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EC number: 233-801-0 | CAS number: 10361-92-9
- 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
Endpoint summary
Administrative data
Description of key information
Repeated dose toxicity - oral
No reliable information has been identified on the oral repeated dose toxicity of yttrium trichloride. Therefore, the endpoint was covered using the results of the key combined repeated dose toxicity and screening reproduction/developmental toxicity test performed with yttrium trinitrate, i.e. an yttrium compound with similar water solubility as yttrium trichloride. This study was performed according to OECD guideline 422 (Rossiello, 2017; Klimisch 1) and conform GLP requirements. In this study, male and female rats were exposed to 0, 250, 500 and 1000 mg/kg bw/day yttrium trinitrate via their diet, during 32-33 days (males) or 41-44 days (females). No treatment-related effects indicating systemic toxicity were observed in male or female animals at any of the dose levels investigated. Based on these results, the NOAEL was concluded to be higher than or equal to 1000 mg/kg bw/day for males and females. This result is considered relevant for yttrium trichloride as well. The read across justification document is attached to IUCLID Section 13.
Repeated dose toxicity - inhalation/dermal
No key studies were identified for repeated dose toxicity after inhalation or dermal exposure.
A key study is available for the oral route of exposure. According to the REACH Regulation, only one route of exposure should be tested for repeated dose toxicity (column 2, annex VIII, section 8.6.1). Therefore, it is not necessary to perform a repeated dose toxicity study via the inhalation or dermal route of exposure.
Key value for chemical safety assessment
Repeated dose toxicity: via oral route - systemic effects
Link to relevant study records
- Endpoint:
- short-term repeated dose toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 2015-10-12 to 2017-11-24
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Reason / purpose for cross-reference:
- reference to other study
- Reason / purpose for cross-reference:
- reference to same study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 422 (Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test)
- Version / remarks:
- adopted on 22 March 1996
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Limit test:
- no
- Species:
- rat
- Strain:
- Sprague-Dawley
- Remarks:
- Crl:CD(SD)BR
- Details on species / strain selection:
- The Sprague Dawley rat is the species and strain of choice because it is accepted by many regulatory authorities, recognised as appropriate for general and reproduction toxicity studies and there is ample experience and background data on this species and strain.
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River Italia S.p.A., Calco (Lecco), Italy.
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 6 to 7 weeks old
- Weight at study initiation: 194-220 g males; 170-184 g females
- Fasting period before study: no
- Housing:
Pretest: Animals were housed up to 5 of one sex to a cage, in polysulphone solid bottomed cages measuring 59.5x38x20 cm. Nesting material was provided inside suitable bedding bags and changes at least twice a week.
Mating: Animals were housed one male to one female in clear polysulphone cages measuring approximately 43x27x18 cm with a stainless steel mesh lid and floor. Each cage tray held absorbent material which was inspected and changed daily.
Post-mating: The males were housed individually and remained in the same cages as during the mating; the females were transferred to individual solid bottomed cages for the gestation period, birth and lactation. Suitable nesting material was provided and changed as necessary.
- Diet (e.g. ad libitum): ad libitum, commercially available laboratory rodent diet
- Water (e.g. ad libitum): ad libitum, drinking water to each cage via water bottles.
- Acclimation period: 13 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22°C +/- 2°C
- Humidity (%): 55% +/- 15%
- Air changes (per hr): 15 to 20 air changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours each day - Route of administration:
- oral: feed
- Details on route of administration:
- The test item was administered orally, via the diet. The oral route was selected as it is a possible route of exposure of the test item in man.
- Vehicle:
- other: powdered rodent diet
- Details on oral exposure:
- PREPARATION OF DOSING SOLUTIONS:
- The test item was formulated using powdered diet, by a premix (using mortar and pestle) followed by dilution with further quantity of diet and mixing. When necessary, the formulation was prepared separated for each group/sex. Inclusion levels (ppm) were reviewed during the study, in order to obtain nominal dose levels of 250, 500 and 1000 mg/kg/day. Fresh diets were prepared at weekly intervals according to available stability data supplied by the Laboratory LAUS which performed the validation study. Concentrations were calculated and expressed in terms of active ingredient (71.3%).
- The concentrations of test item in the diet were adjusted as required in order to maintain the required dose level for each treated group. Initial dietary concentrations were predicted from growth and food intake data collection during the acclimatisation period. The dietary inclusion levels were reviewed at weekly intervals, the day after body weight measurements.
VEHICLE
- Justification for use and choice of vehicle (if other than water): test substance was administered oral via diet
- Concentration in vehicle: not specified
- Amount of vehicle (if gavage): not applicable
- Lot/batch no. (if required): not specified
- Purity: 99.4% - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- The analytical method and the proposed method of formulation had been validated in a separate study (LAUS Study No. 14111201G926) to confirm that the proposed formulation procedure was acceptable and that the stability of the formulation at room temperature for 10 days was satisfactory in the concentration range of 250 - 15000 ppm. Samples of the formulations were prepared at the Test Facility during pre-treatment period and on four occasions during the study and were analysed to check the homogeneity and concentration.
