1,2,4-trimethylbenzene

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro gene mutation study in bacteria

Remarks:

Type of genotoxicity: gene mutation

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: GLP status unknown, near guideline study, published in peer reviewed literature, minor restrictions in design and/or reporting but otherwise adequate for assessment

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

1998

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 (not including TA1535) of E.coli used

GLP compliance:

not specified

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

Mesitylene

EC Number:

203-604-4

EC Name:

Mesitylene

Cas Number:

108-67-8

Molecular formula:

C9H12

IUPAC Name:

1,3,5-trimethylbenzene

Constituent 2

Reference substance name:

1,3,5-trimethylbenzene

IUPAC Name:

1,3,5-trimethylbenzene

Details on test material:

Obtained from Fluka

Method

Species / strain

Species / strain / cell type:

other: TA97a, TA98, TA100, TA102

Additional strain / cell type characteristics:

not applicable

Metabolic activation:

with and without

Metabolic activation system:

Rat S9 fraction prepared from Aroclor 1254-induced male outbred Imp:Lodz rat liver

Test concentrations with justification for top dose:

The compounds were tested up to the cytotoxic concentrations - 1, 5, 10, 20, 30 and 40 µg/plate

Vehicle / solvent:

- Vehicle(s)/solvent(s) used: mineral oil (light white oil) obtained from Sigma Chemical

- Justification for choice of solvent/vehicle: in previous studies when dimethylsulfoxide (DMSO) or ethanol were used for in vitro experiments, the reaction of the compounds appeared to be more toxic for the tester strains of bacteria.

Controls

Controls 1

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

Remarks:

mineral oil

Positive controls:

yes

Positive control substance:

4-nitroquinoline-N-oxide

Remarks:

Migrated to IUCLID6: 0.5 µL or µg

Controls 2

Positive control substance:

sodium azide

Remarks:

Migrated to IUCLID6: 1.5 µL or µg

Controls 3

Positive control substance:

other: 2, aminofluorene 5.0 µL or µg

Controls 4

Positive control substance:

other: 4-nitro-o-phenylenediamine 3.0 µL or µg

Details on test system and experimental conditions:

METHOD OF APPLICATION: in agar (plate incorporation)

DURATION
- Exposure duration: 48 hours at 37ºC

SELECTION AGENT (mutation assays): His+ revertant colonies

NUMBER OF REPLICATIONS: 2

DETERMINATION OF CYTOTOXICITY
- Method: Increase in the number of revertants per plate as compared to the revertants per solvent control plate

Evaluation criteria:

A chemical was considered to be a mutagen if it induced at least a 2-fold increase in the number of revertants per plate as compared to the revertants per solvent control plate, with accompanying dose-effect relationship in at least one tester strain.

Statistics:

Not applicable

Results and discussion

Test results

Species / strain:

other: TA97a, TA98, TA100, TA102

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

all except TA97a

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

valid

Additional information on results:

40 µL/plate mesitylene (the highest dose tested), produced a decrease in the number of revertants to the level below 75%, with and without S9.

A similar, negative effect on the Salmonella tester strains was obtained in an experiment in which the compound was tested using another technique (further information not included in the publication). In the preincubation modification of the standard mutagenicity assay (20 min at 37°C) on S. typhimurium TA98 and TA 100 (- S9; + S9) mesitylene (at doses from 1-20 µL/plate, dissolved in DMSO) induced no gene mutations.

Remarks on result:

other: all strains/cell types tested

Remarks:

Migrated from field 'Test system'.

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information):
negative with metabolic activation
negative without metabolic activation

Mesitylene is negative in the Ames test, with and without metabolic activation, when tested in S. typhimurium TA97a, TA98, TA100 and TA102

Executive summary:

Mesitylene was tested in vitro in the Ames test (plate incorporation method), with Salmonella typhimurium TA97a, TA98, TAI00 and TA102 strains in the presence and absence of rat liver S9 metabolic activation. Mesitylene gave negative results both with and without activation at 40 µL/plate (the highest dose tested).