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EC number: 215-149-9 | CAS number: 1306-25-8
- 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:
- sub-chronic toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- Study plan: signed on 11 Sept 2019. Dosing: initiated on 23 sept 2019. Experimental start date: 11 Sept 2019, Experimental completion date: 19 March 2020. Final report: 25 September 2020
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- test procedure in accordance with generally accepted scientific standards and described in sufficient detail
Cross-referenceopen allclose all
- Reason / purpose for cross-reference:
- reference to other study
- Reason / purpose for cross-reference:
- reference to same study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 020
- Report date:
- 2020
Materials and methods
Test guidelineopen allclose all
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity Study in Rodents)
- Version / remarks:
- 2018
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- EU Method B.26 (Sub-Chronic Oral Toxicity Test: Repeated Dose 90-Day Oral Toxicity Study in Rodents)
- Version / remarks:
- 2008
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- EPA OPPTS 870.3100 (90-Day Oral Toxicity in Rodents)
- Version / remarks:
- 1998
- Principles of method if other than guideline:
- - Principle of test: The objective of this study was to determine the toxicology, accumulation and toxicokinetics of cadmium telluride in the rat and for a direct comparative bioavailability assessment with the chosen reference substance, cadmium chloride. It was proposed that this study should follow, as closely as possible, the experimental design used in the study by Loeser and Lorke, 1977, a study that investigated the sub-chronic toxicity and accumulation of cadmium in the liver and kidney in the rat dosed with cadmium chloride in the diet at 30 ppm (ref: : Loeser and Lorke, 1977. Semichronic oral toxicity of cadmium. I. Studies on rats. Toxicology 7: 215-224 https://doi.org/10.1016/0300-483X(77)90067-1)
-Short description of test conditions:
Wistar Han rats were treated with Cadmium telluride for 13 weeks by dietary administration at dose levels of 750 or 1500 ppm (powder diet). One additional group of Wistar Han rats was treated with 30 ppm Cadmium chloride (reference item) by dietary administration. The rats of the control group received standard powder diet without the test item.
In Weeks 1, 4 and 8 three animals/sex/test item group were sacrificed for bioanalytical purposes. Prior to sacrifice, blood, urine and faeces were collected to determine the Cadmium and Tellurium content. In Week 13, the remaining animals were sacrificed for bioanalytical and toxicological assessment purposes. Control group animals were only sacrificed in Weeks 1 and 13.
Samples of diets were collected for analysis. Chemical analyses of dietary preparations were conducted on Weeks 1 and 6 to assess concentration and homogeneity.
- Parameters analysed / observed:
clinical signs, body weights, food consumption, clinical pathology parameters (haematology, coagulation and clinical chemistry), toxicokinetic parameters, gross necropsy findings and organ weights - GLP compliance:
- yes
Test material
- Reference substance name:
- Cadmium telluride
- EC Number:
- 215-149-9
- EC Name:
- Cadmium telluride
- Cas Number:
- 1306-25-8
- Molecular formula:
- CdTe
- IUPAC Name:
- telluroxocadmium
- Test material form:
- solid: particulate/powder
- Details on test material:
- Batch (Lot) Number: CdTe #217824-B
Expiry date: 13 September 2020 (expiry date)
Physical Description: Black powder
Purity/Composition: 99.999 %
Storage Conditions: At room temperature
Test item handling: No specific handling conditions required
Stability at higher temperatures: Stable
Constituent 1
- Specific details on test material used for the study:
- Batch (Lot) Number: CdTe #217824-B
Expiry date: 13 September 2020
Physical Description: Black powder
Purity/Composition: 99.999 %
Storage Conditions: At room temperature
Test item handling: No specific handling conditions required
Stability at higher temperatures: Stable
Test animals
- Species:
- rat
- Strain:
- Wistar
- Details on species / strain selection:
- Han
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River Deutschland, Sulzfeld, Germany
- Age at study initiation: 5-7 weeks old at initiation of dosing
- Weight at study initiation: males: between 155 and 201g; females: between 120 and 156g
- Housing:
Polycarbonate cages (Makrolon type IV, height 18 cm) containing sterilized sawdust as bedding material (Lignocel S 8-15, JRS -J.Rettenmaier & Söhne GmbH + CO. KG, Rosenberg, Germany) equipped with water bottles. Up to 3 animals of the same sex and same dosing group together. In the cage racks the control group cages were placed on top of the cage rack
followed by Groups 2 and 3. The cages of Group 4 (Cadmium chloride group) were placed in a separate cage rack. T
- Diet: ad libitum, except during designated procedures
- Water: ad libitum
- Acclimation period: 12 days before the commencement of dosing
ENVIRONMENTAL CONDITIONS
- Temperature (°C): Targeted: 18 to 24°C; Actual mean: 19 to 21°C
- Humidity (%): Targeted: 40 to 70% ; Actual mean: 49 to 87%
- Air changes (per hr): Ten or more air changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours light and 12 hours dark (except during designated procedures)
Administration / exposure
- Route of administration:
- oral: feed
- Details on route of administration:
- The oral route of exposure via dietary inclusion was selected because this is a possible route of human exposure during manufacture, handling or use of the test item.
