Registration Dossier
Registration Dossier
Data platform availability banner - registered substances factsheets
Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.
The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.
Diss Factsheets
Use of this information is subject to copyright laws and may require the permission of the owner of the information, as described in the ECHA Legal Notice.
EC number: 915-152-1 | CAS number: -
- 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
- Flammability
- Explosiveness
- Oxidising properties
- 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
- Dissociation constant
- Viscosity
- 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
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- 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
Repeated dose toxicity: oral
Administrative data
- Endpoint:
- short-term repeated dose toxicity: oral
- Remarks:
- combined repeated dose and reproduction / developmental screening
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- from 26-NOV-2012 to 28-MAY-2013
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: the study was performed according to OECD guideline and GLP.
Cross-reference
- Reason / purpose for cross-reference:
- reference to same study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 013
- Report date:
- 2013
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 422 (Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test)
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Limit test:
- no
Test material
- Reference substance name:
- cerium(3+) lanthanum(3+) terbium(3+) triphosphate
- EC Number:
- 915-152-1
- Molecular formula:
- (La,Ce,Tb)PO4
- IUPAC Name:
- cerium(3+) lanthanum(3+) terbium(3+) triphosphate
- Test material form:
- solid: particulate/powder
- Remarks:
- migrated information: powder
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River Laboratories Italia, Calco, Italy
- Age at study initiation: on the first day of treatment, the males were approximately 10 weeks old and the females were approximately 9 weeks old
- Weight at study initiation: on the first day of treatment, the males had a mean body weight of 387 g (range: 328 g to 436 g) and the females had a mean body weight of 222 g (range: 192 g to 249 g)
- Fasting period before study: no
- Housing: the females were individually housed, except during mating and lactation, in polycarbonate cages (Tecniplast 2154, 940 cm²) with stainless steel lids and containing autoclaved sawdust (SICSA, Alfortville, France). The males were individually housed, except during mating, in wire-mesh cages (43.0 x 21.5 x 18.0 cm). A metal tray containing autoclaved sawdust (SICSA, Alfortville, France) was placed under each cage. Toward the end of gestation and during lactation, autoclaved wood shavings (SICSA, Alfortville, France) were provided to females and their litter as nesting material.
- Diet: free access to SSNIFF R/M-H pelleted maintenance diet, batch Nos. 2537604 and 8788036 (SSNIFF Spezialdiäten GmbH, Soest, Germany), distributed weekly
- Water: free access to bottles containing tap water (filtered with a 0.22 µm filter)
- Acclimation period: the animals were acclimated to the study conditions for a period of 7 days before the beginning of the treatment period
ENVIRONMENTAL CONDITIONS
- Temperature: 22 ± 2°C
- Humidity: 50 ± 20%,
- Air changes: about 12 cycles/hour of filtered, non-recycled air
- Photoperiod: 12 hrs dark / 12 hrs light
IN-LIFE DATES: from 27 November 2012 (day of arrival of the animals) to 27 January 2013 (necropsy of last females)
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- other: 0.5% (w/v) methylcellulose aqueous solution
- Details on oral exposure:
- PREPARATION OF DOSING SOLUTIONS:
The test item was administered as a suspension in the vehicle. The test item was ground to a fine powder, using a mortar and pestle, and then mixed with the required quantity of vehicle.
The test item dose formulations were prepared on a daily basis and delivered to the study room at room temperature.
VEHICLE
- Justification for use and choice of vehicle (if other than water): a stable suspension was obtained in this aqueous vehicle
- Concentration in vehicle: 20, 60 and 200 mg/mL, respectively for the dose levels of 100, 300 and 1000 mg/kg bw/day
- Amount of vehicle: a constant dosage-volume of 5 mL/kg/day was used
- Lot/batch no. (if required): the vehicle was prepared using: drinking water treated by reverse osmosis using ELIX 5 (Millipore SA) and methylcellulose (batch No. 079K0054) - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- Concentrations of the test item in the dose formulations were quantified by ICP-MS, a validated analytical method. It consisted of sampling accurate volume of dose formulations, mineralized the sample using acid and micro wave, and diluting it appropriately with diluent to reach the nominal concentration of measurement.
Before the start of treatment, the suitability of the dose formulation process was confirmed. The homogeneity was determined on a range of dose formulations prepared at levels which covered the lowest and highest concentrations proposed for use in this study.
