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EC number: 292-927-4 | CAS number: 91031-27-5
Genetic toxicity: in vitro
Administrative data
- Endpoint:
- in vitro gene mutation study in bacteria
- Remarks:
- Type of genotoxicity: gene mutation
- Type of information:
- migrated information: read-across based on grouping of substances (category approach)
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: see 'Remark'
- Remarks:
- GLP - Guideline study. According to the ECHA guidance document "Practical guide 6: How to report read-across and categories (March 2010)", the reliability was changed from RL1 to RL2 to reflect the fact that this study was conducted on a read-across substance.
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 012
- Report date:
- 2012
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 471 (Bacterial Reverse Mutation Assay)
- Version / remarks:
- (adopted 2008)
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Remarks:
- Harlan Laboratories Ltd., ShaThe department of health of the government of the United Kingdom
- Type of assay:
- bacterial reverse mutation assay
Test material
- Reference substance name:
- Fatty acids, C8-18 and C18-unsatd., esters with neopentyl glycol
- EC Number:
- 286-072-6
- EC Name:
- Fatty acids, C8-18 and C18-unsatd., esters with neopentyl glycol
- Cas Number:
- 85186-86-3
- IUPAC Name:
- 85186-86-3
- Details on test material:
- - Name of test material (as cited in study report): only trade name given
- Physical state: yellow liquid
- Analytical purity: 100 %
- Lot/batch No.: OE10817
- Expiration date of the lot/batch: 21 October 2016
Constituent 1
Method
- Target gene:
- his operon (S. typhimurium strains); trp operon (E. coli strain)
Species / strainopen allclose all
- Species / strain / cell type:
- S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
- Species / strain / cell type:
- E. coli WP2 uvr A
- Metabolic activation:
- with and without
- Metabolic activation system:
- cofactor supplemented post-mitochondrial fraction (10 % liver S9 mix in standard co-factors), prepared from the livers of rats treated with Phenobarbitone/ß-Naphthoflavone
- Test concentrations with justification for top dose:
- - Experiment 1 (plate incorporation assay): 50, 150, 500, 1500, and 5000 µg/plate
- Experiment 2 (pre-incubation): 50, 150, 500, 1500, and 5000 µg/plate - Vehicle / solvent:
- - Vehicle(s)/solvent(s) used: acetone
- Justification for choice of solvent/vehicle: the test substance was fully miscible in acetone at 100 mg/mL in solubility pre-tests.
Controlsopen allclose all
- Untreated negative controls:
- yes
- Remarks:
- concurrent untreated control
- Negative solvent / vehicle controls:
- yes
- Remarks:
- acetone
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- other: Without S9: N-ethyl-N'-nitro-N-nitrosoguanidine (ENNG, 2, 3 or 5 µg/plate for WP2uvrA, TA100, or TA1535), 9-Aminoacridine (9AA, 80 µg/plate for TA1537), 4-Nitroquinoline-1-oxide (4NQO, 0.2 µg/plate for TA98)
- Untreated negative controls:
- yes
- Remarks:
- concurrent untreated control
- Negative solvent / vehicle controls:
- yes
- Remarks:
- acetone
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- other: with S9: 2-Aminoanthracene (2AA, 1 µg/plate for TA100, 2 µg/plate for TA1535 and TA1537, 10 µg/plate for WP2uvrA), Benz(a)pyrene (BP, 5 µg/plate for TA98)
- Details on test system and experimental conditions:
- METHOD OF APPLICATION: in agar (plate incorporation); preincubation
DURATION
- Preincubation period: 20 min
- Exposure duration: 48 h
NUMBER OF REPLICATIONS: three replicates/concentration or control
DETERMINATION OF FREQUENCY OF REVERTANT COLONIES: Domino colony counter
DETERMINATION OF CYTOTOXICITY
- Method: bacterial background lawn - Evaluation criteria:
- A result was considered as positive, when the following criteria were met:
