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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
Description of key information
It is concluded that 1,3,5-trimethylbenzene is irritating to the skin and eyes of rabbits. Respiratory irritation (decreased respiratory rate) was observed in mice with 2551 mg/m3 producing a 50 % decrease. No irritation was noted in human studies but these were conducted at much lower doses than the animal studies.
Key value for chemical safety assessment
Skin irritation / corrosion
Link to relevant study records
- Endpoint:
- skin irritation: in vivo
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Guideline study, GLP status unclear, acceptable for assessment
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
- Principles of method if other than guideline:
- Mesitylene was applied to shaved rabbit skin and erythema and oedema recorded (using Draize criteria) at 1, 24, 48, and 72 hr after removal of the patch. Observations continued thereafter every 2 days until dermal responses had resolved in at least one rabbit.
- GLP compliance:
- not specified
- Species:
- rabbit
- Strain:
- New Zealand White
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Proefstations voor Veeteelt (Merelbeke, Belgium)
- Age at study initiation: 9-24 weeks
- Weight at study initiation: 2.75-5.2 kg
- Housing: individual mesh wire bottom cages
- Conventional Laboratory diet ad libitum
- Tap-water ad libitum
- Acclimation period: At least 7 days
- Normal housing conditions - Type of coverage:
- occlusive
- Preparation of test site:
- shaved
- Vehicle:
- unchanged (no vehicle)
- Controls:
- other: area of untreated skin used for comparison
- Amount / concentration applied:
- 0.5 ml
- Duration of treatment / exposure:
- 4 hours, occluded
- Observation period:
- The animals were examined for signs of erythema and edema formation at 1, 24, 48 and 72 hr after removal of the test patch
- Number of animals:
- 5 or 6 (not specified)
- Irritation parameter:
- erythema score
- Basis:
- mean
- Time point:
- 24/48/72 h
- Score:
- 2.33
- Remarks on result:
- other: time course information not available
- Irritation parameter:
- edema score
- Basis:
- mean
- Time point:
- 24/48/72 h
- Remarks on result:
- not measured/tested
- Interpretation of results:
- Category 2 (irritant) based on GHS criteria
- Conclusions:
- Mesitylene caused erythema (overall mean 2.33) when applied to shaved rabbit skin under occlusion for 4 hr.
- Executive summary:
The skin irritation potential of mesitylene toward shaved rabbit skin was evaluated according to Annex V of directive 67/548 EEC. The sample (0.5 ml) was applied under occlusion for 4 hr with an area of untreated skin serving as control. The overall mean score for erythema (all animals over a 72 hour period) was 2.33; no oedema was reported. The results indicate that mesitylene is irritating to rabbit skin.
Reference
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed (irritating)
Eye irritation
Link to relevant study records
- Endpoint:
- eye irritation: in vivo
- Type of information:
- migrated information: read-across from supporting substance (structural analogue or surrogate)
- Remarks:
- Read-across to the test material (Shellsol A) is justified by the description of its composition – it is described as being composed of predominantly trimethylbenzenes, of which mesitylene is one.
