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EC number: 827-162-2 | CAS number: 2218502-12-4
- 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:
- genetic toxicity in vivo, other
- Type of information:
- read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- key study
- Justification for type of information:
- See the report for the analogue approach justification in section 13 "Other reports"
Cross-referenceopen allclose all
- Reason / purpose for cross-reference:
- read-across source
Reference
- Endpoint:
- in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Study period:
- January from 02 to 26, 1990
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- test procedure in accordance with generally accepted scientific standards and described in sufficient detail
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
- Version / remarks:
- adopted May 26th, 1983
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.12 (Mutagenicity - In Vivo Mammalian Erythrocyte Micronucleus Test)
- GLP compliance:
- yes
- Type of assay:
- mammalian germ cell cytogenetic assay
- Species:
- mouse
- Strain:
- NMRI
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: BRL Tierfarm Füllinsdorf, CH- 4414 Füllinsdorf/Basel, Switzerland.
- Age at start of acclimatization: minimum 10 weeks.
- Weight at study initiation: approx. 30 g.
- Assigned to test groups randomly: yes.
- Fasting period before study: yes, approximately 18 hours before treatment with the test article. Animals could still have water ad libitum during the fasting period.
- Housing: single in a Makrolon Type I, with wire mesh top and granulated soft wood bedding.
- Diet: pelleted standard diet.
- Water: tap water, ad libitum.
- Acclimation period: minimum 5 days.
ENVIRONMENTAL CONDITIONS
- Temperature: 21 ± 3°C.
- Humidity: not regulated.
- Photoperiod: 12 hrs dark / 12 hrs artificial light (6.00 a.m - 6.00 p.m). - Route of administration:
- oral: gavage
- Vehicle:
- - Vehicle used: destilled water.
- Justification for choice of vehicle: chocen for its non-toxicity to the animals. - Details on exposure:
- PREPARATION OF DOSING SOLUTIONS
The test article was dissolved in distilled water and the animals received orally a single standard dose volume of 20 ml/kg b.w. - Frequency of treatment:
- Once at the start of the study.
- Dose / conc.:
- 5 000 mg/kg bw (total dose)
- Remarks:
- Three groups
- No. of animals per sex per dose:
- 6 males and 6 females per dose group.
- Control animals:
- yes, concurrent vehicle
- Positive control(s):
- Cyclophosphamide (CPA)
- Preparation: the substance was dissolved in physiological saline and the solution was prepared on the day of administration.
- Route of administration: orally.
- Dosing: single dose of 40 mg/kg b.w.
- Volume administered: 10 ml/kg b.w.
- Stability: at 20 °C only 1 % of CPA is hydrolysed per day in aqueous solution. - Tissues and cell types examined:
- Bone marrow cells.
- Details of tissue and slide preparation:
- TREATMENT AND SAMPLING TIMES: sampling of the bone marrow was done 24, 48 and 72 hours after treatment.
PREPARATION OF THE ANIMALS
The animals were sacrificed by cervical dislocation. The femora were removed, the epiphyses were cut off and the marrow was flushed out with fetal calf serum, using a 5 ml syringe. The cell suspension was centrifuged at 1,500 rpm for 5 minutes and
the supernatant was discarded.
DETAILS OF SLIDE PREPARATION
A small drop of the resuspended cell pellet was spread on a slide. The smear was air-dried and then stained with May-Grünwald/Giemsa. Cover slips were mounted with EUKITT. At least one slide was made from each bone marrow sample
ANALYSIS OF CELLS
Evaluation of the slides was performed using NIKON microscopes with 100x oil immersion objectives. 1000 polychromatic erythrocytes (PCE) were analysed per animal for micronuclei. To describe a cytotoxic effect the ratio between polychromatic and normochromatic erythrocytes was determined in the same sample and expressed in normochromatic erythrocytes per 1000 PCEs. The analysis was performed with coded slides. Five animals per sex and group were evaluated as described. The remaining animal of each test group was evaluated in case an animal had died in its test group spontaneously or due to gavage error.