The concentration of the test item in samples of each control and test item dose formulation used in weeks 1, 3 and 6 was determined. - Duration of treatment / exposure:
- - in the males: 2 weeks before mating, during the mating period, and until sacrifice (at least 5 weeks in total)
- in the females: 2 weeks before mating, during the mating period, during gestation, during lactation until day 5 p.p. inclusive - Frequency of treatment:
- Once a day, at approximately the same time.
Doses / concentrations
- Remarks:
- Doses / Concentrations:
0, 100, 300 and 1000 mg/kg bw/day
Basis:
other: nominal
- No. of animals per sex per dose:
- 10 males and 10 females per dose-level group
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- - Dose selection rationale: following the results of a previous 2-week toxicity study (CiToxLAB France/Study No. 39259 TSR) in which no obvious test item-related effects occurred during the study up to higher dose tested (1000 mg/kd bw/day).
- Post-exposure recovery period in satellite groups: not applicable - Positive control:
- not applicable (not required)
Examinations
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: each animal was checked for mortality and morbidity once a day before the treatment period and at least twice a day during the treatment period. Each animal was observed once a day, at approximately the same time, for the recording of clinical signs.
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: once before the beginning of the treatment period and then once a week until the end of the study.
Observations included (but were not limited to) changes in the skin, fur, eyes, mucous membranes, occurrence of secretions and excretions and autonomic activity (e.g. lachrymation, piloerection, pupil size, unusual respiratory pattern). Changes in gait, posture and response to handling as well as the presence of clonic or tonic movements, stereotypes (e.g. excessive grooming, repetitive circling) or bizarre behavior (e.g. self-mutilation, walking backwards) were also recorded.
BODY WEIGHT: Yes
- Time schedule for examinations: the body weight of each male was recorded on the first day of treatment (day 1), then once a week until sacrifice. The body weight of each female was recorded on the first day of treatment (day 1), then once a week until mated, on days 0, 7, 14 and 20 post-coitum (p.c.) and days 1 and 5 p.p..
FOOD CONSUMPTION:
The quantity of food consumed by each male was measured once a week, over a 7-day period, from the first day of treatment until the start of the mating period. The quantity of food consumed by each female was measured once a week, over a 7-day period, from the first day of treatment until the start of the mating period, during gestation for the intervals days 0-7, 7-14 and 14-20 p.c. and during lactation for the interval days 1-5 p.p..
During the mating period, food consumption was not measured for males or females.
FOOD EFFICIENCY:
- Body weight gain in kg/food consumption in kg per unit time X 100 calculated as time-weighted averages from the consumption and body weight gain data: No
WATER CONSUMPTION: No
OPHTHALMOSCOPIC EXAMINATION: No
HAEMATOLOGY: Yes
- Time schedule for collection of blood: on day 6 p.p. from each group on the day of sacrifice
- Anaesthetic used for blood collection: Yes (isoflurane)
- Animals fasted: Yes (deprived of food for an overnight period of at least 14 hours)
- How many animals: the first five surviving males and the first five females to be sacrificed on day 6 p.p. from each group on the day of sacrifice
- Parameters checked: Erythrocytes (RBC), Mean cell volume (MCV), Packed cell volume (PCV), Hemoglobin (HB), Mean cell haemoglobin concentration (MCH), Mean cell hemoglobin (MCH), Thrombocytes (PLT), Leucocytes (WBC), Differential white cell count with cell morphology (neutrophils (N), eosinophils (E), basophils (B), lymphocytes and large unstained cells (L+LUC), monocytes (M)), Reticulocytes (RTC), Prothrombin time (PT), Fibrinogen (FIB), Activated partial thromboplastin time (APTT)
CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: on day 6 p.p. from each group on the day of sacrifice
- Animals fasted: Yes (deprived of food for an overnight period of at least 14 hours)
- How many animals: from the first five surviving males and the first five females to be sacrificed on day 6 p.p. from each group on the day of sacrifice
- Parameters checked: Sodium (Na+), Potassium (K+), Chloride (Cl-), Calcium (Ca++), Inorganic phosphorus (I.PHOS), Glucose (GLUC), Urea (UREA), Creatinine (CREAT), Total bilirubin (TOT.BIL.), Total cholesterol (CHOL), Triglycerides (TRIG), Alkaline phosphatase (ALP), Alanine aminotransferase (ALAT), Aspartate aminotransferase (ASAT), Total proteins (PROT), Albumin (ALB), Albumin/globulin ratio (A/G), Bile acids (BIL.AC)
URINALYSIS: No
NEUROBEHAVIOURAL EXAMINATION: Yes
- Time schedule for examinations: once at the end of the treatment period
- Dose groups that were examined: the first five surviving males and the first five females to be sacrificed on day 6 p.p. from each group were evaluated with a functional observation battery
- Battery of functions tested:
>> Detailed clinical examination - The following parameters were assessed and graded:
* in the cage: "touch escape" or ease of removal from the cage,
* in the hand: fur appearance, salivation, lachrymation, piloerection, exophthalmos, reactivity to handling, pupil size (presence of myosis or mydriasis),
* in the standard arena (2-minute recording): grooming, palpebral closure, defecation, urination, tremors, twitches, tonic and clonic convulsions, gait, arousal (hypo- and hyper-activity), posture, stereotypy, behavior, breathing, ataxia and hypotonia.
