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EC number: 235-337-4 | CAS number: 12168-86-4
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
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- Explosiveness
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- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
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- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
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- Nanomaterial pour density
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- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
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- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
Endpoint summary
Administrative data
Description of key information
Skin sensitisation - in vitro
An in vitro or in chemico skin sensitisation study does not need to be conducted because adequate data from an in vivo skin sensitisation study (initiated before October 11th 2016) is available.
Skin sensitisation - in vivo
A reliable skin sensitisation study is available for lutetium oxide silicate (Tarcai, 2017, GPMT study performed according to OECD guideline 406, scored Klimisch 1). In this study, no signs of contact sensitisation were detected after the challenge exposure in guinea pigs previously exposed to the test item during the experiment. In the control and treated animals, the mean of the scores was 0.00 according to the 24- and 48-hour results. Under the conditions of the present assay, lutetium oxide silicate was shown to have no skin sensitisation potential, and is classified as a non-sensitiser, according to current EU-regulations.
Key value for chemical safety assessment
Skin sensitisation
Link to relevant study records
- Endpoint:
- skin sensitisation: in vivo (non-LLNA)
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 2016-10-11 to 2017-06-02
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 406 (Skin Sensitisation)
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Type of study:
- guinea pig maximisation test
- Justification for non-LLNA method:
- The GPMT method (OECD 406) was preferred above LLNA (OECD 429) since previous experience with various rare earth compounds learned that there is an increased risk for false positive results when performing the LLNA. Additionally, insoluble inorganic substances, such as lutetium oxide silicate, are often not able to penetrate the skin.
- Specific details on test material used for the study:
- Correction factor for purity of the test item: 1.05.
Concentrations were calculated to anhydrous form. - Species:
- guinea pig
- Strain:
- other: CRL:HA
- Sex:
- female
- Details on test animals and environmental conditions:
- TEST ANIMALS
- Source: Charles River Laboratories, Research Models and Services, Germany GmbH, Sandhofer Weg 7, D- 97633 Sulzfeld , Germany
- Females, nulliparous and non-pregnant: yes
- Age at first dosing (Day 1): young adult, ~ 9 weeks old
- Weight at randomisation (Day -1): 363 - 435 g
- Housing: Macrolon cages size IV, with up to 5 animals/cage to allow socialisation. Lignocel® 3/4-S Hygienic Animal Bedding produced by J. Rettenmaier & Söhne GmbH+CO.KG (D-73494 Rosenberg, Holzmühle 1, Germany) was available to the animals during the study.
- Diet (e.g. ad libitum): Ad libitum, Cunigra Diet for Rabbits (produced by Bonafarm-Bábolna Takarmány Ltd., Hungary). This diet is classified as being suitable for guinea pigs as the vitamin D level is high enough to meet the needs of this species. This is the diet used by the breeder/supplier and animals are fully adapted to this diet on arrival.
- Water (e.g. ad libitum): Ad libitum, tap water from municipal supply as for human consumption, containing at least 50 mg/100 mL ascorbic acid. The drinking water is routinely analysed and is considered not to contain any contaminants that could reasonably be expected to affect the purpose or integrity of the study.
- Acclimation period: At least 5 days before start of treatment under laboratory conditions. Animals were examined on arrival and only healthy animals were used for the test. The health status was certified by the veterinarian.
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 16.5–21.6°C
- Humidity (%): < 20–60 %
- Air changes (per hr): 15-20 air exchange/hour
- Photoperiod (hrs dark / hrs light): 12 hrs dark / 12 hrs light - Route:
- other: intradermal (main study part I)
- Vehicle:
- other: 1% methylcellulose
- Concentration / amount:
- 1% test item in vehicle
- Day(s)/duration:
- day 1 of treatment
- Route:
- other: dermal (main study part II)
- Vehicle:
- other: 1% methylcellulose
- Concentration / amount:
- 100% test item in vehicle
- Day(s)/duration:
- day 8 of treatment; 48 hours of exposure
- No.:
- #1
- Route:
- epicutaneous, occlusive
- Vehicle:
- other: 1% methylcellulose
- Concentration / amount:
- 100% test item in vehicle; vehicle in right side
- Day(s)/duration:
- day 22 of treatment; 24 hours of exposure
- No. of animals per dose:
- preliminary test: 8 female animals
main test: 10 in the test group, 5 in the control group - Details on study design:
- RANGE FINDING TESTS
- The dose levels for the main study were selected based on the results of the preliminary test.
