Registration Dossier
Registration Dossier
Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.
The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.
Use of this information is subject to copyright laws and may require the permission of the owner of the information, as described in the ECHA Legal Notice.
EC number: 200-712-3 | CAS number: 69-72-7
Endpoint summary
Administrative data
Key value for chemical safety assessment
Genetic toxicity in vitro
Description of key information
The genotoxic potential of SA has been investigated in a number of test systems both in vitro and in vivo. All tests gave negative results, leading to the conclusion that SA is not genotoxic.
For in vitro gene mutation studies in bacteria, a publication describing a study compiled under the supervision of the Ministry of Labour of Japan (2000), similar to OECD guideline 471 (Rel 1), was chosen as key study. Two publications of Rel 2, Jasiewicz et al. (1987) (using acetylsalicylic acid) and Martinez et al. (2000) have been chosen as supporting studies. An in vitro mammalian cell gene mutation study (RCC, 2008) performed according to OECD guideline 476 (Rel 1) has been chosen as key study for this endpoint. For chromosomal aberration in mammalian cells in vitro, a publication by Stich et al. (1981) meeting basic scientific principles (Rel. 2) has been chosen as key study.
Link to relevant study records
- 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
- Study period:
- from 2008/05/14 to 2008/07/21
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: guideline study satisfying the requirement for OECD 476 for in vitro mutagenicity.
- Reason / purpose for cross-reference:
- reference to same study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 476 (In Vitro Mammalian Cell Gene Mutation Test)
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- other: Commission Directive 2000/32/EC, L 1362000, Annex 4E, dated May 19, 2000
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Type of assay:
- mammalian cell gene mutation assay
- Target gene:
- Thymidine kinase locus (TK+/-)
- Species / strain / cell type:
- mouse lymphoma L5178Y cells
- Details on mammalian cell type (if applicable):
- - Type and identity of media: RPMI 1640 medium supplemented with 15% horse serum, 100 U/100 µg/ml Penicillin/Streptomycin,
220 µg/ml sodium-pyruvate, and 0.5-0.75 U/ml Amphotericin used as antifungal.
- Properly maintained: yes
- Periodically checked for Mycoplasma contamination: yes
- Periodically checked for karyotype stability: yes
- Periodically "cleansed" against high spontaneous background: yes - Additional strain / cell type characteristics:
- not applicable
- Metabolic activation:
- with and without
- Metabolic activation system:
- Rat liver S9 induced by Phenobarbital/beta-Naphthoflavone
- Test concentrations with justification for top dose:
- For experiment I and II with and without S9 mix: 87.5, 175.0, 350.0, 1400.0 µg/mL.
- Vehicle / solvent:
- - Vehicle(s)/solvent(s) used: deionised water. The final concentration of deionised water in the culture medium was 10% (v/v).
- Untreated negative controls:
- yes
- Remarks:
- deionised water
- Negative solvent / vehicle controls:
- yes
- Remarks:
- deionised water
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- methylmethanesulfonate
- Remarks:
- Migrated to IUCLID6: without metabolic activation
- Positive controls:
- yes
- Positive control substance:
- cyclophosphamide
- Remarks:
- Migrated to IUCLID6: with metabolic activation
- Details on test system and experimental conditions:
- METHOD OF APPLICATION: in medium
DURATION
- Preincubation period: no
- Exposure duration: 4 h for the first experiment and 24h for the second experiment without S9 mix.
- Expression time (cells in growth medium): 2 days
- Fixation time (start of exposure up to fixation or harvest of cells): 52 h for the first experiment and 72 h for the second experiment.
SELECTION AGENT (mutation assays):
after expression time:
- seeding of 4x1000 cells/well in selective medium (TFT)
- incubation 10-15 day: determination of mutant colonies
NUMBER OF REPLICATIONS: no data
NUMBER OF CELLS EVALUATED:
- Cell density: 10E7 cells/ flask (80 cm2 flasks)
- 4x1000 cells/well for Mutagenicity evaluation.
DETERMINATION OF CYTOTOXICITY
- Method: cloning efficiency:
1- Survival: after treatment time:
- seeding of 2 cells/well in complete culture medium
- incubation 10-15 day: determination of cloning efficiency 1
2- Viability: after expression time:
- seeding of 2 cells/well in medium without TFT
- incubation 10-15 day: determination of cloning efficiency 2
Other:
- The pH and the osmolarity value were determined in culture medium at 1400 µg/ml in the pre-experiment without S9mix:
1- Osmolarity: 265 for solvent control and 286 for SA
2- pH value: 7.35 for solvent control and 7.59 for SA (adjusted with 0.6 ml 2N NaOH). - Evaluation criteria:
- - A test item is classified as mutagenic if the induced mutation frequency reproducibly exceeds a threshold of 126 colonies per 10E6 above the corresponding solvent control.
- A relevant increase of the mutation frequency should be dose-dependant.
- A mutagenic response is considered to be reproducible if it occurs in both parallel cultures.
However, in the evaluation of the test results the historical variability of the mutation rates in negative and vehicle controls and the mutation rates of all negative and vehicle controls of this study are taken into consideration.
Results of test groups are rejected if the relative total growth, and the cloning efficiency 1 is less than 10% of the vehicle control. - Statistics:
- A linear regression was performed to assess a possible dose dependent increase of mutant frequencies using SYSTAT statistics software.
- Species / strain:
- mouse lymphoma L5178Y cells
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity
- Remarks:
- No relevant toxic effects indicated by a relative cloning efficiency 1 or a relative total growth of less than 50% of survival were observed up to the maximum concentration with and without metabolic activation.
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Species / strain:
- mouse lymphoma L5178Y cells
- Metabolic activation:
- without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Additional information on results:
RANGE-FINDING/SCREENING STUDIES:
According the results of the pre-test at least four adequate concentrations were chosen for the muation assay experiment: 87.5, 175.0, 350.0,
1400.0 µg/ml. Following the expression phase of 72 hours the cultures at 43.8 µg/ml in both main experiments were not continued.
