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EC number: 204-815-4 | CAS number: 126-97-6
Endpoint summary
Administrative data
Key value for chemical safety assessment
Genetic toxicity in vitro
Description of key information
The weight of evidence suggests that MeaTG is not genotoxic.
Link to relevant study records
- 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:
- test procedure in accordance with national standard methods with acceptable restrictions
- Reference:
- Composition 0
- Qualifier:
- equivalent or similar to
- Guideline:
- OECD Guideline 471 (Bacterial Reverse Mutation Assay)
- Deviations:
- not specified
- GLP compliance:
- not specified
- Type of assay:
- bacterial reverse mutation assay
- Test material information:
- Composition 1
- Target gene:
- Histidine reversion
- Species / strain:
- other: Strains: TA98, TA100, TA1535 and TA1537
- Metabolic activation:
- with and without
- Metabolic activation system:
- Rat and hamster liver S9 induced with aroclor 1254
- Test concentrations with justification for top dose:
- 0, 10, 33, 100, 333 and 1000 µg/plate
- Vehicle:
- no data
- Negative controls:
- no
- Solvent controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- other: Without activation : sodium azide (TA1535 and TA 100), 9-aminoacridine (TA 97), 4-nitro-o-phenylenediamine (TA98). With activation : 2-aminoanthracene (all strains).
- Details on test system and conditions:
- In the Salmonella assay, a test tube containing a suspension of one strain of Salmonella typhimurium plus S9 mix or plain buffer without S9, is incubated for 20 minutes at 37º C with the test chemical. Control cultures, with all the same ingredients except the test chemical, are also incubated. In addition, positive control cultures are also prepared; these contain the particular bacterial tester strain under investigation, the various culture ingredients, and a known potent mutagen. After 20 minutes, agar is added to the cultures and the contents of the tubes are thoroughly mixed and poured onto the surface of Petri dishes containing standard bacterial culture medium. The plates are incubated for 48 hours and then counted. The substance was tested initially in a toxicity assay to determine the appropriate dose range.
The toxicity assay was performed by using TA 100. Toxic concentrations were those at which a decrease in the number of his+ colonies was seen or at which there was a clearing in the density of the background lawn.
- Test Design . Number of replicates : 3
- Description of follow up repeat study : same conditions than the initial experiment performed 1 week later - Evaluation criteria:
- The positive control plates are counted, and the number of mutant colonies appearing on them must be significantly increased over the spontaneous control number for the test to be considered valid. If no increase in mutant colonies is seen after testing several strains under several different culture conditions, the test chemical is considered to be non mutagenic in the Salmonella test.
- Statistics:
- None
- Key result
- Species / strain:
- other: Strains: TA98, TA100, TA1535 and TA1537
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity:
- yes
- Remarks:
- > 1000 µg/plate
- Vehicle controls valid:
- yes
- Negative controls valid:
- not examined
- Positive controls valid:
- yes
- Remarks on result:
- other: all strains/cell types tested
- Remarks:
- Migrated from field 'Test system'.
- Conclusions:
- Under these experimental conditions, sodium thioglycolate is considered as non-genotoxic
- Executive summary:
In a study performed according to the US NTP protocol, four S. typhimurium strains (TA 98, TA 100, TA 1535 and TA 1537) were exposed to sodium thioglycolate in a preincubation assay. Based on a preliminary toxicity assay, concentrations up to 1000 µg/plate were used with or without metabolic activation (rat and hamster S9) in all four strains. Sodium thioglycolate did not induce mutations in these studies. Positive and solvent controls gave the expected results.
- Endpoint:
- in vitro gene mutation study in bacteria
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Reference:
- Composition 0
- Qualifier:
- according to
- Guideline:
- OECD Guideline 471 (Bacterial Reverse Mutation Assay)
- Deviations:
- no
- GLP compliance:
- yes
- Type of assay:
- bacterial reverse mutation assay
- Test material information:
- Composition 1
- Target gene:
- Histidine reversion
- Species / strain:
- other: Strains: TA1535, TA1537, TA98, TA100 and TA102
- Metabolic activation:
- with and without
- Metabolic activation system:
- S9-mix (from livers of male Sprague-Dawley rats treated by Aroclor 1254)
- Test concentrations with justification for top dose:
- 15, 50, 150, 500, 1500 and 5000 µg a.i./plate.
Two distinct experiments were performed using these doses. - Vehicle:
- sterile distilled water
- Negative controls:
- no
- Solvent controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- other: see below
- Details on test system and conditions:
- METHOD DETAILS:
- Test concentrations:
. Preliminary study (on TA100): 0, 0.15, 0.5, 1.5, 5, 15, 50, 150, 500, 1500 and 5000 µg/plate
. Main study: see the "Test concentration" field
- Number of replicates: 3
- Positive controls:
without S9-mix
. for TA1535 and TA100: N-ethyl-N'-nitro-N-nitrosoguanidine (5 and 2 µg/plate respectively)
. for TA1537: 9-aminoacridine (80 µg/plate)
. for TA98: 4-Nitroquinoline-1-oxide (0.2 µg/plate)
. for TA102: mitomycin C (0.5 µg/plate)
with S9-mix
. for TA1535, TA1357 and TA100: 2-aminoanthracene (2; 2 and 1µg/plate respectively)
. for TA98: benzo(a)pyrene (5 µg/plate)
. for TA102: 1,8-Dihydroxyanthraquinone (10 µg/plate)
- Pre-incubation time: no
- Pre-incubation temperature: no
- Incubation time: 48h
- Incubation temperature: 37°C
EXAMINATION:
- Bacterial toxicity: determined by examination of background lawn growth
- Number of revertants / plate
ANALYTICAL DEVICE: Colonies were counted electronically using a Domino Colony Counter. - Evaluation criteria:
- The reverse mutation assay may be considered valid if the following criteria are met: All tester strain cultures exhibit a characteristic number of spontaneous revertants per plate in the vehicle and untreated controls. Acceptable ranges are presented below with historical control ranges for 2001 and 2002 presented in Table 1.