Two replicates of 5 g were drawn from group 1 and group 3 preparations while 6 replicates of 5 g were drawn from group 2 and group 4 preparations (2 from the top, 3 from the middle and 1 from the bottom of the formulated diet sample) during the pre-treatment, weeks 3, and 7. During weeks 1 and 5, formulations were prepared seperately by sex, therefore, for each sampling date a total of 16 or 24 specimens were prepared for analysis. For each specimen, an additional back up sample of 10 g was retained at the test facility. Samples were labelled as follows: study number, sampling date, nominal concentration and replicate number. - Duration of treatment / exposure:
- Males: 32-33 days; 2 weeks prior to pairing, during pairing with females until the day before necropsy
Females: 41-44 days; 2 weeks prior to pairing, during pairing and throughout the gestation and lactation periods until day 3 post partum - Frequency of treatment:
- Animals were dosed once a day, 7 days a week
- Dose / conc.:
- 0 mg/kg bw/day (nominal)
- Remarks:
- Group 1; control
- Dose / conc.:
- 250 mg/kg bw/day (nominal)
- Remarks:
- Group 2; mean achieved dose 271 mg/kg/day (males), 323 mg/kg/day (females)
- Dose / conc.:
- 500 mg/kg bw/day (nominal)
- Remarks:
- Group 3; mean achieved dose 574 mg/kg/day (males), 584 mg/kg/day (females)
- Dose / conc.:
- 1 000 mg/kg bw/day (nominal)
- Remarks:
- Group 4; mean achieved dose 1096 mg/kg/day (males), 1160 mg/kg/day (females)
- No. of animals per sex per dose:
- 10 animals/sex/dose level
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- - Dose selection rationale: Nominal dose levels of 250, 500 and 1000 mg/kg/day were selected in agreement with the Sponsor, based on a previous preliminary non GLP compliant study (refer to cross-reference Rossiello, 2015).
- Rationale for animal assignment (if not random): on the day of allocation (7 days prior to the start of treatment), all animals were weighed. Animals at the extremis of the weight distribution were excluded to leave the required number of animals. The rats were allocated to the groups by computerised stratified randomisation to give approximately equal intial group mean body weights. - Positive control:
- no
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: Once before commencement of treatment and once daily during the study, each animal was observed and any clinical signs were recorded.
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: Once before commencement of treatment and once a week thereafter. Each animal was removed from the home cage and observed in an open arena.
- Parameters: observation of changes in gait and posture, reactivity to handling, presence of clonic or tonic movements, stereotypies or bizarre behaviour and effects on the autonomic nervous system (eg lachrymation, piloerection, pupil size, unusual respiratory pattern)
BODY WEIGHT: Yes
- Males were weighed on the day of allocation, on the day before treatment commenced, weekly thereafter and just prior to necropsy.
- Females were weighed on the day of allocation, on the day before treatment commenced, weekly thereafter up to positive identification of mating and on gestation Days 0, 7, 14 and 20. Dams were also weighed on Days 1 and 4 post partum.
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): Yes
- Food consumption: Weekly during the pre-mating period starting from allocation. During the mating period the food consumption was recorded daily. After mating for male animals, food consumption was recorded daily until sacrifice. Individual food consumption for the females was measured daily during gestation starting from Day 0 post coitum and daily during post partum period starting from Day 1 post partum.
- Achieved dosage: The group mean achieved intake of test item was calculated for males (before pairing and from pairing up to the end of the study) and for females (before pairing, during post coitum including high dose female not pregnant and excluding mid dose female with mating not detected and during post partum) from the group mean body weight and food consumption data and the dietary inclusion levels of the test item.
The following formula was used: Achieved dosage (mg/kg/day) = (ppm (mg/kg) x mean daily food consumption (g/day)) / mean period body weight (g).
For females during post coitum and during post partum periods, the ppm were changed within the interval of body weight measurement, therefore the calculation was done for single animals and for different day intervals.
HAEMATOLOGY: Yes
- As a part of the sacrificial procedure, after recording the terminal body weight, samples of blood were withdrawn under isofluorane anaesthesia from the abdominal vena cava from 5 males and 5 females (females with viable litters, if possible) randomly selected from each group, under condition of food deprivation.
- Parameters assessed: Haematocrit, Haemoglobin, Red blood cell count, Reticulocyte count, Mean red blood cell volume, Mean corpuscular haemoglobin, Mean corpuscular haemoglobin concentration, White blood cell count, Differential leucocyte count (Neutrophils, Lymphocytes, Eosinophils, Basophils, Monocytes, Large unstained cells), Platelets, Prothrombin time (as coagulation parameter).
CLINICAL CHEMISTRY: Yes
- As a part of the sacrificial procedure, after recording the terminal body weight, samples of blood were withdrawn under isofluorane anaesthesia from the abdominal vena cava from 5 males and 5 females (females with viable litters, if possible) randomly selected from each group, under condition of food deprivation.
- Parameters checked: Alkaline phosphatase, Alanine aminotransferase, Aspartate aminotransferase, Gamma-glutamyl transferase, Urea, Creatinine, Glucose, Triglycerides, Bile acids, Inorganic phosphorus, Total bilirubin, Total cholesterol, Total protein, Albumin, Globulin, A/G Ratio, Sodium, Potassium, Calcium, Chloride
FUNCTIONAL OBSERVATIONS:
- Grip strength and sensory reactivity to stimuli: Once during the study, towards the end of treatment, 5 males and 5 females were randomly selected from each group for evaluation of sensory reactivity to stimuli of different modalities (e.g. auditory, visual and proprioceptive stimuli) and for assessment of grip stregth.
- Motor activity assessment: Once during the study, towards the end of treatment, 5 males and 5 females were randomly selected from each group and the motor activity was measured (for approximately 5 minutes) by an automated activity recording device.
OTHER:
- MORTALITY: Throughout the study, all parental animals were checked early in each working day in the morning and in the afternoon. At weekends and public holidays, a similar procedure was followed except that the final check was carried out at approximately mid-day. This allowed post-mortem examinations to be carried out during the working period of that day. A complete necropsy was performed. - Sacrifice and pathology:
- SACRIFICE
Animals selected for blood collection were killed by exsanguination under isofluorane anaesthesia. Animals not selected for blood collection were killed under carbon dioxide asphyxiation.
- Parental males: Males were killed after the mating of all females and after 32-33 days of treatment.
