Registration Dossier
Registration Dossier
Data platform availability banner - registered substances factsheets
Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.
The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.
Diss Factsheets
Use of this information is subject to copyright laws and may require the permission of the owner of the information, as described in the ECHA Legal Notice.
EC number: 500-109-8 | CAS number: 43011-20-7
- 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
Basic toxicokinetics
Administrative data
- Endpoint:
- basic toxicokinetics in vivo
- Type of information:
- migrated information: read-across based on grouping of substances (category approach)
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Scientifically valid study but predates establishment of guideline methods; not performed under GLP.
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 988
- Report date:
- 1988
Materials and methods
- Objective of study:
- toxicokinetics
Test guideline
- Qualifier:
- no guideline available
- Principles of method if other than guideline:
- Inhalation exposure of radiolabelled test material to rats, with time course assessment of tissue accumulation and elimination in various organs. Additionally, TMA-specific serum antibodies were quantitated for the 32 days after exposure.
- GLP compliance:
- no
Test material
- Reference substance name:
- trimellitic anhydride
- IUPAC Name:
- trimellitic anhydride
- 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-1,3-dihydro-2-benzofuran-5-carboxylic acid
- Test material form:
- aerosol dispenser: not specified
- Remarks:
- migrated information: aerosol
- Details on test material:
- 14C-trimellitic anhydride (TMA), lot No. 2031-236 was synthesized by NE England Nuclear, Boston, MA. The radiolabel was in the 2-carbonyl position. The specific activity was 13.5 mCi/mmole and the radiochemical purity wa 97% by TLC. The test article was stored in a tightly sealed opaque jars in a ventilated cabinet, at room temperature, 22 degrees C.
Constituent 1
Constituent 2
- Radiolabelling:
- yes
- Remarks:
- specific activity was 13.5 mCi 14C-TMA/mmole
Test animals
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River Breeding Laboratories, Portage, MI
- Age at study initiation:
- Weight at study initiation: 135 g
- Fasting period before study:
- Housing: singly housed in disposable plastic cages containing San-I-Cel corn cob bedding.
- Individual metabolism cages: yes/no
- Diet (e.g. ad libitum): ad libitum, Purina Rodent Chow 5001 (Ralston Purina Co., St. Louis, MO)
- Water (e.g. ad libitum): ad libitum, from a reverse-osmosis purifier by means of water bottles
- Acclimation period: 14 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22
- Humidity (%): 40
- Air changes (per hr):
- Photoperiod (hrs dark / hrs light): 12/12
IN-LIFE DATES: From: To: 9 June, 1986 to 11 July 1986
Administration / exposure
- Route of administration:
- inhalation
- Details on exposure:
- A static test atmosphere of the test article was generated by periodically feeding small amounts of the test article into the chamber via a partially encased recirculating blower. As the test article entered the blower encasement, it was blown into the chamber atmosphere and any test article that remained airborn was recirculated through the blower. The remainder of the test article settled on the chamber walls and floor.
The exposure chamber was a 370-liter glass aquarium fitted with a 1/8 inch plexiglass top. The entire chamber was housed in a PVC bag which served as secondary containment. The inhalation chamber, PVC bag, rats and associated materials were contained in a large PVC tent, approximately 8x8x8 ft. - Duration and frequency of treatment / exposure:
- 45 minutes
Doses / concentrations
- Remarks:
- Doses / Concentrations:
950 µg/m3
- No. of animals per sex per dose / concentration:
- 2 per sex per time point
- Details on study design:
- There were seven time points for sacrifice after the 45 minute exposure. Two males and two females were assigned to each time point.
The times were 3 h, 1 day, 2, 4, 8, 16 and 32 days after dosing. - Details on dosing and sampling:
- The dose was approximately 50 µCi of 14 C per rat. The actual concentration of the 14C-TMA in the atmosphere was determined by drawing a known volume of the test atmosphere across an open-face filter. The filter was placed in a vial containing 10% (v/v) acetonitrile in water and shaken for 10 min. A portion of the resultant mixture was injected into an HPLC and compared with known standards for quantitation.
- Statistics:
- The elimination rate constant (Ke) was determined by plotting the natural log (Ln) of the counts per min (cpm) per gram tissue versus the time past exposure and performing a linear fit (RS/1 Statistics, FFN Software Products Corp., Cambridge, MA, USA). Linear regression of the curve yielded a straight line, the negative slope of which equaled the Ke. The half-life (t-1/2) Of the 14C was calculated for each tissue using the following equation: t-1/2 = 0.693/Ke.
