Registration Dossier

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Administrative data

Description of key information

LD50 oral, rat > 2000 mg/kg bw
LD50 dermal, rat > 2000 mg/kg bw
4-hr LC50 inhalation, rat > 5.04 mg/L

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:
from 11-JUNE-2007 to 21-NOVEMBER-2007
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study was performed according to EU / OECD guidelines and GLP
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Deviations:
no
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS:
- Source: Janvier, Le Genest-Saint-Isle, France
- Age at study initiation: approximately 8 weeks old
- Weight at study initiation: 211 ± 12 g
- Fasting period before study: for an overnight period of approximately 18 hours before dosing
- Housing: 3 animals (during the treatment period) per polycarbonate cage with stainless steel lid (48 cm x 27 cm x 20 cm)
- Food consumption: free access to SsniffR/M-H pelleted diet (SSNIFF Spezialdiäten GmbH, Soest, Germany)
- Water consumption: Drinking water filtered by a FG Millipore membrane (0.22 micron) was provided ad libitum
- Acclimation period: at least 5 days before the beginning of the study

ENVIRONMENTAL CONDITIONS :
- Temperature: 22 ± 2°C
- Humidity: 30 to 70%
- Air changes: approximately 12 cycles/hour of filtered, non-recycled air
- Photoperiod: 12 h dark/12 h light

In-life dates: From: 13-JUNE-2007 To: 03-JULY-2007
Route of administration:
oral: gavage
Vehicle:
other: purified water
Details on oral exposure:
* Vehicle:
- Concentration in vehicle: 200 mg/ml
- Amount of vehicle : 10 mL/kg
- Justification for choice of vehicle: data not available
- Lot/batch no. : data not available
- Purity: data not available

* Maximum dose volume applied: 10 mL/kg bw
* Dosage preparation: The test item was prepared at the chosen concentration in the vehicle. The test item preparation was made freshly on the morning of administration by the CIT Pharmacy and any unused material was discarded that same day.
* Class method:
- Rationale for the selection of the starting dose: according to the information provided by the Sponsor
Doses:
2000 mg/kg/bw
No. of animals per sex per dose:
2 x 3 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
> Clinical signs and mortality: frequently during the hours following administration of the test item. Thereafter, observation of the animals was made at least once a day
> Body weight: just before administration of the test item on day 1 and then on days 8 and 15
- Necropsy of survivors performed: yes
- Other examinations performed: none
Statistics:
not applicable
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
no deaths were observed during the study
Clinical signs:
other: no clinical signs were observed during the study
Gross pathology:
macroscopic examination of the main organs of the animals revealed no apparent abnormalities
Other findings:
none
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the experimental conditions of this study, the oral LD50 of the test item Reaction mass of lanthanum phosphate and cerium phosphate and terbium phosphate was higher than 2000 mg/kg in rats. No signs of toxicity were observed at this dose.
Executive summary:
The acute oral toxicity of the test item Reaction mass of lanthanum phosphate and cerium phosphate and terbium phosphate was evaluated in rats according to OECD (No. 423, 17th December 2001) and EC (2004/73/EC, B.1 tris, 29th April 2004) guidelines. The study was conducted in compliance with the principles of Good Laboratory Practice Regulations.

The test item was prepared in purified water and was administered by oral route (gavage), under a volume of 10 mL/kg, to 2 groups of three fasted female Sprague-Dawley rats at a dose level of 2000 mg/kg.

Clinical signs, mortality and body weight gain were checked for a period of up to 14 days following the single administration of the test item. All animals were subjected to necropsy.

No deaths and no clinical signs were noted during the study.

When compared to CIT historical control animals, a slightly lower body weight gain was noted in 2/6 animals between day 8 and day 15. The overall body weight gain of the other animals was not affected by treatment with the test item.

At necropsy, no apparent abnormalities were observed in any animal.

