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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
The acute oral and dermal LD50 values for 1,3,5-trimethylbenzene are concluded to be greater than 3000 mg/kg. In acute inhalation studies the LC50 is reported as 24,000 mg/m3. In human volunteer studies no effects were reported at concentrations up to 150 mg/m3.
Key value for chemical safety assessment
Acute toxicity: via oral route
Link to relevant study records
- Endpoint:
- acute toxicity: oral
- Type of information:
- migrated information: read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- key study
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: GLP, near guideline study, available as published report, adequate for assessment
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- EU Method B.1 (Acute Toxicity (Oral))
- Deviations:
- not specified
- GLP compliance:
- yes
- Test type:
- standard acute method
- Limit test:
- no
- Species:
- rat
- Strain:
- not specified
- Sex:
- male
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Ace Animals
- Age at study initiation: approximately 9 weeks
- Weight on arrival: 200-261 g
- Fasting period before study: 16-20 hours prior to dosing
- Housing: 5 per cage in suspended wire mesh cages
- Diet: Purina rat chow ad libitum except for pre-dose fast
- Water: ad libitum
- Acclimation period: At least 1 week
ENVIRONMENTAL CONDITIONS
- Temperature: "temperature controlled", values not reported
- Humidity (%): no data
- Air changes (per hr): no data
- Photoperiod: 12 hrs dark / 12 hrs light
IN-LIFE DATES: From: 12 September 1980 To: 21 October 1980 - Route of administration:
- oral: gavage
- Vehicle:
- unchanged (no vehicle)
- Doses:
- 3510, 5000, 7120 or 10140 mg/kg
- No. of animals per sex per dose:
- 10 males (no females tested)
- Control animals:
- no
- Details on study design:
- - Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Observations made 3-4 hours after dosing and once daily for 14 days, for mortality, toxicity and pharmacological effects.
- Necropsy of survivors performed: no - Statistics:
- The LD50 was calculated according to the method of Litchfield JT Jr., and Wilcoxon F, JPET 96:99, 1949.
- Key result
- Sex:
- male
- Dose descriptor:
- LD50
- Effect level:
- 6 000 mg/kg bw
- 95% CL:
- 4 920 - 7 320
- Mortality:
- Three rats died at 5.0 g/kg; seven rats died at 7.12 g/kg and all ten rats died following a dose of 10.14 g/kg. There were no deaths at 3.51 g/kg.
- Clinical signs:
- other: Lethargy and ptosis were seen at all four dose levels while ataxia and piloerection were only seen at the three highest levels. Other toxic signs, prostration, flaccid muscle tone, emaciation, tachypnea, diarrhoea, chromorhinorrhea and chromodacryorrhea w
- Interpretation of results:
- other: EU GHS: not classified
- Conclusions:
- The acute oral LD50 of pseudocumene was 6000 mg/kg of body weight.
- Executive summary:
Four groups of ten male rats were dosed orally with 98%+ Pseudocumene at levels of 3.51, 5.0, 7.12 and 10.14 g/kg of body weight. The LD50 calculated from these data was 6.0 g/kg. Lethargy and ptosis were seen at all four dose levels while ataxia and piloerection were only seen at the three highest levels. Other toxic signs, prostration, flaccid muscle tone, emaciation, tachypnea, diarrhoea, chromorhinorrhea and chromodacryorrhea were also noted at the highest levels at various times during the study.