The dose levels were selected based on information provided by the Sponsor, and designed to follow the method described in Loeser and Lorke, 1977: Toxicology 7: 215-224 (https://doi.org/10.1016/0300-483X(77)90067-1). The high-dose level should not produce toxic effects, nor excessive lethality that would prevent meaningful evaluation. The mid-dose level is expected to produce no toxic effects. - Vehicle:
- unchanged (no vehicle)
- Details on oral exposure:
- DIET PREPARATION
- Rate of preparation of diet (frequency):
Diets were prepared freshly for use at room temperature for a maximum of three weeks. Diets were kept at room temperature until use, if not used on the day of preparation. Any remaining
food left after filling the food hoppers was stored at room temperature for a maximum of three weeks for supplementing food during the respective food consumption measurement
interval. Diets were prepared freshly for use at room temperature for a maximum of three weeks in advance of first use.
- Mixing appropriate amounts with (Type of food): The test item was mixed without the use of a vehicle, directly with the required amount of
powder feed. A premix was prepared to gradually mix the test item with the required amount
of powder feed, which included no sieving or mortaring of the test item. Standard powder
rodent diet (SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest, Germany) was used.
- Storage temperature of food: room temperature - Analytical verification of doses or concentrations:
- no
- Details on analytical verification of doses or concentrations:
- Analysis of test item in diet for concentration, stability, homogeneity was not performed, however, to limit the impact, the dietary preparation was performed with approved procedures and documented in detail. Diets were visually inspected for homogeneity prior to use.
Concentration and homogeneity analyses performed previously in conjunction with the method development and validation study (Test Facility Study No. 20170592) demonstrated that the test item is homogeneously distributed in the diet when prepared under the same conditions at concentrations bracketing those used in the present study. - Duration of treatment / exposure:
- 90 days, oral feed exposure
- Frequency of treatment:
- food ad libitum
Doses / concentrationsopen allclose all
- Dose / conc.:
- 750 ppm
- Dose / conc.:
- 1 500 ppm
- No. of animals per sex per dose:
- 3
- Control animals:
- yes
- Details on study design:
- - Dose selection rationale: The dose levels were selected based on results of a 14-day repeated dose toxicity study with oral exposure of Cadmium telluride and Cadmium chloride in rats, Test Facility Reference No. 20170590, where no signs of toxicity were observed in any of the groups and designed to follow the method described in Loeser and Lorke et al (1977). The high-dose level should not produce toxic effects, nor excessive lethality that would prevent meaningful evaluation. The mid- and low-dose level was expected to produce no toxic effects.
- Rationale for animal assignment (if not random): randomization
- Fasting period before bioanalytical sampling colletion: Yes (overnight with a maximum of 24 hours) - Positive control:
- CdCl2 in the diet: 30 ppm
Examinations
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS (MORTALITY/MORIBUNDITY) CHECKS: Yes.
- Time schedule: At least twice daily beginning upon arrival through termination, except on days of receipt and scheduled necropsy where the frequency was at least once daily.
Animals were observed within their cage unless necessary for identification or confirmation of possible findings.
