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EC number: 214-874-8 | CAS number: 1204-28-0
- 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
![](https://echa.europa.eu/o/diss-blank-theme/images/factsheets/A-REACH/factsheet/print_toxicological-information.png)
Skin sensitisation
Administrative data
- Endpoint:
- skin sensitisation: in vivo (non-LLNA)
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- study well documented, meets generally accepted scientific principles, acceptable for assessment
Cross-reference
- Reason / purpose for cross-reference:
- read-across: supporting information
Reference
- Endpoint:
- skin sensitisation, other
- Type of information:
- read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- weight of evidence
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- study well documented, meets generally accepted scientific principles, acceptable for assessment
- Justification for type of information:
- The read across justification document is attached below.
- Reason / purpose for cross-reference:
- read-across source
- Specific details on test material used for the study:
- Trimellitic anhydride chloride
CAS: 1204-28-0 - Key result
- Reading:
- other: 2 weeks after the last exposure
- Group:
- negative control
- Dose level:
- 0
- No. with + reactions:
- 0
- Total no. in group:
- 8
- Remarks on result:
- no indication of skin sensitisation
- Key result
- Reading:
- other: 2 weeks after the last exposure
- Group:
- test chemical
- Dose level:
- 0.30 mg
- No. with + reactions:
- 4
- Total no. in group:
- 8
- Remarks on result:
- positive indication of skin sensitisation
- Key result
- Reading:
- other: 2 weeks after the last exposure
- Group:
- test chemical
- Dose level:
- 1.25 mg
- No. with + reactions:
- 7
- Total no. in group:
- 8
- Remarks on result:
- positive indication of skin sensitisation
- Key result
- Reading:
- other: 2 weeks after the last exposure
- Group:
- test chemical
- Dose level:
- 5 mg
- No. with + reactions:
- 8
- Total no. in group:
- 8
- Remarks on result:
- positive indication of skin sensitisation
- Key result
- Reading:
- other: 2 weeks after the last exposure
- Group:
- test chemical
- Dose level:
- 20
- No. with + reactions:
- 8
- Total no. in group:
- 8
- Remarks on result:
- positive indication of skin sensitisation
Data source
Reference
- Reference Type:
- publication
- Title:
- Unnamed
- Year:
- 2 002
- Report date:
- 2002
Materials and methods
Test guideline
- Qualifier:
- no guideline followed
- Principles of method if other than guideline:
- The present study examines the ability of dry TMA powder to sensitize Brown Norway rats when applied, topically, to the skin.
A patch of hair was carefully clipped with scissors on the rat’s back. Dry TMA powder was administered on days 0, 7, 14 and 21, and the area occluded with surgical tape overnight after each application. Residual powder recovered from the occluded skin was analyzed by proton nuclear magnetic resonance and was still predominantly TMA. Circulating anti-TMA IgE and IgG were measured by ELISA. - GLP compliance:
- not specified
- Type of study:
- patch test
- Justification for non-LLNA method:
- A non-LLNA method is not provided since published data in rats is avaialble. In additon, in vivo study can be waived because the substance is corrosive to skin.
Test material
- Reference substance name:
- Benzene-1,2,4-tricarboxylic acid 1,2-anhydride
- EC Number:
- 209-008-0
- EC Name:
- Benzene-1,2,4-tricarboxylic acid 1,2-anhydride
- Cas Number:
- 552-30-7
- Molecular formula:
- C9H4O5
- IUPAC Name:
- 1,3-dioxo-2-benzofuran-5-carboxylic acid
Constituent 1
- Specific details on test material used for the study:
- Trimellitic anhydride
CAS 552-30-7
In vivo test system
Test animals
- Species:
- other: rat
- Strain:
- other: Brown Norway and Sprague–Dawley
- Sex:
- male
- Details on test animals and environmental conditions:
- - Male, inbred BN rats (150–175 g) and male Sprague–Dawley rats (12 weeks old) from Charles River Laboratories (Wilmington, MA).
- Animals were housed in a facility accredited by the Association for Assessment and Accreditation of Laboratory Animal Care International
- Rats were fed Purina rat chow, and water ad libitum
- Rats kept on a standard 12:12 light:dark cycle.
