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EC number: 610-388-9 | CAS number: 478945-46-9
- 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
- Study period:
- From 27 November 2003 to 12 March 2004
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Remarks:
- No certificate of analysis was provided
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 004
- Report date:
- 2004
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 471 (Bacterial Reverse Mutation Assay)
- Version / remarks:
- adopted 1997
- Deviations:
- no
- GLP compliance:
- yes
- Type of assay:
- bacterial reverse mutation assay
Test material
- Reference substance name:
- 1,5-dimethyl 3-methyl-9-oxo-2,4-bis(pyridin-2-yl)-7-[(pyridin-2-yl)methyl]-3,7-diazabicyclo[3.3.1]nonane-1,5-dicarboxylate dichloroiron hydrate
- EC Number:
- 610-388-9
- Cas Number:
- 478945-46-9
- Molecular formula:
- C28H31N5O6FeCl2
- IUPAC Name:
- 1,5-dimethyl 3-methyl-9-oxo-2,4-bis(pyridin-2-yl)-7-[(pyridin-2-yl)methyl]-3,7-diazabicyclo[3.3.1]nonane-1,5-dicarboxylate dichloroiron hydrate
- Test material form:
- solid: particulate/powder
Constituent 1
- Specific details on test material used for the study:
- SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: Supplied by the sponsor, sample number S2539801
- Expiration date of the lot/batch: not specified
- Purity test date:not specified
STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: at room temperature, in the dark
The characterisation, homogeneity and stability of the test sample were to be assessed in SEAC Study AC030449
TREATMENT OF TEST MATERIAL PRIOR TO TESTING
Test article solutions were prepared by dissolving Stainless E-700-2003 in sterile purified water, with the aid of vortexing, immediately prior to assay to give the maximum required treatment solution concentration. This solution was not filter-sterilised and further dilutions were made using purified water. The test article solutions were protected from light and used within approximately 6¼ hours of the initial formulation of the test article.
Method
Species / strain
- Species / strain / cell type:
- S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and TA 102
- Additional strain / cell type characteristics:
- other: Bacteria were taken from vials of frozen cultures, which had been checked for strain characteristics of histidine dependence, uvrB character, rfa character and resistance to ampicillin (TA98 and TA100) or ampicillin plus tetracycline (TA102).
- Metabolic activation:
- with and without
- Metabolic activation system:
- The mammalian liver post-mitochondrial fraction (S-9) used for metabolic activation was prepared from male Sprague Dawley rats induced with Aroclor 1254
- Test concentrations with justification for top dose:
- An initial toxicity Range-Finder Experiment was carried out in strain TA100 only, in the absence and presence of S-9, using final concentrations of Stainless E-700-2003 at 1.6, 8, 40, 200, 1000 and 5000 µg/plate, plus solvent and positive controls. Evidence of toxicity in the form of a marked decrease in revertant numbers (but no concurrent diminution in the background bacterial lawn) was observed following the top two dose treatments in the absence of S-9 and following the top dose treatment in the presence of S-9. This may be indicative of bacteriostasis.
Experiment 1 treatments of all the test strains in the presence of S-9 retained the same test doses as employed for the Range-Finder Experiment. Treatments of all test strains in the absence of S-9 were performed up to a maximum dose of 1000 µg/plate (an estimate of the lower limit of toxicity) using doses of 0.32, 1.6, 8, 40, 200 and 1000 µg/plate.
