Registration Dossier

Administrative data

Description of key information

Oral toxicity: The study does not need to be conducted because the substance is classified as corrosive to the skin.

Dermal toxicity: The study does not need to be conducted because the substance is classified as corrosive to the skin.

Inhalation toxicity: A LC50 of 460 mg/m³ (4h exposure) was determined for the rat in a reliable study (KEY Acute toxicity: inhalation.7.2.2.001 Kelly 1980)

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via inhalation route

Link to relevant study records
Reference
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.
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
Species:
rat
Strain:
other: ChR-CD
Sex:
male
Details on test animals 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
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
Sex:
male
Dose descriptor:
LC50
Effect level:
0.46 mg/L air (analytical)
95% CL:
0.38 - 0.53
Exp. duration:
4 h
Sex:
male
Dose descriptor:
LC50
Effect level:
1.1 mg/L air (analytical)
95% CL:
0.75 - 1.4
Exp. duration:
2 h
Sex:
male
Dose descriptor:
LC50
Effect level:
1.3 mg/L air (analytical)
95% CL:
1 - 1.6
Exp. duration:
1 h
Sex:
male
Dose descriptor:
LC50
Effect level:
3 mg/L air (analytical)
95% CL:
1.8 - 3.9
Exp. duration:
30 min
Sex:
male
Dose descriptor:
LC50
Effect level:
5.5 mg/L air (analytical)
95% CL:
3.7 - 8.5
Exp. duration:
15 min
Sex:
male
Dose descriptor:
LC50
Effect level:
36 mg/L air (analytical)
95% CL:
29 - 54
Exp. duration:
5 min
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.

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)

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.
Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LC50
Value:
460 mg/m³

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

For acute oral and dermal toxicity no reliable studies are available. In accordance with Column 2 of REACH Annex VII, new acute studies on oral or dermal toxicity study does not have to be carried out because the available information indicates that the substance meets the criteria for classification as corrosive to skin. The acute inhalation toxicity was determined for the rat in a reliable study: LC50 59 ppm (0.46 mg/l air) (analytical).

Justification for classification or non-classification

The available data indicate that classification as very toxic (acute toxicity (inhalation mist) category 2) according to CLP/GHS is appropriate, based on an inhalation study in the rat which indicated an LC50 of 59 ppm (0.46 mg/l air) (analytical).

As the conduction of new, reliable studies on oral and dermal toxicity is scientifically unjustified for animal wellfare reasons (corrosivity), the classification as corrosive to skin and eyes category 1B and the implementation of respective risk management measures is regarded sufficient to cover the acute oral and dermal toxic potential of titanium tetrachloride.