Spontaneous Mutation Ranges:
TA1535 7 to 40
TA100 60 to 200
TA1537 2 to 30
TA98 8 to 60
TA102 180 to 400
The test material may be considered positive in this test system if the following criteria are met: The test material should have induced a reproducible, dose-related and statistically significant increase in the revertant count in at least one strain of bacteria. - Statistics:
- Dunnett's method of linear regression
- Key result
- Species / strain:
- other: Strains: TA1535, TA1537, TA98, TA100 and TA102
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity:
- yes
- Remarks:
- = 5000 µg/plate
- Vehicle controls valid:
- yes
- Negative controls valid:
- not examined
- Positive controls valid:
- yes
- Remarks on result:
- other: all strains/cell types tested
- Remarks:
- Migrated from field 'Test system'.
- Additional information on results:
- CYTOTOXICITY:
The test substance was toxic at 5000 µg/plate in the TA100 strain (without S9 mix: very weak bacterial background lawn, with S9 mix: sparse bacterial background lawn).
GENOTOXICITY:
No significant increases in the number of revertants were observed at any dose level, with or without metabolic activation. - Conclusions:
- Interpretation of results (migrated information):
negative
Ammonium thioglycolate was considered to be non-mutagenic under the conditions of this test. - Executive summary:
Ammonium thioglycolate was tested in a bacterial gene mutations assay performed following a protocol compliant with the OECD guideline # 471. The direct plate incorporation procedure was performed with Salmonella typhimurium TA 98, TA 100, TA 102, TA 1535 and TA 1537 at concentrations up to 5,000 µg/plate. Cytotoxic effects were observed in the absence and in the presence of a metabolic activator (Aroclor 1254-induced rat liver S9) at the concentration of 5,000 µg/plate. Ammonium thioglycolate did not induce mutations in the bacterial mutation test in either the absence or presence of metabolic activator in any strain tested. The positive and negative controls included in the experiment showed the expected results.
- Endpoint:
- in vitro gene mutation study in mammalian cells
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: GLP guideline study
- Reference:
- Composition 0
- Qualifier:
- according to
- Guideline:
- EU Method B.17 (Mutagenicity - In Vitro Mammalian Cell Gene Mutation Test)
- Version / remarks:
- Cited as Directive 2000/32/EC, B.17
- GLP compliance:
- yes
- Type of assay:
- mammalian cell gene mutation assay
- Test material information:
- Composition 1
- Target gene:
- Locus Examined: thymidine kynase, the selection agent used was 5 µg/ml trifluorothymidine
- Species / strain:
- mouse lymphoma L5178Y cells
- Details on mammalian cell lines (if applicable):
- - Type and identity of media: the medium used was RPMI 1640 (complete medium) with 3 or 15 % horse serum.
- Properly maintained: yes
- Periodically checked for Mycoplasma contamination: yes
- Periodically "cleansed" against high spontaneous background: yes - Additional strain characteristics:
- not specified
- Metabolic activation:
- with and without
- Metabolic activation system:
- S9 derived from male Sprague Dawley (phenobarbital/B-naphtoflavone induced rat liver)
- Test concentrations with justification for top dose:
- Non-activated conditions: Initial trial: 13, 50, 100, 200, 400, 800 and 1600 µg/mL; Confirmatory trial: 13, 25, 50, 100, 200, 400 and 600 µg/mL
S9-activated conditions: 50, 100, 200, 400, 800 and 1600 µg/mL
Duplicate cultures were processed for all trials. - Vehicle:
- - Solvent used: deionised water
- Negative controls:
- yes
- Solvent controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- cyclophosphamide
- methylmethanesulfonate
- Details on test system and conditions:
- Experimental Performance:
In the mutation experiment 1x10e7 cells/flask suspended in 10 ml RPMI medium with 3 % horse serum (15 % during 24 h treatment) were exposed to various concentrations of the test item either in the presence or absence of metabolic activation.
After 4 h (after 24 h in the second experiment) the test item was removed by centrifugation and washing twice in "saline G". Subsequently the cells were resuspended in 30 ml complete culture medium and incubated for an expression and growth period of totally 72 h. In the second experiment the expression time without metabolic activation was 48 hours (RPMI medium with 15 % horse serum).
The cell density was determined each day and adjusted to 3x10e5 cells/ml, if necessary. Relative suspension and total growth (RSG and RTG) of the treated tell cultures were calculated after 48 h (72 h following continuous treatment) according to the method of Clive and Spector. One sample of the cells was taken at the end of the treatment (4 h and 24 h, respectively), diluted and seeded into microtiter plates (about 2.5 cells/well), to determine the survival of the cells after treatment (cloning efficiency 1).