CRITERIA FOR DOSE SELECTION
A preliminary study on acute toxicity was performed with the same strain and under identical conditions as in the mutagenicity study. 4 animals (2 males, 2 females) received orally a single dose of 5000 mg/kg b.w of the substance dissolved in aqua dest. The volume administered was 20 ml/kg b.w.
The maximum tolerated dose or the highest dose that can be formulated and administered reproducibly sould be selected. The volume to be administered should be compatible with physiological space available. The maximum tolerated dose level was determined to be the dose that caused toxic reactions without having major effects on survival within 72 hours. Higher dosing than 5000 mg/kg b.w. was not attainable as appropriate solutions could be obtained only up to 250 mg/ml and application volumes higher than 20 ml/kg b.w. were not justifiable for the animals used. - Evaluation criteria:
- A test article is classified as mutagenic if it induces either a statistically significant dose-related increase in the number of micronucleated polychromatic erythrocytes or a reproducible statistically significant positive response for at least one of the test points. A test article producing neither a statistically significant dose-related increase in the number of micronucleated polychromatic erythrocytes nor a statistically significant and reproducible positive response at anyone of the test points is considered non mutagenic in this system.
- Statistics:
- Statistical significance at the five per cent level (p < 0.05) was evaluated by means of the non-parametric Mann-Whitney test.
- Sex:
- male/female
- Genotoxicity:
- negative
- Toxicity:
- yes
- Remarks:
- slight toxic reactions
- Vehicle controls validity:
- valid
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Additional information on results:
- In comparison with the corresponding negative controls there was no substantial enhancement in the frequency of the detected micronuclei at any preparation interval after application of the test article. The mean values of micronuclei observed after treatment with the substance were in the same range as compared to the negative control groups.
POSITIVE CONTROL
40 mg/kg b.w. cyclophosphamide showed a distinct increase of induced micronuleus frequency.
PRE-EXPERIMENT FOR TOXICITY
All treated animals expressed slight toxic reactions such as reduction of spontaneous activity. The mean number of normochromatic erythrocytes was not substantially increased after treatment with the test article as compared to the mean values of NCEs of the corresponding negative controls, indicating that the substance had no cytotoxic properties. - Conclusions:
- The test article did not induce micronuclei in the bone marrow cells of the mouse.
- Executive summary:
The substance was assessed in the micronucleus assay for its potential to induce micronuclei in polychromatic erythrocytes (PCE) in the bone marrow of the mouse, according to the OECD Guideline 474 and EU Method B12. Six male and six female mouses were treated orally with a single dose of 5000 mg/kg b.w. This was the maximum attainable dose as estimated by the pre-experiment. Concurrent positive (use of cyclophosphamide) and negative (use of vehicle-distilled water) control groups run. After 24 h, 48 h and 72 hours the bone marrow cells of ten animals were collected for micronuclei analysis. 1000 polychromatic erythrocytes (PCE) per animal were scored for micronuclei.
In comparison with the corresponding negative controls there was no substantial enhancement in the frequency of the detected micronuclei at any preparation interval after application of the test article. The mean values of micronuclei observed after treatment with the substance were in the same range as compared to the negative control groups.
Conclusion
The test article did not induce micronuclei in the bone marrow cells of the mouse, under the test conditions.
The number of PCEs (Polychromatic Erythrocytes) with micronuclei and the ratio of PCE to NCE ( Normochromatic Erythrocyte) are given for each test group in the table below.
Summary of results.
Test group | dose (mg/kg bw) |
sampling time (h) |
PCEs with micronuclei |
range | PCE/NCE |
solvent | 0 | 24 | 0.09 % | 0-3 | 1000/935 |
test article | 5000 | 24 | 0.09 % | 0-3 | 1000/874 |
cyclophosphamide | 40 | 24 | 0.76 % | 3-11 | 1000/1119 |
solvent | 0 | 48 | 0.02 % | 0-2 | 1000/842 |
test article | 5000 | 48 | 0.04 % | 0-1 | 1000/1000 |
solvent | 0 | 72 | 0.07 % | 0-2 | 1000/892 |
test article | 5000 | 72 | 0.03 % | 0-2 | 1000/769 |
- Reason / purpose for cross-reference:
- read-across source
Reference
- Endpoint:
- in vivo mammalian cell study: DNA damage and/or repair
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Study period:
- From October 22 1990 to April 05, 1991
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- test procedure in accordance with generally accepted scientific standards and described in sufficient detail
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 486 (Unscheduled DNA Synthesis (UDS) Test with Mammalian Liver Cells in vivo)
- Version / remarks:
- The UDS test is an assay for the detection of chemically induced effects on DNA.
