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EC number: 246-910-3 | CAS number: 25376-45-8
- 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
Basic toxicokinetics
Administrative data
- Endpoint:
- basic toxicokinetics
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: Comparable to OECD 417 guideline study (GLP)
Data source
Referenceopen allclose all
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 992
- Report date:
- 1992
- Reference Type:
- publication
- Title:
- Route-dependent comparative metabolism of [14C]toluene 2,4-diisocyanate and [14C]toluene 2,4-diamine in Fischer 344 rats
- Author:
- Timchalk C, Smith FA & Bartels MJ
- Year:
- 1 994
- Bibliographic source:
- Toxicol.Appl.Pharmacol. 124: 181-90
Materials and methods
- Objective of study:
- excretion
- metabolism
Test guideline
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 417 (Toxicokinetics)
- GLP compliance:
- yes (incl. QA statement)
Test material
- Reference substance name:
- 4-methyl-m-phenylenediamine
- EC Number:
- 202-453-1
- EC Name:
- 4-methyl-m-phenylenediamine
- Cas Number:
- 95-80-7
- Molecular formula:
- C7H10N2
- IUPAC Name:
- 4-methylbenzene-1,3-diamine
- Details on test material:
- Unlabelled TDA:
- Name of test material (as cited in study report): 2,4-toluene-diamine (2,4-TDA)
- Analytical purity: >99%
- Lot: AX13004AX
- Supplier: Aldrich Chemical Company (Milwaukee, USA)
Radiolabelled TDA:
- Lot No.: 030H9222
- Supplier: Sigma Chemical Company (St Louis, USA)
- Radiochemical purity (if radiolabelling): 97.7%
- Specific activity (if radiolabelling): 20.7 mCi/mmol
- Locations of the label (if radiolabelling): uniformly ring labelled
Constituent 1
- Radiolabelling:
- yes
- Remarks:
- 14C-labeled
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, Kingston, NY, USA
- Weight at study initiation: approximately 200 g
- Individual metabolism cages: yes
- Diet: Rodent Chow ad libitum
- Water: tap water ad libitum
- Acclimation period: one week
ENVIRONMENTAL CONDITIONS
- Photoperiod (hrs dark / hrs light): 12 h/ 12 h
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- water
- Details on exposure:
- PREPARATION OF DOSING SOLUTIONS:
The radiotracer was diluted with non-radiolabeled compound to obtain a target radioactivity of 67 µCi/g of dosing solution. Adequate non-radiolabeled 2,4-TDA was added to the 3 and 60 mg/kg dose solutions to obtain target concentrations of 1 and 20 mg 2,4-TDA/g dosing solution, respectively. The final administration volume was 3ml dosing solution/kg bw.
The dosing solutions were analyzed for radioactivity and 2,4-TDA. The amount of radioactivity in the TDA dose solutions ranged from 83% to 148% of target, and all solutions were within 10% of their target concentration.
- Duration and frequency of treatment / exposure:
- Single exposure
Doses / concentrations
- Remarks:
- Doses / Concentrations:
3 or 60 mg/kg bw
- No. of animals per sex per dose / concentration:
- 4
- Control animals:
- no
- Details on study design:
- Two groups of four male rats each were administered single oral doses of 3 or 60 mg 14C-2,4-TDA/kg of bw. Following oral administration of 14C-2,4-TDA, four rats/group were placed in glass Roth-type metabolism cages, and urine and feces were collected for up to 48 hr and analyzed for radioactivity. At 48 hr post-dosing the rats were sacrificed and selected tissues were collected and analyzed. Pooled urine specimens were analyzed by GC/MS and GC/MS/MS.
- Details on dosing and sampling:
- - Body fluids sampled: urine, feces, cage washes
- Time and frequency of sampling: Urine 12 h intervals, feces 24 h intervals, expired air 24 h
- From how many animals: samples pooled from 4 animals
- Method types for identification:
Liquid Scintillation Counting: determination of overall radioactivity
HPLC-Analysis: separation of urinary metabolites and quantification of 2,4-TDA
GC/MS and GC/MS/MS analysis: analysis of free 2,4-TDA, acid-labile conjugates of 2,4-TDA and mono and diacetyl TDA.
