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EC number: 200-262-8 | CAS number: 56-23-5
Genetic toxicity: in vitro
Administrative data
- Endpoint:
- in vitro gene mutation study in bacteria
- Remarks:
- Type of genotoxicity: gene mutation
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: - Guideline study (OECD, etc.) - number of replicates to low for some concentrations
Data source
Reference
- Reference Type:
- publication
- Title:
- Mutagenicity of carbon tetrachloride and chloroform in Salmonella typhimurium TA98, TA100, TA1535, and TA1537, and Escherichia coli WP2uvrA/pKM101 and WP2/pKM101, using a gas exposure method.
- Author:
- Araki A, Kamigaito N, Sasaki T, Matsushima T,
- Year:
- 2 004
- Bibliographic source:
- Environmental and molecular mutagenesis, vol. 43, no 2, p. 128-133
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 471 (Bacterial Reverse Mutation Assay)
- Deviations:
- yes
- Remarks:
- : gas exposure method
- GLP compliance:
- not specified
- Type of assay:
- bacterial reverse mutation assay
Test material
- Reference substance name:
- Carbon tetrachloride
- EC Number:
- 200-262-8
- EC Name:
- Carbon tetrachloride
- Cas Number:
- 56-23-5
- Molecular formula:
- CCl4
- IUPAC Name:
- tetrachloromethane
- Details on test material:
- - Name of test material (as cited in study report): carbon tetrachloride
- Physical state: liquid
- Analytical purity: sample No 1: 99.5 %, sample no. 2: 99.9 %
- Supplier: Wako Pure Chemicals Industries
- Lot/batch No.: sample No 1: APE7331, sample no. 2: KSG7670
- Stability under test conditions: not reported, expected to be stable
- Storage condition of test material: not reported
Constituent 1
Method
- Target gene:
- no data
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 pKM 101
- Species / strain / cell type:
- E. coli WP2
- Additional strain / cell type characteristics:
- other: carrying the plasmid pKM101
- Metabolic activation:
- with and without
- Metabolic activation system:
- S9 extract from phenobarbitone + 5,6-benzoflavone treated male Sprague-Dawley rats
- Test concentrations with justification for top dose:
- 100, 500, 1000, 2000, 5000, 10'000, 20'000, 50'000 ppm (= 640, 3200, 6400, 12'800, 32'000, 64'000, 128'000, 320'000 mg/m³)
assuming 500 mL air volume/plate: 0.8 - 160 mg/plate - Vehicle / solvent:
- - Vehicle(s)/solvent(s) used: none
Controls
- Untreated negative controls:
- yes
- True negative controls:
- yes
- Positive controls:
- yes
- Positive control substance:
- other: 2-(2-furyl)-3-(5-nitro-2-furyl)acrylamidMe, MMC: mitomycin C, 2AA: 2-aminoanthracen, see table 1 for details
- Remarks:
- with the gas exposure, sham exposed controls are both negative and true negative controls
- Details on test system and experimental conditions:
- METHOD OF APPLICATION: gas exposure method
DURATION
- Preincubation period: 0 min, no preincubation
- Exposure duration: 24 h
- Expression time (cells in growth medium): 0 h
- Selection time (if incubation with a selection agent): 24 h (+24 h during exposure)