Results and discussion
- Preliminary studies:
- The actual concentation of 14C-TMA in the exposure chamber was 950 µg/m3. The fraction of respirable particles was not determined. Preliminary estimates using assumed respiratory rates, tidal volumes and particle retention suggested that the test conditions allowed sufficiently high 14C doses for adequate in vivo detection of radiolabel.
Main ADME results
- Type:
- absorption
- Results:
- Peak absorption was evident at 3 h after dosing. Half-lives ranged from 3 to 46 days for various organs.
Toxicokinetic / pharmacokinetic studies
- Details on absorption:
- The peak concentrations of 14C in the tissues were found at the first time point (3 h after exposure). The concentration rapidly decreased in all tissues in an approximately exponential fashion. Linear regression of the natural log of the concentration vs. time yielded straight lines, indicating exponential decline. The concentration of 14C (cpm/g tissue) generally throughout the time course was found in feces and urine, and the following tissues: popliteal lymph nodes, esophagus, kidneys, intestines, urinary bladder and abdominal skin. Abdominal skin showed the highest consistent radiolabel content of all tissues. Lung tissue did not show a high concentration of radiolabel at 3 h after dosing (comparable to testes, spinal cord and bone marrow).
The half-life values ranged from 4-23 days in males and from 3-46 days in females. Half-lives were lowest for feces and intestines, stomachs and esophagi, and highest for popliteal and lung-associated lymph nodes, spleen, heart, adrenals, brais and bone marrow. The exponential decline was apparent in all tissues except the lung-associated lymph nodes (LALN), where, after an initial decline, there was a second influx of 14C peaking at day 8 and then declining again. This second peak was particularly apparent in male rats. - Details on distribution in tissues:
- Distribution occurred to all organs examined. Radiolabel showed particular accumulation occurring in the kidneys, urine, bladder, feces and esophagus. Half-lives were lowest for feces, intestines, stomachs and esophagi, and highest for popliteal and lung-associated lymph nodes, spleens, hearts, adrenals, brains and bone marrow.
- Details on excretion:
- Almost all tissues exhibited an exponential elimination of 14C. The elimination rate constant (Ke) ranged from 0.015 to 0.214 in female rats. Total urinary and fecal elimination was not reported.
Metabolite characterisation studies
- Metabolites identified:
- no
Applicant's summary and conclusion
- Conclusions:
- Interpretation of results (migrated information): low bioaccumulation potential based on study results
Groups of rats exposed to inhaled 14C-TMA exhibited typical first order exponential decays of 14C with half-lives ranging from 3 to 46 days. C14 was distributed to all tissues examined with particular accumulation occurring in the kidneys, urine, bladder, feces and esophagus. - Executive summary:
Groups of two male and two female Sprague Dawley rats were exposed for 45 minutes to an atmospher of 14C-trimellitic anhydride aerosol (950 µg/m3) with a specific activity of 13.5 mCi/mmole. Exposure was in a sealed 370 -liter chamber wrapped ina PVC bag, and animals and excretia were appropriately handled as radioactive material. Animals were weighed prior to exposure and weekly thereafter, and prior to sacrifice. Daily observations were made for clinical effects. Animals were euthanized at 3 hours, 1 day and 2,4,8,16 and 32 days after exposure and subjected to an extensive necropsy. Organs were removed, weighed, homogenized and aliquots were prepared and counted for radioactivity. Tissues/fluids/excretia were collected and include popliteal lymph nodes, lung-associated lymph nodes (LALN), lungs, trachea, thymus, whole blood, serum, brain, heart, spleen, liver, kidneys, intestines, stomach, urinary bladder, gonads, urine, feces, skin, abdominal skin and fat, bone marrow, pancreas, esophagus, adrenals, spinal cord, bone marrow and leg muscle. The findings were that 14C was distributed to all tissues examined with particularly high counts in the kidneys, urine, bladder, feces and esophagus. The highest radioactivity level was at 3 hours in all tissues and exretia examined. Half-lives ranged from 3 to 46 days and showed exponential decay in most tissues.
In males, the lung-associated lymph nodes showed a different clearance pattern of radiolabel compared to other tissues: two peaks of radioactivity, one at 3 h and one at 8 days. Hence, males showed no exponential decay of radiolabel. This was not evident in females, and is consistent with results in other studies showing higher and more severe lung lesions after TMA exposure as compared with females. Serum antibody analysis, specific against TMA but not isotype specific, showed there was no significant antibody present until 4 -8 days after exposure. Between 8 and 32 days after exposure, 2 of 12 rats developed antibody and were presumably sensitized to TMA. Therefore, the sensitization incidence was 17%. The conclusion from this study is that TMA does not show signs of bioaccumulation or bioconcentration. Most tissue elimination is exponential. There is toxicokinetic evidence of immunological activity against TMA>
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.