Titanium tetrabutanolate

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

September 21, 1984 - October 19, 1984

Reliability:

3 (not reliable)

Rationale for reliability incl. deficiencies:

other: Non GLP, method deviates from current guideline. Furthermore, the test material contained only 25 % titanium tetrabutanolate. The main component of the test material was kerosene (75 %).

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1985

Report date:

1979

Materials and methods

Principles of method if other than guideline:

Groups of 10 male rats were exposed to the test item aerosol 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:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Titanium tetrabutanolate

EC Number:

227-006-8

EC Name:

Titanium tetrabutanolate

Cas Number:

5593-70-4

Molecular formula:

C16H36O4Ti

IUPAC Name:

titanium(4+) tetrakis(butan-1-olate)

Test material form:

aerosol dispenser: not specified

Remarks:

migrated information: aerosol

Details on test material:

- Name of test material (as cited in study report): 1-Butanol, titanium(4+salt) salt; Tetrabutyl titanate, Haskell No. 15,538
- Substance type: organometal
- Physical state: liquid
- Analytical purity: 95-100 %
- Impurities (identity and concentrations): Possibly 0-5% 1-butanol
- Composition of test material, percentage of components: 25 % titanium tetrabutanolate - 75 % kerosene
- Lot/batch No.: TLF-6171, lot 1

Test animals

Species:

rat

Strain:

other: Crl:CD(SD)BR

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Breeding Laboratories Inc, Kingston, New York
- Age at study initiation: 8 weeks old
- Weight at study initiation: between 234-265 grams
- Housing: in pairs in 8" x 14" x 8" suspended, steel-mesh cages
- Diet (e.g. ad libitum): Purina Certified Rodent Chow #5002 ad libitum, except during exposure
- Water (e.g. ad libitum): ad libitum, except during exposure
- Acclimation period: one week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 24-26°C
- Humidity (%): 36-67%
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

nose only

Vehicle:

air

Details on inhalation exposure:

Aerosol atmospheres of tetrabutyl titanate in kerosene were generated by pumping liquid test material into a Spraying System nebulizer. Air introduced at the nebulizer aerosolized the test material, and swept the aerosol stream into the exposure chamber.

Analytical verification of test atmosphere concentrations:

yes

Remarks:

A gravimetric analysis was used to control the chamber atmosphere during exposure.

Duration of exposure:

4 h

Concentrations:

Mean concentrations 3.7 mg/l, 11.0 mg/l and 13.0 mg/l
Figures represent concentrations of tetrabutyl titanate and kerosene, based on the colorimetric analysis

No. of animals per sex per dose:

10 males per dose

Control animals:

no

Details on study design:

Groups of 10 male rats were restrained in perforated, stainless steel cylinders with conical nose pieces. Each group was exposed for a single, 4-hour period to an aerosol atmosphere of tetrabutyl titanate in air. 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.

Two analytical methods were used in this study. A gravimetric analysis was used to control the chamber atmosphere during the exposure, and a colorimetric analysis was used to determine the total amount of test material in the atmosphere (tetrabutyl titanate and kerosene).
1. Gravimetric Analysis
To control the chamber concentration during exposure, measured volumes of chamber atmosphere were drawn through pre-weighed, glass-fiber filters at approximately 30 minute intervals. Filters were weighed on a Cahn 26 Automatic Electrobalance. Atmospheric concentration of particulate was calculated from the filter weight differential before and after sampling.
2. Colorimetric Analysis
To determine the total amount of test material (tetrabutyl titanate and kerosene) in the atmosphere, a colorimetric analysis for titanium metal was used. The filters from the gravimetric analysis were placed in a solution containing 5 mL of 10% sulfuric acid and 0.2 mL of 30% hydrogen peroxide. This solution reacts with the tetrabutyl titanate to give a yellow solution of free titanium metal. The solutions were centrifuged to remove filter particles, and diluted (if necessary) with H2SO4/H202 solution. Absorbance was read at 400 nm with a Bausch and Lomb Spectronic 2000. Standards were prepared by dissolving a known volume of test material (kerosene and tetrabutyl titanate) in H2SO4/H202 solution. Assuming a constant ratio of tetrabutyl titanate to kerosene in the atmosphere and in solution, the absorbance of chamber samples indicated the total amount of test material in the chamber.

Particle size (mass median diameter and percent respirable) were determined with a Sierra cascade impactor during each exposure. Chamber temperature was measured with a thermometer, chamber oxygen content was measured with a BioMarineB Model 225 oxygen analyzer, and relative humidity was measured with a BendixB Model 566 psychrometer.

Results and discussion

Effect levels

Sex:

male

Dose descriptor:

other: Approximate Lethal Concentration (ALC)

Effect level:

11 mg/L air (analytical)

Based on:

test mat.

Exp. duration:

4 h

Mortality:

3.7 mg/l - 0/10
11.0 mg/l - 1/10
13.0 mg/l - 0/10

Clinical signs:

other: During or immediately following exposure, some rats in all groups were lethargic, had no response when the chamber was tapped, wet perineum, diarrhea, decreased muscle tone, impaired breathing, and fur stained by the test material. Some rats exposed to 3.

Body weight:

Surviving rats in all groups had dose-dependent weight loss ranging from approximately 2-15% of initial body weight 1 day after exposure, followed by normal weight gain.

Gross pathology:

No gross pathology reported.

Any other information on results incl. tables

Atmospheric Characterization of Tetrabutyl Titanate

Concentration (mg/L) (a
Mean	S.D.	Range	Respirable (%) (b	Mass Median Diameter (um)
3.7	1.4	0.98 -5.5	98	1.8
11.0	2.0	7.7 -14	97	2.3
13.0	2.2	8.8 -16	89	3.0

a) Represents concentration of tetrabutyl titanate and kerosene, based on the colorimetric analysis.

b) Percent by weight of particles with aerodynamic diameter less than 10um.

Atmospheres of concentration greater than 13mg/L could not be generated due to an inadequate analytical method.

Applicant's summary and conclusion

Interpretation of results:

sligthly toxic

Remarks:

Migrated information Criteria used for interpretation of results: expert judgment

Conclusions:

The result of this study cannot be used to evaluate the acute inhalation toxicity of titanium tetrabutanolate, since the composition of the tested material was 25 % titanium tetrabutanolate and 75% kerosene. However, an approximate lethal concentration (ALC) of this test material was determined to be 11mg/L under conditions of this study.

Executive summary:

Male rats were exposed to aerosol atmospheres of 25% titanium tetrabutanolate - 75 % kerosene. An LC50 could not be calculated from these data. However, ALC was determined to be 11mg/L. By the study report titanium tetrabutanolate is considered slightly toxic by inhalation.

This study was regarded not reliable since the composition of the tested material contained only 25 % titanium tetrabutanolate. Furthemore, the study report is missing details on test conditions and test results. Thus, the result is used as a weight of evidence in hazard assessment.