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:
experimental study
Adequacy of study:
key study
Study period:
1981
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Comparable to guideline study, basic data given, part of a comprehensive test programme

Data source

Referenceopen allclose all

Reference Type:
publication
Title:
Unnamed
Year:
1986
Reference Type:
publication
Title:
Unnamed
Year:
1981
Reference Type:
publication
Title:
Unnamed
Year:
1992
Report Date:
1992

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Principles of method if other than guideline:
No guideline stated, but study was conducted according to Ames et al. (1975), Mutat. Res. 31, 347-364; comparable to guideline study and in accordance with OECD Guideline 471
GLP compliance:
not specified
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): naphthalene (obtained from Fisher Scientific)
- Physical state: white crystalline powder
- Analytical purity: 99.8%

Method

Target gene:
his¯
Species / strain
Species / strain / cell type:
S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
Metabolic activation:
with and without
Metabolic activation system:
S9 mix from livers of Aroclor 1254 induced male Sprague-Dawley rats or Syrian hamsters
Test concentrations with justification for top dose:
0 (solvent control), 0.3, 1.0, 3.3, 10.0, 33.0, 100.0 µg/plate
Vehicle / solvent:
- Vehicle(s)/solvent(s) used: acetone
- Justification for choice of solvent/vehicle: no data
Controls
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
other: without S9 mix: TA98 4-nitro-o-phenylenediamine, TA100 and TA1535 sodium azide, TA1537 9-aminoacridine; with S9 mix: 2-aminoanthracene
Details on test system and experimental conditions:
METHOD OF APPLICATION: preincubation

DURATION
- Preincubation period: 20 min at 37°C
- Exposure duration: 48 h
- Expression time (cells in growth medium): 48 h at 37°C

NUMBER OF REPLICATIONS: triplicate plating

DETERMINATION OF CYTOTOXICITY
- Method: no data
Evaluation criteria:
Mutagenic response: a dose-related, reproducible increase in the number of revertants over background;
nonmutagenic response: when no increase in the number of revertants was elicited by the chemical;
questionable response: when there was an absence of a clear-cut dose-related increase in revertants,
when the dose related increases in the number of revertants were not reproducable,
when the response was of insufficient magnitude to support a determination of mutagenicity.
Statistics:
Mean and standard error of the mean of replicate plates were calculated.

Results and discussion

Test results
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:
in tests with the highest concentrations, toxicity was observed.
Vehicle controls validity:
valid
Untreated negative controls validity:
not examined
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

Detailed results of the NTP Ames test of naphthalene

Data of both experiments are reported. Individual strain data is presented as mean ± standard error. Abbreviations are noted below the tables. Study number is 471098. Study was completed in 1981.

 

 

Strain: TA1535

 

Dose

No Activation

No Activation

10% HLI

10% HLI

10% RLI

10% RLI

(Negative)

(Negative)

(Negative)

(Negative)

(Negative)

(Negative)

Protocol

Preincubation

Preincubation

Preincubation

Preincubation

Preincubation

Preincubation

µg/Plate

Mean

± SEM

Mean

± SEM

Mean

± SEM

Mean

± SEM

Mean

± SEM

Mean

± SEM

0 (solvent control)

22

1.5

19

2.6

11

2.3

8

0.6

9

0.6

12

2.4

0.3

24

3.1

1

21

3

26

2.7

10

3.3

11

2.9

13

1.2

16

1.5

3.3

22

5.2

23

2.3

10

0.9

11

3.8

9

0.7

10

1.7

10

30

2.6

20

1.2

12

0.6

11

0.3

8

0.7

10

2.6

33

20s

1.2

15

2.3

13

1

11

1.7

11

1.5

13

1.2

100

15t

3.5

6s

1.9

10s

3.2

13s

3.4

11s

2.9

Positive Control

1258

18.8

687

6.4

126

1.7

75

8.9

63

8

48

1.9

 

 

Strain: TA100

 

Dose

No Activation

No Activation

10% HLI

10% HLI

10% RLI

10% RLI

(Negative)

