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The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Key value for chemical safety assessment

Additional information

This endpoint summary considers data from studies on trimethylbenzene isomers and mixtures containing trimethylbenzenes, notably high flash naphtha.

Non-human information

In vitro data

The key studies are considered to be bacterial mutation (Schreiner et al 1989, Janik-Spiechowicz et al 1998), mammalian cell gene mutation (Schreiner et al 1989) and mammalian cell cytogenetic assays (Schreiner et al 1989). These are recognised core assay types for investigating mutation in vitro.

Trimethylbenzene isomers were tested in a standard Ames test (Janik-Spiechowicz et al 1998). Salmonella typhimurium strains TA97a, TA98, TA100 and TA102 were treated with each of the three trimethylbenzene isomers both in the absence and presence of auxiliary metabolic activation (S9). A range of doses was used up to 40 μg/plate where toxicity allowed.  1,2,4-trimethylbenzene did not induce increases in revertant colonies over the controls, both in the absence and presence of S9.

Schreiner et al (1989) examined a sample of High Flash Aromatic Naphtha Type I, which contained 54% as a mixture of the above three trimethylbenzene isomers, in the Ames test.  The content of 1,2,3-TMB, 1,2,4-trimethylbenzene and 1,3,5-trimethylbenzene was approximately 6, 40 and 8% respectively. Salmonella strains TA1535, TA1537, TA98 and TA100 were used, in both the absence and presence of S9 and doses of up to 0.5 µL/plate were used based on a preliminary toxicity study in strain TA100.  No increases in revertant colonies over controls were observed. 

High Flash Aromatic Naphtha Type I was tested in CHO cells for gene mutation at the HPRT locus in both the absence and presence of S9 (Schreiner et al 1989). Doses up to 0.08 µL/mL were used, being limited by toxicity to the cells, and the treatment time was 4 hours. No increases in mutant frequency over controls were observed.

Schreiner et al (1989) also examined High Flash Aromatic Naphtha Type I for the ability to induce chromosomal damage in CHO cells in both the absence and presence of S9. Doses up to 100ug/ml were used, based on toxicity or cell cycle kinetic data. Cells were treated for 7 hours in the absence of S9 and 2 hours in the presence of S9, and then sampled for analysis at approximately 10 hours after the start of treatment. No significant increases in the frequency of chromosomal aberrations over controls were observed.

A negative result was also reported for sister chromatid exchange induction in CHO cells for High Flash Aromatic Naphtha Type I both in the absence and presence of S9 by Schreiner et al (1989).

The above data across a range of core endpoints provide no evidence for genotoxic activity for 1,2,4-trimethylbenzene and 1,3,5-trimethylbenzene, and only limited evidence of genotoxic activity for 1,2,3-trimethylbenzene, in bacteria and only in the absence of S9.

In vivo data

The key study is considered to be a cytogenetic study in the mouse (Janik-Spiechowicz et al 1998).  This is a recognised core assay type for investigating mutation in vivo.

1,2,3 -Trimethylbenzene, 1,2,4-trimethylbenzene and 1,3,5-trimethylbenzene were tested in a rodent bone marrow micronucleus assay (Janik-Spiechowicz et al 1998). Male and female Imp:Balb/c mice were given two intraperitoneal doses of trimethylbenzene isomer 24 hours apart covering a dose range up to 80% of the LD50. Bone marrow was sampled at 30, 48 and 72 hours after the first dose, and the incidence of micronucleated polychromatic erythrocytes (MPEs) recorded. None of the trimethylbenzene isomers induced any increase in MPEs over the controls. 

The cytogenetic endpoint was also examined in vivo by Schreiner et al (1989) who exposed male and female Sprague Dawley rats by the inhalation route (6 hours per day for 5 consecutive days) to High Flash Aromatic Naphtha Type I at dose levels up to 1500 ppm (825 ppm total trimethylbenzene), which was the maximum achievable vapour concentration. Bone marrow was sampled after 6, 24 and 48 hours and metaphase spreads examined for chromosomal aberrations. No significant increases over controls were observed.

The results from these two studies indicate that theTMB isomers are not genotoxic in vivo.

Increases in sister chromatid exchange were reported in male Imp:Balb/cmice administered doses of up to 80% of the LD50 of 1,2,3 -trimethylbenzene, 1,2,4-trimethylbenzene and 1,3,5-trimethylbenzene by the intraperitoneal route. The maximum increase observed was to only approximately 1.5 times the control value (Janik-Spiechowicz et al 1998).

Human information

There is no information indicating any adverse effects of trimethylbenzene. 

Summary and Discussion of Mutagenicity

The individual trimethylbenzene isomers have been examined for mutagenicity both in vitro and in vivo in a range of recognised core assay types. Negative results were obtained in vitro in bacterial and mammalian cell assays. The observation of small increases in sister chromatid exchange in the mouse for the three trimethylbenzene isomers is not considered to indicate a significant genotoxic effect, since the increases were small, SCE are only an indicator, the endpoint is one of uncertain relevance and two in vivo micronucleus assays and one in vivo ctogenicity assay were negative.

It is concluded that the available data indicates that 1,2,4-trimethylbenzene has no significant genotoxicity.


Short description of key information:
It is concluded that the available data indicates that 1,2,4-trimethylbenzene has no significant genotoxicity.

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

No classification is warranted under DSD or CLP as the available data indicate that 1,2,4 -trimethylbenzene has no significant genotoxicity.