 

Under the experimental conditions of this study, the oral LD50 of the test item Reaction mass of lanthanum phosphate and cerium phosphate and terbium phosphate was higher than 2000 mg/kg in rats. No signs of toxicity were observed at this dose.

This acute oral study is classified as acceptable. It does satisfy the guideline requirement for an acute oral study (EU B.1 tris) in the rats.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
Key study quoted as reliability 1 according to Klimisch criteria (performed according to OECD guidelines and in accordance with GLP)

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:
from 14-AUG-2012 to 18-JAN-2013
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study was performed according to EU / OECD guidelines and GLP
Qualifier:
according to guideline
Guideline:
OECD Guideline 436 (Acute Inhalation Toxicity: Acute Toxic Class Method)
Deviations:
yes
Remarks:
the temperatures in the inhalation chamber were slightly increased during the 2d part of the exposure. This deviation had no effect on the purpose and integrity of the study.
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.1300 (Acute inhalation toxicity)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Test type:
acute toxic class method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratories, Research Model and Services, Germany GmbH (Sandhofer Weg 7, D-97633, Sulzfeld)
- Age at study initiation: approximately 10 weeks old (on Day 0)
- Weight at study initiation: 364-374 g (males) and 240-247 g (females) on Day 0
- Fasting period before study: no
- Housing: group caging (3 animals, by sex, per cage) in polycarbonate solid floor cages (type III) with stainless steel mesh lids. (LxWxH in cm: 38x38x18)
- Diet: ad libitum (ssniff SM R/M-Z+H “Autoclavable Complete Feed for Rats and Mice – Breeding and Maintenance”)
- Water: ad libitum (tap water from the municipal supply, as for human consumption from 500 ml bottles)
- Acclimation period: animals were acclimated to laboratory conditions for 21 days prior to involvement in the study. Animals were also acclimatised to the test apparatus (restrain procedures) for a short period prior to testing in order to lessen the stress during exposure.

ENVIRONMENTAL CONDITIONS
- Temperature: 20.4 – 25.0 °C
- Humidity: 36 - 67 %
- Air changes: at least 15 air exchanges per hour
- Photoperiod: 12 hours of continuous artificial light in each twenty-four hour period (from 6.00 a.m. to 6.00 p.m.)

IN-LIFE DATES: from 23 August 2012 (reception of animals) to 27 September 2012 (necropsy)
Route of administration:
inhalation: dust
Type of inhalation exposure:
nose only
Vehicle:
clean air
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: 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. The exposure unit is placed in closed hood in order to avoid cross-contamination and contamination of the laboratory environment. Atmosphere generation was dynamic.
- Exposure chamber volume: no data
- 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 and passed through a suitable filter system prior to introduction to the dust generator. The flow of air through each port was at least 0.5 L/min.
- Method of conditioning air: no data
- System of generating particulates/aerosols: dust particles were produced using a rotating brush dust generator Palas RBG 1000 (Palas GmbH, Karlsruhe, Germany) located at the top of the exposure chamber and compressed air. The dust aerosol produced was then ducted to the exposure system using suitable tubing. In order to improve aerodynamic size distribution, large particles were trapped via impaction in the subsequent simple separator (collision plate).
- The test item was administered after milling the powder to a fine powder.
- 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). 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. From these data, using the software supplied with the impactor (TSE Systems GmbH, Bad Homburg, Germany), the Mass Median Aerodynamic Diameter (MMAD), and Geometric Standard Deviation (GSD) were calculated. In addition, the proportion (%) of aerosol less than 4µm (considered to be the inhalable portion) was determined.
- Treatment of exhaust air: after passing through the animal’s breathing zone, used aerosol entered the outer cylinder from where it was exhausted through a suitable filter system.
- The following variables were monitored continuously and recorded every minute during each exposure period: chamber airflow rates, test atmosphere temperature, test atmosphere relative humidity, test atmosphere carbon dioxide concentration, test atmosphere oxygen concentration