- Parental females: The females with live pups were killed on day 4 post partum. The females with total litter loss were killed on the day of the occurrence of total litter loss or shortly after. Female no. 67 of group 4 which did not give birth after 25 days of post coitum period was sacrificed on day 26 post coitum and was found not pregnant at necropsy.
GROSS PATHOLOGY: Yes
- Clinical history of males and females of the parental generation was studied and a detailed post mortem examination was conducted (including examination of the external surface and orifices).
- Changes were noted, organs weighed and tissue samples preserved.
HISTOPATHOLOGY: Yes
- After dehydration and embedding in paraffin wax, sections of the tissues were cut at 5 µm thickness and stained with haematoxylin and eosine. In addition, testes and epididymides were cut at 2-3 µm thickness and stained with periodic acid schiff.
- The morphological evaluation of the seminiferous epithelium (staging of spermatogenic cycle) was performed.
- Samples of the following tissues and organs were collected and fixed: abnormalities, Adrenal glands, bone marrow (from sternum), Brain (cerebrum, cerebellum, medulla/pons), Caecum, Clitoris, Colon, Duodenum, Epididymides, Heart, Ileum, Jejunum including Peyer's patches, Kidneys, Liver, Lung including mainstem bronchi, Lymph nodes - cervical, Lymph nodes - mesenteric, Nasal cavity, Oesophagus, Ovaries with oviducts, Parathyroid glands, Pituitary gland, Penis, Prostate gland, Rectum, Sciatic nerve, Seminal vesicles with coagulation glands, Spinal column, Spinal cord - cervical, midthoracic, lumbar, Spleen, Stomach, Testes, Thymus, Thyroid, Trachea, Urinary bladder, Uterus-cervix, Vagina
ORGAN WEIGHTS
- For all animals completing the scheduled test period.
- Organs were dissected free of fat and weighed.
- Ratios of organ weight to body weight were recorded.
- Organs: Adrenal glands, Brain, Epididymides, Glans penis, Heart, Kidneys, Liver, Ovaries with oviducts, Parathyroid glands, Prostate gland, Seminal vesicles with coagulating glands, Spleen, Testes, Thymus, Thyroid, Uterus-cervix - Statistics:
- Group mean values were calculated for all parameters.
Data from females with total resorption or non-pregnant were excluded from group mean calculations as considered appropriate by the study director.
The following statistical methods were used to analyse the data:
- Standard deviations were calculated as appropriate.
- For continuous variables, the significance of the differences amongst group means was assessed by Dunnett's-test or modified t-test, depending on the homogeneity of the data.
- The non-parametric Kruskal-Wallis analysis of variance was used for the other parameters.
- Intergroup differences between the control and treated groups were assessed by the non-parametric version of the Williams test.
- The criterion for statistical significance was p<0.05. - Clinical signs:
- no effects observed
- Description (incidence and severity):
- No compound-related effects were observed in treated males and females throughout the study. Observation of animals at removal from the cage and in an open arena (neurotoxicity assessment) did not reveal changes attributable to the test item.
- Mortality:
- no mortality observed
- Description (incidence):
- No mortality occurred throughout the study.
- Body weight and weight changes:
- effects observed, non-treatment-related
- Description (incidence and severity):
- No treatment-related effects on body weight were seen in males. The slight increases in body weight seen in treated female groups, when compared to controls, during the pre-pairing period, statistically significant in the low dose group, were considered of no toxicological significance.
However, transient statistically significant variations in body weight gain were recorded in the mid-dose males and in the low and mid-dose females before pairing, and in the low and high dose females during gestation, with no dose relation, therefore considered not toxicologically relevant. - Food consumption and compound intake (if feeding study):
- effects observed, non-treatment-related
- Description (incidence and severity):
- - Food consumption: No toxicologically relevant effects on food consumption were observed in either males or females of all test item-treated groups when compared to controls. Slight increases in food consumption were seen on occasion troughout the study in mid- and high dose animals.
- Achieved dosage: The calculated mean achieved dosages for 2 weeks of treatment of the pre-pairing period were 270, 539 and 1108 mg/kg/day for males and 289, 579 and 1135 mg/kg/day for females. The achieved dosages for males from mating up to the end of the study were 271, 555 and 1084 mg/kg/day. During the post coitum and post partum periods, females had achieved dosages of 279, 562 and 1127 mg/kg/day and 401, 611 and 1217 mg/kg/day, respectively. During the entire treatment period, the mean achieved dosages were 271, 547 and 1096 mg/kg/day for males and 323, 584 and 1160 mg/kg/day for females, with respect to the nominal dose levels of 250, 500 and 1000 mg/kg/day. - Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- not examined
- Haematological findings:
- effects observed, non-treatment-related
- Description (incidence and severity):
- - One high dose female (no. X0070071) showed marked lymphopenia (83% below mean control data). Due to the low incidence, this change cannot be conclusively attributed to treatment.
- The other statistically significant differences between control and treated animals, such as decrease of reticulocytes in mid-dose males, and increase of reticulocytes in high dose females were not consistent between sexes and/or dose-related, therefore considered unrelated to treatment.
- No change was recorded in the coagulation test. - Clinical biochemistry findings:
- effects observed, non-treatment-related
- Description (incidence and severity):
- - Statistically significant fluctuations of some biochemical parameters were observed, such as: decrease of alkaline phosphatase in low dose males (26%), decrease of creatinine and potassium in mid-dose males (25% and 4%, respectively) and increase of glucose in high dose females (32%). Due to the absence of dose-relation or other related findings, the above changes were considered of no toxicological significance.
