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EC number: 200-018-0 | CAS number: 50-21-5
- 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
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Endpoint summary
Administrative data
Key value for chemical safety assessment
Genetic toxicity in vitro
Description of key information
There is supporting data available to assess the genotoxicity of the target substance, lactic acid. In addition, data from an in vitro genetox testing battery conducted in accordance with OECD guidelines with a suitable read-across partner, L(+)-lactic acid was used in a weight of evidence approach to assess the genotoxicity of lactic acid. For details and justification of read-across please refer to the report attached in section 13 of IUCLID.
L(+)-lactic acid was tested negative in a bacterial reverse gene mutation test conducted according to OECD 471, in an in vitro chromosome aberration assay conducted according to OECD 473 and in a mammalian cell gene mutation assay conducted according to OECD 476 (nowadays OECD 490). In the supporting studies, lactic acid showed no potential to induce any mutagenic or clastogenic effect.
Based on results, lactic acid is considered to not induce genetic toxicity.
Link to relevant study records
- Endpoint:
- in vitro cytogenicity / chromosome aberration study in mammalian cells
- Type of information:
- read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- weight of evidence
- Justification for type of information:
- For details and justification of read-across please refer to the read-across report attached to IUCLID section 13.
- Reason / purpose for cross-reference:
- read-across source
- Key result
- Species / strain:
- lymphocytes: peripheral human lymphocytes
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- based on determination of the mitotic index.
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- True negative controls validity:
- not examined
- Positive controls validity:
- valid
- Additional information on results:
- TEST-SPECIFIC CONFOUNDING FACTORS
- Effects of pH: At the highest concentration of the test substance (10 mM equal to 901 µg/ml) the pH was 7.1 compared to a pH of 7.8 in the solvent control.
- Effects of osmolality: At the highest concentration of the test substance (10 mM equal to 901 µg/mL) the osmolarity was 275 mOsm/kg compared to an osmolarity of 269 mOsm/kg in the solvent control.
- Water solubility: miscible
- Precipitation: No
RANGE-FINDING/SCREENING STUDIES: In the dose range finding test blood cultures were treated with 10, 33, 100, 333, 901 µg/mL L(+)-lactic acid/mL culture medium (equal to concentrations of 0.1, 0.4, 1.1, 3.7 and 10 mM) with and without S9-mix.
COMPARISON WITH HISTORICAL CONTROL DATA: The number of cells with chromosome aberrations found in the solvent control cultures was within the laboratory historical control data range.
For individual results see box 'Any other information on results incl. tables'. - Conclusions:
- L(+)-lactic acid is considered to be not clastogenic in the in vitro mammalian chromosomal aberration test using human lymphocytes, with and without metabolic activation.
- Executive summary:
In a mammalian cell cytogenetic assay conducted according to OECD guideline 473, peripheral human lymphocyte cultures were exposed to L(+)-lactic acid (90% purity), solved in RPMI 1640 cell culture medium. In the first experiment, the doses were 0, 10, 100, 901 µg/mL with and without metabolic activation. In the second experiment doses were 0, 100, 333, 666, 901 µg/mL without metabolic activation and 0, 10, 100, 901 µg/mL with metabolic activation (rat liver S9-mix).
L(+)-lactic acid was tested up to 901 µg/mL, which was cytotoxic based on determination of the mitotic index after an exposure time of 24 and 48 hours. The percentage of the mitotic index after 24 hours of 901 µg/mL was 55%, that after 48 hours of 901 µg/mL 49%. Concentrations lower than 901 µg/mL did not cause a dose-dependent decrease in the percentage of the mitotic index after 24 and 48 hours of exposure. The mitotic index after 3 hours of exposure was lower compared to control (66% in experiment 1, 84% in experiment 2) but did not reach the threshold value of 45 ± 5% according to OECD guideline 473 for cytotoxicity. Positive controls induced the appropriate response. There was no evidence for a concentration related positive response of chromosome aberration induced over background.
This study is classified as acceptable and satisfies the requirement for the in vitro mammalian chromosomal aberration test according to OECD 473.
This information is used in a read-across approach in the assessment of the target substance. For details and justification of read-across please refer to the read-across report attached to IUCLID section 13.