SELECTION AGENT (mutation assays): Salmonella strains: L-histidine, Ecoli strains: L-trytophane
DETERMINATION OF CYTOTOXICITY
- Method: not reported
- Evaluation criteria:
- - a factor of 2 between the average no of revertants on exposed plates compared to the everage no of revertants on unexposed plates
- Statistics:
- - Bartlett's test for evaluation of homogenity of variance,
- one way ANOVA in the case of variance homogenity
- Kruskal-Wallis- rank sum test for non homogenous variance
Results and discussion
Test resultsopen allclose all
- Species / strain:
- S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
- Metabolic activation:
- without
- Genotoxicity:
- positive
- Remarks:
- only at concentrations > 5000 ppm
- Cytotoxicity / choice of top concentrations:
- other: only at the highest concentration
- Vehicle controls validity:
- not applicable
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Species / strain:
- E. coli WP2 uvr A pKM 101
- Metabolic activation:
- with and without
- Genotoxicity:
- positive
- Remarks:
- only at concentrations > 5000 ppm
- Cytotoxicity / choice of top concentrations:
- other: only at the highest concentration
- Vehicle controls validity:
- not applicable
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Species / strain:
- E. coli WP2
- Metabolic activation:
- with and without
- Genotoxicity:
- positive
- Remarks:
- without activation: only at concentrations > 500 ppm, with activation: only at concentrations > 2000 ppm
- Cytotoxicity / choice of top concentrations:
- other: only at the highest concentration
- Vehicle controls validity:
- not applicable
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Additional information on results:
- TEST-SPECIFIC CONFOUNDING FACTORS
- Effects of pH: not expected as CTC is apolarm and stable
- Effects of osmolality: not expected as CTC is apolarm and stable
- Evaporation from medium: not applicable due to gas exposure method
- Water solubility: not applicable due to gas exposure method
- Precipitation: not applicable due to gas exposure method
- Other confounding effects: not expected
RANGE-FINDING/SCREENING STUDIES: No
COMPARISON WITH HISTORICAL CONTROL DATA: No
ADDITIONAL INFORMATION ON CYTOTOXICITY:
The maximum exposure concentration was 2% or 5%; carbon tetrachloride showed toxicity for all strains in tests conducted with 5% of the agents
see tables I - II for detailed results - Remarks on result:
- other: strain/cell type: TA 98
- Remarks:
- Migrated from field 'Test system'.
Any other information on results incl. tables
- Table Ia Mutagenicity Testing of Carbon Tetrachloride in S.typhimurium TA98
TA98 |
||||||||||
Lot. Nr. APE7331 |
Lot No. KSG7670 |
|||||||||
Dose % |
Test 1 (Mean) |
Test 2 (Mean) |
Test 3 (Mean |
Test 1-3 Mean + SD |
||||||
Negative control (Air) |
9 |
16 |
13 |
18 |
8 |
15 |
||||
13 |
16 |
(14) |
17 |
13 |
(15) |
9 |
13 |
(11) |
13+3.3 |
|
Without S 9 mix |
||||||||||
0.005 |
NT |
NT |
13 |
23 |
(18) |
NT |
NT |
18a |
||
0.01 |
NT |
NT |
16 |
20 |
(18) |
NT |
NT |
18a |
||
0.05 |
NT |
NT |
28 |
16 |
(22) |
