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EC number: 204-539-4 | CAS number: 122-39-4
- 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
Description of key information
Two studies from the same authors (Lenz et al., 1990 and 1991), conducted with accepted scientific principles, were used for the evaluation of the oral acute toxicity. Lenz et al., 1990, the selected key study, evaluated the nephrotoxicity of DPA in male Syrian hamsters, male Sprague-Dawley rats, and male Mongolian gerbils, by administering doses of 400, 600 and 800 mg/Kg bw intraperitonally or orally. Lenz et al. 1991, the supporting study, assessed the renal papillotoxicity of diphenylamine dissolved in DMSO, investigated in male Surian hamsters, male Sprague-Dawley rats and female Mongolian gerbils.
Key value for chemical safety assessment
Acute toxicity: via oral route
Link to relevant study records
- Endpoint:
- acute toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- supporting study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Acceptable, well documented publication which meets basic scientific principles
- Qualifier:
- no guideline followed
- Principles of method if other than guideline:
- The renal papillotoxicity of diphenylamine dissolved in DMSO was investigated in male Surian hamsters, male Sprague-Dawley rats and female Mongolian gerbils
- GLP compliance:
- not specified
- Limit test:
- no
- Species:
- other: hamsters, rats, gerbils
- Strain:
- other: Syrian, Sprague-Dawley, Mongolian
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS (Male Hamsters)
- Source: Harlan Sprague-Dawley, Indianapolis, USA
- Weight at study initiation: 50-65 g
- Housing: 5 animals/plastic box
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 5 d
TEST ANIMALS (Male Rats)
- Source: Harlan Sprague-Dawley, Indianapolis, USA
- Weight at study initiation: 50-75 g
- Housing: 5 animals/plastic box
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 5 d
TEST ANIMALS (Female Gerbils)
- Source: Tumblebrook Frams, West Brookfield, USA
- Weight at study initiation: 40-55 g
- Housing: 5 animals/plastic box
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 5 d
ENVIRONMENTAL CONDITIONS (all)
- Temperature (°C): 22
- Humidity (%): 50-60
- Photoperiod (hrs dark / hrs light): 12/12 - Route of administration:
- oral: gavage
- Vehicle:
- other: DMSO (experiments 1,2) and peanut oil (experiment 3)
- Details on oral exposure:
- MAXIMUM DOSE VOLUME APPLIED: 0.5 ml/100 g bw/day
- Doses:
- Experiment 1 (all species): 400, 600 and 800 mg/kg bw/day (single oral dose for 9 consecutive d)
Experiment 2 (Hamsters + Rats): 400, 600 and 800 mg/kg bw/day ( single ip injection for 3 consecutive d)
Experiment 2 (Gerbils): 0, 50, 100, 200, 400, 600 and 800 mg/kg bw/day (single ip injection for 3 consecutive d)
Experiment 3 (Hamsters): 400, 600 and 800 mg/kg (single oral dose for 3 consecutive d) 1 h after or not an oral dose of 0.5 ml/100 g bw DMSO - No. of animals per sex per dose:
- Experiment 1 (all species): 30 animals/dose + 15 animals in a control group
Experiment 2 (Hamsters + Rats): 10 animals/dose + 5 animals in a control group
Experiment 2 (Gerbils): 5 animals/dose
Experiment 3 (Hamsters): 10 animals/dose - Control animals:
- yes
- Statistics:
- chi-square test, P<0.05
- Mortality:
- Experiment 1: Few of animals dosed orally died as a result of chemical-related toxicity
Experiment 2: Most of the hamsters (50 %), rats (83 %) and gerbils (97 %) died within 12-20 hr of the first or second ip dose
Experiment 3: No animals died in the groups given DMSO before diphenylamine - Clinical signs:
- other: other:
- Conclusions:
- The concurrent oral administration of DMSO could reduce the renal papillotoxicity of diphenylamine in male Syrian hamsters, whereas Mongolian gerbils seem to be refractory to diphenylamine-induced renal papillary necrosis, irrespective of the vehicle.