- Urinalysis findings:
- not examined
- Behaviour (functional findings):
- effects observed, non-treatment-related
- Description (incidence and severity):
- Motor activity and sensory reaction to stimuli: No relevant differences were noted in all parameters investigated between control and treated groups, with the exception of a statistically significant increase in the grip strength observed in mid-dose group. In the absence of dose-relationship or other affected parameters, this change was considered incidental.
- Immunological findings:
- not examined
- Organ weight findings including organ / body weight ratios:
- effects observed, non-treatment-related
- Description (incidence and severity):
- - Terminal body weight was unaffected by treatment in both sexes.
- Statistically significant increases in absolute and relative testes weight (9% and 13%, respectively), slight increases in absolute and relative epididymides weight (11% and 14%, respectively) and slight decreases in absolute and relative seminal vescicles weight (-13% and -10%, respectively), were seen in high dose males; decreases in absolute and relative (statistically significant ) adrenals weight (-14% and -20%) and statistically significant decrease in relative heart weight (-8%) were seen in low dose females. Due to the absence of related histopathological findings and/or the lack of dose-relationship, these changes were not considered of toxicological significance. - Gross pathological findings:
- effects observed, non-treatment-related
- Description (incidence and severity):
- The most remarkable changes observed at post mortem examination in treated animals, when compared with controls, were:
- Red/dark red mucoid contents of the stomach in two high dose females without any evident correlation at histopathology.
- Increased size of the adrenals of two high dose males and one mid-dose male. However, this finding did not correspond to any histopathological changes of both cortex and medulla. As morphology is comparable to control animals, a direct treatment-related impact is not considered to be present.
The remaining macroscopic observations were considered to be an expression of spontaneous and/or incidental pathology, seen in this species and age of untreated animals. - Neuropathological findings:
- not examined
- Histopathological findings: non-neoplastic:
- effects observed, non-treatment-related
- Description (incidence and severity):
- No treatment-related changes were noted.
The histopathological changes, reported in control and treated animals, were considered to be an expression of spontaneous and/or incidental pathology, commonly seen in this species and age under the experimental conditions of the test. - Histopathological findings: neoplastic:
- not examined
- Other effects:
- not examined
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- >= 1 000 mg/kg bw/day (nominal)
- Based on:
- act. ingr.
- Remarks:
- anhydrous yttrium trinitrate
- Sex:
- male/female
- Remarks on result:
- not determinable due to absence of adverse toxic effects
- Key result
- Critical effects observed:
- no
- Conclusions:
- The toxicological potential of yttrium trinitrate after repeated oral exposure was investigated in an OECD 422 study. In this study, treatment with yttrium trinitrate via the diet in male and female Sprague Dawley rats at dose levels of 250, 500 and 1000 mg/kg bw/day revealed no adverse effects. Based on these results, the No Observed Adverse Effect Level (NOAEL) was concluded to be higher than or equal to 1000 mg/kg bw/day, i.e. the highest dose tested.
Therefore, the substance is not classified as a repeated dose toxicant (STOT RE) according to the CLP Regulation. - Endpoint:
- short-term repeated dose toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- supporting study
- Study period:
- From 2015-07-07 to 2015-10-13
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- comparable to guideline study
- Reason / purpose for cross-reference:
- reference to other study
- Reason / purpose for cross-reference:
- reference to other study
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity Study in Rodents)
- GLP compliance:
- no
- Limit test:
- no
- Species:
- rat
- Strain:
- Sprague-Dawley
- Details on species / strain selection:
- The Sprague Dawley (SD) rat was the species and strain of choice because it is accepted by many regulatory authorities and international guidelines as a recommended test system. There is ample experience and historical background data on this species and strain.
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: 40 Hsd: Sprague Dawley (SD) rats (20 males and 20 females)
- Age at delivery: 27 - 29 days
- Weight at arrival: 88 - 95 grams for males and 88 - 94 grams for females
- Fasting period before study: no data
- Housing: The animals were housed up to 5 of one sex to a cage, in clear polysulphone solid bottomed cages as indicated in the relevant SOP (SOP/ANI/001). Nesting material was provided inside suitable bedding bags and was changed at least twice a week. The arrangement of cages in batteries was such that cages from each treatment group were evenly distributed across the battery to minimise possible environmental effects.
- Diet (e.g. ad libitum): A commercially available powdered laboratory rodent diet (4 RF 21, Mucedola S.r.l., Via G. Galilei, 4, 20019, Settimo Milanese (MI), Italy) was offered ad libitum throughout the study.
- Water (e.g. ad libitum): ad libitum, via water bottles
- Acclimation period: Approximately 2 weeks, under test conditions, during which time the health status of the animals was assessed by thorough observations. A health check was performed by a veterinarian.
- There was no information available to indicate that any non-nutrient substance likely to influence the effect of the test item was present in the drinking water or the diet.
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22°C +/- 2°C
- Humidity (%): 55% +/- 15%
- Air changes (per hr): 15 to 20
- Photoperiod (hrs dark / hrs light): 12/12
IN-LIFE DATES: From: 2015-07-07 To: 2015-07-28 - Route of administration:
- oral: feed
- Details on route of administration:
- The oral route was selected as it is a possible route of exposure of the test item in man. Administration via diet was selected due to a too low pH in solution with water-based vehicles.
- Vehicle:
- unchanged (no vehicle)
- Details on oral exposure:
- PREPARATION OF DOSING SOLUTIONS:
- The test item was formulated using powdered diet, by a premix followed by dilution with further quantity of diet and mixing. The formulation was prepared separate for each group/sex. Inclusion levels (ppm) were reviewed during the study, in order to obtain nominal dose levels of 250, 500 and 1000 mg/kg/day.
DIET PREPARATION
- Rate of preparation of diet (frequency): Fresh diet was prepared up to 3-4 days according to available stability data supplied by the Laboratory LAUS which performed the validation study (stability in diet up to 10 days at room temperature in the range of 250-15000 ppm).
