<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>      Trichloronaphthalene
      (CAS reg no: 1321-65-9)
      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/029, The Hague, 13 November 2001
029-1
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<pre>      Preferred citation:
      Health Council of the Netherlands: Committee on Updating of Occupational
      Exposure Limits. Trichloronaphthalene; Health-based Reassessment of
      Administrative Occupational Exposure Limits. The Hague: Health Council of the
      Netherlands, 2001; 2000/15OSH/029.
      all rights reserved
029-2
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<pre>1     Introduction
      The present document contains the assessment of the health hazard of
      trichloronaphthalene 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 Ir M Busschers and H Stouten, M.Sc. (TNO
      Nutrition and Food Research, Zeist, the Netherlands).
           The evaluation of the toxicity of trichloronaphthalene has been based on the
      review by the American Conference of Governmental Industrial Hygienists
      (ACG99). Where relevant, the original publications were reviewed and evaluated
      as will be indicated in the text. In addition, literature was retrieved from the online
      data bases Medline, Toxline, and Chemical Abstracts, covering the period 1966
      to 26 April 1999 (19990416/UP), 1965 to 29 January 1999 (19990129/ED), 1967 to 24
      April 1999 (19990424/ED; vol 130, iss 18), respectively, using the following key
      words: trichloronaphthalene, the CAS registry number 1321-65-9, and a number
      of other CAS registry numbers related to positional isomers*. HSDB and
      RTECS, data bases available from CD-ROM, were consulted as well (NIO99,
      NLM99). The final literature search has been carried out in April 1999.
           In April 2001, the President of the Health Council released a draft of the
      document for public review. The committee received no comments.
2     Identity
       name                    :    trichloronaphthalene
       synonyms                :    -
       molecular formula       :    C10H5Cl3
       structural formula      :
       CAS reg no              :    1321-65-9
      Data from ACG99, Ada44
      The technical products of chloronaphthalenes are often called Halowaxes. These
      Halowaxes are graded according to their chlorine content and all are therefore
*     55720-40-6, 55720-39-3, 55720-38-2, 55720-37-1, 55720-36-0, 55720-35-9, 55720-34-8,
      55720-33-7, 51570-44-6, 51570-43-5, 50402-52-3, 50402-51-2, 2437-55-0, and 2437-54-9
029-3 Trichloronaphthalene
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<pre>      mixtures of various isomers with one or two main derivatives predominating
      (Ben94, Cro70). Halowax 1012 is reported to be 'apparently' a
      trichloronaphthalene (Ada44) and Halowax 1001 a mixture of tri- and
      tetrachloronaphthalene (She57) or a mixture of tri- to hexachloronaphthalene,
      predominantly containing tetra- and pentachloronaphthalene (Cro70).
3     Physical and chemical properties
       molecular weight            :     231.5
       boiling point               :     304-354 oC
       melting point               :     93 oC
       flash point:                :     200 oC (open cup)
       vapour pressure             :     at 20 oC: <0.133 kPa
       solubility in water         :     insoluble in water
       log P octanol/water         :     5.43
       conversion factors          :     not applicable
       (20 oC, 101.3 kPa)
      Data from ACG99, Ano86, Gre98, NIO81
      Trichloronaphthalene is a colourless to pale yellow solid with an aromatic odour.
4     Uses
      Trichloronaphthalene is used in lubricants and in the manufacture of insulation
      for electrical wire (ACG99). It was also reported to be used as a paper capacitor
      impregnant and in timber preservatives (Cro70).
5     Biotransformation and kinetics
      The committee did not find data on uptake, distribution, biotransformation, and
      excretion of trichloronaphthalene.
029-4 Health-based Reassessment of Administrative Occupational Exposure Limits
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<pre>6     Effects and mechanism of action
      Human data
      Mayers et al. (May38) described several cases of chloracne among the workers
      in 2 plants employing a mixture of tri- and tetrachloronaphthalene. However,
      according to Crow (Cro70), the evidence for the acnegenic effects of tri- and
      tetrachloronaphthalenes is confusing and most of the studies on this issue are
      incomplete and lacking a full description of all the chemicals the workers were
      exposed to. Therefore, other factors were probably responsible for the acne, for
      example, the use of pitch in these plants. Crow (Cro70) investigated a paper
      capacitor plant where no chloracne was observed between 1956 and 1963 in an
      area where a mixture of tri- and tetrachloronaphthalene was used. In another area
      of this plant, exposure to penta- and hexachlonaphthalenes produced chloracne
      in several workers. When this mixture was abandoned and replaced by a tri- and
      tetrachloronaphthalene mixture with polysterene, chloracne ceased. Moreover,
      daily experimental exposure of the ear (auricle) of 3 men to a mixture of tri- and
      tetrachloronaphthalene (Halowax 1001) in a 50% mineral oil suspension for 30
      days did not result in acne or any other skin effects (She57).
