Registration Dossier
Registration Dossier
Data platform availability banner - registered substances factsheets
Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.
The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.
Diss Factsheets
Use of this information is subject to copyright laws and may require the permission of the owner of the information, as described in the ECHA Legal Notice.
EC number: 605-399-0 | CAS number: 165252-70-0
- 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
Endpoint summary
Administrative data
Key value for chemical safety assessment
Genetic toxicity in vitro
Description of key information
Four in vitro genotoxicity studies were negative for genotoxicity endpoints with and without metabolic activation. Positive control substances in these studies induced positive effects.
Link to relevant study records
- Endpoint:
- in vitro gene mutation study in mammalian cells
- Remarks:
- Type of genotoxicity: gene mutation
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 27/09/2001 - 08/02/2002
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: GLP, Guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 476 (In Vitro Mammalian Cell Gene Mutation Test)
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EPA OPPTS 870.5300 - In vitro Mammalian Cell Gene Mutation Test
- Deviations:
- no
- GLP compliance:
- yes
- Type of assay:
- mammalian cell gene mutation assay
- Species / strain / cell type:
- mouse lymphoma L5178Y cells
- Details on mammalian cell type (if applicable):
- Mycoplasma-free tk+/-
- Additional strain / cell type characteristics:
- not applicable
- Metabolic activation:
- with and without
- Metabolic activation system:
- S9
- Test concentrations with justification for top dose:
- Experiment 1 and 2:
0 (saline), 400, 800, 1200, 1600 and 2022 µg/mL
Both with and without metabolic activation.
See Table 1. - Vehicle / solvent:
- - Vehicle(s)/solvent(s) used: saline
- Untreated negative controls:
- yes
- Remarks:
- saline diluted 10-fold in the treatment medium
- Negative solvent / vehicle controls:
- yes
- Remarks:
- as above
- True negative controls:
- not specified
- Positive controls:
- yes
- Remarks:
- 4-nitroquinoline-1-oxide (without S9) benz(a)pyrene (with S9)
- Positive control substance:
- other: as above
- Details on test system and experimental conditions:
- Dinotefuran was dissolved in saline, under subdued lighting conditions, immediately prior to assay to give the required concentration. Stock solutions were filter-sterilised and further dilutions were made using saline. The dinotefuran solutions were protected from light and used within 2 hours of preparation. No change in osmolality occurred at the highest concentration tested.
- Evaluation criteria:
- The test article was considered to be mutagenic if all the following criteria were met:
• the assay was valid
• the mutant frequency at one or more doses was significantly greater than that of the negative control (p<0.05)
• there was a significant dose-relationship as indicated by the linear trend analysis (p<0.05). - Statistics:
- Statistical significance of mutant frequencies (total wells with clones) was carried out according to the UKEMS guidelines. Thus the control log mutant frequency (LMF) was compared with the LMF from each treatment concentration based on Dunnett's test for multiple comparisons, and secondly the data was checked for a linear trend in mutant frequency with treatment concentration using weighted regression. The test for linear trend is one-tailed, therefore negative trend was not considered significant. These tests required the calculation of the heterogeneity factore to obtain a modified estimate of variance.
- Key result
- Species / strain:
- mouse lymphoma L5178Y cells
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Additional information on results:
- Genotoxicity without metabolic activation:
Experiment 1:
No: relative survival at 2022µg/mL was 102.68 without activation.
Experiment 2:
No: relative survival at 2022µg/mL was 76.16 without metabolic activation.
See Table 3
Genotoxicity with metabolic activation:
Experiment 1:
No: relative survival at 2022µg/mL was 118.06% with metabolic activation.
Experiment 2:
No: relative survival at 2022µg/mL was 100.28% with metabolic activation.
See Table 3
Cytotoxicity:
No: no statistically significant increases in mutation frequency occurred at any dose level in the absence or presence of metabolic activation in either independent experiment. The proportion of small colony mutants for the solvent controls without and with metabolic activation ranged from 38 to 41% in experiment 1 and from 52 to 55% in experiment 2. Marked increases in the numbers of both small and large colony mutants occurred in response to both positive control materials.
Analysis of dinotefuran formulations demonstrated achieved concentrations within 100 ± 10% of nominal concentrations. The assay acceptance criteria were met and the study is considered valid.
