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EC number: - | CAS number: -
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
Genetic toxicity: in vivo
Administrative data
- Endpoint:
- in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus
- Remarks:
- Type of genotoxicity: chromosome aberration
- Type of information:
- migrated information: read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- supporting study
- Study period:
- 1994
- Reliability:
- 1 (reliable without restriction)
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 994
- Report date:
- 1994
Materials and methods
Test guidelineopen allclose all
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
- Deviations:
- yes
- Remarks:
- , but the observed deviation was not considered to have compromised the validity or integrity of the study.
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.12 (Mutagenicity - In Vivo Mammalian Erythrocyte Micronucleus Test)
- Deviations:
- yes
- Remarks:
- , but the observed deviation was not considered to have compromised the validity or integrity of the study.
- Qualifier:
- according to guideline
- Guideline:
- EPA OTS 798.5395 (In Vivo Mammalian Cytogenics Tests: Erythrocyte Micronucleus Assay)
- Deviations:
- yes
- Remarks:
- , but the observed deviation was not considered to have compromised the validity or integrity of the study.
- GLP compliance:
- yes
- Type of assay:
- micronucleus assay
Test material
Reference
- Name:
- Unnamed
- Type:
- Constituent
- Test material form:
- semi-solid (amorphous): gel
- Remarks:
- migrated information: paste
- Details on test material:
- - Name of test material (as cited in study report): P.I.A.S.
- Physical state: brown thisk paste
- Purity: assumed to be 100 % for dose calculation
- Lot/batch No.: B359
- Expiration date of the lot/batch: December 1994
- Storage condition of test material: at refrigerator temperature
Test animals
- Species:
- mouse
- Strain:
- other: OF1 (IOPS Caw)
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: IFFA-CREDO, 69592 L'Arbresle, France
- Age at study initiation: 6 weeks
- Weight at study initiation (main study): 27.2 to 30.8 g for males, 22.5 to 26.9 g for females
- Assigned to test groups randomly: yes
- Housing: animals are housed in groups of 3 animals (preliminary study) or 5 animals (main study) in translucent polypropylene or polycarbonate cages (205 * 118 * 127 mm)
- Diet (e.g. ad libitum): pelleted complete diet ad libitum
- Water (e.g. ad libitum): filtered (0.2µm) mains drinking water ad libitum
- Acclimation period: 3 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22°C +/- 3°C
- Humidity (%): 50 to 20 %
- Air changes (per hr): minimum 8 air changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours light (artificial) / 12 hours dark
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- - Vehicle(s)/solvent(s) used: corn oil
- Justification for choice of solvent/vehicle: corn oil was used for 26 week oral (gavage) toxicity study in the rat.
- Lot/batch no. (if required): A 25127 90043 - Details on exposure:
- PREPARATION OF DOSING SOLUTIONS: Dosing suspensions were performed by using corn oil to obtain the following concentrations:
- preliminary study:
* dose volume: 10 mL/kg b.w.
* concentration of dosing preparation: 500.0, 325.0, 211.3, 137.3, 89.2 mg/mL
* dose administrated: 5000, 3250, 2113, 1373, 892 mg/kg b.w.
- main study:
* dose volume: 10 mL/kg b.w.
* concentration of dosing preparation: 500.0 mg/mL
* dose administrated: 5000 mg/kg b.w. - Frequency of treatment:
- Once, by gavage
- Post exposure period:
- Animals were killed 24, 48 or 72 hours after the administration of the test article.
- No. of animals per sex per dose:
- - preliminary study: 15 males and 15 females (with 3 males and 3 females per treated group)
- main study: 35 males and 35 females (with 5 males and 5 females per treated group) - Control animals:
- yes, concurrent vehicle
- Positive control(s):
- - Positive control: cyclophosphamide
- Route of administration: intraperitoneal route
- Doses / concentrations: 100 mg/kg b.w. (dose volume: 10 mL/kg b.w.)
Examinations
- Tissues and cell types examined:
- - tissues: bone marrow of femurs from each animal
- cell types examined: erythrocytes - Details of tissue and slide preparation:
- CRITERIA FOR DOSE SELECTION:
An initial dose range finding study is performed with the test article at suitable dose levels (5000, 3250, 2113, 1373, 892 mg/kg b.w.)
