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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
Key value for chemical safety assessment
Skin sensitisation
Link to relevant study records
- Endpoint:
- skin sensitisation: in vivo (non-LLNA)
- Type of information:
- migrated information: read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- supporting study
- Reliability:
- 4 (not assignable)
- Rationale for reliability incl. deficiencies:
- other: Non-GLP, near guideline study, available as unpublished report, acceptable with restrictions
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 406 (Skin Sensitisation)
- GLP compliance:
- no
- Type of study:
- guinea pig maximisation test
- Species:
- guinea pig
- Strain:
- Dunkin-Hartley
- Sex:
- male
- Details on test animals and environmental conditions:
- TEST ANIMALS
- Source: Animal Breeding Unit, Imperial Chemical Industries PLC, Pharmaceuticals Division, Alderley Park, Macclesfield, Cheshire, UK
- Age at study initiation: 5-11 weeks
- Weight at study initiation: 354-579 g
- Housing: individually (2 per divided cage), in stainless steel and polycarbonate cages (370 mm x 320 mm x 200 mm)
- Diet: Labsure RGP Guinea Pig Diet ad libitum
- Water: ad libitum
- Acclimation period: at least 6 days
ENVIRONMENTAL CONDITIONS
- Temperature: approximately 21°C
- Humidity: approximately 55%
- Air changes: 20-30 per hr
- Photoperiod: 12hrs dark / 12hrs light
IN-LIFE DATES: January and February 1984 - Route:
- intradermal and epicutaneous
- Vehicle:
- corn oil
- Concentration / amount:
- intradermal induction 5.0% w/v; topical induction 100% (undiluted), challenge 50%, 25% and 5 % w/v, rechallenge 50% and 5%
- Route:
- epicutaneous, occlusive
- Vehicle:
- corn oil
- Concentration / amount:
- intradermal induction 5.0% w/v; topical induction 100% (undiluted), challenge 50%, 25% and 5 % w/v, rechallenge 50% and 5%
- No. of animals per dose:
- 20 test and 10 control animals (plus 10 additional controls used for rechallenge)
- Details on study design:
- RANGE FINDING TESTS: up to 2 dose levels tested on groups of 2 or more guinea pigs to determine dose levels for main study.
MAIN STUDY
A. INDUCTION EXPOSURE (test animals)
- No. of exposures / exposure period: 3 pairs of intradermal injections (0.1 mL each) per guinea pig as follows: (i) Freund's complete adjuvant plus corn oil (1:1), (ii) 5% w/v Aromasol H in corn oil, (iii) 5% w/v Aromasol H, followed one week later by topical application of 0.25 mL of undiluted Aromasol H for 48 hours under an occlusive dressing
- Site: scapular region
INDUCTION EXPOSURE (control animals)
- No. of exposures / exposure period: 3 pairs of intradermal injections (0.1 mL each) per guinea pig as follows: (i) Freund's complete adjuvant plus corn oil (1:1), (ii) corn oil, (iii) Freund's complete adjuvant plus corn oil (1:1), the topical applications were as above except that nothing was applied to the skin
- Site: scapular region
B. CHALLENGE EXPOSURE (test and control animals)
- No. of exposures / exposure period: single 24 hour application of 0.05-0.1 mL of each of a 50%, 25% and 5% solution of Aromasol H in corn oil
- Day(s) of challenge: two weeks after topical induction application
- Site: shorn flank
- Evaluation (hr after challenge): 24 and 48 hours
C. RECHALLENGE EXPOSURE:
- No. of exposures / exposure period: single 24 hour application of 0.05-0.1 mL of each of a 50% and 5% solution of Aromasol H in corn oil
- Day(s) of challenge: 7 days after first challenge
- Site: shorn flank (different from area used for initial challenge)
- Evaluation (hr after challenge): 24 and 48 hours
- A fresh group of 10 negative controls (previously injected with Freund's complete adjuvant) were used - Positive control substance(s):
- not specified
- Reading:
- 1st reading
- Hours after challenge:
- 24
- Group:
- test chemical
- Dose level:
- 50%
- No. with + reactions:
- 7
- Total no. in group:
- 20
- Remarks on result:
- other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 50%. No with. + reactions: 7.0. Total no. in groups: 20.0.
