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EC number: 609-547-5 | CAS number: 38385-95-4
- 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
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- 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 vitro
Administrative data
- Endpoint:
- in vitro gene mutation study in bacteria
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- October 22, 2007 - December 21, 2007
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 008
- Report date:
- 2008
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 471 (Bacterial Reverse Mutation Assay)
- Deviations:
- no
- GLP compliance:
- yes
- Type of assay:
- bacterial reverse mutation assay
Test material
- Reference substance name:
- 2-(piperidin-4-yl)-1H-1,3-benzodiazole
- EC Number:
- 609-547-5
- Cas Number:
- 38385-95-4
- Molecular formula:
- C12H15N3
- IUPAC Name:
- 2-(piperidin-4-yl)-1H-1,3-benzodiazole
Constituent 1
- Specific details on test material used for the study:
- SOURCE OF TEST MATERIAL
- Source: sponsor
- Lot: 0604X10
STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: room temperature in darkness.
- Solubility and stability of the test substance in the solvent/vehicle: Sodium phosphate buffer, 200mM, pH=7.4, was used as the vehicle to prepare the item concentrations. A stock concentration of 100 mg/ml was prepared in DMSO from which 1:5 dilutions were made.
- Reactivity of the test substance with the solvent/vehicle of the cell culture medium: no
Method
- Target gene:
- Histidine
Species / strain
- Species / strain / cell type:
- S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and TA 102
- Additional strain / cell type characteristics:
- not specified
- Metabolic activation:
- with and without
- Metabolic activation system:
- S9
- Test concentrations with justification for top dose:
- The top concentration of the test item was toxic for Salmonella typhimurium so, the following concentrations were tested: 20; 4; 0.8; 0.16; and 0.032 mg/ml
- Vehicle / solvent:
- - Vehicle/solvent used: DMSO
- Justification for choice of solvent/vehicle: Solvent is compatible with the survival of the bacteria and the S9 activity.
Controls
- Untreated negative controls:
- yes
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- 9-aminoacridine
- 2-nitrofluorene
- sodium azide
- cumene hydroperoxide
- other: 2-aminoantracene
- Details on test system and experimental conditions:
- METHOD OF APPLICATION: Preincubation
Each point of the two series of tubes (with and without S9) was tested in duplicate and with the following compposition: phosphate buffer (or S9 micture), 2E9 cell/ml bacterial culture and the solvent (negative control), the test item (each of the five concentrations) or the reference item (positive controls). The tubes were placed in a water bath at 37ºC for 45 minutes. Then 2ml of surface agar supplemented with histidine/biotin 0,5 mM was added to each tube and poured onto a minimum agar plate. The plates were left to set for 1 hour and they were then placed in the incubator at 37 ºC for 48-72 hours.
DURATION
- Preincubation period: 45 minutes
- Exposure duration:48 -72 hours
SELECTION AGENT (mutation assays): The lack of amino-acid in the medium. Only the mutants can grow due to their capability to synthesize an essential amino acid.
NUMBER OF REPLICATIONS: 2.
DETERMINATION OF CYTOTOXICITY
- Method: Visual observation of the colonies.
OTHER EXAMINATIONS:
Phenotype and sterility controls were also performed.
- OTHER:
Solutions preparation: Sodium phosphate buffer, 200mM, pH=7.4, was used as the vehicle to prepare the item concentrations. In all cases, these concentrations were prepared on the day they were used. A stock concentration of 100mg/ml was prepared in DMSO from which 1:5 dilutions were carried out.
Test system: Prior to the study, the master plates of each strain were prepared. The strains were plated out in minimum agar plates enriched with Biotin 0.5 mM and Histidine 0.1 M. In the case of strains TA98 and TA100 the plates also contained ampicillin 8 mg/ml and in the case of strain TA102 they contained Tetracycline 8 mg/ml, in addition to Histidine, Biotin and Ampicillin. The plates were cultivated for 48 hours at 37ºC. - Rationale for test conditions:
- The top concentration of the test item, 100 mg/ml, was toxic for Salmonella typhimurium so, the following concentrations were tested: 20; 4; 0.8; 0.16 and 0.032 mg/ml.
