3,4-dihydro-2-methoxy-2H-pyran

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

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Comparable to guideline with acceptable restrictions (only 4 strains tested).

Data source

Reference

Reference 1

Reference Type:

study report

Title:

Unnamed

Year:

1989

Report date:

1989

Reference 2

Reference Type:

secondary source

Title:

3,4-Dihydro-2-methoxy-2H-pyran (CAS No. 4454-05-1)

Author:

OECD

Year:

2003

Bibliographic source:

cited in OECD SIDS 3,4-Dihydro-2-methoxy-2H-pyran for SIAM 16, 27-30 May 2003, Paris, France.

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Deviations:

yes

Remarks:

Only 4 strains tested

GLP compliance:

no

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

3,4-dihydro-2-methoxy-2H-pyran

EC Number:

224-698-3

EC Name:

3,4-dihydro-2-methoxy-2H-pyran

Cas Number:

4454-05-1

Molecular formula:

C6H10O2

IUPAC Name:

2-methoxy-3,4-dihydro-2H-pyran

Details on test material:

- Name of test material (as cited in study report): 2-Methoxi-2,3-dihydro-4H-pyran
- Analytical purity: >99.9%
- Impurities (identity and concentrations): not reported
- Lot/batch No.: not reported
- Storage condition of test material: Room temperature

Method

Target gene:

Salmonella typhimurium: histidine operon

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 1254 induced rat liver S-9 mix

Test concentrations with justification for top dose:

Experiment 1: 0, 20, 100, 500, 2500 and 5000 µg/plate for all strains;
Experiment 2: 0, 100, 500, 2500, 5000 and 7500 µg/plate for TA100

Vehicle / solvent:

- Vehicle(s)/solvent(s) used: DMSO

Controls

Controls 1

Negative solvent / vehicle controls:

yes

Positive controls:

yes

Positive control substance:

other: 2-aminoanthracene for all strains

Remarks:

with S9 mix

Controls 2

Negative solvent / vehicle controls:

yes

Positive controls:

yes

Positive control substance:

9-aminoacridine

Remarks:

without S9 mix Migrated to IUCLID6: for TA 1537

Controls 3

Negative solvent / vehicle controls:

yes

Positive controls:

yes

Positive control substance:

other: N-methyl-N-nitro-N-nitrosoguanidine for TA100 and TA1535

Remarks:

without S9 mix

Controls 4

Negative solvent / vehicle controls:

yes

Positive controls:

yes

Positive control substance:

other: 4-nitro-o-phenylendiamine for TA98

Remarks:

without S9 mix

Details on test system and experimental conditions:

METHOD OF APPLICATION: in agar (plate incorporation)


DURATION
- Exposure duration: 48-72 hr at 37°C


NUMBER OF REPLICATIONS: 3

Evaluation criteria:

- doubling of the spontaneous mutation rate (control)
- dose-response relationship
- reproducibility of the results

Statistics:

Mean and standard deviation calculated in result tables. No further data.

Results and discussion

Test results

Test results 1

Species / strain:

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

Metabolic activation:

without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Vehicle controls validity:

valid

Positive controls validity:

valid

Test results 2

Species / strain:

S. typhimurium TA 100

Metabolic activation:

with

Genotoxicity:

positive

Remarks:

from 500 µg/plate onwards

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Vehicle controls validity:

valid

Positive controls validity:

valid

Test results 3

Species / strain:

other: S. typhimurium TA 1535, TA 1537, TA 98

Metabolic activation:

with

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Vehicle controls validity:

valid

Positive controls validity:

valid

Additional information on results:

TEST-SPECIFIC CONFOUNDING FACTORS
- Precipitation: the test substance was completely soluble in DMSO

Remarks on result:

other: other: S. typhimurium TA 1535, TA 1537, TA 98

Remarks:

Migrated from field 'Test system'.

Any other information on results incl. tables

Mean reverants/plate

Experiment 1

Dose (µg/ml)	TA 98		TA 100		TA 1535		TA 1537
	-S9	+S9	-S9	+S9	-S9	+S9	-S9	+S9
0	22	35	100	122	16	18	8	8
20	23	31	101	123	12	22	8	9
100	24	30	106	150	18	21	7	8
500	24	42	105	218	18	19	7	7
2500	22	33	119	315	15	22	7	9
5000	22	37	124	418	16	26	11	16
Positive control	1163	1267	1025	1743	775	160	547	180

Experiment 2

Dose (µg/ml)	TA 100
	-S9	+S9
0	104	101
100	94	115
500	103	133
2500	113	272
5000	120	331
7500	127	436
Positive control	903	1477

Applicant's summary and conclusion

Executive summary:

This study was conducted comparable to the OECD Guideline 471 and is reliable with acceptable restrictions (only 4 strains tested). The test substance was tested in the standard plate test with and without metabolic activation (MA) in S. typhimurium TA98, TA100, TA1535 and TA1537 at dose levels of 20 -7500 µg/plate. Significant increase in the number of revertants was detected in TA100 with MA. No increase in the number of revertants was detected in any other strain with and without MA. No bacteriotoxic effect was observed. Vehicle controls and positive controls were valid.

Conclusion: According to the results of the present study, the test substance is mutagenic in the Salmonella typhimurium reverse mutation assay under the experimental conditions chosen here.