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EC number: 239-183-9 | CAS number: 15123-80-5
- 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
- Type of information:
- migrated information: read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Basic data given.
Data source
Reference
- Reference Type:
- publication
- Title:
- Morphologic and functional alterations of erythroid cells induced by long-term ingestion of aluminium.
- Author:
- Vittori et al.
- Year:
- 1 999
- Bibliographic source:
- J Inorg Biochem. 1999 Aug 30; 76(2):113-20.
Materials and methods
- Principles of method if other than guideline:
- Aluminium citrate was administered to ten female Sprague Dawley rats with drinking water at a concentration of 80 mmol/L for 8 months. Eight female rats that received drinking water without added aluminium citrate were used as controls. Blood was collected at the end of the treatment. After blood collection, the animals were sacrificed, femoral bone marrow was removed and smears were prepared. The remaining bone marrow cells were conditioned for in vitro clonal assays of haematopoietic progenitors (late colony-forming unit-erythroid, CFU-E) and in vitro cellular iron uptake. Livers, kidneys, spleens, brains and the remaining femora were removed and prepared for subsequent analysis for Al content. Haemoglobin, hematocrit, reticulocyte counts, circulating haptoglobin, plasma iron and aluminium, free haemoglobin in plasma and total iron-binding capacity were determined. Morphology of circulating erythrocytes and erythropoietic cells in peripheral blood films and bone marrow smears were studied under light and electronic microscopes.
- GLP compliance:
- not specified
Test material
- Reference substance name:
- Aluminium citrate
- EC Number:
- 250-484-4
- EC Name:
- Aluminium citrate
- Cas Number:
- 31142-56-0
- IUPAC Name:
- aluminum citrate
- Details on test material:
- - Name of test material (as cited in study report): Aluminium citrate
- Analytical purity: No data
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: No information.
- Age at study initiation: 21 days
- Weight at study initiation: 101±8 g
- Housing: No information.
- Diet: “Standard diet” was given to all rats. Water to the control rats was provided ad libitum.
- Water: No information about access to water for the treated animals.
ENVIRONMENTAL CONDITIONS
“Controlled temperature, humidity and lighting were maintained throughout the experimental period.” No details provided. “Controlled temperature, humidity and lighting were maintained throughout the experimental period.” No details provided.
Administration / exposure
- Route of administration:
- oral: drinking water
- Vehicle:
- water
- Details on oral exposure:
- PREPARATION OF DOSING SOLUTIONS:
“Al citrate solution (1:1) was freshly prepared by mixing equimolar solutions of aluminium chloride and sodium citrate.”
Al content in the diet was 10 µmol/g food; in the drinking water - 5 µmol/L. Each rat received 6-11 µmol Al/g b.w. daily with food and drinking water. - Analytical verification of doses or concentrations:
- not specified
- Details on analytical verification of doses or concentrations:
- No data.
- Duration of treatment / exposure:
- 8 months
- Frequency of treatment:
- Daily, 7 days per week.
Doses / concentrations
- Remarks:
- Doses / Concentrations:
80 mmol/L
Basis:
nominal in water
- No. of animals per sex per dose:
- 10 animals in the treated group and 8 animals in the control group; all female
- Control animals:
- other: Control animals received drinking water without added aluminium citrate
- Details on study design:
- Random assignment to experimental groups.
- Positive control:
- No data.
Examinations
- Observations and examinations performed and frequency:
- Observations and clinical examination:
- Observation for morbidity and mortality: no information
- Food consumption: no information
- Body weights: only final body weights reported
- Water consumption: no information
Haematology:
Haematology parameters were assessed at the end of treatment: hematocrit, blood haemoglobin (the cyanmethaemoglobin method), reticulocyte count, morphology of circulating erythrocytes (under light and electronic microscopes) and of erythropoietic cells in peripheral blood films and bone marrow smears (under light microscope).
