Registration Dossier

Administrative data

Description of key information

The variations L181 and L175G25C4G were tested for acute oral toxicity.
The variation L175G25C4G was tested for acute toxicity via the inhalation route.
The variation L181 was tested for acute dermal toxicity.
None of the variations showed any acute toxicity or other treatment-related adverse effects in any of the 3 routes.

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
2 000 mg/kg bw
Quality of whole database:
The actual LD50 is > 2000 mg/kg, but IUCLID does not allow to enter this value.
The quality of the entire database is K1.

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:
2010-11-02 to 2011-05-17
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study
Qualifier:
according to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals 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
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"
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
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.
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.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating conc.
Value:
5 140 mg/m³
Quality of whole database:
The actual LC50 is > 51240 mg/kg, but IUCLID does not allow to enter this value.
The quality of the entire database is K1.

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2010-12-09 to 2010-12-29
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study
Reason / purpose:
reference to other study
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River, 97633 Sulzfeld, Germany
- Age at study initiation: males 8 - 9 weeks, females 14 weeks
- Weight at study initiation (administration): males 248 - 252 g, females 208-230 g
- Housing: full barrier in an air-conditioned room
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 6 days

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

IN-LIFE DATES: From: 2010-012-09 To: 2012-12-29
Type of coverage:
occlusive
Vehicle:
water
Remarks:
Aqua ad injectionem (Berlin Chemie, lot no. 01954, expiry date 04/2013)
Details on dermal exposure:
TEST SITE
- % coverage: ca. 10
- Type of wrap if used: additional dressing

REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes; aqua ad injecionem
- Time after start of exposure: 24 h

TEST MATERIAL
- Constant volume or concentration used: yes
- For solids, paste formed: moisted with water

VEHICLE
- Lot/batch no. (if required): Berlin Chemie, lot no. 01954, expiry date 04/2013
Duration of exposure:
24 h
Doses:
2000 mg/kg body weight
No. of animals per sex per dose:
5 each
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Weighing in day 1 (prior to application), day 8, day 15. A careful clinical observation was made several times on the day of dosing (at least during the first 30 minutes and with special attention given during the first 4 hours post dose). thereafter, the animals were observed for clinical signs once daily until the end of the observation period.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, organ weights, histopathology, other: body weight
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality observed.
Clinical signs:
Nasal discharge 1h, 2 h, 3 h and 4 h post dose which is not considered to be test-item related.
Body weight:
body weight [g] and body weight gain [%]
Animal No. / Sex day 1 day 8 day 15 % day 1 -15
21 / M 252 268 300 19
22 / M 252 279 314 25
23 / M 251 270 305 22
24 / M 248 272 300 21
25 / M 250 274 308 23
11 / F 227 223 228 0.4
12 / F 220 217 230 4.5
13 / F 208 206 210 1
14 / F 230 240 249 8
15 / F 220 217 229 4
Gross pathology:
With the exception of acute injection of blood vessels in the abdominal region, which is due to the euthanasia injection, no specific gross pathological changes were recorded for any animal.
Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
After an application period of 24 hours followed by an observation period of 14 days, no mortality and other adverse effects were observed. L181is non-toxic via the dermal route according to CLP
Executive summary:

The acute dermal toxicity of L181 was assessed in a GLP limit test according to OECD 402. 2000 mg/kg body weight of the test item were applied on the skin of Wistar rats (5 males, 5 females). The exposure period was 24 hours followed by an observation period of 14 days.

Erythema grade1 were observed in 2 of 5 female animals. Desquamination was observed in 1 of 5 female animals. Eschar was observed in 3 of 5 female animals. Scratches were observed in 3 of 5 female and 2 of 5 male animals. All sings of irritation were reversible within the observation period.

No mortalities and no treatment-related other adverse effects were observed.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
2 000 mg/kg bw
Quality of whole database:
The actual LD50 is > 2000 mg/kg, but IUCLID does not allow to enter this value.
The quality of the entire database is K1.

Additional information

The variations L181 and L175G25C4G were tested for acute oral toxicity in a GLP guideline studies according to OECD 423.

The variation L175G225C4G was tested for acute toxicity via the inhalation route in a GLP guideline study according to OECD 403.

The variation L181 was tested for acute dermal toxicity in a GLP guideline study according to OECD 402.

Both variations did not exhibit any acute toxicity via any route of exposure.

The studies for the inhalation route and the dermal route are not required under REACH for the tonnage band 1 - 10 t/a. The results of the 4 studies on acute toxicity reveal the same toxicological profile for both variations. The same toxicological profile is expected for other variations of the substance pentaaluminium triyttrium dodecaoxide.


Justification for selection of acute toxicity – oral endpoint
Both studies were selected.

Justification for selection of acute toxicity – inhalation endpoint
Study available

Justification for selection of acute toxicity – dermal endpoint
Study available

Justification for classification or non-classification

Pentaaluminium triyttrium dodecaoxide did not show any acute toxicity via the oral or dermal or the inhalation route. C&L is not required.