          There are several reports of hepatic injury, chloracne and/or mortality among
      humans working in manufacturing plants using chlorinated naphthalenes (Dri37,
      Pop97, Str44, War96). Although it was claimed that the main exposure was to
      chlorinated naphthalenes ('Halowax'), no details about specific types of
      chlorinated naphthalenes or exposure to other chemicals were given. Therefore,
      the committee could not establish the causal role of trichloronaphthalene.
      Animal data
      Irritation
      In a study performed in 1938-40, solutions of trichloronaphthalene (Halowax
      1012; chlorine content: 48%) in olive oil were applied to the ear and abdomen of
      unkown experimental animals (n=1/solution/area). No experimental details were
      presented; no (vehicle) controls were included. Application to the ear of a 10 or
      20% solution, once daily, 5 days/week, for 20 or 17 times, respectively, was
      reported to produce some slight irritation (very slight to slight erythema,
      exfoliation, hair loss, follicle prominence and enlargement, slight hair loss). Upon
029-5 Trichloronaphthalene
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<pre>      microscopic examination, there were no effects in the animal treated with the 10%
      solution while very slight epithelial hyperplasia and pitting and slight exfoliation
      were seen in the animal treated with the 20% solution. Application (bandaged) of
      the same solutions to the abdomen, for 11 or 12 times (over a 15- or 16-day
      period), produced moderate to severe erythema, respectively (Ada44).
      Single exposure
      The 100% survival dose and the 100% fatal dose after a single oral administration
      of trichloronaphthalene (Halowax 1012) to guinea pigs were 400 mg/kg bw and
      1800 mg/kg bw, respectively (Ada44).
      Repeated exposure
      Two groups of rats (n=80/group) were exposed to a mixture of
      trichloronaphthalene with traces of tetrachloronaphthalene (chlorine content:
      49.4%; ratio not given) at an average concentration of either 1.31 mg/m3 (range;
      0.10-2.60 mg/m3), 16 hours/day, 6 days/week, for up to 134 days (total exposure:
      1896 hours), or 10.97 mg/m3 (range: 5.78-16.49 mg/m3), 16 hours/day, 6 days/week,
      for up to 102 days (total exposure: 1232 hours). The animals of the
      low-concentration group revealed only very slight liver injury, which consisted
      of an occasional paler appearance and, microscopically, of low incidences of
      slightly enlarged cells, increased granularity of cytoplasm, vacuolisation, and,
      occasionally, the presence of mitotic figures, whereas the findings in the animals
      of the high-concentration group were similar but increased in severity.
      Additionally, fat vacuoles and hyaline droplets were occasionally observed
      (Ben38, Dri37). The committtee noticed the absence of data on a control group.
      Further, in view of the chlorine contents of pure tri- and tetrachloronaphthalene
      (46.0 and 53.4%, resp), the mixture (with a chlorine content of 49.4%) may have
      contained more than 'traces' of tetrachloronaphthalene.
           When rats (n=10) were given oral (diet) doses of 3000 mg/day/rat (n=10) of a
      mixture of tri- and tetrachloronaphthalene (see above) for up to 182 days, no
      treatment-related mortality, effects on body weight or signs of toxicity were
      observed. After 2 months of exposure, slight swelling of the hepatic cells,
      accompanied by vacuolisation due to accumulation of large amounts of fat was
      seen. These changes only slightly increased with longer exposure (Ben38, Dri37).
      The committee noticed the absence of a control group.
029-6 Health-based Reassessment of Administrative Occupational Exposure Limits
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<pre>          Daily subcutaneous injection of doses of 15 mg/kg/bw of a mixture of tri- and
      tetrachloronaphthalene in paraffin oil, for 2 months, did not affect survival,
      behaviour, body weight, red or white blood cells, or histology (Fli36).
      The committee did not find data on the potential mutagenicity/genotoxicity,
      carcinogenicity, or reproduction toxicity of trichloronaphthalene.
7     Existing guidelines
      The current administrative occupational exposure limit (MAC) for
      trichloronaphthalene in the Netherlands is 5 mg/m3, 8-h TWA.