Femoral bone marrow cells were conditioned for in vitro clonal assays of haematopoietic progenitors (late colony-forming unit-erythroid, CFU-E) and in vitro cellular iron uptake.
CFU-E assay (developmental ability of haematopoietic progenitors)
Bone marrow cells were flushed into minimal essential medium Eagle, -modification (-MEM) containing 2% heat inactivated bovine serum. Single cell suspensions were obtained. Triplicate cell cultures stimulated with 0.25 U/ml recombinant human erythropoietin were carried out in -MEM-methylcellulose medium. Erythroid colonies of 8 or more hemoglobinised cells derived from the most differentiated erythropoietic progenitors were considered as CFU-E
In vitro cellular iron uptake
Bone marrow cells from 6 treated and 4 control animals were suspended in liquid medium, supplemented with 5% foetal bovine serum, 0.4 µM apotransferrin and stimulated with recombinant human erythropoietin (0.75 U/ml). Triplicate cell cultures were incubated for 24 hours at 100% humidity and 37C in an atmosphere containing 5% CO2 in the presence of 59Fe citrate. After the incubation, two aliquots were taken and washed twice with phosphate-buffered saline. In one aliquote, 59Fe radioactivity (characteristic -radiation) was measured to determine cell 59Fe uptake. The cell pellet in the second aliquot was mixed with 1 ml cyanmethaemoglobin, 0.2 ml 0.1 M HCl and vortexed with 1.5 ml cyclohexanone. The emulsion was centrifuged, and the organic layer containing 59Fe-haem as cyanmethematin was counted.
Blood chemistry:
The following parameters were determined in plasma:
- haptoglobin (radial immunodiffusion technique)
- free haemoglobin (a colored product produced by Hb reaction with benzidine in acid solution and hydrogen peroxide was measured spectrophotometrically)
- iron concentration
- total iron-binding capacity (TIBC) - Sacrifice and pathology:
- The animals were sacrificed after the treatment had been terminated and blood drawn. Histopathological examination was not performed.
- Other examinations:
- Toxicokinetics/Biodistribution:
Aluminium in plasma, liver, kidney, spleen, brain and femur samples was determined using an atomic absorption spectrometer coupled with a graphite furnace atomiser.
Aluminium in circulating erythrocytes was determined by scanning electron microscopy in combination with energy dispersive X-ray analysis (EDAX)
Measures to prevent contamination with Al
Double deoinized water was used to prepare solutions and culture media. Laboratory glassware and plastic ware were treated with 30% HCl and then carefully rinsed with double deoinized water. Al-free vials used for acid solutions from digested tissues were prepared by immersion in 15% HNO3 for 48 hours. - Statistics:
- The results were expressed as mean±standard deviation or as median and range. The non-parametric Mann-Whitney U-test was used for comparisons between the experimental groups.
Results and discussion
Results of examinations
- Clinical signs:
- not specified
- Mortality:
- not specified
- Body weight and weight changes:
- effects observed, treatment-related
- Food consumption and compound intake (if feeding study):
- not specified
- Food efficiency:
- not specified
- Water consumption and compound intake (if drinking water study):
- not specified
- Ophthalmological findings:
- not specified
- Haematological findings:
- effects observed, treatment-related
- Clinical biochemistry findings:
- effects observed, treatment-related
- Urinalysis findings:
- not examined
- Behaviour (functional findings):
- not specified
- Organ weight findings including organ / body weight ratios:
- not specified
- Gross pathological findings:
- not examined
- Histopathological findings: non-neoplastic:
- not examined
- Histopathological findings: neoplastic:
- not examined
- Details on results:
- Mortality:
No information
Body weight:
Final body weight was significantly lower in the Al treated group than in the control group (272±25 g and 361±38 g, respectively; p<0.001).
Haematology:
Significantly lower haematocrit (38.8±4.29% vs. 43.1± 3.58%, p<0.05) and blood Hb concentration (137±10.1 g/L vs. 148±8.5 g/L) in the Al treated rats than in the control rats.
