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EC number: 226-540-9 | CAS number: 5421-46-5
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
Endpoint summary
Administrative data
Key value for chemical safety assessment
Genetic toxicity in vitro
Description of key information
The weight of evidence suggests that ammonium thioglycolate 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:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 471 (Bacterial Reverse Mutation Assay)
- Deviations:
- no
- GLP compliance:
- yes
- Type of assay:
- bacterial reverse mutation assay
- Target gene:
- Histidine reversion
- Species / strain / cell type:
- S. typhimurium, 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 / solvent:
- sterile distilled water
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- 4-nitroquinoline-N-oxide
- 9-aminoacridine
- N-ethyl-N-nitro-N-nitrosoguanidine
- benzo(a)pyrene
- mitomycin C
- other:
- Details on test system and experimental 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:
- S. typhimurium, other: Strains: TA1535, TA1537, TA98, TA100 and TA102
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Remarks:
- all strains/cell types tested
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- = 5000 µg/plate
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not examined
- Positive controls validity:
- valid
- 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
- Remarks:
- Type of genotoxicity: gene mutation
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- 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
- Target gene:
- Locus Examined: thymidine kynase, the selection agent used was 5 µg/ml trifluorothymidine
- Species / strain / cell type:
- mouse lymphoma L5178Y cells
- Details on mammalian cell type (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 / cell type 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:
- - Solvent used: deionised water
- Untreated negative controls:
- yes
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- cyclophosphamide
- methylmethanesulfonate
- Details on test system and experimental 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
- Remarks:
- all strains/cell types tested
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- 4-h experiment (+/-S9): > 1600 µg/ml / 24-h experiment (-S9): >= 800 µg/ml
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not examined
- Positive controls validity:
- valid
- 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
- Remarks:
- Type of genotoxicity: chromosome aberration
- Type of information:
- read-across based on grouping of substances (category approach)
- Adequacy of study:
- key study
- Justification for type of information:
- The read-across is a category approach based on the hypothesis that compounds in this category are transformed to a common compound. This approach serves to use existing data on genotoxicity, repeated-dose toxicity, and reproductive toxicity endpoints for substances in this category.
There are no relevant variations in properties among source substances and the same potency is predicted for all target substances. This is Scenario 5 of the RAAF . Substances ATG, MEATG, KTG, CaTG, and NaTG are different inorganic salts of a common acid, thioglycolic acid (TGA; synonym: 2- mercaptoacetic acid). They dissociate rapidly in aqueous media, e.g., the test organism, to the common thioglycolate anion and to their different counter ions. The water solubility of all category members is high, except for CaTG which is only moderately soluble in water.
In the repeated-dose toxicity studies with NaTG, specific toxicity is exerted via the well-investigated inhibition of mitochondrial fatty acid beta-oxidation by the thioglycolate (2-mercaptoacetate) anion 2,3,4. Inhibition of beta-oxidation leads to increased triglycerides and decreased acetyl-CoA in liver, and subsequently reduced gluconeogenesis. The latter presents as hypoglycaemia in NaTGtreated rats, which is aggravated by fasting (Grosdidier, 2011; Report No. 37043 TSR). This mode of action (MoA) is thought to mediate the acute oral toxicity in fasted rats observed with all category members.
It can be predicted with high confidence that the target substances will display the same MoA and lead to the same effects seen with NaTG.
For more detailed information please refer to section 13.2. - Reason / purpose for cross-reference:
- read-across: supporting information
- Key result
- Species / strain:
- lymphocytes: human
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- other: With S9 : 1000 µg/ml. Without S9 : 300 µg/ml
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not examined
- Positive controls validity:
- valid
- Remarks on result:
- other: strain/cell type: Human lymphocytes
- Remarks:
- Migrated from field 'Test system'.
- Conclusions:
- By analogy to TGA, ATG is considered to be non-clastogenic in mammalian cells.
Referenceopen allclose all
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
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (negative)
Genetic toxicity in vivo
Description of key information
By analogy to NaTG, ATG is considered to be non-mutagenic in vivo.
Link to relevant study records
- Endpoint:
- in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus
- Type of information:
- read-across based on grouping of substances (category approach)
- Adequacy of study:
- key study
- Justification for type of information:
- The read-across is a category approach based on the hypothesis that compounds in this category are transformed to a common compound. This approach serves to use existing data on genotoxicity, repeated-dose toxicity, and reproductive toxicity endpoints for substances in this category.