- A day prior to the test, the hair was removed from the right and left sides of the animals (approximately 5x5cm). The hair removal was performed carefully to ensure animals are closely shaven.
- A series of test item concentrations was tested to identify the primary irritation following intradermal injection and dermal application: 1, 2.5 and 5% (w/v) concentrations (5% with FCA as well) were used for intradermal injection and 25, 50, 75 and 100% (w/v) for dermal application.
- For the intradermal application, 0.1 mL per concentration was injected intradermally into the hair free skin of the animals. Two concentrations were injected on the right side and another two concentrations on the left side of the animals. The highest concentration (5%) for intradermal treatment was also used in a 1:1 mixture (v/v) of Freund's complete Adjuvant and 1% mehylcellulose solution. Each concentration was injected in duplicate. Two animals were used per concentration.
- For the dermal application, the volume of the concentrations was 0.5 mL. A closed patch exposure was performed by means of an occlusive bandage using similar treatment procedures as for the main study. The time of exposure for the dermal application was 48 hours. In the preliminary study one concentration was used on the right side and another concentration on the left side of the animals. Two animals per concentrations were used in the preliminary study.
- Local effects were examined and scored 1, 24, 48 and 72 hours after the treatment or after patch removal.
- Skin effects were scored for erythema and oedema; any other observations of changes to the skin were recorded.
MAIN STUDY
A. INDUCTION EXPOSURE
A1 INTRADERMAL INDUCTION EXPOSURE (day 1)
- No. of exposures: 3 pairs of intradermal injections (0.1 mL/site)
- Test groups (the first listed nearest the head): 2 injections of Freund's Complete Adjuvant and 1% MC in a 1:1 (v/v) mixture, 2 injections of 1% test item in 1% MC, 2 injections of 1% test item, formulated in a 1:1 mixture (v/v) of Freund's Complete Adjuvant and 1% MC .
- Control group (the first listed nearest the head): 2 injections of Freund's Complete Adjuvant and 1% MC in a 1:1 (v/v) mixture, 2 injections of 1% MC, 2 injections of vehicle (1% MC), formulated in a 1:1 mixture (v/v) of Freund's Complete Adjuvant and 1% MC.
- Site: Scapular region. On the day before treatment, an area approximately 5x5cm on the scapular region of the animals was clipped free of hair and was carefully shaved.
- Frequency of applications: one application
- Skin reactions were observed and recorded as follows: 1, 24, 48 and 72 hours after the patch removal
A2 DERMAL INDUCTION EXPOSURE (day 8)
- Since 100% concentration of the test item was not skin irritant in the dermal dose range finding study, the test area was painted with 10% sodium dodecyl sulphate approximately 24 hours prior to dermal induction exposure.
- Site: The same scapular region which received the intradermal injections, were used for dermal induction exposure.
- Test groups: Seven days after the intradermal injections, the same hair-free scapular area was treated. A 2.5x2.5cm sterile gauze patch (approximately 4 layers of porous gauze pads) was saturated with approximately 0.5 mL of the test item at 100% concentration and placed over the injections ites (scapular region). The gauze patches were kept in contact with the skin by a patch with a surrounding adhesive hypoallergenic plaster. The treated areas were covered for 48 hours with a fully occlusive foil (Closed Patch Test). After the patch removal, any remaining test item was removed with a wet gauze swab. Following the dermal induction treatment, the animals were left untreated for 14 days prior to challenge applications.
- Control group: The control group was treated with 0.5 mL vehicle (1% MC) using the same method.
- Frequency of application: one application
- Skin reactions were observed and recorded as follows: 24 hours after treatment
B. CHALLENGE EXPOSURE (day 22)
- Day(s) of challenge: day 22
- Exposure period: 24 hours
- Site: Left and right sides, approximately 24 hours before the treatment, the hair was removed from an area of approximately 5x5cm on the left and right sides of each animal.
- Test groups: A 2.5x2.5 cm patch of sterile gauze was saturated with approximately 0.5 mL of test item at 100% concentration (highest achievable and non-irritant dose) and applied to the left side of all animals (both the test and the control). After patch removal, any remaining test item was removed with a wet gauze swab.
- Control group: The right shaved side area of all animals was treated with the vehicle (1% MC).
- Skin reactions were observed and recorded as follows: 24 and 48 hours after the patch removal
OTHER
BODY WEIGHT
Body weight was recorded with a precision of 1 g at randomisation (Day -1), then at least weekly, including Day 25 prior to euthanasia. The mean values and the standard deviations were calculated and reported.