ADDITIONAL INFORMATION ON CYTOTOXICITY:
In the second experiment, 24 h treatment without metabolic activation, relevant toxic effects were noted at 700 µg/ml and above. The data at the
maximum concentration of 1400 µg/ml are considered valid even though the relative total growth fell short of the limit of 10%. The corresponding
relative cloning efficiency 1 however, was in a toxic but fully acceptable range. The recommended toxic range of approximately 10-20% of survival
or RTG was covered in experiment II.- Remarks on result:
- other: strain/cell type: L5178Y cells
- Remarks:
- Migrated from field 'Test system'.
- Conclusions:
- Under the test conditions, salicylic acid pharmaceutical grade 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:
The study was performed to investigate the potential of Salicylic acid pharmaceutical grade to induce mutations at the mouse lymphoma thymidine kinase locus using the cell line L5178Y (Wollny, 2008).
The assay was performed in two independent experiments, using two parallel cultures each at 87.5, 175.0, 350.0, 1400.0 µg/ml SA. The first experiment was performed with and without liver microsomal activation and a treatment period of 4 h. The second experiment was solely performed in the absence of metabolic activation with a treatment period of 24 hours. The highest concentration (1400 µg/ml) was chosen with regard to the molecular weight of the test item corresponding to a molar concentrations of about 10 mM. Relevant cytotoxic effects were solely noted following 24 h treatment in the second experiment at 700 µg/ml and above. 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 (see Table 1).
In conclusion it can be stated that during the mutagenicity test described and under the experimental conditions reported the test item 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. Therefore, salicylic acid pharmaceutical grade is considered to be non-mutagenic in this mouse lymphoma assay.
- Endpoint:
- in vitro cytogenicity / chromosome aberration study in mammalian cells
- Remarks:
- Type of genotoxicity: chromosome aberration
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- no data
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: The test conditions are detailed and close to the current test guideline. Only 2 concentrations were tested and no positive control was used. No data on purity.
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 473 (In Vitro Mammalian Chromosome Aberration Test)
- Deviations:
- yes
- Remarks:
- Only two concentrations were tested instead of three. No positive controls.
- GLP compliance:
- not specified
- Type of assay:
- in vitro mammalian chromosome aberration test
- Species / strain / cell type:
- other: CHO cells
- Metabolic activation:
- with and without
- Metabolic activation system:
- S9 from Aroclor 1254 induced rat liver
- Test concentrations with justification for top dose:
- 12 or 25 mg/ml.
- Vehicle / solvent:
- - Vehicle(s)/solvent(s) used: none
- Untreated negative controls:
- yes
- Negative solvent / vehicle controls:
- no
- True negative controls:
- no
- Positive controls:
- no
- Positive control substance:
- no
- Details on test system and experimental conditions:
- METHOD OF APPLICATION: in medium
DURATION
- Exposure duration: 3h
- Expression time (cells in growth medium): 16h
- Fixation time (start of exposure up to fixation or harvest of cells): 19h
NUMBER OF CELLS EVALUATED: 200 - Evaluation criteria:
- No data
- Statistics:
- No data
- Species / strain:
- Chinese hamster Ovary (CHO)
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- not specified
- Vehicle controls validity:
- not examined
- Untreated negative controls validity:
- not examined
- Positive controls validity:
- not examined
- Additional information on results:
- no data
- Remarks on result:
- other: all strains/cell types tested
- Remarks:
- Migrated from field 'Test system'.
- Conclusions:
- Interpretation of results:
negative with metabolic activation,
negative without metabolic activation
In this study, salicylic acid did not induce clastogenic effect on CHO cells. - Executive summary:
In a mammalian cell cytogenetics assay for chromosome aberration (Stich et al., 1981), CHO cell cultures were exposed to salicylic acid at concentration of 25 mg/ml for 3 hours with and without metabolic activation. The concentration used was half the dose which induced mitotic inhibition, defined as one metaphase or less in 6000 CHO cells. In addition, CHO cells were exposed to 12 mg/ml of Salicylic acid with a transition metal (Cu2 + or Mn2+ at 10 -4 M) without a metabolic activation. Salicylic acid did not induce a clastogenic effect. No positive controls were used. This study is classified as acceptable.
- Endpoint:
- in vitro gene mutation study in bacteria
- Remarks:
- Type of genotoxicity: gene mutation
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- no data
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: The test conditions are not described but study carried out under the supervision of Japanese Authorities. No data on the GLP.
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 471 (Bacterial Reverse Mutation Assay)
- Deviations:
- not applicable
- Remarks:
- Precise details of the protocol not provided
- GLP compliance:
- not specified
- Type of assay:
- bacterial reverse mutation assay
- Species / strain / cell type:
- other: S. typhimurium TA100, TA1535, TA98, TA1537 and E. coli WP2uvrA/pKM101.
- Metabolic activation:
- with and without
- Metabolic activation system:
- +/- S9 (no other information)
- Test concentrations with justification for top dose:
- 1.22, 4.88, 19.5, 78.1, 313, 1250 and 5000 µg/plate (experiment 1)
9.77, 19.5, 39.1, 78.1, 156, 313, 625, 1250, 2500 and 5000 µg/plate (experiment 2) - Vehicle / solvent:
- - Vehicle(s)/solvent(s) used: DMSO
- Justification for choice of solvent/vehicle: no data - Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- other: AF-2, 2-AA, NaN3, 9-AA
- Details on test system and experimental conditions:
- no data
- Evaluation criteria:
- no data
- Statistics:
- no
- Species / strain:
- S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- from 78.1 µg/plate for TA100 and from 313 µg/plate for other strains
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not examined
- Positive controls validity:
- valid
- Species / strain:
- E. coli WP2 uvr A pKM 101
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- from 1250 µg/plate
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not examined
- Positive controls validity:
- valid
- Additional information on results:
- no data
- Remarks on result:
- other: all strains/cell types tested
- Conclusions:
- Interpretation of results:
negative with metabolic activation,
negative without metabolic activation
Under the conditions of this study, no mutagenic effect was induced by salicylic acid. - Executive summary:
In a reverse gene mutation assay in bacteria (Ministry of Labour/Japan, 2000), strains TA1535, TA1537, TA98 and TA100 of S. typhimurium and WP2uvrA/pKM101 of E. coli were exposed to salicylic acid, at concentration of 1.22 to 5000 µg/plate in the presence and absence of mammalian metabolic activation. The positive controls induced the appropriate responses in the corresponding strains. There was no evidence of induced mutant colonies over background. This study is classified as acceptable, satisfying the requirement for Test Guideline OECD 471 for in vitro mutagenicity (bacterial reverse gene mutation) data.