Results and discussion
Toxicokinetic / pharmacokinetic studies
- Details on absorption:
- 93-97% of the administered radioactivity was recovered in urine, feces, tissues, carcass and final cage wash.
Given that the majority of compound is excreted by urine it can be assumed that 14C-TDA is well orally absorbed. - Details on distribution in tissues:
- No data
- Details on excretion:
- The urine was the primary excretion route accounting for ca. 64 % of the administered radioactivity, while 22 - 31 % was recovered in the feces. For all treatment groups the percent radioactivity recovered in the carcass/skin was comparable, accounting for 2 - 5% of the administered dose, and less than 0.5% was recovered in the final cage wash. Comparison of the oral 60 and 3 mg 14 C-2,4-TDA/kg body weight treatment groups indicated no quantitative dose dependent differences in the routes of elimination (table 1).
Half-lives derived from urinary excretion time course:
t1/2 (60mg/kg) = 8h
t1/2 (3mg/kg) = 4.6h
Metabolite characterisation studies
- Metabolites identified:
- yes
- Details on metabolites:
- Monoacetyl 2,4-TDA, Diacetyl 2,4-TDA, free 2,4-TDA and acid-labile conjugates were detected in urine (see table 2).
The amounts of acetylated metabolites and 2,4-TDA detected in the urine from all treatment groups were proportional to the administered dose. Comparison of the ratio between the free + acetylated TDA metabolites with the total acid-labile metabolites indicated that following an oral dose of 60 mg/kg 14C-2,4-TDA approximately 61% of detected metabolites existed as either free or acetylated 2,4-TDA while the remaining 39% existed as other conjugates of 2,4-TDA. Whereas, following the 3 mg/kg dose, between 84% and 87% of the detectable metabolites were identified as either acetylated or free 2,4-TDA. This indicates that at lower doses, 2,4-TDA does not undergo much conjugation other than acetylation.
Any other information on results incl. tables
Table 1: Distribution of radioactivity 48 h after male Fischer 344 rats were given oral doses of 3 or 60 mg 14C-2,4-TDA/kg bw.
Percentage of administered 14C-2,4-TDA | ||
3 mg/kg bw dose group | 60 mg/kg bw dose group | |
Urine | 63.67 ± 15.0 | 64.96 ± 2.47 |
Feces | 30.7 ± 3.78 | 22.57 ± 1.54 |
Skin&Caracass | 2.02 ± 0.36 | 4.62 ± 1.67 |
Cage wash | 0.24 ± 0.11 | 0.49 ± 0.12 |
Recovery | 96.62 ± 12.08 | 92.63 ± 0.67 |
Table 2: Concentration of 2,4 -TDA metabolites expressed as 2,4-TDA equivalents in the 0-12 h urine specimen following oral exposure to 14C-2,4 -TDA; Values are given as µg equivalents 2,4-TDA/ g urine
3 mg/kg bw dose group | 60 mg/kg bw dose group | |
Monoacetyl 2,4-TDA | 1.13 | 24.36 |
Diacetyl 2,4-TDA | 1.88 | 20.34 |
Free 2,4-TDA | 0.73 | 18.03 |
free + acetylated 2,4-TDA | 3.74 | 62.73 |
2,4-TDA acid-labile conjugate | 4.47 | 102.41 |
Table 3: Concentration of 2,4 -TDA metabolites expressed as 2,4 -TDA equivalents in the 0 -12 h urine specimen following oral exposure to 14C-2,4 -TDA; Values are given as absoluteµg equivalents 2,4-TDA.
3 mg/kg bw dose group | 60 mg/kg bw dose group | |
Monoacetyl 2,4-TDA | 6.09 | 247.9 |
Diacetyl 2,4-TDA | 10.13 | 206 |
Free 2,4-TDA | 3.93 | 183.48 |
free + acetylated 2,4-TDA | 20.15 | 638.37 |
2,4-TDA acid-labile conjugate | 24.09 | 1042.18 |
free+acetylated/acid labile | 88% | 62% |
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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