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Non-GLP, near-guideline study, available as unpublished report, restrictions in design and/or reporting but otherwise adequate for assessment
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 405 (Acute Eye Irritation / Corrosion)
- GLP compliance:
- no
- Species:
- rabbit
- Strain:
- New Zealand White
- Details on test animals or tissues and environmental conditions:
- - Source: Ranch Rabbits, Crawley, Sussex, UK
- Age at study initiation: no data
- Weight at study initiation: no data
- Housing: no data
- Diet (e.g. ad libitum): no data
- Water (e.g. ad libitum): no data
- Acclimation period: no data
ENVIRONMENTAL CONDITIONS: no data
IN-LIFE DATES: no data - Vehicle:
- unchanged (no vehicle)
- Controls:
- no
- Amount / concentration applied:
- 0.2 mL undiluted Shellsol A
- Duration of treatment / exposure:
- single instillation
- Observation period (in vivo):
- 7 days
- Number of animals or in vitro replicates:
- 2 male and 2 female
- Details on study design:
- Shellsol A instilled into conjunctival sac of right eye, untreated left eye served as a control. Eye irritation assessed 1,2,3 and 7 days after instillation according to numerical scheme cited in Federal Register (28 (110), 6.6.1963. para 191.12. Test for eye irritation)
- Irritation parameter:
- cornea opacity score
- Basis:
- mean
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 0
- Reversibility:
- fully reversible
- Remarks on result:
- no indication of irritation
- Irritation parameter:
- iris score
- Basis:
- mean
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 0
- Reversibility:
- fully reversible
- Remarks on result:
- no indication of irritation
- Irritation parameter:
- conjunctivae score
- Basis:
- mean
- Time point:
- 24/48/72 h
- Score:
- >= 0 - <= 1
- Max. score:
- 2
- Reversibility:
- fully reversible within: 1 day
- Remarks:
- after 30 min. highest schore of 2 for two animals
- Remarks on result:
- probability of weak irritation
- Irritation parameter:
- chemosis score
- Basis:
- mean
- Time point:
- 24/48/72 h
- Score:
- >= 0 - <= 1
- Max. score:
- 2
- Reversibility:
- fully reversible within: 1 day
- Remarks:
- after 30 min.: score of 2 for one animal and score of 1 for 3 animals
- Irritant / corrosive response data:
- Thirty minutes after instillation, slight to moderate conjunctival redness was present in all 4 rabbits and slight to moderate chemosis was present in 3 rabbits. Conjunctival discharge was present in one rabbit at the 30 minute and day 1 reading but did not persist. These conjunctival effects did not persist, no chemosis was seen after 1 day, very slight redness was seen in 2 rabbits at 1 day but all redness had cleared by day 2. There were no corneal or iridial effects.
- Other effects:
- There was an immediate pain reaction following instillation into the eye.
- Interpretation of results:
- other: EU GHS: not irritating
- Conclusions:
- Shellsol A was practically non-irritating to the rabbit eye.
- Executive summary:
One drop (0.2 mL) of Shellsol A instilled into the rabbit eye caused an immediate pain reaction but thereafter was practically non-irritating.
Reference
Eye irritation scores of Shellsol A
Time |
Cornea |
Iris |
Conjunctiva |
||||||||||||||
|
|
|
|
Redness |
Chemosis |
||||||||||||
|
Animal number |
9 |
10 |
56 |
57 |
9 |
10 |
56 |
57 |
9 |
10 |
56 |
57 |
9 |
10 |
56 |
57 |
after 30 mins |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
2 |
1-2 |
1 |
1 |
2 |
1 |
0-1 |
0 |
|
after 1 day |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0-1 |
0 |
0-1 |
0 |
0 |
0 |
0 |
0 |
|
after 2 days |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
after 3 days |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
after 7 days |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed (irritating)
Respiratory irritation
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed (irritating)
Additional information
Non-human information
Skin
The key study is provided by Jacobs and Martens (1987) where the skin irritation potential of the isomer,1,3,5-trimethylbenzene (mesitylene), was investigated on shaved rabbit skin. A sample (0.5 ml) was applied under occlusion for 4 hr with an area of untreated skin serving as control. The overall mean score for erythema (for all animals over a 72 hour period) was 2.33; no oedema was reported. The results indicate that 1,3,5 trimethylbenzene is irritating to rabbit skin. This study is supported by other data on 1,3,5 trimethylbenzene demonstrating that concentrations in excess of 25% were irritating to rabbit skin (Jacobs et al, 1987). A study on undiluted Shellsol A (a mixture of trimethylbenzenes CAS# 64742-95-6) also showed that this was a moderate skin irritant following a single 24 hour application to abraded and non-abraded occluded rabbit skin.
In conclusion, the data indicate that 1,3,5- trimethylbenzene has the potential to be irritating to skin.
