Titanium 2-hydroxy-1,2,3-propanetricarboxylate (2:5)

Endpoint summary

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