- Endpoint:
- acute toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Acceptable, well documented publication which meets basic scientific principles
- Qualifier:
- no guideline followed
- Principles of method if other than guideline:
- The nephrotoxicity of diphenylamine, the parent compound of the mefenamate family of nonsteroidal anti-inflammatory drugs, was evaluated in male Syrian hamsters, male Sprague-Dawley rats, and male Mongolian gerbils
- GLP compliance:
- not specified
- Limit test:
- no
- Species:
- other: Hamster, Rat, Gerbil
- Strain:
- other: Syrian, Sprague-Dawley, Mongolian
- Sex:
- male
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS (Hamsters)
- Source: Harlan Sprague-Dawley, Indianapolis, IN
- Weight at study initiation: 80-120 g
- Housing: 5 animals/box with wood shavings for bedding
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 5 d
TEST ANIMALS (Rats)
- Source: Harlan Sprague-Dawley, Indianapolis, IN
- Weight at study initiation: 150-175 g
- Housing: 5 animals/box with wood shavings for bedding
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 5 d
TEST ANIMALS (Gerbils)
- Source: Tumblebrook Farms, West Brookfield, MA),
- Weight at study initiation: 45-55 g
- Housing: 5 animals/box with wood shavings for bedding
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 5 d
ENVIRONMENTAL CONDITIONS (all)
- Temperature (°C): 22
- Photoperiod (hrs dark / hrs light): 12/12 - Route of administration:
- other: oral gavage and intraperitoneal injection
- Vehicle:
- peanut oil
- Doses:
- Experiment 1: 400, 600 and 800 mg/kg bw/day (single daily gavage)
Experiment 2: 400, 600 and 800 mg/kg bw/day (single daily ip injection) - No. of animals per sex per dose:
- Experiment 1: 10 animals/dose + 10 animals in a control group
Experiment 2: 10 animals/dose + 5 animals in a control group - Control animals:
- yes
- Details on study design:
- - Duration of observation period following administration: 3 consecutive days of administration + 24 hr observation
- Necropsy of survivors performed: yes - Sex:
- male
- Dose descriptor:
- LD50
- Effect level:
- ca. 600 mg/kg bw
- Based on:
- not specified
- Remarks on result:
- other: Syrian hamsters
- Sex:
- male
- Dose descriptor:
- LD50
- Effect level:
- > 800 mg/kg bw
- Based on:
- not specified
- Remarks on result:
- other: Sprague-Dawley rats
- Sex:
- male
- Dose descriptor:
- LD50
- Effect level:
- > 800 mg/kg bw
- Based on:
- not specified
- Remarks on result:
- other: Mongolian gerbils
- Mortality:
- Experiment 1
- Syrian hamsters: 4/10 (400 mg/kg/d) and 10/10 (600 and 800 mg/kg/d)
-Sprague-Dawley rats and Mongolian gerbils: no mortality
Experiment 2:
- Syrian hamsters: 0/10 (400 mg/kg/d), 5/10 (600 mg/kg/d) and 4/10 (800 mg/kg/d) - Clinical signs:
- other: other:
- Gross pathology:
- Syrian hamsters: brown kidneys and yellow-brown papilla at the highest doses
Sprague-Dawley rats: no significant lesions
Mongolian gerbils: no gross lesions - Interpretation of results:
- harmful
- Remarks:
- Migrated information Criteria used for interpretation of results: not specified
- Conclusions:
- Syrian hamster is more susceptible to the papillotoxic effects of diphenylamine than the Sprague-Dawley rat and the Mongolian gerbil.
The male Syrian hamster may prove useful as an alternative experimental rodent model of non-steroidal, anti-inflammatory, drug-induced papillary necrosis
Referenceopen allclose all
When diphenylamine in DMSO was administered orally to hamsters, the incidence of renal papillary necrosis was almost zero.
Hamsters pretreated with DMSO had significantly reduced incidences of papillary necrosis.
Renal papillary necrosis was not observed in any of the Mongolian gerbils
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed
- Dose descriptor:
- LD50
- Value:
- 800 mg/kg bw
- Quality of whole database:
- K2
Acute toxicity: via inhalation route
Endpoint conclusion
- Endpoint conclusion:
- no study available
Acute toxicity: via dermal route
Endpoint conclusion
- Endpoint conclusion:
- no study available
Additional information
According the results of the key study, the LD50 from the male Sprague-Dawley rats was > 800 mg/Kg bw based on oral route.
Justification for classification or non-classification
Regarding the selected oral acute toxicity LD50, DPA should be classified "Acute Toxicity Category 4" according to the CLP Regulation.
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