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<pre>2-Methylcyclohexanone
(CAS No: 583-60-8)
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/049, The Hague, 31 October 2002
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<pre>Preferred citation:
Health Council of the Netherlands: Committee on Updating of Occupational
Exposure Limits. 2-Methylcyclohexanone; Health-based reassessment of
current administrative occupational exposure limits in the Netherlands.
The Hague: Health Council of the Netherlands, 2002; 2000/15OSH/049.
all rights reserved
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<pre>1     Introduction
      The present document contains the assessment of the health hazard of
      2-methylcyclohexanone 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 AAE Wibowo, Ph.D. (Coronel
      Institute of the Academic Medical Centre, Amsterdam, the Netherlands).
           The evaluation of the toxicity of 2-methylcyclohexanone has been based on
      the review the American Conference of Governmental Occupational Hygienists
      (ACGIH) (ACG96). Where relevant, the original publications were reviewed
      and evaluated as will be indicated in the text. In addition, literature was
      retrieved from the databases Medline, Chemical Abstracts, Embase (starting
      from 1966, 1970 and 1988, respectively), and HSEline, NIOSHTIC, Cisdoc,
      and Mhidas (backwards from 1997) and Poltox (Toxline, Cambr Sc Abstr,
      FSTA) (backwards from 1994), using the following key words:
      2-methylcyclohexanone and 583-60-8. The final search was carried out in
      October 1997.
           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 organisations: P Wardenbach Ph.D. (Bundesanstalt für
      Arbeitsschutz und Arbeitsmedizin, Dortmund, Germany). These comments
      were taken into account in deciding on the final version of the document.
           An additional literature search in May 2002 did not result in information
      changing the committee’s conclusions.
2     Identity
       name                           :     2-methylcyclohexanone
       synonyms                       :     o-methylcyclohexanone; 1-methylcyclohexan-2-one
       molecular formula              :     CH3C5H9CO
       structural formular            :
       CAS number                     :     583 - 60 - 8
049-3 2-Methylcyclohexanone
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<pre>3     Physical and chemical properties
       molecular weight                :     112,2
       boiling point                   :     165oC
       melting point                   :     -13.9oC
       flash point                     :     48oC (closed cup)
       vapour pressure                 :     at 55oC: 1.33 kPa
       solubility in water             :     insoluble
       log Poctanol/water              :     1.54 (estimated)
       conversion factors              :     1 mg/m3 = 0.21 ppm
       (20oC, 101.3 kPa)                     1 ppm = 4.67 mg/m3
      Data from ACG96, http://esc.syrres.com
      2-Methylcyclohexanone is a somewhat viscous colourless liquid with an odour
      similar to that of acetone. The compound is chemically stable, but may darken
      when exposed to light. Although methylcyclohexanones are available as pure
      compounds, they are usually found as isomeric mixtures (ortho-, meta- and
      para-) (ACG96). The odour threshold is not known.
4     Uses
      Methylcyclohexanone is used as a solvent in making lacquers, varnishes, and
      plastics; in the leather industry; and as a rust remover. The commercial product
      is a mixture of isomers (ACG96).
5     Biotransformation and kinetics
      The committeere did not find data on the absorption and distribution of
      methylcyclohexanones. Topping et al. reported that methylcyclohexanones are
      reduced to methylcyclohexanols and excreted in urine as sulphuric and
      glucuronic acid conjugates (Top94).
049-4 Health-based Recommended Occupational Exposure Limits
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<pre>6     Effects
      Human data
      The committee did not find human data on effects due to exposure to
      2-methylcyclohexanone.
      Animal data
       Following application of 0.01 mL of undiluted ester to the uncovered clipped
      abdomen of 5 albino rabbits, 2-methylcyclohexanone scored an injury grade of
      3 (i.e., giving rise to ‘a strong capillary injection’) on a scale from 1 to 10
      (Smy69; see also Smy49).
           The committee did not find data from studies on skin sensitisation in
      experimental animals.