Eye
1,3,5 -Trimethylbenzene is irritating to the eye. This was concluded by SCOEL (1994) in relation to all the trimethylbenzene isomers, but the only reference available is an IUCLID 4 entry (ESBI, 1990) where the results of a rabbit occular irritation test showed that 1,2,4- trimethylbenzene was irritating to the eyes, but details are lacking and the study cannot be sourced. An earlier study on Shellsol A (a mixture of trimethylbenzenes CAS No. 64742-95-6) showed that one drop instilled into the rabbit eye caused an immediate pain reaction but thereafter was practically non-irritating.
In spite of these apparently conflicting results, and in the absence of reliable information to the contrary, the harmonized EU position (indicating the 1,2,4- trimethylbenzene is irritating to the eye) is adopted for 1,3,5-trimethylbenzene.
Respiratory tract
Respiratory sensory irritation effects of 1,2,4-trimethylbenzenes in male Balb/C mice were investigated under conditions of acute exposure (Korsak et al, 1997). Male Balb/C mice were exposed to trimethylbenzenes for 6 min. Respiratory sensory irritation was quantified by determination of the decrease in respiratory rate. 1,3,5 -Trimethylbenzene depressed respiration rate and the concentration at which the respiratory rate was decreased to 50% (RD50) was 519 ppm (2551 mg/m3). A 90 day study is also described in the same publication (see Section on Repeat dose Toxicity). Rats were exposed to 1,2,4-trimethylbenzene for 90 days, at concentrations of 25, 100 and 250 ppm. There was no evidence of systemic toxicity at concentrations up to and including 250 ppm (1230 mg/m3. The total number of cell macrophages, polymorphonuclear leukocytes and lymphocytes in the brochiolar lavage (BAL) fluid at all three test concentrations was increased compared with the controls. Total protein lactate dehydrogenase and acid phosphatase activity in BAL were also increased in all exposed groups. These changes are indicative of mild respiratory irritation, however, a concentration-dependency was not seen, and therefore some adaptation may have taken place.
In conclusion, these data indicate that 1,3,5- trimethylbenzene has the potential to be irritating to the respiratory tract.
Human Information
Some information is available on the potential for trimethylbenzenes to cause irritation in humans. In human volunteer toxicokinetics studies on inhaled trimethylbenzenes, subjects were asked to assess (i) Discomfort in eyes: burning, irritation, or running eyes; (ii) discomfort in nose: burning, irritation, or running nose; (iii) discomfort in throat or airways; (iv) headache; (v) fatigue; (vi) nausea; (vii) dizziness; (viii) intoxication; (ix) difficulty in breathing and (x) smell of solvent. No effects were reported at concentrations up to 120 mg/m3 (Jarnberg et al, 1996).
Conclusions
The available data from animal studies indicates that 1,3,5 - trimethylbenzene, in common with other trimethylbenzene isomers, is irritating to skin, eyes and respiratory tract. Although no adverse effects were noted in human volunteer studies these were conducted at concentrations at least an order of magnitude lower than those in animal studies. ReferenceFirth MJ (2008). Derivation of a chronic reference dose and reference concentration for trimethylbenzenes and C9 aromatic hydrocarbon solvents. Reg Tox. Phamacol. 52, 248 -256
Justification for selection of skin irritation / corrosion endpoint:
The available key and supporting studies indicate that 1,3,5-trimethylbenzene is irritating to the skin
Justification for selection of eye irritation endpoint:
Trimethylbenzenes are classified for eye irritation, Category 2, H319, under CLP
Effects on skin irritation/corrosion: irritating
Effects on eye irritation: irritating
Effects on respiratory irritation: irritating
Justification for classification or non-classification
1,3,5 -Trimethylbenzene is currently classified as irritating to the respiratory tract H335 according to Annex VI of Regulation (EC) No 1272/2008.
Under CLP it is proposed that additional classification is warranted : Eye Irritation Category 2, H319 Causes serious eye irritation; STOT-SE Category 3 H335 May cause respiratory irritation and Skin Irritation H315 Causes skin irritation.
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