Reaction products of 1H-Imidazole-1-ethanol, 4,5-dihydro-, 2-(C7-C17 odd-numbered, C17-unsatd. alkyl) derivs. and sodium hydroxide and chloroacetic acid

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:

key study

Study period:

March 1991 - May 1991

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Conducted equivalent to OECD Guideline 471 and according to GLP, but the study was not conducted with E.coli and/or with S. typhimurium TA102, which have an AT base pair at the primary reversion site.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1991

Report date:

1991

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Deviations:

yes

Remarks:

not conducted with E.coli and/or with S. typhimurium TA102

GLP compliance:

yes (incl. QA statement)

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

Group of constituents (alkyl derivatives) in Reaction products of 1H-Imidazole-1-ethanol, 4,5-dihydro-, 2-(C7-C17 odd-numbered, C17-unsatd. alkyl) derivs. and sodium hydroxide and chloroacetic acid

Molecular formula:

For two representative potential structures: C20H36N2O6Na2 : 446 and C18H35N2O4Na: 367

IUPAC Name:

Group of constituents (alkyl derivatives) in Reaction products of 1H-Imidazole-1-ethanol, 4,5-dihydro-, 2-(C7-C17 odd-numbered, C17-unsatd. alkyl) derivs. and sodium hydroxide and chloroacetic acid

Constituent 2

Reference substance name:

Sodium chloride

EC Number:

231-598-3

EC Name:

Sodium chloride

Cas Number:

7647-14-5

Molecular formula:

ClNa

IUPAC Name:

Sodium chloride

Constituent 3

Reference substance name:

Water

EC Number:

231-791-2

EC Name:

Water

Cas Number:

7732-18-5

Molecular formula:

H2O

IUPAC Name:

Oxidane

Test material form:

other: Aqueous solution

Method

Target gene:

Histidine

Species / strain

Species / strain / cell type:

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

Additional strain / cell type characteristics:

not applicable

Metabolic activation:

with and without

Metabolic activation system:

S9 mix

Test concentrations with justification for top dose:

Based on the dose finding preliminary toxicity test, the doses in the main test were chosen as 1.3, 6.4, 32, 160 and 800 µg/plate (related to active
component of the test article).

Vehicle / solvent:

- Vehicle(s)/solvent(s) used: distilled water
- Justification for choice of solvent/vehicle: Water is regarded as compatible with the Ames test. The minimum required solubility for the test article of 5% (corresponding with 5000 μg/plate) was reached.

Controls

Untreated negative controls:

yes

Remarks:

distilled water

Negative solvent / vehicle controls:

yes

Remarks:

distilled water

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: Without metabolic activation: Na-azide for TA100 and TA1535; 9-Aminoacridinehydrochloride monohydrate for TA1537 and 4-nitro-1,2-phenylene diamine for TA98. Metabolic activation by S9-mix was checked with 2-aminoanthracene for all strains.

Details on test system and experimental conditions:

METHOD OF APPLICATION: in agar (plate incorporation)
DURATION
- Exposure duration: 48 hours
DETERMINATION OF CYTOTOXICITY
- Method: the number of colonies, the number of revertants and the background growth

Evaluation criteria:

After an incubation for 48 hours at 37 degrees Celsius the colonies were counted by Artek Counter Model 982B. The validity of the automatic counts is secured by manual control counting at regular time intervals. The following criteria were used for the acceptance:
-The negative controls have to be within the the expected range as defined by literature data (Maron and Ames 1983)
-The positive controls have to show sufficient effects as defined by the laboratory's experience
-The titer determination must yield a sufficient bacterial density in the suspension

Statistics:

Not applicable

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 / choice of top concentrations:

cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Additional information on results:

Not reported

Remarks on result:

other: all strains/cell types tested

Applicant's summary and conclusion

Conclusions:

Negative at up to cytotoxic concentration (800 µg/plate) with and without metabolic activation in the Salmonella typhimurium reverse mutation assay.This study was not conducted with E.coli and/or S. typhimurium TA102, thus not detecting certain oxidising mutagens, cross-linking agents and hydrazines.