2-[(2-[2-(dimethylamino)ethoxy]ethyl)methylamino]ethanol

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro gene mutation study in bacteria

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1984-02-12 to 1984-02-25

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Remarks:

No analytical provided on test substance, an E. coli strain was not included in study, and negative result was not confirmed in a repeat assay and no justification for not repeating assay was provided. However the study was GLP-compliant, positive and vehicle control were included and the study was performed in the presence and absence of metabolic activation.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1984

Report date:

1984

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Deviations:

yes

Remarks:

No analytical provided on test substance, an E. coli strain was not included in study, and negative result was not confirmed in a repeat assay and no justification for not repeating assay was provided.

GLP compliance:

yes (incl. QA statement)

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Test material form:

liquid

Specific details on test material used for the study:

- Name of test material (as cited in study report): 5601-22-20, Order #J-203
- Analytical purity: purity was the responsibility of the sponsor
- Physical state: yellow liquid
- Storage condition of test material: the test substance was stored at room temperature in a clear glass bottle

Method

Target gene:

histidine locus

Species / strain

Species / strain / cell type:

S. typhimurium, other: TA98, TA100, TA1535, TA1537 and TA1538

Additional strain / cell type characteristics:

not specified

Metabolic activation:

with and without

Metabolic activation system:

Aroclor 1254 induced rat liver S9

Test concentrations with justification for top dose:

100, 333, 1000, 3333 and 10,000 ug/plate

Vehicle / solvent:

- Vehicle(s)/solvent(s) used: deionized water
- Justification for choice of solvent/vehicle: test substance was determined to be soluble in water

Controls

Controls 1

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

Remarks:

deionized water

True negative controls:

no

Positive controls:

yes

Positive control substance:

sodium azide

Remarks:

without metabolic activation Migrated to IUCLID6: used for TA1535 and TA100 at 10 ug/plate

Controls 2

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

Remarks:

deionized water

True negative controls:

no

Positive controls:

yes

Positive control substance:

9-aminoacridine

Remarks:

without metabolic activation Migrated to IUCLID6: used for TA1537 at 150 ug/plate

Controls 3

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

Remarks:

deionized water

True negative controls:

no

Positive controls:

yes

Positive control substance:

2-nitrofluorene

Remarks:

without metabolic activation Migrated to IUCLID6: used for TA1538 and TA98 at 5 ug/plate

Controls 4

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

Remarks:

deionized water

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: 2-aminoanthracene used for all strains at 5 ug/plate

Remarks:

with metabolic activation

Details on test system and experimental conditions:

METHOD OF APPLICATION: in agar (plate incorporation)

DURATION
- Exposure duration: 48-72 hours
- Selection time (if incubation with a selection agent): 48-72 hours (simultaneous with exposure)

SELECTION AGENT (mutation assays): histidine

NUMBER OF REPLICATIONS: 3 (test substance), 2 (positive and vehicle control)

DETERMINATION OF CYTOTOXICITY
- Method: reduction in bacterial background lawn

Evaluation criteria:

A positive result was defined as a reproducible, dose-related increase in the number of histidine-independent colonies. This dose-response relationship occasionally necessitates slight modifications of the original doses in a repeat assay. If the solvent control was within one standard deviation of the historical mean for control values and the test substance produced the highest increase equal to or greater than three times the solvent control value, the test substance was considered positive. A negative result was defined as the absence of a reproducible increase in the number of histidine-independent colonies.

Statistics:

No data

Results and discussion

Test results

Key result

Species / strain:

S. typhimurium, other: TA98, TA100, TA1535, TA1537 and TA1538

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not specified

Remarks:

but no toxicity was observed up to 10000 ug/plate in the range-finding assay.

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

valid

Additional information on results:

RANGE-FINDING/SCREENING STUDIES:
A preliminary toxicity assay was performed with TA1538 and TA100 in the presence and absence of metabolic activation. Tester strains were treated with the test substance at dose levels of 100-10,000 µg/plate for 48 hours using the plate incorporation assay. Following exposure, background lawn and spontaneous revertants were observed and scored as normal growth, inhibited growth or no growth. Inhibition was scored by the presence of pindot colonies and the absence of a confluent lawn of bacteria. No toxicity was observed up to 10000 ug/plate in the presence or absence of metabolic activation.

COMPARISON WITH HISTORICAL CONTROL DATA:
All solvent and positive control values were within the acceptable limits of mean historical data.

Any other information on results incl. tables

all strains/cell types tested

Applicant's summary and conclusion

Conclusions:

The test substance was evaluated for induction of mutagenicity in the Ames Salmonella/Microsome Plate test in the presence and absence of metabolic activation using S. typhimurium tester strains TA98, TA100, TA1535, TA1537 and TA1538. The test substance failed to induce reverse mutations in any of the tester strains both in the presence and absence of metabolic activation up to concentration levels of 10,000 ug/plate.