Diiron titanium pentaoxide

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1990

Report date:

1990

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Diiron titanium pentaoxide

EC Number:

234-679-1

EC Name:

Diiron titanium pentaoxide

Cas Number:

12023-27-7

Molecular formula:

Fe2O5Ti

IUPAC Name:

titanium(4+) diiron(3+) pentaoxidandiide

Test material form:

solid: particulate/powder

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: BRL, Biological Research Laboratory Ltd, Füllinsdorf Switzerland
- Age at delivery:
Males: 8 weeks
Females: 10 weeks
- Weight at delivery:
Males: 180 - 200 g
Females: 180 - 200 g
- Fasting period before study:
- Housing: Groups of 5 in Macrolon type-4 cages
- Diet: Pelleted standard Kliba 343 ad libitum
- Water: Community tab water ad libitum
- Acclimation period:12 or 15 days

ENVIRONMENTAL CONDITIONS
- Temperature: 22°C +/- 3°C
- Humidity: 30 - 70%
- Air changes: 10 - 15 per hr
- Photoperiod: 12 hrs dark / 12 hrs light

Administration / exposure

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

nose only

Vehicle:

air

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: according to the method of Sachsse. The animals are confined separately in tubes which are positioned radially around the exposure chamber.
- Exposure chamber volume: 1 liter
- Method of holding animals in test chamber: Macrolon animal restraint tubes
- Exposure airflow rate: 1.3 L/min/animal
- System of generating particulates/aerosols: Piston/brush aerosol generator (RBG 1000, Palas GmbH, Karlsruhe, germany)
- Method of particle size determination: Mercer 7-stage cascade impactor
- Treatment of exhaust air: Rebreathing of exhaled air is precluded
- Temperature, humidity: 21°C, 10 - 15% humidity

TEST ATMOSPHERE
- Brief description of analytical method used: Gravimetric determination of concentration. The test material was collected on glass fiber filters using a stainless steel filter sampling device. The relative aerosol concentration was monitored using a RAM-1 light scattering type aerosol monitor.
- Samples taken from breathing zone: yes

TEST ATMOSPHERE
- Particle size distribution (in cumulative %):
Group 2 (4.6 mg/L):
> 4.6 µm 3.0 µm 2.13 µm 1.6 µm 1.06 µm 0.715 µm 0.325 µm < 0.325 µm
100 % 81.5 % 71.7 % 57.9 % 40.9 % 26.3 % 15.5 % 6.8 %

Group 3 (14.9 mg/L):
> 4.6 µm 3.0 µm 2.13 µm 1.6 µm 1.06 µm 0.715 µm 0.325 µm < 0.325 µm
100 % 51.4 % 38.8 % 38.2 % 38.0 % 35.9 % 29.1 % 12.8 %

- MMAD (Mass median aerodynamic diameter):
Group 2 (4.6 mg/L): 1.2 µm
Group 3 (14.9 mg/L): 4.6 µm (slightly exceeds the MMAD-range recommended by the guideline)

Analytical verification of test atmosphere concentrations:

yes

Remarks:

gravimetric determination

Duration of exposure:

4 h

Concentrations:

Group 1 (control): 0 mg/L
Group 2: 4.6 mg/L
Group 3: 14.9 mg/L

No. of animals per sex per dose:

5 per sex per group

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 15 days
- Frequency of observations and weighing:
Mortality: Once per h during exposure, twice daily until day 15
Body weights: On days 1 (before exposure), 8 and 15
Clinical signs: At least once daily
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology

Results and discussion

Effect levels

Effect levels 1

Key result

Sex:

male

Dose descriptor:

LC50

Effect level:

> 4.6 - < 14.9 mg/L air (analytical)

Based on:

test mat.

Exp. duration:

4 h

Remarks on result:

other: local effects on overload on the respiratory tract

Effect levels 2

Key result

Sex:

female

Dose descriptor:

LC50

Effect level:

> 14.9 mg/L air (analytical)

Based on:

test mat.

Exp. duration:

4 h

Mortality:

Mortality was observed in 60% of the males exposed to the high conc. (14.9 mg/L).
No mortalities have been observed in the control group and the low conc. group (4.6 mg/L)

Clinical signs:

other: During exposure, restlessness in all rats (both sexes) exposed to the high concentration (14.9 mg/L) and in a few animals of both sexes of the lower conc. (4.6 mg/L). At the high conc. (14.9 mg/L): labored respiration in surviviing males, hunched posture

Body weight:

no effects

Gross pathology:

Slightly increased lung weights (not clearly dose-dependent).
In two of the three rats which died sponatneously in the high dose group, the lumen of the trachea was coated with a thick, resistant layer of particles which appeared to be the test material.

Other findings:

High concentration group:
In the 3 males that died spontaneously, irregular brownish particles were noted in bronchi, bronchioles and alveoli. In addition, one of these rats showed slight alveolar hemorrhage and another showed alveolar edema and acute congestion.
In the 7 rats sacrificed on schedule, a slight to moderate alveolar histiocytosis was noted. Most histiocytes (macrophages) contained mainly brownish birefringent particles. Particles were also noted in the bronchi, bronchioles and alveoli of these rats. Granulomas (slight to marked in extent) containing particles were noted in 6 of these rats. Alveolar hemorrhage was noted in 1 of these rats. Perivascular lymphoid cuffing was noted in 5 rats, and chronic alveolitis in all rats sacrificed on schedule.

Low concentration group:
A slight to moderate alveolar histiocytosis was noted in all rats. Most of these histiocytes contained particles. Slight granulomas were noted in 4 rats. Perivascular lymphoid cuffing and chronic alveolitis were noted in 6 rats in 1 of these rats, slight emphysema was also noted.

Control group:
Minimal to slight perivascular lymphoid cuffing and chronic alveolitis were noted in 4 rats.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The deaths observed in the high concentration group (14.9 mg/L) are assumed to be essential due to local effects of overload on the respiratory tract due to the very high exposure concentration, even in absence of true toxicity of the test material. Deaths may have occured by suffocation produced by overload of inhaled solid particles which exceeded the clearance capacity of the lungs and by partial obstruction of the respiratory airways.

Executive summary:

An acute inhalation toxicity study has been performed. The study was performed according to OECD guideline No. 403 under GLP regulation. Two groups of rats (5 males + 5 females per group) were exposed via the inhalation route (nose only) to the test material at a low or a high concentration (4.6 or 14.9 mg/L, respectively) during a 4h-period. The test material concentrations of both dose groups exceed the limit dose of 2 mg/L as recommended by the guideline. A control group of 5 males and 5 females were exposed under the same conditions to air only.

The MMADs have been determined as 1.2 µm and 4.6 µm for the low and the high concentration, respectively. The MMAD of the high concentration exceeds the specifications of testing guideline of 1 - 4 µm, which is due to the high concentration. Mortality was observed in animals of the high dose group only: 3 of 5 males died spontaneously shortly after start of exposure. Those deaths are assumed to be essential due to local effects of overload on the respiratory tract due to the very high exposure concentration, even in absence of true toxicity of the test material. Deaths may have occured by suffocation produced by overload of inhaled solid particles which exceeded the clearance capacity of the lungs and by partial obstruction of the respiratory airways. No mortality was observed in the females of the high dose group and in the animals of the lower dose group. Therefore, the overall LC50 (male + female rats) was > 4.6 mg/L. Mean body weights were unremarkable and comparable to those of the respective controls. The test material is considered not toxic and the effects observed can be explained by the very high concentrations tested in the course of this study.