Registration Dossier

Toxicological information

Genetic toxicity: in vitro

Currently viewing:

Administrative data

Endpoint:
in vitro gene mutation study in bacteria
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: Similar to guideline study (no cross-linking mutagen evaluation strain used, no data on analytical purity)

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1986

Materials and methods

Principles of method if other than guideline:
NTP standard procedure
GLP compliance:
yes
Remarks:
NTP
Type of assay:
bacterial reverse mutation assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): 1-pentanol
- Analytical purity: no data

Method

Target gene:
His +/-
Species / strainopen allclose all
Species / strain / cell type:
S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
Additional strain / cell type characteristics:
not applicable
Species / strain / cell type:
S. typhimurium TA 97
Additional strain / cell type characteristics:
not applicable
Metabolic activation:
with and without
Metabolic activation system:
S9 mix (metabolic activation enzymes and cofactors from Aroclor 1254-induced male Sprague-Dawley rat or Syrian hamster liver, 5-30%)
Test concentrations with justification for top dose:
0, 33, 100, 333, 1000, 3333, 6666 and 10000 µg/plate
Controls
Untreated negative controls:
yes
Negative solvent / vehicle controls:
yes
Remarks:
DMSO
True negative controls:
no
Positive controls:
yes
Positive control substance:
other: The positive controls in the absence of metabolic activation were sodium azide (TA100 and TA1535), 9-aminoacridine (TA97), 4-nitro-o-phenylenediamine (TA98). The positive control with S9 mix was 2- aminoanthracene in all strains
Details on test system and experimental conditions:
- The test substance was incubated with the Salmonella typhimurium tester strains TA97, TA98, TA100, TA1537, and TA1535 either in buffer or S9 mix for 20 minutes at 37° C.
- Top agar supplemented with L-histidine and d-biotin was added, and the contents of the tubes were mixed and poured onto the surfaces of minimal glucose agar plates.
- Histidine-dependent mutant colonies arising on these plates were counted following incubation for 2 days at 37° C.
Evaluation criteria:
- A positive response was defined as a reproducible, dose-related increase in histidine-independent (revertant) colonies in any one strain/activation combination.
- An equivocal response was defined as an increase in revertants that was not dose related, was not reproducible, or was not of sufficient magnitude to support a determination of mutagenicity.
- A negative response was obtained when no increase in revertant colonies was observed following chemical treatment.
- There was no minimum percentage or fold increase required for a chemical to be judged positive or weakly positive.

Results and discussion

Test resultsopen allclose all
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:
dose units starting from 6666 were generally slightly toxic to toxic for all strains tested
Vehicle controls validity:
valid
Untreated negative controls validity:
not applicable
Positive controls validity:
valid
Species / strain:
S. typhimurium TA 97
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Remarks:
dose units starting from 6666 were generally slightly toxic to toxic for all strains tested
Vehicle controls validity:
valid
Untreated negative controls validity:
not applicable
Positive controls validity:
valid
Remarks on result:
other: all strains/cell types tested
Remarks:
Migrated from field 'Test system'.

Any other information on results incl. tables

Results:

Strain TA1535

Dose No Activation No Activation 10% HLI 30% HLI 10% RLI 30% RLI
(Negative) (Negative) (Negative) (Negative) (Negative) (Negative)
ug/Plate Mean ± SEM Mean ± SEM Mean ± SEM Mean ± SEM Mean ± SEM Mean ± SEM
0      19 4.5 21 0.3 11 1.7 7 1.8 8 0.7 12 0
33          22 3.7                
100      20 2 17 1.8 12 3 13 1.5 10 0.7 12 0.3
333      19 2.6 21 4.5 6 0.9 9 1.8 10 0.9 15 1
1000      19 2.7 16 0.9 7 2.3 9 0.3 8 1.5 11 1.5
3333      21 1.5 17 1 5 1.9 7 1.2 11 2.2 12 1.9
6666                      10 2.8    
10000      4s 1.7     6 1.8 7 2     8 0
Positive Control 423 19.6 498 23.3 263 28.7 375 13 204 7.5 224 10.2

