Chrome tungsten titanium buff rutile

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2021-05-27 to 2021-06-17

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2021

Report date:

2021

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

2009

Deviations:

yes

Remarks:

please refer to the field `Principles of method if other than guideline´

Principles of method if other than guideline:

- The male and female rats were 6 and 7 weeks old on the exposure day, instead of 8 - 12 weeks;
- The GSD of 3.368 is slightly above the boundaries of 1.5 - 3.
- The exposure was interrupted (for 100 minutes) based on a failure of the compressed air system 10 minutes after start, the animals were immediately removed from the restraining tubes and transferred to their cages. Afterwards, the experiment was continued.

GLP compliance:

yes (incl. QA statement)

Remarks:

signed, 2021-03-31

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Chrome tungsten titanium buff rutile

EC Number:

269-054-2

EC Name:

Chrome tungsten titanium buff rutile

Cas Number:

68186-92-5

Molecular formula:

Cr(2x/3)W(x/3)Ti(1-x)O2 0,05≤x≤0,25

IUPAC Name:

tungsten(6+) titanium(4+) dichromium(3+) octaoxidandiide

Test material form:

solid: particulate/powder

Details on test material:

- Test item identification: Chrome tungsten titanium buff rutile
- C.I. name: Pigment Yellow 163
- Substance type: inorganic pigment
- Storage conditions: At room temperature, under moisture protection

Specific details on test material used for the study:

Particle size parameter (equipment: HELOS (H3695) & RODOS/M, R3, Non-GLP determination): x 100 = 30.00 μm (x: particle size; 100: percentage cumulative)

Test animals

Species:

rat

Strain:

other:

Remarks:

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, 97633 Sulzfeld, Germany
- Females nulliparous and non-pregnant: yes
- Age on day of exposure: males: 42 days, females: 49 days
- Weight on day of exposure: males: 237 - 241 g, females: 192 - 203 g
- Fasting period before study: no
- Housing: groups of 3 animals (per sex) in MAKROLON cages (type III plus) with a basal surface of approximately 39 cm (l) x 23 cm (w) x 18 cm (h); bedding material: granulated textured wood (Granulat A2, J. Brandenburg, 49424 Goldenstedt, Germany)
- Diet (ad libitum): ssniff® R/M-H V1534 (ssniff Spezialdiäten GmbH, 59494 Soest, Germany)
- Water (ad libitum): tap water
- Acclimation period: 7 days
- Microbiological status when known: Periodic analysis of the diet, water and bedding material for contaminants based on EPA/USA was conducted by LUFA-ITL

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 55 ± 10
- Air changes (per hr):
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

inhalation: dust

Type of inhalation exposure:

nose only

Vehicle:

air

Mass median aerodynamic diameter (MMAD):

1.257 µm

Geometric standard deviation (GSD):

3.368

Remark on MMAD/GSD:

According to OECD Guideline 436, aerosols with a mean aerodynamic mass diameter (MMAD) of 1 to 4 μm with a geometric standard deviation (σg) in the range of 1.5 to 3.0 are recommended to allow exposure of all relevant respiratory tract areas. The MMAD meets the criteria, but the GSD is slightly elevated.

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: dynamic inhalation apparatus, RHEMA-LABORTECHNIK, 65719 Hofheim/Taunus, Germany
- Exposure chamber volume: 28.5 L
- Method of holding animals in test chamber: cylindrical exposure chamber, which holds the animals in pyrex tubes at the edge of the chamber in a radial position.
- Source and rate of air (airflow): compressed air (5.0 bar) from a compressor (ALUP Kompressorenfabrik, 73257 Köngen, Germany); inflow / outflow: 900 L/h / 800 L/h
- Method of conditioning air: manometer and an air-flow meter (ROTA Yokogawa GmbH & Co. KG, 79664 Wehr/Baden, Germany) controlled the constant supply of compressed air
- System of generating dust: rotating brush dust generator (RBG 1000, PALAS GmbH Partikel und Lasermesstechnik, Karlsruhe, Germany)
- Method of particle size determination: The particle size was determined by a cascade impactor and by laser diffraction.
- Treatment of exhaust air, pressure in air chamber: at the bottom of the exposure chamber, the air was sucked off at a lower flow rate (800L/h) than it was created by the spray-jet (900L/h) in order to produce a homogenous distribution and a positive pressure in the exposure chamber.
- Temperature, humidity, pressure in air chamber: temperature (22°C ± 3 °C) and humidity (55 % ± 15) were checked once every hour with a climate control monitor (testo 175-HZ data logger).

