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Toxicological information

Genetic toxicity: in vitro

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Administrative data

Endpoint:
in vitro gene mutation study in mammalian cells
Remarks:
Type of genotoxicity: gene mutation
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Comparable to guideline study with acceptable restrictions For read-across justification refer to section 13.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1984

Materials and methods

Principles of method if other than guideline:
NTP-Standard Protocol
GLP compliance:
no
Type of assay:
mammalian cell gene mutation assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material: Trisodium EDTA
- Molecular formula (if other than submission substance): C10 H13 N2 O8 Na3
- Molecular weight (if other than submission substance): 358.19
- Smiles notation (if other than submission substance): OC(=O)CN(CCN(CC(=O)(O[Na]))CC(=O)(O[Na]))CC(=O)(O[Na])
- InChl (if other than submission substance): InChI=1S/C10H16N2O8.3Na/c13-7(14)3-11(4-8(15)16)1-2-12(5-9(17)18)6-10(19) 20;;;/h1-6H2,(H,13,14)(H,15,16)(H,17,18)(H,19,20);;;/q;3*+1/p-3
- Structural formula attached as image file (if other than submission substance): see Fig. 150-38-9 Structure.png

Method

Species / strain
Species / strain / cell type:
mouse lymphoma L5178Y cells
Metabolic activation:
with and without
Metabolic activation system:
S9 from the livers of either Aroclor 1254-induced or non-induced male Fischer 344 rats
Test concentrations with justification for top dose:
3000, 4000, 5000 µg/ml
Controls
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
other: - S9 mix: methyl methanesulfonate; + S9 mix: methylcholanthrene

Results and discussion

Test results
Species / strain:
mouse lymphoma L5178Y cells
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
no cytotoxicity
Vehicle controls validity:
valid
Untreated negative controls validity:
not applicable
Positive controls validity:
valid
Remarks on result:
other: strain/cell type: mouse lymphoma L5178Y cells
Remarks:
Migrated from field 'Test system'.

Any other information on results incl. tables

Tables: Results of the mouse lymphoma test with Na3EDTA

Nonactivation Trial: 1 Experiment Call: Negative and Non-Toxic
Conc. Cloning Relative Total Mutant Colonies Mutant Frequency AVG Mutant Frequency
µg/mL Efficiency Growth
Vehicle Control: H2O 0          64 87 113 59 69
63 112 132 70
65 108 133 68
64# 92 148.5 78
Test Chemical: 60          65 107 177 91 83
74 109 165 74
70          58 110 97 56 68
67 113 162 81
80          67 100 131 65 59
63# 116 99 52
90          58 86 119 69 72
63 93 140 75
100          71 111 142 67 73
66 101 159 80
Positive Control: MMS 15          49 42 293 198 181*
53 45 261 164
Trial Notes:
Nonactivation Trial: 2 Experiment Call: Negative and Non-Toxic
Conc. Cloning Relative Total Mutant Colonies Mutant Frequency AVG Mutant Frequency
µg/mL Efficiency Growth
Vehicle Control: FOP 0          78 103 24 10 18
93 91 50 18
103 104 57 18
84 102 63 25
Test Chemical: 1000          80 42 61 25 23
76 51 45 20
2000          87 53 52 20 21
88 52 61 23
3000          79 38 47 20 21
77 50 50 22
4000          93 32 80 29 27
65 30 49 25
5000          79 23 49 21 22
76 29 54 24
Positive Control: MMS 15          52 25 146 93 93*
38 18 107 93
Trial Notes:
Nonactivation Trial: 3 Experiment Call: Negative and Non-Toxic
Conc. Cloning Relative Total Mutant Colonies Mutant Frequency AVG Mutant Frequency
µg/mL Efficiency Growth
Vehicle Control: FOP 0          69 94 88 43 38
62 109 48 26
58 87 79 46
76 110 84 37
Test Chemical: 1000          61 59 95 52 57
55 60 101 61
2000          68 73 111 55 49
61 61 77 42
3000          62 64 110 59 60
52 50 95 61
4000          61 45 74 40 42
61 51 81 45
5000          50 34 68 45 46
55 37 77 47
Positive Control: MMS 15          23 24 163 235 217*
26 23 156 200
EMS 250          41 61 427 347 325*
52 59 474 302
Trial Notes:
Induced S9 Trial: 1 Experiment Call: Negative and Non-Toxic
Conc. Cloning Relative Total Mutant Colonies Mutant Frequency AVG Mutant Frequency
µg/mL Efficiency Growth
Vehicle Control: FOP 0          108 93 101 31 36
102 109 98 32
109 101 119 36
97 97 130 45
Test Chemical: 1000          105 74 137 43 47
100 78 152 51
2000          82 58 101 41 42
97 67 126 43
3000          99 56 159 54 44
109 62 113 35
4000          99 55 106 36 38
85 45 101 40
5000          77 36 124 54 55
85 36 145 57
Positive Control: MCA 2.5        72 44 615 286 305*
70 40 680 323
Trial Notes:
Induced S9 Trial: 2 Experiment Call: Negative and Non-Toxic
Conc. Cloning Relative Total Mutant Colonies Mutant Frequency AVG Mutant Frequency
µg/mL Efficiency Growth
Vehicle Control: FOP 0          60 96 36 20 20
64 110 35 18
56 92 48 29
66 103 25 13
Test Chemical: 1000          52 61 41 26 21
63 75 31 16
2000          67 63 56 28 27
62 61 48 26
3000          61 40 41 22 31
71 48 85 40
4000          66 41 56 28 29
57 35 51 30
5000          70 34 65 31 28
59 36 45 25
Positive Control: MCA 2.5        34 19 231 229 232*
34 17 237 236
Trial Notes:
Footnotes:
Asterisks(*) indicate significant responses.
r = rejected value due to quality control criteria
# = reduced sample size because of the loss of one culture dish due to contamination
MMS = methyl methanesulfonate
MCA = methylcholanthrene
DMSO = dimethylsulfoxide (solvent)

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information):
negative