TEST ATMOSPHERE
- Brief description of analytical method used: the dust aerosol concentration was measured gravimetrically 17 times during the exposure and the particle size distribution of the test aerosol was determined 3 times.
> Samples were taken from an unoccupied exposure port by pulling a suitable volume of test atmosphere through weighed GF10 glass fibre filters (Whatman GmbH, Germany, ref. no. 10370302). 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 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. 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 < 0.550, 0.550, 0.960, 1.550, 2.105, 3.555, 6.655 and 10.550 µm was calculated. From these data, using the software supplied with the impactor (TSE Systems GmbH, Bad Homburg, Germany), the Mass Median Aerodynamic Diameter (MMAD), and Geometric Standard Deviation (GSD) were calculated. In addition, the proportion (%) of aerosol less than 4µm (considered to be the inhalable portion) was determined.
- Samples taken from breathing zone: yes (samples were taken from an unoccupied exposure port)

TEST ATMOSPHERE
- Particle size distribution: Inhalable Fraction (% < 4µm) = 59.7%
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): 3.26 µm / 2.29

CLASS METHOD
- Rationale for the selection of the starting concentration: a limit test was conducted at 5 mg/L, as no toxicity was expected based on inhalation data with similar products. Moreover no toxicity was observed with the test item in other tests (not irritant to eyes and skin, LD50 oral/dermal > 2000 mg/kg bw).
Analytical verification of test atmosphere concentrations:
yes
Remarks:
The dust aerosol concentration was measured gravimetrically 17 times during the exposure and the particle size distribution of the test aerosol was determined 3 times.
Duration of exposure:
4 h
Concentrations:
Target Concentration: 5 mg/L
Mean Achieved Concentration: 5.04 mg/L +/- 0.13mg/L
Nominal Concentration: 8.88 mg/L
(see details and tables below)
No. of animals per sex per dose:
3 males and 3 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
> Morbidity/mortality: hourly during exposure, 1 hour after exposure and twice daily (early and late in the working day) during the observation period.
> Clinical signs: at hourly intervals during exposure, and thereafter twice on the day of exposure (following removal from the restrainer and approximately one hour after completion of the exposure) and subsequently once daily for 14 days.
> Bodyweight: individual bodyweights were recorded prior to treatment on the day of exposure (before the exposure on Day 0) and on Days 1, 3, 7 and 14.
- Necropsy of survivors performed: yes
Statistics:
Not applicable (the method used is not intended to allow the calculation of a precise LC50 value)
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 5.04 mg/L air (analytical)
Based on:
test mat.
Exp. duration:
4 h
Mortality:
No animals died during the study.
Clinical signs:
other: In the exposed group, slight laboured respiration was observed in all animals on the day of exposure and persisted in males up to Day 2. In a single male rat, moderately laboured respiration on Day 0 and slight noisy respiration on Day 0-1 were also noted
Body weight:
Slight bodyweight loss (0-4%) or bodyweight retardation was observed in all animals on Day 0-3. All rats returned to the initial values on up to Day 7.
Gross pathology:
No external finding was recorded at necropsy.
Other findings:
No internal finding was recorded at necropsy.
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the experimental conditions of this study, no lethality occurred in rats when exposed to a test atmosphere at 5.04 mg/L (limit test) for 4 hours. The acute inhalation median lethal concentration (LC50) of Reaction Mass of Lanthanum Phosphate and Cerium Phosphate and Terbium Phosphate in rats was therefore considered to be above 5.04 mg/L.
Executive summary:

The acute inhalation toxicity of the test item Reaction mass of lanthanum phosphate and cerium phosphate and terbium phosphate was evaluated in rats according to OECD Guidelines for the Testing of Chemicals No. 436 “Acute Inhalation Toxicity-Acute Toxic Class Method”. The study was conducted in compliance with the principles of Good Laboratory Practice Regulations.