- Mixing appropriate amounts with (Type of food): Powdered rodent diet (4 RF 21, Mucedola S.r.l., Via G. Galilei, 4, 20019, Settimo Milanese (MI), Italy).
- Storage temperature of food: no data
- Concentrations were calculated and expressed in terms of active ingredient (71.3%).
- The concentrations of test item in the diet were adjusted as required in order to maintain the required dose level for each treated group.
- Initial dietary concentrations were predicted from growth and food intake data collected during the acclimatisation period. The dietary inclusion levels were reviewed twice weekly (on the day of body weight measurements) and new diets supplied the day after body weight measurements. - Analytical verification of doses or concentrations:
- no
- Duration of treatment / exposure:
- 2 weeks
- Frequency of treatment:
- daily, 7 days/week
- Dose / conc.:
- 0 mg/kg bw/day (nominal)
- Remarks:
- in diet
- Dose / conc.:
- 250 mg/kg bw/day (nominal)
- Remarks:
- in diet
- Dose / conc.:
- 500 mg/kg bw/day (nominal)
- Remarks:
- in diet
- Dose / conc.:
- 1 000 mg/kg bw/day (nominal)
- Remarks:
- in diet
- No. of animals per sex per dose:
- 4 males and 4 females/dose
- Control animals:
- yes, plain diet
- Details on study design:
- - Dose selection rationale: no data
- Rationale for animal assignment (if not random): On the day of allocation (7 days prior to the start of treatment) all animals were weighed. Animals at the extremes of the weight distribution were excluded to leave the required number of animals. The rats were allocated to the 4 groups by computerised stratified randomisation to give approximately equal initial group mean body weights. - Positive control:
- no
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS AND DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: Once before commencement of treatment and once daily during treatment, each animal was observed and any clinical signs were recorded.
- Cage side observations were included.
- All clinical signs were recorded for individual animals.
BODY WEIGHT: Yes
- Time schedule for examinations: Each animal was weighed on the day of allocation to treatment group, on the day before treatment commenced (day -1), twice weekly thereafter (i.e. days 4, 7, 11, 14) and just prior to necropsy (day 15).
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): Yes
- The weight of food consumed by each cage of rats was recorded twice weekly following allocation. The group mean daily intake per rat was calculated.
- Twice weekly the group mean achieved intake of test item was calculated from the group mean body weight and food consumption data and the dietary inclusion levels of the test item.
FOOD EFFICIENCY: No
WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): No
OPHTHALMOSCOPIC EXAMINATION: No
HAEMATOLOGY: Yes
- Time schedule for collection of blood: at the end of week 2 of treatment (day 15) prior to necropsy
- Samples of blood were withdrawn from the abdominal vena cava.
- Anaesthetic used for blood collection: yes (light isofluorane anaesthesia)
- Animals fasted: yes, overnight fasting
- How many animals: all surviving animals
- Parameters examined: haematocrit (%), haemoglobin (g/dL), red blood cell count (x 10^6/µL), reticulocyte count (% or x 10^9/L), mean red blood cell volume (fL), mean corpuscular haemoglobin (pg), mean corpuscular haemoglobin concentration (g/dL), white blood cell count (x 10^3/µL), differential leucocyte count, neutrophils (% or x 10^3/L), lymphocytes (% or x 10^3/L), eosinophils (% or x 10^3/L), basophils (% or x 10^3/L), monocytes (% or x 10^3/L), large unstained cells (% or x 10^3/L), platelets (x 10^3/µL), coagulation: prothrombin time (sec)
CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: at the end of week 2 of treatment (day 15) prior to necropsy
- Samples of blood were withdrawn from the abdominal vena cava.
- Animals fasted: yes, overnight fasting
- How many animals: all surviving animals
- Parameters examined: alkaline phosphatase (U/L), alanine aminotransferase (U/L), aspartate aminotransferase (U/L), urea (mg/dL), creatinine (mg/dL), glucose (mg/dL), total bilirubin (mg/dL), total cholesterol (mg/dL), total protein (g/dL), albumin (g/dL), sodium (mmol/dL), potassium (mmol/dL), calcium (mmol/dL), chloride (mmol/dL).
URINALYSIS: No
NEUROBEHAVIOURAL EXAMINATION: No
OTHER:
MORTALITY:
- Time schedule: All animals were checked early in each working day and again in the afternoon. At weekends and Public Holidays a similar procedure was followed except that the final check was carried out at approximately mid-day. - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes
- All animals that completed the scheduled test period, were killed by exsanguination under isofluorane anaesthesia (by inhalation) and were subjected to necropsy after weighing, supervised by a pathologist.
- The clinical history of the animals was studied and a detailed post mortem examination was conducted (including examination of the external surface and orifices). Changes were noted, the requisite organs weighed and the required tissue samples preserved in fixative.
- From all animals completing the scheduled test period, the following organs were dissected free of fat and weighed, tissues were fixed and preserved in 10% neutral buffered formalin (except testes and epididymides which were fixed in Modified Davidson’s fluid and preserved in 70% ethyl alcohol): abnormalities/gross lesions, adrenal glands, bone marrrow (from sternum), brain (cerebrum, cerebellum, medulla/pons), caecum, colon, duodenum, epididymides, heart, ileum, jejunum (including Payer's patches), kidneys, liver, lungs, lymph nodes - mesenteric, lymph nodes - cervical, ovaries, oviducts, parathyroid glands, pituitary gland, prostate gland, rectum, sciatic nerve, seminal vesicles, spinal column, spinal cord, spleen, stomach, testes, thymus (where present), thyroid, trachea, urinary bladder, uterus - cervix
- The ratios of organ weight to body weight and organ weight to brain weight were calculated for each animal.
