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EC number: 235-120-4
CAS number: 12070-08-5
The MN data on TiO2 described here were originally published by Shelby
et al. (1993).
The initial MN experiment on TiO2 (0, 250, 500, 1000 mg/kg bw) gave a
significant trend with the effect at the highest dose (1000 mg/kg bw)
significantly elevated; however, the effects observed were small.
In a second trial on TiO2 (0, 500, 1000, 1500 mg/kg bw) , a single dose
group (1000 mg/kg bw) was significantly elevated. However this result
was only seen in a single dose, was not concentration dependent and only
of minor significance. Therefore this effect is judged as irrelevant
Table1: TiO2 Micronucleus Test (solvent corn oil; bone
Dose (mg/kg bw)
Trend P value
Survival (No. scored)
* Significant positive effect
c Trend test P value after dropping high dose group
In a B6C3F1 mouse bone
marrow micronucleus test, 5 male mice per dose were treated
intraperitoneally with Titanium dioxide at doses of 0, 250, 500, 1000
and 1500 mg/kg bw. The animals were injected intraperitoneally three
times at 24 h intervals. The
vehicle was corn oil.
The initial micronucleus test gave a significant trend with the effect
at the highest dose significantly elevated; the effects observed were
small. In a second trial, effects of a similar magnitude were observed.
However this result was only seen in a single dose, was not
concentration dependent and only of minor significance. Therefore this
effect is judged as irrelevant biological fluctuation.
Therefore, Titanium Dioxide is not considered to be mutagenic according
to the results of the in vivo micronucleus test reported here.
In vitro genetic toxicity tests:
Titanium dioxide did not induce effects in most of the reported in
vitro genotoxicity assays (bacterial mutagenicity (Zeiger, 1988,
Kanematsu, 1984; mouse lymphoma assay (Myhr, 1991), micronucleus assay
(Miller, 1995); Sister Chromatide Exchange & Chromosome aberration assay
(Invett, 1989)). Contradicting results have been reported in CHO cells
by Lu (1998) (positive Sister Chromatide & micronucleus assay). Positive
results have also been reported by Türkez (2007) in human erythrocytes
(Sister Chromatide Exchange & micronucleus assay). However, in the
latter report the activities of antioxidant enzymes in erythrocytes
showed significant decreases with increasing doses of TiO2. Thus, it
seems to be a secondary genotoxic effect caused by an increase in
reactive oxygen species.
In vivo genetic toxicity tests:
Titanium dioxide does not induce micronuclei or chromosome
aberration in the bone marrow of male B6C3F1 mice following a single
intraperitoneal injection of 1500 and 2500 mg titanium dioxide /kg bw,
respectively (Shelby, 1995). In addition TiO2 is negative in a
Drosophila sex-linked recessive lethal (SLRL) assay (Foureman, 1994).
From the available data it can be concluded, that titanium dioxide
is not genotoxic. These data are used for read-across to Titanium
The majority of in vitro genotoxicity studies, among them a bacterial
reverse mutation assays, mammalian cell gene mutation tests (TK assay)
and mammalian cell chromosome aberration are negative, supporting the
negative findings in three in vivo tests as cited above. Therefore,
Titanium dioxide is not considered to be mutagenic. These data are used
for read-across to Titanium carbide.
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