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: Once prior to first administration of the test item diet and at least once daily from start of administration onwards, up to the day prior to necropsy
Animals were observed for specific clinical signs. The time of onset, grade and duration of any observed signs were recorded. Signs were graded for severity and the maximum grade was predefined at 1, 3 or 4. Grades were coded as slight (grade 1), moderate (grade 2), severe (grade 3) and very severe (grade 4). For certain signs, only its presence (i.e. maximum grade 1) was scored. In the data tables, the scored grades are reported, as well as the percentage of animals
affected in summary tables.
BODY WEIGHT: Yes
- Time schedule for examinations: Weekly; from at least Day 1 and throughout the study. In addition, body weight was recorded on the day prior to scheduled necropsy.
Fasted weight on the day of scheduled necropsy.
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study):
Food consumption was quantitatively measured per cage twice weekly; from at least Day 1 and throughout the study. In addition, food consumption was determined on the day prior to scheduled necropsy.
FOOD EFFICIENCY: No
WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): measured on regular basis throughout the study. Water consumption was monitored by visual inspection of the water bottles.
OPHTHALMOSCOPIC EXAMINATION: No
HAEMATOLOGY: Yes
- Time schedule for collection of blood: end of treatment (week 13)
- Anaesthetic used for blood collection: yes
- Animals fasted: Yes : overnight with a maximum of 24 hours
- How many animals: all group 1-4 animals = 84 animals
- Parameters checked : White Blood Cells (WBC), Neutrophil (absolute), Lymphocyte (absolute), Monocyte (absolute), Eosinophil (absolute), Basophil (absolute), Large unstained cells (LUC) (absolute), Red Blood Cell, Reticulocyte (absolute), Red Blood Cell Distribution Width (RDW), Haemoglobin, Haematocrit, Mean corpuscular volume (MCV), Mean corpuscular haemoglobin (MCH), Mean corpuscular haemoglobin concentration, (MCHC), Platelet
CLINICAL CHEMISTRY: yes
- Time schedule for collection of blood: end of treatment (week 13)
- Anaesthetic used for blood collection: Not specified
- Animals fasted: Yes : overnight with a maximum of 24 hours
- How many animals: all group 1-4 animals = 84 animals
- Parameters checked :
Alanine aminotransferase (ALAT), Aspartate aminotransferase (ASAT) , Alkaline Phosphatase (ALP) , Total protein, Albumin, Total Bilirubin, Urea, Creatinine, Glucose, Cholesterol, HDL and LDL Cholesterol, Sodium, Potassium, Chloride, Calcium, Inorganic Phosphate (Inorg. Phos.), Triiodothyronine (T3), Thyroxine (T4), Thyroid-Stimulating Hormone (TSH), Triglycerides
URINALYSIS: Yes
- Time schedule for collection of urine:
Urine was collected separately into specimen vials from animals housed in individual metabolism cages with absence of food, but water was available, overnight prior to necropsy (approximately 15-20 hours).
After collection, the total amount of urine was determined and samples were divided into two aliquots (aliquot A, including ≥ 100 μL) or until possible future analysis (aliquot B, remnant).
- Metabolism cages used for collection of urine: Yes
- Animals fasted: Yes
NEUROBEHAVIOURAL EXAMINATION: No
IMMUNOLOGY:No
OTHER:
Faeces analysis:
faeces were collected separately into specimen vials from animals housed in individual metabolism cages with absence of food, but water was available, overnight prior to necropsy (approximately 15-20 hours).
Representative samples of the faeces (not more than 4 gram) were weighed and collected and preserved in 50 mL centrifuge tubes (Greiner) at ≤-75°C.
Organ weights: weighed at necropsy. Paired organs were weighed together. Organ to body weight ratio (using the terminal body weight) were calculated.
Organs Weighed at Necropsy – Weeks 1, 4 and 8: Kidney and liver
Organs Weighed at Necropsy – At the End of Treatment (week 13):
Brain; Epididymis; Gland, adrenal; Gland, parathyroid; Gland, pituitary; Gland, prostate; Gland, seminal vesicle; Gland, thyroid; Heart; Kidney; Liver; Ovary; Spleen; Testis; Thymus; Uterus/cervix
Urine, faeces, plasma, kidney and liver samples were analyzed for concentration of cadmium and telluride using a validated analytical procedure of Testing Facility Study No. 20170598 - Sacrifice and pathology:
- GROSS PATHOLOGY: yes
Necropsy:
Animals were subjected to a complete necropsy examination, which included evaluation of the carcass and musculoskeletal system; all external surfaces and orifices; cranial cavity and external surfaces of the brain; and thoracic, abdominal, and pelvic cavities with their associated organs and tissues.
