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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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: 262-811-8 | CAS number: 61477-96-1
- 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 vitro
Administrative data
- Endpoint:
- in vitro gene mutation study in bacteria
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- comparable to guideline study with acceptable restrictions
Data source
Reference
- Reference Type:
- publication
- Title:
- Unnamed
- Year:
- 1 994
- Report date:
- 1994
Materials and methods
Test guideline
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 471 (Bacterial Reverse Mutation Assay)
- GLP compliance:
- not specified
- Type of assay:
- bacterial reverse mutation assay
Test material
- Reference substance name:
- 4-Thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid, 6-[[[[(4-ethyl-2,3-dioxo-1-piperazinyl)carbonyl]amino]phenylacetyl]amino]-3,3-dimethyl-7-oxo-, monosodium salt, [2S-[2α,5α,6β(S*)]]-
- EC Number:
- 261-868-6
- EC Name:
- 4-Thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid, 6-[[[[(4-ethyl-2,3-dioxo-1-piperazinyl)carbonyl]amino]phenylacetyl]amino]-3,3-dimethyl-7-oxo-, monosodium salt, [2S-[2α,5α,6β(S*)]]-
- Cas Number:
- 59703-84-3
- Molecular formula:
- C23H26N5O7S.Na
- IUPAC Name:
- sodium;(2S,5R,6R)-6-[(2S)-2-[4-ethyl-2,3-dioxopiperazin-1-yl)carbonylamino]-2-phenylacetamido]-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylate
Constituent 1
- Specific details on test material used for the study:
- SOURCE OF TEST MATERIAL
- Lot/batch No.of test material: 177-700
- Source: Toyama Chemical Industry Co., Ltd.
STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
Stability of PIPC in physiogical saline up to the time of its use was confirmed.
TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Final dilution of a dissolved solid: The powder was dissolved in physiological saline.
FORM AS APPLIED IN THE TEST (if different from that of starting material): solution
Method
- Target gene:
- Histidine-requiring gene in four strains of S. typhimurium, and tryptophan requiring gene in E. coli WP2 uvrA.
Species / strain
- Species / strain / cell type:
- S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and E. coli WP2
- Remarks:
- S. typhimurium TA 100, TA 98, TA 1535, TA 1537 strains dispensed from Dr. Ames, BN (University of California), and 5 strains of E. coli WP 2 uvrA strains dispensed from Dr. Ishikan (National Sanitary Experiment Station) were used as assay strains.
- Metabolic activation:
- with and without
- Metabolic activation system:
- S9 mix
- Test concentrations with justification for top dose:
- Preliminary studies were conducted using 5 strains at doses of 0.16, 0.8, 4.0, 20, 100 µg/plate. Since TA 100 and TA 98 strains did not show antimicrobial activity even at 100 µg/plate, additional tests were conducted at doses of 5000, 1000, 200 and 40 µg/plate. Based on these results, the maximum dose was 500 µg/plate for TA100 strain, 1000 µg/plate for TA 98 strain, 10 µg/plate for TA1535 strain, 5.0 µg/plate for TA1537 strain and WP2 strain.
- Vehicle / solvent:
- - Vehicle(s)/solvent(s) used: water.
- Justification for choice of solvent/vehicle: the test item is a white powder easily soluble in water.
Controls
- Untreated negative controls:
- not specified
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- not specified
- Positive controls:
- yes
- Positive control substance:
- 9-aminoacridine
- 2-nitrofluorene
- N-ethyl-N-nitro-N-nitrosoguanidine
- other: 2-aminoanthracene
- Remarks:
- all in DMSO
- Details on test system and experimental conditions:
- METHOD OF APPLICATION: preincubation.
- The test was carried out according to the preincubation method of Yahagi (1975), which improved the medhod of Ames et al. (1975): 0.1 ml of the test substance solution and 0.1 ml of the bacterial suspension in 0.5 ml of S9 Mix or 100 mM sodium phosphate buffer (pH 7.4) was added to a small test tube and cultured at 37ºC for 20 minutes with shaking. This test tube was mixed with 2 ml of a top agar kept at about 45ºC, then layered on a minimum glucose agar plate medium and cultured at 37ºC for 2 days.