- Evaluation criteria:
- Criteria conclusion: the result of the test is considered as positive if the test item induce an increase of colonies with respect to non-treated plates, dependent on the concentration of one, or several of the 5 strains, without and/or with metabolic activation.
Results and discussion
Test resultsopen allclose all
- Key result
- Species / strain:
- S. typhimurium TA 98
- 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
- Key result
- Species / strain:
- S. typhimurium TA 100
- 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
- Key result
- Species / strain:
- S. typhimurium TA 1535
- 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
- Key result
- Species / strain:
- S. typhimurium TA 1537
- 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
- Key result
- Species / strain:
- S. typhimurium TA 102
- 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:
- TEST-SPECIFIC CONFOUNDING FACTORS
- Precipitation: No
Any other information on results incl. tables
The conditions listed below indicate that the tests are acceptable:
1. The plates show a firm, uniform lawn, which demonstrates that there is no toxicity in the concentrations that were taken as a reference to evaluate the mutagenic power.
2. The number of colonies in the spontaneous mutation plates is within the normal range for each strain.
3. The positive controls induce a clear increase in the number of revertants in all cases.
4. The phenotype control plates show the expected results for each strain.
From the results expressed on the tables below it can be deduced that the test item does not induce an increase in colonies in any of the strains used in this study, neither in the presence of S9 nor in its absence.
Calculation of the mutation index (MI)
MI = nº. of mut. in a dose / nº. of mut. in the control
Strain TA98 |
||||||
|
-S9 |
+S9 |
||||
|
No. Col. |
Average |
MI |
No. Col. |
Average |
MI |
Sp. Mut. |
13/15 |
14.0 |
-- |
19/20 |
19.5 |
-- |
0mg/ml |
16/19 |
17.5 |
-- |
20/22 |
21.0 |
-- |
32mg/ml |
22/15 |
18.5 |
1.057 |
22/17 |
19.5 |
0.929 |
160mg/ml |
14/18 |
16.0 |
0.914 |
16/23 |
19.5 |
0.929 |
800mg/ml |
20/14 |
17.0 |
0.971 |
14/22 |
18.0 |
0.857 |
4000mg/ml |
14/18 |
16.0 |
0.914 |
16/18 |
17.0 |
0.810 |
20000mg/ml |
18/15 |
16.5 |
0.943 |
27/12 |
19.5 |
0.929 |
Control + |
>2000/>2000 |
>2000 |
>114.286 |
>2000/>2000 |
>2000 |
>95.238 |
Strain TA100 |
||||||
|
-S9 |
+S9 |
||||
|
No. Col. |
Average |
MI |
No. Col. |
Average |
MI |
Sp. Mut. |
176/183 |
169.5 |
-- |
192/197 |
194.5 |
-- |
0mg/ml |
180/164 |
172.0 |
-- |
215/207 |
211.5 |
-- |
32mg/ml |
173/169 |
171.0 |
0.994 |
173/162 |
167.5 |
0.794 |
160mg/ml |
168/159 |
163.5 |
0.951 |
168/172 |
170.0 |
0.806 |
800mg/ml |
163/170 |
166.5 |
0.968 |
132/196 |
164.0 |
0.777 |
4000mg/ml |
181/176 |
178.5 |
1.038 |
160/188 |
174.0 |
0.825 |
20000mg/ml |
186/190 |
188.0 |
1.093 |
200/213 |
206.5 |
0.979 |
Control + |
>2000/>2000 |
>2000 |
>11.628 |
>2000/>2000 |
>2000 |
>9.479 |
Strain TA102 |
||||||
|
-S9 |
+S9 |
||||
|
No. Col. |
Average |
MI |
No. Col. |
Average |
MI |
Sp. Mut. |
312/321 |
316.5 |
-- |
412/420 |
416.0 |
-- |
0mg/ml |
326/325 |
325.5 |
-- |
400/410 |
405.0 |
-- |
32mg/ml |
317/329 |
323.0 |
0.992 |