(Negative)

(Negative)

(Negative)

(Negative)

(Negative)

Protocol

Preincubation

Preincubation

Preincubation

Preincubation

Preincubation

Preincubation

µg/Plate

Mean

± SEM

Mean

± SEM

Mean

± SEM

Mean

± SEM

Mean

± SEM

Mean

± SEM

0 (solvent control)

143

4.5

141

4.2

143

11.9

128

6.2

144

2.4

137

8.2

0.3

121

3.5

1

146

5.8

124

3.6

143

13.2

115

7.9

130

2.7

143

16

3.3

124

12

117

8.5

155

4.9

135

2.4

133

13.2

133

5.9

10

145

5.8

113

6.2

140

3.5

118

9.8

135

8.7

121

6.6

33

141s

9.4

113

5.1

147

5.7

133

6.8

142

6.6

121

7.3

100

t

141s

2

145s

9

104s

0.6

127s

5.4

Positive Control

1636

45.5

801

28.7

2534

77.9

754

19.2

1074

13.2

792

26.4

 

 

Strain: TA98

 

Dose

No Activation

No Activation

10% HLI

10% HLI

10% RLI

10% RLI

(Negative)

(Negative)

(Negative)

(Negative)

(Negative)

(Negative)

Protocol

Preincubation

Preincubation

Preincubation

Preincubation

Preincubation

Preincubation

ug/Plate

Mean

± SEM

Mean

± SEM

Mean

± SEM

Mean

± SEM

Mean

± SEM

Mean

± SEM

0 (solvent control)

14

3.8

17

1

35

4.8

20

3.1

29

4.1

23

0.3

0.3

12

2.2

1

15

2.2

17

1.5

30

2.6

29

2.1

27

1.8

23

2.2

3.3

22

2.3

12

2.6

42

5.5

21

1.9

32

1.7

24

0.7

10

16

3.3

12

2.6

32

4.2

26

1.2

25

2.6

21

0.9

33

19s

2.5

12

3.2

32

3.1

21

1.2

29

1.9

24

2.8

100

14s

0.3

34s

1.5

23

2.4

22s

1.2

24

1.2

Positive Control

1772

9.6

1072

40.3

2064

71.4

183

10.1

982

43.1

176

16.6

 

 

Strain TA1537

 

Dose

No Activation

No Activation

10% HLI

10% HLI

10% RLI

10% RLI

(Negative)

(Negative)

(Negative)

(Negative)

(Negative)

(Negative)

Protocol

Preincubation

Preincubation

Preincubation

Preincubation

Preincubation

Preincubation

ug/Plate

Mean

± SEM

Mean

± SEM

Mean

± SEM

Mean

± SEM

Mean

± SEM

Mean

± SEM

0 (solvent control)

8

1.8

8

1.9

10

1.2

6

2.4

11

3.8

10

2.3

0.3

7

1.2

1

8

0.6

5

0.6

11

1.2

8

0.3

10

0.9

8

0.7

3.3

7

1.5

9

0.6

9

3.2

7

0.9

9

0.9

9

0.9

10

8

0.7

9

1.5

12

2

10

1.5

8

1.7

5

2.2

33

6s

2

4

0.9

12

1.5

10

1.5

10

1.9

7

1.5

100

t

10s

1

5s

0.6

5s

1.9

4s

0.6

Positive Control

1010

39.4

185

12

205

22.1

77

5.3

87

5.2

86

2.9

 

 

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

In a reverse gene mutation assay in bacteria according to Ames (1975) using four strains of S. typhimurium (TA 97, TA 98, TA 100, TA 1535, and TA 1537), naphthalene was tested negative at concentrations of 0.3, 1.0, 3.3, 10, 33, and 100 µg/plate in the presence and absence of mammalian metabolic activation (S9 mix from Arochlor 1254 induced rat and hamster liver). At the highest concentration some cytotoxicity was observed. Under the conditions of this test, naphthalene is not mutagenic to bacteria in vitro.