- Endpoint:
- in vitro gene mutation study in mammalian cells
- Type of information:
- read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- weight of evidence
- Justification for type of information:
- For details and justification of read-across please refer to the read-across report attached to IUCLID section 13.
- Reason / purpose for cross-reference:
- read-across source
- Key result
- Species / strain:
- mouse lymphoma L5178Y cells
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity nor precipitates, but tested up to recommended limit concentrations
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- True negative controls validity:
- not examined
- Positive controls validity:
- valid
- Additional information on results:
- TEST-SPECIFIC CONFOUNDING FACTORS
- Effects of pH: At the highest concentration of test substance (0.01 M equal to 901 µg/mL) the pH was 6.84 compared to a pH of 7.31 in the solvent control.
- Effects of osmolality: At the highest concentration of test substance (0.01 M equal to 901 µg/mL) the osmolarity was 0.319 Osm/kg compared to an osmolarity of 0.299 Osm/kg in the solvent control
- Water solubility: miscible
- Precipitation: No
RANGE-FINDING/SCREENING STUDIES:
Cytotoxicity data were obtained by treating 8 x 10^6 cells (10^6 cells/mL for 3 hours treatment) or 5 x 10^6 cells (1.25 x 10^5 cells/mL for 24 hours treatment) with 0, 17, 52, 164, 512 and 901 µg of test substance for 3 hours in the presence of S9-mix and for 3 and 24 hours in the absence of S9-mix.
After exposure, the cells were separated from treatment solutions centrifugation steps and re-suspended in RPM 1640 medium supplemented with 10% (v/v) inactivated horse serum (R10 medium). Cells were counted with the coulter particle counter.
For determination of the cytotoxicity, the surviving cells of the 3 hours treatment were subcultured twice. After 24 hours of subculturing, the cells were counted (day 1) and subcultured again for another 24 hours, after which the cells were counted (day 2). The surviving cells of the 24 hours treatment were subcultured once. After 24 hours of subculturing, the cells were counted. If less than 1.25 x 105 cells/mL were counted no subculture was performed.
The suspension growth expressed as the reduction in cell growth after approximately 24 and 48 hours or only 24 hours cell growth, compared to the cell growth of the solvent control, was used to determine an appropriate dose range for the mutagenicity tests.
COMPARISON WITH HISTORICAL CONTROL DATA:
Spontaneous mutation frequencies in the solvent-treated control cultures were between the minimum and maximum value of the historical control range.
Experiment 1 & 2: For individual results see Tables 3-5 in box 'Any other information on results incl. tables'. - Conclusions:
- In conclusion, L(+)-lactic acid is considered to be non-mutagenic in the in vitro mammalian cell gene mutation test (OECD 476, nowadays OECD 490) in the presence and absence of mammalian metabolic activation.
- Executive summary:
In a mammalian cell gene mutation assay conducted in accordance to OECD guideline 476 (nowadays OECD 490), L5178Y mouse lymphoma cells cultured in vitro were exposed to L(+)-lactic acid (90% purity), solved in RPMI 1640 medium. In the first experiment, L(+)-lactic acid was tested up to concentrations of 901 µg/mL (0.01 M, the highest concentration recommended in the guidelines) in the absence and presence of S9-mix. The incubation time was 3 hours. In the second experiment, L(+)-lactic acid was again tested up to concentrations of 901 µg/mL in the absence S9-mix. The incubation time was 24 hours. No toxicity was observed at this dose level in the absence and presence of S9 mix. The induced mutation frequency with and without metabolic activation was not increased compared to control in all tested concentrations. The positive controls did induce the appropriate response. Based on the results, it can be concluded, that L(+)-lactic acid is not mutagenic in the mouse lymphoma L5178Y test system under the experimental conditions described.
This information is used in a read-across approach in the assessment of the target substance. For details and justification of read-across please refer to the read-across report attached to IUCLID section 13.
- Endpoint:
- in vitro gene mutation study in bacteria
- Type of information:
- read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- weight of evidence
- Justification for type of information:
- For details and justification of read-across please refer to the read-across report attached to IUCLID section 13.
