1,3-benzodioxolane

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:

other information

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Predates implementation of GLP and/or development of study guidelines, restrictions in reporting, acceptable with restrictions

Data source

Reference

Reference Type:

publication

Title:

Mutagenic activity of some centrally active aromatic amines in salmonella typhimurium.

Author:

White T.J.

Year:

1977

Bibliographic source:

Mutation Research, Elsevier/North-Holland Biomedical Press, 1977, Vol. 56, No. 2, pg. 199-202

Materials and methods

Test guideline

Qualifier:

no guideline available

Principles of method if other than guideline:

The method of testing for mutagenic activity was that of Ames et al, Methods for detecting carcinogens and mutagens with the Salmonella/mammalian-microsome mutagenicity test, Mutation Res., 31 (1975) 347-364.

GLP compliance:

not specified

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

1,3-benzodioxolane

EC Number:

205-992-0

EC Name:

1,3-benzodioxolane

Cas Number:

274-09-9

Molecular formula:

C7H6O2

IUPAC Name:

2H-1,3-benzodioxole

Details on test material:

Name: 1,2-methylenedioxybenzene
Source: Aldrich Chemical Co.
Compound was pure by the criteria of melting point and elemental analysis

Method

Target gene:

Histidine

Species / strain

Species / strain 1

Species / strain / cell type:

S. typhimurium TA 1538

Species / strain 2

Species / strain / cell type:

S. typhimurium, other: TA 100, TA 1537, TA 98

Metabolic activation:

with and without

Metabolic activation system:

Phenobarbital, Aroclor 1254 and 3-methyl-cholanthrene induced rat liver S9 mix.

Test concentrations with justification for top dose:

0.02, 0.2, 2.0, 20.0, 200, 1000 and 5000 µg/plate

Vehicle / solvent:

Dimethyl sulfoxide (DMSO, spectrophotometric grade)

Controls

Controls 1

Untreated negative controls:

not specified

Negative solvent / vehicle controls:

not specified

True negative controls:

not specified

Positive controls:

yes

Remarks:

This strain was only used to test the activity of the S-9 preparation.

Positive control substance:

other: 2,5-diaminoanisole and benzidine

Remarks:

strain TA 1538 with metabolic activation

Controls 2

Untreated negative controls:

not specified

Negative solvent / vehicle controls:

yes

True negative controls:

not specified

Positive controls:

yes

Positive control substance:

other: daunomycin

Remarks:

Strain TA 98 without metabolic activation

Controls 3

Untreated negative controls:

not specified

Negative solvent / vehicle controls:

yes

True negative controls:

not specified

Positive controls:

yes

Positive control substance:

other: N-methyl-N'-nitro-N-nitrosoguanidine

Remarks:

Strain TA 100 without metabolic activation

Controls 4

Untreated negative controls:

not specified

Negative solvent / vehicle controls:

yes

True negative controls:

not specified

Positive controls:

yes

Positive control substance:

9-aminoacridine

Remarks:

Strain TA 1537 without metabolic activation

Details on test system and experimental conditions:

Revertant his+ colonies were counted after incubation in the dark at 37°C for 48 hours.
Sterility controls were performed for S9 mix, DMSO and test compound.

Results and discussion

Test results

Test results 1

Species / strain:

S. typhimurium TA 1538

Metabolic activation:

with

Genotoxicity:

not specified

Cytotoxicity / choice of top concentrations:

not specified

Vehicle controls validity:

not specified

Untreated negative controls validity:

not specified

Positive controls validity:

valid

Test results 2

Species / strain:

S. typhimurium, other: TA 1537, TA 98, TA 100

Metabolic activation:

with

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not specified

Vehicle controls validity:

not specified

Untreated negative controls validity:

not specified

Positive controls validity:

not specified

Test results 3

Species / strain:

S. typhimurium, other: TA 1537, TA 98, TA 100

Metabolic activation:

without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not specified

Vehicle controls validity:

not specified

Untreated negative controls validity:

not specified

Positive controls validity:

valid

Additional information on results:

No difference in colony counts could be detected over a dose range of 0.02 - 5000 µg when the test compound and control plates were compared in strains TA 1537, TA 98 and TA 100. Microscopic examination of the plates revealed that an adequate bacterial lawn was present.

Sterility controls of S9 mix, DMSO and test compound were negative. The positive control substances 9-aminoacridine, N-methyl-N'-nitro-N-nitrosoguanidine and daunomycin did produce substantial increases in the number of revertants per plate in strains TA 1537, TA 100 and TA 98, respectively, in the absence of liver homogenate. The activity of the S9 preparation was demonstrated by an increase in the mutagenic activity of benzidine (50µg) or 2,5-diaminoanisole (50µg) in strain TA 1538.

In spite of the sensitivity of the test method and the prescence of the liver microsomal activation system no mutagenic activity could be detected in most of the compounds tested. This may be due to the absence of the appropriate metabolic activity, since a urinary metabolite of safrole is mutagenic in the Salmonella test whereas safrole (with of without Aroclor-induced rat liver homogenate) is not mutagenic. Although safrole may be activated to a carcinogen by liver microsomal enzymes of the type induced by 3-methylcholanthrene, the test compound was not activated to mutagens by liver homogenates prepared from rats induced with phenobarbital, Aroclor of 3-methyl-cholanthrene.

Remarks on result:

other: strains TA 1537, TA 100 and TA 98 were tested

Applicant's summary and conclusion

Conclusions:

Interpretation of results:
negative

No mutagenic activity was observed for 1,2-methylenedioxybenzene over a dose range of 0.02 - 5000µg.

Executive summary:

In an Ames test 1,2-methylenedioxybenzene in DMSO was tested at 0.02, 0.2, 2.0, 20.0, 200, 1000 and 5000 µg/plate in Salmonella typhimurium strains TA 1537, TA 98 and TA 100 with and without rat liver microsomal activation. Revertant his+ colonies were counted after incubation in the dark at 37°C for 48 hours. No difference in colony counts could be detected over a dose range of 0.02 - 5000 µg when compound and control plates were compared.