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EC number: 909-044-3 | CAS number: -
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:
- other information
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Comparable to guideline study with restrictions (No GLP, Only 4 strain tested). However, according to OECD SIDS a reliability of 1 was given.
Data source
Referenceopen allclose all
- Reference Type:
- publication
- Title:
- Salmonella mutagenicity tests: II. results from the testing of 270 chemicals
- Author:
- Mortelmanns K, Haworth S, Lawlor T, Speck W, Tainer B, Zeiger E
- Year:
- 1 986
- Bibliographic source:
- Environ Mutagen 8 suppl 7, 1 - 26
- Reference Type:
- publication
- Title:
- Carcinogenicity of mutagens: predictive capability of the Salmonella mutagenesis assay for rodent carcinogenicity.
- Author:
- Zeiger E
- Year:
- 1 987
- Bibliographic source:
- Cancer Res 47(5): 1287 - 1296
- Reference Type:
- secondary source
- Title:
- Unnamed
- Year:
- 2 004
Materials and methods
Test guideline
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 471 (Bacterial Reverse Mutation Assay)
- Deviations:
- yes
- Remarks:
- No GLP. Only 4 strain tested
- Principles of method if other than guideline:
- According Ames et al (1973), Proc. nat. Acad. Sci. 70, 2281-2285
- GLP compliance:
- not specified
- Type of assay:
- bacterial reverse mutation assay
Test material
- Reference substance name:
- Dimethyl phosphonate
- EC Number:
- 212-783-8
- EC Name:
- Dimethyl phosphonate
- Cas Number:
- 868-85-9
- Molecular formula:
- C2H7O3P
- IUPAC Name:
- dimethyl phosphonate
- Test material form:
- other: liquid
- Details on test material:
- - Name of test material (as cited in study report): dimethyl hydrogen phosphite
- Analytical purity: 97.8%
Constituent 1
Method
- Target gene:
- his operon
Species / strain
- Species / strain / cell type:
- other: S. typhimurium TA 98, 100, 1535, 1537 or TA 97
- Metabolic activation:
- with and without
- Metabolic activation system:
- S9 mix obtained from liver of Aroclor 1254 orally exposed rats and hamsters.
- Test concentrations with justification for top dose:
- 0, 100, 333, 1000, 3333, 5000, 7500, 10000 µg/plate.
- Vehicle / solvent:
- - Vehicle(s)/solvent(s) used: water
Controlsopen allclose all
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- Remarks:
- water
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- sodium azide
- Remarks:
- TA 1535 and TA 100, -S9. The concentration was not reported.
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- Remarks:
- water
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- other: 4-nitro-o-phenylenediamine (TA 98, -S9). The concentration was not reported.
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- Remarks:
- water
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- 9-aminoacridine
- Remarks:
- TA 97 and TA 1537, -S9. The concentration was not reported.
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- Remarks:
- water
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- other: 2-aminoanthracene, +S9. The concentration was not reported.
- Details on test system and experimental conditions:
- METHOD OF APPLICATION: preincubation
DURATION
- Preincubation period: 20 min
- Exposure duration: 48h
- Selection time (if incubation with a selection agent): 48h
PRELIMINARY DOSE-SETTING EXPERIMENT
Dimethyl phosphonate was initially tested with strain TA100 in the presence and absence of metabolic activation systems, over a wide dose range with an upper limit of 10 mg/plate, or less, when solubility problems were encountered. Toxicity was evidenced by one or more of the following phenomena: appearance of his- pinpoint colonies, reduced numbers of revertant colonies per plate, or thinning or absence of the bacterial lawn. Non toxic chemicals were tested in the initial experiment up to the 10 mg/plate dose level, or to a level determined by their solubility. Toxic chemicals were tested up to a high dose which exhibited some degree of toxicity. As a rule, at least one toxic dose was incorporated into the first mutagenicity test; the repeat test(s) occasionally had the doses adjusted so that and apparent toxic dose was not reached. - Evaluation criteria:
- The criteria used for data evaluation are the following: 1) mutagenic response: a dose-related, reproducible increase in the number of revertants over background, even if the increase was less than twofold; 2) non-mutagenic response: when no increase in the number of revertants was elicited by the chemical; 3) questionable response: when there was an absence of a clear-cut dose-related increase in revertants; when the dose-related increases in the number of revertants were not reproducible; or when the response was of insufficient magnitude to support a determination of mutagenicity.
