Iron titanium pseudobrookite

Endpoint summary

Description of key information

Acute inhalation toxicity: LC50 > 5.08 mg/L air (analytical) (OECD 436; GLP)

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

Study period:

2016-12-07 to 2017-01-05

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 436 (Acute Inhalation Toxicity: Acute Toxic Class Method)

Version / remarks:

2009-09-07

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

signed 2014-05-14

Test type:

acute toxic class method

Limit test:

yes

Specific details on test material used for the study:

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: at room temperature, stored in closed original container in a dry place

Species:

rat

Strain:

other: Crl: CD(SD)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories, Research Models and Services Germany GmbH, Sandhofer Weg 7, 97633 Sulzfeld, Germany
- Females nulliparous and non-pregnant: yes
- Age at study initiation: males: approx. 8 weeks; females: approx. 9 weeks
- Weight at study initiation: males: 269 - 283 g; females: 223 - 248 g
- Fasting period before study: approx. 16 hours before exposure; only tap water was then available ad libitum
- Housing: during the 14-day observation period, the animals were kept by sex in groups of 2 - 3 animals in MAKROLON cages (type III plus); bedding material: granulated textured wood (Granulat A2, J. Brandenburg, 49424 Goldenstedt, Germany).
- Diet: commercial diet, ssniff® R/M-H V1534 (ssniff Spezialdiäten GmbH, 59494 Soest, Germany)
- Water (ad libitum): drinking water
- Acclimation period: at least 5 adaptation days

ENVIRONMENTAL CONDITIONS
- Temperature: 22 °C ± 3 °C (maximum range)
- Relative humidity: 55% ± 10 % (maximum range)
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

inhalation: dust

Type of inhalation exposure:

nose only

Vehicle:

clean air

Mass median aerodynamic diameter (MMAD):

>= 2.364 - <= 2.395 µm

Geometric standard deviation (GSD):

2.22

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: study was carried out using a dynamic inhalation apparatus (RHEMA-LABORTECHNIK, 65719 Hofheim/Taunus, Germany) (air changes/h (≥ 12 times)) with a nose-only exposure of the animals according to KIMMERLE & TEPPER. The apparatus consists of a cylindrical exposure chamber (inner diameter: 23.9 cm; height: 63 cm; volume 28.5 L) which holds the animals in pyrex tubes at the edge of the chamber in a radial position.

- System of generating particulates/aerosols: dust of the test material was generated with a rotating brush dust generator (RBG 1000, PALAS GmbH Partikel und Lasermesstechnik, 76229 Karlsruhe, Germany).
The generator was fed with compressed air (5.0 bar) from a compressor (ALUP Kompressorenfabrik, 73257 Köngen, Germany).
At the bottom of the exposure chamber, the air was sucked off at a lower flow rate than it was created by the dust generator in order to produce a homogenous distribution and a positive pressure in the exposure chamber (inflow 900 L/h, outflow 800 L/h).
A manometer and an air-flow meter (ROTA Yokogawa GmbH & Co. KG, 79664 Wehr/Baden, Germany) were used to control the constant supply of compressed air and the exhaust, respectively. Flow rates were checked hourly and corrected if necessary.
The exhaust air was drawn through gas wash-bottles.

- Method of particle size determination: analysis of the particle size distribution was carried out twice during the exposure period using a cascade impactor (Cascade impactor 6.0 L/min (Article No. 700800-CI-060), TSE Systems GmbH, 61352 Bad Homburg, Germany).
The dust from the exposure chamber was drawn through the cascade impactor for 1 minute at a constant flow rate of 5 L/min. The slides were removed from the impactor and weighed on an analytical balance (SARTORIUS, type 1601 004, precision 0.1 mg). Deltas of slides’ weight were determined.
The mass median aerodynamic diameter (MMAD) was estimated by means of non-linear regression analysis. The 10.6 µm particle size range and the filter (particle size range < 0.55 µm) were not included in the determination of the MMAD in order not to give undue weight to these values.
The Geometric Standard Deviation (GSD) of the MMAD was calculated from the quotient of the 84.1%- and the 50%-mass fractions, both obtained from the above mentioned non-linear regression analysis.
In addition, a sample of approx. 10 g test material was taken from the exposure chamber to determine the median physical particle size with a Malvern Mastersizer 2000 by My-Tec, 91325 Adelsdorf, Germany. This determination was non-GLP.

