<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>Potassium hydroxide
(CAS No: 1310-58-3)
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/110, The Hague, March 30, 2004
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<pre>Preferred citation:
Health Council of the Netherlands: Committee on Updating of Occupational
Exposure Limits. Potassium hydroxide; Health-based Reassessment of
Administrative Occupational Exposure Limits. The Hague: Health Council of the
Netherlands, 2004; 2000/15OSH/110.
all rights reserved
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<pre>1     Introduction
      The present document contains the assessment of the health hazard of potassium
      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 potassium hydroxide has been based on the
      review by the American Conference of Governmental Industrial Hygienists
      (ACG91). Where relevant, the original publications were reviewed and evaluated
      as will be indicated in the text. In addition, in June 1998, literature was searched
      in the on-line databases Medline, Toxline, and Chemical Abstracts, covering the
      periods 1966 to 11 June 1998, 1965 to 24 February 1998, and 1967 to 16 June
      1998, respectively, and using the following key words: potassium hydroxide,
      KOH, potash, and 1310-58-3. HSDB and RTECS, databases available from CD-
      ROM, were consulted as well (NIO98, NLM98).
           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 L Whitford (Health and Safety Executive, London,
      England). These comments were taken into account when deciding on the final
      version of the document.
           An additional search in Toxline and Medline in August 2003 did not result in
      information changing the committee’s conclusions.
2     Identity
      name                           :    potassium hydroxide
      synonym                        :    caustic potash, potassium hydrate, potassa
      molecular formula              :    KOH
      structural formula             :    -
      CAS number                     :    1310-58-3
110-3 Potassium hydroxide
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<pre>3     Physical and chemical properties
      molecular weight                 :    56.10
      boiling point                    :    1320-1324oC
      melting point                    :    360oC
      flash point                      :    not available
      vapour pressure                  :    not available
      solubility in water              :    very soluble (at 20oC: 112 g/100 mL)
      log Poctanol/water               :    -3.88 (estimated)
      conversion factors               :    not applicable
      Data from ACG91, Pie93, Ric94, http://esc.syrres.com.
      Potassium hydroxide is a white deliquescent solid that may be formed into white
      or slightly yellow lumps, rods, or pellets. It rapidly absorbs moisture and carbon
      dioxide from the air, and deliquesces. Potassium bicarbonate and carbonate may
      be formed. A 0.1 M aqueous solution has a pH of 13.5. (ACG91, Pie93, Ric94).
4     Uses
      Potassium hydroxide is used in the manufacture of soft and liquid soaps, as a
      mordant for wood, in paint and varnish removers, in electroplating,
      photoengraving, and lithography, in drain cleaners, and for the production of
      other potassium compounds such as high-purity potassium carbonate (K2CO3)
      for use in the manufacture of glass (ACG91, Pie93). It is also used in veterinary
      medicine, and in processing of black olives and cocoa (Ric94).
           Potassium hydroxide is also used in preference to the relatively inexpensive
      sodium hydroxide as a strong alkali when the generally greater solubility of
      potassium compounds, in comparison to those of sodium, is important, e.g., as an
      absorbent for carbon dioxide (ACG91).
5     Biotransformation and kinetics
      The committee did not find data on the metabolism and kinetics of potassium
      hydroxide per se.
           Since potassium hydroxide is fully ionised, data on the toxicokinetics of
      potassium are applicable (Tra74).
110-4 Health-based Reassessment of Administrative Occupational Exposure Limits
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<pre>6     Effects and mechanism of action
      Human data
      Contact with eyes or other tissues can cause serious injury (Kuc93, Ric94).
           There are many accounts of (fatal) accidental and suicidal ingestion of
      potassium hydroxide (ACG91). Following ingestion of (a solution of) potassium
      hydroxide, rapid corrosion and perforation of the oesophagus and stomach,
      stricture of the oesophagus, violent pain in throat and epigastrium,
      haematemesis, and collapse may occur (ACG91, ECB95*, Ric94).