See Table 2. - Remarks on result:
- other: all strains/cell types tested
- Conclusions:
- Interpretation of results :negative
In both experiments relative survival at 2022µg/mL was at least 76.16 % with and without metabolic activation. No statistically significant increases in mutation frequency occurred at any dose level in the absence or presence of metabolic activation in either independent experiment. Marked increases in the numbers of both small and large colony mutants occurred in response to both positive control materials.
It was concluded that dinotefuran technical and/or metabolites does not induce mutation at the tk locus of L5178Y mouse lymphoma cells at concentrations up to 10mM, and is considered not mutagenic in this test system. - Endpoint:
- in vitro DNA damage and/or repair study
- Remarks:
- Type of genotoxicity: DNA damage and/or repair
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 12/06/1996 - 10/07/1996
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: GLP, Guideline study
- Qualifier:
- according to guideline
- Guideline:
- other: JMAFF 59 NohSan no. 4200 (1985)
- Deviations:
- no
- GLP compliance:
- yes
- Type of assay:
- other: Unscheduled DNA synthesis in mammalian cells in vitro
- Species / strain / cell type:
- bacteria, other: Bacillus subtilis: M45 Rec- and H17 Rec+
- Details on mammalian cell type (if applicable):
- Not applicable
- Additional strain / cell type characteristics:
- not applicable
- Metabolic activation:
- with and without
- Metabolic activation system:
- S9
- Test concentrations with justification for top dose:
- 0, 62.5, 250, 1000, 4000 and 16000µg/disc dinotefuran with and without metabolic activation.
- Vehicle / solvent:
- DMSO
- Untreated negative controls:
- yes
- Remarks:
- Kanamycin sulfate (without S9); Streptomycin sulfate (with S9)
- Negative solvent / vehicle controls:
- yes
- Remarks:
- As above
- True negative controls:
- not specified
- Positive controls:
- yes
- Positive control substance:
- other: Mitomycin C (without S9); Trp-P-1 (with S9)
- Details on test system and experimental conditions:
- An 8mm paper disc (2 discs/dose) was treated with 20 µL solvent or test substance solution and placed on the spore-innoculated agar without metabolic activation. With metabolic activation, an 8mm paper disc (2 discs/dose level) was treated with 20 µL coenzyme solution and 20 µL solvent or test substance solution and placed on the spore-innoculated agar containing S9 mix.
- Evaluation criteria:
- Results are judged positive when the difference in diameter of growth inhibition zones between strains H17 and M45 is more than 5mm, and negative if less than 2.5mm. Where differences in inhibition zone diameter are between 2.5 and 5.0mm the results are evaluated by consideration of dose-response and reproducibility.
- Statistics:
- Not reported
- Key result
- Species / strain:
- other: Bacillus subtilis: M45 Rec- and H17 Rec+
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Additional information on results:
- Preliminary study with and without metabolic activation:
No growth inhibition occurred at any dose level in either strain with or without metabolic activation (Table 1).
Based on these results, dinotefuran in DMSO solvent was tested in H17 and M45 (approx. 2 x 107cells/mL) at concentrations of 0 (DMSO only), 1000, 2000, 4000, 8000 and 16000µg/disc with and without S9 metabolic activation.
Main study with and without metabolic activation:
DMSO solvent alone and all doses of DINOTEFURAN employed, up to and including the highest dose, 16000µg/disc, produced no growth inhibition of either strain of B. subtilis either with or without S9 metabolic activation (Table 2). The negative control substances, KM without S9 and SM with S9 produced differences in the inhibition zone diameters of 1.7 and 1.1mm, respectively, whereas the positive control substances, MMC without S9 and Trp-P-1 with S9, produced differences of 7.2 and 6.0mm, respectively. - Remarks on result:
- other: all strains/cell types tested
- Remarks:
- Migrated from field 'Test system'.
