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EC number: 202-974-4 | CAS number: 101-77-9
- 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:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- study well documented, meets generally accepted scientific principles, acceptable for assessment
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 986
- Report date:
- 1986
Materials and methods
- Objective of study:
- distribution
- excretion
- Principles of method if other than guideline:
- 9 male Fischer rats were exposed intravenously to 2 mg/kg labeled 14C-MDA. Excreta and urine was collected after 6, 12, 24, 48, 72, and 96 h. After various time points rats were sacrificed and tissue distributon was determined.
- GLP compliance:
- not specified
Test material
- Reference substance name:
- 4,4'-methylenedianiline
- EC Number:
- 202-974-4
- EC Name:
- 4,4'-methylenedianiline
- Cas Number:
- 101-77-9
- Molecular formula:
- C13H14N2
- IUPAC Name:
- 4,4'-methylenedianiline
Constituent 1
- Specific details on test material used for the study:
- SOURCE OF TEST MATERIAL
- Source and of test material: Aldrich Chemical Company
RADIOLABELLING INFORMATION
- Radiochemical purity: >99% (analysed by HPLC and TLC)
- Specific activity: 14.8 mCi/mmol
- Locations of the label: Ring-labeled 14C-methylenedianiline was prepared by the radiochemical synthesis section of MRI.
OTHER
The compound was received as the free base (3.2 mCi) in 100% ethanol or as the hydrochloride (8.18 mCi). - Radiolabelling:
- yes
- Remarks:
- 14C
Test animals
- Species:
- rat
- Strain:
- Fischer 344
- Sex:
- male
- Details on test animals or test system and environmental conditions:
- - Adult rats were purchased from Charles River Laboratories, North Wilmington, Massachusetts.
- Housing: 10-15 air changes per hour in polycarbonate cages
- Temperature/humidity: 72°C ±2/50% ±10
- 12h-Light/dark cycle
- Acclimatisation time: 7 days
- Diet: Purina Certified Rodent Chow (Ralston Purina Company)
- Drinking water ad libitum
- Weight: 149-218 g
Administration / exposure
- Route of administration:
- intravenous
- Vehicle:
- other: ethanol/water (1:4)
- Duration and frequency of treatment / exposure:
- single dose
Doses / concentrations
- Remarks:
- Doses / Concentrations:
2 mg/kg bw (0.4 ml per animal)
- No. of animals per sex per dose / concentration:
- 9 male rats
- Control animals:
- no
- Details on study design:
- Rats were treated and placed in individual metabolism cages.
- Details on dosing and sampling:
- Dosing was performed through the saphenous vein.
Excreta was collected after 6, 12, 24, 48, 72, and 96 h following administration. Three animals were sacrificed at 6, 24, and 96 h for tissue sampling. Urine was collected in containers kept on dry ice. After collection cages were rinsed and cage washings were analyzed. The animals were sacrificed and blood, tissue and organs were removed. Tissue and organs were washed with saline, blotted with absorbing paper, weighed and prepared for radiochemical analysis. All samples were kept on dry ice during necropsy.
Results and discussion
- Preliminary studies:
- In a preliminary study (data not shown) the appropriate sampling times were selected and the methods of treatment and sampling determined.
In 3 rats most (approx. 95%) of the i.v. dose was eliminated in urine and feces during a 96-h period following dosing.
Toxicokinetic / pharmacokinetic studies
- Details on distribution in tissues:
- Significant amounts of radioactivity (24% at 6h) were recovered in the GI tract, probably through the bile. Blood and tissue contained 19% of the doses at 6h, but their 14C contents declined to 2% of the doses at 96h. The highest 14C-concentrations were demonstrated in the liver (9.5%, 4-9 times the blood level).
- Details on excretion:
- Total recoveries in excreta and tissue averaged 98.3, 98.1, and 99.3% at 6, 24, and 96 h after dosing.
During 96 h following i.v. dosing, 67.0 and 30.7% of doses were eliminated in urine and feces, respectively.
Metabolite characterisation studies
- Metabolites identified:
- not specified
- Details on metabolites:
- No data
Any other information on results incl. tables
Table 1: Recovery of radioactivity in rats treated i.v. with 4,4´-MDA.
recovery |
Percent of dose |
||
dose |
0.4 mg/rat, i.v |
||
time |
6h |
24h |
96h |
blood |
2.8 |
0.44 |
0.22 |
tissue |
16.6 |
4.33 |
1.31 |
GI tract |
23.94 |
4.14 |
0.11 |
urine |
54.65 |
67.35 |
66.96 |
feces |
0.28 |
21.79 |
30.66 |
total absorbed |
98.27 |
98.06 |
99.25 |
dose wash |
- |
- |
- |
application area |
- |
- |
- |
recovery |
98.27 |
98.06 |
99.25 |
Table 2: Radioactivity in blood, tissue, and excreta of rats at 6 and 96 h following intravenous dose (0.4 mg) of 14C-MDA.
n=3 | % of dose (6h) | % of dose (96h) |
Blood | 2.8 | 0.22 |
Plasma | 1.97 | 0.10 |
RBCs | 0.55 | 0.09 |
Liver | 9.47 | 0.86 |
Kidney | 0.48 | 0.03 |
Lungs | 0.26 | 0.02 |
Brain | 0.08 | 0.00 |
Spleen | 0.09 | 0.02 |
Testes | 0.26 | 0.00 |
Adrenals | 0.01 | 0.00 |
Bladder | 0.00 | 0.00 |
Muscle | 2.77 | 0.21 |
Fat | - | - |
GI tract | 23.94 | 0.11 |
Nontreated skin | 3.19 | 0.16 |
Urine | 54.65 | 66.96 |
Feces | 0.28 | 30.66 |
Dose wash | - | - |
Application area | - | - |
Recovery | 98.27 | 99.25 |
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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