Experiment 2 treatments of all strains in the absence of S-9 were performed up to 1000 µ g/plate (an estimate of the lower limit of toxicity) using doses of 1.638, 4.096, 10.24, 25.6, 64, 160, 400 and 1000 µg/plate. Treatments of all strains in the presence of S-9 were performed up to 5000 µg/plate using doses of 8.192, 20.48, 51.2, 128, 320, 800, 2000 and 5000 µg/plate. - Vehicle / solvent:
- - Vehicle(s)/solvent(s) used: purified water
- Justification for choice of solvent/vehicle: Not specified
Controls
- Untreated negative controls:
- yes
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- yes
- Positive controls:
- yes
- Positive control substance:
- 9-aminoacridine
- 2-nitrofluorene
- sodium azide
- benzo(a)pyrene
- other: 2-aminoanthracene for TA100, TA1535, TA1537, TA102, With metabolic activation ; Glutaraldehyde for TA102 strain, without metabolic activation
- Details on test system and experimental conditions:
- METHOD OF APPLICATION: in agar (plate incorporation) Experiment 1 ; preincubation in experiment 2
- Cell density at seeding (if applicable): not specified
DURATION
- Preincubation period: 1 hour (Experiment 2)
- Exposure duration: 72 hours
- Fixation time (start of exposure up to fixation or harvest of cells): after 72 hours
NUMBER OF REPLICATIONS:triplicate or quintuplicate for negative control
METHODS OF SLIDE PREPARATION AND STAINING TECHNIQUE USED: Colonies were counted electronically using a Seescan Colony Counter (Seescan Plc) or manually where confounding factors such as split agar, bubbles in the agar or a dirty plate affected the accuracy of the automated counter. The background bacterial lawn was inspected for signs of toxicity. Some treatment plates were counted manually for accuracy.
NUMBER OF CELLS EVALUATED: Not specified
DETERMINATION OF CYTOTOXICITY
- Method: Background bacterial lawn was inspected - Evaluation criteria:
- The test article was considered to be mutagenic if:
-Dunnett's test gave a significant response (p < 0.01) and the data set(s) showed a significant dose correlation
-The positive responses described above were reproducible. - Statistics:
- The m-statistic was calculated to check that the data were Poisson-distributed, and Dunnett's test was used to compare the counts of each dose with the control. The presence or otherwise of a dose response was checked by linear regression analysis.
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:
- 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:
- cytotoxicity
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Key result
- Species / strain:
- S. typhimurium TA 98
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- 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:
- 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:
- cytotoxicity
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Additional information on results:
