Registration Dossier

Diss Factsheets

Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
23 September 2016 - 21 February 2017
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2017
Report date:
2017

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Version / remarks:
7 September 2009
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.2 (Acute Toxicity (Inhalation))
Version / remarks:
31 May 2008
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.1300 (Acute inhalation toxicity)
Version / remarks:
August 1998
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Test type:
acute toxic class method
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
Ytterbium (III) oxide
EC Number:
215-234-0
EC Name:
Ytterbium (III) oxide
Cas Number:
1314-37-0
Molecular formula:
O3Yb2
IUPAC Name:
ytterbium (III) oxide
Test material form:
solid: particulate/powder
Details on test material:
- Name: diytterbium trioxide
- Appearance: white solid
- Further information on test material confidential.
Specific details on test material used for the study:
- Treatment of test material prior to testing: The test item was used as supplied.
- No correction factor was applied in this study.

Test animals

Species:
rat
Strain:
Wistar
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, Sandhofer Weg 7, D-97633 Sulzfeld
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: Group 0.1: 12 weeks. Group 1: 8-9 weeks.
- Weight at study initiation: Group 0.1: 439 g (male) and 243 g (female). Group 1: 370-424 g (males) and 215-237 g (females).
- Fasting period before study: no data
- Housing: Group caging (5 animals, by sex, per cage), individual caging during the sighting study. Type III polypropylene solid floor cages with stainless steel mesh lids. Lignocel Bedding for Laboratory Animals and Arbocel nesting material were available to animals during the study. Rodents were housed with deep wood sawdust bedding to allow digging and other normal rodent activities.
- Diet (e.g. ad libitum): ssniff SM R/M “Autoclavable Complete Feed for Rats and Mice – Breeding and Maintenance” (ssniff Spezialdiäten GmbH, D-59494 Soest, Germany; batch: 278 5652, expiry: November 2016; batch: 141 8884, expiry: January 2017), ad libitum.
- Water (e.g. ad libitum): Tap water fit for human consumption, ad libitum.
- Acclimation period: 41 days (Sighting), 14 days (Main study)

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18.5 - 25.7°C
- Humidity (%): 31 - 56%
- Air changes (per hr): 15-20 air exchanges/hour
- Photoperiod (hrs dark / hrs light): 12 dark/12 light

Administration / exposure

Route of administration:
inhalation: aerosol
Type of inhalation exposure:
nose only
Vehicle:
clean air
Mass median aerodynamic diameter (MMAD):
3.24 µm
Geometric standard deviation (GSD):
1.97
Remark on MMAD/GSD:
For Group 0.1: MMAD = 3.03, GSD = 2.05
Details on inhalation exposure:
TECHNICAL TRIALS
- Prior to animal exposures, test material atmospheres were generated within the exposure chamber. During these technical trials, air-flow settings and test material input rates were varied to achieve the required atmospheric characteristics.

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- The animals were exposed, nose-only, to an atmosphere of the test item using a TSE Rodent Exposure System (TSE Systems GmbH, Bad Homburg, Germany). This system comprises of two, concentric anodised aluminium chambers and a computer control system incorporating pressure detectors and mass flow controllers.
- Fresh aerosol from the generation system was constantly supplied to the inner plenum (distribution chamber) of the exposure system from where, under positive pressure, it was distributed to the individual exposure ports.
- Method of holding animals in test chamber: The animals were held in polycarbonate restraint tubes located around the chamber which allowed only the animal’s nares to enter the exposure port.
- Source and rate of air: Compressed air was supplied by means of an oil-free compressor passed through a suitable filter system prior to introduction to the nebuliser. The flow of air through each port was at least 0.5 L/min. This flow rate was considered adequate to minimise re-breathing of the test atmosphere as it is about twice the respiratory minute volume of a rat.
- System of generating particulates/aerosols: The test item was aerosolised using Palas RBG1000 (Palas GmbH, Karlsruhe, Germany) located at the top of the exposure chamber and a glass separator. The rate of formulation use was controlled by the rotation speed.
- Method of particle size determination: The particle size of the test atmosphere was determined three times during the exposure period using a 7-stage impactor of Mercer style (TSE Systems GmbH, Bad Homburg, Germany). Such devices employ an inertial separation technique to isolate particles in the discrete aerodynamic size ranges. Samples were taken from an unoccupied exposure port (representing the animal’s breathing zone). The collection substrates and the backup filter were weighed before and after sampling and the weight of test item, collected at each stage, calculated by this difference. The total amount collected for each stage was used to determine the cumulative amount below each cut-off point size. In this way, the proportion (%) of aerosol less than 0.55, 0.96, 1.55, 2.11, 3.56, 6.66 and 10.55 µm was calculated. From these data, using software supplied with the impactor, the Mass Median Aerodynamic diameter (MMAD), and Geometric Standard Deviation (GSD) were calculated. In addition, the proportion (%) of aerosol less than 4 µm (considered to be the inhalable portion) was determined.
- Treatment of exhaust air: After passing through the breathing zone, used aerosol entered the outer cylinder from where it was exhausted through a suitable filter system. Atmosphere generation was therefore dynamic.
- Temperature, humidity (main study): 21.2°C (19.6 - 22.1°C), 3.6% (3.0 - 5.4%) relative humidity