- GLP compliance:
- yes
- Type of assay:
- unscheduled DNA synthesis
- Species:
- rat
- Strain:
- Wistar
- Remarks:
- WU
- Details on species / strain selection:
- The rat is an animals used as suitable experimental animal in genotoxicity investigations (and physiological, pharmacological and toxicological studies) for many years. Many data are available from such investigations that could be helpful in the interpretattion of results and for the design and performance of the UDS test.
- Sex:
- male
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: SAVO-Ivanovas, med. Versuchstierzuchten GmbH.
- Weight at study initiation: appr. 200 g.
- Assigned to test groups randomly: yes.
- Fasting period before receiving test material: starved overnight (4 hours treatment) or appr. 6 hours (16 hours treatment).
- Housing: individually, in Makrolon Type I cages, with wire mesh top and granulated soft wood bedding.
- Diet: pelleted standard diet.
- Water: tap water, ad libitum.
- Acclimation period: minimum 5 days.
- Other: the animals underwent quarantine in the animals house of the laboratory for at least one week after their arrival. During this period the animals did not show signs of illness or altered behaviour.
ENVIRONMENTAL CONDITIONS
- Temperature: 21 ± 3 °C.
- Humidity: 30 - 70 %.
- Photoperiod: 12 hrs dark / 12 hrs artificial light (6.00 a.m - 6.00 p.m). - Route of administration:
- oral: unspecified
- Vehicle:
- - Vehicle: bedistilled water.
- Justification for choice of solvent/vehicle: it was chosen according to its relative nontoxicity for the animals. - Details on exposure:
- - Preparation of dose solution: the test article was formulated in aqua bidestilled, on the day of the experiment immediately before treatment.
- Volume administered: 10 ml/kg bw - Duration of treatment / exposure:
- 4 hours and 16 hours treatment.
- Frequency of treatment:
- Single standard dose.
- Dose / conc.:
- 1 000 mg/kg bw/day (nominal)
- Remarks:
- 4 - hours treatment period.
- Dose / conc.:
- 1 000 mg/kg bw/day (nominal)
- Remarks:
- 16-hours treatment period.
- Dose / conc.:
- 100 mg/kg bw/day (nominal)
- Remarks:
- 16-hours treatment period.
- No. of animals per sex per dose:
- 5 males per test group.
- Control animals:
- yes, concurrent vehicle
- Positive control(s):
- 2-acetylaminofluorene
- Preparation: dissolved in DMSO/polyethylene glycol (1+9). The solution was prepared on day of administration.
- Route and frequency of administration: orally, single.
- Dose: 100 mg/kg b.w.
- Volume administered: 10 ml/kg b.w. - Details of tissue and slide preparation:
- ISOLATION OF THE PRIMARY HEPATOCYTES
The animals were sacrificied by liver perfusion. After anesthetizing the rats with 1.5 ml/kg b.w. Hypnodil i.p. the liver was perfused through the vena portae with Hank's balanced salt solution (HBSS) supplemented with collagenase (0.05 % w/v) adjusted to pH 7.4 and maintained at 37 °C. The hepatocytes were isolated from the liver and washed twice with HBSS. The crude cell suspension was filtered through a 94 μm stainless steel mesh to yield a single cell suspension. The quality of the actual performed perfusion was determined by the tryptan blue dye exclusion method. The number of the isolated cells was also determined.
CULTURE CONDITIONS
The washed hepatocytes were centrifuged and transferred into Williams medium E (WME) supplemented with 2.38 mg/ml hepes, 100 units/ml penicillin, 0.10 mg/ml streptomycin, 0.29 mg/ml glutamin, 0.50 μg/ml insulin and 100 μl/ml fetal calf serum. The medium without the cells was adjusted to pH 7.6. At least 5 cultures were established for each animal. Aliquotes of 2.5 ml with freshly isolated hepatocytes in complete culture medium (1.0 x 10^5 cells/ml) were added to 35 mm six-well cluster dishes containing one gelatinized 25 mm round plastic coverslip per well. After an attachment period of appr. 1.5 h in a 95 % air / 5 % CO2 humidified incubator at 37 °C the culture medium was discarded. Then the cell layer was rinsed once with PBS to remove non-adherent cells.
