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EC number: 247-666-0 | CAS number: 26401-97-8
- 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
![](https://echa.europa.eu./o/diss-blank-theme/images/factsheets/A-REACH/factsheet/print_toxicological-information.png)
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:
- Not specified
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- comparable to guideline study with acceptable restrictions
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 980
- Report date:
- 1980
Materials and methods
Test guideline
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
- GLP compliance:
- no
- Type of assay:
- other: mammalian erythrocyte micronucleus test (migrated information)
Test material
- Reference substance name:
- Diisooctyl 2,2'-[(dioctylstannylene)bis(thio)]diacetate
- EC Number:
- 247-666-0
- EC Name:
- Diisooctyl 2,2'-[(dioctylstannylene)bis(thio)]diacetate
- Cas Number:
- 26401-97-8
- Molecular formula:
- C36-H72-O4-S2-Sn
- IUPAC Name:
- 6-methylheptyl 14-methyl-4,4-dioctyl-7-oxo-8-oxa-3,5-dithia-4-stannapentadecan-1-oate
- Reference substance name:
- Mono-n-octyltin-tri-thioglycol-acid isooctyl ester
- IUPAC Name:
- Mono-n-octyltin-tri-thioglycol-acid isooctyl ester
- Test material form:
- liquid
- Details on test material:
- - Appearance: colourless liquid
Constituent 1
Constituent 2
Test animals
- Species:
- mouse
- Strain:
- other: CFLP
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Weight at study initiation: 19 to 23 g
- Assigned to test groups randomly: yes
- Fasting period before study: animals were starved overnight before dosing
- Housing: each group of 5 mice were kept in a plastic disposable cage
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: one week
ENVIRONMENTAL CONDITIONS
- Temperature: 21 ± 2 °C
- Humidity: 50 ± 5 %
- Air changes (per hr): 20
- Photoperiod: The room was illuminated by artificial light for 12 hours per day
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- - Vehicle(s)/solvent(s) used: CMC (carboxymethyl cellulose)
- Dosing volume: 0.1 mL/10 g bw per dose - Details on exposure:
- PREPARATION OF DOSING SOLUTIONS:
- Preparation: The formulations were prepared using a Silverson high speed mixer. - Duration of treatment / exposure:
- The total doses were given as two equal administrations separated by an interval of 24 hours.
- Frequency of treatment:
- Two equal administrations separated by an interval of 24 hours.
- Post exposure period:
- 6 hours following the second dose.
Doses / concentrationsopen allclose all
- Dose / conc.:
- 2 250 mg/kg bw (total dose)
- Dose / conc.:
- 4 500 mg/kg bw (total dose)
- Dose / conc.:
- 9 000 mg/kg bw (total dose)
- No. of animals per sex per dose:
- Phase I (preliminary toxicity study): 2 animals per sex per dose
Phase II (micronucleus study): 5 animals per sex per dose - Control animals:
- yes, concurrent vehicle
- Positive control(s):
- - Mitomycin C
- Doses / concentrations: Prepared at 0.7 mg/mL for two doses of 7 mg/kg, in 0.9 % saline
- Route of administration: Intra-peritoneally
Examinations
- Tissues and cell types examined:
- - The stained smears were examined by light microscopy to determine the incidence of micronucleated cells per 2000 polychromatic and 2000 normochromatic erythrocytes per animal.
- In addition, the ratio of normochromatic to polychromatic erythrocytes was determined for each animal. - Details of tissue and slide preparation:
- CRITERIA FOR DOSE SELECTION:
- Doses for the micronucleus assay were selected from the results of the preliminary toxicity study.
DETAILS OF SLIDE PREPARATION:
- Following the last dose, the animals were observed for a further six hours before killing and all mortalities and signs of malreaction during the experiment were recorded. The animals were killed by cervical dislocation and both femurs dissected out from each animal. The femurs were cleared of tissue and one epiphysis removed from each bone.
- A direct bone marrow smear was made onto a slide containing a drop of calf serum. The slide was cleaned by immersion in methanol for 24 hours and air-dried immediately before use. One smear was made from each femur. The prepared smears were air-dried and fixed in methanol overnight.