Necropsy procedures were performed by qualified personnel with appropriate training and experience in animal anatomy and gross pathology. A veterinary pathologist, or other suitably qualified person, was available.
HISTOPATHOLOGY: No - Statistics:
- All statistical tests were conducted at the 5% significance level. All pairwise comparisons were conducted using two sided tests and were reported at the 1%
or 5% levels.
Numerical data collected on scheduled occasions was analysed according to sex and occasion.
Descriptive statistics number, mean and standard deviation were reported whenever possible.
Values may also be expressed as a percentage of predose or control values when deemed appropriate. Inferential statistics were performed according to the matrix below when possible, but did exclude semi-quantitative data, and any group with less than 2 observations.
The following pairwise comparisons were made:
Group 2 vs. Group 1
Group 3 vs. Group 1
Group 4 vs. Group 1
Results and discussion
Results of examinations
- Clinical signs:
- no effects observed
- Description (incidence and severity):
- No test item-related clinical signs were noted in males and females at 750 and 1500 ppm Cadmium telluride and in males at 30 ppm Cadmium chloride.
In females at 30 ppm Cadmium chloride, slight alopecia was observed in all three remaining females starting at the end of Week 8 and this was considered test item related.
One female each in the 750 ppm Cadmium telluride group presented with respectively a wound and piloerection (on a single day only). These findings occurred within the range of background findings to be expected for rats of this age and strain which are housed and treated under the conditions in this study and did not show any apparent dose-related trend. At the incidence observed, these were considered to be unrelated to treatment with the test item. - Mortality:
- no mortality observed
- Description (incidence):
- No mortality occurred during the study period.
- Body weight and weight changes:
- no effects observed
- Description (incidence and severity):
- No effects on body weight and body weight gain were noted in males at 750 ppm Cadmium telluride and females at 750 or 1500 ppm Cadmium telluride or 30 ppm Cadmium chloride.
A trend towards a slightly lower body weight and body weight gain was observed in males at 1500 ppm Cadmium telluride throughout the entire treatment period (0.92x at the end of treatment compared to controls). - Food consumption and compound intake (if feeding study):
- no effects observed
- Description (incidence and severity):
- No toxicologically relevant changes in food consumption were recorded throughout the entire treatment period.
- Food efficiency:
- not examined
- Ophthalmological findings:
- not examined
- Haematological findings:
- effects observed, treatment-related
- Description (incidence and severity):
- No test item related changes in haematology parameters were observed in males and females at 750 ppm Cadmium telluride and males and females at 30 ppm Cadmium chloride.
At 1500 ppm Cadmium telluride, lower mean levels of red blood cells and reticulocytes counts, red blood cell distribution width, haemoglobin and haematocrit were observed in males (0.90x, 0.56x, 0.95x, 0.94x and 0.89x respectively, compared to controls). In females at 1500 ppm, only red blood cell distribution width was decreased (0.91x compared to controls).
A high value of reticulocyte counts was observed in one control female (No. 1). This is likely to be caused by the method of blood sampling.
Other differences in haematology parameters, regardless of statistical significance, were considered not test item related based on the absence of a dose response, general overlap of individual values with the range of historical control values, and/or were of a magnitude of change commonly observed in rats under similar study conditions. - Clinical biochemistry findings:
- effects observed, treatment-related
- Description (incidence and severity):
- No test item related changes in clinical chemistry parameters were observed in males and females at 750 ppm and males at 1500 ppm Cadmium telluride.
A decrease in total bilirubin and triglyceride levels were seen in females at 1500 ppm Cadmium telluride (0.67x and 0.63x respectively compared to controls) and females at 30 ppm Cadmium chloride (0.70x and 0.62x respectively compared to controls).
An increase in aspartate aminotransferase activity (ASAT) was seen in one female (no. 70) at 1500 ppm Cadmium telluride. This animal also showed lower total protein and albumin and higher inorganic phosphate levels.