Wistar rats (3 males and 3 females) were exposed to a test atmosphere of the test item at a target concentration of 5 mg/L for 4 hours using a nose-only exposure system. The dust aerosol concentration was measured gravimetrically 17 times during the exposure and the particle size distribution of the test aerosol was determined 3 times. The day of exposure was designated Day 0 and a 14-day observation period followed the exposures.

 

The mean achieved atmosphere concentration was 5.04 mg/L with a standard deviation of 0.13 mg/L. The mass median aerodynamic diameter (MMAD) was 3.26 µm with geometric standard deviation (GSD) 2.29.

No mortality was noted either during the exposure or during the 14-day observation period. No external or internal finding was recorded at necropsy.

Some clinical observations were noted (slight to moderate laboured respiration, noisy respiration, wet fur, red-brown staining and fur stained by test item), but all animals appeared normal within 3 days.

Slight bodyweight loss or bodyweight retardation was observed in all animals on Day 0-3. All rats returned to the initial values on up to Day 7.

 

The acute inhalation median lethal concentration (LC50) of Reaction Mass of Lanthanum Phosphate and Cerium Phosphate and Terbium Phosphate in Wistar rats was considered to be above 5.04 mg/L.

The Reaction Mass of Lanthanum Phosphate and Cerium Phosphate and Terbium Phosphate can be ranked as unclassified according to the UN and EU Globally Harmonized System of Classification and Labelling of Chemicals (GHS).

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
Key study quoted as reliability 1 according to Klimisch criteria (performed according to OECD guidelines and in accordance with GLP)

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:
from 01-JUNE-2007 to 21-NOV-2007
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study was performed according to EU / OECD guidelines and GLP
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS:
- Source: Janvier, Le Genest-Saint-Isle, France.
- Age at study initiation: approximately 8 weeks old
- Weight at study initiation: 341 ± 11 g for the males and 217 ± 9 g for the females.
- Fasting period before study: data not available
- Housing: housed individually in polycarbonate cages with stainless steel lid (35.5 cm x 23.5 cm x 19.3 cm)
- Diet: free access to SsniffR/M-H pelleted diet (SSNIFF Spezialdiäten GmbH, Soest, Germany)
- Water: drinking water filtered by a FG Millipore membrane (0.22 micron) was provided ad libitum
- Acclimation period: at least 5 days before the beginning of the study

* Environmental conditions:
- Temperature: 22 ± 2°C
- Humidity: 30 to 70%
- Air changes: approximately 12 cycles/hour of filtered, non-recycled air
- Photoperiod: 12 h dark/12 h light

* In-life dates : From: 07-JUNE-2007 To: 21-JUNE-2007
Type of coverage:
semiocclusive
Vehicle:
other: none
Details on dermal exposure:
* Test site:
- Area of exposure: dorsal area, approximately 5 cm x 7 cm for males and 5 cm x 6 cm for females
- % coverage: approximately 10% of the total body surface of the animals
- Type of wrap if used: gauze pad held in contact by means of an adhesive hypoallergenic aerated semi-occlusive dressing and a restraining bandage

* Removal of test substance:
- Washing (if done): On removal of the dressing, any residual test item was removed using a moistened cotton pad.
- Time after start of exposure: 24 hours

* Test material:
- Amount(s) applied: 2000 mg/kg bw
- Concentration (if solution): not applicable
- Constant volume or concentration used: yes
- For solids, paste formed: yes (moistened with 2 ml of purified water)

