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EC number: 405-290-6 | CAS number: 12036-37-2
- 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
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- Auto flammability
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- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
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- Stability: thermal, sunlight, metals
- pH
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- 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
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- Endpoint summary
- Stability
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- 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
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- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
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- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
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- 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:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 17 February 1989 - 21 March 1989
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Read across to similar substance. Study conducted to GLP in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of the relevant results.
- Justification for type of information:
- See read-across justification in Section 13.
Cross-reference
- Reason / purpose for cross-reference:
- other: Target substance
Reference
- Endpoint:
- in vivo mammalian somatic cell study: cytogenicity / bone marrow chromosome aberration
- Type of information:
- read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- supporting study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Study conducted on read across material
- Justification for type of information:
- See read-across justification in Section 13.
- Reason / purpose for cross-reference:
- read-across source
- Sex:
- male/female
- Genotoxicity:
- negative
- Toxicity:
- not examined
- Vehicle controls validity:
- valid
- Negative controls validity:
- not applicable
- Positive controls validity:
- valid
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 989
- Report date:
- 1989
Materials and methods
Test guidelineopen allclose all
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.12 (Mutagenicity - In Vivo Mammalian Erythrocyte Micronucleus Test)
- Deviations:
- no
- GLP compliance:
- yes
- Type of assay:
- other: in vivo mammalian cell micronucleus test
Test material
- Reference substance name:
- Automatically generated during migration to IUCLID 6, no data available
- IUPAC Name:
- Automatically generated during migration to IUCLID 6, no data available
- Test material form:
- solid: particulate/powder
- Remarks:
- migrated information: powder
- Details on test material:
- Description: White powder
Constituent 1
Test animals
- Species:
- mouse
- Strain:
- other: Albino BKW
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Age at study initiation: 5 – 8 weeks.
- Weight at study initiation: Males 22 – 28g; Females 20 – 26g
- Housing: The animals were housed in groups of up to five by sex in solid-floor polypropylene cages with sawdust bedding.
- Diet (e.g. ad libitum): ad libitum with the exception of a 3-4 hour fast immediately before dosing and for approximately two hours after dosing; free access to food (Rat and Mouse Expanded Diet No. 1, Special Diet Services Limited, Witham, Essex, U.K.) was allowed throughout the study.
- Water (e.g. ad libitum): ad libitum with the exception of a 3-4 hour fast immediately before dosing and for approximately two hours after dosing; free access to mains drinking water was allowed throughout the study.
- Acclimation period: minimum of 5 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 – 21 °C
- Humidity (%): 52 – 60% relative
- Air changes (per hr): approximately 15
- Photoperiod (hrs dark / hrs light): 12 hours light and 12 hours darkness.
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- Distilled water
- Details on exposure:
- A confirmatory range-finding study was performed to determine a suitable dose level for the micronucleus study. The dose level selected was a maximum practical dose of 5000 mg/kg.
The study was performed using one dose level (the maximum practical dose of 5000 mg/kg) at three kill times of 24, 48 and 72 hours after dosing. - Duration of treatment / exposure:
- One dose administered by gavage.
- Frequency of treatment:
- All animals were dosed once only at the appropriate dose level by gavage using a metal cannula attached to a graduated syringe. The volume administered to each animal was calculated according to its fasted bodyweight at the time of dosing.
- Post exposure period:
- Animals were observed 1 and 4 hours after dosing and subsequently once daily for 3 days.
Doses / concentrations
- Remarks:
- Doses / Concentrations:
5000 mg/kg
Basis:
actual ingested
- No. of animals per sex per dose:
- Three groups, each of ten mice (five males and five females) were dosed once only with test material at the "maximum practical dose level".
- Control animals:
- yes
- Positive control(s):
- Four further groups of ten mice (five males and five females) were included in the study; three groups were treated with the vehicle alone (distilled water) and the fourth group was treated with cyclophosphamide, a positive control material.
Examinations
- Details of tissue and slide preparation:
- PROCEDURE
i) Range-finding Toxicity Study
A confirmatory range-finding study was performed to determine a suitable dose level for the micronucleus study. The dose level selected should ideally be the maximum tolerated dose level or that which produces some evidence of cytotoxicity up to a maximum practical dose of 5000 mg/kg.
Groups of mice were dosed as follows:
DOSE LEVEL CONCENTRATION DOSE VOLUME NUMBER OF MICE
mg/kg mg/mL mL/kg MALE FEMALE
5000 500 10 7 7
All animals were dosed once only at the appropriate dose level by gavage using a metal cannula attached to a graduated syringe. The volume administered to each animal was calculated according to its fasted bodyweight at the time of dosing.
Animals were observed 1 and 4 hours after dosing and subsequently once daily for 3 days. Deaths and evidence of overt toxicity were recorded at each observation. No necropsies were performed. At 72 hours after dosing, up to 2 mice of each sex were sampled for bone-marrow cells to evaluate any specific bone-marrow toxicity in the absence of deaths.
ii) Micronucleus Study
The study was performed using one dose level (the maximum practical dose) at three kill times of 24, 48 and 72 hours after dosing.
Three groups, each of ten mice (five males and five females) were dosed once only with test material at the "maximum practical dose level". One group of mice was killed by cervical dislocation 24 hours following treatment, a second at 48 hours and a third at 72 hours. In addition, four further groups of ten mice (five males and five females) were included in the study; three groups were treated with the vehicle alone (distilled water) and the fourth group was treated with cyclophosphamide, a positive control material known to produce micronuclei under the conditions of the test. The vehicle control groups were killed 24, 48 and 72 hours following treatment and positive control group animals were killed 24 hours following treatment.
