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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:
other: Basic data given.

Data source

Referenceopen allclose all

Reference Type:
publication
Title:
Unnamed
Year:
1992
Reference Type:
secondary source
Title:
Chloroacetic acid, CAS No: 79-11-8
Author:
OECD SIDS
Year:
1996
Bibliographic source:
http://www.inc hem.org/doc uments/sids/s ids/79118.pdf
Reference Type:
publication
Title:
Salmonella mutagenicity tests: II. Results from the testing of 270 chemicals
Author:
Mortelmans, K. et al.,
Year:
1986
Bibliographic source:
Environ. Mutagen. 8 (7), 1-119

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Deviations:
yes
Remarks:
only 4 strains tested; strain with AT reversion site was included in the study
GLP compliance:
no
Type of assay:
bacterial reverse mutation assay

Test material

Constituent 1
Chemical structure
Reference substance name:
Chloroacetic acid
EC Number:
201-178-4
EC Name:
Chloroacetic acid
Cas Number:
79-11-8
Molecular formula:
C2H3ClO2
IUPAC Name:
chloroacetic acid
Details on test material:
- Name of test material (as cited in study report): Monochloroacetic acid
- Analytical purity: no data

Method

Target gene:
his operon
Species / strain
Species / strain / cell type:
S. typhimurium, other: TA 98, TA 100, TA 1537 and TA 1537
Metabolic activation:
with and without
Metabolic activation system:
co-factor supplemented post-mitochondrial fraction (S9 mix), prepared from the livers of Aroclor 1254-induced male Sprague-Dawley rats or Syrian hamster
Test concentrations with justification for top dose:
with metabolic activation: 33 - 3 333 µg/plate
without metabolic activation: 10 - 1000 µg/plate
Controls
Negative solvent / vehicle controls:
yes
Remarks:
distilled water
Positive controls:
yes
Positive control substance:
other: 2-aminoanthracene (+ S9), all strains); 4 - nitrophenylendiamine (-S9, TA 98); sodium azide (- S9, TA 100 and TA 1535); 9-aminoacridine (-S9, TA 1537)
Details on test system and experimental conditions:
METHOD OF APPLICATION: preincubation

DURATION
- Preincubation period: 20 min
- Exposure duration: 48 h

NUMBER OF REPLICATIONS: triplicates each in 2 independent experiments




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, not reproducible, or of insufficient magnitude to support a determination of mutagenicity. A negative response was obtained when no increase in revertant colonies was observed following chemical treatment.

Results and discussion

Test results
Species / strain:
S. typhimurium TA 100
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Remarks:
without metabolic activation: 1000 µg/mL in TA 100 and TA 1535 (first experiment); with metabolic activation: 3 333 µg/mL (all strains)
Vehicle controls validity:
valid
Positive controls validity:
valid
Remarks on result:
other: strain/cell type: TA 100
Remarks:
Migrated from field 'Test system'.

Any other information on results incl. tables

Table 1. Test results for experiment 1

 

With or without S9-Mix

Test substance concentration

(μg/plate)

Mean number of revertant colonies per plate

± standard deviation

Base-pair substitution type

frameshift type

TA100

TA1535

TA98

TA1537

0

134± 3.8

35 ± 1.5

26 ± 1.3

9 ± 1.2

10

128±3.0

31 ± 1.2

22 ± 3.8

5 ± 0.3

33

124 ± 1.0

29 ± 4.5

24 ± 3.4

7 ± 2.5

100

120 ± 8.6

35 ± 0.9

25 ± 2.8

9 ± 0.9

333

122 ± 2.0

25 ± 2.0

24 ± 3.4

6 ± 0.3

1 000

130 ± 5.0s

19 ± 2.3s

21 ± 1.7

8 ± 2.2

Positive controls

SA

SA

4NPD

9AA

Mean No. of colonies/plate

± SD

1 326 ± 14.4

1 555 ± 26.7

1 727 ± 40.8

126 ± 14.8

+ (10% HLI)

0

107 ± 5.7

19 ± 3.2

28 ± 3.8

8 ± 2.0

+ (10% HLI)

33

107 ± 8.5

18 ± 2.3

28 ± 4.3

8 ± 2.1

+ (10% HLI)

100

119 ± 10.1

18 ± 0.9

32 ± 3.3

9 ± 1.5

+ (10% HLI)

333

113 ± 5.8

13 ± 2.3

34 ± 1.5

8 ± 1.7

+ (10% HLI)

1 000

120 ± 0.0

12 ± 1.5

30 ± 6.4

6 ± 1.3

+ (10% HLI)

3 333

114 ± 13.9s

0 ± 0.0s

7 ± 1.2

0 ± 0.0s

+ (10% HLI)