TEST ATMOSPHERE
- The test atmosphere was sampled at regular intervals during each exposure period. Samples were taken from an unoccupied exposure port (representing the animal’s breathing zone) by pulling a suitable, known volume of test atmosphere through weighed GF10 glass fibre filters (Whatman GmbH, Hahnestraße 3 – D-37586 Dassel, Germany).
- The difference in the pre- and post-sampling weights, divided by the volume of atmosphere sampled, was equal to the actual achieved test atmosphere concentration. The nominal concentration was calculated by dividing the mass of test material disseminated into the chamber by the total volume of air that went through the chamber during the same period.

CLASS METHOD
- Rationale for the selection of the starting concentration: no data
Analytical verification of test atmosphere concentrations:
yes
Remarks:
gravimetrical determination
Duration of exposure:
4 h
Concentrations:
Group 0.1: 1.50 mg/L (actual), 35.94 mg/L (nominal)
Group 1: 1.31 mg/L (actual), 37.78 mg/L (nominal)
No. of animals per sex per dose:
Group 0.1: 1 male, 1 female
Group 1: 5 males, 5 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations:
*Morbidity/mortality: hourly during exposure, one hour after exposure, and twice daily during the 14-day observation period
*Clinical signs: at hourly intervals during exposure, as soon as practically possible following removal from restraint at the end of exposure, one hour after exposure and subsequently once daily for fourteen days
* Body weight: prior to treatment on the day of exposure (Day 0) and on Days 1, 3, 7 and 14
- Necropsy of survivors performed: Yes. At the end of the 14-day observation period, the animals were euthanised by exsanguination under anaesthesia (intra-peritoneal injection of pentobarbital solution – Euthanimal 40%) and gross macroscopic examination was performed. All animals were subject to a gross necropsy which included a detailed examination of the abdominal and thoracic cavities. Special attention was given to the respiratory tract for macroscopic signs of irritancy or local toxicity.
Statistics:
No data

Results and discussion

Preliminary study:
During the sighting study, no mortalities were observed in the single exposed male and the single exposed female. Therefore the main study was performed under similar exposure conditions.
Effect levels
Key result
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 1.31 mg/L air (analytical)
Based on:
test mat.
Exp. duration:
4 h
Remarks on result:
not determinable due to absence of adverse toxic effects
Remarks:
1.31 mg/L was the maximum achievable test concentration
Mortality:
No mortality was observed in either group.
Clinical signs:
other: Wet fur, fur staining was recorded mostly on the day of exposure. These observations were considered to be related to the restraint and exposure procedures and, in isolation, were considered not to be biologically significant. In the Group 0.1, laboured r
Body weight:
In both groups, the exposure procedure caused minimal or no body weight loss in the animals (0.0%-3.9%). After Day 3, normal body weight gain was observed.
Gross pathology:
No macroscopic findings.
Other findings:
No other findings reported.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The acute inhalation median lethal concentration (4-h LC50) of the test item ytterbium oxide in CRL: (WI) Wistar strain rats, was considered to be greater than 1.31 mg/L (the maximum achievable concentration), since no mortalities were observed in the exposed groups. Based on these results, ytterbium oxide is considered not classified as acute toxicant via inhalation according to the CLP Regulation.