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Acute Toxicity: inhalation

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Administrative data

acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
supporting study
3 (not reliable)
Rationale for reliability incl. deficiencies:
other: Non GLP, method deviates from current guideline

Data source

Reference Type:
study report
Report date:

Materials and methods

Test guideline
other: Test guideline not reported
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 a 14 day period or until death.
GLP compliance:
not specified
Test type:
fixed concentration procedure
Limit test:

Test material

Constituent 1
Reference substance name:
Titanic Acid, tetraisopropyl ester
Titanic Acid, tetraisopropyl ester
Details on test material:
Titanic Acid, tetraisopropyl ester
Tyzor TPT Haskell No. 12,677

Test animals

other: ChR-CD
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.

Administration / exposure

Route of administration:
inhalation: aerosol
Type of inhalation exposure:
whole body
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:
Duration of exposure:
4 h
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:
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).
The LC50 was calculated using Probit analysis (D.J. Finney, Probit Analysis, 2nd Ed., 1952, Cambridge University Press)

Results and discussion

Effect levels
Dose descriptor:
Effect level:
7.78 mg/L air (analytical)
Based on:
test mat.
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 was considered to be slightly to moderately toxic on an acute inhalation basis.

Applicant's summary and conclusion