- Reading:
- 2nd reading
- Hours after challenge:
- 48
- Group:
- test chemical
- Dose level:
- 50%
- No. with + reactions:
- 1
- Total no. in group:
- 20
- Remarks on result:
- other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 50%. No with. + reactions: 1.0. Total no. in groups: 20.0.
- Reading:
- 1st reading
- Hours after challenge:
- 24
- Group:
- negative control
- Dose level:
- 50%
- No. with + reactions:
- 3
- Total no. in group:
- 10
- Remarks on result:
- other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 50%. No with. + reactions: 3.0. Total no. in groups: 10.0.
- Reading:
- 2nd reading
- Hours after challenge:
- 48
- Group:
- negative control
- Dose level:
- 50%
- No. with + reactions:
- 0
- Total no. in group:
- 10
- Remarks on result:
- other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 50%. No with. + reactions: 0.0. Total no. in groups: 10.0.
- Reading:
- 1st reading
- Hours after challenge:
- 24
- Group:
- test chemical
- Dose level:
- 25%
- No. with + reactions:
- 3
- Total no. in group:
- 20
- Remarks on result:
- other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 25%. No with. + reactions: 3.0. Total no. in groups: 20.0.
- Reading:
- 2nd reading
- Hours after challenge:
- 48
- Group:
- test chemical
- Dose level:
- 25%
- No. with + reactions:
- 2
- Total no. in group:
- 20
- Remarks on result:
- other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 25%. No with. + reactions: 2.0. Total no. in groups: 20.0.
- Reading:
- 1st reading
- Hours after challenge:
- 24
- Group:
- negative control
- Dose level:
- 25%
- No. with + reactions:
- 1
- Total no. in group:
- 10
- Remarks on result:
- other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 25%. No with. + reactions: 1.0. Total no. in groups: 10.0.
- Reading:
- 2nd reading
- Hours after challenge:
- 48
- Group:
- negative control
- Dose level:
- 25%
- No. with + reactions:
- 0
- Total no. in group:
- 10
- Remarks on result:
- other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 25%. No with. + reactions: 0.0. Total no. in groups: 10.0.
- Reading:
- 1st reading
- Hours after challenge:
- 24
- Group:
- test chemical
- Dose level:
- 5%
- No. with + reactions:
- 11
- Total no. in group:
- 20
- Remarks on result:
- other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 5%. No with. + reactions: 11.0. Total no. in groups: 20.0.
- Reading:
- 2nd reading
- Hours after challenge:
- 48
- Group:
- test chemical
- Dose level:
- 5%
- No. with + reactions:
- 10
- Total no. in group:
- 20
- Remarks on result:
- other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 5%. No with. + reactions: 10.0. Total no. in groups: 20.0.
- Reading:
- 1st reading
- Hours after challenge:
- 24
- Group:
- negative control
- Dose level:
- 5%
- No. with + reactions:
- 1
- Total no. in group:
- 10
- Remarks on result:
- other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 5%. No with. + reactions: 1.0. Total no. in groups: 10.0.
- Reading:
- 2nd reading
- Hours after challenge:
- 48
- Group:
- negative control
- Dose level:
- 5%
- No. with + reactions:
- 0
- Total no. in group:
- 10
- Remarks on result:
- other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 5%. No with. + reactions: 0.0. Total no. in groups: 10.0.
- Reading:
- other: rechallenge 1st reading
- Hours after challenge:
- 24
- Group:
- test chemical
- Dose level:
- 50%
- No. with + reactions:
- 9
- Total no. in group:
- 20
- Remarks on result:
- other: Reading: other: rechallenge 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 50%. No with. + reactions: 9.0. Total no. in groups: 20.0.
- Reading:
- other: rechallenge 2nd reading
- Hours after challenge:
- 48
- Group:
- test chemical
- Dose level:
- 50%
- No. with + reactions:
- 6
- Total no. in group:
- 20
- Remarks on result:
- other: Reading: other: rechallenge 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 50%. No with. + reactions: 6.0. Total no. in groups: 20.0.
- Reading:
- other: rechallenge 1st reading
- Hours after challenge:
- 24
- Group:
- negative control
- Dose level:
- 50%
- No. with + reactions:
- 0
- Total no. in group:
- 10
- Remarks on result:
- other: Reading: other: rechallenge 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 50%. No with. + reactions: 0.0. Total no. in groups: 10.0.
