Titanium tetrachloride

Specific investigations: other studies

Administrative data

Endpoint:

specific investigations: other studies

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

1980-05-21 to 1980-05-29

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: The study is well documented and meets generally accepted scientific principles.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1980

Report date:

1980

Materials and methods

Principles of method if other than guideline:

Eight week old male rats were exposed (head only) to TiCl4 vapours in air. Groups of four rats were exposed for single 20 minute periods.
Respiratory rate was monitored by recording pressure fluctuations (due to breathing) in the body plethysmorgraph. Respiratory rate (breaths per
minute) was recorded for a 5 minute control period pre- and post-exposure as well as during exposure. Respiratory rate was determined by
counting breaths for a 10 to 20 second interval each minute. Each animal served as its own control. Percent decrease in respiratory rate from mean
control value (5 minute pre-exposure) was calculated. A group average of respiratory depression (RD) was determined at several time intervals
during exposure. An RD50 value was calculated by linear regression analysis from the interval during which maximum respiratory rate depression
was observed.

During exposure all rats were observed and clinical signs noted. Following each exposure rats were observed and weighed daily for a 48 hour
period.

GLP compliance:

no

Type of method:

in vivo

Endpoint addressed:

respiratory irritation

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

Test animals

Species:

rat

Strain:

other: ChR-CD

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: No information
- Age at study initiation: 8 weeks
- Weight at study initiation: 232-274 g
- Fasting period before study: Not stated
- Housing: Suspended stainless steel wire-mesh cages, in pairs
- Diet: Purina Certified Rodent Chow #5002 ad libitum
- Water: ad libitum
- Acclimation period: one week

Administration / exposure

Route of administration:

inhalation: vapour

Vehicle:

unchanged (no vehicle)

Details on exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: 23 litre rectangular polymethylmethacrylate chamber with four animal ports and four sampling ports.
- Method of holding animals in test chamber: Body plethysmograph positioned such that only the animal's snout protruded into a sealed inner
compartment (ca. 1.5 litres)

TEST ATMOSPHERE
- Brief description of analytical method used: Chloride specific ion electrode
- Samples taken from breathing zone: Yes

Analytical verification of doses or concentrations:

yes

Details on analytical verification of doses or concentrations:

Two samples collected during each exposure. A known volume of test atmosphere was drawn through
two midget impingers, connected in series, which contained 10 ml of a 0.5 M sodium acetate solution as trapping solvent. Samples were analysed
using a chloride specific ion electrode.

Duration of treatment / exposure:

20 minutes

Frequency of treatment:

Once

Post exposure period:

48 hours

Doses / concentrations

Remarks:

Doses / Concentrations:
0.04, 0.11, 0.20, 0.32, 1.23, 2.80, 2.94, 4.30 mg/l
Basis:
analytical conc.
average measured values

No. of animals per sex per dose:

4

Examinations

Examinations:

Respiratory rate
Clinical observations
Body weight

Positive control:

None

Results and discussion

Details on results:

Individual respiratory rate decrease values for each test concentration are shown in Table 1.

The calculated atmospheric concentration of TiCl4 necessary to produce a 50% decrease in respiratory rate was determined to be 2.43 mg/l. A dose response relationship was apparent. The decrease in respiratory rate was observed within the first minute of exposure and reached a relatively stable
level prior to the recovery period. Only a slight return toward the normal respiration rate was observed during the final 5 minutes of the exposure
period. During a 5 minute period following exposure a slight recovery in respiratory rate was observed but remained below control values.

The lower exposure levels produced an apparent increase in respiratory rate. This was also observed, but less pronounced, in rats exposed only to
houseline air.

Rats exhibited lacrimation and clear nasal discharge immediately following exposure. There was mild weight loss observed within 24 hours post-
exposure, followed by normal weight gain within 48 hours. No other adverse signs were observed post-exposure.

Any other information on results incl. tables

Table 1 Respiratory Rate Decrease

Average exposure concentration (mg/l)	% Respiratory rate decrease	Standard deviation (%)
0.04	-18.2	± 12.9
0.11	-6.0	± 35.6
0.20	12.0	± 9.8
0.32	17.8	± 25.8
1.23	42.5	± 10.9
2.80	63.3	± 8.5
2.94	62.0	± 21.8
4.30	75.5	± 5.1

Applicant's summary and conclusion

Conclusions:

Groups of four male ChR-CD rats were exposed to hydrolysis products of TiCl4 in air. Respiratory rate was monitored. The amount of respiratory
rate depression was found to be proportional to the atmospheric concentration of TiCl4. The calculated RD50 is 2.43 mg/l/