Referenceopen allclose all
No relevant shift of the ratio of small versus large colonies was observed up to the maximal concentration of the test item.
Table 1: Clastogenic activity of phenolic compounds in chinese hamster ovary cells
| Concentration of Salicylic acid (mg/ml) | Activation | % Metaphases with chromosome aberrations | Chromatid breaks per cell | Chromatid exchanges per cell | |
| Salicylic acid | 25 | - S9 | 1.5 | 0.02 | 0.00 |
| + S9 | 1.0 | 0.01 | 0.00 | ||
| control | 0 | - S9 | 0.7 | 0.01 | 0.00 |
The presented concentration above is half the dose which induces mitotic inhibition, which is defined as one metaphase or less in 6000 CHO cells. An unexposed replicating cell culture contains between 7.5 % and 9 % metaphase plates following a 3 -h colchicine application prior to sampling time.
Table 2: The effect of transition metals on the clastogenic activity of phenolic compounds
| Concentration of Salicylic acid (mg/ml) | % Metaphases with chromosome aberrations | Chromatid exchanges per cell | |
| Salicylic acid | 12 | 1.4 | 0.00 |
| Salicylic acid + 10 -4 M of Cu2+ | 12 | 1.3 | 0.00 |
| Salicylic acid + 10 -4 M of Mn2+ | 12 | 0.0 | 0.00 |
Experiment 1:
| Conc. µg/plate | number of revertants/plate | |||||||||
| Base-substitution | Frame-shift | |||||||||
| TA100 | TA1535 | WP2uvrA/pKM101 | TA98 | TA1537 | ||||||
| S9- | S9+ | S9- | S9+ | S9- | S9+ | S9- | S9+ | S9- | S9+ | |
| DMSO | 127 | 124 | 9 | 10 | 48 | 85 | 21 | 29 | 6 | 11 |
| 1.22 | 137 134 (136) |
131 145 (138) |
15 5 (10) |
10 13 (12) |
40 46 (43) |
81 82 (82) |
16 24 (20) |
31 38 (35) |
7 6 (7) |
13 7 (10) |
| 4.88 | 128 122 (125) |
148 143 (146) |
6 13 (10) |
8 11 (10) |
57 51 (54) |
76 71 (75) |
18 22 (20) |
24 22 (23) |
6 6 (6) |
3 9 (6) |
| 19.5 | 120 128 (124) |
136 162 (149) |
9 3 (6) |
8 10 (9) |
56 43 (50) |
77 77 (77) |
25 21 (23) |
26 29 (28) |
2 3 (3) |
9 5 (7) |
| 78.1 | 53 47 (50) |
45 39 (42) |
8 8 (8) |
9 9 (9) |
74 56 (65) |
71 76 (74) |
20 22 (21) |
20 26 (23) |
6 6 (6) |
3 2 (3) |
| 313 | 16 11 (14) |
6 3 (5) |
0 0 (0) |
2 3 (3) |
59 60 (60) |
84 68 (76) |
11 21 (16) |
15 23 (19) |
0 0 (0) |
1 3 (2) |
| 1250 | 3 7 (5) |
2 0 (1) |
0 0 (0) |
2 2 (2) |
38 39 (39) |
46 44 (45) |
2 1 (2) |
3 1 (2) |
1 0 (1) |
1 3 (2) |
| 5000 | 0 0 (0) |
2 1 (2) |
0 0 (0) |
2 1 (2) |
0 0 (0) |
2 9 (6) |
0 0 (0) |
0 0 (0) |
0 0 (0) |
0 0 (0) |
| Judgement | - | - | - | - | - | - | - | - | - | - |
| Positive control | AF-2 (747) |
2-AA (1374) |
NaN3 (431) |
2-AA (329) |
AF-2 (1452) |
2-AA (1032) |
AF-2 (544) |
2-AA (449) |
9-AA (705) |
2-AA (218) |
( ) = mean of two replicats
Experiment 2:
| Conc. µg/plate | number of revertants/plate | |||||||||
| Base-substitution | Frame-shift | |||||||||
| TA100 | TA1535 | WP2uvrA/pKM101 | TA98 | TA1537 | ||||||
| S9- | S9+ | S9- | S9+ | S9- | S9+ | S9- | S9+ | S9- | S9+ | |
| DMSO | 130 | 109 | 7 | 9 | 47 | 67 | 18 | 24 | 7 | 12 |
| 9.77 | 113 116 (115) |
145 119 (132) |
7 5 (6) |
11 19 (14) |
8 15 (12) |
40 20 (35) |
6 3 (5) |
15 11 (13) |
||
| 19.5 | 124 104 (114) |
131 141 (136) |
9 5 (7) |
7 26 (16) |
17 14 (16) |
29 28 (29) |
3 11 (7) |
9 5 (7) |
||
| 39.1 | 71 100 (86) |
107 116 (112) |
7 6 (7) |
16 10 (13) |
30 41 (36) |
71 81 (76) |
24 15 (20) |
28 33 (31) |
5 6 (6) |
11 10 (11) |
| 78.1 | 69 66 (68) |
71 47 (59) |
6 7 (7) |
21 6 (14) |
57 56 (57) |
76 70 (73) |
13 11 (12) |
24 20 (22) |
1 2 (2) |
6 3 (6) |
| 156 | 2 2 (2) |
5 2 (4) |
6 5 (6) |
9 10 (10) |
53 49 (51) |
76 86 (81) |
11 10 (11) |
23 18 (21) |
1 9 (5) |
10 2 (6) |
| 313 | 0 0 (0) |
0 6 (3) |
0 0 (0) |
1 2 (2) |
44 54 (49) |
90 69 (80) |
8 8 (8) |
28 22 (25) |
2 2 (2) |
0 2 (1) |
| 625 | 1 0 (1) |
1 1 (1) |
2 1 (2) |
6 3 (5) |
57 59 (58) |
64 68 (66) |
0 2 (1) |
5 5 (5) |
1 0 (1) |
3 5 (4) |
| 1250 | 1 0 (1) |
5 6 (6) |
0 1 (1) |
5 5 (5) |
45 43 (44) |
57 70 (64) |
1 0 (1) |
1 6 (4) |
2 2 (2) |
0 2 (1) |
| 2500 | 0 1 (1) |
2 3 (3) |
0 0 (0) |
5 5 (5) |
32 33 (33) |
40 46 (43) |
0 1 (1) |
3 0 (2) |
2 2 (2) |
1 1 (1) |
| 5000 | 1 1 (1) |
5 0 (3) |
0 0 (0) |
3 5 (4) |
3 1 (2) |
10 7 (9) |
0 2 (1) |
6 0 (3) |
2 3 (3) |
2 1 (2) |
| judgement | - | - | - | - | - | - | - | - | - | - |
| positive control | AF-2 (680) |
2-AA (1299) |
NaN3 (447) |
2-AA (280) |
AF-2 (1095) |
2-AA (880) |
AF-2 (640) |
2-AA (428) |
9-AA (679) |
2-AA (160) |
( ) mean of two replicats
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (negative)
Genetic toxicity in vivo
Description of key information