           When instilled into the eyes of rabbits, 2-methylcyclohexanone scored an
      injury grade of 5 on a scale of 1 to 10, which was defined as producing an
      injury of up to 5.0 points (out of a maximum of 20) 18 to 24 hours after
      instillation of 0.005 mL of undiluted test substance (0.02 mL gives over 5.0
      points) (Smy69; see also Car46)*.
      A 4-hour exposure to a concentration of 2-methylhexanone of 13,090 mg/m3
      (2800 ppm) caused mortality in 3/6 rats (Smy69). Topping et al. cited a study
      from 1938 in which mice, guinea pigs, and rats exposed to 16,345 mg/m3 (3500
      ppm) methylcyclohexanone vapour for 30 minutes showed irritation of the
      mucous membranes and effects on the central nervous system. Rabbits and cats
      became somnolent after a 1-hour exposure to 11,675 mg/m3 (2500 ppm). A
      concentration of 2100 mg/m3 (450 ppm) produced irritation in mice (Top94).
           The oral LD50 for rats was 1980 (range: 1369-2868) mg/kg bw and the
      dermal LD50 for rabbits was 1637 mg/kg bw (Smy69). This suggests absorption
      of the compound through the skin.
           Treon et al. performed a number of acute and repeated-dose experiments
      (Tre43a, Tre43b) with ‘methylcyclohexanone’ but since this was a mixture of
      chiefly 3- and 4-methylcyclohexanone (Tre43b), this studies are not discussed
      here.
*     Grade 5 was also characterised as a ‘severe burn from 0.005 mL’ (Smy54).
049-5 2-Methylcyclohexanone
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<pre>       The committee did not find data on studies on repeated-dose toxicity, including
       carcinogenicity and reproduction toxicity, or on mutagenicity and genotoxicity
       of 2-methylcyclohexanone.
7      Existing guidelines
       The current administrative occupational exposure limit (MAC) of
       2-methylcyclohexanone in the Netherlands is 230 mg/m3 (50 ppm), with a skin
       notation.
           Existing occupational exposure limits for 2-methylcyclohexanone in some
       European countries and in the USA are summarised in the annex.
8      Assessment of health hazard
       The committee did not find human data on effects due to exposure to
       2-methylcyclohexanone or data from studies on repeated-dose toxicity,
       including carcinogenicity and reproduction toxicity, and on mutagenicity or
       genotoxicity were not found.
       In experimental animals, 2-methylhexanone was a skin- and eye-irritating
       compound. Based on acute lethality data, 2-methylhexanone was of low toxicity
       following inhalation (4-hour LC50 rat: 13,090 mg/m3 or 2800 ppm), dermal
       (LD50 rabbit: 1637 mg/kg bw), and oral (LD50 rat: 1980 mg/kg bw) exposure.
       The committtee considers the toxicological database on 2-methylcyclohexanone
       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
ACG96  American Conference of Governmental Industrial Hygienists (ACGIH). o-Methylcyclohexanone. In:
       TLVs and other occupational exposure values - 1996 [CD ROM], version 1.7 - s4 02/01/95.
       Cincinnati OH, USA: ACGIH, 1996.
ACG02a American Conference of Governmental Industrial Hygienists (ACGIH). Guide to occupational
       exposure values -2002. Cincinnati OH, USA: ACGIH®, Inc, 2002: 83.
049-6  Health-based Recommended Occupational Exposure Limits
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<pre>ACG02b American Conference of Governmental Industrial Hygienists (ACGIH). 2002 TLVs® and BEIs®.
       Threshold Limit Values for chemical substances and fysical agents. Biological Exposure Indices.
       Cincinnati OH, USA: ACGIH®, Inc, 2002: 41.
Arb00a Arbejdstilsynet. Grænseværdier for stoffer og materialer. Copenhagen, Denmark: Arbejdstilsynet,
       2000; At-vejledning C.0.1.
Arb00b Arbetarskyddsstyrelsen. Hygieniska gränsvärden och åtgärder mot luftföroreningar. Solna, Sweden:
       Arbetarskyddsstyrelsen, 2000; Ordinance AFS 2000:3.