           When inhaled in any form, potassium hydroxide is strongly irritating to the
      upper respiratory tract. Acute exposures may cause symptoms in the respiratory
      tract including severe coughing and pain. Additionally, lesions may develop
      along with burning of the mucous membranes. Severe injury is usually avoided
      by the self-limiting sneezing, coughing, and discomfort. Inhalation may be fatal
      as a result of spasm, inflammation, and oedema of the larynx and bronchi,
      chemical pneumonitis, and pulmonary oedema (which can develop with a
      latency period of 5-72 hours). Chronic exposures may cause inflammatory and
      ulcerative changes in the mouth and possibly bronchial and gastrointestinal
      disorders (ACG91, Pie93, Ric94).
           It has been reported that 10% of workers exposed to KOH during the
      production of ascorbic acid developed allergic dermatitis (Ric94).
           At least one case of oesophageal carcinoma at the site of hydroxide-induced
      strictures has been reported (ACG91).
      Animal data
      Potassium hydroxide was judged severely irritating and corrosive after (4- and
      24-hour) dermal application of aqueous solutions of 2% (corresponding to 10 mg
      KOH) or more in rabbits (ECB95). Skin irritation and corrosion was assessed
      following OECD test guideline 404. In this test, application of 0.5 mL of a 5%
      solution of KOH to rabbit skin for 4 hours resulted in a primary irritation index
      (PII) of 5.22, and KOH was hence judged to be severely irritating (ECE95). After
*     Following ‘Council Regulation (EEC) 793/93 on the Evaluation and Control of the Risks of Existing Substances’,
      the European chemical industry by means of a lead company is requested to submit data to the International
      Uniform Chemical Information Database (IUCLID) to allow risk assessment of these chemicals by the member
      states of the EC. The database contained a data sheet on potassium hydroxide (last update: October 23, 1995; lead
      company: Huels AG, Marl, Germany). However, these data were not yet evaluated by a EC member state.
110-5 Potassium hydroxide
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<pre>      application of a 10% solution (0.5 mL) for 4 hours, a PII could not be calculated
      because of the severity of the effects (ECE95). In a skin corrosion test in rabbits,
      a 4-hour application of 0.5 mL of a 2% KOH solution resulted in severe skin
      injury in at least 2 out of 6 rabbits. Hence, a 2% KOH solution was judged to be
      corrosive to the skin. A 1% KOH solution was concluded not to be corrosive
      based on this test protocol (Ver77).
          In an in vitro skin corrosion test based on the use of reconstructed human
      skin cultures, a 1% KOH solution (25 µL added to 1 mL culture medium) did not
      significantly reduce cell viability and was therefore judged non-corrosive,
      whereas in the same test system, a 10 % solution was considered corrosive
      (Per96).
          Application of a 8% KOH solution for 30 seconds to the longitudinally
      opened oesophagus of anaesthetised cats produced marked erythematous injury
      with underlying muscle spasms. Microscopically, complete liquefaction of the
      mucosa with oedema formation and mild inflammation in the underlying
      muscularis mucosa and submucosal adventitial layers were observed (Ash74).
          A 5.0% solution (0.1 mL instilled into the rabbit eye for 5 minutes was
      corrosive, a 1.0% solution (5 minutes or 24 hours) was irritating, a 0.5% solution
      (24 hours) was marginally irritating, and a 0.1% solution was ineffective
      (ECB95). In another study, 1 mg instilled into the rabbit eye for 24 hours (rinsed)
      caused moderate irritation (Ric94). As an alternative to in vivo ocular irritancy
      testing, a 51Cr-release assay with cultured corneal endothelial cells was done and
      the ED50 (i.e., 50% maximal effect) for KOH cytotoxicity was determined at
      1.3x10-2 M correlating with severe irritating in the in vivo test (ECB95).
          No sensitisation was observed in guinea pigs after repeated intracutaneous
      injections of 0.1 mL of a 0.1% solution of KOH (3 times/week at separate skin
      sites, 3 weeks) and a challenge with the same dose 2 weeks after the last injection
      (ECB95).
          Oral LD50 values in rat ranging from 214 to 1890 mg/kg have been reported
      (ECB95, Ric94).
