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Toxicological information

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:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study comparable to guideline with acceptable restrictions. Read-across

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1977
Report Date:
1977

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Deviations:
yes
Remarks:
four of the five recommended tester strains were used
Principles of method if other than guideline:
A reference to "Ames BN, McCann J, Yamasaki E, Methods for detecting carcinogens and mutagens with the salmonella/mammalian-microsome mutagenicity test, Mutation Research (1975), 31(6), 347-363" is given.
GLP compliance:
no
Type of assay:
bacterial reverse mutation assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Details on test material:
- Molecular formula: C2Cl3F3 (identical to submission substance)
- Molecular weight: 187.376 g/mol (identical to submission substance)
- Smiles notation: ClC(F)(F)C(Cl)(Cl)F (different from submission substance)
- InChl: InChI=1S/C2Cl3F3/c3-1(4,6)2(5,7)8 (different from submission substance)
- Structural formula: see attachment CAS_76-13-1_Structure.png (under "Illustration (picture/graph)")
- Physical state: liquid

Method

Species / strain
Species / strain:
S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
Metabolic activation:
with and without
Metabolic activation system:
S-9 mix from Aroclor 1254 induced rats
Test concentrations with justification for top dose:
Concentration of the gaseous test substance in air:
Trial I: 0 (solvent control), 2, 6, 10, 19% (with activation) & 0 (solvent control), 2, 6, 10% (without activation)
Trial II: 0 (solvent control), 2, 6, 10% (with and without activation)
Vehicle:
no vehicle and no solvent needed, the liquid test item is directly evaporated into the air
Controls
Negative controls:
yes
Solvent controls:
yes
True negative controls:
no
Positive controls:
yes
Remarks:
only tested with strains TA1535 and TA100
Positive control substance:
other: chloroethylene (CAS# 75-01-4, EC# 200-831-0; vinyl chloride)
Details on test system and conditions:
see below
Evaluation criteria:
valuation of the question: "Does the test substance significantly increase the spontaneous mutation frequency?"
Statistics:
The number of revertants/plate reported are average values of two (without S9) and three plates (with S9), respectively.
No individual plate counts are reported.

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:
no
Remarks:
However some indication of toxicity seen in trial II with strain TA98 (see table)
Vehicle controls valid:
yes
Negative controls valid:
yes
Positive controls valid:
yes
Remarks on result:
other: all strains/cell types tested
Remarks:
Migrated from field 'Test system'. Remarks: Positive controls only tested with strains TA1535 and TA100
Additional information on results:
Result of initial toxicity test: On the basis of the initial toxicity experiment with strain TA1535, nontoxic and slightly toxic concentrations of the test substance were chosen for the mutagenicity assay.

The test substance was tested in Salmonella typhimurium strains TA1535, TA1537, TA98, and TA100. It was not mutagenic for those strains of bacteria in the presence or absence of an activation system, i.e. it did not significantly increase the spontaneous mutation frequency.

Any other information on results incl. tables

Table: Mutagenic activity of 1,1,2-trichloro-1,2,2-trifluoroethane in Salmonella typhimurium strains with and without metabolic activation

Trial

Metabolic activation

Compound

Histidine+ revertants/plate §

TA1535

TA1537

TA98

TA100

1

with

1,1,2-trichloro-1,2,2-trifluoroethane

0 %

17

17

37

133

2 %

17

18

32

133

6 %

14

20

43

122

10 %

13

19

28

83

19 %

6

4

19

61

Chloroethylene

10 %

255

 

 

333

without

1,1,2-trichloro-1,2,2-trifluoroethane

0 %

19

18

18

127

2 %

20

19

20

124

6 %

17

23

15

107

10 %

16

18

19

95

Chloroethylene

10 %

228

 

 

190

2

with

1,1,2-trichloro-1,2,2-trifluoroethane

0 %

10

15

15

130

2 %

10

11

20 §§

96

6 %

13

11

13 §§

98

10 %

6

7

14 §§

74

Chloroethylene

10 %

251

 

 

405

without

1,1,2-trichloro-1,2,2-trifluoroethane

0 %

7

17

12

92

2 %

7

11

11

100

6 %

10

16

18

87

10 %

10

11

13

84

Chloroethylene

10 %

111

 

 

218

§: activated assay: average number of revertants from three plates; nonactivated assay: average from two plates

§§: while these numbers represent revertant colonies, toxic conditions were noted by a thinning of the background lawn. This condition was not noted for the same doses in trial I.

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information):
negative with metabolic activation
negative without metabolic activation

The test item 1,1,2-trichloro-1,2,2-trifluoroethane was non-mutagenic in the 4 strains of Salmonella typhimurium (TA1535, TA1537, TA98, and TA100) tested with and without metabolic activation.

Remark of the registrant:
According to OECD TG 471 the test should be performed with (at least) five strains: i.e. with four S. typhimurium strains with GC base pairs at the primary reversion site (e.g. TA1535, TA1537, TA98 and TA100) and with one strain with an AT base pair at the primary reversion site (e.g. E. coli WP2 or S. typhimurium TA102). The latter strain is needed in order to detect certain oxidising mutagens, cross-linking agents and hydrazines. This study has been performed with the four strains TA1535, TA1537, TA98 and TA100, but not with the additional AT base pair containing strain. Neither 1,1,2-trichloro-1,2,2-trifluoroethane (source chemical of read-across) nor 1,1,1-trichloro-2,2,2-trifluoroethane (target chemical) is an oxidising substance or is a hydrazine. In addition, based on their chemical structure, both chemicals are not expected to have cross-link capabilities. Thus the lack of testing with the additional strain does not significantly restrict the reliability, relevance and adequacy of this study.

The bacterial mutagenicity of the target chemical 1,1,1-trichloro-2,2,2-trifluoroethane is determined by read-across from the Ames test with the source chemical 1,1,2-trichloro-1,2,2-trifluoroethane. The analogue approach is justified in Section 13 (Assessment Reports_Read-Across, in attachment CAS_354-58-5_Read-Across.pdf).

Executive summary:

The test item 1,1,2-trichloro-1,2,2-trifluoroethane was non-mutagenic in the 4 strains of Salmonella typhimurium (TA1535, TA1537, TA98, and TA100) tested with and without metabolic activation.

 

Remark of the registrant:

According to OECD TG 471 the test should be performed with (at least) five strains: i.e. with four S. typhimurium strains with GC base pairs at the primary reversion site (e.g. TA1535, TA1537, TA98 and TA100) and with one strain with an AT base pair at the primary reversion site (e.g. E. coli WP2 or S. typhimurium TA102). The latter strain is needed in order to detect certain oxidising mutagens, cross-linking agents and hydrazines. This study has been performed with the four strains TA1535, TA1537, TA98 and TA100, but not with the additional AT base pair containing strain. Neither 1,1,2-trichloro-1,2,2-trifluoroethane (source chemical of read-across) nor 1,1,1-trichloro-2,2,2-trifluoroethane (target chemical) is an oxidising substance or is a hydrazine. In addition, based on their chemical structure, both chemicals are not expected to have cross-link capabilities. Thus the lack of testing with the additional strain does not significantly restrict the reliability, relevance and adequacy of this study.

 

The bacterial mutagenicity of the target chemical 1,1,1-trichloro-2,2,2-trifluoroethane is determined by read-across from the Ames test with the source chemical 1,1,2-trichloro-1,2,2-trifluoroethane. The analogue approach is justified in Section 13 (Assessment Reports_Read-Across, in attachment CAS_354-58-5_Read-Across.pdf).