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EC number: 201-051-3 | CAS number: 77-71-4
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
- Study period:
- 1982-08-02 to 1982-09-03
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: Study performed according to GLP, comparable to current guidelines with some deviations.
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 982
- Report date:
- 1982
Materials and methods
Test guidelineopen allclose all
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 471 (Bacterial Reverse Mutation Assay)
- Deviations:
- yes
- Remarks:
- No confirmation in an independent experiment. No E. coli strains were investigated.
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- EU Method B.13/14 (Mutagenicity - Reverse Mutation Test Using Bacteria)
- Deviations:
- yes
- Remarks:
- No confirmation in an independent experiment. No E. coli strains were investigated.
- GLP compliance:
- yes
- Type of assay:
- bacterial reverse mutation assay
Test material
- Reference substance name:
- 5,5-dimethylhydantoin
- EC Number:
- 201-051-3
- EC Name:
- 5,5-dimethylhydantoin
- Cas Number:
- 77-71-4
- Molecular formula:
- C5H8N2O2
- IUPAC Name:
- 5,5-dimethylimidazolidine-2,4-dione
- Reference substance name:
- dimethylhydantoin
- IUPAC Name:
- dimethylhydantoin
- Details on test material:
- - Name of test material : Dimethylhydantoin
- Physical state: solid
- Substance type: white crystalline solid
- Analytical purity: not data
- Lot/batch No.: 447:34-2
- Storage condition of test material: room temperature
Constituent 1
Constituent 2
Method
- Target gene:
- All were histidine auxotrophs. The mutations for each strains were; hisG46 for strains TA1535 and TA100, hisC3076 for TA1537 and hisD3052 TA1538 and TA98.
Species / strainopen allclose all
- Species / strain / cell type:
- S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
- Details on mammalian cell type (if applicable):
- no data
- Additional strain / cell type characteristics:
- not specified
- Species / strain / cell type:
- S. typhimurium TA 1538
- Details on mammalian cell type (if applicable):
- no data
- Additional strain / cell type characteristics:
- not specified
- Metabolic activation:
- with and without
- Metabolic activation system:
- S9 mix from male Sprague-Dawley rats liver microsomes
- Test concentrations with justification for top dose:
- 100, 500, 2500, 5000 and 10000 µg/plate
- Vehicle / solvent:
- - Vehicle(s)/solvent(s): deionised distilled water
Controlsopen allclose all
- Untreated negative controls:
- not specified
- Negative solvent / vehicle controls:
- not specified
- True negative controls:
- not specified
- Positive controls:
- yes
- Positive control substance:
- 9-aminoacridine
- Remarks:
- 75 µg without activation with strain TA 1537
- Untreated negative controls:
- not specified
- Negative solvent / vehicle controls:
- not specified
- True negative controls:
- not specified
- Positive controls:
- yes
- Positive control substance:
- other: 2-aminoanthracene
- Remarks:
- 1.0 µg in the presence of activation with TA 98, TA100 and TA 1538 strains and at 4.0 µg with the TA 1535 and TA 1537 strains
- Untreated negative controls:
- not specified
- Negative solvent / vehicle controls:
- not specified
- True negative controls:
- not specified
- Positive controls:
- yes
- Positive control substance:
- other: 2-nitrofluorene
- Remarks:
- 10 µg without activation, with strains TA98 and TA 1538
- Untreated negative controls:
- not specified
- Negative solvent / vehicle controls:
- not specified
- True negative controls:
- not specified
- Positive controls:
- yes
- Positive control substance:
- other: 1,3-propane sultone
- Remarks:
- 0.04 µL without activation, with strains TA 100 and TA 1535
- Untreated negative controls:
- not specified
- Negative solvent / vehicle controls:
- yes
- Remarks:
- distilled , deionised water
- True negative controls:
- not specified
- Positive controls:
- not specified
- Positive control substance:
- not specified
- Details on test system and experimental conditions:
- METHOD OF APPLICATION: preincubation
DURATION
- Exposure duration: 20 minutes at 37 °C
- Selection time (if incubation with a selection agent): 48 hours at 37 °C
NUMBER OF REPLICATIONS: 3
SELECTION AGENT (mutation assays): L-Histidine and D-biotin - Evaluation criteria:
- For a test article to be considered positive, it must cause at least a doubling in the average revertants per plate of at least one tester strain. This increase in the average number of revertants per plate must be accompanied by a dose response to increasing concentrations of the test article, and in those cases where the observed increase is less than three-fold, the response must be reproducible.
- Statistics:
- All platings were done in triplicate. For each triplicate plating, an average and standard deviation were calculated.
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:
- no cytotoxicity
- Remarks:
- tested up to 10000 µg/plate
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Species / strain:
- S. typhimurium TA 1538
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity
- Remarks:
- tested up to 10000 µg/plate
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Additional information on results:
- RANGE-FINDING/SCREENING STUDIES:
A preliminary toxicity determination study of the test substance, DMH, was carried out for eight serial half-log dilutions, 2.9, 9.4, 30, 95, 305, 977, 3125 and 10000 µg, plated with a diluted TA100 culture on non-selective agar (viable counts) and with an undiluted TA100 culture on selective agar (revertants). A negative control with no test substance, DMH, and only 50 µl of H2O, was added to the plate. - Remarks on result:
- other: all strains/cell types tested
- Remarks:
- Migrated from field 'Test system'.
Any other information on results incl. tables
Table 1. Results for Gene Mutation Assay with metabolic activation
Averaged Revertants per plate ± S.D (with rat liver microsomes) |
|||||
Concentration µL/plate |
TA98 |
TA100 |
TA1535 |
TA1537 |
TA1538 |
001 |
35 (4) |
109 (13) |
9 (4) |
11 (4) |
14 (3) |
500 |
36 (2) |
108 (26) |
10 (3) |
11 (2) |
19 (6) |
2500 |
40 (6) |
116 (27) |
8 (2) |
13 (7) |
18 (3) |
5000 |
33 (9) |
80 (4) |
8 (2) |
11 (2) |
16 (1) |
10000 |
38 (5) |
96 (5) |
7 (1) |
8 (2) |
18 (1) |
Solvent control (H2O) |
35 (7) |
107 (31) |
10 (2) |
9 (6) |
20 (6) |
Positive control |
349 (34) |
398 (31) |
212 (5) |
296 (12) |
444 (28) |
Table 2. Results for Gene Mutation Assay without metabolic activation
Averaged Revertants per plate ± S.D (without rat liver microsomes) |
|||||
Concentration µL/plate |
TA98 |
TA100 |
TA1535 |
TA1537 |
TA1538 |
100 |
18 (4) |
111 (23) |
31 (2) |
7 (1) |
9 (5) |
500 |
18 (7) |
131 (11) |
36 (2) |
7 (2) |
6 (3) |
2500 |
17 (6) |
117 (31) |
31 (7) |
6 (2) |
7 (3) |
5000 |
22 (2) |
110 (24) |
35 (4) |
7 (1) |
10 (3) |
10000 |
19 (6) |
107 (20) |
30 (6) |
6 (1) |
6 (4) |
Solvent control(H2O) |
21 (4) |
127 (41) |
24 (4) |
5 (2) |
10 (7) |
Positive control |
874 (29) |
2100 (122) |
2273 (115) |
420 (217) |
1657 (29) |
Applicant's summary and conclusion
- Conclusions:
- Interpretation of results (migrated information):
negative with metabolic activation
negative without metabolic activation
The test material was found not to cause any positive response in any of the Salmonella strains tested, with or without metabolic activation.
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