Strain TA 100

Dose No Activation No Activation 10% HLI 30% HLI 10% RLI 30% RLI
(Negative) (Negative) (Negative) (Negative) (Negative) (Negative)
ug/Plate Mean ± SEM Mean ± SEM Mean ± SEM Mean ± SEM Mean ± SEM Mean ± SEM
0      139 8.8 115 4.3 135 15.3 163 1.7 107 4.9 165 5.8
33          122 3.8                
100      136 12 120 9.1 141 3.8 166 15.5 126 11 142 6.3
333      120 7.6 125 7.8 140 7.7 175 2.7 113 5.5 173 2.4
1000      116 4.2 116 6.4 123 6.8 169 6.1 116 10 176 12.2
3333      119 7.9 96 12.1 130 5.7 141 7 120 2.7 178 9.2
6666      t       109 13.9 126 5.8 96 6.8 126s 16.2
Positive Control 604 4 464 24.9 822 12.8 529 14.2 557 24.5 478 14.7

Strain TA 97

Dose No Activation No Activation 10% HLI 30% HLI 5% RLI 10% RLI 10% RLI 30% RLI
(Negative) (Equivocal) (Negative) (Negative) (Negative) (Equivocal) (Negative) (Equivocal)
ug/Plate Mean ± SEM Mean ± SEM Mean ± SEM Mean ± SEM Mean ± SEM Mean ± SEM Mean ± SEM Mean ± SEM
0      136 10.5 111 7.4 152 9.2 165 6.4 200 16.5 111 6.5 186 5.4 153 2.7
33          147 13.8                        
100      159 12.3 136 2.2 150 12.9 160 17.2 186 6.9 165 0.9 211 7 189 6.8
333      163 6.7 157 9.5 161 3.3 179 8.3 197 5.5 183 5.4 199 6.5 191 3.2
1000      154 3.5 144 10.6 159 4.4 170 4.5 196 2.6 170 12.8 208 1.5 177 11.5
3333      111 8.5 111 1.8 162 2.2 137 11 174 7.9 174 0.9 191 2.8 166 18.6
6666              108 12.5     177 7.3 82 8.7 146s 10.1    
10000      17s 1.7         130s 15.8             119s 7.5
Positive Control 911 28.7 542 20.9 463 27.3 369 45.8 478 22.5 305 23.5 410 10 388 19.2

Strain TA 98

Dose No Activation No Activation 10% HLI 30% HLI 10% RLI 30% RLI
(Negative) (Negative) (Negative) (Negative) (Negative) (Negative)
ug/Plate Mean ± SEM Mean ± SEM Mean ± SEM Mean ± SEM Mean ± SEM Mean ± SEM
0      16 4.1 19 1.2 24 2.9 27 1.8 29 1.5 28 3.2
33          19 2.4                
100      22 0.7 15 2.2 24 1.9 25 4.5 28 0.7 27 0.6
333      17 0.3 20 1.8 26 2.6 24 0.3 25 1.2 29 2.3
1000      21 0 14 2.7 20 0.7 30 3.2 26 1.5 27 0.6
3333      14 2.1 14 1 24 2.1 25 3.2 26 0.9 28 2.3
6666      3t 2.5     17 0.9 21 5 21 2.6 16s 1.2
Positive Control 538 10.7 543 12.7 1359 38.1 373 19.3 250 25.3 160 2.7

Strain TA 1537

Dose No Activation 30% HLI 30% RLI
(Negative) (Negative) (Negative)
ug/Plate Mean ± SEM Mean ± SEM Mean ± SEM
0      8 2.4 13 0.6 12 3.4
100      8 1.2 12 1.9 10 1.7
333      9 1.2 9 2.1 9 1.3
1000      7 1.5 9 1.8 7 1
3333      6 1.5 9 2.3 6 0.9
10000      2s 0.9 4 0.7 3 1.5
Positive Control 425 29.5 40 1.7 39 0.6

Abbreviations:

RLI = induced male Sprague Dawley rat liver S9

HLI = induced male Syrian hamster liver S9

s = Slight Toxicity; p = Precipitate; x = Slight Toxicity and Precipitate; T = Toxic; c = Contamination

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information):
negative