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<pre>sec-Hexyl acetate
(CAS No: 108-84-9)
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/048, The Hague, 31 October 2002
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<pre>      Preferred citation:
      Health Council of the Netherlands: Committee on Updating of Occupational
      Exposure Limits. sec-Hexyl acetate; Health-based Reassessment of
      Administrative Occupational Exposure Limits. The Hague: Health Council of
      the Netherlands, 2002; 2000/15OSH/048.
      all rights reserved
048-2
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<pre>1     Introduction
      The present document contains the assessment of the health hazard of sec-hexyl
      acetate 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 sec-hexyl acetate 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 data bases 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: hexyl acetate,
      methylamyl acetate, methylpentyl acetate, and 108-84-9. The final search was
      carried out in December 1997.
          In July 2000, the President of the Health Council released a draft of the
      document for public review. The committee received no comments.
          An additional literature search in May 2002 did not result in information
      changing the committee’s conclusions.
2     Identity
       name                       :    sec-hexyl acetate
       synonyms                   :    acetic acid, 1,3-dimethylbutyl ester; 1,3-dimethylbutyl
                                       acetate; methyl amyl acetate; methylisobutylcarbinol
                                       acetate; 4-methyl-2-pentanol acetate; methylisoamyl acetate
       molecular formula          :    C8H16O2
       molecular structure        :    CH3-CO-O-CH(CH3)-CH2 -CH(CH3)2
       CAS number                 :    108-84-9
048-3 sec-Hexyl acetate
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<pre>3     Physical and chemical properties
       molecular weight         :    144.2
       boiling point            :    146.3oC
       flash point              :    43oC (open cup); 45oC (closed cup)
       freezing point           :    -64oC
       vapour pressure          :    0.4 kPa
       solubility in water      :    insoluble
       odour threshold          :    not applicable
       log Poctanol/water       :    2.68 (estimated)
       conversion factors       :    1 mg/m3 = 0.17 ppm
       (20oC, 101.3 kPa)             1 ppm = 6.0 mg/m3
      Data from ACG96, http://esc.syrres.com.
      sec-Hexyl acetate is a colourless liquid with a mild, pleasant fruity odour
      (ACG96). The odour threshold of sec-hexyl acetate was reported to be 0.012
      mg/m3 (0.002 ppm) (Rut86).
4     Uses
      sec-Hexyl acetate is used as a lacquer solvent and in fragrances (ACG96). The
      compound occurs naturally in apples and their leaves.
5     Biotransformation and kinetics
      The committee did not find human or experimental animal data on
      biotransformation and kinetics of sec-hexyl acetate.
6     Effects and mechanism of action
      Human data
      Exposure to a concentration of sec-hexyl acetate of 600 mg/m3 (100 ppm) for 15
      minutes caused eye and upper respiratory tract irritation in the majority of 12
      human volunteers of both sexes. Several of the subjects also complained of an
      unpleasant odour and taste at that level (Sil46).
048-4 Health-based Recommended Occupational Exposure Limits
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<pre>      The committee did not find other human data on effects of exposure to
      sec-hexyl acetate.
      Animal data
      Following application of 0.01 mL of undiluted ester to the uncovered clipped
      belly of 5 albino rabbits, sec-hexyl acetate scored an injury grade of 1 (i.e.,
      giving rise to ‘no reaction whatever’) on a scale from 1 to 10 (Smy54; see also
      Smy49).
          The committee did not find data from studies on skin sensitisation in
      experimental animals.
          When instilled into the eyes of rabbits, sec-hexyl acetate scored an injury
      grade of 2 on a scale of 1 to 10, which was defined as producing an injury of
      1.0 to 5.0 points (out of a maximum of 20) 18 to 24 hours after instillation of
      0.5 mL of undiluted test substance (Smy54; see also Car46).
          Rats could tolerate exposure to a concentrated, probably saturated level* of
      sec-hexyl acetate without mortality occurring for a maximum of 2 hours while
      exposure for 4 hours to 24,000 mg/m3 (4000 ppm) caused mortality in 2/6 rats
      (observation time: 14 days) (Smy54).
          The dermal LD50 in rabbits was >20 mL/kg bw (i.e., >ca. 18 g/kg bw). The
      oral LD50 in rats was 6160 mg/kg bw (observation times: 14 days) (Smy54).