- Rats were acclimated in the facility for 1 week prior to use.
Study design: in vivo (non-LLNA)
Induction
- Route:
- other: patch on fur on the back
- Vehicle:
- unchanged (no vehicle)
- Concentration / amount:
- 0, 0.3, 1.25, 5 and 20 mg was applied topically to BN rats (n=8/dose)
- Day(s)/duration:
- duration: 20h (overnight)
Challengeopen allclose all
- No.:
- #1
- Route:
- other: patch on fur on the back
- Vehicle:
- unchanged (no vehicle)
- Concentration / amount:
- 0, 0.3, 1.25, 5 and 20 mg
- Day(s)/duration:
- on day 7 / duration: 20h (overnight)
- No.:
- #2
- Route:
- other: patch on fur on the back
- Vehicle:
- unchanged (no vehicle)
- Concentration / amount:
- 0, 0.3, 1.25, 5 and 20 mg
- Day(s)/duration:
- on day 14 / duration: 20h (overnight)
- No.:
- #3
- Route:
- other: patch on fur on the back
- Vehicle:
- unchanged (no vehicle)
- Concentration / amount:
- 0, 0.3, 1.25, 5 and 20 mg
- Day(s)/duration:
- on day 21 / duration: 20h (overnight)
- No. of animals per dose:
- 8 males / dose
- Details on study design:
- Dry TMA powder preparation:
TMA flakes were ground in a water-cooled analytical mill. The fine powder was collected and stored in the presence of a desiccant. The particle size distribution was determined using particles suspended in balanced electrolyte solution and measured by Coulter H Multisizer II.
Topical skin exposure to dry TMA powder:
Brown Norway rats were anesthetized using 40 mg/kg, i.p., methohexital sodium.
A patch of fur on the back was carefully clipped with scissors (avoid skin irritation and trauma). Dry TMA powder was applied to the
clipped area. TMA exposed areas were occluded with a nonabrasive dermal surgical tape overnight, after which the skin area of application was washed with water to remove any residual TMA.
Controls included:
- a clipped, occluded, untreated group;
- powder Trimellitic acid ( (20 mg) treated group;
- and TMA treated but gauze occluded group (gauze was placed in between the tape and TMA treated skin to test whether the tape occlusion could alter dermal/TMA interaction).
Dose-response and antibody production time course studies following single and multiple TMA applications were conducted.
- Dose–response relationship after TMA exposure: dry TMA powder at doses of 0, 0.3, 1.25, 5 and 20 mg was applied topically to BN rats (n=8/dose) on days 0, 7, 14 and 21. Blood was collected, intracardially, after anesthetization on day 35 for serum-specific IgE and IgG analyzes.
- Time course of antibody formation after single TMA exposure: a single TMA dose (20 mg) was applied to the skin of rats (n=8) with blood collected from the tail vein on days 0, 7, 14, 21 and 28 and intracardially on day 35 for serum-specific IgE and IgG analyses.
- Time course of antibody formation after repeated TMA exposure: dry TMA powder (20 mg) was applied to the skin of rats (n=8/group) on days 0, 7, 14 and 21. Blood was collected from the tail veins on days 0, 7, 14, 21 and 28 and intracardially on day 35 for serum-specific IgE and IgG analyzes.