- Reason / purpose for cross-reference:
- read-across source
- Key result
- Species / strain:
- S. typhimurium TA 1535
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not examined
- True negative controls validity:
- not examined
- Positive controls validity:
- valid
- Key result
- Species / strain:
- S. typhimurium TA 1537
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not examined
- True negative controls validity:
- not examined
- Positive controls validity:
- valid
- Key result
- Species / strain:
- S. typhimurium TA 98
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not examined
- True negative controls validity:
- not examined
- Positive controls validity:
- valid
- Key result
- Species / strain:
- S. typhimurium TA 100
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not examined
- True negative controls validity:
- not examined
- Positive controls validity:
- valid
- Key result
- Species / strain:
- E. coli WP2 uvr A
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not examined
- True negative controls validity:
- not examined
- Positive controls validity:
- valid
- Additional information on results:
- TEST-SPECIFIC CONFOUNDING FACTORS
- Precipitation: No
RANGE-FINDING/SCREENING STUDIES: Dose range finding test performed with TA100 and WP2uvrA. Doses tested: 0, 3, 10, 33, 100, 333, 1000, 3330, 5000 µg/plate. Based on the results, the following doses were selected for the main experiment with TA1535, TA1537 and TA98 in the presence and absence of S9-mix: 100, 333, 1000, 330 and 5000 µg/plate.
COMPARISON WITH HISTORICAL CONTROL DATA: The negative control values were within the laboratory historical control data ranges, except for TA100 in the absence of S9-mix, second experiment. Evaluation: The mean plate count (146) was just outside the limit of the range (144) and clear negative results are observed in all experiments. Therefore, this deviation in the mean plate count of the solvent control had no effect on the results of the study. The strain-specific positive control values were within the laboratory historical control data ranges indicating that the test conditions were adequate and that the metabolic activation system functioned properly, except the response for TA1535 in the absence of S9-mix, first experiment. Evaluation: The value (257) was just below the limit of the range (262). The purpose of the positive control is as a reference for the test system, where a positive response is required to check if the test system functions correctly. Since the value was more than 3 times greater than the concurrent solvent control values, this deviation in the mean plate count of the positive control had no effect on the results of the study.
ADDITIONAL INFORMATION ON CYTOTOXICITY:
No reduction of the bacterial background lawn and no biologically relevant decrease in the number of revertants were observed.
MUTAGENICITY:
Experiment 1: No increase in the number of revertants was observed upon treatment with the test item under all conditions tested.
Experiment 2: Based on the results from the first experiment, the test item was tested up to 5000 µg/plate. No increase in the number of revertants was observed. - Conclusions:
- In conclusion, L(+)-lactic acid is not genotoxic in the bacterial reverse gene mutation assay (OECD 471) in the presence and absence of mammalian metabolic activation.
- Executive summary:
In a reverse gene mutation assay in bacteria conducting according to OECD guideline 471, Salmonella typhimurium strains TA1535, TA1537, TA98, TA100 and E. coli strain WP2uvrA were exposed to L(+)-lactic acid (90% purity) at concentrations of 0, 100, 333, 1000, 3330 and 5000 µg/plate in the presence and absence of mammalian metabolic activation.
L(+)-lactic acid was tested up to the limit concentration of 5000 µg/plate. The positive controls induced the appropriate responses in the corresponding strains. There was no evidence of induced mutant colonies over background. Based on the results, the test item can be considered to be non-mutagenic.
This study is classified as acceptable and satisfies the requirement for Test Guideline OECD 471 for in vitro mutagenicity (bacterial reverse gene mutation assay).
This information is used in a read-across approach in the assessment of the target substance. For details and justification of read-across please refer to the read-across report attached to IUCLID section 13.