- After fixation, the smears were air-dried and placed in buffered distilled water (pH 6.8) for 10 minutes prior to staining in Giemsa (dilution factor 1 part Giemsa: 9 parts buffered distilled water pH 6.8) for 10 minutes. After rinsing in buffered distilled water (pH 6.8), the slides were air-dried. Prior to mounting in DPX, the slides were defatted by immersion in xylene for 10 minutes.
METHOD OF ANALYSIS:
- The stained smears were examined by light microscopy to determine the incidence of micronucleated cells per 2000 polychromatic and 2000 normochromatic erythrocytes per animal. In addition, the ratio of normochromatic to polychromatic erythrocytes was determined for each animal. - Statistics:
- STATISTICAL ANALYSIS OF THE RATIOS OF NORMOCHROMATIC TO POLYCHROMATIC ERYTHROCYTES
- Due to heterogeneity of variance (Barlett's test; P < 0.001) non-parametric methods based on Kruskal-Wallis mean ranks were used to analyse the ratios of normochromatic to polychromatic erythrocytes. These methods have been found to be more robust against inequality of variance than classical analysis of variance methods.
- The positive control group dosed with Mitomycin C and the groups dosed with the test material were compared with the vehicle control using the non-parametric equivalent of the method of L.S.D.'s (least significant differences).
- After administration of the test material at a total dosage of 2250 mg/kg bodyweight, the ratio of normochromatic to polychromatic erythrocytes was not significantly different from the concurrent control value. At total dosages of 4500 and 9000 mg/kg body weight the ratios were significantly different from the concurrent control value, P < 0.01 and P < 0.001 respectively
- The positive control group dosed with Mitomycin C, gave a ratio which was significantly different from the concurrent control value, P < 0.001.
STATISTICAL ANALYSIS OF THE MICRONUCLEATED NORMOCHROMATIC AND POLYCHROMATIC ERYTHROCYTE COUNTS
- The non-parametric methods of statistical analysis detailed above were used to analyse the micronucleated normochromatic and polychromatic erythrocyte counts.
- After administration of the test material at all dosages, the micronucleated normochromatic and polychromatic erythrocyte counts were not significantly different from the respective concurrent control values.
- The positive control group dosed with Mitomycin C gave micronucleated cell counts which were significantly different from the respective concurrent control values, P < 0.001
Results and discussion
Test results
- Key result
- Sex:
- male/female
- Genotoxicity:
- negative
- Toxicity:
- yes
- Remarks:
- Bone marrow depression
- Vehicle controls validity:
- valid
- Negative controls validity:
- not examined
- Positive controls validity:
- valid
- Additional information on results:
- RESULTS OF RANGE-FINDING STUDY
- Dose range: 2000, 4000, 8000, 9000, 10000, 11000, 12000, 14000 and 20000 mg/kg bw
- Clinical signs of toxicity in test animals: No toxic reactions were observed at 2000, 4000, 8000 and 9000 mg/kg bw. At 10000 and 11000 mg/kg bw, a toxic reaction consisting of hypopnoea was observed. At total dosages of 12000, 14000 and 20000 mg/kg bw, a toxic reaction consisting of hypopnoea and a period of lethargy was observed.
- From the above results, a top dosage of 9000 mg/kg bodyweight was chosen for the micronucleus test which, it was indicated, would cause one or two deaths.
RESULTS OF DEFINITIVE STUDY
SIGNS AND MORTALITIES
- After administration of 1 % methylcellulose, the vehicle control, no toxic reactions or mortalities were observed.
- After administration of the test material at all dosages, no toxic reactions were observed. At a total dosage of 9000 mg/kg bodyweight, there were three mortalities. Two animals died overnight after the administration of the first dose, between 8 and 24 hours. Advanced visceral autolysis prevented any post-mortem examination. The third died after administration of the second dose between 24 and 30 hours. Macroscopic examination at post-mortem failed to reveal any abnormalities.
- After administration of Mitomycin C, the positive control compound, no toxic reactions or mortalities were observed.
MICRONUCLEUS COUNTS
- The group mean counts and ranges obtained with the test material are shown in Table 1.