- Conclusions:
- Interpretation of results :
negative
It was concluded that under the conditions of the study, dinotefuran and/or metabolites does not exhibit DNA-damaging activity in B. subtilis under the conditions of the study at doses up to 16000µg/disc - Endpoint:
- in vitro cytogenicity / chromosome aberration study in mammalian cells
- Remarks:
- Type of genotoxicity: chromosome aberration
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 14/06/1996 - 15/10/1996
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: GLP, Guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 473 (In Vitro Mammalian Chromosome Aberration Test)
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.10 (Mutagenicity - In Vitro Mammalian Chromosome Aberration Test)
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EPA OPPTS 870.5375 - In vitro Mammalian Chromosome Aberration Test
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- other: JMAFF 59 NohSan no. 4200 (1985)
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- other: JMHW, Part 1 (1990); Japan Ministry of Labor, Appendix 1, Notification nos. 143 (1987)
- Deviations:
- no
- GLP compliance:
- yes
- Type of assay:
- in vitro mammalian chromosome aberration test
- Species / strain / cell type:
- other: Chinese hamster lung (CHL/IU)
- Details on mammalian cell type (if applicable):
- Mycoplasma-free
- Additional strain / cell type characteristics:
- not applicable
- Metabolic activation:
- with and without
- Metabolic activation system:
- S9
- Test concentrations with justification for top dose:
- 2000 µg/mL
- Vehicle / solvent:
- - Vehicle(s)/solvent(s) used: saline for direct method and S9 method.
- Untreated negative controls:
- yes
- Remarks:
- saline
- Negative solvent / vehicle controls:
- yes
- Remarks:
- as above
- True negative controls:
- not specified
- Positive controls:
- yes
- Remarks:
- Mitomycin C (without S9) Cyclophosphamide (with S9)
- Positive control substance:
- other: as above
- Details on test system and experimental conditions:
- Dinotefuran was dissolved in saline. For preparation of the original solution and serial dilution of dinotefuran, the solution in 11-fold of each final concentration was prepared. In the cell growth inhibition test, 101.6 mg of dinotefuran dissolved in 4.6 mL of saline (final concentration is 2000 mg/mL which was equal to 10 mM) both with and without S9. In the main study, 146.3 mg of of dinotefuran dissolved in 6.65 mL of saline without S9 and 86.8 mg of dinotefuran dissolved in 3.9 mL of saline with S9 (final concentration is 2000 mg/mL which was equal to 10 mM).
Mitomycin C (MMC - 0.03µg/mL) was the positive control material for 24 and 48 hour exposures without activation and cyclophosphamide (CP - 12µg/mL) for 6 hour exposures with and without activation. - Evaluation criteria:
- The test substance was to be considered as, negative (-) if the total incidence of structural aberrant cells (including gaps)or numberical aberration cells obtained from 2 dishes (total 200 metaphase) was less than 5%, suspected positive (±) if it was more than 5% and less than 10%, and positive (+) if it was more than 10%.
- Statistics:
- Not conducted
- Species / strain:
- other: Chinese hamster lung (CHL/IU)
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Additional information on results:
- Genotoxicity without metabolic activation: No.
Structural or numerical aberrations were not induced after 6 hours exposure to dinotefuran either in the absence of metabolic activation. Cell survival was unaffected at all dose levels after 6 hours exposure.
MMC in the absence of metabolic activation produced marked increases in the incidences of structural aberrations, notably chromatid breaks and exchanges.
See Table 1 and Table 2.
Genotoxicity with metabolic activation:
No. Structural or numerical aberrations were not induced after 6 hours exposure to dinotefuran either in the presence of metabolic activation. Cell survival was unaffected at all dose levels after 6 hours exposure.
Cyclophosphamide in the presence of metabolic activation produced marked increases in the incidences of structural aberrations, notably chromatid breaks and exchanges.
See Table 1 and Table 2.
Cytotoxicity:
No. In the main study, structural or numerical aberrations were not induced by dinotefuran either after 24 or 48 hours exposure to dose levels up to 2000 µg/mL. However, slight growth inhibition occurred at 2000 µg/mL, 28% after 24 hours and 38% after 48 hours exposure.
See Table 1 and Table 2. - Remarks on result:
- other: all strains/cell types tested
- Conclusions:
- Interpretation of results: negative
In the main study, structural or numerical aberrations were not induced by dinotefuran either after 24 or 48 hours exposure to dose levels up to 2000µg/mL. However, slight growth inhibition occurred at 2000µg/mL, 28% after 24 hours and 38% after 48 hours exposure. Similarly, structural or numerical aberrations were not induced after 6 hours exposure to dinotefuran either in the presence or absence of metabolic activation. Cell survival was unaffected at all dose levels after 6 hours exposure.
