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EC number: 234-042-8 | CAS number: 10508-09-5
- 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
Genetic toxicity: in vivo
Administrative data
- Endpoint:
- in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 2005-2006
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: GLP guideline study, Klimisch 1a
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 006
- Report date:
- 2006
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
- GLP compliance:
- yes (incl. QA statement)
- Type of assay:
- micronucleus assay
Test material
- Reference substance name:
- Di-tert-pentyl peroxide
- EC Number:
- 234-042-8
- EC Name:
- Di-tert-pentyl peroxide
- Cas Number:
- 10508-09-5
- Molecular formula:
- C10H22O2
- IUPAC Name:
- 2-methyl-2-[(2-methylbutan-2-yl)peroxy]butane
- Test material form:
- other: liquid
- Details on test material:
- • name: Study plan: DI-TERT-AMYL PEROXIDE
• CAS number: 10508-09-5
• batch number: 11650 920511-025
• description: at receipt: colorless to slightly yellowish liquid
• date of receipt: 26 January 2006
• storage conditions: at room temperature and protected from humidity
• peroxid content : 98.3%
• expiry date: July 2006
Constituent 1
Test animals
- Species:
- mouse
- Strain:
- Swiss
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- - Breeder: Charles River Laboratories, l'Arbresle, France.
- Age: on the day of treatment, the animals were approximately 6 weeks old.
- Weight: at the beginning of treatment the mean body weight was 31.8 g for males (ranging from 30.3 to 33.2 g) and 22.8 g for females (ranging from 19.1 to 25.1 g).
- Veterinary care at CIT: upon their arrival at CIT, the animals were given a complete examination to ensure that they were in good clinical conditions.
- Acclimation: at least 5 days before the day of treatment.
- Constitution of groups: upon arrival, the animals were randomly allocated to the groups by sex.
- Subsequently, each group was assigned to a different treatment group.
- Identification: individual tail marking upon treatment.
Upon their arrival at CIT, the animals were housed in an animal room, with the following
environmental conditions:
• temperature: 22 ± 2°C,
• relative humidity: 30 to 70%,
• light/dark cycle: 12 h/12 h (07:00 - 19:00),
• ventilation: at least 12 cycles/hour of filtered non-recycled fresh air.
The temperature and relative humidity were under continuous control and recording. The
housing conditions (temperature, relative humidity and ventilation) and corresponding
instrumentation and equipment were verified and calibrated at regular intervals.
Food and water: were provided ad libitum
Administration / exposure
- Route of administration:
- intraperitoneal
- Vehicle:
- corn oil
- Duration of treatment / exposure:
- 2 days
- Frequency of treatment:
- Frequency: two treatments separated by 24 hours, volume: 10 mL/kg
- Post exposure period:
- 24 hours
Doses / concentrations
- Remarks:
- Doses / Concentrations:
0, 500, 1000, 2000 mg/kg
Basis:
nominal conc.
- No. of animals per sex per dose:
- 5 males and 5 females at 500 mg/kg
5 males and 5 females at 1000 mg/kg
8 males and 8 females at 2000 mg/kg (but since no mortality occurred, only five animals of each sex were subjected to bone marrow analysis. The
supplementary animals were humanely killed and bone marrow smears were not prepared)
3 additional males and 3 additional females at 2000 mg/kg for determination of plasma level of the test item - Control animals:
- yes, concurrent vehicle
- Positive control(s):
- The positive control was Cyclophosphamide (CPA, Endoxan, Baxter, Maurepas, France), batch No. 4A121 dissolved in distilled water at a concentration of 5 mg/mL. The preparation was stored at -20°C and thawed immediately before use.
Examinations
- Details of tissue and slide preparation:
- Preparation of the bone marrow smears
At the time of sacrifice, all the animals were killed by CO2 inhalation in excess. The femurs of the animals were removed and the bone marrow was flushed out using fetal calf serum. After centrifugation, the supernatant was removed and the cells in the sediment were resuspended by shaking. A drop of this cell suspension was placed and spread on a slide. The slides were air-dried and stained with Giemsa. The slides were coded so that the scorer is unaware of the treatment group of the slide under evaluation ("blind" scoring).
Microscopic examination of the slides
For each animal, the number of the micronucleated polychromatic erythrocytes (MPE) was counted in 2000 polychromatic erythrocytes; the polychromatic (PE) and normochromatic (NE) erythrocyte ratio was established by scoring a total of 1000 erythrocytes (PE + NE).
The analysis of the slides was performed at Microptic, cytogenetic services (2 Langland Close Mumbles, Swansea SA3 4LY, UK), in compliance with GLP, and the Principal Investigator was Natalie Danford. Details concerning the method used, the format of the data, communication, quality assurance and archiving are indicated in the corresponding PIDS (Principal Investigator Data Sheet) reported in appendix 3. - Evaluation criteria:
- For a result to be considered positive, a statistically significant increase in the frequency of MPE must be demonstrated when compared to the concurrent vehicle control group. Reference to historical data (appendix 4), or other considerations of biological relevance was also taken into account in the evaluation of data obtained.
- Statistics:
- Normality and homogeneity of variances were tested using a Kolmogorov Smirnov test and a
Bartlett test.
If normality and homogeneity of variances were demonstrated, the statistical comparison was
performed using a Student "t" test (two groups) or a one-way analysis of variance
(= three groups) followed by a Dunnett test (if necessary).
If normality or homogeneity of variances was not demonstrated, a Mann/Withney test
(two groups) or a Kruskall Wallis test (= three groups) was performed followed by a Dunnett test
(if necessary).
All these analyses were performed using the software SAS Enterprise Guide V2 (2.0.0.417, SAS Institute Inc), with a level of significance of 0.05 for all tests.