Results and discussion
Test results
- Species / strain:
- other: S. typhimurium TA 98, 100, 1535, 1537 or TA 97
- Metabolic activation:
- with and without
- Genotoxicity:
- positive
- Remarks:
- S. typhimurium TA 100
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- TA 100 (+S9, 10% HLI, 10000 mg/plate); TA1535 (+S9, 10% HLI, 10000 mg/plate ), TA 98 (+S9, 10% HLI and RLI, 10000 mg/plate )
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not examined
- Positive controls validity:
- valid
- Additional information on results:
- The mutagenicity of dimethyl phosphonate was tested in two laboratories. In one laboratory (Case Western University) it was judged equivocal, in the other laboratory (EGG Mason Research Institute, later Microbiological Associates) it was tested with a positive result in strain S. typhimurium TA 100.
Conclusion: dimethyl phosphonate was evaluated to be positive with TA 100, negative with TA 98, 1535, 1537 or 97.
Any other information on results incl. tables
Table 1. Mutagenicity of dimethyl phosphonate (Case Western University)
| TA 100 | TA 1535 | TA 1537 | TA 98 | |||||||||||||
| Dose (µg/plate) | NA |
NA |
10% HLI |
10% HLI |
10% HLI |
10% RLI |
10% RLI | NA | 10% HLI | 10% HLI | NA | 10% HLI | 10% RLI | NA | 10% HLI | 10% RLI |
| 0 | 145±10.4 | 149±5.4 | 223±3.5 | 209±3.5 | 110±6.1 | 188±1.9 | 197±8.4 | 26±3.0 | 13±2.2 | 11±1.7 | 16±8.9 | 22±3.2 | 19±1.5 | 31±3.2 | 43±4.2 | 39±2.7 |
| 100 | 144±13.8 | 152±11.5 | 177 ±17.9 | 200 ±7.8 | 92±3.3 | 188 ±21.9 | 170 ±4.4 | 34±3.3 | 13 ±2.0 | 10±3.0 | 14±2.2 | 27±4.3 | 27±1.9 | 35±2.6 | 36 ±8.5 | 35±2.1 |
| 333 | 192±12.0 | 156±9.8 | 192 ±15.3 | 225 ±1.5 | 112±6.2 | 239 ±11.9 | 186±17.7 | 33±1.9 | 11±1.2 | 13±1.5 | 13±0.7 | 19±2.9 | 18±2.4 | 33±1.8 | 39±4.3 | 36±2.5 |
| 1000 | 161±16.2 | 151 ±6.5 | 204± 5.8 | 248±8.3 | 110±4.3 | 225±22.2 | 189±13.3 | 32±2.8 | 12 ±0.3 | 12±2.0 | 18±2.7 | 25±2.4 | 19±4.2 | 37±4.4 | 31±3.5 | 26±6.0 |
| 3333 | 283 ±6.4 | 179 ±9.6 | 197±18.2 | 242 ±11.3 | 84 ±13.8 | 268±2.4 | 199±5.9 | 32 ±1.9 | 13 ±2.4 | 14±4.1 | 14±0.6 | 24 ±1.8 | 19 ±2.6 | 37±3.2 | 29±6.1 | 34±1.9 |
| 10000 | 204 ±13.5 | 168 ±9.1 | 206 ±9.3 | 234 ±10.1 | t | 269±22.9 | 224±3.6 | 26 ±1.5 | t | t | 11±1.2 | 17±4.2 | 15±0.9 | 42±5.9 | t | t |
| POS | 1882±197.2 | 1505 ±23.3 | 3362 ±176.8 | 1014±68.0 | 1919 ±139.9 | 1405 ±77.4 | 2073±71.3 | 816 ±93.2 | 367 ±45.1 | 447±23.4 | 275 ±84.8 | 281 ±20.8 | 142±21.1 | 228 ±8.6 | 1213±142.9 | 1125±80.5 |