All animals were observed for signs of overt toxicity and death 1 and 4 hours after dosing and then once daily as applicable.
iii) Slide Preparation
Immediately following sacrifice (i.e. 24, 48 or 72 hours following dosing), one femur was dissected from each animal, aspirated with foetal calf serum and bone marrow smears prepared following centrifugation and re-suspension. The smears were air-dried, fixed in absolute methanol, and stained in May-Grünwald/Giemsa.
iv) Evaluation of Slides
Stained bone marrow smears were examined at random using light microscopy at x 1000 magnification. The incidence of micronucleated cells per 1000 polychromatic erythrocytes PCE (blue stained immature cells) per animal was scored. In addition, the number of normochromatic erythrocytes NCE (pink stained mature cells) associated with 1000 polychromatic erythrocytes were counted; these cells were also scored for incidence of micronuclei.
The ratio of normochromatic to polychromatic erythrocytes was calculated together with appropriate group mean values for males and females separately and combined. - Evaluation criteria:
- Interpretation of Results
A comparison was made between the number of micronucleated polychromatic erythrocytes occurring in each of the three test material groups and the number occurring in the corresponding vehicle control groups.
A positive mutagenic response is demonstrated when a statistically significant increase in the number of micronucleated polychromatic erythrocytes is observed for either the 24, 48 or 72 hour kill times.
If the above criteria are not demonstrated, then the test material is considered to be non-mutagenic under the conditions of the test.
A positive response for bone marrow toxicity is demonstrated when the treatment group mean normochromatic to polychromatic ratio is twice the vehicle control value or when a treatment related increase is shown to be statistically significant. - Statistics:
- If necessary, and where possible, all data were statistically analysed using the Kruskal-Wallis one-way analysis of variance by ranks (Kruskal W.H. and Wallis W.A. 1952 J. Am. Statist. Soc. 47 583).
Results and discussion
Test results
- Sex:
- male/female
- Genotoxicity:
- negative
- Toxicity:
- not examined
- Vehicle controls validity:
- valid
- Negative controls validity:
- not applicable
- Positive controls validity:
- valid
- Additional information on results:
- RANGE-FINDING TOXICITY STUDY
The mortality data are summarised as follows:
Dose Level Sex Number of Deaths on day TOTAL DEATHS
mg/kg animals treated 0 1 2 3
5000 Male 7 0 0 0 0 0/14
Female 7 0 0 0 0
No adverse clinical symptoms were observed in any of the animals treated with Substance 1658/5 and there were no premature mortalities.
MICRONUCLEUS STUDY
i) Mortality Data and Clinical Observations
No adverse clinical symptoms were observed in any of the animals treated with Substance 1658/5 in the micronucleus study and there were no premature mortalities.
ii) Evaluation of Bone Marrow Slides
A summary of the results of the micronucleus study is given in Table 1.
There were no significant increases in the frequency of micronucleated PCE's in any of the groups of animals treated with Substance 1658/5 when compared to the corresponding vehicle control group. Furthermore, there was no increase in the frequency of micronucleated NCE's or in the NCE/PCE ratio after treatment with Substance 1658/5.
The positive control group showed a marked increase in the incidence of micronucleated polychromatic erythrocytes hence confirming the known mutagenic activity of cyclophosphamide under the conditions of the test.
The test material, Substance 1658/5, was found not to produce micronuclei in polychromatic erythrocytes of mice under the conditions of the test.
Any other information on results incl. tables
Summary of Group Mean Data (Males and Females Combined)
Table 1
Treatment group |
Number of PCE with Micronuclei per 1000 PCE |
Number of NCE with Micronuclei per 1000 PCE |
NCE PCE Ratio |
|||
Group Mean |
SD |
Group Mean |
SD |
Group Mean |
SD |
|
Vehicle Control 72 hour sampling time |
0.8 |
0.9 |
0.4 |
0.6 |
1.00 |
1.07 |
Vehicle Control 48 hour sampling time |
0.6 |
0.7 |
0.3 |
1.0 |
0.59 |
0.30 |
Vehicle Control 24 hour sampling time |
0.9 |
1.3 |
0.4 |
0.7 |
0.79 |
0.22 |
PositiveControl 24 hour sampling time |
41.5 |
9.1 |
0.7 |
0.5 |
1.22 |
0.36 |
Substance 1658/5 5000mg/kg 72 hour sampling time |
0.9 |
1.1 |
0.3 |
1.1 |
0.92 |
0.28 |
Substance 1658/5 5000mg/kg 48 hour sampling time |
1.1 |
1.3 |
0.2 |
0.5 |
0.81 |
0.37 |
Substance 1658/5 5000mg/kg 24 hour sampling time |
0.7 |
0.8 |
0.3 |
0.7 |
0.75 |
0.17 |
PCE = polychromatic erythrocytes
NCE = normochromatic erythrocytes
SD = standard deviation
Applicant's summary and conclusion
- Conclusions:
- Interpretation of results (migrated information): negative
The test material was considered to be non-mutagenic under the conditions of the study. - Executive summary:
The test material was considered to be non-mutagenic under the conditions of the study. The test followed the OECD Guidelines for Testing of Chemicals No. 474 "Genetic Toxicology: Micronucleus Test" and Annex V method B12 of EEC Commission Directive 84/449/EEC.
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