OTHER
Three animals per group were evaluated for UDS. The two remaining animals per test group would be evaluated if an animal dies spontaneously or in case of technical problems concerning the isolation of hepatocytes.
DETERMINATION OF UDS
3HTdR (5 μCi/ml, specific activity 20 Ci/mol) in 2.0 ml culture medium (WME, 1 % FCS) was added to the cultures. After a labelling time of 4 hours the cells were washed twice with WME supplemented with 1 % FCS and 0.25 mM unlabelled thymidine. Cultures were incubated overnight using the same medium. The medium was then replaced by a hypotonic solution of 1 % sodium citrate for 10 minutes to swell the nuclei for better grain quantification. The cells on the coverslips were then fixed by three changes of methanol:acetic acid (3+1 v/v) for 15 mins each, rinsed with 96 % ethanol and air dried. Two of the cultures were used for determination of cytotoxicity and attachment efficiency with the neutral red assay whereas three cultures were used for the UDS assay.
ANALYSIS-AUTORADIOGRAPHIC PROCESSING
The cover slips were mounted the side carrying the cells up on a glass slides and coated with ILFORD K-2 photographic emulsion in the dark. The coated slides were stored in light-proof boxes in the presence of a drying agent for 12-14 days at 4 °C. The photographic emulsion was then developed with KODAK D-19 at room temperature, fixed in TETENAL and stained with 0.4 % aceto orcein.
QUANTIFICATION OF UDS
Evaluation was performed microscopically on coded slided using NIKON microscopes with 100 x oil immersion objectives. The number of siver grains above the nucleus was counted automatically using the ARTEK 880 counter. The number of grain counts of one nuclear-sized cytoplasm adjacent to the nucleus was estimated. At least two slides per animal and 50 cells per slide were evaluated. Heavily labelled S-phase cells were excluded from counting.
ASSESSMENT OF ATTACHMENT OF CELLS
Two cultures of each animals were examined by using the neutral red absorption assay. After an attachement period of 1.5 hours the cells were washed and refed with medium containing neutral red (50 μg/ml). After an incubation period of 3 hours the cultures were rinsed and the incorporated dye eluted with 50 % ethanol supplemented with 1 % acetic acid.
CRITERIA FOR DOSE SELECTION
The highest recommended dose level to be used in the assay is 1000 mg/kg b.w. The toxicity data of the test article available indicated that 1000 mg/kg b.w. is the maximum tolerated dose causing toxic reactions without having major effects on the survival of the animals, therefore no pre-experiment was performed. - Evaluation criteria:
- A test article is classified as positive if it induces either a statistically significant dose-related increase in radiolabel incorporation expressed as grains per nucleus or a reproducible and statistically significant positive response for at least one of the test points. A test article producing neither a statistically significant dose related increase in radiolabel incorporation expressed as grain per nucleus nor a statistically significant and reproducible positive response at any one of the test points is considered non-effective in this system.
- Statistics:
- Statistical significance can be evaluated by means of the non-parametric Mann-Whitney test. A statistical evaluation of the results of biometry was not necessary to perform as the number of nuclear an net grain counts of the groups treated with the test article were in the range of the corresponding controls.
- Sex:
- male
- Genotoxicity:
- negative
- Toxicity:
- no effects
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Additional information on results:
- No toxic reactions of the animals occurred at any of the tratement periods or dose groups. In addition, neither the viability nor the in vitro attachment of the hepatocytes was dramatically affected due to the in vivo pre-treatment with the test article.
The interindividual variations obtained for the numbers of isolated hepatocytes as well as for the attachment-efficiency (NR-assay) are in the range of the testing laboratory historical laboratory control. In case of hepatotoxicity the NR-vales expected would be approximately zero.