- RANGE-FINDING/SCREENING STUDIES:
An initial toxicity Range-Finder Experiment was carried out in strain TA100 only, in the absence and presence of S-9, using final concentrations of Stainless E-700-2003 at 1.6, 8, 40, 200, 1000 and 5000 µg/plate, plus solvent and positive controls. Evidence of toxicity in the form of a marked decrease in revertant numbers (but no concurrent diminution in the background bacterial lawn) was observed following the top two dose treatments in the absence of S-9 and following the top dose treatment in the presence of S-9. This may be indicative of bacteriostasis.
HISTORICAL CONTROL DATA (with ranges, means and standard deviation and confidence interval (e.g. 95%)
- Positive historical control data:
Lower Upper
TA98
546.2 1469.2
(293.7) (1614.0)
149.3 383.1
(122.7) (419.0)
TA100
201.7 637.8
(218.3) (745.7)
327.5 2147.8
-(72.6) (2121.9)
TA1535
220.9 605.3
(269.3) (640.0)
43.7 330.6
-(5.8) (303.0)
TA1537
54.1 313.1
-(3.4) (325.7)
48.1 503.2
-(76.7) (447.6)
TA102
144.0 548.9
(48.1) (511.6)
527.1 1497.1
(309.0) (1712.9)
- Negative (solvent/vehicle) historical control data:
Lower Upper
TA98
14.8 34.6
(10.5) (33.1)
20.2 39.6
(13.7) (43.3)
TA100
86.2 141.6
(81.6) (147.6)
88.2 157.8
(71.1) (163.9)
TA1535
13.4 23.8
(9.8) (25.4)
10.0 32.2
(8.7) (31.8)
TA1537
5.6 17.0
(3.4) (16.3)
7.4 20.6
(4.1) (19.9)
TA102
212.0 420.6
(105.9) (447.3)
209.6 461.5
(87.5) (485.1)
ADDITIONAL INFORMATION ON CYTOTOXICITY:
- Measurement of cytotoxicity used: Background bacterial lawn was inspected - Remarks on result:
- other: In experiment 1 and 2
Any other information on results incl. tables
Table1 : Range Finding study
Test strain: TA100 +S-9
Treatment (µg/plate) |
Revertant numbers/plate |
||||
Solvent - Water |
124 |
143 |
136 |
143 |
126 |
1.6 |
157 |
150 |
128 |
|
|
8 |
142 |
116 |
136 |
|
|
40 |
150 |
128 |
128 |
|
|
200 |
130 |
126 |
134 |
|
|
1000 |
119 |
150 |
115 |
|
|
5000 |
20 |
44 |
34 |
|
|
Positive |
1171 |
1441 |
1346 |
|
|
Treatment (µg/plate) |
Mean (of) |
N |
Fold Increase |
Standard Deviation |
Correlation Coefficient |
Slope of best fit |
Dunnett's t value |
||
Solvent - Water |
134.40 |
5 |
|
9.07 |
|
||||
1.6 |
145.00 |
3 |
1.08^ |
15.13 |
0.46 |
NS |
6.63 |
0.95 |
NS |
8 |
131.33 |
3 |
0.98 |
13.61 |
0.19 |
NS |
-0.66 |
-0.30 |
NS |
40 |
135.33 |
3 |
1.01 |
12.70 |
0.07 |
NS |
-0.05 |
0.08 |
NS |
200 |
130.00 |
3 |
0.97 |
4.00 |
0.23 |
NS |
-0.03 |
-0.40 |
NS |
1000 |
128.00 |
3 |
0.95 |
19.16 |
0.25 |
NS |
-0.01 |
-0.63 |
NS |
5000 |
32.67 |
3 |
0.24 |
12.06 |
0.94 |
NS |
-0.02 |
-12.70 |
NS |
Positive |
1319.33 |
3 |
9.82 |
136.96 |
|
||||
|
M Statistic = 1.606 |
Key to significance:
* p<0.05 ** p<0.01 *** p<0.005 NS notsignificantKeytopostfixes:
^ Maximumincreaseabovecontrol
Table2 :Range Finding Study Test strain: TA98 -S-9
Treatment(µg/plate) |
Revertantnumbers/plate |
|||||||
