FAO Nutrition Meetings 
    Report Series No. 48A 
    WHO/FOOD ADD/70.39


    The content of this document is the 
    result of the deliberations of the Joint 
    FAO/WHO Expert Committee on Food Additives 
    which met in Geneva, 24 June  -2 July 19701

    Food and Agriculture Organization of the United Nations
    World Health Organization


    1 Fourteenth report of the Joint FAO/WHO Expert Committee on Food
    Additives, FAO Nutrition Meetings Report Series in press; Wld Hlth
    Org. techn. Rep. Ser., in press.


    Biological Data

    Biochemical aspects

          Acetone is readily absorbed by solution into the blood after
    inhalation (Kagan, 1924) and progressive accumulation in tissues has
    been noted after 6 hours inhalation (Haggard et al,, 1944). Skin
    absorption occurs only slowly in animals (Lazarew et al., 1931). Large
    oral doses are mostly excreted unchanged through the lungs (40-70%)
    and the kidneys (15-30%) but small amounts are metabolised slowly to
    formate and acetate within 24 hours (Williams, 1959). Dogs excrete in
    their urine some 1-4% of acetone when administered orally at rates of
    0.2-1.6 g/kg. Some 60% is excreted through the lungs (Schwarz, 1898).
    Small doses (1.7 mg/kg body weight) are oxidised mainly to CO2 (53%)
    while some 7-14% is exhaled unchanged (Price & Rittenberg, 1950;
    Sakami & Lafaye, 1950).

          Acetone labelled with C14 in the methyl group was shown to be
    converted by rats to liver glycogen, serine, choline and methionine
    via formate and acetate (Sakami & Lafaye, 1950), while another
    metabolic pathway involved direct conversion to pyruvate in the liver
    (Sakami & Lafaye, 1951). Acetone injected into dogs produced high
    hepatic levels of ß-hydroxybutyric acid (Valdiguie, 1935). Of 1 g.
    administered to man some 24% are excreted through the lungs (Rothkopf,
    1936). I.v. injection into rabbits markedly increased acetoacetic acid
    and ß-hydroxybutyric acid and glucose levels in their blood (Caccuri,
    1937). After i.v. injection at constant rate of 10 g acetone into man
    over 2 hours some 110 mg were lost through the lungs (1 normal, 5
    diabetic subjects). Total urinary ketone excretion did not rise
    significantly in 7 fasting normal subjects but some 360 mg acetone
    were excreted in 24 hours by this route. 12 normal subjects maintained
    high blood levels of acetone for 4 hours after injection but almost
    all had disappeared from the blood after 24 hours. Acetoacetic acid
    levels rose less high in the blood and also remained elevated for 4
    hours after injection. No ß-hydroxybutyric acid appeared. Simultaneous
    i.v. glucose or i.v. insulin did not affect blood acetone levels in 7
    normal fasting subjects. I.v injection of acetone into 12 diabetics
    showed similar levels as in 19 normal subjects. Hence no impairment in
    ability to destroy acetone occurs in diabetics. The rate of breakdown
    is so slow, however, as to preclude that more than a small part of
    normal fat metabolism passes through an acetone stage (Koehler et al.,
    1941). The rat and the dog excrete acetone from the blood at
    approximately similar rates (Abshagen & Rietbrock. 1969).

    Acute toxicity


    Animal     Route             LD50            LD100           References
                                 mg/kg           mg/kg 
                                 bodyweight      bodyweight

    Mouse      inhalation        -               46000 ppm       Schultze, 1932
               oral              10700           -               (Smyth et al., 1962
                                                                 (Shell Chemical Co., 1969
                                 9700            -               Spector, 1956
               i.v.              -               4ml/kg          Walton et al., 1928
               inhalation        -               32000 ppm/      (Smyth et al., 1962
                                                 4 hrs           (Shell Chemical Co., 1969
    Rabbit     intragastric      5340            -               Spector, 1956
                                 -               5-10ml/kg       Walton et al., 1928
               i.v.              -               6-8 ml/kg       Walton et al., 1928
               percutaneous      > 20 ml/kg      -               (Smyth et al., 1962 
                                                                 (Shell Chemical Co., 1969)
    Dog        intragastric      -               8 g/kg          Albertoni, 1884
    The acute effects of acetone are essentially that of a fairly strong
    anaesthetic (Browning, 1965). Repeated intragastric administration of
    8 ml to rabbits for 5-22 days or 8-10 ml to dogs for 8-35 days
    produced albuminuria and epithelial necrosis of convoluted renal
    tubules (Albertoni and Pisenti, 1887). Daily administration of 1-2.5
    g/kg acetone intragastrically to 5 dogs for 9-19 days produced
    nephritis with tubular destruction (Poliak, 1925).

    Special tests


    Acetone was painted on the clipped dorsal skin of 60 female mice three
    times a week for 447 days (64 weeks) as part of another experiment. No
    local papillomata or carcinomata were seen (van Duuren et al., 1965).


          The single injection of 0.1 ml, as part of another experiment,
    into one or both salivary glands of 35 male and 7 female rats produced
    local necrosis and complete regenerative repair after 3 weeks. Animals
    observed for 8 months showed no local or distant tumour formation
    either macroscopically or histologically (Cherry & Glücksmann, 1965).