HISTOPATHOLOGY: No - Other examinations:
- No
- Statistics:
- Standard deviations were calculated as considered appropriate. For continuous variables the significance of the differences amongst groups was assessed by analysis of variance. Differences between each treated group and the control group were assessed by Dunnett’s test using a pooled error variance. The homogeneity of the data was verified by Bartlett’s test before Dunnett’s test.
- Clinical signs:
- no effects observed
- Description (incidence and severity):
- No toxicologically relevant or treatment-related clinical signs were recorded during the study.
- Mortality:
- no mortality observed
- Description (incidence):
- No mortality occurred during the study.
- Body weight and weight changes:
- no effects observed
- Description (incidence and severity):
- No treatment related effects were seen on body weight.
- Food consumption and compound intake (if feeding study):
- no effects observed
- Description (incidence and severity):
- - No toxicologically relevant differences in food consumption were noted between control and treated groups.
- The achieved dosages throughout the study were calculated to be 260, 634 and 1221 mg/kg/day for males and 322, 582 and 1187 mg/kg/day for females. - Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- not examined
- Haematological findings:
- no effects observed
- Description (incidence and severity):
- - No changes of toxicological relevance were recorded. Statistically significant decreases between control and treated females (haemoglobin and monocytes) were recorded in animals dosed with 250 and/or 500 mg/kg/day, therefore considered unrelated to treatment.
- No changes were recorded in coagulation parameters. - Clinical biochemistry findings:
- no effects observed
- Description (incidence and severity):
- - A statistically significant decrease of alanine aminotransferase was recorded in males dosed with 250 and 1000 mg/kg/day (26% and 29%, respectively). In addition, urea was decreased in females dosed with 1000 mg/kg/day (28%). Due to the absence of dose-relation, the direction and/or the severity of changes, the above findings were considered of no toxicological significance.
- Urinalysis findings:
- not examined
- Behaviour (functional findings):
- not examined
- Immunological findings:
- not examined
- Organ weight findings including organ / body weight ratios:
- no effects observed
- Description (incidence and severity):
- - No relevant differences were noted in the organ weights (absolute and relative organ weights to terminal body weight or to brain weight) and terminal body weights, with the exception of a slight statistically significant decrease in relative liver weight (-13%) seen in low dose males, and hence considered not treatment-related or toxicologically relevant.
- Gross pathological findings:
- no effects observed
- Description (incidence and severity):
- - Animals killed at termination did not show relevant macroscopic changes that could be treatment related. However, enlarged spleen was observed in two high dose males sacrificed at final sacrifice. The remaining observed changes are suggested to be incidental, having a comparable incidence in control and treated groups, and/or are characteristically seen in untreated SD rats of the same age.
- Neuropathological findings:
- not examined
- Histopathological findings: non-neoplastic:
- not examined
- Histopathological findings: neoplastic:
- not examined
- Other effects:
- not specified
- Details on results:
- No further data
- Dose descriptor:
- NOAEL
- Effect level:
- >= 1 000 mg/kg bw/day (nominal)
- Based on:
- act. ingr.
- Remarks:
- anhydrous yttrium trinitrate
- Sex:
- male/female
- Remarks on result:
- not determinable due to absence of adverse toxic effects
- Critical effects observed:
- no
- Conclusions:
- The purpose of this study was to investigate the toxicity of yttrium trinitrate in a preliminary 2-week dietary study in rats which received medicated diet at nominal dose levels of 250, 500 and 1000 mg/kg/day.
The achieved dosages troughout the study were calculated to be 260, 634 and 1221 mg/kg/day for males and 322, 582 and 1187 mg/kg/day for females.
No mortality occurred during the study.
No significant effects were seen in the in vivo parameters (clinical signs, body weight and food consumption).
Statistically significant decreases were observed in haemoglobin and monocytes when comparing control and females dosed at 250 and/or 500 mg/kg/day. Statistically significant decreases in alanine aminotransferase in males dosed at 250 and 1000 mg/kg/day and in urea in females dosed at 1000 mg/kg/day, were observed. All abovementioned changes were considered not toxicologically relevant.
No relevant differences were noted in the organ weights and terminal body weights.
No relevant macroscopic changes were seen in treated animals compared to controls. No clear significance could be attributed to the enlarged spleen, seen in 2 high dose males, in the absence of other correlated changes.
Based on the results obtained in this study, the administration of the test item was considered well tolerated up to the high nominal dose level of 1000 mg/kg/day. Doses of 250, 500 and 1000 mg/kg/day could be used in the subsequent OECD 422 study. - Endpoint:
- short-term repeated dose toxicity: oral
- Type of information:
- read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- key study
- Justification for type of information:
- Since no reliable studies have been identified on oral repeated dose toxicity of yttrium trichloride, the endpoint was covered using the results of the key OECD 422 study performed with yttrium trinitrate, i.e. an yttrium compound with similar water solubility as yttrium trichloride. The read across justification document is attached to IUCLID Section 13.
- Reason / purpose for cross-reference:
- read-across source
- Reason / purpose for cross-reference:
- read-across source
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- >= 1 000 mg/kg bw/day (nominal)
- Based on:
- act. ingr.
- Remarks:
- yttrium trinitrate anhydrous
- Sex:
- male/female
- Remarks on result:
- not determinable due to absence of adverse toxic effects
- Remarks:
- This NOAEL is obtained in the key OECD 422 study performed with yttrium trinitrate. No treatment-related systemic effects of toxicological relevance have been observed in parent animals up to and including at the highest dose tested, i.e. 1000 mg yttrium trinitrate/kg bw/day. This result is considered relevant for yttrium trichloride as well.
