Trichlorotrifluoroethane

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro gene mutation study in bacteria

Remarks:

Type of genotoxicity: gene mutation

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1976

Report date:

1976

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Deviations:

yes

Remarks:

4 of 5 recommended tester strains were used

GLP compliance:

no

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

1,1,2-trichlorotrifluoroethane

EC Number:

200-936-1

EC Name:

1,1,2-trichlorotrifluoroethane

Cas Number:

76-13-1

IUPAC Name:

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

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 1

Species / strain / cell type:

S. typhimurium TA 1535, TA 1537, TA 98 and TA 100

Species / strain 2

Species / strain / cell type:

S. typhimurium TA 1538

Metabolic activation:

with and without

Metabolic activation system:

rat-liver S9 mix

Test concentrations with justification for top dose:

Concentration of the gaseous test item in air:
Trial 1: 0 (solvent control), 4.8 and 12 %
Trial 2: 0 (solvent control), 4.6 and 12 %

Vehicle / solvent:

no vehicle and no solvent needed, the liquid test item is directly evaporated into the air

Controls

Untreated negative controls:

yes

Negative solvent / vehicle 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 experimental conditions:

see below

Evaluation criteria:

Evaluation 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 plates.
No individual plate counts are reported.

Results and discussion

Test results

Test results 1

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:

no cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Test results 2

Species / strain:

S. typhimurium TA 1538

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

not applicable

Additional information on results:

The test substance was tested in Salmonella typhimurium strains TA1535, TA1537, TA1538, TA98, and TA100. It was not mutagenic in the microbial assays either in the presence or absence of a liver microsomal system, i.e. it did not significantly increase the spontaneous mutation frequency.

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

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	Compound	Histidine^+revertants per plate §
		TA1535	TA1537	TA1538	TA98	TA100
With metabolic activation (Table I of original report) §§
1	1,1,2-Trichloro-1,2,2-trifluoroethane
	0%	13	6	25	39	100
	4.8%	11	11	34	36	103
	12.0%	10	14	36	42	109
	Chloroethylene
	20%	231				542
2	1,1,2-Trichloro-1,2,2-trifluoroethane
	0%	12	7	20	39	86
	4.6%	10	5	24	21	81
	12.0%	11	6	20	36	91
	Chloroethylene
	20%	169				475
Without metabolic activation (Table II of original report) §§
1	1,1,2-Trichloro-1,2,2-trifluoroethane
	0%	24	7	19	20	85
	4.8%	13	13	18	31	109
	12.0%	19	11	17	15	93
	Chloroethylene
	20%	84				276
2	1,1,2-Trichloro-1,2,2-trifluoroethane
	0%	18	11	15	27	78
	4.6%	22	9	16	30	80
	12.0%	10	5	17	17	75
	Chloroethylene
	20%	96				224

§: average of two plates

§§: remark of the registrant: in the original study report both tables (i.e. Table I and Table II) contain "with metabolic activation" in the header. However since it is clearly stated in the text of the report that the test has been conducted with and without metabolic activation, it is obvious that one of the table headers has a typographical error. The most probable correct assignment is "Table I: with metabolic activation" and "Table II: without metabolic activation".

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 5 strains of Salmonella typhimurium (TA1535, TA1537, TA1538, 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 5 strains of Salmonella typhimurium (TA1535, TA1537, TA1538, 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).