TREATMENT AND SAMPLING TIMES ( in addition to information in specific fields):
The main study is performed with the test article at the dose concentration of 5000 mg/kg b.w.. A single administration is perfomed by oral route, and animals are sacrified 24, 48 or 72 hours after the treatment.
DETAILS OF SLIDE PREPARATION:
The animals are first treated, and then sacrificed ; the femurs are removed and the bone marrow extracted in foetal calf serum.
The homogenized centrifugate is spread on slides and stained (May Grünwald-Giemsa technique). - Evaluation criteria:
- - Study: slides are scored and decoded to determine the ratio of PCE/NCE and the frequency of micronucleated PCE/1000 PCE. A mean and a standard deviation are calculated for each group.
- Control: the PCE/NCE ratios and frequencies of micronucleated PCE in vehicle control animals are compared with historical control ranges to determine whether or not the assay is acceptable.
PCE = polychromatic erythrocytes
NCE = normochromatic erythrocytes - Statistics:
- Student's t test
Results and discussion
Test results
- Sex:
- male/female
- Genotoxicity:
- negative
- Toxicity:
- no effects
- Vehicle controls validity:
- valid
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Additional information on results:
- RESULTS OF RANGE-FINDING STUDY
- Dose range: 5000, 3250, 2113, 1373 and 892 mg/kg b.w.
- Clinical signs of toxicity/mortality, in test animals: no clinical signs and no mortality were observed over 3 days after dosing any group.
RESULTS OF DEFINITIVE STUDY
- Dose: 5000 mg/kg b.w.
- Clinical signs/mortality: no clinical signs and no mortality were observed over 3 days after dosing any group.
- Induction of micronuclei (for Micronucleus assay):
* Positive control: it induced a clear and statistically significant increase in the number of micronucleated NCE: the group mean for both sexes combined (46.5/1000) was approximately 29 times the mean in the concurrent negative control.
* Negative control: the incidence of micronucleated PCE in the vehicle control groups was within the range anticipated in this type of study at testing facility.
* Treated groups: no statistically significant increase in the number of micronucleated PCE was observed in any of the treated groups, compared to the concurrent negative control group.
- Ratio of PCE/NCE (for Micronucleus assay):
* Positive control: a statistically significant decrease (p < 0.05) in the number of PCE was noted.
* Negative control: PCE/NCE ratios were within the range anticipated in this type of study at testing facility.
* Treated group: a statistically significant decrease (p < 0.05) in the number of PCE was noted in the treated group sacrified 48 hours after dosing when compared to the values of the negative control group at the same kill time.
No cytotoxicity was noted in the treated group sacrified 24 and 72 hours after dosing.
Applicant's summary and conclusion
- Conclusions:
- Interpretation of results (migrated information): negative
Under the experimental conditions, the test article P.I.A.S (Batch B359), did not induce micronuclei in the polychromatic erythrocytes of the bone marrow of mice treated at 5000 mg/kg b.w.. Although this dose level did not cause mortality and did not induce any clinical signs, it did however induce a statistically significant decrease in the number of PCE in the treated group killed 48 hours after dosing.
In conclusion, P.I.A.S. induced no genotoxic activity under these experimental conditions. - Executive summary:
The mutagenic potential of the test article P.I.A.S. was evaluated by means of the micronucleus test in mice. The product was administered orally at the dose level of 5000 mg/kg b.w. to groups of 10 mice (5 males and 5 females), sacrificed 24, 48 and 72 hours post-dose. Negative (corn oil) and positive control (cyclophosphamide) were included in this study.
The frequency of micronuclei and the ratio poly/normochromatic erythrocytes were calculated for each animal and for each group.
Under the experimental conditions, the test article P.I.A.S. (Batch B359), did not reveal any mutagenic activity on 1000 polychromatic erythrocytes per mice treated at 5000 mg/kg b.w. compared with a positive control group.
Although this dose level did not cause mortality and did not induce any clinical signs, only a decrease in the number of polychromatic erythrocytes was observed in the animals examined 48 hours after administration.
In conclusion, P.I.A.S. induced no genotoxic activity under these experimental conditions.
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