<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>Calcium hydroxide
(CAS No: 1305-62-0)
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/096 The Hague, March 30, 2004
</pre>

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

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

<pre>Preferred citation:
Health Council of the Netherlands: Committee on Updating of Occupational
Exposure Limits. Calcium hydroxide; Health-based Reassessment of
Administrative Occupational Exposure Limits. The Hague: Health Council of the
Netherlands, 2004; 2000/15OSH/096.
all rights reserved
</pre>

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

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

<pre>1     Introduction
      The present document contains the assessment of the health hazard of calcium
      hydroxide 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 C de Heer, Ph.D. and H Stouten, M.Sc. (TNO
      Nutrition and Food Research, Zeist, the Netherlands).
           The evaluation of the toxicity of calcium hydroxide has been based on the
      review by the American Conference of Governmental Industrial Hygienists
      (ACGIH) (ACG91). Where relevant, the original publications were reviewed and
      evaluated as will be indicated in the text. In addition, in May 1998, literature was
      searched in the on-line databases Medline, Toxline, and Chemical Abstracts
      starting from 1966, 1965, and 1967, respectively, and using the following key
      words: calcium hydroxide, calcinosis, and 1305-62-2.
           In March 2000, the President of the Health Council released a draft of the
      document for public review. The committee received comments by the following
      individuals and organisations: A Aalto (Ministry of Social Affairs and Health,
      Tampere, Finland) and P Wardenbach, Ph.D. (Bundesanstalt für Arbeitsschutz
      and Arbeitsmedizin, Dortmund, FRG). These comments were taken into account
      when deciding on the final version of the document.
           An additional search in Toxline and Medline in November 2003 did not
      result in information changing the committee’s conclusions.
2     Identity
      name                      :   calcium hydroxide
      synonyms                      calcium dihydroxide; calcium hydrate; carboxide; hydrated lime; slaked
                                    lime; caustic lime; lime milk; lime water
      molecular formula         :   CaH2O2
      structural formula            Ca(OH)2
      CAS number                :   1305-62-0
096-3 Calcium hydroxide
</pre>

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

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

<pre>3     Physical and chemical properties
      molecular weight           :    74.09
      boiling point              :    -
      melting point              :    decomposes at 580oC (dehydrates to form CaO)
      flash point                :    not flammable
      vapour pressure            :    -
      solubility in water        :    slightly soluble (at 20oC: 1.7 g/100 mL)
      log Poctanol/water         :    -0.87 (estimated)
      conversion factors         :    not applicable
      Data from ACG91, EC03a*, NLM03, http://esc.syrres.com.
      Calcium hydroxide is a soft, white, odourless, crystalline powder with an
      alkaline bitter taste.
4     Uses
      Calcium hydroxide has many industrial applications. Its major uses are in mortar,
      plaster, cement, and other building and paving materials. It is also used in
      lubricants, drilling fluids, fireproofing coatings, and pesticides, in the
      manufacture of paper pulp, in dehairing animal hides, in water and sewage
      treatment, in flue gas purification, and, in the chemical industry, as a scrubbing
      and neutralising agent (ACG91, EC03a).
      In routine dental practice, calcium hydroxide is used as a constituent of root
      canal sealers (Eco95).
5     Biotransformation and kinetics
      The committee did not find data on the kinetics of calcium hydroxide.
6     Effects and mechanism of action
      Human data
      Acute exposures to calcium hydroxide may cause irritation, along with coughing,
      pain, and possibly burns of the mucous membranes with, in severe acute
*     See remark in ‘References’.
096-4 Health-based Reassessment of Administrative Occupational Exposure Limits
</pre>