After the expression period the tells were seeded into microtiter plates. Cells from each experimental group were seeded into 2 microtiter plates so that each well contained approximately 4x10e3 tells in selective medium with TFT. The viability (cloning efficiency 2) was determined by seeding about 2.5 cells per well into 2 microtiter plates (same medium without TFT). The plates are incubated at 37 °C in 4.5 %C02 and 95.5 % humidified air for 10 - 15 days to determine the cloning efficiency and to evaluate mutagenicity. Then the plates were evaluated manually.
Size Distribution of the Colonies:
The numbers of colonies were counted manually. The colony size distribution was determined in the controls and at all concentrations of the test item
Data Recording:
All plates were evaluated manually.
The mutation frequency was derived from the cloning efficiency under selective conditions compared to the corresponding viability under non-selective conditions - Evaluation criteria:
- Acceptability of the Assay:
A mutation assay is considered acceptable if it meets the following criteria:
a) Both plates, from either the survival or the TFT resistance-testing portion of the experiment are analysable.
b) The absolute cloning efficiency 2 of the negative and/or solvent controls is > 0.5 (50 %).
c) The spontaneous mutant frequency in the negative and/or solvent controls are in the range of the historical control data .
d) The positive controls (MMS and CPA) induce significant (at least 2-fold) increases in the mutant frequencies. The values of the cloning efficiencies and the relative total growth are greater than 10 % of the concurrent vehicle control group.
Evolution of results:
A test item is classified as positive if it induces either a reproducible concentration-related increase in the mutant frequency or a reproducible positive response for at least one of the test points - Statistics:
- The survival rate and viability was determined based on the Poisson distribution method. The zero term of the Poisson distribution, [P(0)] method, was used.
- Key result
- Species / strain:
- mouse lymphoma L5178Y cells
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity:
- other: 4-h experiment (+/-S9): > 1600 µg/ml / 24-h experiment (-S9): >= 800 µg/ml
- Vehicle controls valid:
- yes
- Negative controls valid:
- not examined
- Positive controls valid:
- yes
- Remarks on result:
- other: all strains/cell types tested
- Remarks:
- Migrated from field 'Test system'.
- Additional information on results:
- No substantial and reproducible dose dependent increase in mutant colony numbers was observed in both main experiments. No relevant shift of the ratio of small versus large colonies was observed up to the maximal concentration of the test item.
Appropriate reference mutagens were used as positive controls and showed a distinct increase in induced mutant colonies, indicating that the tests were sensitive and valid. - Conclusions:
- Interpretation of results (migrated information):
negative
Ammonium Thioglycolate did not induce mutations in the mouse lymphoma thymidine kinase locus assay using the cell line L5178Y in the absence and presence of metabolic activation. - Executive summary:
Ammonium thioglycolate was tested in an in vitro gene mutation assay using mammalian cells cultures both in the absence and presence of metabolic activation (S9 mix), according to the Directive 2000/32/EC, B17 and in compliance with the Principles of Good Laboratory Practice.
In a mammalian cell gene mutation assay (TK+/-), mouse lymphoma L5178Y cells cultured in vitro were exposed to ammonium thioglycolate (purity 71.1%) in deionised water. Two parallels culture were used. The first main experiment was performed without microsomal activation at concentrations of 0, 13, 50, 100, 200, 400, 800 and 1600 µg/ml, and with activation at concentrations of 0, 50, 100, 200, 400,800 and 1600 µg/ml
with a treatment period of 4 h. The second experiment was solely performed in the absence of metabolic activation at concentrations of 0, 13, 25, 50, 100, 200, 400 and 600 µg/ml, with a treatment period of 24 h. Appropriate positive controls were used and showed a statistical increase in mutant colonies, indicating that the tests were sensitive and valid.
After a 48 rest period, cells were incubated mutagenicity evaluation with trifluorothymidine (TFT).
No substantial and reproductible dose dependant increase in mutant colony numbers was observed in both main experiments. No relevant shift of the ratio of small versus large colonies was observed up to the maximal concentration of the test item.
Under these experimental conditions, ammonium thioglycolate did not induce any increase in mutant colonies and is not considered as mutagenic in this mouse lymphoma mouse.
- Endpoint:
- in vitro cytogenicity / chromosome aberration study in mammalian cells
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: GLP guideline study
- Reference:
- Composition 0
- Qualifier:
- according to
- Guideline:
- OECD Guideline 473 (In Vitro Mammalian Chromosome Aberration Test)
- Deviations:
- no
- Qualifier:
- according to
- Guideline:
- EU Method B.10 (Mutagenicity - In Vitro Mammalian Chromosome Aberration Test)
- Deviations:
- no
- GLP compliance:
- yes
- Type of assay:
- in vitro mammalian chromosome aberration test
- Test material information:
- Composition 1
- Species / strain:
- other: Human lymphocytes
- Metabolic activation:
- with and without
- Metabolic activation system:
- 10% S9 mix, prepared from a liver microsomal fraction (S9) of rats induced with Aroclor 1254.
