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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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: 219-330-3 | CAS number: 2416-94-6
- 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:
- experimental study
- Adequacy of study:
- supporting study
- Study period:
- no data
- Reliability:
- 3 (not reliable)
- Rationale for reliability incl. deficiencies:
- other: An other test substance was used, 2,3,6-trimethylphenol was identified as metabolite.
Data source
Reference
- Reference Type:
- publication
- Title:
- Distribution and metabolism of 1,2,4-trimethylbenzene (pseudocumene) in the rat.
- Author:
- Huo Ji-Z et al.
- Year:
- 1 989
- Bibliographic source:
- Xenobiotica 19: 161-170.
Materials and methods
- Objective of study:
- distribution
- metabolism
Test guideline
- Qualifier:
- no guideline followed
- Principles of method if other than guideline:
- Rats were fasted overnight before receiving an oral dose 1,2,4-trimethylbenzene. The animals were transferred to separate metabolism cages and urine was collected over ice for 24 h. Water was freely available during the collection period. Urine or urine hydrolysates were analysed for free and total (conjugated) metabolites using gas-liquid chromatography-mass spectrometry (GLC-MS)
- GLP compliance:
- not specified
Test material
- Reference substance name:
- 1,2,4-trimethylbenzene
- EC Number:
- 202-436-9
- EC Name:
- 1,2,4-trimethylbenzene
- Cas Number:
- 95-63-6
- Molecular formula:
- C9H12
- IUPAC Name:
- 1,2,4-trimethylbenzene
- Details on test material:
- - Name of test material (as cited in study report): 14C-1,2,4-trimethylbenzene (CAS No. 95-63-6),
Constituent 1
- Radiolabelling:
- yes
- Remarks:
- 14C
Test animals
- Species:
- rat
- Strain:
- Wistar
- Sex:
- male
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Weight at study initiation: approximately 200 g
- Fasting period before study: overnight
- Individual metabolism cages: yes
ENVIRONMENTAL CONDITIONS
- No data
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- olive oil
- Details on exposure:
- PREPARATION OF DOSING SOLUTIONS:
0.8mmol ≡ 0.49 µCi/kg in olive oil (48 mg/ml) - Duration and frequency of treatment / exposure:
- once
Doses / concentrations
- Remarks:
- Doses / Concentrations:
Distribution: 0.8mmol ≡ 0.49 µCi/kg in olive oil (48 mg/ml).
Metabolism: 0.08 mmol/kg or 0.8 mmol/kg in olive oil (4.8 or 48 mg/ml).
- No. of animals per sex per dose / concentration:
- 3
- Control animals:
- no
- Positive control reference chemical:
- no
- Details on study design:
- Tissue distribution study:
- Rats received an oral dose of 14C-124TMB, were transferred to separate metabolism cages and killed at different times.
- Samples of blood, major organs, muscle and adipose tissue were removed and weighed. Any urine voided prior to slaughter was also collected. The total weights of muscle, adipose tissue, skin and serum were calculated according to the method of Adolph (1949).
- Approximately 100 mg of each tissue was placed separately in glass screw-cap vials and Soluene® (Packard Instrument Co., 0.5 ml) was added. After sealing, the vials were incubated at 70°C overnight. Highly coloured samples (e.g. spleen, lung) were bleached by the addition of H202 (30% w/v, 0.1 ml) and allowing to stand for at least 1 hour.
- After addition of Insta-Gel® (Packard Instrument Co., 5 ml) the radioactivity was determined in an LKB Rackbeta II liquid scintillation counter operated in the external standard channels ratio mode. Counting efficiency was determined by reference to a previously prepared quench curve.
Metabolism study:
Rats received 124TMB, were transferred to separate metabolism cages and urine was collected over ice for 24 h. Water was freely available during the collection period. Urine samples were stored frozen until required for analysis.
Urine extracts were prepared for analysis of free and total (conjugated) metabolites. Recoveries from urine of rats dosed with 14C-124TMB showed that this method recovered 87.7% (range 86-90%, n=3) of the radioactivity. Urine or urine hydrolysates were analysed by GLC-MS using a Hewlett Packard 5890 GC coupled with an HP 5970 mass selective detector and an HP 59970A data system. - Details on dosing and sampling:
- PHARMACOKINETIC STUDY (Absorption, distribution, excretion)
- Tissues and body fluids sampled (delete / add / specify): blood, major organs, muscle, adipose tissue and urine
- Time and frequency of sampling: 3, 6, 12 and 24 hours after treatment
METABOLITE CHARACTERISATION STUDIES
- Tissues and body fluids sampled (delete / add / specify): urine, faeces, tissues, cage washes, bile
- Time and frequency of sampling:
- From how many animals: (samples pooled or not)
- Method type(s) for identification (e.g. GC-FID, GC-MS, HPLC-DAD, HPLC-MS-MS, HPLC-UV, Liquid scintillation counting, NMR, TLC)
- Limits of detection and quantification:
- Other:
TREATMENT FOR CLEAVAGE OF CONJUGATES (if applicable): - Statistics:
- no data
Results and discussion
Toxicokinetic / pharmacokinetic studies
- Details on absorption:
- No data
- Details on distribution in tissues:
- 14C-124TMB was rapidly and widely distributed throughout the body with the highest levels in adipose tissue. No other preferential uptake of 14C-124TMB by any of the organs or tissues examined was evident. Tissue levels declined rapidly within 24h after dosage, with more than 99% of the administered radioactivity recovered in the urine during this period.
- Details on excretion:
- No data
Metabolite characterisation studies
- Metabolites identified:
- yes
- Details on metabolites:
- 2,3,6-trimethylphenol was identified as a metabolite of 124TMB.
A complex mixture of isomeric trimethylphenols, dimethylbenzyl alcohols, dimethylbenzoic acids and dimethylhippuric acids excreted in the urine accounted for more than 81% of the administered dose. The major metabolites were 3,4-dimethylhippuric acid (30.2 %dose), 2,4 -dimethylbenzyl alcohol (12.7% dose, primarily as sulphate and glucuronide conjugates) and 2,5-dimethylbenzyl alcohol (11.7% dose, primarily as sulphate and glucuronide conjugates). The influence of steric factors on oxidation at aromatic carbon adjacent to methyl substituent site appears to be minimal given that the proportion of the phenolic metabolites, including 2,3,6-trimethylphenol with 4.0 % are formed in approximately equal proportions.
Applicant's summary and conclusion
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.