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Genetic toxicity: in vitro

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Administrative data

Endpoint:
in vitro gene mutation study in bacteria
Remarks:
Type of genotoxicity: gene mutation
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
data from handbook or collection of data
Justification for type of information:
Data is from peer reviewed publication

Data source

Referenceopen allclose all

Reference Type:
publication
Title:
Salmonella mutagenicity tests. IV. Results from the testing of 300 chemicals
Author:
Zeiger, E., Anderson, B., Haworth, S., Lawlor, T., and Mortelmans, K.
Year:
1998
Bibliographic source:
Environ. Molec. Mutagen. Vol. 11 (Suppl 12) (1988) 1-158
Reference Type:
other: Authoritative data base
Title:
NTP Study ID:528732
Author:
NTP
Year:
2012
Bibliographic source:
NTP (National Toxicological Program)by Agency for Toxic Substances and Disease Registry; Division of Toxicology/Toxicology Information Branch, 1600 Clifton Road NE, E-29, Atlanta, Georgia 30333
Reference Type:
other: Authoritative data base
Title:
GCID : 45725
Author:
ACToR Database
Year:
2011
Bibliographic source:
ACToR (Aggregated Computational Toxicology Resource):ZEIGER,E, ANDERSON,B, HAWORTH,S, LAWLOR,T AND MORTELMANS,K; SALMONELLA MUTAGENICITY TESTS: IV. RESULTS FROM THE TESTING OF 300 CHEMICALS; ENVIRON. MOL. MUTAGEN. 11(SUPPL.12):1-158, 1988

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
other: Refer below principle
Principles of method if other than guideline:
The test chemical Pigment yellow 100 (C.I. 19140) was studied for its ability to induce mutations in strains of Salmonella typhimurium.
GLP compliance:
not specified
Type of assay:
bacterial reverse mutation assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of the test material: Pigment yellow 100- IUPAC name: aluminum tris(4-{[3-carboxy-5-oxo-1-(4-sulfophenyl)-4,5-dihydro-1H-pyrazol-4-yl]diazenyl}benzenesulfonate) - Molecular formula: C48H33AlN12O27S6- Molecular weight: 495.4038 g/mol- Substance type: Organic- Inchi: 1S/C16H12N4O9S2.Al/c21-15-13(18-17-9-1-5-11(6-2-9)30(24,25)26)14(16(22)23)19-20(15)10-3-7-12(8-4-10)31(27,28)29;/h1-8,13H,(H,22,23)(H,24,25,26)(H,27,28,29);/b18-17+;
Specific details on test material used for the study:
- Name of the test material: Pigment yellow 100- IUPAC name: aluminum tris(4-{[3-carboxy-5-oxo-1-(4-sulfophenyl)-4,5-dihydro-1H-pyrazol-4-yl]diazenyl}benzenesulfonate) - Molecular formula: C48H33AlN12O27S6- Molecular weight: 495.4038 g/mol- Substance type: Organic- Purity: Labelled: 26%; Analyzed: 27%- Inchi: 1S/C16H12N4O9S2.Al/c21-15-13(18-17-9-1-5-11(6-2-9)30(24,25)26)14(16(22)23)19-20(15)10-3-7-12(8-4-10)31(27,28)29;/h1-8,13H,(H,22,23)(H,24,25,26)(H,27,28,29);/b18-17+;

