<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>      o-Chlorostyrene
      (CAS reg no: 2039-87-4)
      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/020, The Hague, 13 November 2001
020-1
</pre>

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

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

<pre>      Preferred citation:
      Health Council of the Netherlands: Committee on Updating of Occupational
      Exposure Limits. o-Chlorostyrene; Health-based Reassessment of Administrative
      Occupational Exposure Limits. The Hague: Health Council of the Netherlands,
      2001; 2000/15OSH/020.
      all rights reserved
020-2
</pre>

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

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

<pre>1     Introduction
      The present document contains the assessment of the health hazard of
      o-chlorostyrene 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 MA Maclaine Pont, M.Sc. (Wageningen University,
      Wageningen, the Netherlands).
           The evaluation of the toxicity of o-chlorostyrene 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 data
      bases Toxline, Medline, and Chemical Abstracts covering the period of 1981 until
      October 1999, 1966 until December 1999, and 1937 until September 1999,
      respectively, and using the key words: o-chlorostyrene, 2-chlorostyrene, and
      benzene, 1-chloro-2-ethenyl- and styrene, o-chloro- 2039-87-4. The final
      literature search has been carried out in December 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                           :     o-chlorostyrene
       synonyms                       :     1-chloro-2-ethenylbenzene; 2-chlorostyrene
       molecular formula              :     C8H7Cl
       structural formula             :
       CAS reg no                     :     2039-87-4
      Data from How92 .
020-3 o-Chlorostyrene
</pre>

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

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

<pre>3     Physical and chemical properties
       molecular weight            :     138.6
       boiling point               :     188.7 oC
       melting point               :     -63.1 oC
       flash point                 :     58 oC
       vapour pressure             :     at 25 0C: 0.13 kPa
       solubility in water         :     at 20 oC: <1 mg/mL
       odour threshold             :     approximately 5.8 mg/m 3
       log P octanol/water         :     3.54 (estimated)
       conversion factors          :     1 ppm = 5.76 mg/m 3
       (20 oC, 101.3 kPa)                1 mg/m 3 = 0.174 ppm
      Data from Dow47, Dow72, Kei87, Lid96, http://esc.syrres.com.
      o-Chlorostyrene has a disagreeable odour at relatively low vapour
      concentrations (Dow72).
4     Uses
      o-Chlorostyrene is used in organic synthesis and in the preparation of speciality
      polymers (ACG99).
5     Biotransformation and kinetics
      There is no indication, from the skin irritation tests conducted, that this material
      is absorbed through the skin in toxic amounts (Dow61). No further data are
      available.
6     Effects and mechanism of action
      Human data
      No data have been found.
020-4 Health-based Reassessment of Administrative Occupational Exposure Limits
</pre>

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

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

<pre>      Animal data
      o-Chlorostyrene is moderately irritating to the skin of rabbits. Single applications
      to the ears caused only very slight irritation, while repeated applications caused
      a slight to moderate irritation characterised by hyperaemia, exfoliation, hair loss,
      and mild blistering. A marked reaction characterised by hyperaemia, oedema, and
      necrosis resulted from bandaging the material onto the shaven bellies of rabbits
      (Dow46). There are no quantitative data. From another source, quantitative data
      are available: 10 mg irritates the skin of rabbits, and 500 mg is irritating to the
      eyes of rabbits (Lew92).
      The following acute toxicity data were found (Lew92):
           LD50 oral rat: 5200 mg/kg body weight
           LD50 dermal rabbit: 20,000 mg/kg body weight.
      Rats (n=2) survived exposure by inhalation to a saturated atmosphere*, for 7
      hours. Some kidney injury was observed at autopsy. The animals were drowsy
      and unsteady upon removal from the chamber. The eyes and nose were slightly
      wet (Dow61).
           Groups of 24 rats, 3 rabbits, 12 guinea pigs, and 1 dog of each sex were
      exposed 7 hours/day, 5 days/week, for 6 months to a concentration of 101 ppm
      (580 mg/m3). On the basis of appearance, growth, behaviour, mortality,
      haematology, blood urea nitrogen, alkaline phophatase, serum glutamic pyruvic
      transaminase (alanine aminotransferase), blood serum protein, organ weights,
      and macroscopic examinations, there were no adverse effects in any species.
      Microscopic examination of rats, rabbits, guinea pigs, and dogs indicated no
      clear-cut compound-related effect, but there appeared to be a slightly higher
      incidence of those liver and kidney changes usually found in controls (no further
      details are presented) (Dow72).
      o-Chlorostyrene was not mutagenic when tested in S. typhimurium strains TA97,
      TA98, TA100, and TA1535 with and without rat or hamster liver metabolic
      activation (Zei88).
*     The (theoretic) concentration in saturated air can be calculated using the formula: (vapour pressure in Pa
      x 10 6 ppm)/10 5 Pa. Using a vapour pressure of 130 Pa (at 25°C), the committee estimates that these
      animals could have been exposed to, at most, 1300 ppm or (roughly) 7540 mg/m 3.
020-5 o-Chlorostyrene
</pre>