Referenceopen allclose all
Mitotic Indices:
Table1: Mitotic index of human lymphocyte cultures treated with L(+)-lactic acid in the dose range finding test
L(+)-lactic acid concentration (µg/ml) |
Number of metaphases:
Absolute |
Number of metaphases:
Number of cells scored |
Number of metaphases:
Percentage of control |
Without metabolic activation (-S9-mix) |
|
|
|
3 h exposure time, 24 h fixation time |
|
|
|
Control a) |
96 |
1004 |
100 |
10 |
99 |
1007 |
103 |
33 |
80 |
1045 |
83 |
100 |
60 |
1008 |
63 |
333 |
66 |
1009 |
69 |
901 |
63 |
1003 |
66 |
24 h exposure time, 24 h fixation time |
|
|
|
Control a) |
65 |
1007 |
100 |
10 |
62 |
1042 |
95 |
33 |
71 |
1041 |
109 |
100 |
66 |
1016 |
102 |
333 |
68 |
1048 |
105 |
901 |
36 |
1028 |
55 |
48h exposure time,48h fixation time |
|
|
|
Control a) |
68 |
1017 |
100 |
10 |
64 |
1026 |
94 |
33 |
51 |
1013 |
75 |
100 |
65 |
1010 |
96 |
333 |
57 |
1017 |
84 |
901 |
33 |
1033 |
49 |
With metabolic activation (+S9-mix) |
|
|
|
3 h exposure time, 24 h fixation time |
|
|
|
Control a) |
85 |
1044 |
100 |
10 |
70 |
1013 |
82 |
33 |
71 |
1008 |
84 |
100 |
68 |
1006 |
80 |
333 |
66 |
1020 |
78 |
901 |
71 |
1007 |
84 |
a.) culture medium
Table 2: Mitotic index of human lymphocyte cultures treated with L(+)-lactic acid in the first cytogenetic assay
L(+)-lactic acid concentration (µg/ml) |
Number of metaphases a)
Absolute |
Number of metaphases a)
Number of cells scored |
Percentage of control
|
Without metabolic activation (-S9-mix) |
|
|
|
3 h exposure time, 24 h fixation time |
|
|
|
Control b) |
3-36 |
1009-1028 |
100 |
10 |
3-35 |
1002-1012 |
103 |
100 |
3-28 |
1008-1033 |
90 |
901 |
1-9 |
1002-1040 |
34 |
MMC-C; 0.5 µg/ml |
4-7 |
1026-1031 |
16 |
MMC-C; 0.75 µg/ml |
7-5 |
1029-1004 |
17 |
With metabolic activation (+S9-mix) |
|
|
|
3 h exposure time, 24 h fixation time |
|
|
|
Control b) |
3-48 |
1040-1028 |
100 |
10 |
3-27 |
1013-1007 |
79 |
100 |
4-35 |
1035-1001 |
101 |
901 |
4-32 |
1008-1007 |
93 |
CP; 10 µg/ml |
21-14 |
1005-1025 |
43 |
a) Duplicate cultures
b) Culture medium
Table 3: Mitotic index of human lymphocyte cultures treated with L(+)-lactic acid in the second cytogenetic assay
L(+)-lactic acid concentration (µg/ml) |
Number of metaphasesa
Absolute |
Number of metaphasesa
Number of cells scored |
Percentage of control |
Without metabolic activation (-S9-mix) |
|
|
|
24 h exposure time, 24 h fixation time |
|
|
|
Control b) |
90-85 |
1000-1000 |
100 |
100 |
75-83 |
1000-1003 |
90 |
333 |
67-65 |
1008-1000 |
75 |
666 |
73-66 |
1001-1000 |
79 |
901 |
39-42 |
1002-1000 |
46 |
MMC-C; 0.2 µg/ml |
24-34 |
1000-1003 |
33 |
MMC-C; 0.3 µg/ml |
21-33 |
1003-1000 |
31 |
48 h exposure time, 48 h fixation time |
|
|
|
Control b) |
93-88 |
1005-1000 |
100 |
100 |
71-87 |
1001-1000 |
87 |
333 |
66-51 |
1000-1000 |
65 |
666 |
34-37 |
1000-1002 |
39 |
901 |
22-24 |
1003-1000 |
25 |
MMC-C; 0.1 µg/ml |
18-20 |
1002-1003 |
21 |
MMC-C; 0.15 µg/ml |
17-19 |
1000-1004 |
20 |
With metabolic activation (+S9-mix) |
|
|
|
3 h exposure time, 48 h fixation time |
|
|
|
Control b) |
88-87 |
1000-1000 |
100 |
10 |
66-75 |
1000-1045 |
81 |
100 |
62-64 |
1003-1005 |
72 |
901 |
71-63 |
1000-1000 |
77 |
CP; 10 µg/ml |
22-18 |
1005-1000 |
-c.) |
a) Duplicate cultures
b) Culture medium
c) CP was fixed after 24 hours. Therefore, the mitotic index could not be calculated as percentage of control.