          The committee did not find data from studies on repeated-dose toxicity
      including carcinogenicity and reproduction toxicity or on mutagenicity and
      genotoxicity.
7     Existing guidelines
      The current occupational exposure limit (MAC) of sec-hexyl acetate in the
      Netherlands is 300 mg/m3 (50 ppm), 8-hour TWA.
          Existing occupational exposure limits for sec-hexyl acetate in some
      European countries and in the USA are summarised in the annex.
8     Assessment of health hazard
      Human volunteers experienced exposure to 600 mg/m3 (100 ppm) for 15
      minutes as irritating to eyes and respiratory tract.
*     Theoretically, the concentration in saturated vapour can amount to 4000 ppm (calculated from: vapour pressure in
      Pa/105 Pa) x 106 ppm.
048-5 sec-Hexyl acetate
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<pre>       In experimental animals, liquid sec-hexyl acetate was not and only slightly
       irritating to the skin and eyes of rabbits, respectively. Two out of 6 rats died
       following a 4-hour exposure to 24,000 mg/m3 (4000 ppm). The dermal (in
       rabbits) and oral (in rats) LD50 values were >18,000 and 6160 mg/kg bw,
       respectively.
            The committee did not find data from studies on repeated-dose toxicity
       including carcinogenicity and reproduction toxicity or on mutagenicity and
       genotoxicity.
       The committee considers the toxicological database on sec-hexyl acetate too
       poor to justify recommendation of a health-based occupational exposure limit.
       Furthermore, the committee considers a factor of 2 between the present
       MAC-value and the concentration at which human volunteers experienced eye
       and upper respiratory tract irritation as very small. Therefore, the committee
       concludes that the present MAC-value for sec-hexyl acetate of 300 mg/m3 (50
       ppm), 8-hour TWA, may be too high.
       References
ACG96  American Conference of Governmental Industrial Hygienists (ACGIH). sec-Hexyl acetate. 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, 2002: 67.
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, 2002: 35.
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.
048-6  Health-based Recommended Occupational Exposure Limits
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<pre>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: 53 (rep no 38).
HSE02 Health and Safety Executive (HSE). EH40/2002. Occupational exposure limits 2002. Sudbury
      (Suffolk), England: HSE Books, 2002: 17.
Rut86 Ruth JH. Threshold and irritation levels of several chemical substances: a review. Am Ind Hyg
      Assoc J 1986; 47: A-142-A-151.
Sil46 Silverman L, Schulte HF, First MW. Further studies on sensory response to certain industrial solvent
      vapors. J Ind Hyg Toxicol 1946, 28: 262-6.
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.
SZW02 Ministerie van Sociale Zaken en Werkgelegenheid (SZW). Nationale MAC-lijst 2002. The Hague,
      the Netherlands: Sdu, Servicecentrum Uitgevers, 2002: 30.
TRG00 TRGS 900. Grenzwerte in der Luft am Arbeitsplatz; Technische Regeln für Gefahrstoffe. BArbBl
      2000; 2.
048-7 sec-Hexyl acetate
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<pre>             Annex
Occupational exposure limits for sec-hexyl acetate compounds in various countries
country                              occupational                  time-weighted      type of exposure   notaa    referenceb
 -organisation                       exposure limit                average            limit
                                     ppm          mg/m3
the Netherlands
 - Ministry of Social Affairs        50           300              8h                 administrative              SZW02
and Employment
Germany
 - AGS                               50           300              8h                                             TRG00
                                     50           300              15 min
- DFG MAK-Kommission                 -c           -                8h                 MAK                         DFG02
                                                                   30 min
Great Britain
 - HSE                               50           299              8h                 OES                         HSE02
                                     100          599
Sweden                               -            -                8h                                             Arb00b
Denmark                              50           300              8h                                             Arb00a
USA
 - ACGIH                             50           -                8h                 TLV                         ACG02b
 - OSHA                              50           300              8h                 PEL                         ACG02a
 - NIOSH                             50           300              10 h               REL                         ACG02a
European Union
 - SCOEL                             -            -                                                               CEC00
a
      S = skin notation; this 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
      Listed among compounds for which studies on effects in man or experimental animals have yielded insufficient
      information for the establishment of MAK values.
048-8        Health-based Recommended Occupational Exposure Limits
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