It was concluded that under the conditions of this study dinotefuran and/or metabolites does not induce structural or numerical chromosomal aberrations in Chinese hamster lung cells at dose levels up to and including 2000µg/mL (equivalent to 10 mM). - Endpoint:
- in vitro gene mutation study in bacteria
- Remarks:
- Type of genotoxicity: gene mutation
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 12/07/1996 - 02/10/1996
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: GLP, Guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 471 (Bacterial Reverse Mutation Assay)
- Version / remarks:
- 1994
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 472 (Genetic Toxicology: Escherichia coli, Reverse Mutation Assay)
- Version / remarks:
- 1994
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- other: EU Method B.14
- Deviations:
- no
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- EPA OPPTS 870.5100 - Bacterial Reverse Mutation Test (August 1998)
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EPA OPPTS 870.5265 (The Salmonella typhimurium Bacterial Reverse Mutation Test)
- Deviations:
- no
- Principles of method if other than guideline:
- Deviations: Yes, in addition to the required 4 S. typhimurium strains, one strain of E. coli was also included since this is a requirement for Japanese authorities. The deviation does not affect the validity of the study.
- GLP compliance:
- yes
- Type of assay:
- bacterial reverse mutation assay
- Species / strain / cell type:
- S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
- Details on mammalian cell type (if applicable):
- S. typhimurium: histidine-auxotrophic strains
- Additional strain / cell type characteristics:
- not applicable
- Species / strain / cell type:
- E. coli WP2 uvr A
- Details on mammalian cell type (if applicable):
- E. coli: tryptophan-auxotrophic strain
- Additional strain / cell type characteristics:
- not applicable
- Metabolic activation:
- with and without
- Metabolic activation system:
- S9
- Test concentrations with justification for top dose:
- Pre-incubation: 0 (solvent control), 313, 625, 1250, 2500 and 5000g/plate
Main assay: 0 (solvent control), 1.2, 4.9, 20, 78, 313, 1250 and 5000 µg/plate dinotefuran and the relevant positive controls both with and without metabolic activation. - Vehicle / solvent:
- - Vehicle(s)/solvent(s) used: DMSO
- Untreated negative controls:
- yes
- Remarks:
- DMSO
- Negative solvent / vehicle controls:
- yes
- Remarks:
- Same as negative control
- True negative controls:
- not specified
- Positive controls:
- yes
- Remarks:
- Without S9: 2-(2-furyl)-3-(5-nitro-2-furyl)-acrylamide (AF-2), 9-Aminoacridine and Sodium azide With S9: 2-Aminoanthracene. See Table 1.
- Positive control substance:
- other: See above positive controls
- Details on test system and experimental conditions:
- METHOD OF APPLICATION: dissolved in medium
DURATION
- Preincubation period: 20 minutes at 37°C - Evaluation criteria:
- Evaluated for colonies by an automatic counter and for precipitation and growth inhibition of the background lawn by microscopy.
Dinotefuran was considered positive if at least one dose produced a mean reversion frequency in a given strains that was at least two times greater than that of the corresponding negative control plates, and the response was dose-dependent and reproducibility were observed. - Statistics:
- Not reported
- Key result
- Species / strain:
- S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity
- Remarks:
- Dinotefuran did not influence the growth of any strain tested at dose levels of up to 5000µg/plate.
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Additional information on results:
- Genotoxicity without metabolic activation:
Dose range-finding study:
No, normal background growth occurred in all strains without metabolic activation. None of the strains showed an appreciable increase in the reversion frequency at any of the dose levels tested.
Main study:
No appreciable increase in the reversion frequencies occurred in any strain tested in the dose range 313 - 5000µg/plate.
See Table 2 and Table 3.
Genotoxicity with metabolic activation:
Dose range-finding study:
No, normal background growth occurred in all strains with metabolic activation. None of the strains showed an appreciable increase in the reversion frequency at any of the dose levels tested.
Main study:
No appreciable increase in the reversion frequencies occurred in any strain tested in the dose range 313 - 5000µg/plate.
See Table 2 and Table 3.
Cytotoxicity:
Dose range-finding study:
No appreciable cytotoxicity was observed at up to 5000µg/plate, the highest concentration evaluated.
Main study:
Dinotefuran did not influence the growth of any strain tested at dose levels of up to 5000µg/plate. - Remarks on result:
- other: all strains/cell types tested
- Remarks:
- Migrated from field 'Test system'.