          Dogs given oral doses (levels not reported) developed haemorrhagic gastritis
      with pronounced necrosis in the antrum. Oesophageal necrosis has been
      documented in cats after a 1-second ingestion of 1 ml of a 25% to 36% aqueous
      hydroxide solution. The most important factor is clearly the concentration, rather
      than the volume of the ingested or instilled solution (ACG91). Many authors
      have evaluated the pathogenesis of hydroxide-induced chemical burns of the
      gastrointestinal tract.
110-6 Health-based Reassessment of Administrative Occupational Exposure Limits
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<pre>      Mutagenicity and genotoxicity
      Mutagenic effects were not observed at concentrations up to 0.019% in an in
      vitro genotoxicity test system with E. coli (ECB95). An in vitro genotoxicity test
      with Chinese hamster ovary K1 cells, with metabolic activation was positive
      (Mor89). KOH at 0.0002-0.001 M interferes with the G- and C-banding patterns
      of human chromosomes in vitro (Ber75).
      Carcinogenicity
      Repeated applications of aqueous solutions (3-6%) of KOH to the skin of mice
      for 46 weeks resulted in an increased incidence of skin tumours (males 14%,
      females 15%). Since tumourigenesis was associated with severe skin damage
      inducing marked epidermal hyperplasia, a non-genotoxic mechanism was
      assumed (Ing91).
      Reproduction toxicity
      The committee did not find data on reproduction toxicity studies with potassium
      hydroxide.
7     Existing guidelines
      The current administrative occupational exposure limit (MAC) for potassium
      hydroxide in the Netherlands is a ceiling limit of 2 mg/m3.
           Existing occupational exposure limits for potassium hydroxide in some
      European countries and in the USA are summarised in the annex.
8     Assessment of health hazard
      There are no human data from which an inhalation exposure concentration-effect
      relation can be estimated. However, potassium is a normal body electrolyte. The
      average daily intake was estimated to be 4 grams (Tra74).
           Potassium hydroxide is a corrosive compound. Solutions of 0.5-2.0% are
      irritating to eyes and skin.
           Based on oral LD50 values of 214-1890 mg/kg in rats, the committee
      considers KOH to be harmful if swallowed. There are no data from repeated-
      dose toxicity studies in experimental animals apart from mouse skin painting
      studies. Although repeated application of potassium hydroxide induced an
110-7 Potassium hydroxide
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<pre>       increased incidence of skin tumours, the committee is of the opinion that this is
       not relevant for man, since these skin effects were considered a consequence of
       marked epidermal hyperplasia following repeated and sustained severe skin
       damage.
           Potassium hydroxide was not mutagenic when tested in E. coli; a
       chromosome aberration test in hamster ovary K1 cells (with metabolic
       activation) was positive. In an in vitro test, KOH interfered with G- and C-
       banding patterns of human chromosomes. However, the positive responses are
       more likely due to a high pH in the culture medium than to an intrinsic
       clastogenic activity of KOH.
       The committee considers the toxicological database on potassium 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). Potassium hydroxide. In:
       Documentation of the threshold limit values and biological exposure indices. 6th ed. Cincinnati OH,
       USA: ACGIH®, Inc, 1991: 1284-5.
ACG03a American Conference of Governmental Industrial Hygienists (ACGIH). Guide to occupational
       exposure values - 2003. Cincinnati OH, USA: ACGIH®, Inc, 2003: 111.
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: 48.
Arb02  Arbejdstilsynet. Grænseværdier for stoffer og materialer. Copenhagen, Denmark: Arbejdstilsynet,
       2002: 29 (At-vejledning C.0.1).
Ash74  Ashcraft KW, Padula RT. The effect of dilute corrosives on the esophagus. Pediatrics 1974; 53: 226-
       32.
Ber75  Berger R. Action de l'hydroxide de potassium sur les chromosomes humains. Ann Biol Anim
       Biochim Biophys 1975; 15: 745-50.
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.
EC03   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.
110-8  Health-based Reassessment of Administrative Occupational Exposure Limits
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<pre>ECB95  European Commission (EC): European Chemicals Bureau - Existing Chemicals. Potassium
       hydroxide. IUCLID Data Sheet. Ispra, Italy: EC - JRC Environment Institute, 1995.
ECE95  European Centre for Ecotoxicology and Toxicology of Chemicals (ECETOC). Skin irritation and
       corrosion: reference chemicals data bank. Brussels, Belgium: ECETOC, 1995; Techn Rep No 66.