11 |
16 |
(14) |
18+7.2 |
|
0.1 |
13 |
20 |
(17) |
22 |
23 |
(23) |
11 |
13 |
(12) |
17+5.3 |
0.2 |
NT |
NT |
NT |
NT |
15 |
17 |
(16) |
16a |
||
0.5 |
29 |
20 |
(25) |
28 |
31 |
(30) |
10 |
22 |
(16) |
23+7.8* |
1 |
40 |
24 |
(32) |
21 |
21 |
(21) |
26 |
21 |
(24) |
26+7.4** |
2 |
NT |
NT |
NT |
NT |
32 |
36 |
(34) |
34a |
||
5 |
36 |
38 |
(37) |
34 |
30 |
(32) |
31 |
17 |
(24) |
31+7.5 |
AF2 0.1 μg/plate |
719 |
680 |
(700) |
627 |
614 |
(621) |
584 |
596 |
(590) |
|
AF2 0.005 μg/plate |
||||||||||
TA98 |
||||||||||
Lot. Nr. APE7331 |
Lot No. KSG7670 |
|||||||||
Dose % |
Test 1 (Mean) |
Test 2 (Mean) |
Test 3 (Mean |
Test 1-3 Mean + SD |
||||||
Negative control (Air) |
22 |
28 |
26 |
39 |
14 |
28 |
||||
24 |
26 |
(25) |
36 |
32 |
(33) |
24 |
23 |
(22) |
27+6.6 |
|
With S 9 mix |
||||||||||
0.005 |
NT |
NT |
37 |
29 |
(33) |
NT |
NT |
33a |
||
0.01 |
NT |
NT |
32 |
26 |
(29) |
NT |
NT |
29a |
||
0.05 |
NT |
NT |
22 |
32 |
(27) |
11 |
23 |
(17) |
22+8.6 |
|
0.1 |
29 |
30 |
(30) |
37 |
22 |
(30) |
29 |
23 |
(26) |
28+5.4 |
0.2 |
NT |
NT |
NT |
NT |
21 |
26 |
(24) |
24a |
||
0.5 |
25 |
26 |
(26) |
25 |
28 |
(25) |
28 |
28 |
(28) |
26+1.5 |
1 |
33 |
36 |
(35) |
31 |
38 |
(35) |
31 |
24 |
(28) |
32+4.9 |
2 |
NT |
NT |
NT |
NT |
36 |
32 |
(34) |
34a |
||
5 |
52 |
38 |
(45) |
30 |
36 |
(33) |
24 |
28 |
(26) |
35+9.9 |
2AA 0.5 μg/plate |
332 |
355 |
(344) |
343 |
450 |
(397) |
444 |
436 |
(440) |
|
2AA 2.0 μg/plate |
||||||||||
* P<0.05
** P<0.01, compared with results of negative control group in each strain
NT not ested
AF2: 2-(2-furyl)-3-(5-nitro-2-furyl)acrylamide
2AA 2-aminoanthracene
a Statistical analysis was not applied because number of measurements was less than three
- Table Ib Mutagenicity Testing of Carbon Tetrachloride in E.coli WP2uvrA/pKM101
TA98 |
||||||||||
Lot. Nr. APE7331 |
Lot No. KSG7670 |
|||||||||
Dose % |
Test 1 (Mean) |
Test 2 (Mean) |
Test 3 (Mean |
Test 1-3 Mean + SD |
||||||
Negative control (Air) |
9 |
16 |
13 |
18 |
8 |
15 |
||||
13 |
16 |
(14) |
17 |
13 |
(15) |
9 |
13 |
(11) |
13+3.3 |
|
Without S 9 mix |
||||||||||
0.005 |
NT |
NT |
13 |
23 |
(18) |
NT |
NT |
18a |
||
0.01 |
NT |
NT |
16 |
20 |
(18) |
NT |
NT |
18a |
||
0.05 |
NT |
NT |
28 |
16 |
(22) |
11 |
16 |
(14) |
18+7.2 |
|
0.1 |
13 |
20 |
(17) |
22 |
23 |
(23) |
11 |
13 |
(12) |
17+5.3 |
0.2 |
NT |
NT |
NT |
NT |
15 |
17 |
(16) |
16a |
||
0.5 |
29 |
20 |
(25) |
28 |
31 |
(30) |
10 |
22 |
(16) |
23+7.8* |
1 |
40 |
24 |
(32) |
21 |
21 |
(21) |
26 |
21 |
(24) |
26+7.4** |
2 |
NT |
NT |
NT |
NT |
32 |
36 |
(34) |
34a |
||
5 |
36 |
38 |
(37) |
34 |
30 |
(32) |
31 |
17 |
(24) |
31+7.5 |
AF2 0.1 μg/plate |
719 |
680 |
(700) |
627 |
614 |
(621) |
584 |
596 |
(590) |
|
AF2 0.005 μg/plate |
||||||||||
TA98 |
||||||||||
Lot. Nr. APE7331 |
Lot No. KSG7670 |
|||||||||
Dose % |
Test 1 (Mean) |
Test 2 (Mean) |
Test 3 (Mean |
Test 1-3 Mean + SD |
||||||
Negative control (Air) |
22 |
28 |
26 |
39 |
14 |
28 |
||||
24 |
26 |
(25) |
36 |
32 |
(33) |
24 |
23 |
(22) |
27+6.6 |
|
With S 9 mix |
||||||||||
0.005 |
NT |
NT |
37 |
29 |
(33) |
