hexachloronaphthalene of 0.2
       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; 745-6.
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; 250-7.
Arb96  Arbejdstilsynet. Exposure limit values for substances and materials. Copenhagen, Denmark: The
       Working Environment Service; Instruction no. 3.1.0.2. 1996.
Asp86  Asplund L, Jansson B, Sundström G, et al Characterisation of a strongly bioaccumulating
       hexachloronaphthalene. Chemosphere 1986; 15: 619-28.
Asp94  Asplund L, Jakobsson E, Haglund P, et al 1,2,3,5,6,7-Hexachloronaphthalene and
       1,2,3,4,6,7-hexachloronaphthalene - selective retention in rat liver and appearance in wildlife.
       Chemosphere 1994; 28: 2075-86.
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.
Cam83  Campbell MA, Bandeira S, Robertson K, et al Hepta-, hexa-, tetra- and dichloronaphthalene congeners
       as inducers of hepatic microsomal drug-metabolizing enzymes. Toxicology 1983; 26: 193-205.
007-10 Health-based Reassessment of Administrative Occupational Exposure Limits
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<pre>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.
DFG97  Deutsche Forschungsgemeinschaft (DFG). [Toxikologisch-arbeitsmedizinische Begründung von
       MAK-Werten. Chlorierte Naphthaline.] German. Chlorinated naphthalenes. Weinheim, Germany: VCH
       Verlagsgesellschaft mbH 1997. 10 pp.
Dri37  Drinker CK, Warren MF, Bennett GA. The problem of possible systemic effects from certain
       chlorinated hydrocarbons. J Ind Hyg Toxicol 1937; 19: 283-99. Chem Abstr 31:86813.
Ham57  Hambrick GW jr. The effect of substituted naphthalenes on the pilosebaceous apparatus of rabbit and
       man. J Invest Dermatol 1957; 28: 89-103.
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.
Hub62  Huber WG, Link RP. Toxic effects of hexachloronaphthalene on swine. Toxicol Appl Pharmacol 1962;
       4: 257-62.
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.
Lin58  Link RP, Smith JC, Newton DI. Toxic effect of chlorinated naphthalenes in pigs. J Am Vet Med Assoc
       1958; 133: 83-5.
NBO96  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. Hexachloornaftaleen. Alphen aan den Rijn, the Netherlands: Samsom HD Tjeenk Willink,
       1998; 587.
Pop97  Popp W, Norpoth K, Vahrenholz C, Hamm S, et al Polychlorinated naphthalene exposures and liver
       function changes. Am J Ind Med 1997; 32: 413-6.
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  Shelly WB, Kligman AM. The experimental production of acne by penta- and hexachloronaphthalene.
       AMA Arch Dermatol 1957; 689-95.
Str44  Strauss N. Hepato-toxic effects following occupational exposure to Halowax (chlorinated
       hydrocarbons). Rev Gastroenterol 1944; 11: 381-96.
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.
007-11 Hexachloronaphthalene
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<pre>War96  Ward EM, Ruder AM, Suruda A, et al Acute and chronic liver toxicity resulting from exposure to
       chlorinated naphthalenes at a cable manufacturing plant during World War II. Am J Ind Med 1996; 30:
       225-33.
Wei62  Weil CS, Goldberg ME. Toxicological and pharmacological criteria of repeated doses of a hepatotoxic
       agent. Acta Pharmacol Toxicol 1962; 19: 129-38.
007-12 Health-based Reassessment of Administrative Occupational Exposure Limits
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<pre>             Annex
Occupational exposure standards for hexachloronaphthalene in various countries.
country                              occupational               time-weighted        type of exposure     notea      lit refb
-organisation                        exposure limit             average              limit
                                     ppm         mg/m3
the Netherlands
- Ministry                           -           0.2            8h                   administrative       S          SZW00
Germany
- AGS                                            0.2c           8h                   administrative                  TRG00
- DFG MAK-Kom.                       -           -d                                                                  DFG99
Great Britain
- HSE                                -           -                                                                   HSE99
                                                 e
Sweden                               -                                                                               NBO96
Denmark                              -           0.2            8h                                        S          Arb96
USA
- ACGIH                              -           0.2            8h                   TLV                  S          ACG00
- OSHA                               -           0.2            8h                   PEL                  S
- NIOSH                              -           0.2            10 h                 REL                  S
European Union                                                                                                       Hun97
- SCOEL                              -           -
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.
007-13       Hexachloronaphthalene
</pre>

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<pre>007-14 Health-based Reassessment of Administrative Occupational Exposure Limits</pre>

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