          Existing occupational exposure limits for trichloronaphthalene in some
      European countries and in the USA are summarised in the annex.
8     Assessment of health hazard
      Occupational exposure to a mixture of tri- and tetrachloronaphthalenes was
      associated with several cases of chloracne (May38). However, it is more likely
      that other factors were responsible for the acne, for example the use of pitch in
      these plants (Cro70). Moreover, daily experimental dermal exposure of humans to
      a mixture of tri- and tetrachloronaphthalenes did not result in acne or any other
      skin effects (She57) and Halowax 1012 (reported to be 'apparently' a
      trichloronaphthalene) produced irritation but no acnegenic effects after dermal
      exposure in an unknown animal species (Ada44). Liver injury and mortality have
      been associated with exposure to chlorinated naphthalenes as well (Dri37, Pop97,
      Str44, War96), but since no details about specific types of chlorinated
      naphthalenes or exposure to other chemicals were given, the committee cannot
      draw a conclusion with respect to a causal role of trichloronaphthalene per se.
          Single oral dosing of guinea pigs at 1800 mg/kg bw resulted in 100%
      mortality, whereas all guinea pigs survived a dose of 400 mg/kg bw (Ada44).
          Following repeated exposure, the liver was shown to be the target organ.
          Inhalation studies in rats with trichloronaphthalene including unkown
      amounts of tetrachloronaphthalene resulted in very slight liver injury (1.31
      mg/m3, 16 h/day, for up to 134 days) or more severe liver injury with some fatty
      degeneration (10.97 mg/m3, 16 h/day, for 102 days) (Ben38, Dri37). Due to the
      mentioned shortcomings (no control group, wide range in exposure
      concentration, uncertainties in the composition of the exposure mixture), this
029-7 Trichloronaphthalene
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<pre>       study is considered not suitable as a starting point for deriving an occupational
       exposure limit.
            Dietary administration (3000 mg/day/rat, up to 136 days) of a similar mixture
       of tri- and tetrachloronaphthalene resulted in fatty infiltration of the liver (Ben38,
       Dri37).
            No effects were observed after subcutaneous injection of high doses (15
       mg/kg bw, for 2 months) of a mixture of tri- and tetrachloronaphthalene to rabbits
       (Fli36).
            No data were found on the potential mutagenicity/genotoxicity,
       carcinogenicity, or reproduction toxicity of trichloronaphthalene.
       The committee considers the data base on trichloronaphthalene too poor to
       justify recommendation of a health-based occupational exposure limit.
       The committee concludes that, based on the slight liver injury observed in a
       subchronic inhalation study in rats with average exposure concentrations of
       approximately 1 and 11 mg/m3, the present MAC value of 5 mg/m3 is at least one
       order of magnitude too high.
       References
ACG99  American Conference of Governmental Industrial Hygienists (ACGIH).
       Trichloronaphthalene. In: TLVs ® and other occupational exposure values - 1999.
       [CD-ROM]. Cincinnati OH, USA: ACGIH, 1999.
ACG00  American Conference of Governmental Industrial Hygienists (ACGIH). Guide to occupational
       exposure values - 2000. Cincinnati OH, USA: ACGIH® , Inc, 2000: 123.
ACG01  American Conference of Governmental Industrial Hygienists (ACGIH). 2001 TLVs ® and
       BEIs® . Threshold Limit Values for chemical substances and fysical agents. Biological
       Exposure Indices. Cincinnati OH, USA: ACGIH® , Inc, 2001: 57.
Ada44  Adams EM. The toxicity of chlorinated naphthalenes. Midland MI, USA: Dow Chem Co,
       Biochem Res Lab, 1944 (available from NTIS, Springfield VA, USA; order no
       NTIS/OTS0206141).
Ano86  Anonymous. Trichloronaphthalene. Dangerous Prop Ind Mater Rep 1986; 6(6): 78-80.
Arb00a Arbejdstilsynet. Grænseværdier for stoffer og materialer. Copenhagen, Denmark:
       Arbejdstilsynet, 2000; At-vejledning C.0.1.
Arb00b Arbetarskyddstyrelsen. Hygieniska gränsvärden och åtgärder mot luftföroreningar. Solna,
       Sweden: National Board of Occupational Safety and Health, 2000; Ordinance AFS 2000/3.
029-8  Health-based Reassessment of Administrative Occupational Exposure Limits
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<pre>Ben38 Bennett GA, Drinker CK, 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, eds.
      Toxicology. 4th ed. New York: John Wiley & Sons, 1994: 2507-13. (Patty’s industrial
      hygiene and toxicology; Vol II, Pt D).