One male at 30 ppm Cadmium chloride (No. 40) showed a range of changes in clinical chemistry parameters compared to control animals. These changes consisted of an increase in alanine aminotransferase (ALAT), ASAT, urea, creatinine and glucose levels and a decrease in total protein, albumin, (HDL and LDL) cholesterol and calcium levels. Thyroid-stimulating hormone (TSH) and triiodothyronine (T3) levels were also decreased in this animal. The remaining males of this group were comparable with the control group.
One male (No. 42) and one female at 30 ppm Cadmium chloride (No. 83) showed an increase in TSH levels (2.47x and 4.53x respectively compared to control means).
Other differences in clinical chemistry and thyroid hormone parameters, regardless of statistical significance, were considered not test item related based on the absence of a dose response, general overlap of individual values with the range of historical control values, and/or were of a magnitude of change commonly observed in rats under similar study conditions. - Description (incidence and severity):
- Cd and Te concentrations measurement in urine is reported in section 7.1 Toxicokinetics
- Behaviour (functional findings):
- no effects observed
- Immunological findings:
- not examined
- Organ weight findings including organ / body weight ratios:
- no effects observed
- Description (incidence and severity):
- No test item-related organ weight changes were observed in males and females at 750 ppm and males at 1500 ppm Cadmium telluride and in males and females at 30 ppm Cadmium chloride.
An increase in absolute and relative uterus weights were observed in females at 1500 ppm Cadmium telluride (relative: 2.65x and 2.69x respectively, compared to controls), which correlated with uterus containing fluid. This increase in uterus weight is related to a stage in the oestrous cycle and is a normal finding.
Lower relative spleen weight was observed in males at 30 ppm Cadmium chloride (0.88x compared to controls). As this was only a slight decrease and remained well within the historical control range3, this change was considered to be not toxicological relevant.
Any differences, including those that reached statistical significance were considered not to be test item-related due to the lack of dose-related pattern, had a general overlap of individual values with the range of historical control values or were considered to be the result of a test item-related effect on final body weight. - Gross pathological findings:
- no effects observed
- Description (incidence and severity):
- No test item-related gross lesions were observed in males and females at 750 and 1500 ppm Cadmium telluride and in females at 30 ppm Cadmium chloride.
In the 30 ppm Cadmium chloride group, two males were noted with an isolated reddish/blackbrown focus on the glandular mucosa of their stomach; one male in Week 4 (No. 36) and another male in Week 13 (No. 40).
All of the remaining macroscopic findings were within the range of background gross observations encountered in rats of this age and strain. Uterus containing fluid is related to a stage in the oestrous cycle and is a normal finding.. - Neuropathological findings:
- not examined
- Histopathological findings: non-neoplastic:
- not examined
- Histopathological findings: neoplastic:
- not examined
- Other effects:
- no effects observed
- Description (incidence and severity):
- Coagulation: No toxicologically relevant changes were noted in coagulation parameters. All means remained within the range of available historical control values.
Effect levels
- Dose descriptor:
- NOAEL
- Effect level:
- 1 500 ppm
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- body weight and weight gain
- clinical biochemistry
- clinical signs
- food consumption and compound intake
- gross pathology
- haematology
- mortality
- organ weights and organ / body weight ratios
Target system / organ toxicity
- Critical effects observed:
- no
Applicant's summary and conclusion
- Conclusions:
- Administration of Cadmium telluride by dietary administration for at least 90 days was well tolerated in rats at levels up to 1500 ppm (corresponding to a mean test article intake of 103 and 121 mg/kg body weight in males and females, respectively). Only slight non-adverse changes in haematology and clinical chemistry parameters were seen. The findings observed in animals treated with 30 ppm Cadmium chloride were limited to alopecia and changes in several clinical chemistry parameters.
- Executive summary:
The objective of this study was to determine the toxicology, accumulation and toxicokinetics of cadmium telluride in the rat and for a direct comparative bioavailability assessment with the chosen reference substance, cadmium chloride. It was proposed that this study should follow, as closely as possible, the experimental design used in the study by Loeser and Lorke, 1977 ((https://doi.org/10.1016/0300 -483X(77)90067-1)
, a study that investigated the sub-chronic toxicity and accumulation of cadmium in the liver and kidney in the rat dosed with cadmium chloride in the diet at 30 ppm.