No dose level of the test article revealed UDS induction in the hepatocytes of the trated animals as compared to the current negative controls. Neither the nuclear grains nor the resulting net grains were enhanced due to the in vivo treatment of the animals with the test article for 4 hours or 16 hours, respectively.
POSITIVE CONTROL
An appropriate reference mutagen (2-AAF, 100 mg/kg bw) was used as positive control. In vivo treatment with 2-AAF revealed disctinct increases in the number of nuclear and net grain counts.
PRE-EXPERIMENT
The highest recommended dose level to be used in the assay resulted to be 1000 mg/kg bw. since the toxicity data of the test article given by the sponsor indicated that 1000 mg/kg bw should have no makor effects on the survival of the animals a pre-experiment was not necessary to perform. - Conclusions:
- The test article did not induce DNA-damage leading to repair synthesis in the hepatocytes of the treated rats.
- Executive summary:
The substance was assessed in the in vivo UDS assay for its potential to induce DNA repair (UDS) in the hepatocytes of rats. The substance was orally administered the substance in concentrations of 1000 mg/kg b.w for the 4 -hours treatment period and in concentrations of 100 and 1000 mg/kg b.w for the 16 -hours treatment period. Bedistilled water was used as vehicle and served as the negative control while an appropriate reference mutagen (2 -AAF) was used as the positive control. Five male rats were used in each dose group. After the treatment period the animals were narcotized and sacrificied by liver perfusion. Primary hepatocyte cultures were established and exposed to 3HTdR which is incorporated if UDS occurs. For each dose level hepatpcytes from three treated animals were assessed for occurence of UDS.
No toxic reactions of the animals occured at any of the treatment periods or dose group. The viability and the in vitro attachment of the hepatocytes was not affected due to the in vivo pre-treatment with the test article. The interindividual varriations obtained for the numbers of isolated hepatocytes as well as for the attachment efficiency were in the range of the historical laboratory control. No dose level of the test article revealed UDS induction in the hepatocytes of the treated animals as compared to the concurrent negative controls. Neither the nuclear grains nor the resulting net grains were enhanced due to the in vivo treatment ofthe animals with the test article for 4 or 16 hours.
Conclusion
The test article did not induce DNA-damage leading to repair synthesis in the hepatocytes of the treated rats.
The viability and attachment of the hepatocytes.
Viability and attachment of hepatocytes.
Dose (mg/kg b.w.) |
Tretament period |
animal no. | Viability * | Number of isolated cells (x 106) |
Attachement (O.D 540 mm)** |
1000 | 4h | 1 | 71 | 102 | 0.367 |
4h | 2 | 74 | 367 | 0.495 | |
4h | 4 | 65 | 152 | 1.030 | |
Vehicle (aqua bidest.) |
16h | 6 | 81 | 392 | 0.428 |
16h | 7 | 67 | 326 | 0.321 | |
16h | 8 | 81 | 321 | 0.554 | |
100 | 16h | 11 | 82 | 270 | 0.226 |
16h | 12 | 76 | 629 | 0.198 | |
16h | 13 | 73 | 424 | 0.536 | |
1000 | 16h | 18 | 69# | 304 | 0.270 |
16h | 19 | 79# | 373 | 0.355 | |
16h | 20 | 72# | 272 | 0.366 | |
100 (2AAF) | 16h | 21 | 81 | 376 | 0.410 |
16h | 22 | 77 | 343 | 0.449 | |
16h | 23 | 71 | 169 | 0.438 |
* = viability determined by means of trypan blue dye exclusion assay.
** = mean value of two independent cultures.
# = some of the dead cells elicited black pigmentation indicating an accumulation of the test article in hepatocytes.
The counts of grains per nucleus, grains per cytoplasm area and the net grains per nucleus are summarised for each animal.
Summary of results for individual animals.
