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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
Basic toxicokinetics
Administrative data
- Endpoint:
- basic toxicokinetics in vivo
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: GLP study, comparable to guideline study
Data source
Referenceopen allclose all
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 991
- Report date:
- 1991
- Reference Type:
- publication
- Title:
- Oral and dermal absorption studies in Sprague-dayley rats with 4-aminodiphenylamine
- Author:
- Healy CE et al.
- Year:
- 1 993
- Bibliographic source:
- The Toxicologist 13, 1993
Materials and methods
- Objective of study:
- toxicokinetics
- Principles of method if other than guideline:
- Method: other: see Test Condition
- GLP compliance:
- yes
Test material
- Reference substance name:
- N-(4-aminophenyl)aniline
- EC Number:
- 202-951-9
- EC Name:
- N-(4-aminophenyl)aniline
- Cas Number:
- 101-54-2
- Molecular formula:
- C12H12N2
- IUPAC Name:
- N1-phenylbenzene-1,4-diamine
- Details on test material:
- IUCLID4 Test substance: other TS: purity: 98,3% (C14-labeled)
Constituent 1
- Radiolabelling:
- yes
- Remarks:
- 14C
Test animals
- Species:
- rat
- Strain:
- other: CRL:CD(R) (SD) rats
- Sex:
- female
Administration / exposure
- Route of administration:
- other: Oral gavage; Intravenous injection; dermal
- Vehicle:
- other: Corn oil / Propylene glycol; dermal: ethanol; intravenous: emulphor/ethanol mixture
- Duration and frequency of treatment / exposure:
- 7 days for oral administration, 7 days for i.v. administration, 3 days for dermal administration
Doses / concentrations
- Remarks:
- Doses / Concentrations:
Females: 2 mg/kg/bw via intravenous injection and skin
200 mg/kg/bw via oral gavage
- No. of animals per sex per dose / concentration:
- 4/dose/application
- Control animals:
- not specified
Results and discussion
- Preliminary studies:
- 2 groups of 4 females for method development
Main ADME resultsopen allclose all
- Type:
- absorption
- Results:
- 20 % dermal absorption
- Type:
- excretion
- Results:
- Approximately 80% of the oral/corn oil dose, 88% of the oral/propylene glycol dose, 80% of the iv dose, and 15% of the dermal dose were eliminated in the urine and feces
Toxicokinetic / pharmacokinetic studies
- Details on absorption:
- 20 % dermal absorption
- Details on excretion:
- Approximately 80% of the oral/corn oil dose, 88% of the oral/propylene glycol dose, 80% of the iv dose, and
15% of the dermal dose were eliminated in the urine and feces
Any other information on results incl. tables
RS-Freetext:
The total 4-ADPA derived radioactivity recovered in the test animal
Groups 3-6 ranged from 82.0% to 93.9% of the administered dose.
The majority of the test material was eliminated in the feces. The
urine:feces ratio was approximately 1:2. Propylene glycol caused a significant
increase in the amount of activity excreted in the urine as compared to corn oil,which may be a result of increased absorption. There was little difference in
fecal elimination of 4-ADPA derived activity regardless of the method of
treatment, and very little 4-ADPA remained in the carcass. The body burden
of animals administered 4-ADPA via IV injection was significantly greater
than all other routes of administration. For dermal administration,
the majority of activity remained at the site of application. Nearly 42% of
the administered dose was removable with alcohol swabbing. 20% was associated
with the skin, and 8% was associated with the metal cap used to cover the site
of application. Approximately 23% of the absorbed dermal dose was eliminated
in the urine, and 56% in the feces. This indicates that there was little
difference between oral, iv or dermal administration with respect to the
amount eliminated in the urine and feces.
ABSORPTION: Absorption of 4-ADPA in propylene glycol was approximately
1.4 times greater than that of 4-ADPA in corn oil. Based upon urinary
elimination, about 17% of the dose was absorbed through the skin. The
total amount of absorbed 4-ADPA derived activity which was detected in
the urine, feces, carcass, blood, and in the cage washings of dermally-treated
animals was about 20% of the administered dose. The vehicle produced a
significant effect on blood levels. 4-ADPA/corn oil reached a maximum
concentration of 0.5% of the administered dose two hours after gavage.
In contrase, peak blood concentrations of 4-ADPA/propylene glycol were
almost double that of corn oil vehicle, and was not reached until 24 hours
after dosing. These results indicate that the rate of absorbtion of
4-ADPA/propylene glycol was faster, and the total amount absorbed was greater
than that of 4-ADPA/corn oil.
BLOOD CLEARANCE: The halflife of 4-ADPA in the blood was calculated as
11.6 days for 4-ADPA/corn oil and 13.7 days for 4-ADPA/propylene glycol.
Plasma clearance after iv injection consisted of a short alpha phase with
a halflife <1 day, followed by a much longer beta phase of 12 days. There
was about a 1.8 fold increase in the area under the blood elimination
curve from animals that received 4-ADPA/propylene glycol compared to
those treated with 4-ADPA/corn oil. The bioavailability of material in
the 4-ADPA/corn oil animals was about 54% of those administered
4-ADPA/propylene glycol.
WHOLE BODY ELIMINATION: Treatment had little effect on the profile of
total urinary and fecal elimination. Approximately 80% of the oral/corn
oil dose, 88% of the oral/propylene glycol dose, 80% of the iv dose, and
15% of the dermal dose were eliminated in the urine and feces combined
over the 7 day observation period.
Applicant's summary and conclusion
- Executive summary:
The absorption and elimination of 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 1991).
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