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EC number: 226-164-5 | CAS number: 5307-14-2
Basic toxicokinetics
Administrative data
- Endpoint:
- basic toxicokinetics in vivo
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Reliability:
- 4 (not assignable)
Data source
Reference
- Reference Type:
- publication
- Title:
- Metabolism of the Hair Dye Component, Nitro-p-phenylenediamine, in the Rat
- Author:
- MITSUO NAKAO,*'a YUKIKO GOTOH,a YASUHIKO MATSUKI,a AKIRA HIRATSUKA,b and TADASHI WATABEb
- Year:
- 1 987
- Bibliographic source:
- Chem. Pharm. Bull. 35( 2 ) 785-791 (1987)
Materials and methods
- Objective of study:
- metabolism
- Principles of method if other than guideline:
- In Vivo metabolism of Nitro-p-phenylenediamine orally in rats
- GLP compliance:
- not specified
Test material
- Reference substance name:
- 2-nitro-p-phenylenediamine
- EC Number:
- 226-164-5
- EC Name:
- 2-nitro-p-phenylenediamine
- Cas Number:
- 5307-14-2
- Molecular formula:
- C6H7N3O2
- IUPAC Name:
- 2-nitrobenzene-1,4-diamine
- Reference substance name:
- Nitro-p-phenylenediamine
- IUPAC Name:
- Nitro-p-phenylenediamine
- Details on test material:
- - Name of test material (as cited in study report):Nitro-p-phenylenediamine (2-nitro-1,4-diaminobenzene)- Molecular formula (if other than submission substance):C6-H7-N3-O2- Molecular weight (if other than submission substance):153.1403 g/mole - Substance type:Organic- Physical state:No data available- Impurities (identity and concentrations):No data available
Constituent 1
Constituent 2
- Radiolabelling:
- no
Test animals
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male
Administration / exposure
- Route of administration:
- intraperitoneal
- Vehicle:
- not specified
- Remarks:
- 2 % carboxymethyl cellulose sodium salt
- Details on exposure:
- The rats were injected intraperitoneally with Nitro-p-phenylenediamine dissolved in a 2% carboxymethyl cellulose sodium salt solution were administered at 100 mg/5 ml/kg.
- Duration and frequency of treatment / exposure:
- 1 day
Doses / concentrations
- Remarks:
- Doses / Concentrations:100 mg/kg
- No. of animals per sex per dose / concentration:
- 5
- Control animals:
- not specified
- Positive control reference chemical:
- Data not available
- Details on study design:
- The urine was collected for 24 h. Prior to the collection of the urine, a concentrated solution ofsodium bisulfite had been put in the urine container, so that at the end of 24 h, its final concentration would be 0.2- 0.5%. The combined urine was frozen until use.
- Details on dosing and sampling:
- No data available
- Statistics:
- No data available
Results and discussion
- Preliminary studies:
- No data available
Main ADME results
- Type:
- metabolism
- Results:
- the metabolism of Nitro-p-phenylenediamine appears to proceed through regioselective N-acetylation of the amino groups.
Toxicokinetic / pharmacokinetic studies
- Details on absorption:
- No data available
- Details on distribution in tissues:
- No data available
- Details on excretion:
- No data available
Metabolite characterisation studies
- Metabolites identified:
- yes
- Details on metabolites:
- Nitro-p-phenylenediamine appears to be metabolized successively to N4-acetyl-2-nitro-1,4-diaminobenzene, N4-acetyl-1,2,4-triaminobenzene and N1,N4-diacety1-1,2,4-triaminobenzene by regioselective N4-acetylation and subsequent nitro reduction, followed by regioselective N1-acetylation, because rats given N4-acetyl-2-nitro-1 ,4-diaminobenzene or N4-acetyl-1,2,4-triaminobenzene excreted N1,N4-diacety1-1,2,4-triaminobenzene in the urine. Nitro-p-phenylenediamine might be also metabolized through an alternative pathway to N1,N4-diacety1-1,2,4-triaminobenzene via 1,2,4-triaminobenzene formed by direct nitro reduction, because N1,N4-diacety1-1,2,4-triaminobenzene was excreted as a urinary metabolite in rats given 1,2,4-triaminobenzene or its N1- monoacetylated product. Thus, the metabolism of Nitro-p-phenylenediamine appears to proceed through regioselective N-acetylation of the amino groups.
Bioaccessibility (or Bioavailability)
- Bioaccessibility (or Bioavailability) testing results:
- No data available
Any other information on results incl. tables
Urinary Metabolites of Nitro-p-phenylenediamine and Its Derivatives in the Rat
|
|
|
| Administration | |||||
R1 | R2 | R3 |
| I | II | III | III-I | IV | VI |
|
|
|
| of dose | |||||
NH2 | NO2 | NHAc | (II) | 4.7 | 4.8 | - | - | - | - |
NHAc | NO2 | NH2 | (II-1) | ND | ND | - | - | - | - |
NHAc | NO2 | NHAc | (II-2) | ND | ND | - | - | - | - |
NH2 | NH2 | NHAc | (III) | ND | ND | ND | ND | ND | ND |
NHAc | NH2 | NH2 | (III-1) | ND | ND | ND | ND | ND | ND |
NH2 | NHAc | NH2 | (III-2) | ND | ND | ND | ND | ND | ND |
NHAc | NH2 | NHAc | (IV) | 16.9 | 15.4 | 31.7 | 28.0 | 61.8 | 9.7 |
NH2 | NHAc | NHAc | (IV-1) | ND | ND | ND | ND | ND | ND |
NHAc | NHAc | NH2 | (IV-2) | ND | ND | ND | ND | ND | ND |
NHAc | NHAc | NHAc | (V) | ND | ND | ND | ND | ND | ND |
R1, R2and R3represent the substituents at the 1-, 2-, and 4-position of the benzene nucleus, respectively. ND: Not detectable (≤ 0.1 ‘’ ,, of dose compounds).
Applicant's summary and conclusion
- Conclusions:
- Interpretation of results (migrated information): low bioaccumulation potential based on study resultsNitro-p-phenylenediamine expected to have Low bio-accumulation potential based on study results.
- Executive summary:
In a in vivo metabolism study, Sprague-Dawley were treated with Nitro-p-phenylenediamine dissolved in a 2% carboxymethyl cellulose sodium salt solution at 100 mg/5 ml/kginjected intraperitoneally. Nitro-p-phenylenediamineappears to be metabolized successively to N4-acetyl-2-nitro-1,4-diaminobenzene, N4-acetyl-1,2,4-triaminobenzene and N1,N4-diacety1-1,2,4-triaminobenzene by regioselective N4-acetylation and subsequent nitro reduction, followed by regioselective N1-acetylation, because rats given N4-acetyl-2-nitro-1 ,4-diaminobenzene or N4-acetyl-1,2,4-triaminobenzene excreted N1,N4-diacety1-1,2,4-triaminobenzene in the urine.Nitro-p-phenylenediaminemight be also metabolized through an alternative pathway to N1,N4-diacety1-1,2,4-triaminobenzene via 1,2,4-triaminobenzene formed by direct nitro reduction, because N1,N4-diacety1-1,2,4-triaminobenzene was excreted as a urinary metabolite in rats given 1,2,4-triaminobenzene or its N1- monoacetylated product. Thus, the metabolism ofNitro-p-phenylenediamineappears to proceed through regioselective N-acetylation of the amino groups. Therefore,Nitro-p-phenylenediamine considered to haveLow bio-accumulation potential based on study results.
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