Treatment | Animal no. | Grains per nucleus | Grains per cytoplasm area | Net grains per nucleus | |||
Mean * | ± SD | Mean * | ± SD | Mean * | ± SD | ||
Solvent control (a.dest/16h) |
1 | 4.95 | 3.42 | 7.01 | 3.10 | -2.06 | 2.41 |
2 | 3.57 | 2.18 | 5.69 | 2.28 | -2.12 | 2.61 | |
3 | 3.79 | 2.32 | 7.86 | 3.27 | -4.07 | 3.48 | |
Positive control - (2AAF 100 mg/kg /16h) |
1 | 37.01 | 19.15 | 9.68 | 4.94 | 27.33 | 19.10 |
2 | 22.44 # | 9.27 | 11.50 | 4.61 | 10.94 | 8.74 | |
3 | 17.93 | 8.10 | 12.74 | 4.56 | 5.19 | 8.76 | |
Dose level 1 (100 mg/kg / 16h) |
1 | 5.88 | 3.50 | 9.15 | 4.13 | -3.27 | 3.66 |
2 | 4.93 | 2.59 | 7.27 | 2.19 | -2.34 | 2.89 | |
3 | 6.35 | 3.15 | 7.51 | 3.26 | -1.16 | 3.45 | |
Dose level 2 (1000 mg/kg / 4h) |
1 | 4.10 | 2.27 | 6.18 | 2.32 | -2.08 | 2.51 |
2 | 3.92 | 2.01 | 6.59 | 2.63 | -2.67 | 2.22 | |
3 | 4.48 | 2.26 | 5.73 | 2.47 | -1.25 | 2.54 | |
Dose level 3 (1000 mg/kg / 16h) |
1 | 4.92 | 2.66 | 7.40 | 3.00 | -2.48 | 2.53 |
2 | 4.08 | 2.40 | 6.49 | 2.88 | -2.41 | 2.73 | |
3 | 8.80 | 6.00 | 13.69 | 8.27 | -4.89 | 5.88 |
* = mean of 100 cells
# = mean of 50 cells; due to technical reasons only one slide was scorable.
The counts of grains per nucleus, grains per cytoplasm area and the net grains per nucleus are summarised for each dose group.
Summary of results for dose groups.
Treatment | Dose level | Grains per nucleus | Grains per cytoplasm area | Net grains per nucleus | |||
Mean * | ± SD | Mean * | ± SD | Mean * | ± SD | ||
Solvent control | a.dest/16h | 4.10 | 2.75 | 6.85 | 3.04 | -2.75 | 3.01 |
Positive control - 2AAF |
100 mg/kg /16h | 26.46 # | 16.31 | 11.27 | 4.90 | 15.20 | 17.13 |
Dose level 1 |
100 mg/kg / 16h | 5.72 | 3.15 | 7.98 | 3.38 | -2.26 | 3.45 |
Dose level 2 |
1000 mg/kg / 4h | 4.17 | 2.19 | 6.17 | 2.50 | -2.00 | 2.49 |
Dose level 3 |
1000 mg/kg / 16h | 5.93 | 4.52 | 9.19 | 6.22 | -3.26 | 4.17 |
* = mean of 3 animals, 100 cells each.
# = mean of 3 animals, two animals 100 cells each, one animal 50 cells.
Data source
Materials and methods
Test material
- Reference substance name:
- [x·sodium, y·lithium, x+y=3] 4-amino-3[[4-[[4-[(2-amino-4-hydroxyphenyl)diazenyl]phenyl]amino]-3-sulfonato phenyl]diazenyl]-5-hydroxy-6-(phenydiazenyl)naphthalene-2,7-disulfonat, mixture of isomers
- EC Number:
- 827-162-2
- Cas Number:
- 2218502-12-4
- Molecular formula:
- C34H24N9O11S3.NaxLiy
- IUPAC Name:
- [x·sodium, y·lithium, x+y=3] 4-amino-3[[4-[[4-[(2-amino-4-hydroxyphenyl)diazenyl]phenyl]amino]-3-sulfonato phenyl]diazenyl]-5-hydroxy-6-(phenydiazenyl)naphthalene-2,7-disulfonat, mixture of isomers
- Test material form:
- solid
1
Results and discussion
Test resultsopen allclose all
- Sex:
- male/female
- Genotoxicity:
- negative
- Toxicity:
- yes
- Remarks:
- slight toxic reactions
- Sex:
- male
- Genotoxicity:
- negative
- Toxicity:
- no effects
- Remarks on result:
- other: unscheduled DNA synthesis
Applicant's summary and conclusion
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Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.