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Diss Factsheets
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EC number: 212-052-3 | CAS number: 756-79-6
- 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
Specific investigations: other studies
Administrative data
- Endpoint:
- mechanistic studies
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: scientifically acceptable publication
Data source
Reference
- Reference Type:
- publication
- Title:
- Quantitation of Alpha2u-Globulin in Rat Kidney Cytosol by Capillary Electrophoresis
- Author:
- Pähler A, Blumbach K, Herbst J, and Dekant W
- Year:
- 1 999
- Bibliographic source:
- Analytical Biochemistry 267: 203–211
Materials and methods
- Principles of method if other than guideline:
- Alpha2u-globulin in renal enal cytosol fractions was analyzed by capillary electrophoresis as protein–SDS complexes after treatment with test substance.
- GLP compliance:
- no
- Remarks:
- welldocumented publication
- Type of method:
- in vivo
- Endpoint addressed:
- carcinogenicity
Test material
- Reference substance name:
- Kaolin
- Cas Number:
- 1332-58-7
- IUPAC Name:
- Kaolin
- Details on test material:
- - Name of test material (as cited in study report): dimethyl methylphosphonate (DMMP) obtained from Aldrich Chemical Company (Deisenhofen, Germany)
No additional details provided; all chemicals used were reagent, electrophoresis, or gradient grade as commercially available.
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Fischer 344
- Sex:
- male
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Fischer F344/N rats were obtained from Harlan Winkelmann (Borchen, FRG)
- Age at study initiation: adult animals were used
- Acclimation period: 3 days (before the experiments, the animals were accustomed to the metabolic cages for 3 days and control urine was collected for 12 h before the exposures.)
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21°C
- Photoperiod (hrs dark / hrs light): 12-h light/dark cycle
No additional data provided
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- corn oil
- Details on exposure:
- PREPARATION OF DOSING SOLUTIONS:
No details data provided - Analytical verification of doses or concentrations:
- no
- Duration of treatment / exposure:
- 5 days
- Frequency of treatment:
- once daily
- Post exposure period:
- At the end of treatment, animals were sacrificed by cervical dislocation and kidney cytosolic subcellular fractions were prepared.
Doses / concentrations
- Remarks:
- Doses / Concentrations:
0, 500 and 1000 mg/kg bw per day
Basis:
actual ingested
- No. of animals per sex per dose:
- 5
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- no further details provided
Examinations
- Examinations:
- Rat kidney cytosolic subcellular fractions of treated rats were prepared and protein concentrations in liquid samples determined. The protein separation was then performed with an anion-exchange column and a high-performance liquid chromatography system. The eluent representing a2u-globulin was collected, pooled, desalted by gel filtration chromatography, lyophilized, and stored at 280°C.
Renal cytosol fractions were analyzed by capillary electrophoresis as protein–SDS complexes. Using a2u-globulin purified from urine of male rats, the limit of detection was 10 mg/ml sample in routine analyses. Excellent run to run reproducibility in migration time (CV≤4%) and peak areas corresponding to a2u-globulin (CV≤3%) after normalization to the internal standard was observed. - Positive control:
- The test substance was evaluated together with 4 other compounds, some of which also showed a positive response
Results and discussion
- Details on results:
- Significant increases in renal alpha2u-globulin content (up to 85% of total protein content) compared to controls (approx 15%) were observed in kidney cytosol of rats treated with alpha2u-globulin nephropathy-inducing agents such as trimethylpentane or the alkylphosphonates dimethyl methylphosphonate and diethyl ethylphosphonate, but not in kidney cytosol of male rats treated with tris-(2- chloroethyl)phosphate or the nephrotoxic agent hexachlorobutadiene (see Tables 1&2). A good correlation of the alpha2u-globulin contents determined by capillary electrophoresis and immunoblotting with an a2u-globulin-specific antibody (r2=0.997) was obtained. Capillary electrophoresis provides a simple, rapid, and highly reproducible quantitation of a2u-globulin accumulation for renal tumorigens and may assist in the risk assessment process for these chemicals.
Any other information on results incl. tables
Table 1: Alpha2u-Globulin Content (Determined by Capillary Electrophoresis) in Kidney Cytosol of Male Rats Treated with Several Nephrotoxic Compounds(a)
Treatment |
Alpha2u-Globulin Content (% of total protein) |
CV(%) (= SD/mean*100) |
Untreated control |
14.7 ± 4.8 |
32 |
TCEP, 250 mg/kg |
19.4 ± 6.1 |
31 |
HCBD, 200 mg/kg |
9.1 ± 7.5 |
82 |
DMMP, 500 mg/kg |
68.9 ± 3.4 |
5 |
DMMP, 1000 mg/kg |
78.4 ± 5.1 |
7 |
DEEP, 50 mg/kg |
56.4 ± 8.3 |
15 |
DEEP, 100 mg/kg |
62.4 ± 4.2 |
7 |
TMP, 50 mg/kg |
85.2 ± 7.0 |
8 |
Note: data are shown as means ± SD and show interanimal variation; (a) n = 5 animals per treatment group, samples of individual animals were run as triplicates |
Table 2: Comparison of the Intraassay Variation in Determined alpha2u-Globulin Content in Individual Kidney Cytosol Samples from Untreated Male Rats and Male Rats Treated with alpha2u-Globulin-Inducing Agents by Western Blot Analysis with an alpha2u-Globulin-Specific Antibody or by Capillary Electrophoresis
Treatment |
alpha2u-Globulin Conte |
|||
Western blot/specific antibody (intensity relative to control) |
CV(%) (SD/mean*100) |
CE-SDS (% of total cytosolic protein) |
CV(%) (SD/mean*100) |
|
Untreated control |
1.0 ± 0.1 |
14 |
15.3 ± 0.5 |
3 |
TCEP, 250 mg/kg |
1.4 ± 0.4 |
31 |
17.5 ± 1.1 |
6 |
HCBD, 200 mg/kg |
0.9 ± 0.2 |
23 |
10.2 ± 0.7 |
7 |
DMMP, 500 mg/kg |
4.5 ± 0.7 |
16 |
69.5 ± 0.5 |
1 |
DMMP, 1000 mg/kg |
5.4 ± 1.1 |
22 |
79.8 ± 2.6 |
3 |
DEEP, 50 mg/kg |
3.6 ± 0.6 |
16 |
53.3 ± 4.1 |
8 |
DEEP, 100 mg/kg |
4.4 ± 0.7 |
17 |
65.2 ± 1.0 |
2 |
TMP, 50 mg/kg |
4.8 ± 1.0 |
20 |
81.0 ± 4.7 |
6 |
Note: data are means ± SD, n = 3, and were determined in three samples from one animal per treatment group |
Applicant's summary and conclusion
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
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