For genotoxicity in vivo, a publication by Giri et al. (1996) describes oral and intraperitoneal studies on chromosome aberrations (CA) and sister chromatid exchange (SCE) in the bone marrow cells of mice. Salicylic acid was administered intraperitoneally (i.p.) or orally by gavage. These tests were carried out according to a scientifically acceptable standard which is similar to EPA OPPTS 870.5915.
Link to relevant study records
- Endpoint:
- in vivo mammalian somatic cell study: cytogenicity / bone marrow chromosome aberration
- Remarks:
- Type of genotoxicity: chromosome aberration
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- no data
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: The test conditions are similar to the OECD test guideline. The test conditions and the results are well described. Only one dose level was tested by oral route, and compliance with GLP was not mentioned.
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 475 (Mammalian Bone Marrow Chromosome Aberration Test)
- Deviations:
- yes
- Remarks:
- only one dose level was used
- GLP compliance:
- not specified
- Type of assay:
- mammalian germ cell cytogenetic assay
- Species:
- mouse
- Strain:
- Swiss
- Sex:
- male
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Division of laboratory animals, Central drug research institute, Lucknow
- Age at study initiation: 10-12 weeks old
- Weight at study initiation: 30 g
- Assigned to test groups randomly: no data
- Fasting period before study: no data
- Housing: no data
- Diet : ad libitum, standard rodent pellet diet (Gold Mohor, Lipton India Ltd., Chandigarh, India)
- Water : ad libitum
- Acclimation period: no data
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 28 +/- 2
- Humidity (%): 60 +/- 5
- Air changes (per hr): no data
- Photoperiod : 12 hrs dark / 12 hrs light
IN-LIFE DATES: no data - Route of administration:
- oral: gavage
- Vehicle:
- - Vehicle(s)/solvent(s) used: solution of gum acacia in water at 2 %
- Justification for choice of solvent/vehicle: no data
- Concentration of test material in vehicle: no data - Details on exposure:
- Salicylic acid was suspended with 2% gum acacia in distilled water and gavaged (350 mg/kg bw) to a group of 5 mice (0.3 ml/mouse). Negative control mice were gavaged only 2 % gum acacia in distilled water.
- Duration of treatment / exposure:
- 24 hours
- Frequency of treatment:
- once
- Post exposure period:
- 24 hours
- Dose / conc.:
- 350 other: mg/kg
- Remarks:
- Basis: nominal conc.
- No. of animals per sex per dose:
- 5 male mice per dose
- Control animals:
- yes, concurrent vehicle
- Positive control(s):
- none
- Tissues and cell types examined:
- Cells from the bone marrow were examined.
- Details of tissue and slide preparation:
- After 22 hr of chemical treatment, the animals were injected with colchicine (2 mg/kg) and 2 hr later they were killed by cervical dislocation. Bone marrow chromosomes were prepared and slides were stained with Giemsa. All the slides were coded and 100 well spread metaphase cells
were scored per animal. Mitotic indices (MI) were calculated from 1000 cells/animal. CA were scored. - Evaluation criteria:
- Statistically significant dose-related increase in the number of CA.
- Statistics:
- Student's t-test was used to compare the results.
- Sex:
- male
- Genotoxicity:
- negative
- Toxicity:
- no effects
- Vehicle controls validity:
- valid
- Negative controls validity:
- not examined
- Positive controls validity:
- not examined
- Additional information on results:
- none
- Conclusions:
- Interpretation of results: negative
Under the condition of this test, salicylic acid did not induce a genotoxic effect. - Executive summary:
In an in vivo chromosome aberrations assay (Giri et al., 1996), Swiss albino male mice were treated with salicylic acid, suspended with 2% gum acacia in distilled water (0.3 ml/mouse), by gavage at the dose of 350 mg/kg. Five mice were used for treated group along with a negative control. Negative control mice were gavaged with 2% gum acacia in distilled water. No significant increase in CA was observed for salicylic acid when compared with solvent control. A significant increase in MI was observed for salicylic acid. Positive control chemical cyclophosphamide induced high chromosome aberrations over solvent control. This study is classified as acceptable. This study satisfies the requirement for Test Guideline OECD 475.