- Conclusions:
- Interpretation of results:
negative
No appreciable cytotoxicity was observed in all strains, with and without metabolic activation at up to 5000µg/plate, the highest concentration evaluated. None of the strains showed an appreciable increase in the reversion frequency at any of the dose levels tested.
In the main assay, dinotefuran did not influence the growth of any strain tested at dose levels of up to 5000µg/plate. No appreciable increase in the reversion frequencies occurred in any strain tested in the dose range 313 - 5000µg/plate. In contrast, the positive control substances produced marked increases in the number of revertant colonies in all strains tested.
Under the conditions of this study, dinotefuran and/or metabolites does not induce gene mutations in the strains of S. typhimurium and E. coli used in the study at doses up to 5000µg/plate.
Referenceopen allclose all
Table 1: Dose levels in two preliminary studies and main assay
Study |
Dose levels ofdinotefuranused (µg/mL) |
||||||||
Cytotoxicity ± S9, 3h |
62.5 |
125 |
250 |
500 |
1000 |
2022 |
|
|
|
Cytotoxicity-S9, 24h |
7.81 |
15.63 |
31.25 |
62.5 |
125 |
250 |
500 |
1000 |
2022 |
Experiment 1 in main assay ± S9, 3h |
400 |
800 |
1200 |
1600 |
2022 |
|
|
|
|
Experiment 2 inmain assay-S9, 24h; +S9, 3h |
400 |
800 |
1200 |
1600 |
2022 |
|
|
|
|
Table 2: Summary of relative survival in the cytotoxicity range-finding study
Compound |
Dose level |
Relative survival (%): |
||
|
(µg/mL) |
3-hour exposure (-S9) |
3-hour exposure (+S9) |
24-hour exposure (-S9) |
DMSO |
0 |
= 100 |
= 100 |
= 100 |
Dinotefuran |
7.81 |
- |
- |
150.17 |
|
15.63 |
- |
- |
122.63 |
|
31.25 |
- |
- |
116.22 |
|
62.5 |
47.60 |
58.55 |
101.05 |
|
125 |
103.20 |
72.40 |
111.20 |
|
250 |
97.81 |
82.08 |
109.29 |
|
500 |
93.43 |
94.94 |
133.42 |
|
1000 |
132.27 |
66.25 |
97.63 |
|
2022 |
87.00 |
70.00 |
109.58 |
- not assayed
Table 3: Relative survival and mutant frequency – main experiments
Concn. |
Experiment 1 |
|||||
(mg/mL) |
3-hr exposure (-S9) |
3-hr exposure (+S9) |
||||
|
%RSa |
RTGb |
MFc |
%RSa |
RTGb |
MFc |
0 |
= 100 |
1.00 |
67.92 |
= 100 |
1.00 |
81.65 |
400 |
100.42 |
0.87 |
70.05 |
103.94 |
1.11 |
80.01 |
800 |
98.63 |
1.06 |
70.70 |
116.66 |
1.18 |
54.15 |
1200 |
112.29 |
1.12 |
60.56 |
105.90 |
1.12 |
64.32 |
1600 |
103.08 |
0.99 |
85.24 |
105.69 |
1.14 |
68.82 |
2022 |
102.68 |
0.91 |
81.84 |
118.06 |
1.03 |
61.05 |
NQO 0.05 0.01 0.02 0.04 |
102.70 94.13 - - |
0.85 0.54 - - |
149.24 337.64 - - |
- - - - |
- - - - |
- - - - |
BP 2.0 3.0 |
- - |
- - |
- - |
91.27 81.81 |
