Registration Dossier

Administrative data

Description of key information

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records

Referenceopen allclose all

Endpoint:
sub-chronic toxicity: oral
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study
Justification for type of information:
Read across valid as the substnace tested is also titanate complex with glycol and alkylamine, degrading in water to similar degradation products.
Reason / purpose:
read-across source
Related information:
Composition 1
Reference:
Composition 0
Qualifier:
according to
Guideline:
OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity in Rodents)
Deviations:
no
GLP compliance:
yes
Limit test:
no
Test material information:
Composition 1
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
Method of administration:
Oral gavage
Duration of treatment / exposure:
28 d
Frequency of treatment:
7 d / wk
Dose / conc.:
0 mg/kg bw/day (nominal)
Dose / conc.:
50 mg/kg bw/day (nominal)
Dose / conc.:
250 mg/kg bw/day (nominal)
Dose / conc.:
1 000 mg/kg bw/day (nominal)
No. of animals per sex per dose:
Male: 5 animals at 0 mg/kg bw/day
Male: 5 animals at 50 mg/kg bw/day
Male: 5 animals at 250 mg/kg bw/day
Male: 5 animals at 1000 mg/kg bw/day
Female: 5 animals at 0 mg/kg bw/day
Female: 5 animals at 50 mg/kg bw/day
Female: 5 animals at 250 mg/kg bw/day
Female: 5 animals at 1000 mg/kg bw/day
Clinical signs:
no effects observed
Haematological findings:
no effects observed
Clinical biochemistry findings:
no effects observed
Urinalysis findings:
no effects observed
Organ weight findings including organ / body weight ratios:
no effects observed
Details on results:
Clinical observations:
No deaths and no signs of toxicity were observed.

Only limited details provided in NONS summary
Laboratory findings:
No treatment-related changes in haematological parameters
were observed.

Slight (1-3%) increases in plasma sodium and chloride were
observed in males at all doses as were slight (20-30%)
decreases in triglycerides. These changes were not observed

in males which received 1000 mg/kg/day and were allowed to
recover for 2 weeks.

Effects in organs:
No treatment-related gross or microscopic findings were
observed.
Key result
Dose descriptor:
NOAEL
Effect level:
ca. 1 000 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
clinical signs
Key result
Critical effects observed:
no
Conclusions:
Dosing Sprague-Dawley rats with dose levels of up to 1000 mg/day produced only equivocal haematology and clinical
chemistry effects in either sex not considered to be related to the test material.
Therefore is was concluded that the test material is not classified under the test conditions.


No adverse effects noted up to 1000 mg/kg/day
Endpoint:
sub-chronic toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Reference:
Composition 0
Qualifier:
according to
Guideline:
OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity in Rodents)
Deviations:
no
GLP compliance:
yes
Limit test:
no
Test material information:
Composition 1
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
Method of administration:
Oral gavage
Duration of treatment / exposure:
28 d
Frequency of treatment:
7 d / wk
Dose / conc.:
0 mg/kg bw/day (nominal)
Dose / conc.:
50 mg/kg bw/day (nominal)
Dose / conc.:
250 mg/kg bw/day (nominal)
Dose / conc.:
1 000 mg/kg bw/day (nominal)
No. of animals per sex per dose:
Male: 5 animals at 0 mg/kg bw/day
Male: 5 animals at 50 mg/kg bw/day
Male: 5 animals at 250 mg/kg bw/day
Male: 5 animals at 1000 mg/kg bw/day
Female: 5 animals at 0 mg/kg bw/day
Female: 5 animals at 50 mg/kg bw/day
Female: 5 animals at 250 mg/kg bw/day
Female: 5 animals at 1000 mg/kg bw/day
Clinical signs:
no effects observed
Haematological findings:
no effects observed
Clinical biochemistry findings:
no effects observed
Urinalysis findings:
no effects observed
Organ weight findings including organ / body weight ratios:
no effects observed
Details on results:
Clinical observations:
No deaths and no signs of toxicity were observed.

Only limited details provided in NONS summary
Laboratory findings:
No treatment-related changes in haematological parameters
were observed.

Slight (1-3%) increases in plasma sodium and chloride were
observed in males at all doses as were slight (20-30%)
decreases in triglycerides. These changes were not observed

in males which received 1000 mg/kg/day and were allowed to
recover for 2 weeks.

Effects in organs:
No treatment-related gross or microscopic findings were
observed.
Key result
Dose descriptor:
NOAEL
Effect level:
ca. 1 000 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
clinical signs
Key result
Critical effects observed:
no
Conclusions:
Dosing Sprague-Dawley rats with dose levels of up to 1000 mg/day produced only equivocal haematology and clinical
chemistry effects in either sex not considered to be related to the test material.
Therefore is was concluded that the test material is not classified under the test conditions.


No adverse effects noted up to 1000 mg/kg/day
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Mode of Action Analysis / Human Relevance Framework

Additional information

Extensive testing and reviews have been conducted on titanium dioxide, triethanolamine and propylene glycol, demonstrating limited adverse effects over repeat application. Propan-2-ol vapour may cause some adverse effects at very high levels, but it is not considered likely that even under condition of rapid degradation in water, propan-2-ol vapour will form due to the high water solubility of the alcohol.

 

Propan-2-ol NOAEL 1000 mg/kg/day, but with slight liver weight increase. This is reported as part of a reproduction toxicity assay. Review by the EU Scientific Committee on Health and Environmental Risks conclude low toxic risk (25th plenary on 9 September 2008)

 

http://ec.europa.eu/health/archive/ph_risk/committees/04_scher/docs/scher_o_105.pdf

 

Triethanolamine, NOAEL 1000 mg/kg/day over 90 days (Disseminated dossier, Source: European Chemicals Agency,http://echa.europa.eu/)

Titanium complexes of ammonium lactate, triisopropanolamine and polyethylene glycol is included as a supporting study, with only a slight change in blood parameters that were not considered to be adverse.

 

90 day inhalation,Propan-2-ol Regul Toxicol Pharmacol.1996 Jun; 23(3):183-92. Isopropanol: summary of TSCA test rule studies and relevance to hazard identification. Kapp RW JR et al) the study result was to be NOAEL 5000 ppm

Justification for classification or non-classification