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EC number: 202-951-9 | CAS number: 101-54-2
- 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
Endpoint summary
Administrative data
Link to relevant study record(s)
Description of key information
Key value for chemical safety assessment
Additional information
In vitro studies
In vitro studies with everted rat intestine showed that 4-Aminodiphenylamine (4-ADPA) passes from the mucosal to the serosal side of gut in a concentration dependent manner, probably by passive diffusion (Raza 1982a).
In vitro studies demonstrated that 4-ADPA can be bound to proteins and collagen in rat skin (Khanna 1987, Tewari 1989). 4-ADPA binds to liver tissue proteins after incubation of liver slices (Srivastava 1982a) and to mucosal proteins of everted gut sacs (Raza 1982b). The 4-ADPA protein association is dependent from pH, the presence of metal ions and the absence of reducing agents. The authors suggested formation of a quinine structure which then binds to dicaboxylic acids of the proteins (Raza 1982b, Srivastava 1982a). In vitro studies on the binding of 4-ADPA to rat serum proteins showed that 4-ADPA has a higher binding affinity to serum globulin than to serum albumin. Electrophoretic studies indicated a stable binding involving electrostatic forces and hydrophobic interactions (Raza 1983).
In vivo studies
The absorption and elimination of 4-Aminodiphenylamine (4-ADPA) were evaluated in female CD® rats. Groups of four female rats received single doses of 14C labeled 4-ADPA by the oral (gavage), dermal or intravenous routes. In order to investigate whether the vehicle has an influence on the absorption of 4-ADPA from the gastro-intestinal tract, one group was given the test substance (200 mg/kg bw) in corn oil, and another group received the same dose in propylene glycol. In-life blood samples were taken from each animal 2 hours after dosing, and then in 24-hours intervals until sacrifice. Samples of urine and feces were collected from each animal at 24-hour intervals. The body burden of 14C at the end of the 7day observation period was determined by analyzing blood and carcasses. The use of propylene glycol caused a significant increase in the amount of 4-ADPA derived radioactivity excreted in the urine as compared to corn oil, which, according to the authors, may have been the result of an about 1.4 times greater absorption of 4-ADPA from the propylene glycol preparation as compared to the corn oil preparation. Peak blood concentrations of 4-ADPA derived radioactivity from the propylene glycol vehicle were almost double that of corn oil vehicle, and were not reached until 24 hours after dosing. The half-life of 4-ADPA in the blood was calculated as 11.6 days for 4-ADPA derived radioactivity from the corn oil preparation and 13.7 days for ADPA derived radioactivity from propylene glycol preparation. Plasma clearance after intravenous injection (2 mg/kg bw) consist of a short alpha-phase with a half-life of less than one day, followed by much longer beta phase of 12 days. The bioavailability of 4-ADPA in the 4-ADPA/corn oil animals was only about 54 % of those administered 4-ADPA in propylene glycol.
About 20 % of the applied dermal dose (2 mg/kg bw in ethanol) was absorbed through the skin. Approximately 80 % of the oral dose in corn oil, 88% of the oral dose in propylene glycol, 80% of the intravenous and 15 % of the dermal dose were eliminated in the urine and feces (combined) over the 7 day observation period. Independent of the route of administration, the majority of the test substance derived radioactivity was eliminated in the feces (urine: feces ratio 1:2) (Monsanto Co.1991a).
Human information
No quantitative information is available on the extent of absorption and excretion of 4-ADPA in humans. From biological monitoring it is known that 4-ADPA can be detected in the urine and haemoglobin adducts in blood (Bayer AG 2003). Following an accidental dermal exposure to an unidentified amount of the substance, 4-ADPA was detected in the urine of the affected worker (Bayer AG 2003).
Summary and discussion on toxicokinetics
4-Aminodiphenylamine (4-ADPA) can be taken up into the body by the oral and dermal routes of exposure as evidenced by the results of animal studies. About 20 % of the applied dermal dose was shown to be absorbed through the skin, whereas the respective absorption was ca. 80 % of the oral dose In rats the substance and/or its metabolites are eliminated mainly with the feces but can also be detected in the urine. An indirect evidence of dermal absorption in humans is provided by the detection of 4-ADPA in the urine of one worker after single dermal contact with the substance. 4-ADPA can bind to haemoglobin and protein.
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