- Key result
- Critical effects observed:
- no
- Endpoint:
- short-term repeated dose toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- supporting study
- Reliability:
- 4 (not assignable)
- Rationale for reliability incl. deficiencies:
- documentation insufficient for assessment
- Remarks:
- The study is in Japanese.
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity Study in Rodents)
- GLP compliance:
- not specified
- Limit test:
- no
- Species:
- rat
- Strain:
- Wistar
- Remarks:
- Slc
- Details on species / strain selection:
- Slc:Wistar rats of both sexes.
No further information reported in English abstract. - Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- No details given in English abstract.
- Route of administration:
- oral: gavage
- Vehicle:
- not specified
- Remarks:
- not specified in English abstract
- Analytical verification of doses or concentrations:
- not specified
- Remarks:
- not specified in English abstract
- Duration of treatment / exposure:
- 28 days
- Frequency of treatment:
- daily
- Dose / conc.:
- 0 mg/kg bw/day (nominal)
- Remarks:
- YCl3.6H2O
- Dose / conc.:
- 40 mg/kg bw/day (nominal)
- Remarks:
- YCl3.6H2O
- Dose / conc.:
- 200 mg/kg bw/day (nominal)
- Remarks:
- YCl3.6H2O
- Dose / conc.:
- 1 000 mg/kg bw/day (nominal)
- Remarks:
- YCl3.6H2O
- No. of animals per sex per dose:
- Not specified in English abstract.
- Control animals:
- yes, concurrent no treatment
- Details on study design:
- Additionally, two groups of rats (0 and 1000 mg/kg bw/day) of both sexes were maintained for a 14-d recovery period after the 28-day administration.
- Positive control:
- No
- Observations and examinations performed and frequency:
- Body weight and food consumption were measured, and hematological and serum-biochemical examinations were performed.
- Sacrifice and pathology:
- Histopathological examinations were performed.
- Clinical signs:
- not examined
- Mortality:
- not examined
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- A slightly lower food consumption and body weight were observed mainly in the high-dose group (more clear in males than in females). No indiciation is given on the statistical significance of the observed effects. Nevertheless, these findings were clearly related to the irritating effect of the test substance in the (fore)stomach (see further). The effects are therefore considered treatment-related, however, they are the result of local irritation in the stomach and do not represent signs of systemic toxicity.
- Food consumption and compound intake (if feeding study):
- effects observed, treatment-related
- Description (incidence and severity):
- A slightly lower food consumption and body weight were observed mainly in the high-dose group (more clear in males than in females). No indiciation is given on the statistical significance of the observed effects. Nevertheless, these findings were clearly related to the irritating effect of the test substance in the (fore)stomach (see further). The effects are therefore considered treatment-related, however, they are the result of local irritation in the stomach and do not represent signs of systemic toxicity.
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- not examined
- Haematological findings:
- effects observed, treatment-related
- Description (incidence and severity):
- The number of eosinophilic leucocytes increased in rats of both sexes dose-dependently.
- Clinical biochemistry findings:
- effects observed, treatment-related
- Description (incidence and severity):
- At doses higher than 200 mg/kg bw/day, a significant decrease of the serum cholinesterase activity was observed in females.
There were no changes in serum transaminase activity in either sex. - Urinalysis findings:
- not examined
- Behaviour (functional findings):
- not examined
- Immunological findings:
- not examined
- Organ weight findings including organ / body weight ratios:
- not examined
- Gross pathological findings:
- effects observed, treatment-related
- Description (incidence and severity):
- At 1000 mg/kg bw/day, hyperkeratosis in the forestomach of both sexes, eosinophilic leucocyte infiltration in the submucosa of the stomach of both sexes, erosion and dilation of gastric gland of the glandular stomach in males, and swelling of the glandular stomach epithelium in females were found.
- Neuropathological findings:
- not examined
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Description (incidence and severity):
- At 1000 mg/kg bw/day, hyperkeratosis in the forestomach of both sexes, eosinophilic leucocyte infiltration in the submucosa of the stomach of both sexes, erosion and dilation of gastric gland of the glandular stomach in males, and swelling of the glandular stomach epithelium in females were found.
- Histopathological findings: neoplastic:
- not examined
- Conclusions:
- This 28-d oral gavage repeated dose toxicity study in rats reported treatment-related effects on body weight, food consumption, serum cholinesterase activity and number of eosinophilic leucocytes. However, at the same time, local effects were observed in the (fore)stomach, resulting from the irritating potential of the test item. These local effects in the (fore)stomach likely have triggered the other observed effects. There is no evidence of systemic toxicity. Therefore, the results of this study can be considered as supporting information.
Referenceopen allclose all
Analytical verification: results
Samples of formulations were sent to the test site LAUS during pre-treatment, week 1 and the last week (week 5, both sexes present). Since measurements of week 1 and of the last week were not acceptable, repetitions in week 3 and week 7 (last week with only females present) were performed and were found acceptable. Generally, high heterogeneity of the analytical replicates was found, probably due to clumps and aggregates easily formed in the diet by the hygroscopic test item. However, the heterogeneity found in the diet is not a concern regarding the administered dose since the analytical sampling carried out in LAUS laboratory was 1 g which is a fairly small amount compared to the daily food consumption of the animals (approximately 30 g).