- Test concentrations with justification for top dose:
- Without S9: 0, 30, 100 and 300 µg/ml
With S9: 0, 100, 300 and 1000 µg/ml - Vehicle:
- distilled water
- Negative controls:
- no
- Solvent controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- cyclophosphamide
- mitomycin C
- Details on test system and conditions:
- For each culture, heparinised whole blood were added to culture medium containing a mitogen (phytohaemogglutinin) and incubated at 37°C. After 48 hours, the conditions of treatment were as follows, using 2 cultures/experimental point: . without S9 mix, the test or control substances remained in the culture medium either for 24 hours or for 48 hours, until harvest, . with S9 mix, the test or control substances remained in the culture medium for 2 hours. The cells were then rinsed and fresh culture medium was added. The cultures were then incubated until the appropriate harvest time, 24 and 48 hours. Each culture was then treated for 2 hours with a colcemid solution to block them at the metaphase-stage of mitosis and harvested. The chromosomal preparations were stained and screened microscopically for mitotic index and for aberrations: 200 well-spread metaphases per dose were read, whenever possible.
- Evaluation criteria:
- A reproducible and statistically significant increase in the aberrant cells frequency for at least one of the doses is considered as a positive response.
- Statistics:
- X² test
- Key result
- Species / strain:
- lymphocytes: human
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity:
- other: With S9 : 1000 µg/ml. Without S9 : 300 µg/ml
- Vehicle controls valid:
- yes
- Negative controls valid:
- not examined
- Positive controls valid:
- yes
- Remarks on result:
- other: strain/cell type: Human lymphocytes
- Remarks:
- Migrated from field 'Test system'.
- Executive summary:
The potential of 2-thioglycolic acid to induce structural chromosome aberrations in human lymphocytes was evaluated according to OECD 473 and EC 92/69/EEC B.10 guidelines in compliance with the Principles of Good Laboratory Practice. The 2-thioglycolic acid was tested with or without a metabolic activation system (rat liver S9 mix) (2 cultures/experimental point) at the dose levels of 30, 100 and 300 µg/ml without S9 mix, and 100, 300 and 1000 µg/ml with S9 mix. Without S9 mix: the cultures were incubated with the test or control substances which remained in the culture medium, until the appropriate harvest time : 24 and 48 hours, with S9 mix: the test or control substances remained in a culture medium containing 15% S9 mix (10% S9/S9 mix) for 2 hours. The cells were then centrifuged, the treatment medium removed, the cells resuspended in fresh culture medium. The cultures were then incubated until the appropriate harvest time: 24 and 48 hours. Two hours before harvesting, the cells were treated with a colcemid solution to block them at the metaphase-stage of mitosis. The chromosomal preparations were stained and screened microscopically for mitotic index and for aberrations: 200 well-spread metaphases per dose were read, whenever possible. 2-thioglycolic acid did not induce any noteworthy increase in the number of cells with structural chromosome aberration, both with and without S9 mix, in either harvest time.
Referenceopen allclose all
Chemical Name: | Sodium thioglycolate |
CAS Number: | 367-51-1 |
Study Type: | Salmonella |
Study ID: | 471613 |
Study Result: | Negative |
Year Completed: | 1979 |
Vehicle Control: | Water |
Protocol: | Preincubation |
Individual strain data is presented as mean ± standard error. |
Abbreviations are noted at bottom of page. |
Trial summary calls are shown in parentheses. |
Strain: TA1535 | |||||||||||
Dose | No Activation | No Activation | 10% HLI | 10% HLI | 10% RLI | ||||||
(Negative) | (Negative) | (Negative) | (Negative) | (Negative) | |||||||
ug/Plate | Mean | ± SEM | Mean | ± SEM | Mean | ± SEM | Mean | ± SEM | Mean | ± SEM | |
0 | 7 | 0.7 | 7 | 0.6 | 6 | 0.9 | 7 | 2.6 | 7 | 0.7 | |