0.76 0.69 |
365.23 525.10 |
|
Experiment 2 |
|||||
|
24-hr exposure (-S9) |
3-hr exposure (+S9) |
||||
|
%RSa |
RTGb |
MFc |
%RSa |
RTGb |
MFc |
0 |
= 100 |
1.00 |
72.69 |
= 100 |
|
101.87 |
400 |
96.10 |
1.04 |
61.05 |
105.89 |
|
78.81 |
800 |
88.13 |
0.99 |
62.01 |
112.71 |
|
82.82 |
1200 |
83.95 |
1.09 |
85.11 |
116.11 |
|
129.05 |
1600 |
107.55 |
1.01 |
56.23 |
101.87 |
|
105.00 |
2022 |
76.16 |
0.94 |
82.33 |
100.28 |
|
107.68 |
NQO 0.05 0.01 0.02 0.04 |
- - 61.06 55.07 |
- - 0.84 0.92 |
- - 194.58 196.02 |
- - - - |
- - - - |
- - - - |
BP 2.0 3.0 |
- - |
- - |
- - |
102.04 62.54 |
0.58 0.41 |
423.87 606.07 |
a% relative survival adjusted by post-treatment cell count;
brelative total growth;
c5-TFT resistant mutants/106viable cells 2 days after treatment;
- not assayed
Table 1:Summary of growth inhibition for the dose range-finding study
Compound |
Dose level |
± S9 |
Growth inhibition zone (mm): |
||
|
(µg/disc) |
|
M45 (Rec-) |
H17 (Rec+) |
Difference (M45 –H17) |
DMSO |
0 |
- |
0 |
0 |
0 |
Dinotefuran |
1000 |
- |
0 |
0 |
0 |
|
2000 |
- |
0 |
0 |
0 |
|
4000 |
- |
0 |
0 |
0 |
|
8000 |
- |
0 |
0 |
0 |
|
16000 |
- |
0 |
0 |
0 |
KM |
10 |
- |
10.0 |
8.4 |
1.6 |
MMC |
0.01 |
- |
6.9 |
0 |
6.9 |
DMSO |
0 |
+ |
0 |
0 |
0 |
Dinotefuran |
1000 |
+ |
0 |
0 |
0 |
|
2000 |
+ |
0 |
0 |
0 |
|
4000 |
+ |
0 |
0 |
0 |
|
8000 |
+ |
0 |
0 |
0 |
|
16000 |
+ |
0 |
0 |
0 |
SM |
100 |
+ |
3.3 |
2.7 |
0.6 |
Trp-P-1 |
3 |
+ |
5.6 |
0 |
5.6 |
Table 2:Summary of growth inhibition for the main assay
Compound |
Dose level |
± S9 |
Growth inhibition zone (mm): |
||
|
(µg/disc) |
|
M45 (Rec-) |
H17 (Rec+) |
Difference (M45 – H17) |
DMSO |
0 |
- |
0 |
0 |
0 |
Dinotefuran |
1000 |
- |
0 |
0 |
0 |
|
2000 |
- |
0 |
0 |
0 |
|
4000 |
- |
0 |
0 |
0 |
|
8000 |
- |
0 |
0 |
0 |
|
16000 |
- |
0 |
0 |
0 |
KM |
10 |
- |
10.5 |
8.8 |
1.7 |
MMC |
0.01 |
- |
7.2 |
0 |
7.2 |
DMSO |
0 |
+ |
0 |
0 |
0 |
Dinotefuran |
1000 |
+ |
0 |
0 |
0 |
|
2000 |
+ |
0 |
0 |
0 |
|
4000 |
+ |
0 |
0 |
0 |
|
8000 |
+ |
0 |
0 |
0 |
|
16000 |
+ |
0 |
0 |
0 |
SM |
100 |
+ |
4.0 |
2.9 |
1.1 |
Trp-P-1 |
3 |
+ |
6.0 |
0 |
6.0 |
Table 1: Cell growth rate (%) relative to solvent control
Dose level |
Preliminary study exposed for: |
Main study exposed for: |
||||
(µg/mL) |
48hr (-S9) |
6hr (+S9) |
24hr (-S9) |
48hr (-S9) |
6hr (+S9) |
6hr (-S9) |
0 |
=100 |
=100 |
=100 |
=100 |
=100 |
=100 |
7.81 |
99 |
100 |
- |
- |
- |
- |
15.6 |
88 |
93 |
- |
- |
- |
- |
31.3 |
96 |
102 |
- |
- |
- |
- |
62.5 |
93 |
88 |
- |
- |
- |
- |
125 |
92 |
85 |
- |
- |
- |
- |
250 |
92 |
85 |
- |
- |
- |
- |
500 |
88 |
90 |
85 |
93 |