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

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

<pre>      exposures, pulmonary oedema and hypotension with weak and rapid pulse
      (Pie93, Ric93). There are numerous case reports on accidental exposures to
      calcium hydroxide resulting in corneal and skin alkali burns and caustic ulcers
      (e.g., Ear85, Fis85, Gel92, Koo92, Kuc93, Luo95, OGr89). Generally, these
      effects are caused by the solid material and less commonly or rarely by solutions
      (see EC03a).
          Ingestion of alkali is reported to be followed by severe pain, vomiting
      (containing blood and desquamated mucosal lining), diarrhoea, and collapse. If
      death does not occur within the first 24 hours, the patient may improve in 2-4
      days (EC03a, NLM03).
          According to (not documented) statements in ACG91 and EC03a,
      ‘epidemiological syndromes’ related to lime exposure during production and
      application are not known, and workers in lime factories exposed to lime for up
      to 40 years have not experienced adverse effects.
          In an explorative epidemiological study, mortality was studied by multiple
      testing in 607 male cement workers employed in 1939 in England and Wales.
      Person-years at risk were calculated from 1948-1981. Expected numbers of
      deaths for the causes of death analysed were calculated on the basis of the
      corresponding male mortality rates for England and Wales. The standardised
      mortality ratio (SMR) for stomach cancer was significantly raised in the overall
      cohort (SMR 175, based on 22 deaths), was significantly increased under control
      of social class, and was associated with an index of cement plant dust exposure
      (McD84). However, no information was available on latency and tenure, and a
      surrogate measure of cement plant dust exposure was employed (job held in
      1939) which is not an accurate surrogate measure of cumulative or average
      respirable dust exposure.
          In another study, the mortality from stomach cancer of United States cement
      plant and quarry workers was addressed. A cohort of 5292 men who had been
      employed for at least 5 years in a non-asbestos cement plant between 1950 and
      1960 was traced to 1 January 1980. The mortality experience was evaluated for
      4231 white men for whom complete work histories and demographic
      information were available. The expected number of deaths was computed using
      age-year specific death rates from the United States white male population.
      Deaths from stomach cancer were significantly increased during 1965-1969, but
      not over the entire follow-up period (1950-1980) (SMR 135, based on 27
      deaths). Additionally, stomach cancer mortality was not significantly associated
      with tenure under separate control for age at follow-up, latency, nativity, or year
      of birth (Ama86). Amandus concluded that there is no association between
      exposure to cement-plant dust and death from stomach cancer possibly because
096-5 Calcium hydroxide
</pre>

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

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

<pre>      of the low statistical power. Therefore, a conclusion awaits a study with a
      sufficient number of cases with information on gastric-cancer risk factors.
          Based on the available data, McDowell concluded that epidemiological
      evidence is insufficient to reach any definite conclusions on the association
      between cement-dust exposure and stomach cancer (McD86).
          Chronic oral exposures may cause inflammatory and ulcerative changes in
      the mouth and gastrointestinal problems (Pie93).
          Betel-quid chewing is a popular habit in Southeast Asian countries held
      responsible for the very high incidence of oral cancers in these areas (Jen94,
      Kiy92, Tho92). Although the composition of betel quid varies in different
      geographic locations, it generally consists of betel nut (Areca catechu), Piper
      betle leaf, and slaked lime (calcium hydroxide) with or without tobacco.
      Aqueous extracts of such lime (50-800 µg/mL) increased proliferation of oral
      mucosal fibroblasts in vitro by 20-40% (Jen94), but did not induce cytotoxicity
      (up to concentrations of 800 µg/mL) or DNA strand breaks (at concentrations up
      to 3 mg/mL). The site of oral squamous cell tumours in betel-quid chewers
      corresponded strongly (p<0.0001) with the predominant site of contact with
      slaked lime (Jen94). Therefore, reactive oxygen species from betel-quid
      ingredients together with sustained lime-induced cell proliferation was suggested
      as a possible mechanism underlying the induction of these tumours (Jen94,
      Kiy92, Tho92). However, the relevance of these epidemiological observations
      for the evaluation of calcium hydroxide carcinogenicity is questionable because
      in addition to calcium hydroxide, lime also consists of secret seasoning additives
      (Jen94).
      Animal data
      Calcium hydroxide was reported not to be irritating in rabbits when tested
      according to OECD guideline 404 (acute dermal irritation/corrosion), but no
      reference to a particular study was made (EC03a). It was stated not to be
      sensitising (no reference given) (EC03a). When placed as a dry powder (10-100
      mg) on the cornea of rabbits (Draize test), calcium hydroxide was corrosive
      (Gri80). Rabbits exposed for 1 minute to a paste of calcium hydroxide in the eyes
      followed by cleaning and rinsing with a physiological salt solution displayed a
      gradual decrease in mucopolysaccharides of the cornea, reaching a maximum at
      24 hours, which did not return to normal levels within 3 months (Pie93).
          The oral LD50 values in rats and mice were 7340 and 7300 mg/kg bw,
      respectively (NIO03, Smy69).
096-6 Health-based Reassessment of Administrative Occupational Exposure Limits
</pre>