10 | 6 | 1 | 6 | 0.9 | 5 | 0.9 | 6 | 2 | 8 | 1.2 | |
33 | 5 | 1.5 | 6 | 0.9 | 7 | 1.5 | 9 | 1.2 | 6 | 1.3 | |
100 | 8 | 3.5 | 9 | 1.3 | 7 | 0.6 | 9 | 0.7 | 6 | 0.9 | |
333 | 6 | 0.6 | 6 | 0.9 | 5 | 1.2 | 7 | 1.5 | 8 | 1.2 | |
1000 | 5 | 1.2 | 8 | 2 | 5 | 0.3 | 8 | 1.2 | 8 | 0.9 | |
Positive Control | 288 | 32.3 | 251 | 40.8 | 106 | 16 | 43 | 4.1 | 135 | 9.7 | |
Strain: TA100 | |||||||||||||
Dose | No Activation | No Activation | 10% HLI | 10% HLI | 10% RLI | 10% RLI | |||||||
(Negative) | (Negative) | (Negative) | (Equivocal) | (Negative) | (Negative) | ||||||||
ug/Plate | Mean | ± SEM | Mean | ± SEM | Mean | ± SEM | Mean | ± SEM | Mean | ± SEM | Mean | ± SEM | |
0 | 100 | 5 | 110 | 5.8 | 185 | 26.5 | 179 | 11.7 | 175 | 27.8 | 189 | 8.7 | |
10 | 95 | 5 | 126 | 11.4 | 160 | 18 | 164 | 6.2 | 140 | 30.4 | 204 | 37.7 | |
33 | 105 | 31.2 | 129 | 7.5 | 195 | 30 | 174 | 7.6 | 170 | 40.9 | 189 | 3.5 | |
100 | 115 | 10 | 121 | 3.8 | 220 | 18 | 221 | 4.2 | 145 | 18 | 175 | 9 | |
333 | 125 | 13.2 | 122 | 8.5 | 160 | 5 | 173 | 10.1 | 135 | 8.7 | 221 | 8.1 | |
1000 | 120 | 30 | 124 | 8.8 | 215 | 13.2 | 202 | 4.3 | 155 | 35 | 181 | 18.1 | |
Positive Control | 430 | 27.8 | 599 | 36.4 | 558 | 5.9 | 836 | 172.5 | 300 | 11.1 | 430 | 70.3 | |
Table 1:Spontaneous Mutation Rates (Concurrent Negative Controls)
EXPERIMENT 1
Number of revertants (mean number of colonies per plate) | |||||||||
Base-pair substitution type | Frameshift type | ||||||||
TA100 | TA1535 | TA102 | TA98 | TA1537 | |||||
136 | 9 | 351 | 15 | 5 | |||||
139 | (135) | 14 | (10) | 350 | (358) | 18 | (15) | 5 | (6) |
129 | 7 | 373 | 13 | 8 | |||||
EXPERIMENT 2
Number of revertants (mean number of colonies per plate) | |||||||||
Base-pair substitution type | Frameshift type | ||||||||
TA100 | TA1535 | TA102 | TA98 | TA1537 | |||||
62 | 18 | 267 | 12 | 6 | |||||
97 | (73) | 11 | (14) | 318 | (301) | 12 | (12) | 5 | (5) |
60 | 13 | 318 | 12 | 5 | |||||
Table 2: Test Results: Experiment 1 – Without Metabolic Activation
Test Period | From : 25 March 2003 | To : 28 March 2003 | ||||||||||
With or without S9-Mix | Test substance concentration (µg/plate) | Number of revertants (mean number of colonies per plate) | ||||||||||
Base-pair substitution type | Frameshift type | |||||||||||
TA100 | TA1535 | TA102 | TA98 | TA1537 | ||||||||
- | 0 | 153 121 131 | (135) 16.4# | 9 7 8 | (8) 1.0 | 367 310 385 | (354) 39.2 | 13 16 24 | (18) 5.7 | 6 7 11 | (8) 2.6 | |
- | 15 | 128 114 130 | (124) 8.7 | 6 9 5 | (7) 2.1 | 353 296 434 | (361) 69.3 | 16 17 17 | (17) 0.6 | 5 5 3 | (4) 1.2 | |
- | 50 | 104 129 118 | (117) 12.5 | 12 12 5 | (10) 4.0 | 399 360 399 | (386) 22.5 | 16 14 12 | (14) 2.0 | 5 6 4 | (5) 1.0 | |
- | 150 | 144 113 118 | (125) 16.6 | 11 8 8 | (9) 1.7 | 406 372 360 | (379) 23.9 | 15 7 16 | (13) 4.9 | 4 5 6 | (5) 1.0 | |
- | 500 | 101 106 118 | (108) 8.7 | 11 13 11 | (12) 1.2 | 362 359 393 | (371) 18.8 | 15 8 12 | (12) 3.5 | 5 3 3 | (4) 1.2 | |
- | 1500 | 116 104 106 | (109) 6.4 | 5 3 11 | (6) 4.2 | 382 356 368 | (369) 13.0 | 17 15 18 | (17) 1.5 | 7 7 4 | (6) 1.7 | |
- | 5000 | 0 V 0 V 0 V | (0) 0.0 | 3 S 9 S 5 S | (6) 3.1 | 204 221 153 | (193) 35.4 | 17 S 14 S 13 S | (15) 2.1 | 0 S 0 S 4 S | (1) 2.3 | |
Positive controls S9-Mix - | Name Concentration (µg/plate) No. colonies per plate | ENNG | ENNG | MMC | 4NQO | 9AA | ||||||
3 | 5 | 0.5 | 0.2 | 80 | ||||||||
553 474 505 | (511) 39.8 | 287 284 256 | (276) 17.1 | 862 859 903 | (875) 24.6 | 75 81 80 | (79) 3.2 | 2605 2689 2688 | (2661) 48.2 | |||
Table 3: Test Results: Experiment 1 – With Metabolic Activation
Test Period | From : 25 March 2003 | To : 28 March 2003 | ||||||||||
With or without S9-Mix | Test substance concentration (µg/plate) | Number of revertants (mean number of colonies per plate) | ||||||||||
Base-pair substitution type | Frameshift type | |||||||||||
TA100 | TA1535 | TA102 | TA98 | TA1537 | ||||||||
+ | 0 | 173 145 180 | (166) 18.5# | 16 11 15 | (14) 2.6 | 380 373 370 | (374) 5.1 | 21 26 28 | (25) 3.6 | 5 6 7 | (6) 1.0 | |
