Registration Dossier

Administrative data

Description of key information

The substance lutetium aluminium oxide, cerium and gallium doped, garnet (variation L173) was tested for acute oral toxicity and for acute dermal toxicity.
The substance did not show any acute toxicity or other treatment-related adverse effects in both routes.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2009-04-14 to 2009-05-12
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
acute toxic class method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River, 97633 Sulzfeld, Germany
- Age at study initiation: 8 - 12 weeks
- Weight at study initiation: animals 1 - 3: 181 - 197 g; animals 4 - 6: 174 - 177 g
- Fasting period before study: 16 - 19 h. Access to water was permitted.
- Housing: Semi-barrier in an air-conditioned room
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: all animals 6 days

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

IN-LIFE DATES: From: all animals: 2009-04-21 To: animals 1 - 3: 2009-04-29; animals 4 - 6: 2009-05-12
Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 0.2 g /mL
- Amount of vehicle (if gavage): 10 mL
- Justification for choice of vehicle: non-toxic characteristics
- Lot/batch no. (if required): B. Braun Melsungen, lot no. 7494A191

MAXIMUM DOSE VOLUME APPLIED: 2000 mg/kg body weight

DOSAGE PREPARATION (if unusual): Homogeneity of the test item in the vehicle was maintained by vortexing the prepared suspension thoroughly before every dose administration.

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: No severe toxicity expected.
Doses:
2000 mg/kg body weight
No. of animals per sex per dose:
6
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days)
- Frequency of observations and weighing: day 0 (pre-dose, 30 minutes and 4 h post dose), day 7, day 14 as a minimum
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, organ weights, histopathology, other: no
Sex:
female
Dose descriptor:
LD50
Effect level:
5 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: LD50 cut off
Mortality:
No mortality observed
Clinical signs:
Prior to the administration a detailed clinical observation was made of all animals.
A careful clinical observation was made several times on the day of dosing; at least once during the first 30 minutes and with special attention during the first 4 hours post-dose. Thereafter, the animals were observed for clinical signs once daily until the end of the observation period.

Clinical signs were not observed during the whole observation period.
Body weight:
Absolute body weights in g and body weight gain in %
day 0 day 7 day 14 day 0 - 14
animal 1 181 194 194 7
animal 2 186 199 199 7
animal 3 197 218 219 11
animal 4 177 208 226 28
animal 5 174 192 210 21
animal 6 177 224 245 38
Gross pathology:
No special gross pathological changes were recorded for any animal.
Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The LD50 cut off (rat) of L173 via the oral route was 5000 mg/kg body weight.
Executive summary:

The oral toxicity of L173 was examined in a GLP guideline study according to OECD 423.

Under the conditions of the study, a single oral application to rats at a dose of 2000 mg/kg body weight was neither associated with signs of toxicity nor mortality.

The median lethal dose of L173 after single oral administration to female rats, observed over a period of 14 days is:

LD50 cut off (rat): 5000 mg/kg body weight.

The substance does not require classification.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
5 000 mg/kg bw
Quality of whole database:
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:
2009-04-07 to 2009-05-12
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
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: 8 - 12 weeks
- Weight at study initiation (administration): males 311 - 360 g, females 208 - 216 g
- Housing: Semi barrier in an air-conditioned room
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 20 days

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

IN-LIFE DATES: From: 2009-04-07 To: 2009-05-12
Type of coverage:
semiocclusive
Details on dermal exposure:
TEST SITE
- Area of exposure: dorsal area
- % coverage: 10
- Type of wrap if used: Gauze dressing and non-irritating tape, fixed with an additional dressing

REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes, lukewarm water
- Time after start of exposure: 24 h

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

VEHICLE
- Lot/batch no. (if required): B. Braun Melsungen, lot. no. 7494A191
- Purity: aqua ad injectionem
Duration of exposure:
24 h
Doses:
2000 mg/kg body weight
No. of animals per sex per dose:
5 males, 5 females
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: daily observation, weighing on day 0, day 7 and day 14
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, 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:
No findings.
Body weight:
body weight [g] and body weight gain [%]
Animal no. / sex day 0 day 7 day 14 % day 0 - 14
11 F 208 212 222 7
12 F 208 208 218 5
13 F 216 226 241 12
14 F 213 222 240 13
15 F 212 220 233 10
21 M 360 369 409 14
22 M 331 338 372 12
23 M 331 335 395 19
24 M 332 345 373 12
25 M 311 327 353 14

Gross pathology:
No special gross pathological changes
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. L173 is non-toxic via the dermal route according to CLP
Executive summary:

The acute dermal toxicity of L173 was assessed in a GLP guideline study according to OECD 402. 2000 mg/kg of the test item were applied on the skin of Wistar rats (5 females, 5 males). The exposure period was 24 h followed by an observation period of 14 days.

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

The substance is considered non-toxic via the dermal route.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
K1
LD50 > 2000 mg/kg bw

Additional information

The substance lutetium aluminium oxide, cerium and gallium doped, garnet (variation L173) was tested for acute oral toxicity and for acute dermal toxicity. The substance did not exhibit any acute toxicity or other treatment-related adverse effects in both routes of exposure. The same toxicological profile is expected for other variations than L173 of the substance lutetium aluminium oxide, cerium and gallium doped, garnet.


Justification for selection of acute toxicity – oral endpoint
Available GLP guideline study

Justification for selection of acute toxicity – dermal endpoint
Available GLP guideline study

Justification for classification or non-classification

Lutetium aluminium oxide, cerium and gallium doped, garnet did not reveal any toxicity via the oral or dermal route. C&L is not required.