- Endpoint:
- in vivo mammalian somatic cell study: cytogenicity / bone marrow chromosome aberration
- Remarks:
- Type of genotoxicity: chromosome aberration
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- no data
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: The test conditions are similar to the OECD test guideline. The test conditions and the results are well described. Only one dose level was tested by oral route, and compliance with GLP was not mentioned.
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 475 (Mammalian Bone Marrow Chromosome Aberration Test)
- Deviations:
- yes
- Remarks:
- only one sex was used and 4 animals per sex (instead of 5)
- GLP compliance:
- not specified
- Type of assay:
- mammalian germ cell cytogenetic assay
- Species:
- mouse
- Strain:
- Swiss
- Sex:
- male
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Division of laboratory animals, Central drug research institute, Lucknow
- Age at study initiation: 10-12 weeks old
- Weight at study initiation: 30 g
- Assigned to test groups randomly: no data
- Fasting period before study: no data
- Housing: no data
- Diet : ad libitum, standard rodent pellet diet (Gold Mohor, Lipton India Ltd., Chandigarh, India)
- Water : ad libitum
- Acclimation period: no data
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 28 +/- 2
- Humidity (%): 60 +/- 5
- Air changes (per hr): no data
- Photoperiod : 12 hrs dark / 12 hrs light
IN-LIFE DATES: no data - Route of administration:
- intraperitoneal
- Vehicle:
- - Vehicle(s)/solvent(s) used: DMSO
- Justification for choice of solvent/vehicle: the non-polar nature of these compounds required the use of DMSO as the solvent for its i.p. administration.
- Concentration of test material in vehicle: no data - Details on exposure:
- Salicylic acid was dissolved in DMSO and injected i.p (75 µl/mouse). Four mice were used for each dose along with a negative control. Negative control mice received equal volume of only DMSO. Five mice were injected cyclophosphamide (25 mg/kg) in equal volume of DMSO (75 µl/mouse) and served as positive control.
- Duration of treatment / exposure:
- 24 hours
- Frequency of treatment:
- once
- Post exposure period:
- 24 hours
- Dose / conc.:
- 50 other: mg/kg
- Remarks:
- Basis: nominal conc.
- Dose / conc.:
- 100 other: mg/kg
- Remarks:
- Basis: nominal conc.
- Dose / conc.:
- 200 other: mg/kg
- Remarks:
- Basis: nominal conc.
- No. of animals per sex per dose:
- 4 male mice per dose
- Control animals:
- yes, concurrent vehicle
- Positive control(s):
- cyclophosphamide
- Justification for choice of positive control(s): usual positive control substances
- Route of administration: intraperitoneal
- Doses / concentrations: 25 mg/kg - Tissues and cell types examined:
- Cells from the bone marrow were examined.
- Details of tissue and slide preparation:
- After 22 hr of chemical treatment, the animals were injected with colchicine (2 mg/kg) and 2 hr later they were killed by cervical dislocation. Bone marrow chromosomes were prepared and slides were stained with Giemsa. All the slides were coded and 100 well spread metaphase cells
were scored per animal. Mitotic indices (MI) were calculated from 1000 cells/animal. CA were scored. - Evaluation criteria:
- Statistically significant dose-related increase in the number of CA or a reproducible and statistically significant positive response for at least one of the test points
- Statistics:
- Student's t-test was used to compare the results.
- Sex:
- male
- Genotoxicity:
- negative
- Toxicity:
- no effects
- Vehicle controls validity:
- valid
- Negative controls validity:
- not examined
- Positive controls validity:
- valid
- Additional information on results:
- none
- Conclusions:
- Interpretation of results: negative
Under the condition of this test, salicylic acid did not induce a genotoxic effect. - Executive summary:
In an in vivo chromosome aberrations assay (Giri et al., 1996), Swiss albino male mice were treated with salicylic acid, dissolved in DMSO (75 µl/mouse), in an i.p. administration at the doses of 50, 100 and 200 mg/kg. Four mice were used for each dose along with a negative control. Negative control mice received equal volume of only DMSO. Five mice were injected cyclophosphamide (25 mg/kg) in equal volume of DMSO (75 µl/mouse) and served as positive control. No significant increase in CA was observed for salicylic acid when compared with solvent control. A significant increase in MI was observed at the lowest dose for salicylic acid. Positive control chemical cyclophosphamide induced high chromosome aberrations over solvent control. This study is classified as acceptable. This study satisfies the requirement for Test Guideline OECD 475.
- Endpoint:
- in vivo mammalian cell study: DNA damage and/or repair
- Remarks:
- Type of genotoxicity: DNA damage and/or repair
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- no data
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: The test conditions are similar to the EPA test guideline. The test conditions and the results are well described. Compliance with GLP was not mentioned.