* Vehicle:
- Amount(s) applied: no
- Concentration (if solution): not applicable
Duration of exposure:
24 hours
Doses:
2000 mg/lg bw
No. of animals per sex per dose:
5 males and 5 females
Control animals:
not required
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
> Clinical signs and mortality: frequently during the hours following administration of the test item. Thereafter, observation of the animals was made at least once a day until day 15.
> Body weight: just before administration of the test item on day 1 and then on days 8 and 15.
- Necropsy of survivors performed: yes (digestive tract, heart, kidneys, liver, lungs, pancreas, spleen and any other organs with obvious abnormalities)
- Other examinations performed: local cutaneous reactions at application site were recorded from day 2.
Statistics:
not applicable
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
No deaths occurred during the study.
Clinical signs:
other: No clinical signs and no cutaneous reactions at the treatment site were observed during the study.
Gross pathology:
Macroscopic examination of the main organs of the animals revealed no apparent abnormalities.
Other findings:
no other information
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the experimental conditions of this study, the dermal LD50 of the test item Reaction mass of lanthanum phosphate and cerium phosphate and terbium phosphate was higher than 2000 mg/kg in rats.
Executive summary:

The acute dermal toxicity of the test item Reaction mass of lanthanum phosphate and cerium phosphate and terbium phosphate was evaluated in rats according to OECD (No. 402, 24th February 1987) and EC (92/69/EEC, B.3, 31st July 1992) guidelines. The study was conducted in compliance with the principles of Good Laboratory Practice Regulations.

The test item was applied to the skin of one group of ten Sprague-Dawley rats (five males and five females).

The application was performed with the test item in its original form (moistened with 2 ml of purified water) at the dose-level of 2000 mg/kg. The test site was then covered by a semi-occlusive dressing for 24 hours. Clinical signs, mortality and body weight gain were checked for a period of 14 days following the single application of the test item. All animals were subjected to necropsy.

No deaths, no clinical signs and no cutaneous reactions at the treatment site were observed during the study. When compared to CIT historical control animals, a slightly lower body weight gain was noted in 1/5 females between day 1 and day 8, without any relevant consequence at the end of the observation period. The overall body weight gain of the other animals was not affected by treatment with the test item. No apparent abnormalities were observed at necropsy in any animal.

Under the experimental conditions of this study, the dermal LD50 of the test item Reaction mass of lanthanum phosphate and cerium phosphate and terbium phosphate was higher than 2000 mg/kg in rats.

This acute dermal study is classified as acceptable. It does satisfy the guideline requirement for an acute dermal study (EU B.3) in the rats.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
Key study quoted as reliability 1 according to Klimisch criteria (performed according to OECD guidelines and in accordance with GLP)

Additional information

Reaction mass of lanthanum phosphate and cerium phosphate and terbium phosphate was tested in rats using the three following routes of administration: oral, dermal and inhalation. These key studies are quoted as reliability 1 according to Klimisch criteria since the studies were performed according to OECD guidelines and in accordance with GLP.

Acute toxicity: oral

The acute oral toxicity of the test item Reaction mass of lanthanum phosphate and cerium phosphate and terbium phosphate was evaluated in rats according to OECD (No. 423, 17th December 2001) and EC (2004/73/EC, B.1 tris, 29th April 2004) guidelines (CIT, 2007). The study was conducted in compliance with the principles of Good Laboratory Practice Regulations.

The test item was prepared in purified water and was administered by oral route (gavage), under a volume of 10 mL/kg, to 2 groups of three fasted female Sprague-Dawley rats at a dose level of 2000 mg/kg.

Clinical signs, mortality and body weight gain were checked for a period of up to 14 days following the single administration of the test item. All animals were subjected to necropsy.

No deaths and no clinical signs were noted during the study.

When compared to CIT historical control animals, a slightly lower body weight gain was noted in 2/6 animals between day 8 and day 15. The overall body weight gain of the other animals was not affected by treatment with the test item.

At necropsy, no apparent abnormalities were observed in any animal.

 

Under the experimental conditions of this study, the oral LD50 of the test item Reaction mass of lanthanum phosphate and cerium phosphate and terbium phosphate was higher than 2000 mg/kg in rats, therefore warranting no classification.

