Registration Dossier

Diss Factsheets

Administrative data

Description of key information

Titanium salts are considered to be of low toxicity by ingestion.

Citric acid / citrates are metabolic products in cells and conisdered to be of low toxicity.

Further animal testing cannot be justified.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records
Reference
Endpoint:
sub-chronic toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
90 days
Reliability:
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:
The substance will readily dissociate under biological conditions and it is valid to consier the ions separately for long-term toxicity.
Titanium salts are considered to be of low toxicity by ingestion.
Citric acid / citrates are metabolic products in cells and conisdered to be of low toxicity.
Further animal testing cannot be justified.
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity Study in Rodents)
GLP compliance:
yes
Limit test:
no
Specific details on test material used for the study:
Not specifed.
Described as 'nano', but appears to be grade for paints.
Species:
rat
Strain:
Crj: CD(SD)
Sex:
male/female
Route of administration:
oral: gavage
Vehicle:
CMC (carboxymethyl cellulose)
Details on oral exposure:
Dosed with the vehicle at a volume of 10 mL/kg of body weight.
Analytical verification of doses or concentrations:
yes
Details on analytical verification of doses or concentrations:
Samples taken at different times during the study. Ti measured by ICP methods
Duration of treatment / exposure:
Daily dosing over 90 days
Frequency of treatment:
Daily
Dose / conc.:
100 mg/kg bw/day (nominal)
Dose / conc.:
300 mg/kg bw/day (nominal)
Dose / conc.:
1 000 mg/kg bw/day (nominal)
No. of animals per sex per dose:
10
Control animals:
yes, concurrent vehicle
Details on study design:
Note that recovery from analysis indicated slightly reduced dosing from nominal.
Observations and examinations performed and frequency:
Twice daily observations.
Body weight checked weekly
Sacrifice and pathology:
Gross pathology and histology performed
Clinical signs:
no effects observed
Mortality:
no mortality observed
Body weight and weight changes:
no effects observed
Food consumption and compound intake (if feeding study):
not examined
Food efficiency:
no effects observed
Water consumption and compound intake (if drinking water study):
not examined
Ophthalmological findings:
no effects observed
Haematological findings:
no effects observed
Clinical biochemistry findings:
no effects observed
Urinalysis findings:
no effects observed
Behaviour (functional findings):
no effects observed
Immunological findings:
not specified
Organ weight findings including organ / body weight ratios:
no effects observed
Gross pathological findings:
no effects observed
Neuropathological findings:
no effects observed
Histopathological findings: non-neoplastic:
not specified
Histopathological findings: neoplastic:
no effects observed
Other effects:
no effects observed
Dose descriptor:
NOAEL
Effect level:
> 1 000 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: No effects
Remarks on result:
not determinable due to absence of adverse toxic effects
Critical effects observed:
no
Conclusions:
No adverse effects when treated by gavage over 90 days at up to 1000 mg/kg/day nominal
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Additional information

Justification for classification or non-classification