- Reading:
- other: rechallenge 2nd reading
- Hours after challenge:
- 48
- Group:
- negative control
- Dose level:
- 50%
- No. with + reactions:
- 0
- Total no. in group:
- 10
- Remarks on result:
- other: Reading: other: rechallenge 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 50%. No with. + reactions: 0.0. Total no. in groups: 10.0.
- Reading:
- other: rechallenge 1st reading
- Hours after challenge:
- 24
- Group:
- test chemical
- Dose level:
- 5%
- No. with + reactions:
- 8
- Total no. in group:
- 20
- Remarks on result:
- other: Reading: other: rechallenge 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 5%. No with. + reactions: 8.0. Total no. in groups: 20.0.
- Reading:
- other: rechallenge 2nd reading
- Hours after challenge:
- 48
- Group:
- test chemical
- Dose level:
- 5%
- No. with + reactions:
- 7
- Total no. in group:
- 20
- Remarks on result:
- other: Reading: other: rechallenge 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 5%. No with. + reactions: 7.0. Total no. in groups: 20.0.
- Reading:
- other: rechallenge 1st reading
- Hours after challenge:
- 24
- Group:
- negative control
- Dose level:
- 5%
- No. with + reactions:
- 0
- Total no. in group:
- 10
- Remarks on result:
- other: Reading: other: rechallenge 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 5%. No with. + reactions: 0.0. Total no. in groups: 10.0.
- Reading:
- other: rechallenge 2nd reading
- Hours after challenge:
- 48
- Group:
- negative control
- Dose level:
- 5%
- No. with + reactions:
- 0
- Total no. in group:
- 10
- Remarks on result:
- other: Reading: other: rechallenge 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 5%. No with. + reactions: 0.0. Total no. in groups: 10.0.
- Interpretation of results:
- Category 1 (skin sensitising) based on GHS criteria
- Conclusions:
- Aromasol H appeared to be a sensitiser to guinea pig skin. The response may have been due to irritation.
- Executive summary:
Guinea pigs were challenged with 5 % Aromasol H in corn oil, with occlusion. Following challenge with either a 50 % or 25 % preparation in corn oil, a weak sensitisation response was elicited but irritation was also noted. The animals were rechallenged 7 days later with either a 50 % or a 5 % preparation in corn oil and a moderate sensitisation response was recorded.
Reference
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (not sensitising)
- Additional information:
There is no information on sensitisation in humans after exposure to trimethylbenzenes.
In animals a key study is provided by Shell Toxicology Laboratory (1977). Guinea pigs were challenged with Shellsol A (a mixture of trimethylbenzenes CAS No 64742 -95 -6) in a maximization test. No sensitisation response was elicited immediately, 24 or 48 hours after the challenge. The test was therefore negative. This result is supported by a poorly reported guinea pig maximization test (IUCLID 4 record; EBSI, 1983) where no sensitisation occurred after exposure to 1,2,4-trimethylbenzene (study unavailable).
In contrast, dermal responses were reported when Aromasol H (a mixture of C8 aromatics (xylenes and benzenes), C9 aromatics (trimethylbenzenes and ethyl toluenes), and C10 aromatics (diethyl ethyl benzenes and diethyl benzenes)) was tested in a guinea pig maximization test (CTL1984). The study report concluded that Aromasol H was a weak sensitizer but irritation was also noted. Irritation has been reported to be a factor in false positive results obtained on other substances in the guinea pig maximization test (Basketter, 2008). The substituted aromatics present in Aromasol H are known to be non-sensitising, hence the weight of evidence therefore indicates that this result is a false positive.
In conclusion, the available evidence indicates that 1,3,5-trimethylbenzeneis not a skin sensitiser.
References
Basketter D (2008). Information derived from sensitization test methods: Test sensitivity, false positives, and false negatives. Reg. Tox. Pharm. 50, 68–169.
Migrated from Short description of key information:
A weight of evidence evaluation indicates that of 1,3,5- trimethylbenzene is not-sensitising. Two guinea pig maximization tests with mixtures containing trimethylbenzenes were negative. One study gave a positive result but this is believed to be a false positive due to irritation.
Justification for selection of skin sensitisation endpoint:
Results from a guinea pig maximisation test performed using trimethylbenzenes indicate that 1,3,5-trimethylbenzene is unlikely to induce or elicit skin sensitisation
Justification for classification or non-classification
1,3,5-Trimethylbenzene is not considered to be sensitizing. It does not therefore warrant classification under DSD or CLP.
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