The evaluations contained in this publication were prepared by the
    Joint FAO/WHO Expert Committee on Food Additives which met in Rome,
    4-13 June 19741

    World Health Organization     Geneva     1975


    1  Eighteenth Report of the Joint FAO/WHO Expert Committee on
    Food Additives, Wld Hlth Org. techn. Rep. Ser., 1974, No. 557.
    FAO Nutrition Meetings Report Series, 1974, No. 54.



         This compound has been evaluated for acceptable daily intake by
    the Joint FAO/WHO Expert Committee on Food Additives (see Annex 1,
    Ref. No. 10) in 1966.

         Since the previous evaluation additional data have become
    available and are summarized and discussed in the following monograph.
    The previously published monograph has been expanded and is reproduced
    in its entirety below.



         In man 30-90% of ingested beta-carotene is excreted in the faeces
    and concomitant intake of fat does not improve absorption. Excessive
    doses depress the Vitamin A activity of the absorbed fraction. Only
    small amounts appear in the serum. Beta-carotene dissolved in oil is
    much better absorbed, 10-41% for adults, 50-80% for children (Fraps &
    Meinke, 1945).

         Vitamin E is necessary to prevent enzymatic destruction and bile
    acids are necessary for absorption (Wagner, 1962).

         Other workers quote 11% absorption by adults and 2.6% by babies
    of a dose of 20 mg carotene (Kübler, 1963).

         The major fraction of absorbed beta-carotene passes unchanged
    through the gut wall and reaches the liver via the portal system and
    to a small extent via the lymphatics. Some beta-carotene is stored in
    the liver but is never released as such, and some is converted to
    Vitamin A in jejunum, liver, lung, muscle and serum and stored in the
    liver as Vitamin A. Large doses lead to a rise in serum carotene and
    subsequent deposition in organs and the horny layer of the skin
    without necessarily raising the Vitamin A serum level (Zbinden &
    Studer, 1958).

         Gastrointestinal and liver and renal disease, diabetes mellitus
    and phosphor poisoning reduce the conversion to Vitamin A and
    myxoedema blocks conversion. Infants and small children have a smaller
    capacity for this conversion (Wagner, 1962).

         Beta-carotene is transmitted in milk. In infants a single
    administration of 20 mg of beta-carotene in milk produces a rise in
    the beta-carotene blood level, peaking in 24 hours and a rise in the
    Vitamin A ester blood level but practically no change in the Vitamin A
    alcohol blood level (Auckland, 1952).


    Special studies

    Special studies on hypercarotenemia

         Hypercarotenemia per se is harmless and causes no symptoms nor
    is there normally any evidence of hypervitaminosis A. It disappears if
    excess intake of beta-carotene is discontinued (Abrahamson et al.,
    1962; Nieman et al., 1954). No hypervitaminosis A was noted in
    volunteers given beta-carotene over extended periods (Bagdon et al.,

         The possibility of producing hypervitaminosis A in animals by
    hypercarotenemia has never been completely proven because of the poor
    absorption and slow conversion. No effects have been shown in rats
    given the equivalent of 40 000-70 000 IU Vitamin A esters/day either
    i.v., i.p. or orally. However, oral or s.c. doses equivalent to
    1500 IU Vitamin A/day caused accelerated epithelial growth in adult
    rats and changes in oestrus (Nieman et al., 1954). In another
    experiment, 20 mg/kg bw of beta-carotene was fed to 30 young rats on a
    Vitamin A-deficient diet for 6 to 11 months without any deleterious
    effects, particularly without evidence of hypervitaminosis A or liver

         High doses of beta-carotene reduce liver storage of labelled
    dl-gamma-tocopherol acetate to 70% (Brubacher et al., 1965).

    Acute toxicity

    Animal    Route          mg/kg bw         Reference

    Rat       i.m. (oil)     > 1 000          Zbinden & Studer, (1958)

    Dog       Oral           > 8 000          Nieman et al., (1954)

    Short-term studies

         Several short-term studies in rat and dog showed the same results
    as the human studies reported (Anonymous, 1960).

    Long-term studies


         A four-generation study at dietary levels of 0 ppm and 1000 ppm
    of beta-carotene for 110 weeks showed no adverse effects in any of the
    generations (Bagdon et al., 1960).


         Fifteen subjects received 60 mg beta-carotene daily for three
    months. Serum carotene levels rose from 128 µg to a maximum of
    308 µg/100 ml after one month while Vitamin A levels remained
    unchanged. No clinical signs of hypervitaminosis A were seen.
    (Greenberg et al., 1959). Other subjects ate several pounds of raw
    carrots daily, resulting in some skin discoloration. Beta-carotene
    appeared in the milk (Zbinden & Studer, 1958).


         Beta-carotene is a normal constituent of the human diet and is
    commonly ingested over the entire lifespan of man. Its biological
    importance rests on the provitamin A function. Concerning the known
    clinical syndrome of hypervitaminosis A in man, evidence from human
    experience indicates that in very exceptional circumstances excessive
    dietary intakes can occur. Such cases have been reported in the
    literature but do not relate to food additive use of this colour.
    Despite poor absorption from the gastrointestinal tract cases of human
    hypervitaminosis have occurred. The results of short-term toxicity
    studies in rats and dogs have shown that over a wide range of doses
    toxic effects have not been produced. Similarly, multigeneration tests
    in rats using levels up to 1000 ppm have not revealed any adverse

         In the light of the above comments it appears justifiable to
    apply a smaller safety factor to the no-effect level established in
    long-term studies.


    Level causing no toxicological effect

         Rat: 0.1% (= 1000 ppm) in the diet equivalent to 50 mg/kg bw.

    Estimate of acceptable daily intake for man

         0-5 mg/kg bw*


    Abrahamson, I. A. sr & Abrahamson, I. A. jr (1962) Arch. Ophth., 68, 4

    Auckland, G. (1952) Brit. Med. J., 2, 267

    Bagdon, R. E., Zbinden, G. & Studer, A. (1960) Toxic. Appl. Pharm., 2,

    Bernhard, K. (1963) Wiss. Veröff. Dtsch. Gesellsch. Ernährung, 9, 169

    Brubacher, G. et al. (1965) Z. Ernährw., 5, 190

    Fraps, G. S. & Meinke, W. W. (1945) Arch. Biochem., 6, 323

    Greenberg, R., Cornbleet, T. & Joffay, A. I. (1959) J. Invest.
         Dermatol., 32, 599

    Hoffmann-La Roche (1960) Unpublished report submitted to WHO

    Kübler, W. (1963) Wiss. Veröff. Dtsch. Gesellsch. Ernährung., 9, 222

    Nieman, C. & Klein, Obbink, H. J. (1954) Vit. Horm., 12, 60

    Wagner, K. (1962) Wien, Kl. Wschr., 74, 909

    Zbinden, J. & Studer, A. (1958) Z. Lebensm. Unters. Forsch., 108, 114


    *    As sum of the carotenoids;    Beta-carotene


                                       Beta-carotenoic acid methyl ester

                                       Beta-carotenoic acid ethyl ester

    See Also:
       Toxicological Abbreviations