TEST ATMOSPHERE
- Brief description of analytical method and equipment used:
Analysis of the dust concentration
The aerosol was generated using a rotating brush dust generator. the actual dust concentration in the inhalation chamber was measured gravimetrically with an air sample filter (0.45 μm, Minisart SM 17598) and pump (Membrane Pump MZ 2C,Vacuubrand GmbH + Co. KG, 97877 Wertheim/Main, Germany) controlled by a rotameter (Rota Yokogawa Deutschland GmbH, 40880 Rattingen, Germany). Dust samples were taken once every hour during the exposure 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 60 seconds. The filters were weighed before and after sampling (accuracy 0.1 mg). The nominal concentration (total amount of the substance fed into the inhalation equipment divided by volume of air), was calculated.
Particle size distribution (PSD), Mass median aerodynamic diameter (MMAD) and geometric standard deviation (GSD):
The dust from the exposure chamber was drawn through a 7 stage cascade impactor (Cascade impactor 6.0 L/min (Article No. 700800-CI-060), TSE Systems GmbH, 61352 Bad Homburg, Germany) twice (70 min and 160 min) during the exposure period, for 5 minutes at a constant flow rate of 5 L/min. The slides were removed and weighed; deltas of slides’ weight were determined.
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 GSD of the MMAD was calculated from the quotient of the 84.1 % fraction and the 50 % mass fraction, both obtained from the non-linear regression analysis.
A sample of approx. 10 g test material was taken from the exposure chamber and send on 26 May 2021 to My-Tec GmbH, 91325 Adelsdorf, Germany, to determine the median physical particle size with a HELOS (H3695) & RODOS/M, R.

- Samples taken from breathing zone: yes
- Time needed for equilibrium of exposure concentration before animal exposure: 15 min

VEHICLE: no vehicle used

CLASS METHOD (if applicable)
- Rationale for the selection of the starting concentration: a limit dose at a concentration of 5 mg/L was conducted by a request of the Sponsor

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

4 h

Remarks on duration:

The exposure was interrupted (for 100 min) based on a failure of the compressed air system 10 minutes after start, the animals were immediately removed from the restraining tubes and transferred to their cages. Afterwards, the experiment was continued.

Concentrations:

- Gravimetric (actual) concentration of chrome tungsten titanium buff rutile ± standard deviation [mg/L air]: 5.08 ± 0.03
- Nominal concentration [mg/L air]: 55.56
- Relation of actual to nominal concentration: 0.09

No. of animals per sex per dose:

Limit test:
6 (3 male and 3 female) animals, 2 (1 male and 1 female) reserve animals were additionally employed to the study.

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
clinical observations: on the day of exposure, frequently during exposure and twice thereafter; during the observation period (14 days) at least once daily
Body weights: once during the adaptation period, before the exposure, on test days 4, 8, 15 and at time of death.
- Necropsy of survivors performed: yes
- Clinical signs including body weight: changes in the skin and fur, eyes, mucous membranes, respiratory, circulatory, autonomic and central nervous system, somatomotor activity and behaviour pattern, tremor, convulsions, salivation, diarrhoea, lethargy, sleep and coma, indications of respiratory irritation such as dyspnoea.
- Other examinations performed: observations on mortality, isolation or sacrifice of weak or moribund animals; necropsy and macroscopic inspections, lung weights, fixation of organs in 10% (nose (5 levels of the nasal turbinates), i.e. head without brain, eyes, and lower jaw) or 7% buffered formalin (larynx, trachea, lungs (five levels)) for a potential histopathological examination.

Statistics:

not specified

Results and discussion

Preliminary study:

not specified

Effect levels

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:

no mortality occured

Clinical signs:

other: None of the animals revealed any signs of toxicity

Body weight:

The body weight gain was in the expected range at the end of the study on test day 15, thus no treatment-related effects were observed.

Gross pathology:

The macroscopic examination did not reveal any changes. No influence on the respiratory tract or the lung weights was noted. Hence, no histopathological examination was performed.

Other findings:

not specified

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Under the conditions of this study, the 4-hour inhalation LC50 of Chrome tungsten titanium buff rutile/L air. is >5.08 mg/L air, and hence, the LC50 cut-off value 'unclassified'.
According to the EC Regulation 1272/2008 and subsequent regulations, the test material is not classified for acute inhalation toxicity.

Executive summary:

Three male and three female rats were exposed to an aerosol of chrome tungsten titanium buff rutile at gravimetrically determined concentrations of 5.08 ± 0.03 mg/L air (limit test) for 4 hours by inhalation using a dynamic nose-only exposure chamber.
No signs of toxicity were observed in any of the rats after the 4-hour exposure to the aerosol and the MMAD values (mean 1.257 µm) were within the boundaries of 1 and 4 μm as required by the OECD guideline 436.

Under the present test conditions, the following LC50 value was determined for rats (males and females combined) following a 4-hour inhalation of chrome tungsten titanium buff rutile (gravimetric concentration): LC50 is > 5.08 mg/L air.