Reaction mass of (2S,6S)-2,6-Dimethylmorpholine and (2R,6R)-2,6-Dimethylmorpholine

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:

no data

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: GLP guideline study. Test with Escherichia coli not included.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1995

Report date:

1995

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Deviations:

no

GLP compliance:

yes

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

cis-2,6-dimethylmorpholine

EC Number:

229-353-0

EC Name:

cis-2,6-dimethylmorpholine

Cas Number:

6485-55-8

Molecular formula:

C6 H13 N O

IUPAC Name:

(2S,6R)-2,6-Dimethylmorpholine

Details on test material:

- Name of test material (as cited in study report): cis-2,6-dimethylmorpholin
- Physical state: colourless liquid
- Analytical purity: 87.2%
- Impurities (identity and concentrations): no data
- Purity test date: no data
- Lot/batch No.: CP 16021
- Expiration date of the lot/batch: no data; data of manufacturing: 1992-09-22
- Storage condition of test material: refrigerator

Method

Species / strain

Species / strain / cell type:

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

Metabolic activation:

with and without

Metabolic activation system:

Aroclor-induced rat liver S9-mix

Test concentrations with justification for top dose:

20, 100, 500, 2500, 5000 µg/plate

Vehicle / solvent:

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

Controls

Untreated negative controls:

yes

Remarks:

sterility control

Negative solvent / vehicle controls:

yes

Remarks:

water

True negative controls:

not specified

Positive controls:

yes

Positive control substance:

other: 2-aminoantracene, N-methyl-N'-nitro-N-nitroso-guanidine, 4-nitro-phenylenediamine, 9-aminoacridine hydrochloride

Remarks:

positive control substances depending on metabolic activation conditions and tester strain

Details on test system and experimental conditions:

METHOD OF APPLICATION: in agar (plate incorporation); preincubation

Evaluation criteria:

In general, a substance to be characterized as positive in the Ames test has to fulfill the following requirements:
- doubling of the spontaneous mutation rate (control)
- dose-response relationship
- reproducibility of the results

Statistics:

no data

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:

no cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Additional information on results:

TEST-SPECIFIC CONFOUNDING FACTORS
- Water solubility: The test substance was completely soluble;
- Precipitation: no precipitation was noted at any concentration.

Remarks on result:

other: all strains/cell types tested

Remarks:

Migrated from field 'Test system'.

Any other information on results incl. tables

Standart plate test:

Dose (µg/plate)	TA1535		TA100		TA1537		TA98
	+S9	-S9	+S9	-S9	+S9	-S9	+S9	-S9
0	17±3	16±3	114±4	132±11	9±2	10±2	27±4	43±8
20	17±3	16±4	104±7	123±13	9±3	10±1	27±3	37±6
100	18±1	15±2	113±7	122±11	7±2	8±2	27±3	30±4
500	18±3	13±3	108±4	128±8	9±2	9±3	31±4	31±6
2500	19±1	14±3	113±9	129±9	8±1	10±3	28±6	26±2
5000	23±6	16±2	131±9	132±6	8±2	8±2	24±4	32±5
2-AA	-	106±8	-	1177±93	-	128±24	-	827±104
MNNG	1623±240	-	1687±95	-	-	-	-	-
AAC	-	-	-	-	571±36	-	-	-
NPD	-	-	-	-	-	-	961±131	-

 

 

Preincubation-test:

Dose (µg/plate)	TA1535		TA100		TA1537		TA98
	+S9	-S9	+S9	-S9	+S9	-S9	+S9	-S9
0	19±1	17±4	102±10	105±23	12±1	13±5	30±4	38±2
20	22±4	21±2	114±8	122±14	9±2	14±2	33±8	34±9
100	19±3	19±3	131±7	122±18	13±3	10±3	29±6	43±8
500	23±3	17±4	131±11	131±15	17±4	12±5	26±2	44±4
2500	27±3	24±3	143±6	124±7	13±1	9±4	28±11	44±8
5000	28±6	28±3	98±11	123±7	14±4	12±4	25±3	48±6
2AA	-	88±9	-	559±17	-	88±7	-	341±9
MNNG	899±7	-	698±22	-	-	-	-	-
AAC	-	-	-	-	653±88	-	-	-
NPD	-	-	-	-	-	-	756±32	-

2-AA: 2-aminoanthracene;

MNNG; N-methyl-N-nitro-N-nitrosoguanidine

NPD: 4-nitro-o-phenylendiamine

AAC: 9-aminoacridine chloride monohydrate

 

No increase in the number of revertants was observed with any strain under any test conditions. No bacteriotoxicity (indicated by reduced number of revertants) was observed. The positive controls led to the expected increase of revertants.

According to the results of the present study, the test substance cis-2,6-dimethylmorpholine is not mutagenic in the Ames test under the experimental conditions chosen here.