2,2,2-trichloroethane-1,1-diol

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro gene mutation study in bacteria

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Justification for type of information:

Data is from peer reviewed journal

Data source

Reference

Reference Type:

publication

Title:

A STUDY OF THE MUTAGENICITY OF ANESTHETICS AND THEIR METABOLITES

Author:

LUCY WASKELL

Year:

1978

Bibliographic source:

Mutation Research, 57 (1978) 141-153

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: as mentioned below

Principles of method if other than guideline:

Chloral hydrate was screened for mutagenicity in the Salmonella/rat-liver microsomal assay system developed by Dr. B. Ames et al.

GLP compliance:

not specified

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

2,2,2-trichloroethane-1,1-diol

EC Number:

206-117-5

EC Name:

2,2,2-trichloroethane-1,1-diol

Cas Number:

302-17-0

Molecular formula:

C2H3Cl3O2

IUPAC Name:

2,2,2-trichloroethane-1,1-diol

Test material form:

solid: crystalline

Details on test material:

- Name of test material: 2,2,2-Trichloroethane-1,1-diol (Chloral hydrate)
- Molecular formula: C2-H3-Cl3-O2
- Molecular weight: 165.4026g/mol
- Smiles notation: C(C(O)O)(Cl)(Cl)Cl
- InChl: RNFNDJAIBTYOQL-UHFFFAOYSA-N
- Substance type: Organic
- Physical state: Solid

Specific details on test material used for the study:

- Name of test material: 2,2,2-Trichloroethane-1,1-diol (Chloral hydrate)
- Molecular formula: C2-H3-Cl3-O2
- Molecular weight: 165.4026g/mol
- Smiles notation: C(C(O)O)(Cl)(Cl)Cl
- InChl: RNFNDJAIBTYOQL-UHFFFAOYSA-N
- Substance type: Organic
- Physical state: Solid

Method

Species / strain

Species / strain / cell type:

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

Details on mammalian cell type (if applicable):

not specified

Additional strain / cell type characteristics:

not specified

Cytokinesis block (if used):

not specified

Metabolic activation:

with and without

Metabolic activation system:

rat liver microsomal S9 metabolic activation system.

Test concentrations with justification for top dose:

0.5 - 10 mg (maximum non-toxic dose)

Vehicle / solvent:

not specified

Controls

Untreated negative controls:

yes

Negative solvent / vehicle controls:

not specified

True negative controls:

not specified

Positive controls:

not specified

Details on test system and experimental conditions:

Bacteria 0.1 ml of a stationary culture of Salmonella typhimurium strains in broth, 60 ƛ of microsomes and a NADPH-generating system (5 µmoles glucose 6-phosphate, 4 µmoles NADP, 1 unit glucose-6-phosphate dehydrogenase) were mixed in a final volume of 1 ml in either 0.1 M sodium phosphate buffer, pH 7.4 or 0.05 M Tris-HCl buffer pH 7.4 at 37°C. The anesthetic concentration in the final reaction mix was 2 mM. This reaction mixture was incubated in a sealed 5-ml vial for 30 min at 37°C before being added to the top agar and plated.

Rationale for test conditions:

not specified

Evaluation criteria:

Number of his+ revertants above control

Statistics:

Student’s t test

Results and discussion

Test results

Test results 1

Key result

Species / strain:

S. typhimurium, other: TA 98 and TA 1535

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not specified

Vehicle controls validity:

valid

Untreated negative controls validity:

not specified

Positive controls validity:

not specified

Test results 2

Key result

Species / strain:

S. typhimurium TA 100

Metabolic activation:

with and without

Genotoxicity:

positive

Cytotoxicity / choice of top concentrations:

not specified

Vehicle controls validity:

valid

Untreated negative controls validity:

not specified

Positive controls validity:

not specified

Additional information on results:

not specified

Applicant's summary and conclusion

Conclusions:

Chloral hydrate was determined to induce mutations in Salmonella typhimurium TA 100 whwereas unable to induce in strains TA 98 and TA 1535 with and without rat liver microsomal S9 metabolic activation system.

Executive summary:

Chloral hydrate was screened for mutagenicity in the Salmonella/rat-liver microsomal assay system developed by Dr. B. Ames et.al. (Standard plate incorporation assay of Ames test). The study was performed using Salmonella typhimurium strains TA98, TA100 and TA1535 in the presence and absence of rat liver microsomal S9 metabolic activation system. The test chemical was used at dose levels of 0.5 to 10 mg/plate. The number of his+ revertants above control was evaluated for each strain. The test material did not exhibit induction of his+ revertants in Salmonella typhimurium TA98 and TA1535, either with or without rat liver microsomal S9 metabolic activation system. While in strain TA100 it did induces the number of revertants with statistically significant result by Student’s t test with p values of <0.01, both with and without metabolic activation system.

Thus the substance Chloral hydrate is determined to be ambiguous in nature for in vitro genetic toxicity test.