Method

Target gene:
Histidine
Species / strain
Species / strain / cell type:
other: TA100, TA1535, TA1537, TA97 and TA98
Details on mammalian cell type (if applicable):
Not applicable
Additional strain / cell type characteristics:
not specified
Cytokinesis block (if used):
No data
Metabolic activation:
with and without
Metabolic activation system:
10% and 30% HLI and RLI S-9 (9,000 g supernatant) fractions were prepared from Aroclor 1254-induced, male Sprague- Dawley rat and male Syrian hamster livers
Test concentrations with justification for top dose:
0, 100, 333, 1000, 3333, 6666 or 10000 µg/plate
Vehicle / solvent:
- Vehicle(s)/solvent(s) used: Dimethyl Sulfoxide (DMSO)- Justification for choice of solvent/vehicle: The test chemical was soluble in DMSO
Controlsopen allclose all
Untreated negative controls:
not specified
Negative solvent / vehicle controls:
yes
Remarks:
DMSO
True negative controls:
not specified
Positive controls:
yes
Positive control substance:
other: 2-aminoanthracene
Remarks:
For strains tested with S9
Untreated negative controls:
not specified
Negative solvent / vehicle controls:
yes
Remarks:
DMSO
True negative controls:
not specified
Positive control substance:
sodium azide
Remarks:
For strains TA100 and TA1535 tested in the absence of S9
Untreated negative controls:
not specified
Negative solvent / vehicle controls:
yes
Remarks:
DMSO
True negative controls:
not specified
Positive controls:
yes
Positive control substance:
9-aminoacridine
Remarks:
For strains TA97 and TA1537 tested in the absence of S9
Untreated negative controls:
not specified
Negative solvent / vehicle controls:
yes
Remarks:
DMSO
True negative controls:
not specified
Positive controls:
yes
Positive control substance:
other: 4-nitro-o-phenylenediamine
Remarks:
For strain TA98 tested in the absence of S9
Details on test system and experimental conditions:
METHOD OF APPLICATION: preincubationDURATION- Preincubation period: 20 mins- Exposure duration: 48 hrs- Expression time (cells in growth medium): 48 hrs- Selection time (if incubation with a selection agent): No data available - Fixation time (start of exposure up to fixation or harvest of cells): No data availableSELECTION AGENT (mutation assays): No data availableSPINDLE INHIBITOR (cytogenetic assays): No data availableSTAIN (for cytogenetic assays): No data availableNUMBER OF REPLICATIONS: TriplicateNUMBER OF CELLS EVALUATED: No data availableDETERMINATION OF CYTOTOXICITY- Method: mitotic index; cloning efficiency; relative total growth; other: No data availableOTHER EXAMINATIONS:- Determination of polyploidy: No data available- Determination of endoreplication: No data available- Other: No data availableOTHER: No data available
Rationale for test conditions:
No data
Evaluation criteria:
Evaluations were made at both the individual trial and overall chemical levels.Individual trials were judged mutagenic (+), weakly mutagenic (+ W), questionable(?), or nonmutagenic (-), depending on the magnitude of the increase of his+ revertants, and the shape of the dose-response. A trial was considered questionable (?) if the dose-response was judged insufficiently high to support a call of “ +W,” if only a single dose was elevated over the control, or if the increase seen was not dose related. The distinctions between a questionable mutagenic response and a nonmutagenic or weak mutagenic response, and between a weak mutagenic response and mutagenic response are highly subjective. It was not necessary for a response to reach two fold over background for a chemical to be judged mutagenic.A chemical was judged mutagenic (+) or weakly mutagenic (+ W) if it produced a reproducible dose-related reponse over the solvent control in replicate trials. A chemical was judged questionable (?) if the results of individual trials were not reproducible, if increases in his+ revertants did not meet the criteria for a “+W” response, or if only single doses produced increases in his+ revertants in repeat trials.Chemicals were judged nonmutagenic (-) if they did not meet the criteria for a mutagenic or questionable response. The chemicals were decoded by the chemical repository only after a determination had been made regarding their mutagenicity or nonmutagenicity.
Statistics:
Mean ± SD

Results and discussion

Test results
Species / strain:
other: TA100, TA1535, TA1537, TA97 and TA98
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
not specified
Vehicle controls validity:
valid
Untreated negative controls validity:
not specified
Positive controls validity:
valid
Additional information on results:
TEST-SPECIFIC CONFOUNDING FACTORS- Effects of pH: No data available- Effects of osmolality: No data available- Evaporation from medium: No data available- Water solubility: No data available- Precipitation: No data available- Other confounding effects: No data availableRANGE-FINDING/SCREENING STUDIES: All chemicals were tested initially in a toxicity assay to determine the appropriate dose range for the mutagenicity assay. The toxicity assay was performed using TA100. Toxic concentrations were those that produced a decrease in the number of his+ colonies, or a clearing in the density of the background lawn, or both. COMPARISON WITH HISTORICAL CONTROL DATA: YesADDITIONAL INFORMATION ON CYTOTOXICITY: No data available
Remarks on result:
other: No mutagenic potential