Table 2. Mutagenicity of dimethyl phosphonate (EGG Mason Research Institute, later Microbiological Associates)
| TA 100 | TA 1535 | TA 1537 | TA 98 | |||||||||||||
| Dose (µg/plate) | NA | NA | 10% HLI | 10% HLI | 30% HLI | 10% RLI | 10% RLI | NA | 10% HLI | 10% HLI | NA | 10% HLI | 10% RLI | NA | 10% HLI | 10% RLI |
| 0 | 144± 5.5 | 134±1.7 | 136±2.4 | 142±6.7 | 165±7.8 | 126±4.3 | 148± 4.0 | 37±0.4 | 12±2.2 | 13±2.3 | 5±1.0 | 8±1.8 | 6±1.3 | 19±1.9 | 30±1.2 | 31±1.7 |
| 100 | 139±6.6 | 149±2.6 | 143 ±9.9 | |||||||||||||
| 333 | 145±3.7 | 153 ±6.0 | 148 ±8.7 | |||||||||||||
| 1000 | 156±2.0 | 162 ±2.8 | 139± 2.6 | 147±3.5 | 155±5.8 | 143±9.1 | 133±5.8 | 31±5.8 | 19 ±2.3 | 13±1.3 | 4±0.6 | 10±1.2 | 7±2.0 | 18±1.2 | 29±3.2 | 20±1.8 |
| 3333 | 157 ±1.8 | 173 ±1.2 | 170 ±8.3 | 174 ±13.9 | 171 ±11.1 | 146±12.1 | 166±5.5 | 31±2.8 | 18 ±2.1 | 19±3.8 | 3±0.6 | 6 ±2.1 | 7 ±0.9 | 19±2.2 | 27±4.2 | 25±3.5 |
| 5000 | 175 ±6.0 | 187 ±11.7 | 177 ±15.6 | 170±4.4 | 33 ±2.0 | 17±2.4 | 16±2.7 | 7±2.0 | 7±1.2 | 7±2.2 | 18±1.8 | 26±4.3 | 28±1.5 | |||
| 7500 | 193 ±2.3 | 200 ±6.4 | 189 ±12.9 | 162 ±7.4 | 34±1.7 | 21 ±2.6 | 13±1.2 | 6±1.5 | 9±0.7 | 6±0.6 | 17± 4.8 | 26±4.1 | 25±1.5 | |||
| 10000 | 172±9.8 | 190 ±2.9 | 190 ±1.0 | 193±10.0 | 196 ±9.7 | 156 ±6.6 | 161±7.8 | 33 ±1.0 | 18±2.7 | 19±2.2 | 3 ±0.4 | 9±2.3 | 5±1.2 | 18 ±1.2 | 32±4.9 | 34±2.6 |
| POS | 1210±14.0 | 1000±3.2 | 804±24.5 | 1004±168 | 1105 ±37.3 | 563±13.5 | 1450±43.1 | 920±38.9 | 237±28.5 | 73 ±4.2 | 341±49.1 | 136±16.5 | 200 ±14.5 | 1433±41.3 | 1056±75.2 | 2011 ± 47.5 |
Applicant's summary and conclusion
- Conclusions:
- Interpretation of results:
positive S. typhimurium TA 100 - Executive summary:
Mortelmans (1986)
Salmonella typhimurium strains TA1535, TA1537, TA98 and TA100 were treated with dimethyl phosphonate diluted in H2O using the Ames preincubation method equivalent to OECD Guideline No. 471 with deviations (No GLP. Only 4 strain tested), both with and without the addition of a rat and hamster liver homogenate metabolising system. The dose range was determined in a preliminary toxicity assay with upper dose 10 mg/plate. The mutagenicity of dimethyl phosphonate was tested in two laboratories. In one laboratory (Case Western University) it was judged equivocal, in the other laboratory (EGG Mason Research Institute, later Microbiological Associates) it was tested with a positive result in strain TA 100.
Dimethyl phosphonate was evaluated to be positive with TA 100, negative with TA 98, 1535, 1537 or 97.
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