Chromosome aberrations in human lymphocyte cultures treated with L(+)-lactic acid
1. Cytogenetic Assay:
Conc | Exposure Time [h] | Fixation Time [h] | Metabolic Activation | Culture | Mitotic Index [%] | Cells scored |
Cells + gaps |
Cells - gaps |
Culture medium | 3 | 24 | without | A+B | 100 | 200 | 0 | 0 |
10 µg/ml | 3 | 24 | without | A+B | 103 | 200 | 5 | 5 |
100 µg/ml | 3 | 24 | without | A+B | 90 | 200 | 0 | 0 |
901 µg/ml | 3 | 24 | without | A+B | 34 | 200 | 4 | 4 |
MMC-C 0.5 µg/ml | 3 | 24 | without | A+B | 16 | 150 | 76*** | 76*** |
Culture medium | 3 | 24 | with | A+B | 100 | 200 | 2 | 2 |
10 µg/ml | 3 | 24 | with | A+B | 79 | 200 | 3 | 3 |
100 µg/ml | 3 | 24 | with | A+B | 101 | 200 | 2 | 2 |
901 µg/ml | 3 | 24 | with | A+B | 93 | 200 | 2 | 2 |
CP 10 µg/ml | 3 | 24 | with | A+B | 43 | 200 | 59*** | 59*** |
*) Significantly different from control group (Chi-square test), p < 0.001
2. Cytogenetic Assay:
Conc | ExposureTime [h] | FixationTime [h] | Metaboic Activation | Culture | Mitotic Index [%] |
Cells scored |
Cells + gaps |
Cells - gaps |
Culture medium | 3 | 48 | with | A+B | 100 | 200 | 2 | 1 |
10 µg/ml | 3 | 48 | with | A+B | 81 | 200 | 1 | 1 |
100 µg/ml | 3 | 48 | with | A+B | 72 | 200 | 0 | 0 |
10 µg/ml | 3 | 48 | with | A+B | 77 | 200 | 3 | 3 |
CP 10 µg/ml | 3 | 48 | with | A+B | n.d.b | 100 | 53*** | 53*** |
Culture medium | 24 | 24 | without | A+B | 100 | 200 | 1 | 1 |
100 µg/ml | 24 | 24 | without | A+B | 90 | 200 | 1 | 1 |
666 µg/ml | 24 | 24 | without | A+B | 79 | 200 | 0 | 0 |
901 µg/ml | 24 | 24 | without | A+B | 46 | 200 | 3 | 3 |
MMC- 0.1 µg/ml | 24 | 24 | without | A+B | 33 | 100 | 53*** | 53*** |
Culture medium | 48 | 48 | without | A+B | 100 | 200 | 1 | 1 |
100 µg/ml | 48 | 48 | without | A+B | 87 | 200 | 3 | 3 |
333 µg/ml | 48 | 48 | without | A+B | 65 | 200 | 2 | 2 |
666 µg/ml | 48 | 48 | without | A+B | 39 | 200 | 2 | 2 |
MMC- 0.1 µg/ml | 48 | 48 | without | A+B | 21 | 100 | 53*** | 53*** |
bCP was fixed after 24 hours. Therefore, the mitotic index could not be calculated as percentage of control.