There are no relevant variations in properties among source substances and the same potency is predicted for all target substances. This is Scenario 5 of the RAAF . Substances ATG, MEATG, KTG, CaTG, and NaTG are different inorganic salts of a common acid, thioglycolic acid (TGA; synonym: 2- mercaptoacetic acid). They dissociate rapidly in aqueous media, e.g., the test organism, to the common thioglycolate anion and to their different counter ions. The water solubility of all category members is high, except for CaTG which is only moderately soluble in water.
In the repeated-dose toxicity studies with NaTG, specific toxicity is exerted via the well-investigated inhibition of mitochondrial fatty acid beta-oxidation by the thioglycolate (2-mercaptoacetate) anion 2,3,4. Inhibition of beta-oxidation leads to increased triglycerides and decreased acetyl-CoA in liver, and subsequently reduced gluconeogenesis. The latter presents as hypoglycaemia in NaTGtreated rats, which is aggravated by fasting (Grosdidier, 2011; Report No. 37043 TSR). This mode of action (MoA) is thought to mediate the acute oral toxicity in fasted rats observed with all category members.
It can be predicted with high confidence that the target substances will display the same MoA and lead to the same effects seen with NaTG.
For more detailed information please refer to section 13.2. - Reason / purpose for cross-reference:
- read-across: supporting information
- Key result
- Sex:
- male/female
- Genotoxicity:
- negative
- Toxicity:
- yes
- Remarks:
- clinical signs
- Vehicle controls validity:
- valid
- Negative controls validity:
- not examined
- Positive controls validity:
- valid
- Conclusions:
- By analogy to NaTG, ATG is considered to be non-mutagenic in vivo.
Reference
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (negative)
Additional information
Additional information from genetic toxicity in vitro:
Several in vitro and in vivo genotoxicity studies were performed with thioglycolic acid and its sodium and ammonium salts. In aqueous solution – experimental tests and biological systems – the ions of the thioglycolate salts will act separately. Therefore any mutagenicity data on thioglycolic acid or one of its salts can be bridged to thioglycolic acid and the other salts, given that their counter-ions do not contribute any mutagenic properties to the molecule.
The most recent bacterial gene mutations assay was conducted with ammonium thioglycolate 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 (Thompson, 2003).
In other reverse gene mutations assays with multiple strains of Salmonella typhimurium performed with methods compliant or comparable to the OECD guideline 471, thioglycolic acid and its sodium salt were not mutagenic in the presence and absence of metabolic activation (Zeiger, 1987).
Ammonium thioglycolate was tested in a Mouse Lymphoma Forward Mutation Assay performed according to the OECD guideline 476. At concentrations up to 1,600 µg/ml (10 mM), ammonium thioglycolate did not induce gene mutations in the mouse lymphoma L5178Y heterozygous TK+/-cells, with or without metabolic activation. The spontaneous mutation frequencies and the levels of activity of the positive controls confirmed the sensitivity of the test system (Wollny, 2004).
In a gene TK+/-mutation assay in mouse lymphoma L5178Y cells, performed following the OECD guideline 476, ammonium thioglycolate was also not mutagenic in the presence and absence of metabolic activation (Wollny 2004). As well, thioglycolic acid was not clastogenic, with or without metabolic activation, in a n in vitro chromosomal aberration assay in human lymphocytes performed following the OECD guideline 473 (Molinier, 1994).
In a micronucleus assay on the peripheral blood of mice treated dermally for 13 weeks with sodium thioglycolate, a slight but statistically significant increase of the frequency of the micronucleated normochromatic erythrocytes was only observed in female mice at the top dose level of 360 mg/kgbw/d (NTP). This result seems of doubtful significance because thioglycolic acid did not induce structural chromosomal in vitro, and thioglycolic acid and its sodium salt failed to show any evidence of clastogenic potential when administered acutely by the dermal and oral routes up to the maximum tolerated dose in two mouse bone marrow micronucleus assays performed following the OECD guideline 474 (Haddouk 2006, Honarvar 2005). In the sex-linked recessive lethal mutations test, sodium thioglycolate was not mutagenic (Gocke 1981).
Justification for selection of genetic toxicity endpoint
One of several negative test results
Justification for classification or non-classification
Conclusive but not sufficient for classification.
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
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