+ | 15 | 150 125 163 | (146) 19.3 | 17 14 12 | (14) 2.5 | 361 352 376 | (363) 12.1 | 24 21 25 | (23) 2.1 | 5 7 12 | (8) 3.6 | |
+ | 50 | 156 158 149 | (154) 4.7 | 9 6 12 | (9) 3.0 | 332 362 403 | (366) 35.6 | 22 22 19 | (21) 1.7 | 5 6 5 | (5) 0.6 | |
+ | 150 | 127 140 150 | (139) 11.5 | 13 19 17 | (16) 3.1 | 419 369 363 | (384) 30.7 | 33 20 18 | (24) 8.1 | 9 3 6 | (6) 3.0 | |
+ | 500 | 119 136 164 | (140) 22.7 | 17 15 18 | (17) 1.5 | 389 337 345 | (357) 28.0 | 19 24 20 | (21) 2.6 | 12 3 6 | (7) 4.6 | |
+ | 1500 | 133 130 121 | (128) 6.2 | 8 6 9 | (8) 1.5 | 404 412 304 | (373) 60.2 | 23 25 19 | (22) 3.1 | 3 14 2 | (6) 6.7 | |
+ | 5000 | 98 82 77 | (86) 11.0 | 6 6 7 | (6) 0.6 | 75 88 94 | (86) 9.7 | 7 25 16 | (16) 9.0 | 0 0 0 | (0) 0.0 | |
Positive controls S9-Mix + | Name Concentration (µg/plate) No. colonies per plate | 2AA | 2AA | DAN | BP | 2AA | ||||||
1 | 2 | 10 | 5 | 2 | ||||||||
1982 2219 1854 | (2018) 185.2 | 378 376 401 | (385) 13.9 | 789 787 779 | (785) 5.3 | 220 262 259 | (247) 23.4 | 284 336 315 | (312) 26.2 | |||
Table 4: Test Results: Experiment 2 – Without Metabolic Activation
Test Period | From : 11 April 2003 | To : 14 April 2003 | ||||||||||
With or without S9-Mix | Test substance concentration (µg/plate) | Number of revertants (mean number of colonies per plate) | ||||||||||
Base-pair substitution type | Frameshift type | |||||||||||
TA100 | TA1535 | TA102 | TA98 | TA1537 | ||||||||
- | 0 | 95 102 128 | (108) 17.4# | 17 11 16 | (15) 3.2 | 345 350 358 | (351) 6.6 | 19 16 14 | (16) 2.5 | 14 6 C | (10) 5.7 | |
- | 15 | 66 50 63 | (60) 8.5 | 4 19 11 | (11) 7.5 | 364 322 393 | (360) 35.7 | 16 C 16 | (16) 0.0 | 4 7 6 | (6) 1.5 | |
- | 50 | 63 66 55 | (61) 5.7 | 4 11 7 | (7) 3.5 | 391 383 362 | (379) 15.0 | 16 18 17 | (17) 1.0 | 5 9 1 | (5) 4.0 | |
- | 150 | 84 82 66 | (77) 9.9 | 13 8 11 | (11) 2.5 | 380 345 398 | (374) 27.0 | 13 14 9 | (12) 2.6 | 9 7 4 | (7) 2.5 | |
- | 500 | 82 92 95 | (90) 6.8 | 8 17 14 | (13) 4.6 | 376 326 397 | (366) 36.5 | 15 12 15 | (14) 1.7 | 7 6 5 | (6) 1.0 | |
- | 1500 | 86 103 85 | (91) 10.1 | 11 8 6 | (8) 2.5 | 326 390 329 | (348) 36.1 | 11 13 22 | (15) 5.9 | 9 6 3 | (6) 3.0 | |
- | 5000 | 0 S 0 S 0 S | (0) 0.0 | 7 S 3 S 0 S | (3) 3.5 | 22 23 25 | (23) 1.5 | 0 S 0 S 0 S | (0) 0.0 | 0 S 0 S XS | (0) 0.0 | |
Positive controls S9-Mix - | Name Concentration (µg/plate) No. colonies per plate | ENNG | ENNG | MMC | 4NQO | 9AA | ||||||
3 | 5 | 0.5 | 0.2 | 80 | ||||||||
419 381 274 | (358) 75.2 | 305 227 222 | (251) 46.5 | 1080 1040 C | (1060) 28.3 | 160 170 151 | (160) 9.5 | 1379 1196 1552 | (1376) 178.0 | |||
Table 5: Test Results: Experiment 2 – With Metabolic Activation
Test Period | From : 11 April 2003 | To : 14 April 2003 | ||||||||||
With or without S9-Mix | Test substance concentration (µg/plate) | Number of revertants (mean number of colonies per plate) | ||||||||||
Base-pair substitution type | Frameshift type | |||||||||||
TA100 | TA1535 | TA102 | TA98 | TA1537 | ||||||||
+ | 0 | 94 113 115 | (107) 11.6# | 11 8 11 | (10) 1.7 | 397 326 384 | (369) 37.8 | 22 26 24 | (24) 2.0 | 5 7 7 | (6) 1.2 | |
+ | 15 | 135 92 107 | (111) 21.8 | 5 11 14 | (10) 4.6 | 380 399 396 | (392) 10.2 | 23 23 29 | (25) 3.5 | 12 7 5 | (8) 3.6 | |
+ | 50 | 128 107 129 | (121) 12.4 | 13 8 14 | (12) 3.2 | 345 381 394 | (373) 25.4 | 29 29 28 | (29) 0.6 | 7 16 7 | (10) 5.2 | |
+ | 150 | 110 137 114 | (120) 14.6 | 8 11 11 | (10) 1.7 | 422 424 425 | (424) 1.5 | 21 29 33 | (28) 6.1 | 6 11 4 | (7) 3.6 | |
+ | 500 | 116 119 134 | (123) 9.6 | 5 12 13 | (10) 4.4 | 399 405 361 | (388) 23.9 | 31 C 29 | (30) 1.4 | 6 3 5 | (5) 1.5 | |
+ | 1500 | 76 85 92 | (84) 8.0 | 11 7 9 | (9) 2.0 | 434 380 376 | (397) 32.4 | 36 22 25 | (28) 7.4 | 7 5 6 | (6) 1.0 | |
+ | 5000 | 46 46 37 | (43) 5.2 | 5 5 7 | (6) 1.2 | 39 74 44 | (52) 18.9 | 15 12 21 | (16) 4.6 | 3 7 1 | (4) 3.1 | |
Positive controls S9-Mix + | Name Concentration (µg/plate) No. colonies per plate | 2AA | 2AA | DAN | BP | 2AA | ||||||