- Temperature, humidity, pressure in air chamber, oxygen content and carbon dioxide content: oxygen content in the inhalation chamber was 21%. It was determined at the beginning and at the end of the exposure with a DRÄGER Oxygen-analysis test set (DRÄGER Tube Oxygen 67 28 081). Carbon dioxide concentration did not exceed 1%.
Temperature (21.4°C ± 0.2°C (main study) or 20.7°C ± 0.1°C (satellite group)) and humidity (63.7% ± 0.2% (main study) or 53.3% ± 0.1% (satellite group)) were measured once every hour with a climate control monitor (testo 175-HZ data logger).

Exposition started by locating the animals into the exposure chamber after equilibration of the chamber concentration for at least 15 minutes (t95 approximately 8 minutes).

Before initiating the study with the animals, a pre-test was carried out with the exposure system in order to verify that under the experimental settings chosen, the limit concentration of 5 mg/L air could be achieved by gravimetric analysis.

TEST ATMOSPHERE
- Brief description of analytical method used: actual dust concentration in the inhalation chamber was measured gravimetrically with an air sample filter (Minisart SM 17598 0.45 µm) and pump (Vacuubrand, MZ 2C (Membrane Pump, Vacuubrand GmbH + Co. KG, 97877 Wertheim/Main, Germany)) controlled by a rotameter. Dust samples were taken once every hour during the exposure. For that purpose, a probe was placed close to the animals' noses and air was drawn through the air sample filter at a constant flow of air of 5 L/min for 1 minute. The filters were weighed before and after sampling (accuracy 0.1 mg).
- Samples taken from breathing zone: yes

TEST ATMOSPHERE
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.):
Main study: 2.364 µm (GSD: 2.22)
Satellite group: 2.395 µm (GSD: 2.22)

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

4 h

Concentrations:

Main study (limit test):
- actual concentration: 5.08 ± 0.03 mg/L air
- nominal concentration: 33.33 mg/L air
Satellite group:
- actual concentration: 5.06 ± 0.02 mg/L air
- nominal concentration: 33.33 mg/L air

No. of animals per sex per dose:

Main study (limit test):
3 males / 3 females
Satellite group:
3 males / 3 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 24 hours (satellite group) and 14 days (main study)

- Frequency of observations and weighing: during and following exposure, observations were made. Clinical examinations were made at least once daily until all symptoms subsided, thereafter each working day. Observations on mortality were made at least once daily with appropriate actions taken to minimize loss of animals to the study (e.g. necropsy).
Individual weights of animals were determined once during the acclimatisation period, before the exposure on test day 1, on test days 4, 8 and 15. Changes in weight were calculated and recorded when survival exceeded one day. At the end of the test, all animals were weighed and sacrificed.

- Necropsy of survivors performed: yes
Necropsy of all animals was carried out and all gross pathological changes were recorded.
- Satellite animals: necropsy at 24 hours after end of exposure, as this is likely to be the time at which any signs of respiratory irritation would have manifested themselves;
- Main study animals: necropsy at the end of the 14-day observation period

Statistics:

not applicable

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 5.08 mg/L air (analytical)

Based on:

test mat.

Exp. duration:

4 h

Mortality:

5.08 mg/L air (main study) and 5.06 mg/L air (satellite group): no animal died prematurely.

Clinical signs:

other: 5.08 mg/L air (main study) and 5.06 mg/L air (satellite group): slight dyspnoea (reduced frequency of respiration with increased volume) until 3 hours post exposure in all males and all females This effect is considered to be an overall clinical sign of g

Body weight:

All 3 female animals of the main study appeared to be reduced in body weight gain.

Gross pathology:

5.08 mg/L air (main study) and 5.06 mg/L air (satellite group): no pathological changes were observed during necropsy.

Interpretation of results:

GHS criteria not met

Conclusions:

LC50 (rats; 4 hours) > 5.08 mg/L air (actual concentration)
According to the EC-Regulation 1272/2008 and subsequent regulations, the test item is not classified as acute toxic via the inhalation route.
Furthermore, no signs of respiratory tract irritation were observed.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Acute inhalation toxicity

One reliable study described in Haferkorn (2017; OECD 436 (2009); GLP) is considered to be reliable without restrictions and is used as key study for this endpoint. The LC50 was determined to be greater than 5.08 mg/L air (actual concentration).

Justification for classification or non-classification

Acute inhalation toxicity

The available guideline-conform study conducted under GLP indicate that test item is not acutely toxic via the inhalation route. Thus, according to Regulation (EC) No 1272/2008 and subsequent regulations, no classification or labelling is required.

Specific target organ toxicant (STOT) – single exposure: inhalation

Reversible or irreversible adverse health effects were not observed immediately or after exposure in an acute inhalation toxicity test (OECD 436). Thus, the classification criteria as specific target organ toxicant (STOT) – single exposure, inhalation are not met and the substance does not require classification according to Regulation (EC) No 1272/2008 and subsequent adaptations.