Pentaaluminium triyttrium dodecaoxide

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2010-11-02 to 2011-05-17

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2011

Report date:

2011

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Pentaaluminium triyttrium dodecaoxide

EC Number:

234-465-8

EC Name:

Pentaaluminium triyttrium dodecaoxide

Cas Number:

12005-21-9

Molecular formula:

Al5O12Y3

IUPAC Name:

pentaaluminium triyttrium dodecaoxide

Details on test material:

- Name of test material (as cited in study report): L175G25C4G
- Substance type: inorganic
- Physical state: solid
- Analytical purity: presumably > 99.9 %
- Lot/batch No.: Lot# 411
- Expiration date of the lot/batch: not applicable
- Stability under test conditions: stable
- Storage condition of test material: room temperature

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan, Indianapolis, Indiana, USA
- Age at study initiation: 8 - 9 weeks
- Weight at study initiation: males 224 - 238 g, females 177 - 190 g
- Housing: Singly housed in suspended stainless steel cages with mesh floors. Litter paper was placed beneath the cage and was changed at least 3 times per week.
- Diet (e.g. ad libitum): ad libitum except during exposure
- Water (e.g. ad libitum): ad libitum except during exposure
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 23 °C
- Humidity (%): 42 - 66 %
- Air changes (per hr): 12
- Photoperiod (hrs dark / hrs light): 12 / 12

IN-LIFE DATES: From: 2011-04-26 To: 2011-05-17

Administration / exposure

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

nose only

Vehicle:

clean air

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Nose Only Inhalation chamber, ADG Developments Ltd.
- Exposure chamber volume: 28 L
- Method of holding animals in test chamber: Animals were individually housed in polycarbonate holding tubes which seal to the chamber with an "O" ring during exposure.
- Source and rate of air: 40 L/min of filtered air by an air compressor (Airgas) to the dust generator. 65 L/min of compressed mixing air, supplied using air from a compressed air tank (Airgas) ---> total of 105 L/min.
- Method of conditioning air: Compressed mixing air was introduced into the chamber to help uniformly distribute the test atmosphere by creating a vortex at the chamber inlet.
- System of generating particulates/aerosols: The ungrounded substance was aerosolised using a Dust generator (fluid Energy jet-Mill, Serial # J296L with an Accurate series 100 Dry Material Feeder apparatus.
- Method of particle size determination: An eight stage ACFM Andersen ambient Particle Sizing Sampler was used to assess the particle size distribution of the test atmosphere. Samples were withdrawn from the breathing zone of the animals in 2 intervals. The filtre paper collection stages were weighed before and after sampling to determine the mass collected upon each stage. the aerodynamic mass median diameter and geometric standard deviation were determined graphically using tow-cycle logarithmic probit axis.
- Treatment of exhaust air: no data
- Temperature, humidity, pressure in air chamber: Exposure tube: 20 - 22 °C, 59 - 67 %. Room temperature 20 - 22 °C, 53 - 60 %.

TEST ATMOSPHERE
- Brief description of analytical method used: see particle size determination
- Samples taken from breathing zone: yes

VEHICLE
- Composition of vehicle (if applicable): air
- Concentration of test material in vehicle (if applicable): 5.14 mg/l

TEST ATMOSPHERE (if not tabulated)
- Particle size distribution: see table in "divers1.doc", attached documents
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): see table in "divers1.doc", attached documents

CLASS METHOD (if applicable)
- Rationale for the selection of the starting concentration: Desired chamber concentration was 5.0 mg/L. 12 pre-test trials were conducted to establish generation procedures to achieve, to the extent possible, the desired chamber concentration. The procedures and aerosolisation equipment finally chosen for the full test provided a chamber concentration of 5.14 mg/L.

Analytical verification of test atmosphere concentrations:

yes

Remarks:

Chamber concentration and particle size distribution were determined periodically during the exposure period

Duration of exposure:

ca. 241 min

Remarks on duration:

Animals exposed to the test atmosphere for 241 min. Exposure period extended beyond 4 h to allow the chamber to reach equilibrium (T99). 99% equlibration was reached after 1 min.

Concentrations:

5.14 mg/L

No. of animals per sex per dose:

5 males, 5 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Weighing prior to test substance exposure Initial) and on days 1, 3, 7 and 14. Observation for mortality during exposure period. Examinations for gross toxicity and behavioral changes upon removal from the exposure tube and at least once daily thereafter for 14 days.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, organ weights, histopathology, other: body weight

Statistics:

As for particle size distribution see "GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION"

Results and discussion

Preliminary study:

The desired chamber concentration was 5.0 mg/L and the desired chamber particle size distribution (mass median aerodynamic diameter) was 1 and 4 µm. 12 pre-test trials were conducted to establish generation procedures to achieve, to the extent possible, the desired chamber concentration and particle size distribution. in these trials the following adjustemnts were made in an attempt to achieve these objectives:
- generation system
- test substance concentration
- compressed mixing air
- total airflow
- test substance delivery method
- chamber size
- pump setting / motor setting

Effect levels

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 5.14 mg/L air

Based on:

test mat.

Exp. duration:

241 min

Mortality:

No mortality observed

Clinical signs:

other: Following exposure of the test atmosphere, 1 male and 2 females exhibited irregular respiration, but recovered by day 2 and along with the other animals appeared active and healthy for the remainder of the study. Although mist animals lost weight by day 1

Body weight:

Body weights [g]
Animal No. Sex initial day 1 day 3 day 7 day 14
3301 M 227 228 242 269 304
3302 M 235 240 244 272 292
3303 M 224 221 231 257 283
3304 M 238 239 251 283 313
3305 M 235 231 245 270 299
3306 F 177 173 177 189 200
3307 F 190 187 197 200 218
3308 F 185 186 189 207 210
3309 F 188 183 194 204 219
3310 F 189 187 193 205 214

Gross pathology:

No gross abnormalities were noted.

Applicant's summary and conclusion

Interpretation of results:

practically nontoxic

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under the conditions of this study, the single exposure acute inhalation LC50 of L175G25C4G is > 5.14 mg/L in male and female rats. Based on the results of this study L175G25C4G does not require C&L as to the CLP-Regulation 1272/2008.

Executive summary:

An acute inhalation toxicity test was conducted with rats to determine the potential for L175G25C4G to produce toxicity from a 4 -hour exposure via the inhalation route.

After establishing the desired generation procedures during pre-test trials, 5 healthy female and male rats were exposed to the test atmosphere for 4 hours. Chamber concentration and particle size distribution were determined periodically during the exposure period. The animals were observed for mortality, signs of gross toxicity, and behavioral changes at least once daily for 14 days following exposure. Body weights were recorded prior to exposure and again on days 1,3, 7 and 14. Necropsies were performed on all animals at terminal sacrifice. No gross abnormalities were noted.

Under the conditions of this study, the single exposure acute inhalation LC50 of L175G25C4G is > 5.14 mg/L in male and female rats. Based on the results of this study L175G25C4G does not require C&L as to the CLP-Regulation 1272/2008.