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 µg) 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