HSE02  Health and Safety Executive (HSE). EH40/2002. Occupational Exposure Limits 2002. Sudbury
       (Suffolk), UK: HSE Books, 2002: 24.
Ing 91 Ingram AJ, Grasso P. Evidence for and possible mechanisms of non-genotoxic carcinogenesis in
       mouse skin. Mutat Res 1991; 248: 333-40.
Kuc93  Kuckelkorn R, Makropoulos W, Kottek A, et al. Retrospektive Betrachtung von schweren
       Alkaliverätzungen der Augen. Klin Mbl Augenheilk 1993; 203: 397-402.
Mor89  Morita T, Watanabe Y, Takeda K, et al. Effects of pH in the in vitro chromosomal aberration test.
       Mutat Res 1989; 225: 55-60.
NIO98  National Institute for Occupational Safety and Health (NIOSH), ed. Potassium hydroxide. In:
       Registry of Toxic Effects of Chemical Substances (RTECS) [CD-ROM], issue April 1998.
       SilverPlatter International, 1998 (last update potassium hydroxide file: December 1997).
NLM98  US National Library of Medicine (NLM), ed. Potassium hydroxide. In: Hazardous Substances Data
       Bank (HSDB) [CD-ROM], issue April 1998. SilverPlatter International, 1998 (last update potassium
       hydroxide file: March 1998).
Per96  Perkins MA, Osborne R, Johnson GR. Development of an in vitro method for skin corrosion testing.
       Fundam Appl Toxicol 1996; 31: 9-18.
Pie93  Pierce JO. Alkaline materials. In: Clayton GD, Clayton FE, eds. Toxicology. 4th ed. New York: John
       Wiley & Sons, 1993: 766-8 (Patty's industrial hygiene and toxicology; Vol II, Pt A).
Ric94  Richardson ML, Gangolli S, eds. P236 Potassium hydroxide. In: The dictionary of substances and
       their effects. Cambridge, UK: Royal Society of Chemistry, 1994: 761-2 (Vol 2).
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.
SZW03  Ministerie van Sociale Zaken en Werkgelegenheid (SZW). Nationale MAC-lijst 2003. The Hague,
       the Netherlands: Sdu, Servicecentrum Uitgevers, 2003: 31.
Tra74  Tracor-Jitco, Inc. Scientific literature reviews on generally recognized as safe (GRAS) food
       ingredients - sodium and potassium hydroxides. Rockville MD, USA: Tracor-Jitco, Inc, 1974; rep no
       FDABF-GRAS-231 (available from the National Technical Information Service, Springfield VA,
       USA; order no PB-234899).
TRG00  TRGS 900: Grenzwerte in der Luft am Arbeitsplatz; Technische Regeln für Gefahrstoffe. BArbBl
       2000; 2.
Ver77  Vernot EH, MacEwen JD, Haun, CC, et al. Acute toxicity and skin corrosion data for some organic
       and inorganic compounds and aqueous solutions. Toxicol Appl Pharmacol 1977; 42: 417-23.
110-9  Potassium hydroxide
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<pre>              Annex
Occupational exposure limits for potassium hydroxide in various countries.
country                              occupational            time-weighted       type of exposure limit notea     referenceb
- organisation                       exposure limit          average
                                     ppm        mg/m3
the Netherlands
- Ministry of Social Affairs and     -          2            ceiling             administrative                   SZW03
Employment                                                                                                        -
Germany
- AGS                                -          -                                                       -         TRG00
- DFG MAK-Kommission                 -          -                                                                 DFG03
Great-Britain
- HSE                                -          2            15 min              OES                    -         HSE02
Sweden                               -          -                                                                 Swe00
Denmark                              -          2            ceiling                                              Arb02
USA
-ACGIH                               -          2            ceiling             TLV-ceiling                      ACG03b
- OSHA                               -          -            -                   -                                ACG03a
- NIOSH                              -          2            10 h                REL                              ACG03a
European Union
- SCOEL                              -          -                                                                 EC03
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.
110-10        Health-based Reassessment of Administrative Occupational Exposure Limits
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