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

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

<pre>      The committee did not find data from genotoxicity tests in mammalian cell
      systems in vitro or in mammals in vivo or on the potential carcinogenicity or
      reproduction toxicity of o-chlorostyrene.
7     Existing guidelines
      The current administrative occupational exposure limit (MAC) for
      o-chlorostyrene in the Netherlands is 285 mg/m3 (50 ppm), 8-hour TWA.
           Existing occupational exposure limits for o-chlorostyrene in some European
      countries and in the USA are summarized in the annex.
8     Assessment of health hazard
      o-Chlorostyrene was moderately irritating to the skin and eyes of rabbits; in skin,
      it induced hyperaemia, oedema, and necrosis (Dow46, Lew92).
           Based on rat oral and rabbit dermal LD 50-values of 5200 and 20,000 mg/kg bw,
      o-chlorostyrene would not be classified regarding its acute toxicity.
           After inhalation exposure to saturated atmospheres (estimated to be ca. 1700
      ppm or 7540 mg/m3), for 7 hours, drowsiness and unsteadiness, as well as some
      kidney injury were observed.
           In a 6-month inhalation study in which rats, rabbits, guinea pigs, and dogs
      were exposed to 101 ppm (580 mg/m3), 7 hours/day, 5 days/week, for 6 months,
      slightly higher incidences of kidney and liver changes were found in exposed
      animals when compared to controls (Dow72). Due to the absence of detailed
      data, the committee could not draw definite conclusions from this study.
           o-Chlorostyrene did not induce mutations in an in vitro bacterial test system.
           The committee did not find data from genotoxicity tests in mammalian cell
      systems in vitro or in mammals in vivo or on the potential carcinogenicity or
      reproduction toxicity of o-chlorostyrene.
      The committee considers the toxicological data base on o-chlorostyrene too poor
      to justify recommendation of a health-based occupational exposure limit.
      Based on a slightly higher incidence of microscopic kidney and liver changes in
      experimental animals exposed to 580 mg/m3, for 6 months, the committee
      concludes that the present MAC-value of 285 mg/m3 (50 ppm), as an 8-hour
      time-weighted average, for o-chlorostyrene may be too high.
020-6 Health-based Reassessment of Administrative Occupational Exposure Limits
</pre>

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

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

<pre>       References
ACG99  American Conference of Governmental Industrial Hygienists (ACGIH). o-Chlorostyrene. In:
       TLVs ® and other occupational exposure values - 1999. [CD-ROM]. Cincinnati OH, USA;
       ACGIH® , Inc, 1999.
ACG00  American Conference of Governmental Industrial Hygienists (ACGIH). Guide to occupational
       exposure values - 2000. Cincinnati OH, USA: ACGIH® , Inc, 2000: 27.
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: 22.
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.
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.
DFG01  Deutsche Forschungsgemeinschaft (DFG): Commission for the Investigation of Health
       Hazards of Chemical Compounds in the Work Area. List of MAK and BAT values 2001.
       Maximum concentrations and biological tolerance values at the workplace. Weinheim, FRG:
       Wiley-VCH, 2001; rep no 37.
Dow46  The Dow Chemical Company. Brief study relative to the toxicity of chlorostyrenes.
       Confidential report, file T16.4-112-1, Switzerland, 1946, 2 pp.
Dow47  The Dow Chemical Company. Preliminary toxicity tests of o-chlorostyrene. Confidential
       report, file T16.4-112-1, Switzerland, 1947, 2 pp.
Dow61  The Dow Chemical Company. Results of range finding toxicological tests on
       ortho-chlorostyrene. Confidential report, file T16.4-112-2, Switzerland, 1961, 3 pp.
Dow72  The Dow Chemical Company. Summary report of suggested TLV Documentation on
       o-chlorostyrene. File 16.4-112-(M), K495, Switzerland, 1972, 3 pp.
How92  Howard PH, Neil M, ed. Dictionary of chemical names and synonyms. Chelsea MA, USA:
       Lewis Publishers, 1992.
HSE01  Health and Safety Executive (HSE). EH40/2001. Occupational exposure limits 2001. Sudbury
       (Suffolk), England: HSE Books, 2001.
Kei87  Keith LH, Walters DB, ed. o-Chlorostyrene. In: Compendium of safte data sheets for
       research and industrial chemicals. New York, USA: VCH Publishers Inc, 1987: 2216-7.
020-7  o-Chlorostyrene
</pre>

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

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

<pre>Lew92 Lewis RJ Sr, ed. Sax's dangerous properties of industrial materials. 8th ed. New York, USA:
      Van Nostrand Reinhold, 1992: 875-6
Lid96 Lide DR, Frederikse HPR, ed. CRC Handbook of chemistry and physics. 77th ed. Boca Raton
      FL, USA: CRC Press, 1996: 3-34.
SZW01 Ministerie van Sociale Zaken en Werkgelegenheid (SZW). Nationale MAC-lijst 2001. The
      Hague, the Netherlands: Sdu, Servicecentrum Uitgevers, 2001: 21.
TRG00 TRGS 900. Grenzwerte in der Luft am Arbeitsplatz; Technische Regeln für Gefahrstoffe.
      BArbBl 2000; 2.
Zei88 Zeiger E, Anderson B, Haworth S, et al. Salmonella mutagenicity tests: IV: results from the
      testing of 300 chemicals. Environ Mol Mutagen 1988; 11 (Suppl 12): 1-157.
020-8 Health-based Reassessment of Administrative Occupational Exposure Limits
</pre>

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

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

<pre>            Annex
Occupational exposure limits for o-chlorostyrene 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                     50            285              8h             administrative              SZW01
Germany
- AGS                          -             285                                               S         TRG00
- DFG MAK-Kom.                 -             -                                                           DFG01
Great Britain
- HSE                          -             -                                                           HSE01
Sweden                         -             -                                                           Arb00b
Denmark                        50            285              8h                                         Arb00a
USA
- ACGIH                        50            -                8h             TLV                         ACG01
                               75            -                15 min         STEL
- OSHA                         -             -                                                           ACG00
- NIOSH                        50            285              10 h           REL                         ACG00
                               75            430              15 min         STEL
European Union
  - SCOEL                      -             -                                                           CEC00
a
      S = skin notation, which means that skin absorption may contribute considerably to body burden; sens =
      substance can cause sensitisation
b
      Reference to the most recent official publication of occupational exposure limits
020-9       o-Chlorostyrene
</pre>

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

<br><br>