In Weeks 1, 4 and 8 three animals/sex/test item group were sacrificed for bioanalytical purposes. Prior to sacrifice, blood, urine and faeces were collected to determine the Cadmium and Tellurium content. In Week 13, the remaining animals were sacrificed for bioanalytical and toxicological assessment purposes. Control group animals were only sacrificed in Weeks 1 and 13.
Samples of diets were collected for analysis. Chemical analyses of dietary preparations were conducted on Weeks 1 and 6 to assess concentration and homogeneity.
The following parameters and endpoints were evaluated in this study: clinical signs, body weights, food consumption, clinical pathology parameters (haematology, coagulation and clinical chemistry), toxicokinetic parameters, gross necropsy findings and organ weights.
Test diets prepared were considered homogeneous at the concentrations tested in Week 1 and analysis of the accuracy revealed acceptable levels in Weeks 1 and 6. The diets of Groups 2 and 3 prepared for use in Week 1 were not homogeneous. As the homogeneity results were slightly outside the acceptable range (≤ 20%) and based on the evaluation made prior to start of the study (documented in appendix 3 of report), these results had no impact on the outcome of the study.
Overall, dietary analyses confirmed that diets were prepared accurately and were acceptable homogenously for the purposes of this study.
At 750 ppm Cadmium telluride, no test item-related findings were observed.
At 1500 ppm Cadmium telluride, no test item-related clinical signs were observed. A trend towards a non-adverse slightly lower body weight and body weight gain was seen in males. Results of the haematology examinations showed lower mean levels of red blood cells and reticulocytes, red blood cell distribution width, haemoglobin and haematocrit were observed in males at 1500 ppm Cadmium telluride. In females at 1500 ppm Cadmium telluride, only red blood cell distribution width was decreased. Given the slight degree of these variations and as they were mostly within historical control range, these were considered to be not adverse.
Clinical chemistry findings were a decrease in total bilirubin and triglyceride levels in females at 1500 ppm Cadmium telluride. As these changes were relatively slight and remained within the historical control range, these findings were considered to be not adverse.
At 30 ppm Cadmium chloride, alopecia was observed in females, which is likely to be test item-related. No changes in body weights and haematology parameters were observed. Clinical chemistry findings included a decrease in total bilirubin and triglyceride levels in females at 30 ppm Cadmium chloride, which remained within the historical control range and was therefore considered to be not adverse. One male showed increases in alanine aminotransferase (ALAT) and aspartate aminotransferase (ASAT) activities and urea, creatinine and glucose levels and decreases in total protein, albumin, (HDL and LDL) cholesterol and calcium levels. Furthermore, thyroid-stimulating hormone (TSH) and triiodothyronine (T3) levels were also decreased in this animal. In one male and one female also an increase in TSH levels were observed. At the severity affected, but in absence of histopathology, these findings were considered to be not adverse. At necropsy, a foci in the stomach was seen in one male in Week 4 and one male at the end of treatment. In absence of any related changes in food consumption and body weight, this isolated finding was considered to be not adverse.
No test item-related changes were noted in any of the remaining parameters investigated in this study (i.e. food consumption, coagulation and organ weights).
In conclusion, administration of Cadmium telluride by dietary administration for at least 90 days was well tolerated in rats at levels up to 1500 ppm (corresponding to a mean test article intake of 103 and 121 mg/kg body weight in males and females, respectively). Only slight non-adverse changes in haematology and clinical chemistry parameters were seen. The findings observed in animals treated with 30 ppm Cadmium chloride were limited to alopecia and changes in several clinical chemistry parameters.
The results of this study have demonstrated a significant difference in bioavailability potential between a relatively soluble cadmium compound, Cadmium chloride (the reference substance) and a relatively insoluble cadmium compound, cadmium telluride (test substance).
Cadmium telluride exhibited no evidence of bioavailability by dietary administration for 90 days at high dose levels of 750 and 1500 ppm. No detectable and/or reliable levels of either cadmium or tellurium were detected in the target organs (liver and kidney), plasma and urine.
In contrast, in the Cadmium chloride group, at a much lower dose level of (30 ppm), the Cadmium levels increased in the kidney and liver in line with the Loeser and Lorke study (1977).
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