Solvent - Water |
23 |
|
27 |
|
20 |
|
16 |
22 |
0.32 |
28 |
|
26 |
|
24 |
|
|
|
1.6 |
25 |
|
18 |
|
24 |
|
|
|
8 |
16 |
|
15 |
|
23 |
|
|
|
40 |
21 |
|
20 |
|
21 |
|
|
|
200 |
20 |
|
28 |
|
33 |
|
|
|
1000 |
0 |
M |
1 |
M |
2 |
M |
|
|
Solvent - DMSO |
20 |
|
26 |
|
24 |
|
26 |
21 |
Positive |
718 |
|
908 |
|
739 |
|
|
|
Treatment (µg/plate) |
Mean (of) |
N |
Fold Increase |
Standard Deviation |
Correlation Coefficient |
Slope of best fit |
Dunnett'st value |
||
Solvent - Water |
21.60 |
5 |
|
4.04 |
|
||||
0.32 |
26.00 |
3 |
1.20 |
2.00 |
0.58 |
NS |
13.75 |
1.35 |
NS |
1.6 |
22.33 |
3 |
1.03 |
3.79 |
0.01 |
NS |
-0.06 |
0.24 |
NS |
8 |
18.00 |
3 |
0.83 |
4.36 |
0.49 |
NS |
-0.65 |
-1.18 |
NS |
40 |
20.67 |
3 |
0.96 |
0.58 |
0.22 |
NS |
-0.06 |
-0.25 |
NS |
200 |
27.00 |
3 |
1.25^ |
6.56 |
0.38 |
* |
0.02 |
1.56 |
NS |
1000 |
1.00 |
3 |
0.05 |
1.00 |
0.81 |
NS |
-0.02 |
-11.07 |
NS |
Solvent - DMSO |
23.40 |
5 |
|
2.79 |
|
||||
Positive |
788.33 |
3 |
33.69 |
104.16 |
|||||
|
M Statistic = 0.746 |
Key to significance:
* p<0.05 ** p<0.01 *** p<0.005 NS notsignificantKeytopostfixes:
M Platecountedmanually
^ Maximumincreaseabovecontrol
Table3 :Summary of mean revertant colonies (-S-9) - Experiment 1
Substance |
Dose Level µg/plate |
TA98 |
TA100 |
TA1535 |
TA1537 |
TA102 |
Mean ± SD |
Mean ± SD |
Mean ± SD |
Mean ± SD |
Mean ± SD |
||
Solvent - Water |
100 µl |
22 ± 4 |
141 ± 8 |
14 ± 4 |
10 ± 2 |
265 ± 11 |
Stainless E-700-2003 |
0.32
1.6
8
40
200
1000 |
26 ± 2 |
139 ± 4 |
17 ± 3 |
11 ± 4 |
252 ± 30 |
22 ± 4 |
141 ± 3 |
13 ± 4 |
12 ± 6 |
290 ± 12 |
||
18 ± 4 |
145 ± 28 |
19 ± 7 |
11 ± 3 |
286 ± 4 |
||
21 ± 1 |
131 ± 9 |
17 ± 3 |
13 ± 1 |
302 ± 20 |
||
27 ± 7 |
129 ± 8 |
18 ± 2 (M) |
15 ± 5 |
252 ± 44 |
||
1 ± 1 (M) |
1 ± 1 |
3 ± 3 |
0 ± 0 (M) |
3 ± 4 (S) |
||
Solvent - DMSO |
100 µl |
23 ± 3 |
NT |
NT |
11 ± 4 |
NT |
Positive controls |
Compound
Dose Level
Mean ± SD |
2NF |
NaN3 |
NaN3 |
AAC |
GLU |
5 µg |
2 µg |
2 µg |
50 µg |
25 µg |
||
788 ± 104 |
742 ± 25 |
598 ± 25 |
231 ± 24 |
823 ± 16 |
SD Standarddeviation
2NF 2-Nitrofluorene
NaN3 Sodium azide AAC 9-AminoacridineGLUGlutaraldehyde
S Slight thinningofbackgroundlawn
M Platescountedmanually
NT Platesnottreated
Table 4:Summary ofmean revertant colonies (+S-9)-Experiment1
Substance |
Dose Level µg/plate |
TA98 |
TA100 |
TA1535 |
TA1537 |
TA102 |
Mean ± SD |
Mean ± SD |
Mean ± SD |
Mean ± SD |
Mean ± SD |
||
Solvent - Water |
100 µl |
28 ± 5 |
119 ± 13 |
18 ± 5 |
15 ± 2 |
315 ± 23 |
Stainless E-700-2003 |
1.6
8
40
200
1000
5000 |
28 ± 9 |
141 ± 3 |
24 ± 5 |
13 ± 5 |
271 ± 23 |
26 ± 3 |
133 ± 8 |
18 ± 3 |
17 ± 3 |
289 ± 9 |
||
28 ± 8 |
128 ± 19 |
23 ± 7 |
15 ± 3 |
307 ± 12 |
||
30 ± 7 |
127 ± 12 |
20 ± 12 |
11 ± 4 |
324 ± 4 |
||
24 ± 6 |
145 ± 17 |
23 ± 6 |
8 ± 5 |
225 ± 42 |
||
14 ± 2 |
9 ± 5 |
3 ± 2 |
2 ± 2 |
69 ± 11 |
||
Solvent - DMSO |
100 µl |
29 ± 6 |
133 ± 16 |
23 ± 7 |
