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EC number: 203-604-4 | CAS number: 108-67-8
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
Endpoint summary
Administrative data
Key value for chemical safety assessment
Genetic toxicity in vitro
Description of key information
OECD 471, Mesitylene was tested in vitro in the Ames test (plate incorporation method), with Salmonella typhimurium TA97a, TA98, TA100 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).
Link to relevant study records
- 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: GLP status unknown, near guideline study, published in peer reviewed literature, minor restrictions in design and/or reporting but otherwise adequate for assessment
- 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
- 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. - 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
- Positive control substance:
- sodium azide
- Remarks:
- Migrated to IUCLID6: 1.5 µL or µg
- Positive control substance:
- other: 2, aminofluorene 5.0 µL or µg
- 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
- Key result
- 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
- Conclusions:
- Interpretation of results:
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, TA100 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).
Reference
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (negative)
Genetic toxicity in vivo
Description of key information
It is concluded that the available data indicates that 1,3,5-trimethylbenzene has no significant genotoxicity.
Link to relevant study records
- Endpoint:
- in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus
- Remarks:
- Type of genotoxicity: chromosome aberration
- Type of information:
- experimental study
- 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
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
- Deviations:
- yes
- Remarks:
- positive control substance tested only in males (considered not to affect scientific validity)
- GLP compliance:
- not specified
- Type of assay:
- micronucleus assay
- Species:
- mouse
- Strain:
- Balb/c
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Age at study initiation: 9 weeks
- Weight at study initiation: Approximately 23 g
ENVIRONMENTAL CONDITIONS - not reported
IN-LIFE DATES: Not reported - Route of administration:
- intraperitoneal
- Vehicle:
- - Vehicle(s)/solvent(s) used: mineral oil
- Duration of treatment / exposure:
- Administration by i.p. injection (two equal parts of dose given after a 24 hour interval). 2-stage model followed: First: 1 mL mineral oil or test substance at a dose equal to 80% of LD50 was dosed to males. Second: Doses administered equal to 40 and 80% of LD50 in males and 80% of LD50 in females.
- Frequency of treatment:
- Two i.p. injections, 24 hrs apart
- Post exposure period:
- 30, 48 and 72 hours after the first injection bone marrow samples were collected
- Remarks:
- Doses / Concentrations:
1800, 2960, 3600
Basis:
nominal conc. - No. of animals per sex per dose:
- 8 male and 4 female/0 mg/kg (solvent control - mineral oil); 12 male/1800 mg/kg; 12 female/2960 mg/kg; 24 male/3600 mg/kg
- Control animals:
- yes, concurrent vehicle
- Positive control(s):
- mitomycin C;
- Route of administration: not reported
- Doses / concentrations: 2.5 mg/kg; 0 mg/kg (solvent control - distilled water) - Tissues and cell types examined:
- Bone marrow polychromatic erythrocytes (NCEs)
- Details of tissue and slide preparation:
- CRITERIA FOR DOSE SELECTION: not reported
DETAILS OF SLIDE PREPARATION: bone marrow samples were collected from each mouse 30, 48 and 72 hours after 1st injection and 4 bone marrow smears were prepared from each mouse.
METHOD OF ANALYSIS: 1000 polychromatic erythrocytes (PCEs) per mouse were analysed for the number of micronucleated cells (mPCEs). The ratio of PCEs to mPCEs was determined by counting both cell types until the level of 200 NCEs was reached. - Evaluation criteria:
- A test substance was considered genotoxic if the test substance induced a statistically significant and reproducible increase in the number of mPCEs for at least one of the study points.
- Statistics:
- One way analysis of variance with multiple comparison test by Domański, 1979
- Key result
- Sex:
- male/female
- Genotoxicity:
- negative
- Toxicity:
- yes
- Vehicle controls validity:
- valid
- Positive controls validity:
- valid
- Additional information on results:
-
RESULTS OF DEFINITIVE STUDY
- Induction of micronuclei (for Micronucleus assay): No induction at 30, 48 or 72 hours after dosing
- Ratio of PCE/NCE (for Micronucleus assay): In males, the highest dose (80% of LD50) induced a statistically significant decrease in the PCEs to NCEs
ratio (the cytotoxicity index was 0.40 and 0.42 for 30 and 72 hours respectively, compared with 0.61 in the control male mice. The study performed on females using the equivalent of 80% of LD50 revealed that the animals survived but at the same time these doses were found not to induce cytotoxicity on bone marrow cells. - Conclusions:
- Interpretation of results´: negative
Negative micronucleus response in polychromatic erythrocytes of the bone marrow. - Executive summary:
Mesitylene was tested in the in vivo micronucleus assay using bone marrow cells of the Imp:Balb/c mouse. There was no effect on the frequency of micronucleated polychromatic erythrocytes.
Reference
Table: Induction of micronuclei in PCEs in mice
(based on Janik-Spiechowicz et al 1998, Mutation Research 412 (299 -305), Table 2)
Dose |
Number and sex |
% mPCEs |
ratio PCEs : mPCEs |
||||
harvest time (hours) |
harvest time (hours) |
||||||
30 |
48 |
72 |
30 |
48 |
72 |
||
Mesitylene |
|||||||
1 mL mineral oil |
8 male |
|
0.21 ± 0.08 |
|
|
0.61 |
|
|
4 female |
|
0.20 ± 0.08 |
|
|
0.60 |
|
1800 mg/kg |
12 male |
0.20 ± 0.00 |
0.10 ± 0.09 |
0.17 ± 0.09 |
0.62 |
0.56 |
0.58 |
2960 mg/kg |
12 female |
0.17 ± 0.09 |
0.20 ± 0.00 |
0.22 ± 0.05 |
0.51 |
0.60 |
0.58 |
3600 mg/kg |
24 male |
0.24 ± 0.11 |
0.17 ± 0.05 |
0.14 ± 0.05 |
0.40* |
0.33 |
0.42* |
Mitomycin C (positive control) |
|||||||
1 mL distilled water |
4 male |
|
|
0.15 ± 0.05 |
|
|
1.37 |
2.5 mg/kg |
12 male |
4.15 ± 0.38* |
4.22 ± 0.35* |
1.25 ± 0.15* |
0.71* |
0.48* |
0.14* |
* p ≥ 0.05 data for males treated at 80% LD50 and mineral oil expressed as mean values ± S.D. for 2-stage experiments |
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (negative)
Additional information
Additional information from genetic toxicity in vivo:
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. 1,3,5-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 0.5ul/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 ul/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 1,3,5-trimethylbenzene has no significant genotoxicity.
Justification for selection of genetic toxicity endpoint
Available data indicate that trimethylbenzenes have no significant genotoxicity in bacterial and mammalian systems in vitro and/or in vivo
Justification for classification or non-classification
No classification is warranted under Regulation (EC) No 1272/2008 as the available data indicate that 1,3,5 -trimethylbenzene has no significant genotoxicity.
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