- Reason / purpose for cross-reference:
- reference to same study
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- EPA OPPTS 870.5915 (In Vivo Sister Chromatid Exchange Assay)
- Deviations:
- yes
- Remarks:
- only one dose level was used
- GLP compliance:
- not specified
- Type of assay:
- sister chromatid exchange assay
- Species:
- mouse
- Strain:
- Swiss
- Sex:
- male
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Division of laboratory animals, Central drug research institute, lucknow
- Age at study initiation: 10-12 weeks old
- Weight at study initiation: 30 g
- Assigned to test groups randomly: no data
- Fasting period before study: no data
- Housing: no data
- Diet : ad libitum, standard rodent pellet diet (Gold Mohor, Lipton India Ltd., Chandigarh, India)
- Water : ad libitum
- Acclimation period: no data
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 28 +/- 2
- Humidity (%): 60 +/- 5
- Air changes (per hr): no data
- Photoperiod : 12 hrs dark / 12 hrs light
IN-LIFE DATES: no data - Route of administration:
- oral: gavage
- Vehicle:
- - Vehicle(s)/solvent(s) used: solution of gum acacia in water at 2 %
- Justification for choice of solvent/vehicle: no data - Details on exposure:
- PREPARATION OF DOSING SOLUTIONS: Salicylic acid was suspended with 2 % gum acacia in distilled water
Salicylic acid was administered by gavage as a single-dose (0.3 ml/mouse) at the dose of 350 mg/kg. - Duration of treatment / exposure:
- 23 h 30
- Frequency of treatment:
- once
- Post exposure period:
- 23 h 30
- Dose / conc.:
- 350 other: mg/kg
- Remarks:
- Basis: nominal conc.
- No. of animals per sex per dose:
- 5 males per dose
- Control animals:
- yes, concurrent vehicle
- Positive control(s):
- none
- Tissues and cell types examined:
- Cells from the bone marrow were examined.
- Details of tissue and slide preparation:
- CRITERIA FOR DOSE SELECTION: Doses were selected based on the oral LD50 (1.1 g/kg bw) of acetyl salicylic acid in mice available in the literature. The oral dose was approximately 1/3 of the oral LD50 of mice reported above.
DETAILS OF SLIDE PREPARATION: After preparation of the slides, the chromosomes were differentially stained with fluorescence-plus-Giemsa technique.
METHOD OF ANALYSIS: A number of 30 second division metaphase cells (40 +/- 2 chromosomes) per animal were scored per dose tested. Randomly selected metaphase cells (100/ animal) were scored for replicative indices (RI) analysis by their staining pattern as first (M1), second (M2) and third (M3) division metaphases. The RI were calculated as follows: RI = (1M1 + 2M2+ 3M3)/100. - Evaluation criteria:
- Statistically significant dose-related increase in the number of SCE.
- Statistics:
- Student's t-test was used to compare the results of the treated series with the controls.
- Sex:
- male
- Genotoxicity:
- negative
- Toxicity:
- not specified
- Vehicle controls validity:
- valid
- Negative controls validity:
- not examined
- Positive controls validity:
- not examined
- Additional information on results:
- none
- Conclusions:
- Interpretation of results: negative
Under the condition of this test, salicylic acid did not induce a genotoxic effect. - Executive summary:
In an in vivo sister chromatid exchange assay (Giri et al., 1996), Swiss albino male mice were treated with salicylic acid, suspended in distilled water in 2 % gum acacia (0.3 ml/mouse), in a single oral administration at the dose of 350 mg/kg. Negative control mice were administered with gum acacia. No positive control was used. No significant increase in SCE was observed for salicylic acid (4.94 +/- 0.30) when compared with solvent control (4.54 +/- 0.43). This study is classified as acceptable. Nevertheless, this study does not completely satisfy the requirement for Test Guideline OPPTS 870.5915 as only one dose level was used.
- Endpoint:
- in vivo mammalian cell study: DNA damage and/or repair
- Remarks:
- Type of genotoxicity: DNA damage and/or repair
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- no data
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: The test conditions are similar to the EPA test guideline. The test conditions and the results are well described. Compliance with GLP was not mentioned.
- Reason / purpose for cross-reference:
- reference to same study
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- EPA OPPTS 870.5915 (In Vivo Sister Chromatid Exchange Assay)
- Deviations:
- no
- GLP compliance:
- not specified
- Type of assay:
- sister chromatid exchange assay
- Species:
- mouse
- Strain:
- Swiss
- Sex:
- male
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Division of laboratory animals, Central drug research institute, lucknow
- Age at study initiation: 10-12 weeks old
- Weight at study initiation: 30 g
- Assigned to test groups randomly:no data
- Fasting period before study: no data
- Housing:
- Diet : ad libitum, standard rodent pellet diet (Gold Mohor, Lipton India Ltd., Chandigarh, India)
- Water : ad libitum
- Acclimation period: no data
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 28 +/- 2
- Humidity (%): 60 +/- 5
- Air changes (per hr): no data
- Photoperiod : 12 hrs dark / 12 hrs light
IN-LIFE DATES: no data - Route of administration:
- intraperitoneal
- Vehicle:
- - Vehicle(s)/solvent(s) used: DMSO
- Justification for choice of solvent/vehicle: The non-polar nature of these compounds required the use of DMSO as the solvent for their i.p. administration. - Details on exposure:
- The test chemical was administered as a single I.P. injection 1h after tablet implantation. Three doses of salicylic acid were injected i.p. in DMSO (75 µl/mouse) to different groups of 5 animals each. Colchicine (4 mg/kg) was injected (i.p.) 22h after Brdu-tablet implantation. Two hours later, the bone marrow was expelled with 0.075 M KCl.
- Duration of treatment / exposure:
- 23 h
- Frequency of treatment:
- once
- Post exposure period:
- 23 h
- Dose / conc.:
- 25 other: mg/kg
- Remarks:
- Basis: nominal conc.
- Dose / conc.:
- 50 other: mg/kg
- Remarks:
- Basis: nominal conc.
- Dose / conc.:
- 100 other: mg/kg
- Remarks:
- Basis: nominal conc.
- No. of animals per sex per dose:
- 5 males per dose
- Control animals:
- yes, concurrent vehicle
- Positive control(s):
- mitomycin C
- Route of administration: intraperitoneal
- Doses / concentrations: 1.5 mg/ kg bw - Tissues and cell types examined:
- Cells from the bone marrow were examined.
- Details of tissue and slide preparation:
- CRITERIA FOR DOSE SELECTION: Doses were selected based on the oral LD50 (1.1 g/kg bw) of acetyl salicylic acid in mice available in the literature. The highest i.p. dose was approximately 1/10 of the oral LD50 (100 mg/kg). The other two lower doses were the serial dilutions of the highest dose selected.