1 | 2 | 10 | 5 | 2 | ||||||||
1099 1410 1350 | (1286) 165.0 | 236 292 243 | (257) 30.5 | 1135 1103 1090 | (1109) 23.2 | 383 477 536 | (465) 77.2 | 876 723 678 | (759) 103.8 | |||
S Sparse bacterial background lawn
V Very weak bacterial background lawn
# Standard deviation
C Contaminated
Frequency of aberrant cells (%)
-S9 | +S9 | |||||||
Dose | 24 hours | 48 hours | 24 hours | 48 hours | ||||
(µg/ml) | +Gap -Gap | +Gap -Gap | +Gap -Gap | +Gap -Gap | ||||
0 | 0 | 0 | 1.5 | 0 | 0 | 0 | 0.5 | 0 |
30 | 0 | 0 | 1.0 | 0.5 | ||||
100 | 0.5 | 0.5 | 0.5 | 0 | 0 | 0 | 0 | 0 |
300 | 2.0 | 0 | 4.5 | 1.5 | 2.0 | 0.5 | 0.5 | 0 |
1000 | 1.0 | 0.5 | 0 | 0 | ||||
+ve control | 23.8 | 21.3 | 13.5 | 13.5 | ||||
Mitotic index (% of control)
Dose | -S9 | + S9 | ||
µg/ml | 24 hours | 48 hours | 24 hours | 48 hours |
30 | 136 | 78 | 82 | 81 |
100 | 100 | 95 | 124 | 81 |
300 | 39 | 89 | 93 | 100 |
1000 | 0 | 0 | 91 | 73 |
3000 | 0 | 0 | 0 | 12 |
5000 | 0 | |||
+ve control | 67 | 33 | ||
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (negative)
Genetic toxicity in vivo
Description of key information
The weight of evidence suggests that MeaTG is not genotoxic.
Link to relevant study records
- Endpoint:
- in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus
- Remarks:
- Type of genotoxicity: chromosome aberration
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Reference:
- Composition 0
- Qualifier:
- according to
- Guideline:
- OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
- GLP compliance:
- yes
- Type of assay:
- mammalian erythrocyte micronucleus test
- Test material information:
- Composition 1
- Species:
- mouse
- Strain:
- NMRI
- Sex:
- male/female
- Details on test animals and environmental conditions:
- - Animals .
. Source: Harlan Winkelmann GmbH D-33178 Borchen
. Number of Animals: 72 (36 males/36 females), 6 males and 6 females per group
. Initial Age at Start of Acclimatisation: 8-10 weeks
. Acclimatisation: minimum 5 days
. Initial Body Weight at Start of Treatment: males mean value 37.1 g (SD ± 2.9 g) females mean value 31.5 g (SD ± 1.9 g)
- Environmental conditions
. Housing: single Cage Type: Makrolon Type I, with wire mesh top (EHRET GmbH, D-79302 Emmendingen)
. Bedding: granulated soft wood bedding (Harlan Winkelmann GmbH, D-33178 Borchen)
. Temperature 22 ± 3 °C
. Relative humidity 30 - 70 %
. Artificial light 6.00 a.m. - 6.00 p.m.
- Food and water
. Feed: pelleted standard diet, ad libitum (Harlan Winkelmann GmbH, D-33178 Borchen)
. Water: tap water, ad libitum, (Gemeindewerke, D-64380 Roßdorf) - Route of administration:
- oral: gavage
- Vehicle:
- Name: deionised water
Route and Frequency of Administration: orally, once
Volume Administered: 10 mL/kg b.w. - Duration of treatment / exposure:
- single administration
- Frequency of treatment:
- single
- Post exposure period:
- 24 and 48 hours
- Dose / conc.:
- 62.5 mg/kg bw/day
- Dose / conc.:
- 125 mg/kg bw/day
- Dose / conc.:
- 250 mg/kg bw/day
- No. of animals per sex per dose:
- 5
- Control animals:
- yes, concurrent vehicle
- Positive control(s):
- Name: CPA; Cyclophosphamide
Dissolved in: deionised water
Dosing: 40 mg/kg b.w.
Route and frequency of administration: orally, once
Volume administered: 10 mL/kg b.w. - Tissues and cell types examined:
- Bonne marrow
- Details of tissue and slide preparation:
- - Preparation of the bone marrow smears
Ten animals (5 males, 5 females) per test group (all groups after 24 hours and only the high dose group after 48 hours) were killed by CO2 inhalation, following by bleeding. The femurs of the animals were removed and the bone marrow was flushed out using foetal calf serum. After centrifugation, the supernatant was removed and the cells in the sediment were resuspended by shaking. A drop of this cell suspension was placed and spread on a slide. The slides were air dried and stained with May-Grünwald. The slides were coded so that the scorer is unaware of the treatment group of the slide under evaluation ("blind" scoring).