- In this experiment the negative control group gave a mean count of 2.8 micronucleated polychromatic cells which was just outside the range for previous unrelated experiments. However, the individual counts were within the laboratory standard range of individual counts for negative controls obtained in previous unrelated experiments.
- After administration of the test material at all dosages, the group mean polychromatic cell counts were comparable with the concurrent control value and within the laboratory standard range for negative controls obtained in previous unrelated experiments. In addition, the group mean micronucleated normochromatic cell counts of the treatment groups were comparable with the concurrent control value.
- The positive control, Mitomycin C, administered intraperitoneally gave a mean count of 89.5 micronucleated cells per 2000 polychromatic erythrocytes. This group also gave a mean count of 11.4 micronucleated cells per 2000 normochromatic erythrocytes.
Any other information on results incl. tables
Table 1: Group mean number of micronucleated cells per 2000 normochromatic erythrocytes and 2000 polychromatic erythrocytes per animal and the group mean ratio of normochromatic to polychromatic erythrocytes
Treatment |
Total dosage over 24 h (mg/kg) |
Number of micronucleated cells per 2000 erythrocytes per animal |
Ratio of normochromatic to polychromatic erythrocytes |
||||
Normochromatic |
Polychromatic |
|
|||||
Mean |
Range |
Mean |
Range |
Mean |
Range |
||
Vehicle |
- |
2.5 |
0 to 6 |
2.8 |
1 to 6 |
1.09 |
0.93 to 1.22 |
Test material |
2250 |
2.3 |
0 to 6 |
2.5 |
0 to 5 |
1.38 |
1.19 to 1.69 |
4500 |
2.4 |
0 to 5 |
2.4 |
0 to 6 |
1.72** |
1.47 to 2.09 |
|
9000 |
2.3 |
0 to 6 |
2.6 |
1 to 5 |
3.93*** |
2.56 to 5.39 |
|
Positive control |
14 |
11.4*** |
8 to 15 |
89.5*** |
74 to 115 |
10.46*** |
7.75 to 15.38 |
** P < 0.01
*** P < 0.001
Applicant's summary and conclusion
- Conclusions:
- Under the conditions of this study, it was concluded that the test material failed to show any evidence of mutagenic potential, when administered orally. However, at the higher dose levels evidence of toxicity, as shown by bone marrow depression, was observed.
- Executive summary:
A study was performed to investigate the genetic toxicity in vivo of the test material. The study was conducted in a style similar to OECD 474.
In this assessment of the effect of the test material on the incidence of micronucleated polychromatic erythrocytes in mice, total dosages of 2250, 4500 and 9000 mg/kg bodyweight were administered by oral gavage, in two equal dosages, separated by an interval of 24 hours.
A negative control group was dosed in an identical manner with the vehicle, 1 % methylcellulose. A positive control group was dosed by intraperitoneal injection with Mitomycin C, at a total dosage of 14 mg/kg bodyweight. The mice were sacrificed six hours after the second dose and bone marrow smears examined for the presence of micronuclei in 2000 polychromatic and 2000 normochromatic erythrocytes per mouse. The ratio of normochromatic to polychromatic cells was also examined in each mouse.
A preliminary toxicity study indicated that a top dosage of 9000 mg/kg bodyweight would cause one or two deaths and led to the selection of the dose concentrations for the main test.
At all dosages of the test material both of the group mean micronucleated cell counts were comparable with the concurrent control values.
After administration of the test material at a total dosage of 2250 mg/kg bodyweight, the ratio of normochromatic to polychromatic cells was comparable with the concurrent control value. At total dosages of 4500 and 9000 mg/kg bodyweight, the ratios were higher than the concurrent control value. Statistical analysis, using Kruskal-Wallis methods, showed these increases to be significantly different. The positive control compound, Mitomycin C, produced the expected large increase in the group mean polychromatic micronucleated cell count and in the normochromatic to polychromatic cell ratio. This group also produced a small increase in the group mean micronucleated normochromatic cell count.
Under the conditions of this study, it was concluded that the test material failed to show any evidence of mutagenic potential, when administered orally. However, at the higher dose levels evidence of toxicity, as shown by bone marrow depression, was observed.
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