          At dose levels of 39, and 78 mg/egg hatchability of fresh fertile
    unincubated eggs injected into the yolk sac was reduced to 76% and 47%
    of the normal (McLaughlin et al., 1964). Preincubation injection of a
    maximum dose of 0.1 ml/egg resulted in a 37% hatch, the remainder
    being killed due to yolk coagulation. The hatchability of 3 days
    incubated eggs injected at similar doses was reduced to 20% (Waller,

    Observations in man

          Widespread industrial use over many years (e.g. 2000 ppm inhaled
    for 15 years) only yielded a few cases of mild intoxication, but no
    reports of permanent haematological or organ damage (Browning 1965;
    Rowe & Wolf, 1963; Fassett, 1963). Reversible effects resulting from
    high oral doses occur on liver and kidney and are manifest by
    albuminuria, presence of red and white cells in urine sediment,
    urobilinuria. and increased serum bilirubin, Acute lethal doses are
    estimated to be about 50 ml/man and death is a result of respiratory
    depression, (API Toxicological Reviews. 1955). The TLV is 1000 ppm
    (Amer. Conf. Gov. Industr. Hygienists, 1969).

          15.20g given orally daily to man over several days produced only
    slight drowsiness but no other ill effects (Albertoni, 1884).

          Acute massive intoxication in man has caused collapse and
    possible liver and kidney injury (Sack, 1940, Smith & Mayers, 1944,
    Harris & Jackson, 1952). Dermatitis from frequent sustained skin
    contact and irritation of eyes and the nasal mucosa have been observed
    in man (Browning 1965). Some 10% of inhaled acetone is excreted
    through human skin (Parmeggiani & Sassi, 1954).


          The principal toxic action of large doses results in narcosis and
    repeated smaller doses have produced headache, drowsiness and
    irritation of eyes and mucosal surfaces in man. There is minor
    circumstantial evidence of some toxic effect on the liver and kidney
    in man after acute massive intoxication. Early findings suggest severe
    toxicity in dogs and rabbits on prolonged oral administration of large
    doses. The small amounts likely to be found as residues in food are
    probably oxidised and metabolized by well known pathways. Many years
    of human industrial experience have shown no evidence of significant
    organ damage.

    Tentative Evaluation

          The use of this solvent should be restricted to that determined
    by good manufacturing practice, which is expected to result in minimal
    residues. Within these limits residues are unlikely to have any
    significant toxicological effect.


    1. Abshager, U & Rietbrock, N. (I969) N. Schmied. Arch. Pharmak.,
    264, 110

    2. Albertoni, P. (1884) Arch. Exptl. Pathol. Pharmakol., 18, 219

    3. Albertoni, P. & Pisenti, G. (1887) Arch. Exptl. Pathol. Pharmakol
    23. 393

    4. Amer. Conf. Gov. Ind. Hyg. (1969) Threshold limit values for 1969

    5. A.P.I. Toxicological Review (1965) Unpublished data

    6. Browning, E. (1965) Toxicity and metabolism of industrial
    solvents, Elsevier, Amsterdam

    7. Caccuri, S. (1937) Biochim. e terap. sper., 24, 168

    8. Cherry, C.P. & Glüksmarn, A. (1965) Brit. J. Cancer, 19 287

    9. Fassett, D.W. (1963) in F.A. Patty, Industrial Hygiene and
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    10. Haggard, A.W., Greenberg, L.A. & Turner, J.M. (1944) J. Ind. 
    Hyp. Toxilcol., 26, 133

    11. Harris, L.C. & Jackson, R.H. (1952) B.M.J., 2, 1024

    12. Kagan, E. (1924) Arch. Hyg. Berlin, 94, 41

    13. Koehler, A.E., Windsor, E. & Hill, E. (1941) J. Biol. Chem.,
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    14. Lazarew, N.U., Brussilowskaja, A.J. & Lawrow, J.M. (1931) Arch.
    Gewerbepathol. Gewerbehyg., 2, 641

    15. McLaughlin, J. et al. (1964) Amer. Ind. Hyg. Ass. J., 25, 282

    16. Parmeggiani, L. & Sassi, C. (1954) Med. Lavoro, 45, 431

    17. Poliak, B. (1925) Arch. Exptl. Path. Pharmakol., 205, 220

    18. Price, T.O. & Rittenberg, D. (1950) J. Biol. Chem., 185, 449

    19. Rothkopf, H. (1936) Z. ges exp. Med., 99 464

    20. Rowe, V.K. & Wolf, M.A. (1963) in F.A. Patty, Industrial Hygiene
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    21. Sack, G. (1940) Arch. Gewerbepathol. Gewerbehyg., 10, 80

    22. Sakami, W. & Lafaye, J.M. (1950) J. Biol. Chem., 187, 369

    23. Sakami, W. & Lafaye, J.M. (1951) J. Biol. Chem., 193, 199

    24. Schultze, D. (1932) Dissertation, Univ. Würzburg

    25. Schwarz, L. (1898) Arch. Exptl. Pathol. Pharmakol., 40, I68

    26. Shell Chemicals Co. (1969) Industr. Hyg. Bull., 69-10

    27. Smith, A.R. & Mayers, M.R. (1944) Ind. Bull, New York, State
    Dept. Labor., 23, 174

    28. Smyth, H.F. Jr. et al. (1962) Ind. Hyg. J., 23, 95

    29. Spector, W.S. (1956) Handbook of Toxicology, Vol.1

    30. Valdiguie, P. (1935) Compt. rend. Soc. biol 118 858

    31. Van Duuren, B.L., Orris, L. & Nelson, N. (1965) J. Nat. Conc.
    Inst., 35, 707

    32. Walker, N.E. (1967) Tox. appl. Pharm., 10, 290

    33. Walton, D.C., Kehr, E.F, & Loevenhart, A.S. (1928) J. Pharm.
    Exptl. Ther., 33, 175

    34. Williams, R.T. (1959) Detoxication Mechanisms, Chapman & Hall,

    See Also:
       Toxicological Abbreviations
       Acetone (EHC 207, 1998)
       Acetone (ICSC)
       ACETONE (JECFA Evaluation)