- Microscopic examination of the slides
For each animal, the number of the micronucleated polychromatic erythrocytes (MPE) was counted in 2000 polychromatic erythrocytes; the polychromatic (PE) and normochromatic (NE) erythrocyte ratio was established by scoring a total of 1000 erythrocytes (PE + NE). - Evaluation criteria:
- The study was considered valid as the following criteria are met:
- the negative controls are in the range of our historical control data.
- the positive controls are in the range of our historical control data.
- at least 4 animals per group and sex can be evaluated
- PCE to erythrocyte ratio should not be less than 20 % of the negative control.
A test item is classified as mutagenic if it induces either a dose-related increase or a clear increase in the number of micronucleated polychromatic erythrocytes in a single dose group. - Statistics:
- Statistical methods (nonparametric Mann-Whitney test (8)) will be used as an aid in evaluating the results. However, the primary point of consideration is the biological relevance of the results. A test item that fails to produce a biological relevant increase in the number of micronucleated polychromatic erythrocytes is considered non-mutagenic in this system.
- Key result
- Sex:
- male/female
- Genotoxicity:
- negative
- Toxicity:
- yes
- Remarks:
- clinical signs
- Vehicle controls valid:
- yes
- Negative controls valid:
- not examined
- Positive controls valid:
- yes
- Additional information on results:
- As estimated by a pre-experiment 250 mg Sodium Thioglycolate 98%, Pure per kg b.w. was suitable.
The mean number of polychromatic erythrocytes was not decreased after treatment with the test item as compared to the mean value of PCEs of the vehicle control indicating that Sodium Thioglycolate 98%, Pure had no cytotoxic properties in the bone marrow. In comparison to the corresponding vehicle controls there was no statistically significant or biologically relevant enhancement in the frequency of the detected micronuclei at any preparation interval and dose level after administration of the test item.
The mean values of micronuclei observed after treatment with Sodium Thioglycolate 98%, Pure were below or near to the value of the vehicle control group.
40 mg/kg b.w. cyclophosphamide administered orally was used as positive control which showed a statistically significant increase of induced micronucleus frequency. - Conclusions:
- Interpretation of results (migrated information): negative
Sodium Thioglycolate 98%, Pure is considered to be non-mutagenic in this micronucleus assay. - Executive summary:
The clastogenic potential of sodium thioglycolate was evaluated in a micronucleus assay on mouse bone marrow performed according to the OECD guideline # 474. Sodium thioglycolate was administered by single gavage to three groups of five male and five female NMRI mice at dose-levels of 0, 62.5, 125 and 250 mg/kg bw. The positive control was the cyclophosphamide administered orally. The polychromatic erythrocytes/normochromatic erythrocytes ratio (PE/NE) in the treated groups were equivalent to those of the control groups. However, systemic exposure (and thus bone marrow exposure) was confirmed by the clinical signs observed in males and females receiving 250 mg/kg bw of sodium thioglycolate. No increase of the frequency of the micronucleated polychromatic erythrocytes was observed in the bone marrow harvested 24 or 48 hours after the treatment. Positive and vehicle controls gave the expected results.
Reference
Summary of Micronucleus Test Results
test group | dose (mg/kg b.w) | sampling time (h) | PCEs with micronuclei (%) | range | PCE per 2000 erythocytes |
vehicle | 0 | 24 | 0.050 | 0 - 2 | 1098 |
test item | 62.5 | 24 | 0.060 | 0 - 2 | 1124 |
test item | 125 | 24 | 0.025 | 0 - 1 | 1123 |
test item | 250 | 24 | 0.055 | 0 - 3 | 1100 |
Positive control | 40 | 24 | 1.500 | 10 -43 | 1099 |
test item | 250 | 48 | 0.095 | 0 - 6 | 1123 |
Historical Controls (1999 – 2004)
Vehicle Controls | Positive Controls (CPA) | |||||
Males | Females | Total | Males | Females | Total | |
Mean*±SD | 0.078±0.04 | 0.058±0.033 | 0.069±0.028 | 1.867±0.57 | 1.368±0.497 | 1.632±0.468 |
Range** | 0.01 - 0.23 | 0.0 - 0.19 | 0.01 - 0.15 | 0.70 -3.46 | 0.49 -3.55 | 0.77 - 3.48 |
No. of Experiments | 229 | 217 | 230 | 228 | 217 | 229 |
*: mean value (percent micronucleated cells)
**: range of the mean group values (percent micronucleated cells)
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (negative)
Additional information
Additional information from genetic toxicity in vivo:
Several in vitro and in vivo genotoxicity studies were performed with thioglycolic acid and its salts. The conducted genotoxicity studies on thioglycolic acid or its salts described in this chapter can be bridged to each other, because in aquous solutions only the organic thioglycolate anion may have the potential to cause genotoxic effects in vitro or in vivo. All genotoxicity studies conducted to date have either negative results or are of douptful significance. Therefore, the weight of evidence suggests that thioglycolic acid and its salts are non-genotoxic.
Justification for classification or non-classification
Conclusive, but not sufficient for classification.
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