100 |
103 |
1000 |
82 |
88 |
84 |
95 |
99 |
104 |
2000 |
65 |
100 |
72 |
62 |
104 |
106 |
MMC 0.03 CP 12.0 |
- - |
- - |
70 - |
74 - |
- 86 |
- 99 |
Table 2: Summary of results from the main assay
Compound |
Dose |
Cell survival |
No. cells |
No. cells with structural aberrations: |
Total less |
Polyploidy |
|||||
|
(µg/mL) |
(%) |
|
gap |
ctb |
cte |
csb |
cse |
other |
gaps (%) |
(%) |
|
|
6-hour exposure, without S9 |
|||||||||
Saline |
0 |
100 |
200 |
0.5 |
0 |
0 |
0 |
0 |
0 |
0.5 |
0.5 |
Dinotefuran |
500 |
103 |
200 |
0 |
0 |
0.5 |
0 |
0 |
0 |
0.5 |
1.0 |
|
1000 |
104 |
200 |
0.5 |
0 |
0 |
0 |
0 |
0 |
0.5 |
0 |
|
2000 |
106 |
200 |
0 |
0.5 |
0.5 |
0 |
0 |
0 |
1.0 |
1.0 |
CP |
12.0 |
99 |
200 |
1.0 |
0 |
0 |
0.5 |
0 |
0 |
1.5 |
0.5 |
|
|
6-hour exposure with S9 |
|||||||||
Saline |
0 |
100 |
200 |
0 |
0.5 |
0 |
0 |
0 |
0 |
0.5 |
1.0 |
Dinotefuran |
500 |
100 |
200 |
0 |
0.5 |
0 |
0 |
1.0 |
0 |
1.5 |
1.0 |
|
1000 |
99 |
200 |
0 |
0.5 |
0 |
0 |
0 |
0 |
0.5 |
2.5 |
|
2000 |
104 |
200 |
0 |
0 |
0 |
0 |
1.0 |
0 |
1.0 |
1.0 |
CP |
12.0 |
86 |
200 |
0 |
15.5 |
43.5 |
0 |
0.5 |
0 |
51.0 |
1.0 |
|
|
24-hour exposure, without S9 |
|||||||||
Saline |
0 |
100 |
200 |
0.5 |
0.5 |
0 |
0 |
1.5 |
0 |
2.5 |
0 |
Dinotefuran |
500 |
85 |
200 |
0 |
2.5 |
2.0 |
0 |
0 |
0 |
4.5 |
0 |
|
1000 |
84 |
200 |
0.5 |
1.0 |
1.0 |
0 |
0 |
0 |
2.5 |
0.5 |
|
2000 |
72 |
200 |
0.5 |
2.0 |
0.5 |
0.5 |
0 |
0 |
3.5 |
0 |
MMC |
0.03 |
70 |
200 |
2.0 |
42.5 |
38.5 |
1.0 |
0.5 |
0 |
65.5 |
0.5 |
|
|
48-hour exposure, without S9 |
|||||||||
Saline |
0 |
100 |
200 |
1.0 |
1.5 |
0 |
0.5 |
0 |
0 |
3.0 |
2.5 |
Dinotefuran |
500 |
93 |
200 |
0 |
1.0 |
0.5 |
0 |
0.5 |
0 |
2.0 |
0.5 |
|
1000 |
95 |
200 |
1.0 |
0 |
0 |
0 |
1.0 |
0 |
2.0 |
0.5 |
|
2000 |
62 |
200 |
0 |
1.0 |
0 |
0 |
0 |
0 |
1.0 |
1.5 |
MMC |
0.03 |
74 |
200 |
2.0 |
36.0 |
66.5 |
0 |
0.5 |
0 |
76.0 |
0.5 |
ctb-chromatid break;
cte-chromatid exchange;
csb-chromosome break;
cse-chromosome exchange including dicentric and ring chromosomes;
other-otheraberrations including fragmentation;
gap - includes both chromatid and chromosome gaps
Table 1: Strain specific positive control substances and dose levels employed
Strain |
Without S9 |
With S9 |
||
Positive control |
Dose (µg/plate) |
Positive control |
Dose (µg/plate) |
|
S. typhimurium TA100 |
AF-2 |
0.01 |
2-AA |
1.0 |
S. typhimurium TA98 |
AF-2 |
0.01 |
2-AA |
2.0 |
S. typhimurium TA1535 |
NaN3 |
0.5 |
2-AA |
2.0 |
S. typhimurium TA1537 |
9-AA |
80.0 |
2-AA |
1.5 |
E. coli WP2uvrA |
AF-2 |
0.01 |
2-AA |
10.0 |
AF-2:2-(2-furyl)-3-(5-nitro-2-furyl)-acrylamide;NaN3: sodium azide; 9-AA:9-Aminoacridine;
