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Diss Factsheets
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EC number: 701-017-2 | CAS number: -
- 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
- 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: Comparable to OECD 417 guideline study (GLP)
Cross-reference
- Reason / purpose for cross-reference:
- reference to other study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 987
- Report date:
- 1987
Materials and methods
- Objective of study:
- absorption
- distribution
- excretion
- metabolism
Test guideline
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 417 (Toxicokinetics)
- GLP compliance:
- yes
Test material
- Reference substance name:
- m-tolylidene diisocyanate
- EC Number:
- 247-722-4
- EC Name:
- m-tolylidene diisocyanate
- Cas Number:
- 26471-62-5
- IUPAC Name:
- 2,4-diisocyanato-1-methylbenzene
- Details on test material:
- Unlabeled:
- Name of test material (as cited in study report): Technical grade TDI (Mondur TD-80)
- Isomers composition: ca. 80% 2,4-TDI, ca. 20% 2,6-TDI
- Supplier: Mobay Chemical Corporation
Labeled
- Isomers composition: 82% 2,4-TDI; 18% 2,6-TDI
- Lot/batch No.: 84-68-19
- Supplier: Midwest Research Institute
- Radiochemical purity: >=99%
- Specific activity: 23.5 mCi/mmol
- Storage condition of test material: frozen at -80°C
Constituent 1
- Radiolabelling:
- yes
- Remarks:
- 14C
Test animals
- Species:
- rat
- Strain:
- Fischer 344
- Sex:
- male
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River Breeding Laboratory
- Age at study initiation: 51-53 days
- Weight at study initiation: 128-143 g
- Housing: Polycarbonate cages on Ab-Sorb-Dri hardwood chip bedding
- Individual metabolism cages: yes
- Diet: Purina rodent chow ad libitum
- Water: tap water ad libitum
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 + / - 1.5
- Humidity (%): 50 + / - 15%
- Air changes (per hr): 10 - 15
- Photoperiod (hrs dark / hrs light): 12/12
Administration / exposure
- Route of administration:
- inhalation: vapour
- Vehicle:
- unchanged (no vehicle)
- Details on exposure:
- TYPE OF INHALATION EXPOSURE: glass chamber designed for head only exposure
GENERATION OF TEST ATMOSPHERE
The 14C-TDI atmosphere was generated by continuously bubbling dried air through a micro-generator containing 14C-TDI. The doses were prepared by transferring neat 14C-labeled TDI directly into the micro-generator. Volumes were determined by weight. In preparing the high dose, measured amounts of nonlabeled TDI were added to the micro-generator. The ideal volume of material in the micro-generator was ca. 0.175 mL and the maximum flow rate of air through the micro-generator was 200 cm3/min. During exposure, the micro-generator was kept in a constant temperature water bath (25-28°C). Airflow through the exposure chamber was controlled by the exhaust pump. The minimum exhaust rate was one air exchange per minute (1000 cm3/min). TDI was removed from the exhaust air by first bubbling the air through aliquots of ethylene glycol monoethyl ether and Marcali absorbing solutions in four serial impingers, and then adsorbance onto activated charcoal. The solvent solution was frozen at -20°C for later extraction.
Chamber atmospheres of TDI were monitored every 30 min during the 4-hr exposure with concentration analyzed by the Marcali method. The adjustion of the concentration was conducted by variation of the air flow through the chamber (exhaust rate) and/or the air flow through the generator (generation rate).
The Marcali method is resulting in a one value for both TDI-isoforms. No differentiation between 2,4-TDI and 2,6-TDI is possible. - Duration and frequency of treatment / exposure:
- 4 h
Doses / concentrations
- Remarks:
- Doses / Concentrations:
0.6 ppm, 2 ppm (0.004272 mg/l; 0.01424 mg/l conversion according to "The toxicologist's pocket handbook", Derelanko, Informa Healthcare, 2008)
- No. of animals per sex per dose / concentration:
- 4
- Control animals:
- no
- Details on dosing and sampling:
- - following exposure animals were placed in metabolic cages for tissue and body fluid sampling
- Tissues and body fluids sampled: urine, feces, cage washes, expired CO2, tissues (liver, pancreas, nasal tissues, kidneys, spleen, skin (ears), lungs, adrenals, skeletal muscle, brain, testes, retroperitoneal fat, heart, thyroids, GI tract plus contents, carcass homogenates)
- Sacrifice:
one rat of each dose was sacrificed at the end of exposure or 4 h, 24 h and 96 h following exposure
- Sampling:
from rats sacrificed at 24 h, serial blood samples were taken by tail bleeding at 0, 0.5, 1, 2, 4, 6, 12, 24 h.