>> Reactivity to manipulation and different stimuli - The following measurements, reflexes and responses were recorded:
* touch response, forelimb grip strength, pupillary reflex, visual stimulus response, auditory startle reflex, tail pinch response, righting reflex, landing foot splay, at the end of observation: rectal temperature.
>> Motor activity was measured once by automated infra-red sensor equipment over a 60 minute period. - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes (see table)
HISTOPATHOLOGY: Yes (see table)
Results and discussion
Results of examinations
- Clinical signs:
- no effects observed
- Mortality:
- no mortality observed
- Body weight and weight changes:
- no effects observed
- Food consumption and compound intake (if feeding study):
- no effects observed
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- not examined
- Haematological findings:
- no effects observed
- Clinical biochemistry findings:
- no effects observed
- Urinalysis findings:
- not examined
- Behaviour (functional findings):
- no effects observed
- Organ weight findings including organ / body weight ratios:
- no effects observed
- Gross pathological findings:
- no effects observed
- Histopathological findings: non-neoplastic:
- no effects observed
- Histopathological findings: neoplastic:
- not examined
- Details on results:
- CLINICAL SIGNS AND MORTALITY
One male given 1000 mg/kg/day was found dead on day 22. The death was considered to be related to the gavage procedure and thus not test item-related. No other animals died during the study.
There were no test item-related clinical signs in males and females from all groups.
BODY WEIGHT AND WEIGHT GAIN (see table 1)
There were no statistically significant effects of treatment with the test item on mean body weight and mean body weight gain in males and females from all groups.
FOOD CONSUMPTION
There were no effects of treatment with the test item on mean food consumption in males and females from all groups.
HAEMATOLOGY
There were no effects of the treatment with the test item on mean hematology data in males and females from all groups.
CLINICAL CHEMISTRY
There were no effects of the treatment with the test item on mean blood biochemistry data in males and females from all groups.
NEUROBEHAVIOUR
There were no toxicologically relevant effects on FOB and motor activity in treated groups as compared to control groups.
ORGAN WEIGHTS
There were no test item-related organ weight differences.
When compared with controls, there were not statistically significant increases in mean absolute and relative-to-body spleen weights in test item-treated males. In the absence of microscopic correlates, these poorly dose-related differences were considered not to be related to test item treatment.
The other mean organ weight differences were considered not to be test item treatment-related in the absence of dose-relationships and microscopic correlates and because of the low magnitude in these differences.
GROSS PATHOLOGY
There were no macroscopic test item-related findings in males and females.
The few macroscopic findings were considered as not test item effects because they were consistent with spontaneously occurring findings described in the literature or their appearance was similar to findings found in controls.
HISTOPATHOLOGY: NON-NEOPLASTIC
There were no microscopic test item-related findings in any males or females as compared to control animals.
The microscopic findings were considered not as related to the test item because they were consistent with spontaneously occurring findings described in the literature, the findings were distributed randomly among groups, or their appearance was similar to findings found in controls.