CEC00 Commission of the European Communities (CEC). Commission Directive 2000/39/EC of 8
      June 2000 establishing a first list of indicative occupational exposure limit values in
      implementation of Council Directive 98/24/EC on the protection of the health and safety of
      workers from the risks related to chemical agents at work. Official Journal of the European
      Communities 2000; L142 (16/06/2000): 47-50.
Cro70 Crow KD. Chloracne. Trans St John’s Hosp Dermatol Soc 1970; 56(2): 79-99.
DFG01 Deutsche Forschungsgemeinschaft (DFG): Commission for the Investigaton of Health
      Hazards of Chemical compounds in the Work Area. List of MAK and BAT values 2001.
      Weinheim, FRG: Wiley-VCH, 2001: 35, 112 (rep no 37).
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.
Fli36 Flinn FB, Jarvik NE. Action of certain chlorinated naphthalenes on the liver. Proc Soc Biol
      Med 1936; 35: 118-20.
Gre98 Greim H, ed. Chlorierte Naphthaline. In: Gesundheidsschädliche Arbeitsstoffe.
      Toxikologisch-arbeitsmedizinische Begründungen von MAK-Werte (Maximale
      Arbeitsplatz-Konzentrationen). 1st-27th ed. Weinheim, FRG: Wiley-VCH, 1998.
HSE01 Health and Safety Executive (HSE). EH40/2001. Occupational Exposure Limits 2001.
      Sudbury (Suffolk), England: HSE Books, 2001.
May38 Mayers MR, Silverberg MG. Skin conditions resulting from exposure to certain chlorinated
      hydrocarbons. J Ind Hyg Toxicol 1938; 20: 244-58.
NIO81 National Institute of Occupational Safety and Health (NIOSH). Occupational health guideline
      for trichloronaphthalene. In: Occupational health guidelines for chemical hazards.
      Washington DC, USA:NIOSH, 1981; DHHS (NIOSH) pub no 81-123.
NIO99 National Institute of Occupational Safety and Health (NIOSH). Naphthalene, trichloro-. In:
      Registry of Toxic Effects of Chemical Substances (RTECS). [CD-ROM], issue July 1999.
      SilverPlatter International, 1999 (last update trichloronaphthalene file: July 1999).
NLM99 US National Library of Medicine (NLM). Trichloronaphthalene. In: Hazardous Substances
      Data Bank (HSDB). [CD-ROM], issue July 1999. SilverPlatter International, 1999 (last
      update trichloronaphthalene file: January 1999).
She57 Shelley WB, Kligman AM. The experimental production of acne by penta- and
      hexachloronaphthalenes. AMA Arch Dermatol 1957; 75: 689-95.
SZW01 Ministerie van Sociale Zaken en Werkgelegenheid (SZW). Nationale MAC-lijst 2001. The
      Hague, The Netherlands: Sdu, Servicecentrum Uitgevers, 2001: 42.
029-9 Trichloronaphthalene
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<pre>TRG00       TRGS 900. Grenzwerte in der Luft am Arbeitsplatz; Technische Regeln für Gefahrstoffe.
            BArbBl 2000; 2.
            Annex
Occupational exposure limits for trichloronaphthalene in various countries.
country                       occupational               time-weighted      type of exposure notea     lit refb
-organisation                 exposure limit             average            limit
                              ppm         mg/m 3
the Netherlands
-Ministry                     -           5              8h                 administrative             SZW01
Germany
-AGS                          -           5c             8h                                  S         TRG00
-DFG MAK-Kom.                 -           -d                                                 S         DFG01
Great-Britain
-HSE                          -           -                                                            HSE01
Sweden                        -           -                                                            Arb00b
Denmark                       -           5                                                            Arb00a
USA
-ACGIH                        -           5              8h                 TLV              S         ACG01
-OSHA                         -           5              8h                 PEL              S         ACG00
-NIOSH                        -           5              10 h               REL              S         ACG00
European Union
-SCOEL                        -           -                                                            CEC00
a
     S = skin notation; which means that skin absorbtion may contribute considerably to the body burden; sens =
     substance can cause sensitisation
b
     Reference to the most recent official publication of occupational exposure limits
c
     Inhalable fraction
d
     As chlorinated naphthalenes, these compounds are listed among substances for which studies of the effects in
     man or in experimental animals have yielded insufficient information for the establishment of MAK values
029-10      Health-based Reassessment of Administrative Occupational Exposure Limits
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