1. A dose-related increase in mutant frequency over the dose range tested.
2. A reproducible increase at one or more concentrations.
3. Biological relevance against in-house historical control ranges.
4. Statistical analysis of data as determined by UKEMS.
5. Fold increase greater than two times the concurrent solvent control for any tester strain (especially if accompanied by an out-of-historical range response)
Results and discussion
Test resultsopen allclose all
- 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:
- other: 1. no cytotoxicity (plate incorparation assay); 2. cytotoxicity at 5000 µg/plate in TA100, TA1535 and TA1537 without S9 (pre-incubation assay)
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Species / strain:
- E. coli WP2 uvr A
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity nor precipitates, but tested up to recommended limit concentrations
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Additional information on results:
- RANGE-FINDING/SCREENING STUDIES:
A preliminary test was carried out to determine the toxicity of the test item using TA100 and WP2uvrA. The concentrations tested were 0, 0.15, 0.5, 1.5, 5, 15, 50, 150, 500, 1500 and 5000 µg/plate. In addition, a vehicle control (acetone) and a sterility control were run in parallel.
The test item was non-toxic to the strains of bacteria used (TA100 and WP2uvrA). - Remarks on result:
- other: all strains/cell types tested
- Remarks:
- Migrated from field 'Test system'.
Any other information on results incl. tables
Table 1. Test results of experiment 1 (plate incorporation)
With or without S9-Mix |
Test substance concentration (μg/plate) |
Mean number of revertant colonies per plate (average of 3 plates ± standard deviation) |
||||
Base-pair substitution type |
Frameshift type |
|||||
TA 100 |
TA1535 |
WP2uvrA |
TA98 |
TA1537 |
||
– |
0 |
84 ± 2.1 |
14 ± 3.5 |
22 ± 2.3 |
30 ± 5.9 |
19 ± 4.6 |
– |
50 |
72 ± 14.2 |
17 ± 3.5 |
24 ± 2.6 |
30 ± 6.4 |
20 ± 5.0 |
– |
150 |
76 ± 2.3 |
13 ± 4.4 |
21 ± 8.1 |
31 ± 8.5 |
13 ± 3.5 |
– |
500 |
82 ± 6.9 |
18 ± 3.8 |
23 ± 8.7 |
23 ± 2.6 |
13 ± 3.5 |
– |
1500 |
82 ± 16.5 |
14 ± 5.9 |
15 ± 4.0 |
24 ± 8.3 |
10 ± 1.5 |
– |
5000 |
84 ± 2.6 |
12 ± 1.2 |
21 ± 7.5 |
25 ± 6.4 |
15 ± 2.1 |
Positive controls, –S9 |
Name |
ENNG |
ENNG |
ENNG |
4NQO |
9AA |
Concentrations (μg/plate) |
3 |
5 |
2 |
0.2 |
80 |
|
Mean No. of colonies/plate (average of 3 ± SD) |
557 ± 12.1 |
96 ± 20.6 |
639 ± 25.1 |
107 ± 11.5 |
360 ± 52.9 |
|
+ |
0 |
88 ± 7.0 |
13 ± 3.1 |
33 ± 6.7 |
17 ± 2.5 |
14 ± 4.0 |
+ |
50 |
86 ± 3.6 |
12.± 2.5 |
29 ± 7.5 |
14 ± 1.0 |