Any other information on results incl. tables

Strain: TA100

Dose No Activation 
(Negative)
No Activation 
(Negative)
30% RLI 
(Negative)
30% HLI 
(Negative)
10% RLI 
(Negative)
10% HLI 
(Negative)
Protocol Preincubation Preincubation Preincubation Preincubation Preincubation Preincubation
ug/Plate Mean ±SEM Mean ±SEM Mean ±SEM Mean ±SEM Mean ±SEM Mean ±SEM
 0         
146 10 127 7.5 145 14.7 167 6.8 107 10.1 107 6.8
100         
133 3.7 137 7.5 143 4.7 165 17.8 123 16.5 117 11.4
333         
130 3.8 152 5 116 5 155 10.8 122 4.4 128 8.7
1000         
146 6.1 136 6.7 127 .7 116 16.5 130 13.5 117 13.1
3333         
109 4 65 7.9 130 15.3 118 5.9 106 5.8 85 8.7
6666         
16 .7 75 11.4 53 8.9
10000         
37 9 65 8.2 61 12.6
Positive Control 604 4 550 21.1 478 14.7 529 14.2 515 46 548 52.7

Strain: TA1535

Dose No Activation 
(Negative)
No Activation 
(Negative)
30% RLI 
(Negative)
30% HLI 
(Negative)
10% RLI 
(Negative)
10% HLI 
(Negative)
Protocol Preincubation Preincubation Preincubation Preincubation Preincubation Preincubation
ug/Plate Mean ±SEM Mean ±SEM Mean ±SEM Mean ±SEM Mean ±SEM Mean ±SEM
 0         
31 1 20 .6 15 1.8 9 2 8 .6 10 1.5
100         
26 1.5 20 1.5 14 1.9 10 1.8 11 1.2 12 2
333         
30 5.2 16 .6 16 2.2 8 1.2 7 2.5 7 .9
1000         
30 4 25 6.9 15 1.9 8 1.5 9 .9 8 .9
3333         
24 3.7 15 2.5 11 1.2 8 3.1 9 2.7 6 1.5
6666         
14 2.6 6 .9 6 .3
10000         
21 1.9 13 1.9 7 .7
Positive Control 357 22.3 499 21.5 218 6.6 388 17.1 121 8.4 219 4.6

Strain: TA1537

Dose No Activation 
(Negative)
30% RLI 
(Negative)
30% HLI 
(Negative)
Protocol Preincubation Preincubation Preincubation
ug/Plate Mean ±SEM Mean ±SEM Mean ±SEM
 0         
8 .7 14 1.5 15 .6
100         
6 1.5 11 1.7 12 3.5
333         
10 1.9 15 1.8 12 1.9
1000         
11 1.8 12 .6 10 .3
3333         
6 .6 9 1.5 6 0
10000         
5 1.2 8 1.9 4 0
Positive Control 309 5 41 2.3 46 3.3

Applicant's summary and conclusion

Conclusions:
Pigment yellow 100 is not mutagenic to the Salmonella typhimurium TA100, TA1535, TA1537, TA97 and TA98 in the presence and absence of rat and hamster liver S9 metabolic activation system and hence it is not likely to classify as a gene mutant in vitro.
Executive summary:

Pigment yellow 100 was studied for its ability to induce mutations in strains of Salmonella typhimurium.

 

The test compound was dissolved in DMSO and was tested at concentration of 0, 100, 333, 1000, 3333, 6666 or 10000 µg/plate using Salmonella typhimurium TA100, TA1535, TA1537, TA97 and TA98 in the presence and absence of 10 % and 30 % rat and hamster liver S9 metabolic activation system. Preincubation assay was performed with a preicubation for 20 mins. The plates were observed for histidine independence after 2 days incubation period. Concurrent solvent and positive controls were included in the study.

 

Pigment yellow 100 is not mutagenic to the Salmonella typhimurium TA100, TA1535, TA1537, TA97 and TA98 in the presence and absence of rat and hamster liver S9 metabolic activation system  and hence it is not likely to classify as a gene mutant in vitro.