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Long-term toxicity to fish

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fish short-term toxicity test on embryo and sac-fry stages
Test on titanium
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
Total exposure period 8 days
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Justification for type of information:
Peer-reviewed study on titanium salts.
Barium titanium trioxide is known to dissociate partially with loss of barium, resulting in exposure to titanium dioxide if released to the environment
This report relates to nano-forms and will reflect precipitated titanium dioxide
Reason / purpose for cross-reference:
exposure-related information
Exposure will be to titanium dioxide in solution due to dissociation of barium ions from the complex
dissociation constant
Type of information:
experimental study
Non-guideline research in view of chemical identity.
Adequacy of study:
key study
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
test procedure in accordance with generally accepted scientific standards and described in sufficient detail
Justification for type of information:
Dissociation characteristics were investigated as part of estimation for solubility of ions at biological and environmental pH.
no guideline followed
Principles of method if other than guideline:
Samples of Barium Titanium Trioxide (hereafter barium titanate) were examined in order to investigate dissociation under dilute environmental and biological conditions, and determine the
concentrations of barium and titanium ions in solution under these conditions.

Five different conditions were examined; hydrochloric acid to simulate gastric fluid, spring water at pH 9, 5 and 7 (adjusted with sodium hydroxide) to simulate environmental conditions and MiliO ultrapure deionised water as a control. A sixth sample was prepared by complete digestion in concentrated nitric acid in order to examine the sample as supplied.

Dilution in each case was 25mg/ml.

Following dissolution and filtration, sample solutions were examined by ICP analysis to determine the concentration of dissociated barium and titanium.
GLP compliance:
This was special research using non-guideline methods, making GLP inappropriate.
Specific details on test material used for the study:
Nominal 100% technical grade
Dissociating properties:
Relative solubility of ions determined at different pH using different aqueous media
Remarks on result:
not determinable because of methodological limitations
Standard method was not possible to perform and therefore pKa could not be determined The measurement of pKa was not an intended output of the research

Results of the ICP analysis of the sample solutions are summarised below.

Sample as supplied (conc. Nitric acid) Ba 58.46 %, Ti 15.91 % (ie completely dissociated)

Simulated gastric fluid Ba 689 ppm, Ti 13 ppm (slight dissociation, pH 1.5 molar HCl)

Titanium was not detected in natural buffered water or deionised water
MilliQ DI pure water Ba 74 ppm
Buxton spring water pH 5 solution Ba 42 ppm 
Buxton spring water pH 7 solution Ba 64 ppm 
Buxton spring water pH 9 solution Ba 69 ppm 

The results for titanium are below the limit of detection of the measurement as determined by the quality control samples (1 ppm) for all samples except for the samples digested in Simulated Gastric Fluid and Conc. Nitric Acid. The concentration of these elements is therefore determined to be close to zero for all other samples.

The study has shown that Barium Titanate exhibits a very slight dissociation of the Barium ion under environmental conditions, with no dissociation of the titanium ion.  

Under simulated gastric conditions there is a higher dissociation of the barium ion, with a very slight dissociation of the titanium ion also seen.

Testing has shown that Barium Titanate exhibits a very slight dissociation of the Barium ion under environmental conditions, with no dissociation of the titanium ion.  

Under simulated gastric conditions there is a higher dissociation of the barium ion, with a very slight dissociation of the titanium ion also seen.

The titanium ions were not significantly soluble under environmental conditions and can be disregarded as having the potential to cause toxicity to aquatic and terrestrial organisms. Barium has been considered for environmental effects.

Barium and titanium were marginally soluble under gastric conditions with apparent dissociation. Therefore, for toxicological effects, barium and titanium can be considered separately because to be biologically available in solution, they will need to dissociate from each other.

Data source

Reference Type:
Titanium dioxide nanoparticles produce phototoxicity in the developing zebrafish
Bar-Ilan, O. et al.
Bibliographic source:

Nanotoxicol. 6, 670-679

Materials and methods

Test guideline
equivalent or similar to guideline
OECD Guideline 212 (Fish, Short-term Toxicity Test on Embryo and Sac-Fry Stages)
Principles of method if other than guideline:
Although apparently following guidelines, not all method details were reported
The research included impact of ultraviolet light in conjunction with the exposure to the test material
GLP compliance:
not specified
The publication from which this end point data has been takendoes not indicate whether GLP conditions were observed.

Test material

Constituent 1
Chemical structure
Reference substance name:
Titanium dioxide
EC Number:
EC Name:
Titanium dioxide
Cas Number:
Molecular formula:
Test material form:
solid: nanoform

Sampling and analysis

Analytical monitoring:
not specified

Test solutions

Water dispersion of nanomaterial

Test organisms

Test organisms (species):
Danio rerio (previous name: Brachydanio rerio)

Study design

Test type:
Water media type:
Limit test:
Total exposure duration:
8 d
Remarks on exposure duration:
Period after fertilisation of eggs

Test conditions

Not specified
Test temperature:
30 C
Not specified
Dissolved oxygen:
Not specified
Not applicable
Not specified
Nominal and measured concentrations:
Nominal 0, 1, 10, 100, 500 and 1000 mg/l

Results and discussion

Effect concentrations
Key result
8 d
Dose descriptor:
Effect conc.:
> 1 000 mg/L
Nominal / measured:
Conc. based on:
test mat.
Basis for effect:
larval development
Including mortality / survival
Remarks on result:
other: Note that the reported concentration is a dispersion of nanomaterials and not a solution.
Details on results:
Where light was shone on the embryos, there were mortalities and malformations. The effect of light was considered to be depending on the impact played by nanomaterials and are not relevant to dissolved Ti ions.

Applicant's summary and conclusion

Validity criteria fulfilled:
not specified
Titanium ions are poorly soluble in environmental conditions and have no apparent biological impact. However, nanoforms in the presence of light may have an impact on embryo development.