Reference
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- LD50
- Value:
- 6 000 mg/kg bw
- Quality of whole database:
- The available data provide information that is adequate for the purpose of hazard assessment
Acute toxicity: via inhalation route
Link to relevant study records
- Endpoint:
- acute toxicity: inhalation
- 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: Non-GLP, non-guideline study, available as unpublished report, restrictions in design and/or reporting but otherwise adequate for assessment
- Qualifier:
- no guideline followed
- Principles of method if other than guideline:
- 2 rats/sex exposed (whole body) for 4 hours to atmospheres of Shellsol A and observed for the following 14 days
- GLP compliance:
- no
- Test type:
- standard acute method
- Limit test:
- yes
- Species:
- rat
- Strain:
- other: CD (COBS)
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- - Source: Charles River (UK) Ltd., Manston, Kent, UK
- Age at study initiation: 7-8 weeks
- Weight at study initiation: no data
- Housing: no data
- Diet: ad libitum (except during exposure)
- Water: ad libitum (except during exposure)
- Acclimation period: no data - Route of administration:
- inhalation
- Type of inhalation exposure:
- whole body
- Vehicle:
- other: air
- Details on inhalation exposure:
- GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: tubular glass chamber (2 rats/sex/chamber)
- Exposure chamber volume: no data
- System of generating atmosphere: Atmospheres generated dynamically by the near saturation of air supplied to the test chamber
TEST ATMOSPHERE
- Brief description of analytical method used: monitored continuously by means of a high temperature total hydrocarbon analyser (calibrated using a gravimetric procedure) - Analytical verification of test atmosphere concentrations:
- yes
- Duration of exposure:
- 4 h
- Concentrations:
- 10.2 mg/L
- No. of animals per sex per dose:
- 2
- Control animals:
- no
- Details on study design:
- - Duration of observation period following administration: 14 days
- Frequency of observations and weighing: no data
- Necropsy of survivors performed: no - Statistics:
- not applicable
- Key result
- Sex:
- male/female
- Dose descriptor:
- LC50
- Effect level:
- 10 200 mg/m³ air
- Exp. duration:
- 4 h
- Remarks on result:
- other: no mortalities at highest dose tested
- Mortality:
- no mortalities
- Clinical signs:
- other: lethargic behaviour
- Interpretation of results:
- other: EU GHS: not classified
- Conclusions:
- The acute (4 hour) inhalation LC50 of Shellsol A to male and female rats was greater than 10,200 mg/m3 (10.2 mg/L)
- Executive summary:
Rats were exposed for 4 hours to a near saturated atmosphere of Shellsol A (a mixture of trimethylbenzenes) at 10.2 mg/L. There were no deaths and no adverse signs other than lethargic behaviour; The acute LC50 was greater than 10,200 mg/m3.
Reference
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- LC50
- Value:
- 24 000 mg/m³ air
- Quality of whole database:
- The available data provide information that is adequate for the purpose of hazard assessment
Acute toxicity: via dermal route
Link to relevant study records
- Endpoint:
- acute toxicity: dermal
- 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: Non-GLP, non-guideline study, available as unpublished report, restrictions in design and/or reporting but otherwise adequate for assessment
- Qualifier:
- no guideline followed
- Principles of method if other than guideline:
- As described by Noakes DN and Sanderson DM (1969), A method for determining the dermal toxicity of pesticides. Br. J. Indust. Med., 26, 59-64
- GLP compliance:
- no
- Test type:
- standard acute method
- Limit test:
- no
- Species:
- rat
- Strain:
- other: CD (COBS)
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- - Source: Charles River (UK) Ltd., Manston, Kent, 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 - Type of coverage:
- not specified
- Vehicle:
- unchanged (no vehicle)
- Duration of exposure:
- 24 hours
- Doses:
- 1, 2, 4 mL/kg bw
- No. of animals per sex per dose:
- 2
- Control animals:
- no
- Details on study design:
- - Duration of observation period following administration: no data
- Frequency of observations and weighing: no data
- Necropsy of survivors performed: no - Statistics:
- not applicable
- Key result
- Sex:
- male/female
- Dose descriptor:
- LD50
- Effect level:
- > 4 mL/kg bw
- Remarks on result:
- other: no mortalities at 4 mL/kg bw (highest dose tested)
- Mortality:
- no mortalities
- Clinical signs:
- other: none
- Interpretation of results:
- not classified
- Remarks:
- Migrated information Criteria used for interpretation of results: EU
- Conclusions:
- The acute dermal LD50 of Shellsol A was greater than 4 mL/kg bw to male and female rats.
- Executive summary:
The acute dermal toxicity of Shellsol A was low, the 24 hour LD50 in rats was greater than 4 mL/kg bw to male and female rats (i.e. >2000 mg/kg).
Reference
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- LD50
- Value:
- 3 440 mg/kg bw
- Quality of whole database:
- The available data provide information that is adequate for the purpose of hazard assessment
Additional information
A comparison of toxicological data available for the individual isomers of trimethylbenzene demonstrates that effects reported and the corresponding effect and no effect levels obtained are generally similar.
Non-human information
Oral
In a key (read-across) study (MB Research Laboratories Inc, 1980) rats were given single oral doses of from 3000-10,000 mg/kg body weight of 1,2,4 –trimethylbenzene (pseudocumene). Lethargy and ptosis were seen at all four dose levels while ataxia and piloerection were only seen at the three highest levels. The LD50 in this study was 6000 mg/kg. This result is supported by the studies of Litton Bionetics Inc (1976) where the LD50s of 1,2,4 -trimethylbenzene in male and female rats were 3550 and 3280 mg/kg respectively and Lewis (2003) where oral LD50 values of greater than 5000 mg/kg have been reported in rats.