14 ± 5 |
317 ± 12 |
Positive controls |
Compound
Dose Level
Mean ± SD |
B[a]P |
AAN |
AAN |
AAN |
AAN |
10 µg |
5 µg |
5 µg |
5 µg |
20 µg |
||
190 ± 11 |
1445 ± 31 |
289 ± 35 |
334 ± 25 |
1854 ± 106 |
SD Standarddeviation
B[a]P Benzo[a]pyreneAAN 2-Aminoanthracene
Table5 :Summary of mean revertant colonies (-S-9) - Experiment 2
Substance |
Dose Level µg/plate |
TA98 |
TA100 |
TA1535 |
TA1537 |
TA102 |
Mean ± SD |
Mean ± SD |
Mean ± SD |
Mean ± SD |
Mean ± SD |
||
Solvent - Water |
100 µl |
25 ± 6 |
149 ± 7 |
20 ± 2 |
10 ± 4 |
435 ± 20 |
Stainless E-700-2003 |
1.638
4.096
10.24
25.6
64
160
400
1000 |
32 ± 7 |
171 ± 15 |
16 ± 5 |
10 ± 4 |
382 ± 41 |
26 ± 2 |
167 ± 9 |
25 ± 1 |
17 ± 1 |
389 ± 29 |
||
20 ± 8 |
157 ± 32 |
18 ± 3 |
14 ± 10 |
525 ± 69 |
||
26 ± 8 |
156 ± 54 |
19 ± 5 |
13 ± 6 |
455 ± 21 |
||
29 ± 16 |
144 ± 25 |
14 ± 5 |
12 ± 3 |
342 ± 97 |
||
16 ± 5 |
146 ± 46 |
22 ± 7 |
11 ± 4 |
358 ± 107 |
||
27 ± 8 |
117 ± 38 (S) |
14 ± 2 |
9 ± 6 |
370 ± 16 |
||
4 ± 3 (S) |
28 ± 10 (S) |
3 ± 2 (S) |
1 ± 1 (S) |
34 ± 27 (S) |
||
Solvent - DMSO |
50 µl |
23 ± 5 |
NT |
NT |
12 ± 5 |
NT |
Positive controls |
Compound
Dose Level
Mean ± SD |
2NF |
NaN3 |
NaN3 |
AAC |
GLU |
5 µg |
2 µg |
2 µg |
50 µg |
25 µg |
||
1691 ± 443 |
669 ± 48 |
679 ± 41 |
244 ± 50 |
645 ± 76 |
SD Standarddeviation
2NF 2-Nitrofluorene
NaN3 Sodium azide AAC 9-AminoacridineGLUGlutaraldehyde
S Slight thinningofbackgroundlawn
NT Platesnottreated
Table6 :Summary of mean revertant colonies (+S-9)-Experiment2
Substance |
Dose Level µg/plate |
TA98 |
TA100 |
TA1535 |
TA1537 |
TA102 |
Mean ± SD |
Mean ± SD |
Mean ± SD |
Mean ± SD |
Mean ± SD |
||
Solvent - Water |
100 µl |
32 ± 6 |
163 ± 12 |
24 ± 8 |
18 ± 2 |
435 ± 33 |
Stainless E-700-2003 |
8.192
20.48
51.2
128
320
800
2000
5000 |
29 ± 3 |
132 ± 19 |
22 ± 14 |
19 ± 1 |
311 ± 40 |
30 ± 3 |
154 ± 13 |
22 ± 6 |
10 ± 6 |
343 ± 13 |
||
23 ± 3 |
151 ± 9 |
18 ± 2 |
14 ± 4 |
341 ± 25 |
||
31 ± 8 |
177 ± 9 |
17 ± 2 |
12 ± 4 |
358 ± 41 |
||
22 ± 6 |
159 ± 20 |
24 ± 6 |
9 ± 4 |
328 ± 6 |
||
29 ± 6 |
169 ± 7 |
19 ± 8 |
13 ± 4 |
327 ± 34 |
||
27 ± 5 |
155 ± 36 |
22 ± 5 |
13 ± 2 |
239 ± 40 |
||
22 ± 7 |
56 ± 12 (S) |
13 ± 3 |
2 ± 1 |
99 ± 44 (S) |
||
Solvent - DMSO |
50 µl |
25 ± 9 |
141 ± 21 |
21 ± 5 |
14 ± 4 |
326 ± 67 |
Positive controls |
Compound
Dose Level
Mean ± SD |
B[a]P |
AAN |
AAN |
AAN |
AAN |
10 µg |
5 µg |
5 µg |
5 µg |
20 µg |
||
295 ± 41 |
787 ± 13 |
83 ± 7 |
115 ± 4 |
1403 ± 79 |
SD Standard deviation
B[a]P Benzo[a]pyreneAAN 2-Aminoanthracene
S Slight thinningofbackgroundlawn
Applicant's summary and conclusion
- Conclusions:
- Under the experimental conditions of the study, the Stainless E-700-2003 did not induce mutation in five histidine-requiring strains of Salmonella typhimurium (TA98, TA100, TA1535, TA1537 and TA102)