2-AA:-Aminoanthracene
Table 2: Summary of the incidences of revertant colonies for the dose range-finding assay
Treatment |
Dose |
Mean (n = 3) ± SD revertant colonies/plate for strain: |
||||
|
(µg/plate) |
TA100 |
TA1535 |
WP2uvrA |
TA98 |
TA1537 |
|
|
Without S9 |
||||
DMSO |
0 |
119 |
7 |
14 |
11 |
3 |
Dinotefuran |
1.2 |
138 |
4 |
17 |
9 |
4 |
|
4.9 |
128 |
5 |
13 |
13 |
3 |
|
20 |
129 |
9 |
17 |
10 |
4 |
|
78 |
129 |
6 |
16 |
10 |
2 |
|
313 |
134 |
7 |
13 |
8 |
4 |
|
1250 |
122 |
6 |
15 |
5 |
4 |
|
5000 |
124 |
6 |
17 |
9 |
3 |
AF-2 |
0.01 |
829 |
- |
- |
- |
- |
NaN3 |
0.5 |
- |
180 |
- |
- |
- |
AF-2 |
0.01 |
- |
- |
104 |
- |
- |
AF-2 |
0.1 |
- |
- |
- |
475 |
- |
9-AA |
80 |
- |
- |
- |
- |
376 |
|
|
With S9 |
||||
DMSO |
0 |
121 |
8 |
15 |
17 |
9 |
Dinotefuran |
1.2 |
106 |
10 |
18 |
22 |
9 |
|
4.9 |
119 |
10 |
15 |
19 |
8 |
|
20 |
121 |
10 |
14 |
17 |
8 |
|
78 |
120 |
10 |
12 |
19 |
5 |
|
313 |
116 |
7 |
18 |
13 |
7 |
|
1250 |
118 |
10 |
13 |
14 |
6 |
|
5000 |
112 |
10 |
11 |
14 |
8 |
2-AA |
1 |
1006 |
- |
- |
- |
- |
|
2 |
- |
208 |
- |
- |
- |
|
10 |
- |
- |
845 |
- |
- |
|
0.5 |
- |
- |
- |
286 |
- |
|
2 |
- |
- |
- |
- |
71 |
Table 3: Summary of the incidence of revertant colonies for the main assay
Treatment |
Dose |
Mean (n = 3) ± SD revertant colonies/plate for strain: |
||||
|
(µg/plate) |
TA100 |
TA1535 |
WP2uvrA |
TA98 |
TA1537 |
|
|
Without S9 |
||||
DMSO |
0 |
101 |
5 |
25 |
12 |
3 |
Dinotefuran |
313 |
111 |
7 |
26 |
12 |
3 |
|
625 |
104 |
7 |
18 |
7 |
3 |
|
1250 |
121 |
9 |
22 |
11 |
2 |
|
2500 |
103 |
6 |
19 |
9 |
5 |
|
5000 |
103 |
9 |
18 |
16 |
5 |
AF-2 |
0.01 |
727 |
- |
- |
- |
- |
NaN3 |
0.5 |
- |
244 |
- |
- |
- |
AF-2 |
0.01 |
- |
- |
106 |
- |
- |
AF-2 |
0.1 |
- |
- |
- |
460 |
- |
9-AA |
80 |
- |
- |
- |
- |
578 |
|
|
With S9 |
||||
DMSO |
0 |
104 |
9 |
24 |
18 |
12 |
Dinotefuran |
313 |
102 |
8 |
24 |
21 |
8 |
|
625 |
107 |
10 |
25 |
16 |
8 |
|
1250 |
111 |
9 |
27 |
26 |
10 |
|
2500 |
112 |
7 |
28 |
25 |
13 |
|
5000 |
106 |
7 |
25 |
19 |
13 |
2-AA |
1 |
665 |
- |
- |
- |
- |
|
2 |
- |
210 |
- |
- |
- |
|
10 |
- |
- |
799 |
- |
- |
|
0.5 |
- |
- |
- |
209 |
- |
|
2 |
- |
- |
- |
- |
81 |
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (negative)
Genetic toxicity in vivo
Description of key information
2019 in vivo MN study additionally covered the endpoint aneugenicity and was negative.
Additional information
Justification for classification or non-classification
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
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.