OBSERVATIONS
- Mortatlity/Clinical signs: Daily during the test.
- Detailed clinical observations were made on all animals outside the home cage in a standard arena before the first treatment (on the day of randomisation) and at least weekly thereafter. The dermal irritation scores (in cases of dermal induction exposures) were evaluated according to the scoring system by Draize (1959)
TERMINAL PROCEDURE
Terminally animals were sacrificed under pentobarbital anaesthesia.
- Challenge controls:
- A 2.5x2.5 cm patch of sterile gauze was saturated with approximately 0.5 mL of test item at 100% concentration (highest achievable and non-irritant dose) and applied to the left side of all animals. The right shaved side area of all animals was treated with the vehicle (1% MC)
- Positive control substance(s):
- yes
- Remarks:
- 2-mercaptobenzothiazole
- Positive control results:
- Challenge with the test item 2-mercaptobenzothiazole elicited discrete erythema (score 1) on the skin surface of previously sensitised guinea pigs. The mean of the scores was 0.80 (80% of animals) at 24 hours observation and 0.70 (70% of animals) at 48 hours observation. In the control group, the mean of the scores was 0.00. On the basis of the results of the present study, the test item 2-mercaptobenzothiazole was classified as a skin sensitiser. This demonstrates that the Magnusson and Kligman method (OECD 406) in this laboratory is considered to be reliable.
- Key result
- Reading:
- 1st reading
- Hours after challenge:
- 24
- Group:
- test chemical
- Dose level:
- 100%
- No. with + reactions:
- 0
- Total no. in group:
- 10
- Clinical observations:
- No signs of systemic or local toxicity were observed. No mortality was observed.
- Remarks on result:
- no indication of skin sensitisation
- Key result
- Reading:
- 2nd reading
- Hours after challenge:
- 48
- Group:
- test chemical
- Dose level:
- 100%
- No. with + reactions:
- 0
- Total no. in group:
- 10
- Clinical observations:
- No signs of systemic or local toxicity were observed. No mortality was observed.
- Remarks on result:
- no indication of skin sensitisation
- Key result
- Reading:
- 1st reading
- Hours after challenge:
- 24
- Group:
- negative control
- Dose level:
- 100%
- No. with + reactions:
- 0
- Total no. in group:
- 5
- Clinical observations:
- No signs of systemic or local toxicity were observed. No mortality was observed.
- Key result
- Reading:
- 2nd reading
- Hours after challenge:
- 48
- Group:
- negative control
- Dose level:
- 100%
- No. with + reactions:
- 0
- Total no. in group:
- 5
- Clinical observations:
- No signs of systemic or local toxicity were observed. No mortality was observed.
- Key result
- Reading:
- 1st reading
- Hours after challenge:
- 24
- Group:
- positive control
- Dose level:
- 50% w/v (2-mercaptobenzothiazole)
- No. with + reactions:
- 8
- Total no. in group:
- 10
- Clinical observations:
- Discrete erythema (score 1) on the skin of the animals
- Remarks on result:
- positive indication of skin sensitisation
- Key result
- Reading:
- 2nd reading
- Hours after challenge:
- 48
- Group:
- positive control
- Dose level:
- 50% w/v (2-mercaptobenzothiazole)
- No. with + reactions:
- 7
- Total no. in group:
- 10
- Clinical observations:
- Discrete erythema (score 1) on the skin of the animals
- Remarks on result:
- positive indication of skin sensitisation
- Interpretation of results:
- GHS criteria not met
- Conclusions:
- Challenge with test item (lutetium oxide silicate) evoked no positive responses in the test animals previously sensitised with the test item or in the control group. The net response value represented an incidence rate of 0% and the net score value of 0.00.
In conclusion, under the conditions of the present assay the test item lutetium oxide silicate was shown to have no skin sensitisation potential and does not need to be classified as a skin sensitiser, according to current GHS criteria and EU-regulations. - Endpoint:
- skin sensitisation: in vitro
- Data waiving:
- study scientifically not necessary / other information available
- Justification for data waiving:
- other:
Referenceopen allclose all
Preliminary study
- The concentration of 2.5%, 5% and 5% with FCA caused a maximum of well-defined erythema (score 2), whereas the concentration of 1% caused very slight erythema (score 1). The formulation of 5% with FCA could not be administered as a whole (the skin resisted to the injection), thus two additional animals were used after the end of the first preliminary study to check the maximum concentration (with saline or 1% methylcellulose) that is administrable as a whole injection (0.1 mL). Concentrations of 5%, 2.5% and 1% with FCA:saline, and 5% and 2.5% FCA:1% methylcellulose were not appropriate for intradermal treatment (not possible to inject or not possible to inject as a whole). The highest applicable concentration was 1% in FCA:1% methylcellulose, therefore this concentration and vehicle were considered to be appropriate for the main study intradermal treatment.
