Titanium, diethylene glycol ethylene glycol triisopropanolamine complexes

Endpoint summary

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute 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:

comparable to 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 for cross-reference:

read-across source

Qualifier:

according to guideline

Guideline:

other: Annex V (limit test)

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Vehicle:

water

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Mortality:

Male: 5000 mg/kg bw; Number of animals: 5; Number of deaths: 0
Female: 5000 mg/kg bw; Number of animals: 5; Number of deaths: 0

Clinical signs:

Signs of toxicity related to dose levels:
No deaths and no signs of toxicity were observed

Body weight:

not specified.

Gross pathology:

Effects on organs:
No treatment-related macroscopic findings were observed.

Interpretation of results:

GHS criteria not met

Conclusions:

LD50 concluded to be > 5000 mg/kg bw read-across from structural analogue.

Reference 2

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study

Qualifier:

according to guideline

Guideline:

other: Annex V (limit test)

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Vehicle:

water

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Mortality:

Male: 5000 mg/kg bw; Number of animals: 5; Number of deaths: 0
Female: 5000 mg/kg bw; Number of animals: 5; Number of deaths: 0

Clinical signs:

Signs of toxicity related to dose levels:
No deaths and no signs of toxicity were observed

Body weight:

not specified.

Gross pathology:

Effects on organs:
No treatment-related macroscopic findings were observed.

Interpretation of results:

GHS criteria not met

Conclusions:

LD50 concluded to be > 5000 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

5 000 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: inhalation

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

the study does not need to be conducted because exposure of humans via inhalation is not likely taking into account the vapour pressure of the substance and/or the possibility of exposure to aerosols, particles or droplets of an inhalable size

other:

Justification for type of information:

The substance is a viscous liquid and exposure assessments would suggest no exposure to spray or particulates
The degradation products triisopropanolamine, titanium dioxide, propan-2-ol and ethylene glycol have been tested and appear to be of low hazard by inhalation

Reference 2

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: other

Justification for type of information:

Read-across to titanium tetraisopropanoate (EC 208-909-6) and analogue substances
Non GLP, method deviates from current guideline. However, study report contains necessary information for assessment.

Qualifier:

no guideline followed

Principles of method if other than guideline:

Groups of 6 male rats were exposed to the test item aerosol in a 40-l glass chamber at 26°C for a single 4-hour period. Following exposure the rats were observed for clinical signs and weighed daily throughout a 14 day period or until death.

GLP compliance:

not specified

Test type:

fixed concentration procedure

Limit test:

no

Species:

rat

Strain:

other: ChR-CD

Sex:

male

Details on test animals or test system and environmental conditions:

The rats were sourced from Charles River Breeding Laboratories Inc, North Wilmington, Massachusetts, USA. and were in the initial weight range of 230-298g and approximately 60 days old. They were quarantined for 1 week prior to use.
Following exposure the animals were returned to their cages (suspended stainless steel, wire mesh cages), housed in pairs and provided food (Purine Rat Chow, Purina Company, St. Louis, Missouri, USA) and water ad libitum.

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

whole body

Vehicle:

air

Details on inhalation exposure:

A dynamic air flow system was employed to produce constant and uniform atmospheric concentrations. A syringe driver (Harvard Apparatus Compact Infusion Pump) supplied a continuous amount of the test item into a spraying systems nebuliser, incorporated with a diluent air supply (anhydrous, 20 p.s.i.g.) creating an aerosol atmosphere.

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

ca. 4 h

Concentrations:

0.04 mg/l, 3.23 mg/l, 4.56 mg/l, 6.71 mg/l, 7.78 mg/l, 10.26 mg/l
concentrations were reported as time weighted averages

No. of animals per sex per dose:

6 males

Control animals:

no

Details on study design:

Groups of 6 male ChR-CD albino rats, initially in the weight range 230-298g and approximately 60 days old, were exposed to the test item aerosols in a 40-l glass chamber at 26°C, for a single 4 hour period. Following exposure the rats were returned to their cages, housed in pairs and provided food and water ad libitum. The rats were observed for clinical signs and weighed daily (excluding week-ends) throughout a 14-day recovery period or until death.