DETAILS OF SLIDE PREPARATION: After preparation of the slides, the chromosomes were differentially stained with fluorescence-plus-Giemsa technique.
METHOD OF ANALYSIS: A number of 30 second division metaphase cells (40 +/- 2 chromosomes) per animal were scored per dose tested. Randomlyselected metaphase cells (100/ animal) were scored for replicative indices (RI) analysis by their staining pattern as first (M1), second (M2) and third (M3) division metaphases. The RI were calculated as follows: RI = (1M1 + 2M2+ 3M3)/100. - Evaluation criteria:
- Statistically significant dose-related increase in the number of SCE or a reproducible and statistically significant positive response for at least one of the test points
- Statistics:
- Student's t-test was used to compare the results of the treated series with the controls.
- Sex:
- male
- Genotoxicity:
- negative
- Toxicity:
- not specified
- Vehicle controls validity:
- valid
- Negative controls validity:
- not examined
- Positive controls validity:
- valid
- Additional information on results:
- none
- Conclusions:
- Interpretation of results: negative
Under the condition of this test, salicylic acid did not induce a genotoxic effect. - Executive summary:
In an in vivo sister chromatid exchange assay (Giri et al., 1996), Swiss albino male mice were treated with salicylic acid in DMSO (75 µl/mouse) in a single i.p. injection at the dose of 25, 50 and 100 mg/kg. Negative control mice were injected with 75 µl DMSO while mitomycin C was used as a positive control at a dose of 1.5 mg/kg bw. No significant increase in SCE was observed for salicylic acid when compared with solvent control. Positive control chemical mitomycin C gave a very high frequency of SCE (19.8/cell) over those of solvent control (4.66/cell). This study is classified as acceptable. This study satisfies the requirement of Test Guideline OPPTS 870.5915.
Referenceopen allclose all
| Treatment | Gapsa | Aberrations/cellb | Aberrant cells % (mean +/- SD)c | Mitotic indices (mean +/- SD)c | |
| Chromatid type | Chromosome type | ||||
| Negative control DMSO | 8 | 0.015 | 0.002 | 1.75 +/- 0.50 | 2.79 +/- 0.65 |
| 50 mg/kg SA | 9 | 0.0150 | 0.000 | 1.50 +/- 0.58 | 4.11 +/- 0.69* |
| 100 mg/kg SA | 7 | 0.0175 | 0.000 | 1.75 +/- 0.50 | 3.46 +/- 0.96 |
| 200 mg/kg SA | 11 | 0.0150 | 0.0025 | 2.75 +/- 0.96 | 3.20 +/- 0.98 |
| Positive control cyclophosphamide (25 mg/kg) | 34 | 0.130 | 0.020 | 12.20 +/- 2.16 | 3.50 +/- 0.78 |
Table 1: In vivo chromatid exchanges induced by salicylic acid (SA) in mice after oral administration
| Treatment | SCE/cell of 5 animals | SCE/cell (mean +/- SD)a | Replicative indices (mean +/- SD)a | |||
| Solvent control (Gum acacia) | 4.4/ 3.9/ 5.1/ 4.6/ 4.7 | 4.54 +/- 0.43 | 1.83 +/- 0.10 | |||
| 350 mg/kg SA | 5.3/ 4.6/ 5.2/ 4.7/ 4.9 | 4.94 +/- 0.30 | 1.87 +/- 0.10 | |||
a Mean SD of five animals (30 cells per animal). Results of each dose were compared with the control using Student's t-test (* p < 0.001).
Table 1: In vivo chromatid exchanges induced by salicylic acid (SA) in mice after i.p. administration
| Treatment | SCE/cell of 5 animals | SCE/cell (mean +/- SD)a | Replicative indices (mean +/- SD)a | |||
| Solvent control | 4.5/ 4.5/ 4.0/ 4.8/ 5.5 | 4.66 +/- 0.55 | 1.86 +/- 0.09 | |||
| 25 mg/kg SA | 4.5/ 4.2/ 5.7/ 4.4/ 4.8 | 4.72 +/- 0.58 | 1.85 +/- 0.09 | |||
| 50 mg/kg SA | 5.1/ 4.4/ 5.5/ 4.9/ 3.8 | 4.74 +/- 0.65 | 1.86 +/- 0.07 | |||
| 100 mg/kg SA | 4.3/5.2/ 4.9/ 5.6/ 5.3 | 5.06 +/- 0.49 | 1.84 +/- 0.12 | |||
| Positive control Mitomycin C (1.5 mg/kg) |
18.5/ 19.5/ 23.2/ 18.1/ 16.6 | 19.18 +/- 2.47* | 1.77 +/- 0.18 | |||
a Mean SD of five animals (30 cells per animal). Results of each dose were compared with the control using Student's t-test.
* significantly different from control.
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (negative)
Additional information
Genotoxicity in vitro:
The genotoxic potential of SA has been investigated in a number of test systems in vitro.Gene mutation studies have been carried out using bacteria, eukariotic cells and mammalian cells. Chromosomal aberration has been investigated in mammalian cells.
In a reverse gene mutation assay in bacteria (Ministry of Labour/Japan, 2000), strains TA1535, TA1537, TA98 and TA100 of S. typhimurium and WP2uvrA/pKM101 of E. coli were exposed to salicylic acid, at concentration of 1.22 to 5000 µg/plate in the presence and absence of mammalian metabolic activation. The positive controls induced the appropriate responses in the corresponding strains. There was no evidence of induced mutant colonies over background. This key study satisfies the requirement of Test Guideline OECD 471 for in vitro mutagenicity (bacterial reverse gene mutation).