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

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

<pre>          The long-term exposure (70-98 weeks, 3-5 times/week) of the cheek pouch to
      several ingredients of betel quid was studied in Syrian hamsters. It was shown
      that repeated applications of calcium hydroxide (50 mg, alone or in combination
      with other ingredients) severely injured the hamster cheek pouch. Three of the
      inflammatory and hyperplastic lesions that developed in the pouches of 26
      calcium hydroxide-treated hamsters progressed to epithelial atypia (Dun66).
          In male rats, subchronic exposure to calcium hydroxide in drinking water
      (50 and 350 mg/l)* for 3 months resulted in restlessness, aggression, reduced
      food intake, and body weight loss. In addition, decreased counts for erythrocytes
      and phagocytes, and decreased haemoglobin were noted. At sacrifice, gross
      necropsy showed inflammation of the small intestine and dystrophic changes in
      the stomach, kidneys, and liver (Pie93, EC03a).
      The committee did not find data from genotoxicity, mutagenicity, reproduction
      and developmental toxicity studies.
7     Existing guidelines
      The current administrative occupational exposure limit (MAC) for calcium
      hydroxide in the Netherlands is 5 mg/m3 (total dust), 8-hour TWA.
          Existing occupational exposure limits for calcium hydroxide in some
      European countries and in the USA are summarised in the annex.
8     Assessment of health hazard
      Solid calcium hydroxide is corrosive to the eyes and may cause severe injury to
      the skin. Aqueous solutions are (far) less irritating. There are no adequate human
      data from which inhalation exposure concentration-effect relationships can be
      derived. Two epidemiological studies that addressed the association between
      cement-dust exposure and stomach cancer were considered insufficient to reach
      any conclusions on the association between cement dust exposure and stomach
      cancer (McD84, McD86). However, no adverse effects have been experienced
      by long-term exposed workers.
          Oral LD50 values of approximately 7300 mg/kg bw were reported for rats and
      mice. No adequate repeated-dose toxicity (including carcinogenicity and
      reproduction toxicity) or genotoxicity/mutagenicity studies were available.
*     Equivalent to 5 and 35 mg/kg bw/day, assuming a daily water consumption of 25 mL and a body
      weight of 250 g.
096-7 Calcium hydroxide
</pre>