Analytical verification of the test item aerosols was performed by spectrophotometric analysis employing a Beckman Scanning Spectrophotometer (Model number 25) measuring absorbance at 230 nm. Samples of test item atmospheres were collected at approximately 30-minute intervals by drawing a known volume through 100% ethanol contained in 2 midget impingers, connected in series. A time weighted average (T.W.A.) concentration was calculated.
Chamber atmospheric concentrations determined as above were supported with gravimetric analyses (6 samples per exposure).

Statistics:

The LC50 was calculated using Probit analysis (D.J. Finney, Probit Analysis, 2nd Ed., 1952, Cambridge University Press)

Key result

Sex:

male

Dose descriptor:

LC50

Effect level:

ca. 7 780 mg/m³ air (analytical)

Based on:

test mat.

Exp. duration:

4 h

Mortality:

0.04 mg/l - 0/6
3.23 mg/l - 0/6
4.56 mg/l - 0/6
6.71 mg/l - 0/6
7.78 mg/l - 3/6
10.26 mg/l - 6/6

Clinical signs:

other: Due to high concentrations involved, a dense aerosol cloud formed in the chamber and made clinical observation difficult. Immediately after exposure, animals in 3.23 mg/l or greater exposure groups were fully covered with white dust and were completely in

Body weight:

Surviving animals in the 3.23 mg/l or greater exposure groups exhibited a mild to moderate weight loss 24 hours post exposure followed by normal weight gain throughout the 14-day recovery.

Gross pathology:

No gross pathology reported.

Other findings:

The LC50 value of 7.78 mg/l (=7780mg/m3) was considered to be slightly to moderately toxic on an acute inhalation basis.

Interpretation of results:

Category 5 based on GHS criteria

Conclusions:

Acute inhalation toxicity of Titanium tetraisopropanolate was evaluated using a LC50 test. The LC50 value calculated after single 4-hour exposure was 7 780 mg/m3.

Executive summary:

Male rats were exposed to aerosol atmospheres of titanium tetraisopropanolate. By the study report, titanium tetraisopropanolate is considered slightly to moderately toxic by inhalation.

This study was regarded as reliable with restrictions since the study report is missing details on test conditions and test results. The result of this study is used as a weight of evidence in hazard assessment.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Acute toxicity: via dermal route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: dermal

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 for cross-reference:

read-across source

Qualifier:

according to guideline

Guideline:

other: Annex V (Limit test)

GLP compliance:

yes

Test type:

standard acute method

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

No. of animals per sex per dose:

5

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

Male: 2000 mg/kg bw; Number of animals: 5; Number of deaths: 0
Female: 2000 mg/kg bw; Number of animals: 5; Number of deaths: 0

Gross pathology:

Effects on organs:
No treatment-related macroscopic findings were observed.

Other findings:

Signs of toxicity (local):
No deaths and no signs of toxicity were observed

Interpretation of results:

GHS criteria not met

Conclusions:

LD50 > 2000 mg/kg bw read-across from structural analogue. No hazard identified.

Reference 2

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

other: Annex V (Limit test)

GLP compliance:

yes

Test type:

standard acute method

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

No. of animals per sex per dose:

5

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

Male: 2000 mg/kg bw; Number of animals: 5; Number of deaths: 0
Female: 2000 mg/kg bw; Number of animals: 5; Number of deaths: 0

Gross pathology:

Effects on organs:
No treatment-related macroscopic findings were observed.

Other findings:

Signs of toxicity (local):
No deaths and no signs of toxicity were observed

Interpretation of results:

GHS criteria not met

Conclusions:

The recorded degradation products are titanium dioxide, propan-2-ol, triethanolamine and propylene glycol.
These organic products are known to have low acute dermal toxicity
Further animal testing is not justified

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Additional information

The substance is unstable in water and moist atmosphere and testing would record the results of the key degradation products.These are titanium dioxide, propan-2-ol, triisopropanolamine and ethylene glycol. These are all well evaluated low-hazard substances and further animal testing is not justified.

No studies were conducted on the traget substance. Studies read-across from structural analogue indicate no or low toxicity in oral, dermal or inhlation route.