These conditions included treatments at concentrations up to either 5000 µg/plate, or the lower limit of toxicity, in the absence and in the presence of a rat liver metabolic activation system (S-9). - Executive summary:
In this GLP-compliant sutdy, Stainless E-700-2003 was assayed for mutation in five histidine-requiring strains of Salmonella typhimurium (TA98, TA100, TA1535, TA1537 and TA102), both in the absence and in the presence of metabolic activation by an Aroclor 1254-induced rat liver post-mitochondrial fraction (S-9), in two separate experiments (performed according to OECD Guideline 471 method).
An initial toxicity Range-Finder Experiment was carried out in strain TA100 only, in the absence and presence of S-9, using final concentrations of Stainless E-700-2003 at 1.6, 8, 40, 200, 1000 and 5000 µg/plate, plus solvent and positive controls. Evidence of toxicity was observed following the top two dose treatments in the absence of S-9, and following the top dose treatment in the presence of S-9.
Experiment 1 treatments of all the test strains in the presence of S-9 retained the same test doses as employed for the Range-Finder Experiment. Treatments of all test strains in the absence of S-9 were performed up to a maximum dose of 1000 µg/plate (an estimate of the lower limit of toxicity) using doses 0.32, 1.6, 8, 40, 200, 1000 µg/plate. Evidence of toxicity was observed following the top dose treatment of all strains in the absence and presence of S-9.
Experiment 2 treatments of all strains in the absence of S-9 were performed using a maximum test dose of 1000 µ g/plate (an estimate of the lower limit of toxicity) and doses of 1.638, 4.096, 10.24, 25.6, 64, 160, 400 and 1000 µ g/plate. Treatments of all strains in the presence of S-9 were performed up to 5000 µ g/plate using doses of 8.192, 20.48, 51.2, 128, 320, 800, 2000 and 5000 µ g/plate. In addition, pre-incubation methodology was used for all treatments in the absence and presence of S-9. Evidence of toxicity was observed following the top one or two dose treatments of all strains in the absence and presence of S-9, except strain TA98 in the presence of S-9 where no clear evidence of toxicity was seen.
No statistically significant, dose-related and reproducible increases in revertant numbers were observed following any strain treatments in the absence or presence of metabolic activation, and therefore this study was considered to have provided no evidence of any Stainless E-700-2003 mutagenic activity.
Under the experimental conditions of the study, the Stainless E-700-2003 did not induce mutation in five histidine-requiring strains of Salmonella typhimurium (TA98, TA100, TA1535, TA1537 and TA102)
These conditions included treatments at concentrations up to either 5000 µg/plate, or the lower limit of toxicity, in the absence and in the presence of a rat liver metabolic activation system (S-9).
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