In a reverse gene mutation assay in bacteria (Jasiewicz and Richardson, 1987), S. typhimurium strains TA1535, TA1537, TA1538, TA97, TA98 and TA100 were exposed to aspirin (acetylsalicylic acid) in DMSO at concentration of 0.01 -5 mg/plate in the presence and absence of mammalian metabolic activation. The positive controls induced the appropriate responses in the corresponding strains. Aspirin did not show any evidence of mutagenic activity, with and without metabolic activation. This study in the read-across substance acetylsalicylic acid is considered acceptable in support of the key study for bacterial mutation.
In a reverse gene mutation assay in bacteria called WP2 Mutoxitest (Martinez et al., 2000), E. coli strains WP2 uvrA/pKM101 (= IC188) and its derivative IC203 deficient in OxyR function were exposed to salicylic acid at least twice with five to six dose levels, including a toxic dose, in the absence of mammalian metabolic activation. WP2 Mutoxitest was developed for the screening of oxidising mutagens. BOOH and menadione, two reference oxidative mutagens, were included as positive controls. They induced the appropriate responses in the corresponding strains. Salicylic acid was non-mutagenic under the assay conditions. This study is considered acceptable in support of the key study for bacterial mutation.
A study was performed to investigate the potential of Salicylic acid pharmaceutical grade to induce mutations at the mouse lymphoma thymidine kinase locus using the cell line L5178Y (RCC, 2008). The assay was performed in two independent experiments, using two parallel cultures each at 87.5, 175.0, 350.0, 1400.0 µg/ml SA. The first experiment was performed with and without liver microsomal activation and a treatment period of 4 h. The second experiment was solely performed in the absence of metabolic activation with a treatment period of 24 hours. The highest concentration (1400 µg/ml) was chosen with regard to the molecular weight of the test item corresponding to a molar concentrations of about 10 mM. Relevant cytotoxic effects were solely noted following 24 h treatment in the second experiment at 700 µg/ml and above. 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. Salicylic acid 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 and is considered to be non-mutagenic in this mouse lymphoma assay. This key study satisfies the requirement of Test Guideline OECD Guideline 476 (In vitro Mammalian Cell Gene Mutation Test).
In a mammalian cell cytogenetics assay for chromosome aberration (Stich et al., 1981), CHO cell cultures were exposed to salicylic acid at concentration of 25 mg/ml for 3 hours with and without metabolic activation. The concentration used was half the dose which induced mitotic inhibition, defined as one metaphase or less in 6000 CHO cells. Salicylic acid did not induce a clastogenic effect. Although no positive controls were used in this study, the protocol was equivalent to OECD Guideline 473 (In vitro Mammalian Chromosome Aberration Test) and is considered to be acceptable to satisfy the testing requirement under this endpoint.
Genotoxicity in vivo:
Two studies on in vivo chromosome aberrations have been published by Giri et al. (1996). In the first study, Swiss albino male mice were treated with salicylic acid, dissolved in DMSO (75 µl/mouse), in an i.p. administration at the doses of 50, 100 and 200 mg/kg. Four mice were used for each dose along with a negative control. Negative control mice received equal volume of only DMSO. Five mice were injected cyclophosphamide (25 mg/kg) in equal volume of DMSO (75 µl/mouse) and served as positive control. No significant increase in CA was observed for salicylic acid when compared with solvent control. A significant increase in MI was observed at the lowest dose for salicylic acid. Positive control chemical cyclophosphamide induced high chromosome aberrations over solvent control. In the second study, Swiss albino male mice were treated with salicylic acid, suspended with 2% gum acacia in distilled water (0.3 ml/mouse), by gavage at the dose of 350 mg/kg. Five mice were used for treated group along with a negative control. Negative control mice were gavaged with 2% gum acacia in distilled water. No significant increase in CA was observed for salicylic acid when compared with solvent control. A significant increase in MI was observed for salicylic acid. Positive control chemical cyclophosphamide induced high chromosome aberrations over solvent control. Although each for these key studies had minor deviations from current guidelines, taken together they are considered as acceptable, satisfying the requirement for Test Guideline OECD 475 (Mammalian Bone Marrow Chromosomal Aberration Test).
The publication by Giri et al (1996) also reports two in vivo sister chromatid exchange assays. In the first study, Swiss albino male mice were treated with salicylic acid in DMSO (75 µl/mouse) in a single i.p. injection at the dose of 25, 50 and 100 mg/kg. Negative control mice were injected with 75 µl DMSO while mitomycin C was used as a positive control at a dose of 1.5 mg/kg bw. No significant increase in SCE was observed for salicylic acid when compared with solvent control. Positive control chemical mitomycin C gave a very high frequency of SCE (19.8/cell) over those of solvent control (4.66/cell). In the second study, Swiss albino male mice were treated with salicylic acid, suspended in distilled water in 2 % gum acacia (0.3 ml/mouse), in a single oral administration at the dose of 350 mg/kg. Negative control mice were administered with gum acacia. No positive control was used. No significant increase in SCE was observed for salicylic acid (4.94 +/- 0.30) when compared with solvent control (4.54 +/- 0.43). Taken together, these studies are acceptable, satisfying the requirement of Test Guideline OPPTS870.5915(In Vivo Sister Chromatid Exchange Assay).
Conclusion:
Salicylic
acid did not show any mutagenicity in bacteria (S. typhimurium or E.coli)
or in mammalian cells and did not cause structural chromosome
aberrations in CHO cells, from in vitro studies. Salicylic acid
did not induce either chromosome aberrations or sister chromatid
exchanges in i.p. or oral studies in vivo in mice, indicating
that salicylic acid is not genotoxic in the bone marrow cells of mice.
Taken together, these results indicate that salicylic acid is not
genotoxic.
Justification for classification or non-classification
Not genotoxic according to EU and GHS (UN/EU) criteria.
Based on absence of mutagenicity in bacterial or mammalian cells, absence of clastogenicity in chromosome aberration studiesin vitroand absence of induction of either chromosome aberrations or sister chromatid exchangesin vivoin mice. These results indicate that salicylic acid is not genotoxic.
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.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.