from rats sacrificed at 96 h urine and feces were sampled at 6, 12, 48 and 96 h
- Method types for identification:
Marcali method (indirect, colorimetric assay) for determination of the TDI concentration in the test atmosphere
Liquid scintillation counting for determination of overall radioactivity
High performance liquid chromatography for metabolic profiling / peak determination
Thin layer chromatography for metabolic profiling / differentiation of polar and non-polar metabolites
Results and discussion
Toxicokinetic / pharmacokinetic studies
- Details on absorption:
- It is assumed that 100% of the TS inhaled is absorbed.
- Details on distribution in tissues:
- Most of the radioactivity was recovered in the GI tract. The concentration peaked after 4 h reaching 39.6 % (0.6 ppm) and 38.8 % (2 ppm), after 96 h this concentration declined to 1.5 % (0.6 ppm) and 2.2 % (2 ppm).
Furthermore the concentrations in blood, plasma and nasal tissue and lungs were highest directly after exposure (2.6% [blood], 1.8% [plasma], 2.1% [nasal tissue], 0.3% [lungs] for the 0.6 ppm dose; 2.1% [blood], 1.2% [plasma], 1.2% [nasal tissue] and 2.2% [lungs] for the 2 ppm dose). Those concentrations declined during the next 96 h to 0.5%, 0.3% 0.8% and 0.06% (0.6 ppm) or 0.4%, 0.2%, 0.026% and 0.2% (2 ppm). The concentrations of the remaining tissues were below 1%.
- Details on excretion:
- Urinary excretion was most rapid over 0 to 6 hr but was still continuing at 96 hr. More than 50% of the dose is excreted by feces, independently of the dose. The urinary excretion was ca. 24% for the 0.6 ppm dose and ca. 20% for the 2 ppm dose (see table 1).
Metabolite characterisation studies
- Metabolites identified:
- no
- Details on metabolites:
- Chromotagraphic profiles of urine, feces and gastrointestinal contents were obtained. The HPLC profiles were complex therefore metabolite identification was not attempted. For comparison radioactivity was divided in polar and nonpolar. More polar products were recovered from the urine. There were no apparent differences in the distribution of polar and nonpolar products due to dose.
Any other information on results incl. tables
Table 1: Recovery of 14C (% of the dose) following a 4 h exposure to 14C-toluene diisocyanate
0.6 ppm | 2 ppm | |||||||
Tissue/ Excretum | 0 h | 4 h | 24 h | 96 h | 0 h | 4 h | 24 h | 96 h |
Blood | 2.623% | 1.730% | 1.642% | 0.541% | 2.107% | 1.265% | 0.911% | 0.359% |
Tissue | 4.480% | 2.902% | 5.955% | 1.637% | 5.207% | 3.661% | 2.707% | 1.147% |
GI tract | 12.693% | 39.612% | 16.248% | 1.473% | 6.551% | 38.784% | 12.917% | 2.228% |
Urine | not sampled | 5.761% | 17.475% | 24.095% | not sampled | 2.461% | 13.531% | 19.894% |
Feces | not sampled | 0.020% | 21.046% | 54.073% | not sampled | not sampled | 26.240% | 52.716% |
Carcass | 80.194% | 49.959% | 37.590% | 18.130% | 86.131% | 53.828% | 43.674% | 23.638% |
Recovery | 99.990% | 99.984% | 99.956% | 99.949% | 99.996% | 99.999% | 99.980% | 99.982% |
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.
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