Car46  Carpenter CP, Smyth HF Jr. Chemical burns of the rabbit cornea. Am J Ophthalmol 1946; 29:
       1363-72.
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.
DFG02  Deutsche Forschungsgemeinschaft (DFG): Senatskommission zur Prüfung gesundheitsschädlicher
       Arbeitsstoffe. MAK- und BAT-Werte-Liste 2002. Maximale Arbeitsplatzkonzentrationen und
       Biologische Arbeitsstofftoleranzwerte. Weinheim, FRG: Wiley-VCH, 2002: 79 (rep no 38).
HSE02  Health and Safety Executive (HSE). EH40/2002. Occupational exposure limits 2002. Sudbury
       (Suffolk), England: HSE Books, 2002: 21.
Smy49  Smyth HF Jr, Carpenter CP, Weil CS, et al. Range-finding toxicity data, List III. J Ind Hyg Toxicol
       1949; 31: 60-2.
Smy54  Smyth HF Jr, Carpenter CP, Weil CS, et al. Range-finding toxicity data. List V. AMA Arch Ind Hyg
       Occup Med 1954; 10: 61-8.
Smy69  Smyth HF Jr, Carpenter CP, Weil CS, et al. Range finding toxicity data: List VII. Am Ind Hyg Ass J
       1969; 30: 470-6.
SZW02  Ministerie van Sociale Zaken en Werkgelegenheid (SZW). Nationale MAC-lijst 2002. The Hague,
       the Netherlands: Sdu, Servicecentrum Uitgevers, 2002: 34.
Tre43a Treon JF, Crutchfield WE Jr, Kitzmiller KV. The physiogical response of rabbits to cyclohexane,
       methylcyclohexane, and certain derivatives of these compounds. I. oral administration and cutaneous
       application. J Ind Hyg Toxcicol 1943; 25: 199-214.
Tre43b Treon JF, Crutchfield WE Jr, Kitzmiller KV. The physiogical response of rabbits to cyclohexane,
       methylcyclohexane, and certain derivatives of these compounds. II. Inhalation. J Ind Hyg Toxicol
       1943; 25: 323-7.
Top94  Topping DC, Morgott DA, David RM, et al. Methylcyclohexanones. In: Clayton GD, Clayton FE,
       eds. Toxicology. 4th ed. New York, USA: John Wiley & Sons, Inc, 1994: 1842-3.(Patty’s industrial
       hygiene and toxicology; Vol II, Pt C.
TRG00  TRGS 900. Grenzwerte in der Luft am Arbeitsplatz; Technische Regeln für Gefahrstoffe. BArbBl
       2000; 2.
049-7  2-Methylcyclohexanone
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<pre>             Annex
Occupational exposure limits for 2-methylcyclohexanone in various countries.
country                              occupational                  time-weighted     type of        notea       referenceb
-organisation                        exposure limit                average           exposure limit
                                     ppm         mg/m3
the Netherlands
-Ministry of Social Affairs          50          230               8h                administrative S           SZW02
and Employment
Germany
-AGS                                 50          230               8h                               S           TRG00
                                     200         920               15 min
-DFG MAK-Kommission                  -c          -                                   MAK            S           DFG02
Great-Britain
-HSE                                 50          233               8h                OES                        HSE02
                                     75          350               15 min            STEL
Sweden                               -           -                                                              Arb00b
Denmark                              50          230               8h                OEL            S           Arb00a
USA
-ACGIH                               50          -                 8h                TLV            S           ACG02b
                                     75          -                 15 min            STEL
-OSHA                                100         460               8h                PEL            S           ACG02a
-NIOSH                               50          230               10 h              REL            S           ACG02a
                                     75          345               15 min            STEL
European Union
-SCOEL                               -           -                                                              CEC00
a
     S = skin notation; which mean 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
     Listed among substances for which studies of the effects in man or experimental animals have yielded insufficient
     information for the establishment of MAK values.
049-8        Health-based Recommended Occupational Exposure Limits
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