- Adverse effects were not observed during the dermal treatment of the preliminary study in each concentration (25%, 50%, 75% and 100%).
- On the basis of results of the preliminary dose range finding study, the following treatments were chosen for the main study:
*Intradermal induction: 1% test item formulated in 1% MC in the test group and 1% MC in the control group.
*Dermal induction: 100% test item formulated in 1% MC in the test group and 1% MC in control group. Since the 100% test item was not skin irritant in the dermal dose range finding study, 0.5 mL of 10% sodium dodecyl sulphate in vaseline was applied 24 hours prior to the topical induction application, in order to create local irritation. Therefore, six days after the intradermal injections, the same scapular area (approximately 5x5 cm) was clipped free of hair (if necessary) prior to the application.
*Challenge phase: 100% test item in 1% MC on the left side and 1% MC on the right side for all animals (treatment and control group) as a challenge exposure. This concentration was the highest which caused no irritation.
Main study
- Test group: After the challenge with the test item at a concentration of 100% formulated in 1% MC, no positive response was observed in the treated animals on the left flank. The mean of scores was 0.00 according to the 24 and 48-hour results. The right shaved side of test animals was treated with 1% MC and no reaction was noted.
- Control group: After the challenge with the test item at a concentration of 100% formulated in 1% MC, no visible changes were found at the 24 and 48-hours examinations on the left flank. The right shaved side of control animals was treated with 1% MC and no reaction was noted.
- Clinical observations: No signs of systemic or local toxicity were observed. No mortality was observed during the study.
- Body weight: There were no notable differences between the test animal group and the control group.
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (not sensitising)
- Additional information:
Skin sensitisation - in vitro
An in vitro or in chemico skin sensitisation study does not need to be conducted because adequate data from an in vivo skin sensitisation study (initiated before October 11th 2016) is available.
Skin sensitisation - in vivo
A skin sensitisation study was performed in the guinea pig according to the Magnusson and Kligman method, using a maximisation method, with Freund's Complete Adjuvant to evaluate the sensitisation potential of the test item. The study was performed according to OECD guideline 406 and in compliance with GLP guidelines (Tarcai, 2017, scored Klimisch 1). This skin sensitisation potential test method (OECD 406) was preferred above the LLNA (OECD 429) since previous experience with various rare earth compounds learned that there is an increased risk for false positive results when performing the LLNA. Additionally, insoluble inorganic substances, such as lutetium oxide silicate, are often not able to penetrate the skin.
Based on the results of a preliminary test, 10 test animals were subjected to sensitisation procedures in a two-stage process incorporating an induction phase using an intradermal treatment followed by a 48-hour topical application (dermal treatment under an occlusive dressing). The test item was used at a concentration of 1% (w/v) in 1% methylcellulose for intradermal injections, and at a concentration of 100% (w/v) in 1% methylcellulose for topical sensitisation treatment. Since the 100% formulation was not skin irritant in the dermal dose range-finding study, the test area was painted with 0.5 mL of 10% SDS in vaseline 24 hours prior to the topical induction application, in order to create local irritation. Five control guinea pigs were simultaneously exposed to 1% methylcellulose during the sensitisation phase (intradermal and dermal treatment). Two weeks after the last induction exposure, a challenge dose at a concentration of 100% (w/v) in 1% methylcellulose was dermally administered on the left side of all animals for 24 hours. The right side of the animals was treated with 1% methylcellulose only. Skin reactions were measured 24 and 48 hours after patch removal. No test item-related signs of systemic toxicity were observed in any animal. No signs of contact sensitisation were detected after the challenge exposure in guinea pigs previously exposed to the test item during the experiment. In the control and treated animals, the mean of the scores was 0.00 according to the 24- and 48-hour results. Under the conditions of the present assay, the test item was shown to have no sensitisation potential, and is classified as a non-sensitiser, according to current EU-regulations.
Respiratory sensitisation
Endpoint conclusion
- Endpoint conclusion:
- no study available
Justification for classification or non-classification
Skin sensitisation
The test item is considered to be non-sensitising, based on the results of a GPMT study (OECD guideline 406).
Respiratory sensitisation
No reliable study is available.
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