Mature erythrocyte morphology
Anisocytosis (abnormal cell size), anisochromia (non-uniformity of cell staining) and poikilocytosis (abnormal cell shape) were observed in the blood films from the Al-treated rats. Scanning electron microscopy showed red cell fragments (schistocytes), unusually thin cells (leptocytes), crenated and target cells and other abnormal cells not seen in control samples.
Reticulocyte count
Significantly higher in the Al treated group than in the control group (1.8% vs. 1.2%; p<0.05).
Bone marrow
A significant inhibition of CFU-E growth (≈65% relative to the control group; p<0.005) was seen in the Al treated group.
A significant (p<0.05) reduction of 59Fe uptake in the bone marrow cells of Al exposed rats compared to the control rats.
Clinical Chemistry (blood):
Plasma iron concentration and total iron-binding capacity: no significant group differences (indicates that the Al treated animals were not depleted of iron).
Plasma Hb concentrations: no significant group differences.
Plasma haptoglobin concentration: significantly lower in the Al treated animals than in the control animals (p<0.05). This decrease and the presence of erythrocytes with abnormal shape are indicative of intravascular haemolysis.
Blood urea concentration: no significant group differences (indicates that kidney function was not altered by Al administration).
Target system / organ toxicity
- Critical effects observed:
- not specified
Any other information on results incl. tables
Tissue Metal Levels
Al concentrations in the bone, spleen, liver, kidney and plasma were significantly higher in the Al treated group than in the control group. No significant group differences in brain Al concentrations. There was no correlation between plasma Al concentrations and Al levels in the organs or any other biochemical data.
Scanning electron microscopy combined with EDAX detected Al inside circulating erythrocytes with abnormal shape from animals in the Al treated group.
Applicant's summary and conclusion
- Conclusions:
- The results of this study suggest that Al affects erythropoiesis in rats with normal renal function.
- Executive summary:
Aluminium citrate was administered to ten female Sprague Dawley rats with drinking water at a concentration of 80 mmol/L for 8 months. Eight female rats that received drinking water without added aluminium citrate were used as controls. Blood was collected at the end of the treatment. After blood collection, the animals were sacrificed, femoral bone marrow was removed and smears were prepared. The remaining bone marrow cells were conditioned for in vitro clonal assays of haematopoietic progenitors (late colony-forming unit-erythroid, CFU-E) and in vitro cellular iron uptake. Livers, kidneys, spleens, brains and the remaining femora were removed and prepared for subsequent analysis for Al content. Haemoglobin, hematocrit, reticulocyte counts, circulating haptoglobin, plasma iron and aluminium, free haemoglobin in plasma and total iron-binding capacity were determined. Morphology of erythrocytes and erythropoietic cells in peripheral blood films were studied under light and electronic microscopes. Plasma iron concentration and total iron-binding capacity were not different in the control and the Al treated rats, indicating that the Al treated animals were not depleted of iron. There were no significant group differences in blood urea concentration, which suggests that kidney function was not altered by Al administration. Significantly lower haematocrit and blood Hb concentration were observed in the Al treated rats than in the control rats. Significantly higher reticulocyte count, abnormal erythrocyte morphology, a significant inhibition of CFU-E growth and a significant reduction of59Fe uptake in the bone marrow were reported in the Al treated rats. Plasma haptoglobin concentration was significantly lower in the Al treated animals than in the control animals. This and the presence of abnormal erythrocytes in the Al treated rats are indicative of intravascular haemolysis.Scanning electron microscopy combined with EDAX detected Al inside circulating erythrocytes with abnormal shape from animals in the Al treated group. Al concentrations in the bone, spleen, liver, kidney and plasma were significantly higher in the Al treated group than in the control group. No significant group difference in brain Al concentrations was seen. There was no correlation between plasma Al concentrations and Al levels in the organs or any other biochemical data.The results of this study suggest that Al affects erythropoiesis in rats with normal renal function.
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