438/422 |
430.0 |
1.062 |
160mg/ml |
330/322 |
326.0 |
1.002 |
407/410 |
408.5 |
1.009 |
800mg/ml |
327/333 |
330.0 |
1.014 |
428/430 |
429.0 |
1.059 |
4000mg/ml |
315/320 |
317.0 |
0.974 |
410/412 |
411.0 |
1.015 |
20000mg/ml |
317/321 |
319.0 |
0.980 |
426/410 |
418.0 |
1.032 |
Control + |
>2000/>2000 |
>2000 |
>6.144 |
920/880 |
900.0 |
2.222 |
Strain TA1535 |
||||||
|
-S9 |
+S9 |
||||
|
No. Col. |
Average |
MI |
No. Col. |
Average |
MI |
Sp. Mut. |
6/6 |
6.0 |
-- |
17/16 |
16.5 |
-- |
0mg/ml |
7/4 |
5.5 |
-- |
19/17 |
18.0 |
-- |
32mg/ml |
8/5 |
6.5 |
1.182 |
20/22 |
21.0 |
1.167 |
160mg/ml |
7/5 |
6.0 |
1.091 |
21/19 |
20.0 |
1.111 |
800mg/ml |
6/5 |
5.5 |
1.000 |
17/23 |
20.0 |
1.111 |
4000mg/ml |
5/5 |
5.0 |
0.909 |
26/18 |
22.0 |
1.222 |
20000mg/ml |
5/6 |
5.5 |
1.000 |
22/23 |
22.5 |
1.250 |
Control + |
>1500/>1500 |
>1500 |
>272.727 |
253/249 |
251.0 |
13.944 |
Strain TA1537 |
||||||
|
-S9 |
+S9 |
||||
|
No. Col. |
Average |
MI |
No. Col. |
Average |
MI |
Sp. Mut. |
4/5 |
4.5 |
-- |
8/10 |
9.0 |
-- |
0mg/ml |
7/6 |
6.5 |
-- |
9/11 |
10.0 |
-- |
32mg/ml |
6/6 |
6.0 |
0.923 |
4/7 |
5.5 |
0.550 |
160mg/ml |
8/6 |
7.0 |
1.077 |
10/7 |
8.5 |
0.850 |
800mg/ml |
5/7 |
6.0 |
0.923 |
6/1 |
3.5 |
0.350 |
4000mg/ml |
6/7 |
6.5 |
1.000 |
3/5 |
4.0 |
0.400 |
20000mg/ml |
4/6 |
5.0 |
0.769 |
13/4 |
8.5 |
0.850 |
Control + |
165/179 |
172.0 |
26.462 |
192/184 |
188.0 |
18.800 |
--: It was not possible to count colonies
Results of the phenotype control
|
TA98 |
TA100 |
TA1535 |
TA1537 |
TA102 |
Ampicilyne |
Resistant |
Resistant |
Sensitive |
Sensitive |
Resistant |
Violet Crystal |
Sensitive |
Sensitive |
Sensitive |
Sensitive |
Sensitive |
UV light |
Sensitive |
Sensitive |
Sensitive |
Sensitive |
Sensitive |
Tetracycline |
n.t |
n.t |
n.t |
n.t |
Resistant |
n.t.: not tested
Applicant's summary and conclusion
- Conclusions:
- The test item does not induce a dose-dependent increase in Salmonella typhimurium strains: TA98, TA100, TA102, TA1535 and TA1537. Therefore, it was not considered as mutagenic under test conditions.
- Executive summary:
A Bacterial reverse mutation test was performed according OECD guideline 471 with GLP. Bases on previous toxicity test, 1 -2E9 cell/mL os Salmonella typhimurium strains TA98, TA100, TA1535, TA1537 and TA102 were exposed to 0.032, 0.16, 0.8, 4 and 20 mg/mL test item, solvent and positive controls with and without metabolic activation (two replicates each). The incubation mixtures were pre-incubated at 37 ºC for 45 minutes and incubated at 37 ºC for 48 -72 hours. Then, the revertant colonies were counted. Phenotype and sterility controls were also performed. The plates showed a firm, uniform lawn, which demostrates that there was no toxicity. The number of colonies in the spontaneous mutation plates was within the normal range for each strain. The positive controls induced a clear inclease in the number of revertants in all cases and the phenotype control plates show the expected results for each strain. The test item do not induce a dose-dependent increase in Salmonella typhimurium strains: TA98, TA100, TA102, TA1535 and TA1537. Therefore, it was not considered as mutagenic under test conditions.
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