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
- Study duration:
- subacute
- Species:
- rat
Repeated dose toxicity: inhalation - systemic effects
Link to relevant study records
- Endpoint:
- short-term repeated dose toxicity: inhalation
- Data waiving:
- other justification
- Justification for data waiving:
- other:
- Critical effects observed:
- not specified
Reference
Endpoint conclusion
- Endpoint conclusion:
- no study available
Repeated dose toxicity: inhalation - local effects
Link to relevant study records
- Endpoint:
- short-term repeated dose toxicity: inhalation
- Data waiving:
- other justification
- Justification for data waiving:
- other:
- Critical effects observed:
- not specified
Reference
Endpoint conclusion
- Endpoint conclusion:
- no study available
Repeated dose toxicity: dermal - systemic effects
Link to relevant study records
- Endpoint:
- short-term repeated dose toxicity: dermal
- Data waiving:
- other justification
- Justification for data waiving:
- other:
- Critical effects observed:
- not specified
Reference
Endpoint conclusion
- Endpoint conclusion:
- no study available
Repeated dose toxicity: dermal - local effects
Link to relevant study records
- Endpoint:
- short-term repeated dose toxicity: dermal
- Data waiving:
- other justification
- Justification for data waiving:
- other:
- Critical effects observed:
- not specified
Reference
Endpoint conclusion
- Endpoint conclusion:
- no study available
Additional information
Repeated dose toxicity - oral
Only one relevant study has been identified on the oral repeated dose toxicity of yttrium trichloride. The study of Ogawa et al. (1994) investigated the repeated dose toxicity of yttrium trichloride to rats via oral gavage during 28 days. The study reported treatment-related effects on body weight, food consumption, serum cholinesterase activity and number of eosinophilic leucocytes. However, at the same time, local effects were observed in the (fore)stomach, resulting from the irritating potential of the test item. These local effects in the (fore)stomach likely have triggered the other observed effects. There is no evidence of systemic toxicity. The reliability of this study was considered not assignable (Klimisch 4) since the study was in Japanese and only the abstract, figures and tables were in English. The results of this study can be considered as supporting information.
Because no reliable study is available for yttrium trichloride, the endpoint was covered using a combined repeated dose toxicity study with the reproduction/developmental toxicity screening test performed with yttrium trinitrate, i.e. an yttrium compound with similar water solubility as yttrium trichloride. This study was performed in rats according to OECD guideline 422 and conform GLP requirements (Rossiello, 2017; Klimisch 1). Male and female rats (10/sex/group) were exposed daily to 0, 250, 500 and 1000 mg yttrium trinitrate/kg bw/day via their diet. The vehicle used was powdered rodent diet and the test solutions were prepared weekly and administered once a day. Males were treated for 2 weeks prior to pairing, during pairing with females until the day before necropsy, for a total of 32-33 days. Females were treated for 2 weeks prior to pairing, during pairing and throughout the gestation and lactation periods until day 3 post partum, for 41-44 days.
No mortality occurred throughout the study. No treatment-related effects were observed in treated males and females during clinical and detailed observations throughout the study. Observation of animals at removal from the cage and in an open arena (neurotoxicity assessment) did not reveal changes attributable to the test item. No treatment-related effects on body weight were seen in males. In treated females, a slight increase (statistically significant in the low dose group) was seen in body weight compared to controls during the premating period but this was considered of no toxicological significance. Any transient, statistically significant variations in body weight gain recorded in males and females showed no dose-relationship and were therefore not considered of toxicological relevance. No toxicologically relevant effects on food consumption, motor activity and sensory reactivity to stimuli, and haematology were observed in either males or females of all test substance-treated groups when compared to controls. Any significant changes observed were either not consistent between sexes or showed no relation to the dose level and were therefore considered not toxicologically relevant. Some clinical chemistry parameters showed statistically significant fluctuations (e.g. alkaline phosphatase, creatinine, potassium), but in the absence of a dose-relation or relation to other (histopathological) findings, these fluctuations were considered incidental. No significant changes and no treatment-related effects were detected in males and females during the in vivo phase. No relevant changes were detected at post mortem examination in treated animals, when compared with control animals. No treatment-related changes were seen in organs/tissues evaluated nor in the abnormalities detected in all groups at post mortem examination.
In conclusion, no treatment-related effects indicating systemic toxicity were observed in male or female animals at any of the dose levels investigated (nominal dose levels of 250, 500 and 1000 mg/kg bw/day, corresponding to mean achieved dose levels of 271, 547 and 1096 mg/kg bw/day for males and 323, 584 and 1160 mg/kg bw/day for females).
Based on these results, the NOAEL was concluded to be higher than or equal to 1000 mg/kg bw/day for males and females. Based on the similar water solubility of yttrium trinitrate and yttrium trichloride, both compounds are expected to have a similar capacity of releasing bioavailable yttrium forms. Therefore, the results of this study are considered relevant for yttrium trichloride as well and no separate study needs to be performed with yttrium trichloride. The read across justification document is attached to IUCLID Section 13.
Repeated dose toxicity - inhalation
A key study is available for the oral route of exposure. According to the REACH Regulation, only one route of exposure should be tested for repeated dose toxicity (column 2, annex VIII, section 8.6.1). Therefore, it is not necessary to perform a repeated dose toxicity study via the inhalation route of exposure.
Repeated dose toxicity - dermal
A key study is available for the oral route of exposure. According to the REACH Regulation, only one route of exposure should be tested for repeated dose toxicity (column 2, annex VIII, section 8.6.1). Therefore, it is not necessary to perform a repeated dose toxicity study via the dermal route of exposure.
Justification for classification or non-classification
Repeated dose toxicity: oral
In the key combined repeated dose toxicity and screening reproduction/developmental toxicity test performed with the read across substance yttrium trinitrate, a NOAEL of at least 1000 mg/kg bw/day was established. Consequently, yttrium trinitrate is not to be classified for specific target organ toxicity after repeated exposure (STOT RE) according to the CLP Regulation. Since the results of this read across study are considered relevant for yttrium trichloride as well, it can be concluded that yttrium trichloride does not need to be classified for STOT RE either according to the CLP Regulation.
Repeated dose toxicity: dermal
No key repeated dose toxicity study via dermal administration is available.
Repeated dose toxicity: inhalation
No key repeated dose toxicity study via inhalation is available.
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