14 ± 3.5 |
+ |
150 |
83 ± 7.0 |
13 ± 3.2 |
25 ± 10.1 |
19 ± 1.7 |
13 ± 3.2 |
+ |
500 |
97 ± 14.8 |
13 ± 3.5 |
24 ± 6.7 |
16 ± 3.5 |
7 ± 0.6 |
+ |
1500 |
97 ± 27.8 |
12 ± 2.3 |
28 ± 5.3 |
19 ± 7.6 |
17 ± 2.1 |
+ |
5000 |
87 ± 5.8 |
12 ± 2.0 |
29 ± 3.6 |
22 ± 2.5 |
13 ± 0.6 |
Positive controls, +S9 |
Name |
2AA |
2AA |
2AA |
BP |
2AA |
Concentrations (μg/plate) |
1 |
2 |
10 |
5 |
2 |
|
Mean No. of colonies/plate (average of 3 ± SD) |
554 ± 36.4 |
412 ± 20.8 |
206 ± 11.5 |
114 ± 1.5 |
268 ± 19.5 |
|
ENNG = N-ethyl-N-nitro-N-nitrosoguanidine
4NQO = 4-nitroquinoline-N-oxide
9AA = 9-aminoacridine
2AA = 2-Aminoanthracene
BP = Benzo(a)pyrene
P = Precipitate
C = contaminated
Table 2. Test results of experiment 2 (pre-incubation)
With or without S9-Mix |
Test substance concentration (μg/plate) |
Mean number of revertant colonies per plate (average of 3 plates ± standard deviation) |
||||
Base-pair substitution type |
Frameshift type |
|||||
TA 100 |
TA1535 |
WP2uvrA |
TA98 |
TA1537 |
||
– |
0 |
87 ± 2.1 |
16 ± 2.6 |
32 ± 4.6 |
20 ± 6.8 |
10 ± 1.7 |
– |
50 |
84 ± 14.3 |
17 ± 4.5 |
24 ± 3.0 |
23.± 4.4 |
12 ± 7.1 |
– |
150 |
78 ± 5.0 |
15 ± 2.6 |
22 ± 2.3 |
21 ± 4.5 |
10 ± 3.0 |
– |
500 |
95 ± 12.1 |
19 ± 5.3 |
33 ± 7.0 |
20 ± 2.3 |
11 ± 2.6 |
– |
1500 |
83 ± 5.0 |
17 ± 3.6 |
33 ± 4.5 |
22 ± 1.7 |
11 ± 2.6 |
– |
5000 |
83 ± 6.0 t |
9 ± 1.5 t |
34 ± 1.2 |
14 ± 4.0 |
12 ± 4.5 t |
Positive controls, –S9 |
Name |
ENNG |
ENNG |
ENNG |
4NQO |
9AA |
Concentrations (μg/plate) |
3 |
5 |
2 |
0.2 |
80 |
|
Mean No. of colonies/plate (average of 3 ± SD) |
532 ± 3.2 |
170 ± 4.0 |
769 ± 54.8 |
127 ± 20.6 |
1319 ± 210.8 |
|
+ |
0 |
104 ± 14.5 |
21 ± 6.1 |
33 ± 3.2 |
12 ± 1.2 |
11 ± 1.2 |
+ |
50 |
99 ± 4.9 |
19 ± 12.2 |
28 ± 7.6 |
12 ± 1.7 |
9 ± 1.5 |
+ |
150 |
92 ± 1.2 |
20 ± 8.1 |
33 ± 3.1 |
13 ± 3.1 |
10 ± 2.1 |
+ |
500 |
109 ± 20.4 |
16 ± 2.6 |
29 ± 3.8 |
13 ± 1.7 |
10 ± 1.0 |
+ |
1500 |
94 ± 12.0 |
15 ± 2.5 |
36 ± 6.8 |
11 ± 0.6 |
10 ± 2.9 |
+ |
5000 |
100 ± 2.6 |
11 ± 0.0 |
34 ± 4.0 |
10 ± 3.1 |
7 ± 4.9 |
Positive controls, +S9 |
Name |
2AA |
2AA |
2AA |
BP |
2AA |
Concentrations (μg/plate) |
1 |
2 |
10 |
5 |
2 |
|
Mean No. of colonies/plate (average of 3 ± SD) |
1354 ± 153.5 |
357 ± 6.1 |
147 ± 5.3 |
286 ± 1.0 |
295 ± 1.7 |
|
ENNG = N-ethyl-N-nitro-N-nitrosoguanidine
4NQO = 4-nitroquinoline-N-oxide
9AA = 9-aminoacridine
2AA = 2-Aminoanthracene
BP = Benzo(a)pyrene
P = Precipitate
C = contaminated
t= citotoxic effects
Applicant's summary and conclusion
- Conclusions:
- Interpretation of results (migrated information):
negative
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