Results and discussion
Test results
- Sex:
- male/female
- Genotoxicity:
- positive
- Toxicity:
- yes
- Vehicle controls validity:
- valid
- Negative controls validity:
- not examined
- Positive controls validity:
- valid
- Additional information on results:
- For both males and females, the mean values of MPE in the groups treated with the test item DI-TERT-AMYL PEROXIDE, were higher than the concurrent vehicle control groups and out of the vehicle control historical range: 1.5-3.7 MPE/1000 PE for males versus 0.2-1.7 MPE/1000 PE for historical mean vehicle control value and 1.2-3.3 MPE/1000 PE for females versus 0.0-1.4 MPE/1000 PE for historical mean vehicle control value.
Statistical significance was observed only in groups of females treated at 1000 and 2000 mg/kg/day. However, in view of the dose-related increase observed in both males and females and the frequencies of MPE which were all (except for the low dose groups) out of the vehicle control historical range, the effect observed was considered as biologically significant in both males and females.
The mean values of MPE as well as the PE/NE ratio for the vehicle and positive controls were consistent with the historical data. Cyclophosphamide induced a significant increase in the frequency of MPE, indicating the sensitivity of the test system under our experimental conditions. The study was therefore considered valid.
Any other information on results incl. tables
Clinical signs:
Piloerection was noted in all animals treated at 500, 1000 or 2000 mg/kg/day. In one male from the high dose group (supplementary animal) half-closed eyes were also observed at 24 hours following the second treatment.
One female from the 1000 mg/kg/day dose group was found dead (cannibalised animal) 24 hours following the second treatment.
Results:
Results of the cytogenetic test: data summary | |||||||
MPE/1000PE | PE/NE ratio | ||||||
Group | Doses (mg/kg/day) | mean | sd | mean | sd | time of sacrifice after the last administration | |
Males | Vehicle | _ | 1,4 | 0,7 | 0,4 | 0,1 | 24 h |
DTA | 500 | 1,5 | 1,1 | 0,5 | 0,1 | ||
DTA | 1000 | 2,8 | 1,2 | 0,4 | 0 | ||
DTA | 2000 | 3,7 | 1,8 | 0,4 | 0,1 | ||
cyclophosphamide | 50 | 27,6* | 2,2 | 0,8** | 0,1 | ||
Females | Vehicle | _ | 0,8 | 0,6 | 0,5 | 0,1 | |
DTA | 500 | 1,2 | 1 | 0,6 | 0,2 | ||
DTA | 1000 | 2,4* | 1,1 | 0,5 | 0,3 | ||
DTA | 2000 | 3,3** | 0,8 | 0,4 | 0,1 | ||
cyclophosphamide | 50 | 21,2** | 6,8 | 0,6 | 0,3 |
Five animals per group (except for females treated at 1000 mg/kg/day: 4 animals) MPE: Micronucleated Polychromatic Erythrocytes |
PE: Polychromatic Erythrocytes NE: Normochromatic Erythrocytes sd: standard deviation |
Vehicle and test item: |
Number of administrations: two administrations separated by a 24-hour interval |
Route: intraperitoneal route |
Vehicle: corn oil |
Cyclophosphamide: |
Number of administrations: one |
Route: oral |
Vehicle: water |
Statistical significance: |
* p<0,05 |
** p<0,01 |
Applicant's summary and conclusion
- Conclusions:
- Di-tert-amyl peroxide induced an increase damage to the chromosomes or the mitotic apparatus of mice bone marrow cells after two intraperitoneal administrations, at a 24-hour interval, at the dose-levels of 500, 1000 and 2000 mg/kg/day.
- Executive summary:
The objective of this study was to evaluate the potential of di-tert-amyl peroxide, to induce structural or numerical damage in bone marrow cells of mice. The study was performed according to the international guidelines (OECD 474) and in compliance with the Principles of Good Laboratory Practice Regulations.
Three groups of 5 male and five female mice were given intraperitoneal route administrations of di-tert-amyl peroxide at dose-levels of 0, 500, 1000 and 2000 mg/kg/day in corn oil, over a 2-day period.
One group of five males and five females received the positive control test item (Cyclophosphamide) once by oral route at the dose-level of 50 mg/kg. The animals were killed 24 hours after the last. Bone marrow smears were then prepared.
For each animal, the number of the micronucleated polychromatic erythrocytes (MPE) was counted in 2000 polychromatic erythrocytes. The polychromatic (PE) and normochromatic (NE) erythrocyte ratio was established by scoring a total of 1000 erythrocytes (PE +NE).
For both males and females, the mean values of MPE in the groups treated with the di-tert-amyl peroxide, were higher than the concurrent vehicle control groups and out of the vehicle control historical range: 1.5-3.7 MPE/1000 PE for males versus 0.2-1.7 MPE/1000 PE for historical mean vehicle control value and 1.2-3.3 MPE/1000 PE for females versus 0.0-1.4 MPE/1000 PE for historical mean vehicle control value.
Statistical significance was observed only in groups of females treated at 1000 and
2000 mg/kg/day. However, in view of the dose-related increase observed in both males and females and the frequencies of MPE which were almost all out of the vehicle control historical range, the effect observed was considered as biologically significant in both males and females.
The mean values of MPE as well as the PE/NE ratio for the vehicle and positive controls were consistent with the historical data. Cyclophosphamide induced a significant increase in the frequency of MPE, indicating the sensitivity of the test system under our experimental conditions. The study was therefore considered valid.
Under these experimental conditions, di-tert-amyl induced an increase damage to the chromosomes or the mitotic apparatus of mice bone marrow cells after two intraperitoneal administrations, at a 24-hour interval, at the dose-levels of 500, 1000 and 2000 mg/kg/day.
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