DURATION
- Preincubation period: 20min
- Exposure duration: 48h
NUMBER OF REPLICATIONS: 3
DETERMINATION OF CYTOTOXICITY
- Method: relative total growth. The presence or absence of growth inhibition of the test bacteria was examined with a stereoscopic microscope. - Rationale for test conditions:
- In the preliminary tests, no observations of insolubility of the test item or clear inhibitory or toxic effect of the test item were detected at the doses tested.
- Evaluation criteria:
- The number of revertant colonies was measured using a colony analyzer (CA-7, Toyo) and the presence or absence of growth inhibition was examined with a stereoscopic microscope. The average number of colonies per plate was calculated and evaluated according to the criteria in the guideline of toxicity test method (Ministry of Health and Welfare Ministry of Pharmaceutical Affairs Review, 1984).
Results and discussion
Test resultsopen allclose all
- 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:
- not applicable
- 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:
- not applicable
- Positive controls validity:
- valid
- 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:
- not applicable
- 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:
- not applicable
- Positive controls validity:
- valid
- Key result
- Species / strain:
- E. coli WP2 uvr A
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not applicable
- Positive controls validity:
- valid
- Additional information on results:
- TEST-SPECIFIC CONFOUNDING FACTORS
- Other confounding effects: no.
RANGE-FINDING/SCREENING STUDIES: Preliminary studies were conducted using 5 strains at doses of 0.16, 0.8, 4.0, 20, 100 µg/plate. Since TA 100 and TA 98 strains did not show antimicrobial activity even at 100 µg/plate, additional tests were conducted at doses of 5000, 1000, 200 and 40 µg/plate. Based on these results, the maximum dose was 500 µg/plate for TA100 strain, 1000 µg/plate for TA 98 strain, 10 µg/plate for TA1535 strain, 5.0 µg/plate for TA1537 strain and WP2 strain. In TA 100 and TA 98 strains, no antibacterial action was observed even at the highest dose of PIPC, so a confirmatory test at a high dose was conducted.
ADDITIONAL INFORMATION ON CYTOTOXICITY:
- Measurement of cytotoxicity used: relative total growth. Reduction of the number of revertant colonies was observed in TA 1535, TA 1537 and WP2 strains at the highest dose of PIPC, but at 1000 μg/plate of TA 100, no antibacterial action was observed, or at 500 μg/plate of TA 98 strain. Therefore, TA 100 and TA 98 strains were further tested at higher doses.
Any other information on results incl. tables
Table 1. Reverse mutation test on PIPC in S. typhimurium and E. coli strains with or without S9 mix.
Chemical |
Dose (μg/plate) |
S9 mix |
Revertants/plate |
Dose (μg/plate) |
|
|||||||||||||
TA100 |
TA98 |
TA1535 |
TA1537 |
WP2uvrA |
||||||||||||||
DW |
… |
- |
122 |
101 |
92 (105a) |
27 |
33 |
31 (30) |
… |
5 |
11 |
3 (6a) |
4 |
2 |
5 (4) |
13 |
10 |
16 (13) |
PIPC |
5 |
- |
79 |
104 |
93 (92) |
…b |
0.05 |
… |
2 |
2 |
4 (3) |
19 |
24 |
13 (19) |
||||
|
10 |
- |
99 |
83 |
77 (86) |
38 |
38 |
35 (37) |
0.10 |
2 |
5 |
10 (6) |
1 |
5 |
3 (3) |
17 |
12 |
17 (15) |
|
25 |
- |
84 |
89 |
80 (84) |
35 |
38 |
22 (32) |
0.25 |
9 |
7 |
6 (7) |
4 |
2 |
6 (4) |
15 |
12 |
9 (12) |
|
50 |
- |
76 |
74 |
90 (80) |
27 |
32 |
33 (31) |
0.50 |
6 |
5 |
5 (5) |
4 |
3 |
6 (4) |
14 |
18 |
16 (16) |
|
100 |
- |
71 |
84 |