Positive controls

2AA

2AA

2AA

2AA

Mean No. of colonies/plate

± SD

1 147 ± 48.8

115 ± 9.5

1,024 ± 88.6

126 ± 3.5

+ (10% RLI)

0

132 ± 6.4

22 ± 5.2

31 ± 4.4

6 ± 1.2

+ (10% RLI)

33

124 ± 3.1

21 ± 1.0

30 ± 3.4

6 ± 0.9

+ (10% RLI)

100

123 ± 4.7

17 ± 2.5

27 ± 2.6

9 ± 0.3

+ (10% RLI)

333

127 ± 3.8

15 ± 3.2

30 ± 3.2

8 ± 2.2

+ (10% RLI)

1 000

137 ± 3.5

15 ± 1.5

20 ± 3.2

6 ± 1.0

+ (10% RLI)

3 333

121 ± 8.7s

0 ± 0.0s

9 ± 1.5s

0 ± 0.0s

+ (10% RLI)

Positive controls

2AA

2AA

2AA

2AA

Mean No. of colonies/plate

± SD

2 094 ± 45.9

46 ± 5.4

854 ± 3.9

67 ± 2.7

SA = sodium azide

9AA = 9-aminoacridine

4NPD = 4-nitro-o-phenylenediamine

2AA = 2-aminoanthracene

SD = standard deviation

HLI = induced male Syrian hamster liver S9

RLI = induced male Sprague Dawley rat liver S9

s = slight toxicity

Table 2. Test results for experiment 2

 

With or without S9-Mix

Test substance concentration

(μg/plate)

Mean number of revertant colonies per plate

± standard deviation

Base-pair substitution type

frameshift type

TA100

TA1535

TA98

TA1537

0

135 ± 3.2

21 ± 0.9

23 ± 3.3

7 ± 1.2

10

143 ± 5.5

25 ± 4.7

16 ± 1.9

7 ± 0.9

33

134 ± 5.2

20 ± 1.2

20 ± 1.2

6 ± 1.5

100

135 ± 14.3

18 ± 1.0

18 ± 2.0

10 ± 1.2

333

135 ± 2.6

12 ± 2.3

17 ± 1.2

7 ± 0.6

1000

131 ± 10.3

9 ± 1.2

18 ± 1.5

8 ± 0.3

Positive controls

SA

SA

4NPD

9AA

Mean No. of colonies/plate

± SD

1 207 ± 21.9

824 ± 10.2

1 614 ± 39.2

225 ± 22.3

+ (10% HLI)

0

109 ± 3.6

9 ± 1.3

30 ± 3.7

9 ± 0.9

+ (10% HLI)

100

114 ± 3.3

10 ± 1.3

28 ± 3.8

9 ± 1.5

+ (10% HLI)

333

110 ± 4.4

9 ± 1.2

28 ± 2.7

7 ± 2.0

+ (10% HLI)

1 000

116 ± 9.6

8 ± 0.6

25 ± 1.7

9 ± 2.2

+ (10% HLI)

2 000

113 ± 7.1

0 ± 0.3

20 ± 4.3

2 ± 0.7

+ (10% HLI)

3 333

78 ± 8.5s

0 ± 0.0s

13 ± 1.9

0 ± 0.0s

+ (10% HLI)

Positive controls

2AA

2AA

2AA

2AA

Mean No. of colonies/plate

± SD

2 405 ± 109.4

173 ± 7.8

2 657 ± 71.9

313 ± 18.8

+ (10% RLI)

0

136 ± 6.5

10 ± 2.3

28 ± 4.1

11 ± 3.0

+ (10% RLI)

100

146 ± 7.7

12 ± 2.1

26 ± 3.8

9 ± 1.8

+ (10% RLI)

333

131 ± 7.4

9 ± 2.0

28 ± 2.3

10 ± 22

+ (10% RLI)

1 000

139 ± 0.9

12 ± 2.6

28 ± 3.0

7 ± 0.6

+ (10% RLI)

2 000

143 ± 6.4

3 ± 0.9

18 ± 2.4

1 ± 0.9

+ (10% RLI)

3 333

111 ± 7.8s

0 ± 0.0s

9 ± 2.2

0 ± 0.3s

+ (10% RLI)

Positive controls

2AA

2AA

2AA

2AA

Mean No. of colonies/plate

± SD

1 114 ± 51.1

66 ± 0.7

941 ± 46.9

104 ± 8.5

SA = sodium azide

9AA = 9-aminoacridine

4NPD = 4-nitro-o-phenylenediamine

2AA = 2-aminoanthracene

SD = standard deviation

HLI = induced male Syrian hamster liver S9

RLI = induced male Sprague Dawley rat liver S9

s = slight toxicity

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information):
negative

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