Trichloroacetaldehyde

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro gene mutation study in bacteria

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Justification for type of information:

Data is from NTP.

Data source

Reference

Reference Type:

review article or handbook

Title:

Gene mutation toxicity study of the test chemical

Author:

National Institute of Environmental Health Sciences

Year:

2018

Bibliographic source:

National Toxicology Program (NTP), 2019

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Principles of method if other than guideline:

To evaluate the mutagenic potential of test chemical in Salmonella Typhimurium TA98,TA 100,TA 1535 and TA 97 by AMES test.

GLP compliance:

not specified

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

Trichloroacetic acid

EC Number:

200-927-2

EC Name:

Trichloroacetic acid

Cas Number:

76-03-9

Molecular formula:

C2HCl3O2

IUPAC Name:

2,2,2-Trichloroacetic acid

Test material form:

solid

Details on test material:

IUPAC name: 2,2,2-trichloroacetate
Mol. formula: C2HCl3O2
Molecular Weight: 163.3869 gm/mol
Smiles: C(C(=O)O)(Cl)(Cl)Cl
InChI: 1S/C2HCl3O2/c3-2(4,5)1(6)7/h(H,6,7)

Method

Target gene:

Histidine

Species / strain

Species / strain / cell type:

S. typhimurium, other: TA98,TA 100,TA 1535 and TA 97

Metabolic activation:

with and without

Metabolic activation system:

RLI = induced male Sprague Dawley rat liver S9
HLI = induced male Syrian hamster liver S9

Test concentrations with justification for top dose:

0, 33, 100, 333, 1000, 3333, 10000 µg/plate

Vehicle / solvent:

- Vehicle(s)/solvent(s) used: Distilled water
- Justification for choice of solvent/vehicle: The test substance is soluble in Distilled water

Controls

Untreated negative controls:

not specified

Negative solvent / vehicle controls:

yes

Remarks:

Distilled water

True negative controls:

not specified

Positive controls:

yes

Positive control substance:

9-aminoacridine

sodium azide

other: 2-Aminoanthracene: 1.0 ug/Plate : TA 100, TA 97, TA 98 (+S9); 2.0 ug/Plate: TA 100, TA 97, TA 98, TA 1535 (+S9); 5.0 ug/Plate: TA 100, TA 97, TA 98, TA 1535 (+S9); 10.0 ug/Plate : TA 1535 (+S9). 4-Nitro-O-Phenylenediamine: TA 98 (-S9)

Details on test system and experimental conditions:

NUMBER OF REPLICATIONS:
- Number of independent experiments : 3

Evaluation criteria:

If the substance under test is mutagenic, the chemical-treated plates will have a much greater number of colonies than the negative control plates. A positive response is a reproducible, dose-related increase in mutant colonies in any single strain, with or without the addition of S9 metabolic enzymes. While there is no minimum percentage of increase required for a result to be considered positive, a twofold increase in mutant colonies in a treated plate is usually considered to be a positive (mutagenic) response. An equivocal response is any increase that is not reproducible, not dose-related, or not high enough in magnitude to be considered positive. A negative response occurs when no increases in mutant colonies are seen in the cultures treated with the test chemical, compared with the control.

Statistics:

Mean or Mean ± Standard Error Mean.

Results and discussion

Test results

Species / strain:

S. typhimurium, other: TA 100, TA 98, TA 97 and TA 1535

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Vehicle controls validity:

valid

Remarks:

Water

Untreated negative controls validity:

not specified

True negative controls validity:

not specified

Positive controls validity:

valid

Additional information on results:

No data

Remarks on result:

other: No mutagenic potential observed

Any other information on results incl. tables

Table 1: TA100

Dose (ug/Plate)	Metabolic activation
	Without S9	Without S9	With 10% Rat S9	With 30% Rat S9	With 10% Hamster S9	With 30% Hamster S9
Vehicle Control	124±7.1	124±3.2	133±9.7	144±6.9	119±7.7	130±9.6
33.0	120±5.8	123±7.7
100.0	118±11.1	133±7.7	131±3.5	135±5.8	124±7.4	129±2.6
333.0	106±4.3	127±9.3	124±5.0	134±3.8	123±8.4	139±2.1
1000.0	114±10.3	116±1.3	126±9.9	133±4.3	127±2.1	127±9.5
3333.0	95±4.0	110±5.9	132±8.4	140±10.2	118±5.5	135±4.2
10000.0			119±6.3	78±6.1	117±3.8	110±9.7
Positive control	951±25.6	974±25.5	593±13.8	629±50.7	641±19.1	1022±22.5