*) Significantly different from control group (Chi-square test), p < 0.001
Table 1: Dose-rangefindingtest: Cytotoxicity of L(+)-lactic acid (3 hours treatment)
Dose (µg/mL) |
Cell count after 3 hours of treatment (cells/mL x 10^5) | Cell count after 24 hours of subculture (cells/mL x 10^5) | Cell count after 48 hours of subculture (cells/mL x 10^5) | SG(1) x 10^5 cells/mL) |
RSG (2) % |
without metabolic activation |
|||||
SC | 6.9 | 5.0 | 6.9 | 152 | 100 |
17 | 6.3 | 5.0 | 7.4 | 149 | 98 |
52 | 7.0 | 5.2 | 6.9 | 161 | 106 |
164 | 7.3 | 5.2 | 7.1 | 173 | 113 |
512 | 7.6 | 5.2 | 6.8 | 172 | 113 |
901 | 6.8 | 5.4 | 7.0 | 166 | 109 |
with metabolic activation |
|||||
SC | 5.3 | 4.9 | 7.8 | 130 | 100 |
17 | 5.2 | 5.2 | 7.5 | 130 | 100 |
52 | 4.2 | 5.2 | 7.6 | 106 | 82 |
164 | 4.1 | 5.3 | 7.2 | 100 | 77 |
512 | 5.0 | 5.1 | 7.5 | 122 | 94 |
901 | 4.3 | 5.1 | 7.4 | 104 | 80 |
Note: all calculations were made without rounding off
SC = solvent control = exposure medium
(1) = suspension growth
(2) relative suspension growth
SG= (Cell count after 3 h treatment) x (Cell count after 24 h subculture)/(Cells subcultured (at t=3 h)(1.25x10^5 c/mL)) x (Cell count after 48 h subculture)/(Cells subcultured (at t=24 h) (1.25 x 10^5 c/mL))
RSG = [SG(test)/SG(control)] x 100
Table 2: Dose-rangefindingtest: Cytotoxicity of L(+)-lactic acid (24 hours treatment)
Dose (µg/mL) |
Cell count after 24 hours of treatment (cells/mL x 10^5) | Cell count after 24 hours of subculture (cells/mL x 10^5) | SG(1) x 10^5 cells/mL) |
RSG (2) % |
without metabolic activation |
||||
SC |
9.5 | 5.9 | 45 | 100 |
17 | 8.9 | 5.9 | 42 | 93 |
52 | 9.3 | 5.7 | 42 | 93 |
164 | 9.1 | 5.2 | 39 | 85 |
512 | 8.8 | 5.5 | 39 | 87 |
901 | 7.2 | 4.6 | 26 | 58 |
Note: all calculations were made without rounding off
SC = solvent control = exposure medium
(1) = suspension growth
(2) relative suspension growth
SG = (Cell count after 24 h treatment) x (Cell count after 24 h subculture)/(Cells subcultured after treatment (1.25 x 10^5 c/mL)
RSG = [SG(test)/SG(control)] x 100
Cytotoxic and mutagenic response of L(+)-lactic acid in the mouse lymphoma L5178Y test system
Abbreviations:
RSG: Relative Suspension Growth
CE: Cloning Efficiency
RS: Relative Survival
RTG: Relative Total Growth
MF: Mutation Frequency per 10^6 Survivors
SC: Solvent Control (= Exposure Medium)
MMS: Methylmethanesulfonate
CP: Cyclophosphamide
Experiment 1
Table 3: 3 h treatment, without metabolic activation
Dose [µg/mL] |
RSG [%] |
CEday2 [%] |
RSday2 [%] |
RTG [%] |
MF total |
MF small |
MS large |
SC1 | 100 | 97 | 100 | 100 | 89 | 70 | 16 |
SC2 | 100 | 80 | 100 | 100 | 86 | 66 | 18 |
0.54 | 107 | 86 | 98 | 105 | 98 | 71 | 25 |
1.7 | 118 | 79 | 89 | 106 | 98 | 72 | 23 |
5.4 | 126 | 83 | 93 | 117 | 94 | 62 | 28 |
17 | 129 | 77 | 87 | 112 | 122 | 91 | 26 |
52 | 108 | 75 | 84 | 91 | 124 | 97 | 23 |
164 | 112 | 78 | 88 | 99 | 104 | 66 | 34 |
512 | 106 | 72 | 82 | 87 | 147 | 99 | 41 |
901 | 101 | 88 | 99 | 100 | 116 | 89 | 23 |
MMS | 79 | 41 | 47 | 37 | 1149 | 870 | 191 |
Table 4: 3 h treatment, with metabolic activation
Dose [µg/mL] |
RSG [%] |
CEday2 [%] |
RSday2 [%] |
RTG [%] |
MF total |
MF small |
MS large |
SC1 | 100 | 68 | 100 | 100 | 51 | 26 | 23 |
SC2 | 100 | 64 | 100 | 100 | 55 | 30 | 25 |
0.54 | 92 | 78 | 118 | 108 | 53 | 31 | 20 |
1.7 | 78 | 111 | 168 | 132 | 26 | 17 | 8 |
5.4 | 56 | 93 | 140 | 79 | 38 | 28 | 10 |
17 | 60 | 97 | 146 | 88 | 31 | 22 | 9 |
52 | 65 | 66 | 100 | 65 | 62 | 47 | 14 |
164 | 92 | 74 | 111 | 102 | 53 | 45 | 7 |
512 | 64 | 77 | 116 | 74 | 45 | 12 | 32 |
901 | 93 | 81 | 123 | 114 | 45 | 25 | 19 |
CP | 37 | 29 | 43 | 16 | 849 | 647 | 167 |