Results and discussion
In vivo (non-LLNA)
Resultsopen allclose all
- Key result
- Reading:
- other: 2 weeks after the last exposure
- Group:
- negative control
- Dose level:
- 0
- No. with + reactions:
- 0
- Total no. in group:
- 8
- Key result
- Reading:
- other: 2 weeks after the last exposure
- Group:
- test chemical
- Dose level:
- 0.30 mg
- No. with + reactions:
- 4
- Total no. in group:
- 8
- Remarks on result:
- positive indication of skin sensitisation
- Key result
- Reading:
- other: 2 weeks after the last exposure
- Group:
- test chemical
- Dose level:
- 1.25 mg
- No. with + reactions:
- 7
- Total no. in group:
- 8
- Remarks on result:
- positive indication of skin sensitisation
- Key result
- Reading:
- other: 2 weeks after the last exposure
- Group:
- test chemical
- Dose level:
- 5 mg
- No. with + reactions:
- 8
- Total no. in group:
- 8
- Remarks on result:
- positive indication of skin sensitisation
- Key result
- Reading:
- other: 2 weeks after the last exposure
- Group:
- test chemical
- Dose level:
- 20 mg
- No. with + reactions:
- 8
- Total no. in group:
- 8
- Remarks on result:
- positive indication of skin sensitisation
- Key result
- Reading:
- other: 2 weeks after the last exposure
- Group:
- test chemical
- Dose level:
- 20 mg
- No. with + reactions:
- 8
- Total no. in group:
- 8
- Remarks on result:
- positive indication of skin sensitisation
- Remarks:
- Occluded with gauze after TMA application
- Reading:
- other: 2 weeks after the last exposure
- Group:
- positive control
- Dose level:
- no positive control
- No. with + reactions:
- 0
- Total no. in group:
- 0
- Remarks on result:
- not measured/tested
Any other information on results incl. tables
TMA particle size:
The repeated analysis of particles suspended in the solution did not change over time suggesting that surface hydrolysis did not alter the particle size. The particle diameter sizes ranged from < 1.88 mm (lower size limit capability of instrument) to 62.15 mm, with a mean +- SD of 2.77 +- 0.94 mm. Greater than 90% of the particles had diameters < 4 mm and very few of the particles (<1%) had diameters > 10 mm.
NMR analysis:
Residual TMA powder was collected from the occlusion tape and the skin surface 20 h after application. Two chemical forms of TMA and the acid hydrolysis product (Trimellitic acid) could be identified and relative amounts quantified by NMR. At the lowest dose (1.25 mg) the predominant species recovered was Type 1 TMA and no hydrolysis product was noted. The hydrolysis product, Trimellitic acid, tended to increase with increasing dose. There was also a dose dependent shift in the type of TMA found. The specific differences between Type 1 and Type 2 TMA could not be distinguished by the NMR methodology used.
See table 1 below.
Specific antibodies
Dose–response Table 1 shows the dose-dependent relationship between TMA exposure and specific antibody response, and the antibody production in the group occluded with gauze after TMA application.
Both the concentration and prevalence (i.e., number of animals that produce TMA specific IgE and IgG) of specific antibodies) were dose-dependent. TMA specific antibodies were not detectable in a powder application control group given the TMA hydrolysis product, Trimellitic acid.
See table2 below.
Time course
TMA-specific IgE and IgG was significantly increased (P<0.001) by day 14 in sera from the BN rats given a single or multiple dermal exposures
(on days 0, 7, 14 and 21) to TMA. Antibody levels peaked after 2 weeks. Multiple TMA exposure produced higher antibody levels than a single exposure and tended to delay the peak response for approximately 1 week.
PCA
The production of TMA-specific IgE was confirmed using the PCA test. Sera from BN rats exposed to 1.25 mg, 5 mg and 20 mg TMA produced positive PCA reactions in naïve Sprague–Dawley rats. Heat treatment of the sera caused loss of PCA reactivity consistent with an IgE-mediated mast-cell activation.
(Fig. 2).
Applicant's summary and conclusion
- Interpretation of results:
- Category 1 (skin sensitising) based on GHS criteria
- Conclusions:
- The data of this study suggest that topical skin exposure to dry TMA powder can induce allergic/immunological sensitization as demonstrated by the production of specific antibodies
- Executive summary:
The present study examines the ability of dry TMA powder to sensitize Brown Norway rats when applied, topically, to the skin.
A patch of hair was carefully clipped with scissors on the rat’s back. Dry TMA powder (0.3, 1.25, 5 and 20 mg) was administered on days 0, 7, 14 and 21, and the area occluded with surgical tape overnight after each application.
Residual powder recovered from the occluded skin was analyzed by proton nuclear magnetic resonance and was still predominantly TMA.
Circulating anti-TMA IgE and IgG were measured by ELISA.
TMA elicited dose-dependent production of specific IgE and IgG. Specific antibodies were detectable 2 weeks after the first TMA exposure and peaked between 3 and 4 weeks.
In conclusion, these results suggest that topical skin exposure to dry TMA powder can induce allergic/immunological sensitization as demonstrated by the production of specific antibodies.
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