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    INTERNATIONAL PROGRAMME ON CHEMICAL SAFETY

    WORLD HEALTH ORGANIZATION



    TOXICOLOGICAL EVALUATION OF SOME
    FOOD COLOURS, EMULSIFIERS, STABILIZERS,
    ANTI-CAKING AGENTS AND CERTAIN
    OTHER SUBSTANCES



    FAO Nutrition Meetings Report Series 
    No. 46A WHO/FOOD ADD/70.36




    The content of this document is the result of the deliberations of the
    Joint FAO/WHO Expert Committee on Food Additives which met in Rome,
    27 May - 4 June 19691





    Food and Agriculture Organization of the United Nations

    World Health Organization



                   
    1 Thirteenth 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.


    TITANIUM DIOXIDE

    Biological Data

    Biochemical aspects

    Rats given seven days a diet of 0.2 per cent., one per cent. and two
    per cent. TiO2 did not appear to absorb any colour from the
    gastro-intestinal tract (Fournier, 1950). Another group of rats was
    given 0.25 per cent. of TiO2 in the diet for a week. Ninety-two per
    cent. of the administered pigment appeared in the faeces. It was
    concluded that no absorption took place (Lloyd, et al. 1955). Five
    male volunteers ingested 5 g of N.F. Grade Ti02 suspended in milk on
    three consecutive days. Urines were collected for five days after
    starting the ingestion. No detectable change in urinary titanium
    levels was detected, thus indicating absence of any significant
    absorption of titanium ion (West, B. & Wyzan, H. 1963).

    Acute toxicity

                                                                     

    Animal   Route            LD50              Reference 
                        mg/kg body weight
                                                                     

    Rat      oral       >12 000 as Ba, Bi,      Brown & Mastromatteo,
                        Ca and Pb titanate      1962

             i.p.       2000-5300 as above               "
                                                                     

    Rats were given 0.66 g/kg body weight of pigment for 15 days. No
    titanium was found in the blood, liver, kidney and urine (sensitivity
    of analysis 10 g) Fournier, 1950).

    Short-term studies

    Rat. Two groups of 10 male and 10 female rats were given 0 per cent.
    or 10 per cent. N.F. grade TiO2 in their diet for 30-34 days. All
    animals remained healthy and normal. Weight gain and food intake were
    comparable for the two groups. No relevant gross pathology was
    observed. No evidence of an increase in titanium was found in any of
    seven different tissues analyzed except muscle where the increase was
    0.1 ppm compared with control tissues (West, B.Wyzan, H., 1963).

    Dog. Three groups of two dogs were given orally 0.05, 0.1 and 0.15 g
    of TiO2. Every five days the dose was increased by the same amounts.
    One dog of each group was kept for one month, the other for two
    months. No toxic effects were seen (Vernetti-Blina, 1928).

    Three dogs received weekly s.c. injections of a suspension of TiO2
    in oil; the initial dose of 500 mg was raised progressively to 3 g
    over seven weeks. A fourth dog received initially 250 mg/kg rising to
    2 g/kg body weight. Three dogs survived without adverse effects, the
    fourth died of a cause unconnected with the administration of TiO2
    (Vernetti-Blina, 1928).

    Long-term studies

    Mixed species

    Two guinea-pigs, two rabbits, two cats and one dog were fed technical
    grade TiO2 for 390 days. The dog received 9 g/day, rabbits and cats
    3 g/day, guinea pigs 0.6 g/day. Two additional cats received 3 g
    pigment daily for 175 and 300 days respectively. No adverse effects
    were seen and histopathological examination revealed no abnormality.
    There was less than 5 mg of Ti in bile, heart, spleen and skeletal
    muscle (Lehmann & Herget, 1927).

    Comments

    Titanium dioxide is a very insoluble compound. The studies in several
    species, including man, show neither significant absorption nor tissue
    storage following ingestion of titanium dioxide. Studies on soluble
    titanium compound have therefore not been reviewed. It is useful to
    note that following absorption of small amounts of Ti ions no toxic
    effects were observed. Establishment of an acceptable daily intake for
    man is considered unnecessary.

    EVALUATION

    Not limited except for good manufacturing practice.

    REFERENCES

    Brown,  J. R. & Mastromatteo, E. (1962) Industr. Med. Surg., 31, 302

    Fournier, P. (1950) C. R. Acad. Sci. (Paris), 231, 1343

    Lehman, K. B, & Herget, L. (1927) Chem. Ztg., 51, 793

    Lloyd, L. E., Rutherford, B. E. & Crampton, E. W. (1955) J. Nutr.,
    56, 265

    Vernetti-Blina, L. (1928) Rif. Med., 47, 1516

    West, B. & Wyzan, H. (1963) Unpublished report by American Cyanamid
    Company
    


    See Also:
       Toxicological Abbreviations
       Titanium dioxide (ICSC)
       TITANIUM DIOXIDE (JECFA Evaluation)
       Titanium Dioxide (IARC Summary & Evaluation, Volume 47, 1989)