HISTORICAL CONTROL DATA (if applicable)
OTHER FINDINGS
Effect levels
- Dose descriptor:
- NOAEL
- Effect level:
- 1 000 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: No relevant effects up to highest dose tested
Target system / organ toxicity
- Critical effects observed:
- not specified
Any other information on results incl. tables
Table 1: Mean body weights and mean body weight changes (g)
Sex |
Male |
Female |
|||||||
Dose level (mg/kg/day) |
0 |
100 |
300 |
1000 |
0 |
100 |
300 |
1000 |
|
Pre-mating |
|
|
|
|
|
|
|
|
|
Day 1 |
383 |
387 (+1) |
390 (+2) |
389 (+2) |
222 |
222 (0) |
223 (0) |
222 (0) |
|
Day 15 |
437 |
446 (+2) |
454 (+4) |
456 (+4) |
242 |
244 (+1) |
246 (+2) |
246 (+2) |
|
Day 36 |
464 |
493 (+6) |
494 (+6) |
499 (+8) |
/ |
/ |
/ |
/ |
|
Days 1 - 15 |
+54 |
+59 |
+64 |
+67 |
+20 |
+22 |
+24 |
+24 |
|
Days 15 - 36 |
+27 |
+47 |
+40 |
+38 |
/ |
/ |
/ |
/ |
|
Days 1 - 36 |
+81 |
+106 (+31) |
+104 (+28) |
+107 (+32) |
/ |
/ |
/ |
/ |
|
Gestation |
|
|
|
|
|
|
|
|
|
Day 0p.c. |
/ |
/ |
/ |
/ |
252 |
250 |
248 |
256 |
|
Day 20p.c. |
/ |
/ |
/ |
/ |
421 |
415 |
403 |
416 |
|
Days 0 - 20p.c. |
/ |
/ |
/ |
/ |
+169 |
+165 |
+155 |
+160 |
|
Lactation |
|
|
|
|
|
|
|
|
|
Day 1p.p. |
/ |
/ |
/ |
/ |
316 |
313 |
305 |
321 |
|
Day 5p.p. |
/ |
/ |
/ |
/ |
333 |
321 |
319 |
333 |
|
Days 1 - 5p.p. |
/ |
/ |
/ |
/ |
+17 |
+7 |
+14 |
+12 |
|
Applicant's summary and conclusion
- Conclusions:
- The No Observed Adverse Effect Level (NOAEL) of the test item is 1000 mg/kg/day for both male and female rats.
- Executive summary:
In a combined repeated dose toxicity study with the reproduction/developmental toxicity screening test scored as validity 1 according to Klimisch criteria (OECD guideline 422, GLP, CitoxLab report No.39260 RSR, 2013) Reaction mass of Lanthanum Phosphate and Cerium Phosphate and Terbium Phosphate was administered to 10 Sprague-Dawley rats/sex/dose by gavage,following daily oral administration (gavage) from before mating, through mating and, for females, through gestation until day 5 post-partum (p.p.).
The test item was administered as a suspension in the vehicle,0.5% methylcellulose aqueous solution, at dose-levels of 0 (vehicle), 100, 300 or 1000 mg/kg/day.
The concentration of the dose formulation was checked in study weeks 1, 3 and 6.
The animals were checked at least twice daily during the dosing period for mortality and morbidity and at least once daily for clinical signs. Body weight and food consumption were recorded once a week. Detailed clinical observation was performed once a week, and a functional observation battery was performed at the end of the treatment period.
Hematological investigations and blood chemistry analyses were performed in the first five surviving males and the first five females to be sacrificed on day 6p.p.from each group on the day of sacrifice. Final body weights and selected organs weights (adrenals, brain, epididymes, heart, kidneys, liver, spleen, testes and thymus) were recorded and a complete macroscopic post-mortem examination was performed, with particular attention paid to the reproductive organs. A microscopic examination was performed on selected organs from the first five males and females to deliver in the control and high-dose groups, on the found dead male, and on all macroscopic lesions.
No treatment-related death or clinical signs occurred during the study. There were no effects on body weight, body weight gain or food consumption at any dose level. The Functional Observational Battery assessment, haematology and blood chemistry parameters revealed no treatment-related effects. Macroscopic and microscopic examinations at necropsy did not reveal any treatment-related findings and there were no treatment-related changes in organ weights.
The No Observed Adverse Effect Level (NOAEL) for systemic toxicity was therefore considered to be 1000 mg/kg bw/d for both male and females rats.
No classification for repeat-dose toxicity is warranted based on the absence of relevant effects in this study, according to the criteria of Annex VI Directive 67/548/EEC or UN/EU GHS.
This study is classified as acceptable. It satisfies the OECD 422 guideline requirements on repeated dose toxicity testing.
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.