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: Acceptable, well documented publication/study report which meets basic scientific principles

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
1992

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
GLP compliance:
not specified
Type of assay:
bacterial reverse mutation assay

Test material

Constituent 1
Details on test material:
- Name of test material (as cited in study report): Lanthanum nitrate 6*H2O
- Molecular formula (if other than submission substance): La(NO3)3 * 6H2O
- CAS No.: 10277-43-7
- Analytical purity: > 99%

Method

Target gene:
his operon
Species / strain
Species / strain / cell type:
S. typhimurium, other: TA100, TA1535, TA97, TA98
Metabolic activation:
with and without
Metabolic activation system:
Liver S-9 Fraction of Aroclor 1254-induced male Sprague-Dawley rat and Sprague-Dawley hamster. 10 and 30% S-9 mixes were tested.
Test concentrations with justification for top dose:
TA100/TA1535:
without and with activation (10% HLI, 10% RLI): 0, 3.3, 10, 33, 100 and 333 µg/plate;
with activation (30% HLI, 30% RLI): 0, 33, 100, 333, 1000 and 3333 µg/plate

TA97/TA98:
without activation and with activation (10% RLI): 0, 100, 333, 1000, 3333 and 10000 µg/plate
with activation (10% HLI, 30%HLI, 30% RLI): 0, 33, 100, 333, 1000 and 3333 µg/plate
Vehicle / solvent:
- Vehicle(s)/solvent(s) used: water
Controls
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
other: without metabolic activation: sodium azide (TA1535 and TAlOO), 9-aminoacridine (TA97), 4-nitro-o-phenylenediamine (TA98); with metabolic activation: 2-aminoanthracene for all strains.
Details on test system and experimental conditions:
METHOD OF APPLICATION: preincubation

DURATION
- Preincubation period: 20 min.
- Exposure duration: 2 days

NUMBER OF REPLICATIONS: 3

DETERMINATION OF CYTOTOXICITY
- Method: relative total growth
Evaluation criteria:
The colonies were machine counted unless precipitate was present. If precipitate were present, the colonies were counted visually. Mean values and standard deviations were calculated (three replicates).
A substance was judged mutagenic (+) or weakly mutagenic (+W) if it produced a reproducible, dose-related response over the solvent control, under a single metabolic activation condition, 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. It was not necessary for a response to reach two-fold over background for a trial to be judged mutagenic.
Chemicals were judged nonmutagenic (-) if they did not meet the criteria for a mutagenic or questionable response.

Results and discussion

Test results
Species / strain:
S. typhimurium, other: TA100, TA 1535, TA 97, TA98
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Remarks:
only observed with TA97 at 333 µg/plate and higher concentrations
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

Mean number (with standard deviation, SEM) of revertants/plate with each bacterial strain:

(NA = without activation, HLI = liver S-9 fraction from hamster, RLI = liver S-9 frcation from rat, p = precipitate present in plates, x = precipitate present with toxicity, s = slight clearing of background lawn)

TA100

 

NA

10% HLI

30% HLI

10% RLI

30% RLI

µg/plate

mean

sem

mean

sem

mean

sem

mean

sem

mean

sem

0

94

4.7

124

3.4

137

8.5

105

7.4

132

4.7

3.3

94

8.0

120

2.0

 

 

122

9.1

 

 

10

93p

1.7

111p

13.5

 

 

132p

1.5

 

 

33

102p

7.5

116p

8.5

147

7.5

123p

11.8

143

7.2

100

101p

6.4

107p

3.5

116

1.5

121p

5.2

141p

3.3

333

97p

0.9

113p

4.4

143

7.6

112p

10.1

149p

2.2

1000

 

 

 

 

130p

1.0

 

 

132p

5.0

3333

 

 

 

 

117p

7.3

 

 

106p

5.8

pos

746

19.2

302

13.5

679

12.3

755

18.2

1416

29.8

TA1535

 

NA

10% HLI

30% HLI

10% RLI

30% RLI

µg/plate

mean

sem

mean

sem

mean

sem

mean

sem

mean

sem

0

11

2.1

11

1.5

10

1.9

10

1.8

10

0.3

3.3

6

1.5

13

3.4

 

 

12

2.1

 

 

10

11p

2.7

13p

1.5

 

 

12p

3.8

 

 

33

7p

2.2

12p

1.2

13

1.7

14p

0.7

10

2.4

100

9p

0.9

10p

1.0

13

2.6

10p

2.1

10

0.3

333

10p

0.7

11p

0.6

9p

1.8

10p

0.6

13p

1.5

1000

 

 

 

 

12p

2.1

 

 

8p

0.7

3333

 

 

 

 

10p

0.9

 

 

8p

0.9

pos

385

17.3

39

4.8

96

10.7

184

6.2

156

15.5

TA97

 

NA

10% HLI

30% HLI

10% RLI

30% RLI

µg/plate

mean

sem

mean

sem

mean

sem

mean

sem

mean

sem

0

127

8.7

114

11.7

156

13.0

115

3.2

199

2.8

33

 

 

128p

5.3

161

4.8

 

 

184

3.7

100

127p

1.0

123p

9.9

159

6.7

79p

4.6

163p

12.2

333

131p

2.0

105p

10.1

155p

3.8

92p

4.6

129p

3.8

1000

119p

7.1

94p

7.0

122p

5.2

109p

0.9

118p

1.0

3333

99p

4.3

86x

3.9

99p

6.4

80p

6.6

118p

9.4

10000

86x

2.0

 

 

 

 

60p

7.5

 

 

pos

260

19.5

1078

29.4

1088

24.1

2819

19.2

1016

13.2

TA98

 

NA

10% HLI

30% HLI

10% RLI

30% RLI

µg/plate

mean

sem

mean

sem

mean

sem

mean

sem

mean

sem

0

41

5.9

31

3.5

37

1.5

29

5.8

32

1.5

33

 

 

35

1.9

27

4.5

 

 

32

3.5

100

31p

4.9

38

4.9

27

1.0

32

1.7

30

0.3

333

37p

4.4

34

4.1

26p

1.7

33

4.7

36

1.2

1000

48p

2.3

28p

4.0

26p

3.5

32

4.1

32

3.0

3333

45s

5.6

27p

3.8

26p

4.1

25p

0.3

29p

2.3

10000

37s

2.8

 

 

 

 

30p

3.6

 

 

pos

313

30.7

201

22.0

149

0.0

350

24.6

486

17.3

Applicant's summary and conclusion