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Toxicological information

Acute Toxicity: inhalation

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Administrative data

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.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1979
Report Date:
1979

Materials and methods

Test guideline
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

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Titanium tetraisopropanolate, referred in the study report 2-Propanol titanium (4+) salt batch number V0303339, was received on 01 April 2010 (100 ml). An expiry date of 07 April 2011 was arbitrarily allocated. The purity was reported to be ≥90% on documentation supplied by the Sponsor.
Subsequent to the receipt of the test article, further information was received from the Sponsor detailing the following purity profile for the batch: 2-propanol, titanium (4+) salt >99%, heptanes (naphtha) 0.56%, iso-propanol <0.5%.

When not in use the test article was stored in a sealed container, at room temperature in the dark. The test article was stored over a desiccant from 14 April 2010 in accordance with the definitive protocol. It was considered that storage without desiccant prior to this date did not have any adverse effect on the test article as the container was not opened during this period.
Although not specified in the protocol, the container was purged with nitrogen each time it was opened from 26 April 2010, to further protect the test article from moist air.

Test animals

Species:
rat
Strain:
other: ChR-CD
Sex:
male
Details on test animals 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.

Administration / exposure

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)

Results and discussion

Effect levels
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:
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 incapacitated. Clinical signs include gasping and laboured respiration.
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.

Applicant's summary and conclusion

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.