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Toxicological information

Genetic toxicity: in vitro

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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:
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

Reference
Name:
Unnamed
Type:
Constituent
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 resultsopen allclose all
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
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.