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

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

<pre>       Because of the likely occurrence of local effects, repeated inhalation studies
       would be the preferred type of study.
       The committee considers the toxicological database on calcium hydroxide too
       poor to justify recommendation of a health-based occupational exposure limit.
       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). Calcium hydroxide. In:
       Documentation of the threshold limit values and biological exposure indices. 6th ed. Cincinnati OH,
       USA; ACGIH®, Inc, 1991: 199.
ACG03a American Conference of Governmental Industrial Hygienists (ACGIH). Guide to occupational
       exposure values - 2003. Cincinnati OH, USA: ACGIH®, Inc, 2003: 21.
ACG03b American Conference of Governmental Industrial Hygienists (ACGIH). 2003 TLVs® and BEIs®
       based on the documentation of the Threshold Limit Values for chemical substances and physical
       agents & Biological Exposure Indices. Cincinnati OH, USA: ACGIH®, Inc, 2003: 19.
Ama86  Amandus HE. Mortality from stomach cancer in United States cement plant and quarry workers,
       1950-80. Br J Ind Med 1986; 43: 526-8.
Arb02  Arbejdstilsynet. Grænseværdier for stoffer og materialer. Copenhagen, Denmark: Arbejdstilsynet,
       2002: 19 (At-vejledning C.1.0).
DFG03  Deutsche Forschungsgemeinschaft (DFG): Commission for the Investigation of Health Hazards of
       Chemical Compounds in the Work Area. List of MAK and BAT values 2003. Maximum
       concentrations and Biological Tolerance Values at the workplace Weinheim, FRG: Wiley-VCH
       Verlag GmbH & Co. KGaA, 2003; rep no 39.
Dun66  Dunham LJ, Muir CS, Hamner JE III. Epithelial atypia in hamster cheek pouches treated repeatedly
       with calcium hydroxide. Br J Cancer 1966; 20: 588-93.
Ear85  Early SH, Simpson RL. Caustic burns from contact with wet cement. JAMA 1985; 254: 528-9.
EC03a  European Commission (EC): European Chemicals Bureau (ECB). IUCLID Dataset - calcium
       hydroxide. In: Public data on high volume chemicals IUCLID CD-ROM. Year 2000 ed. Ispra, Italy:
       European Commission, Joint Research Centre, Institute for Health and Consumer Protection,
       European Chemicals Bureau, 2000*.
*      This dossier is a compilation based on data reported by the European Chemicals Industry following ‘Council
       Regulation (EEC) No 793/93 on the Evaluation and Control of the Risks of Existing substances’ to allow a risk
       assessment by member states of the EC. However, the data in the dossier have not undergone any evaluation by
       any EC member state yet.
096-8  Health-based Reassessment of Administrative Occupational Exposure Limits
</pre>