 

Acute toxicity: dermal

The acute dermal toxicity of the test item Reaction mass of lanthanum phosphate and cerium phosphate and terbium phosphate was evaluated in rats according to OECD (No. 402, 24th February 1987) and EC (92/69/EEC, B.3, 31st July 1992) guidelines (CIT, 2007). The study was conducted in compliance with the principles of Good Laboratory Practice Regulations.

The test item was applied to the skin of one group of ten Sprague-Dawley rats (five males and five females).

The application was performed with the test item in its original form (moistened with 2 ml of purified water) at the dose-level of 2000 mg/kg. The test site was then covered by a semi-occlusive dressing for 24 hours. Clinical signs, mortality and body weight gain were checked for a period of 14 days following the single application of the test item. All animals were subjected to necropsy.

No deaths, no clinical signs and no cutaneous reactions at the treatment site were observed during the study. When compared to CIT historical control animals, a slightly lower body weight gain was noted in 1/5 females between day 1 and day 8, without any relevant consequence at the end of the observation period. The overall body weight gain of the other animals was not affected by treatment with the test item. No apparent abnormalities were observed at necropsy in any animal.

Under the experimental conditions of this study, the dermal LD50 of the test item Reaction mass of lanthanum phosphate and cerium phosphate and terbium phosphate was higher than 2000 mg/kg in rats, therefore warranting no classification.

Acute toxicity: inhalation

The acute inhalation toxicity of the test item Reaction mass of lanthanum phosphate and cerium phosphate and terbium phosphate was evaluated in rats according to OECD Guidelines for the Testing of Chemicals No. 436 “Acute Inhalation Toxicity-Acute Toxic Class Method” (CiToxLAB, 2013). The study was conducted in compliance with the principles of Good Laboratory Practice Regulations.

Wistar rats (3 males and 3 females) were exposed to a test atmosphere of the test item at a target concentration of 5 mg/L for 4 hours using a nose-only exposure system. The dust aerosol concentration was measured gravimetrically 17 times during the exposure and the particle size distribution of the test aerosol was determined 3 times. The day of exposure was designated Day 0 and a 14-day observation period followed the exposures.

 

The mean achieved atmosphere concentration was 5.04 mg/L with a standard deviation of 0.13 mg/L. The mass median aerodynamic diameter (MMAD) was 3.26 µm with geometric standard deviation (GSD) 2.29.

No mortality was noted either during the exposure or during the 14-day observation period. No external or internal finding was recorded at necropsy.

Some clinical observations were noted (slight to moderate laboured respiration, noisy respiration, wet fur, red-brown staining and fur stained by test item), but all animals appeared normal within 3 days.

Slight bodyweight loss or bodyweight retardation was observed in all animals on Day 0-3. All rats returned to the initial values on up to Day 7.

 

The acute inhalation median lethal concentration (LC50) of Reaction Mass of Lanthanum Phosphate and Cerium Phosphate and Terbium Phosphate in Wistar rats was considered to be above 5.04 mg/L.

The Reaction Mass of Lanthanum Phosphate and Cerium Phosphate and Terbium Phosphate can be ranked as unclassified according to the UN and EU Globally Harmonized System of Classification and Labelling of Chemicals (GHS).


Justification for selection of acute toxicity – oral endpoint
Only one study is available.

Justification for selection of acute toxicity – inhalation endpoint
Only one study is available.

Justification for selection of acute toxicity – dermal endpoint
Only one study is available.

Justification for classification or non-classification

Based on the data available in which no mortality was induced in the rat following a single exposure by oral and dermal route up to a limit dose of 2000 mg/kg bw or a 4 -hr exposure to 5.04 mg/L by inhalation, Reaction Mass of Lanthanum Phosphate and Cerium Phosphate and Terbium Phosphate should not be classified for acute toxicity via the oral, dermal and inhalation route as defined by the criteria of Annex VI Directive 67/548/EEC or UN/EU GHS classification criteria.