 

Table 2: TA1535

Dose (ug/Plate)	Metabolic activation
	Without S9	Without S9	With 10% Rat S9	With 30% Rat S9	With 10% Hamster S9	With 30% Hamster S9
Vehicle Control	8±0.9	19±2.5	23±2.5	13±1.2	18±3.0	10±1.2
33.0		19±0.3
100.0	8±0.7	17±2.0	19±0.3	10±0.9	21±2.0	9±0.3
333.0	7±1.5	17±2.2	15±0.7	14±2.6	22±3.5	9±0.6
1000.0	7±0.0	16±1.7	23±4.1	12±2.3	17±4.2	6±0.7
3333.0	5±0.3	16±1.5	23±1.2	11±0.6	18±2.0	9±1.8
10000.0	Toxic		19±0.9	9±0.3	14±0.3	9±2.0
Positive control	980±23.7	1017±44.8	209±10.3	134±9.8	232±21.0	170±3.1

 

Table 3: TA97

Dose (ug/Plate)	Metabolic activation
	Without S9	Without S9	With 10% Rat S9	With 30% Rat S9	With 10% Hamster S9	With 30% Hamster S9
Vehicle Control	144±9.4	156±3.9	181±8.1	173±11.9	185±4.4	170±4.8
33.0		153±7.6
100.0	147±9.0	169±11.1	180±7.4	149±10.0	152±9.2	176±11.3
333.0	160±5.9	145±11.0	192±6.5	170±9.5	151±11.5	150±3.9
1000.0	172±3.0	169±2.3	180±8.9	172±10.5	182±8.2	165±2.0
3333.0	163±10.7	155±10.7	164±2.8	177±5.5	178±5.5	169±5.7
10000.0	Toxic		167±10.0	88±5.8	161±8.6	98±10.0
Positive control	491±14.6	499±6.6	462±20.5	544±17.2	590±16.6	605±4.9

 

Table 4: TA98

Dose (ug/Plate)	Metabolic activation
	Without S9	Without S9	With 10% Rat S9	With 30% Rat S9	With 10% Hamster S9	With 30% Hamster S9
Vehicle Control	19±3.3	22±2.3	24±3.2	24±2.0	20±1.9	25±3.0
33.0	21±1.7	19±0.3
100.0	21±1.5	15±0.7	19±0.3	20±0.7	19±1.2	23±2.4
333.0	20±2.3	16±1.5	18±3.3	20±2.3	22±1.7	20±3.5
1000.0	23±2.6	21±4.2	26±2.4	23±1.3	22±1.0	21±1.5
3333.0	10±0.9	13±3.1	27±2.1	16±1.2	24±2.0	24±1.5
10000.0			21±1.7	9±0.9	20±2.7	10±1.5
Positive control	319±7.7	347±16.8	250±19.5	511±34.1	448±17.4	841±75.9

 

 

Applicant's summary and conclusion

Conclusions:

Test chemical was evaluated for its mutagenic potential in Salmonella typhimurium TA100, TA1535, TA98 and TA97 by AMES test. The test result was considered to be negative in all strain in the presence and absence of metabolic activation S9.

Executive summary:

Genetic toxicity in vitro study was assessed for test chemical. For this purpose AMES test was performed. The test material was exposed to Salmonella typhimurium TA100, TA1535, TA98 and TA97 in the presence and absence of metabolic activation S9. The S9 mix were prepared from 10% and 30% induced male Sprague Dawley rat liver S9 and induced male Syrian hamster liver S9 repectively. The concentration of test material used in the presence and absence of metabolic activation were 0, 33, 100, 333, 1000, 3333, 10000 µg/plate. No mutagenic effects were observed in any strains, in the presence and absence of metabolic activation. Therefore, test chemical was considered to be not mutagenic in Salmonella typhimurium TA100, TA1535, TA98 and TA97 by AMES test. Hence, the substance cannot be classified as gene mutant in vitro.