NT |
NT |
33a |
||
0.01 |
NT |
NT |
32 |
26 |
(29) |
NT |
NT |
29a |
||
0.05 |
NT |
NT |
22 |
32 |
(27) |
11 |
23 |
(17) |
22+8.6 |
|
0.1 |
29 |
30 |
(30) |
37 |
22 |
(30) |
29 |
23 |
(26) |
28+5.4 |
0.2 |
NT |
NT |
NT |
NT |
21 |
26 |
(24) |
24a |
||
0.5 |
25 |
26 |
(26) |
25 |
28 |
(25) |
28 |
28 |
(28) |
26+1.5 |
1 |
33 |
36 |
(35) |
31 |
38 |
(35) |
31 |
24 |
(28) |
32+4.9 |
2 |
NT |
NT |
NT |
NT |
36 |
32 |
(34) |
34a |
||
5 |
52 |
38 |
(45) |
30 |
36 |
(33) |
24 |
28 |
(26) |
35+9.9 |
2AA 0.5 μg/plate |
332 |
355 |
(344) |
343 |
450 |
(397) |
444 |
436 |
(440) |
|
2AA 2.0 μg/plate |
||||||||||
* P<0.05
** P<0.01, compared with results of negative control group in each strain
NT not ested
AF2: 2-(2-furyl)-3-(5-nitro-2-furyl)acrylamide
2AA 2-aminoanthracene
a Statistical analysis was not applied because number of measurements was less than three
- Table II Mutagenicity Testing of Carbon Tetrachloride and chloroform in E.coli WP2/pKM101
Carbon Tetrachloride Lot No. APE7331 |
|||
Dose (%) |
Mean |
||
Negative control (Air) |
20 |
37 |
|
29 |
38 |
(30) |
|
Without S9 mix |
|||
0.01 |
44 |
43 |
(44)* |
0.05 |
54 |
61 |
(58)* |
0.1 |
74 |
83 |
(79)* |
0.2 |
NT |
NT |
|
0.5 |
138 |
155 |
(147)* |
1 |
243 |
230 |
(237)* |
2 |
320 |
367 |
(344)* |
5 |
232 |
208 |
(12)* |
AF2 0.1μg/plate 0.1μg/plate |
460 |
456 |
(220)* |
Negative Control (Air) |
48 |
71 |
|
53 |
51 |
(56) |
|
With S9 mix |
|||
0.01 |
55 |
59 |
(57)* |
0.05 |
70 |
39 |
(55)* |
0.1 |
91 |
85 |
(88)* |
0.2 |
NT |
NT |
|
0.5 |
150 |
180 |
(165)* |
1 |
288 |
284 |
(286)* |
2 |
445 |
395 |
(420)* |
5 |
101 |
71 |
(86)* |
2AA 10μg/plate |
272 |
358 |
(315) |
* P<0.05
** P<0.01, compared with results of negative control group in each strain
NT not ested
AF2: 2-(2-furyl)-3-(5-nitro-2-furyl)acrylamide
2AA 2-aminoanthracene
a Statistical analysis was not applied because number of measurements was less than three
Applicant's summary and conclusion
- Conclusions:
- Interpretation of results (migrated information):
ambiguous
- A CTC concentration dependent rise of the no. of revertants was found in the strains TA98, E. coli WP2 uvr A pKM 101 and E. coli WP2 pKM 101
- The used concentrations are very high
- Ambiguous results - Executive summary:
The study Araki (2004) presents an ambigous result concerning genotoxicity of CTC in the bacterial reverse mutation assay.
Salmonella strains S. typhimurium TA 1535, TA 1537, TA 98 and TA 100 and E. coli strains E. coli WP2 uvr A pKM 101 and E. coli WP2 pKM 101 were exposed to CTC using the gas exposure method.
A CTC concentration dependent rise of the no. of revertants was found in the strains TA98, E. coli WP2 uvr A pKM 101 and E. coli WP2 pKM 101. But for TA98, E. coli WP2 uvr A pKM 101 the concentrations where the criterion of 2 fold increase of no. of revertants compared to controls were reached were 10´000 ppm. And the results for E. coli WP2 pKM 101 (criterion reached at 1000 ppm) were not reproduced and based only on 2 replicate plates per concentration.
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