Titanium tetrachloride

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: The study is well-documented and meets generally accepted scientific principles, but was not conducted according to GLP.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1980

Report date:

1980

Materials and methods

Principles of method if other than guideline:

Groups of six male rats were exposure to TiCl4 atmospheric hydrolysis products for 2, 5, 15, 30, 60, 120 and 240 minutes. These dynamic,
head-only exposures were conducted in a 33 litre cylindrical glass chamber. After the exposure, the surviving animals were kept for a 2-week
recovery period.

Median lethal concentrations were calculated for each exposure time. The LC50 was based on the number of animals which died during the exposure and during the recovery period. A minimum of 4 separate experiments were required for each exposure time to calculate an LC50.

GLP compliance:

no

Test type:

other:

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Titanium tetrachloride

EC Number:

231-441-9

EC Name:

Titanium tetrachloride

Cas Number:

7550-45-0

Molecular formula:

Cl4Ti

IUPAC Name:

titanium tetrachloride

Details on test material:

Purity = 99.5%

Test substance hydrolyses on contact with water or moist air.

Test animals

Species:

rat

Strain:

other: ChR-CD

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Not stated
- Age at study initiation: Not stated
- Weight at study initiation: 240 - 300 g
- Fasting period before study: Not stated
- Housing:Not stated
- Diet (e.g. ad libitum): Not stated
- Water (e.g. ad libitum): Not stated
- Acclimation period: Not stated


ENVIRONMENTAL CONDITIONS
- Temperature (°C): Not stated
- Humidity (%): Not stated
- Air changes (per hr): Not stated
- Photoperiod (hrs dark / hrs light): Not stated


IN-LIFE DATES: No information

Administration / exposure

Route of administration:

other: Mixture of vapour and particulate hydrolysis products

Type of inhalation exposure:

head only

Vehicle:

other: unchanged (no vehicle)

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Cylindrical glass chamber
- Exposure chamber volume: 33 litres
- Method of holding animals in test chamber: Not stated
- Source and rate of air: Not stated
- Method of conditioning air: Not stated
- Method of particle size determination: Sierra cascade impactor
- Treatment of exhaust air: Not stated
- Temperature, humidity, pressure in air chamber: Not stated


TEST ATMOSPHERE
- Brief description of analytical method used: Atmospheric particulates and vapour were trapped by a filter in tandem with an impinger which
contained 20 ml of a 0.5 M sodium acetate solution. The chamber TiCl4 concentration was calculated from the total chloride found in the sampling train. An Orion chloride ion selective electrode was used to analyse the filter and impinger solution. The chloride method agreed well with atomic absorption measurements for titanium performed on several samples.
- Samples taken from breathing zone: No


TEST ATMOSPHERE (if not tabulated)
- Particle size distribution: 0.3 to 1.6 micron
- MMAD: 0.9 micron

Analytical verification of test atmosphere concentrations:

yes

Remarks on duration:

2 minutes to 4 hours

Concentrations:

See Table 1.

No. of animals per sex per dose:

6

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:Not reported
- Necropsy of survivors performed: Yes
- Other examinations performed: Clinical observations

Statistics:

No information

Results and discussion

Effect levels

Effect levels 1

Sex:

male

Dose descriptor:

LC50

Effect level:

0.46 mg/L air (analytical)

95% CL:

0.38 - 0.53

Exp. duration:

4 h

Effect levels 2

Sex:

male

Dose descriptor:

LC50

Effect level:

1.1 mg/L air (analytical)

95% CL:

0.75 - 1.4

Exp. duration:

2 h

Effect levels 3

Sex:

male

Dose descriptor:

LC50

Effect level:

1.3 mg/L air (analytical)

95% CL:

1 - 1.6

Exp. duration:

1 h

Effect levels 4

Sex:

male

Dose descriptor:

LC50

Effect level:

3 mg/L air (analytical)

95% CL:

1.8 - 3.9

Exp. duration:

30 min

Effect levels 5

Sex:

male

Dose descriptor:

LC50

Effect level:

5.5 mg/L air (analytical)

95% CL:

3.7 - 8.5

Exp. duration:

15 min

Effect levels 6

Sex:

male

Dose descriptor:

LC50

Effect level:

36 mg/L air (analytical)

95% CL:

29 - 54

Exp. duration:

5 min

Effect levels 7

Sex:

male

Dose descriptor:

LC50

Effect level:

108 mg/L air (analytical)

95% CL:

99 - 139

Exp. duration:

2 min

Mortality:

See Table 1.

Clinical signs:

other: During the exposures rats showed signs of irritation including eye closing and gasping. Deaths occurred during exposure and up to one week post- exposure. Clinical signs post-exposure included corneal opacity, weight loss and lung congestion.

Body weight:

No details available.

Gross pathology:

Similar lesions were seen in rats which died during or immediately after experiments at 2, 5, 15, 30 and 240 minutes. The air passages were
inflamed and showed hypermucous secretion, epithelial denudation, severe necrotic laryngitis, pulmonary congestion and haemorrhage. A white-
grey powder was found in the air passages.

Death was considered to probably have been induced by pulmonary oedema due to increased permeability of the damaged alveolar capillaries.

Ten rats which survived exposure to the 30-minute LC10 (1.2 mg/l) were autopsied two at a time after recovery periods of 1, 3, 7, 21 or 49 days.
One day post-exposure severe respiratory inflammation was observed. After 3 days the respiratory-inflammatory exudate was already organising,
at 7 days the acute inflammation had subsided and the denuded epithelium was partially repaired. After 14 to 21 days the lesions had almost disappeared and the damaged epithelium was repaired. By 49 days post-exposure the respiratory tract showed a normal architecture.

Any other information on results incl. tables

Table 1: Concentration and mortality data for 4-hour exposure

Dose (ppm)	Mortalities
35.0	0/6
52.0	1/6
66.0	5/6
82.6	6/6

LD50 = 59 ppm (0.46 mg/l)

Applicant's summary and conclusion

Interpretation of results:

toxic

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The 4-hour LC50 of titanium tetrachloride was determined as 0.46 mg/l in male rats. Exposure was to a mixture of vapour and particulate hydrolysis products.