Experiment 2
Table 5: 24 h treatment, without metabolic activation
Dose [µg/mL] |
RSG [%] |
CEday2 [%] |
RSday2 [%] |
RTG [%] |
MF total |
MF small |
MS large |
SC1 | 100 | 98 | 100 | 100 | 57 | 26 | 30 |
SC2 | 100 | 102 | 100 | 100 | 50 | 19 | 30 |
0.54 | 92 | 84 | 84 | 77 | 63 | 19 | 42 |
1.7 | 91 | 86 | 86 | 78 | 71 | 40 | 28 |
5.4 | 99 | 89 | 89 | 88 | 65 | 25 | 38 |
17 | 90 | 89 | 89 | 80 | 49 | 11 | 38 |
52 | 86 | 98 | 98 | 84 | 51 | 16 | 34 |
164 | 85 | 88 | 87 | 74 | 72 | 34 | 36 |
512 | 78 | 90 | 90 | 71 | 50 | 22 | 26 |
901 | 64 | 107 | 107 | 68 | 53 | 9 | 43 |
MMS | 80 | 61 | 61 | 49 | 621 | 198 | 368 |
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (negative)
Genetic toxicity in vivo
Endpoint conclusion
- Endpoint conclusion:
- no study available
Additional information
For the assessment of the potential to induce genetic toxicity supporting information are available for the target substance, lactic acid. In addition, data from the suitable read-across partner L(+)-lactic acid was used to assess genetic toxicity of the target substance. For details and justification of read-across please refer to the report attached in section 13 of IUCLID.
L(+)-lactic acid was tested in an in vitro test battery, which were performed in accordance to the OECD testing guidelines 471 (Ames test), 473 (chromosome aberration) and 476 (MLA, nowadays OECD 490).
In the bacterial reverse mutation test four strains of Salmonella typhimurium, TA1535, TA1537, TA100 and TA98 plus the Escherichia coli strain WP2uvrA were treated with L(+)-lactic acid up to the limit concentration of 5000 µg/plate. No increase in the rate of revertant colonies was observed in all tested concentrations (0, 100, 333, 1000, 3330 and 5000 µg/plate) with and without addition of S9-mix. Thus, L(+)-lactic acid can be considered as not mutagenic in the bacterial reverse mutation assay.
In a gene mutation assay conducted according to OECD 476 (nowadays OECD 490), L5178Y mouse lymphoma cells were exposed for 3 hours (with and without S9 mix) and 24 hours (without S9 mix). Eight doses between 0.54 and 901 µg/mL L(+)-lactic acid were tested, not resulting in an increase of mutation frequency per 10^6 survivors in the presence or absence of metabolic activation with 3 or 24 hours exposure time. Thus, L(+)-lactic acid is considered as not mutagenic.
The third in vitro test was a chromosome aberration test conducted according to OECD 473. Five doses of L(+)-lactic acid were tested ranging from 10 to 901 µg/mL in peripheral human lymphocytes. Assessment of the results showed no significant increase over control levels for all exposure and fixation times tested in the presence and absence of metabolic activation.
In addition to these three OECD guideline studies with the source substance L(+)-lactic acid, five publications report further results on the genotoxic potential of the target substance lactic acid. No positive results were reported, with exception of Morita (1990), where some chromosome aberrations had been found under non-physiological conditions, i.e. low pH. The same study reports negative findings under physiological conditions, whereas the positive finding is of no toxicological relevance.
Therefore, in view of all genotoxicity tests, lactic acid is considered as not genotoxic.
Justification for classification or non-classification
Based on the available results, the target substance lactic acid is not considered to be genotoxic and no classification is warranted in accordance with CLP Regulation 1272/2008.
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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