98 (84) |
31 |
21 |
43 (32) |
1.0 |
6 |
7 |
10 (8) |
0 |
5 |
2 (2) |
15 |
13 |
15 (14) |
|
250 |
- |
90 |
93 |
77 (87) |
38 |
23 |
38 (33) |
2.5 |
6 |
6 |
1 (4) |
2 |
4 |
3 (3) |
21 |
13 |
16 (17) |
|
500 |
- |
53 |
70 |
58 (60) |
24 |
43 |
22 (30) |
5.0 |
1 |
2 |
1 (1) |
3 |
0 |
2 (2) |
9 |
9 |
3 (7) |
|
1000 |
- |
… |
15 |
25 |
23 (21) |
10.0 |
0 |
0 |
1 (0) |
… |
… |
||||||
ENNG |
3.0 |
- |
1215 |
1157 |
1088(1153) |
… |
2.0 |
… |
… |
464 |
398 |
373 (412) |
||||||
2NF |
1.0 |
|
… |
153 |
165 |
178 (165) |
5.0 |
2263 |
3471 |
2396 (2710) |
… |
… |
||||||
9AA |
… |
|
|
|
80 |
… |
286 |
229 |
244 (253) |
… |
||||||||
DW |
… |
+ |
84 |
97 |
70 (84) |
29 |
30 |
33 (31) |
… |
4 |
2 |
2 (3) |
3 |
6 |
7 (5) |
9 |
12 |
14 (12) |
PIPC |
5 |
+ |
82 |
82 |
108 (91) |
… |
0.05 |
… |
7 |
2 |
2 (4) |
14 |
11 |
13 (13) |
||||
|
10 |
+ |
94 |
85 |
90 (90) |
38 |
38 |
38 (38) |
0.10 |
2 |
4 |
2 (4) |
4 |
8 |
3 (5) |
17 |
18 |
19 (18) |
|
25 |
+ |
103 |
95 |
94 (97) |
40 |
29 |
23 (31) |
0.25 |
8 |
7 |
8 (5) |
3 |
10 |
6 (6) |
14 |
22 |
18 (18) |
|
50 |
+ |
83 |
101 |
97 (94) |
33 |
29 |
36 (33) |
0.50 |
3 |
6 |
5 (6) |
5 |
8 |
2 (5) |
16 |
14 |
… (15)c |
|
100 |
+ |
78 |
74 |
93 (82) |
38 |
34 |
29 (34) |
1.0 |
4 |
7 |
6 (5) |
3 |
2 |
3 (3) |
15 |
10 |
15 (13) |
|
250 |
+ |
69 |
67 |
64 (67) |
32 |
27 |
30 (30) |
2.5 |
5 |
10 |
8 (3) |
1 |
2 |
1 (1) |
7 |
8 |
13 (9) |
|
500 |
+ |
74 |
74 |
90 (79) |
19 |
23 |
35 (26) |
5.0 |
7 |
3 |
2 (1) |
0 |
3 |
0 (1) |
11 |
7 |
6 (8) |
|
1000 |
+ |
… |
29 |
23 |
36 (29) |
10.0 |
0 |
0 |
0 (0) |
… |
… |
||||||
2AA |
0.5 |
+ |
… |
199 |
260 |
253 (237) |
2.0 |
121 |
101 |
115 (112) |
104 |
122 |
94 (107) |
… |
||||
|
1.0 |
+ |
828 |
900 |
933 (907) |
… |
20 |
… |
… |
331 |
330 |
289 (317) |
*a: mean of 3 plates; b: not tested. Abbreviations: DW = distilled water, PIPC = piperacillin, ENNG = N-ethyl-N’-nitro-N-nitrosoguanidine, 2NF = 2-nitrofluorene, 2AA = 2-aminoanthracene.
Except for the metabolic activation method in strain TA 1535, no increase in the number of revertant mutant colonies was observed more than 2-fold as compared with the solvent control group with or without metabolic activation in the strains tested. In the metabolic activation method with TA1535 strain, the number of revertant colonies increased from 2.0 to 2.7 times in the solvent control group at 0.25, 1.0 and 2.5 ug / plate, but there was no dose correlation.
Applicant's summary and conclusion
- Conclusions:
- No biologically significant increase in the number of revertants was noted in any strain at any dose level, either with or without metabolic activation. Therefore, the test item was not mutagenic.
- Executive summary:
The test item was studied for potential mutagenic activity using the Bacterial Reverse Mutation Assay, by a method similar to OECD 471 (non-GLP). Four histidine requiring strains of S. typhimurium (TA1535, TA 1537, TA 98, TA 100) and tryptophan requiring E.coli WP2uvrA were tested in triplicate, with and without metabolic activation (post mitochondrial supernatant S9 mix), at 5 concentrations per strain 1000 µg/plate based on the results of a range-finding test. Vehicle and positive controls were run in parallel. Under the experimental conditions applied, the test item did not induce an increase in the number of revertants in any strain at any dose level, either with or without metabolic activation. Therefore, the test item was not mutagenic.
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.