The oral toxicity of 1,3,5 –trimethylbenzene is similar to that the other trimethylbenzene isomers in comparative studies on the isomers (Lewis, 2003) and studies on isomer mixtures (Shellsol A -a mixture of trimethylbenzenes CAS# 64742-95-6) where an acute oral LD50 of greater than 8 mL/kg bw ( 6880 mg/kg) and approximately 4 mL/kg bw (3440 mg/kg) were reported for male and female rats respectively (Shell Toxicology Laboratory, 1977).
In conclusion, the oral LD50 of 1,3,5-trimethylbenzene in rats is greater than 3000 mg/kg
Inhalation
Information from robust studies on the inhalational acute toxicity of 1,3,5 –trimethylbenzene is lacking. An LC50 values of 24,000 mg/m3 in rats has been reported for 1,3,5 -TMB (Lewis, 2003), although details of the original studies are lacking. Further details are given in the review of Firth et al (2008).
An adequate, key study is provided by Shell Toxicology Laboratory (1977). Rats were exposed for 4 hours to Shellsol A (a mixture of trimethylbenzenes CAS# 64742-95-6) at 10,200 mg/m3. There were no deaths and no adverse signs other than lethargic behaviour. The acute LC50 was greater than 10,200 mg/m3. Korsak et al (1997) investigated the effect of 1,3,5 –trimethylbenzene on respiratory sensory irritation in male mice after acute exposure to 2551 mg/m3 but this study is described in the “Irritation Section”.
In conclusion, the available data indicates that 1,3,5 -trimethylbenzene has low acute inhalational toxicity at exposures up to approximately 10,200 mg/m3. The secondary reference of Lewis indicates an LC50 in rats greater than 20,000 mg/m3.
Dermal
Some information is available for the acute toxicity of 1,3,5- trimethylbenzene by dermal application. One dermal acute study showed an LD50 value of greater than 3440 mg/kg after exposure of rats to Shellsol A (a mixture of trimethylbenzenes CAS# 64742-95-6) for 24 (Shell Toxicology Laboratory, 1977).
Human information
There is no information available on the effects of trimethylbenzenes in humans after oral and dermal exposure. Information on the effects of inhaled 1,3,5-trimethylbenzene is available from human volunteer toxicokinetics studies and indicates no signs of toxicity for exposures up to 150 mg/m3. Jarnberg et al (1996) assessed the toxicokinetics of inhaled trimethylbenzenes in man. Ten male volunteers were exposed to 120 mg/m3 of 1,3,5-TMB for 2 hours in an exposure chamber at a constant work load of 50 W on an ergometer bicycle. Before, during and after exposure the subjects rated symptoms related to irritation or the central nervous system from "no effect at all" to "almost unbearable" for (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. Kostrzewski et al (1997) also exposed human volunteers to up to 150 mg/m3 for 4 or 8 hours. Clinical examinations (internal, laryngologic, neurologic and haematologic) were carried out before the onset of exposure, after exposure and repeatedly after the experiment at 3 month intervals but no abnormalities were detected.
Conclusions
Exposure via the oral and inhalational routes are the most relevant for 1,3,5 -trimethylbenzene. Data in rats indicate a low potential for acute oral toxicity with the oral LD50 of 1,3,5 -trimethylbenzene in rats being greater than 3000 mg/kg. Inhalational exposure of humans up to 150 mg/m3 resulted in no acute toxicity and the LC50 in rats is reported as 24,000 mg/m3.
Justification for selection of acute toxicity – oral endpoint
The available key and supporting studies indicate that the acute oral toxicity of 1,2,4-trimethylbenzene is low (LD50 >3000 mg/kg)
Justification for selection of acute toxicity – inhalation endpoint
Trimethylbenzenes are classified Acute Tox Category 4, H332: Harmful if inhaled under CLP
Justification for selection of acute toxicity – dermal endpoint
The available key study indicates that the acute dermal toxicity of trimethylbenzene isomers is low (LD50 >3000 mg/kg)
Justification for classification or non-classification
No classification for acute oral, inhalation or dermal toxicity is warranted under DSD or CLP.
The kinematic viscosity of 1,3,5 -trimethylbenzene justifies classification Xn, R65, under DSD and, under CLP, Aspiration Tox Category 1, H304.
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