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

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

<pre>EC03b European Commission: Directorate General of Employment and Social Affairs. Occupational
      exposure limits (OELs). http://europe.eu.int/comm/employment_social/h&s/areas/oels_en.htm.
Eco95 Economides N, Kotsaki-Kovatsi VP, Poulopoulos A, et al. Experimental study of the
      biocompatibility of four root canal sealers and their influence on the zinc and calcium content of
      several tissues. J Endod 1995; 21: 122-7.
Fis86 Fischer G, Commens C. Cement burns: rare or rarely reported? Australas J Dermatol 1986; 27: 8-10.
Gel92 Gelmetti C, Cecca E. Caustic ulcers caused by calcium hydroxide in 2 adolescent football players.
      Contact Dermatitis 1992; 27: 265-6.
Gri80 Griffith JF, Nixon GA, Bruce RD, et al. Dose-response studies with chemical irritants in the albino
      rabbit eye as a basis for selecting optimum testing conditions for predicting hazard to the human eye.
      Toxicol Appl Pharmacol 1980; 55: 501-13.
HSE02 Health and Safety Executive (HSE). EH40/2002. Occupational Exposure Limits 2002. Sudbury
      (Suffolk), UK: HSE Books, 2002: 14.
Jen94 Jeng JH, Kuo ML, Hahn LJ, et al. Genotoxic and non-genotoxic effects of betel quid ingredients on
      oral mucosal fibroblasts in vitro. J Dent Res 1994; 73: 1043-9.
Kiy92 Kiyingi KS. Slaked lime and betel nut cancer in Papua New Guinea. (Letter). Lancet 1992; 340:
      1357-8.
Koo92 Koo CC, Morgan BDG, Parkhouse N. Cement water - the hidden hazard. Burns 1992; 18: 513-4.
Kuc93 Kuckelkorn R, Makropoulos W, Kottek A, et al. Retrospektive Betrachtung von schweren
      Alkaliverätzungen der Augen. Klin Mbl Augenheilk 1993; 203: 397-402.
Luo95 Luong KVQ, Nguyen LTH. Cement burn. J Fam Pract 1995; 41: 601-2.
McD84 McDowall ME. A mortality study of cement workers. Br J Ind Med 1984; 41: 179-82.
McD86 McDowall M. Cement workers and cancer: epidemiology at work? Br J Ind Med 1986; 43: 505-6.
NIO03 US National Institute for Occupational Safety and Health (NIOSH), ed. Calcium hydroxide. In:
      Registry of Toxic Effects of Chemical Substances (RTECS) (last update calcium hydroxide file:
      October 2002); http://www.cdc.gov/niosh.
NLM03 US National Library of Medicine (NLM), ed. Calcium hydroxide. In: Hazardous Substances Data
      Bank (HSDB) (last revision data calcium hydroxide file: March 2003; last review date: September
      1994); http://toxnet.nlm.nih.gov.
OGr89 O'Grady TC. Mass eye casualties at sea. Mil Med 1989; 154: 596-8.
Pie93 Pierce JO. Alkaline materials. In: Clayton GD, Clayton FE, eds. Toxicology. 4th ed. New York: John
      Wiley & Sons, 1993: 762-4. (Patty's industrial hygiene and toxicology; Vol II, Pt A).
Ric93 Richardson ML, Gangolli S, eds. C31 Calcium hydroxide. In: The dictionary of substances and their
      effects. Cambridge, UK: Royal Society of Chemistry, 1993: 53-4 (Vol 2).
Smy69 Smyth HF Jr, Carpenter CP, Weil CS, et al. Range-finding toxicity data: list VII. Am Ind Hyg Assoc
      J 1969; 30: 470-6.
Swe00 Swedish National Board of Occupational Safety and Health. Occupational exposure limit values and
      measures against air contaminants. Solna, Sweden: National Board of Occupational Safety and
      Health, 2000; Ordinance AFS 2000:3.
096-9 Calcium hydroxide
</pre>

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

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

<pre>SZW03  Ministerie van Sociale Zaken en Werkgelegenheid (SZW). Nationale MAC-lijst 2003. The Hague,
       the Netherlands: Sdu, Servicecentrum Uitgevers, 2003: 20.
Tho92  Thomas SJ, MacLennan R. Slaked lime and betel nut cancer in Papua New Guinea. Lancet 1992;
       340: 577-8.
TRG00  TRGS 900: Grenzwerte in der Luft am Arbeitsplatz; Technische Regeln für Gefahrstoffe. BArbBl
       2000; 2.
096-10 Health-based Reassessment of Administrative Occupational Exposure Limits
</pre>

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

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

<pre>              Annex
Occupational exposure limits for calcium hydroxide in various countries.
country                           occupational             time-weighted       type of exposure notea       referenceb
- organisation                    exposure limit           average             limit
                                  ppm          mg/m3
the Netherlands
- Ministry of Social Affairs and -             5           8h                  administrative               SZW03
Employment                        -            -
Germany
- AGS                             -            5c          8h                                               TRG00
- DFG MAK-Kommission              -            -                                                            DFG03
Great-Britain
- HSE                             -            5           8h                  OES                          HSE03
Sweden                            -            -                                                            Swe00
Denmark                           -            5           8h                                               Arb02
USA
- ACGIH                           -            5           8h                  TLV                          ACG03b
- OSHA                            -            5d          8h                  PEL                          ACG03a
                                  -            15e         8h
- NIOSH                           -            5           10 h                REL                          ACG03a
European Union
- SCOEL                           -            5                               ILVf                         EC03b
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.
c
     Inhalable dust.
d
     Respirable fraction.
e
     Total dust.
f
     Listed among compounds for which OELs are already included in Commission Directives.
096-11        Calcium hydroxide
</pre>

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

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

<pre>096-12 Health-based Reassessment of Administrative Occupational Exposure Limits</pre>

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

<br><br>