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Diss Factsheets

Administrative data

Endpoint:
basic toxicokinetics in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
4 (not assignable)

Data source

Reference
Reference Type:
publication
Title:
Characterization of N-Acetylcysteine conjugate in yellow urine by oral administration of 1,4-Dichloro-2-Nitrobenzene
Author:
Makoto Ohnishi,a Kazunori Yamazaki, Seigo Yamamoto, and Taijiro Matsushima
Year:
2004
Bibliographic source:
Journal of health science, 50 (3) 319-322 (2004)

Materials and methods

Objective of study:
metabolism
Principles of method if other than guideline:
In Vivo Metabolism of 1,4-Dichloro-2-Nitrobenzene in F344/DuCrj male rats
GLP compliance:
not specified

Test material

Constituent 1
Chemical structure
Reference substance name:
1,4-dichloro-2-nitrobenzene
EC Number:
201-923-3
EC Name:
1,4-dichloro-2-nitrobenzene
Cas Number:
89-61-2
Molecular formula:
C6H3Cl2NO2
IUPAC Name:
1,4-dichloro-2-nitrobenzene
Details on test material:
- Name of test material (as cited in study report): 1,4-Dichloro-2-Nitrobenzene
- Molecular formula (if other than submission substance): C6-H3-Cl2-N-O2
- Molecular weight (if other than submission substance): 192.001 g/mole
- Substance type: Organic
- Physical state: No data available
- Impurities (identity and concentrations): No data available

Test animals

Species:
rat
Strain:
Fischer 344/DuCrj
Sex:
male
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles river Japan, Inc. (Atsugi, Japan)
- Age at study initiation: No data available
- Weight at study initiation: No data available
- Fasting period before study: No data available
- Housing: Animals were housed in polycarbonate metabolic cages.
- Diet (e.g. ad libitum): CRF-1 powdered diet, ad libitum
- Water (e.g. ad libitum): No data available
- Acclimation period: No data available

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 23± 1°C
- Humidity (%): 58 ±8 %
- Air changes (per hr): No data available
- Photoperiod (hrs dark / hrs light): No data available

IN-LIFE DATES: From: To: No data available

Administration / exposure

Route of administration:
oral: feed
Vehicle:
other: CRF-1 powdered diet
Details on exposure:
Doses were administrated by mixing 1,4-Dichloro-2-Nitrobenzene into CRF-1 powdered diet
Duration and frequency of treatment / exposure:
2 days
Doses / concentrations
Remarks:
Doses / Concentrations:
1.0 %
No. of animals per sex per dose / concentration:
Total : 6
0 %: 3 male
1.0 %: 3 male
Control animals:
yes, concurrent vehicle
Positive control reference chemical:
No data available
Details on study design:
No data available
Details on dosing and sampling:
No data available
Statistics:
No data available

Results and discussion

Preliminary studies:
No data available
Main ADME resultsopen allclose all
Type:
absorption
Results:
No data available
Type:
distribution
Results:
No data available
Type:
metabolism
Results:
N-acetylcysteine and N-acetyl-S-(4-chloro-3-nitrophyenyl)-L-cysteine conjugates were from

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:
Metabolisum of 1,4-Dichloro-2-Nitrobenzene resulting in the formation of N-acetylcysteine and N-acetyl-S-(4-chloro-3-nitrophyenyl)-L-cysteine conjugates from glutathione conjugates.

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): low bioaccumulation potential based on study results
1,4-Dichloro-2-Nitrobenzene expected to have Low bio-accumulation potential based on study results.
Executive summary:

In a vivoToxico-kinetics study, F344/DuCrj male rats were treated with 1,4-Dichloro-2-Nitrobenzene in the concentration of 1.0 % orally in diet. Urine samples were collected after 24 hr in metabolic cage and analyzed by usingUV,IH-NMR and LC-MS/MS analyses. Metabolisum of 1,4-Dichloro-2-Nitrobenzene resulting in the formation of N-acetylcysteine and N-acetyl-S-(4-chloro-3-nitrophyenyl)-L-cysteine conjugates from glutathione conjugates detected by LC-MS/MS analyses. Therefore, On the basis of given result1,4-Dichloro-2-Nitrobenzene expected to have Low bio-accumulation potential based on study results.