Registration Dossier

Administrative data

Endpoint:
basic toxicokinetics in vivo
Type of information:
experimental study
Adequacy of study:
other information
Study period:
1957
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Basic data given

Data source

Reference
Reference Type:
publication
Title:
The Metabolism of 2:3 -, 2:6 - and 3:5 -Dichloronitrobenzene and the Formation of a Mercapturic Acid from 2:3:4:5-Tetrachloronitrobenzene in the Rabbit
Author:
Bray, H.G. et al.
Year:
1957
Bibliographic source:
Biochem J. 67(4):607-16

Materials and methods

Objective of study:
metabolism
Principles of method if other than guideline:
Determination of metabolites excreted in urine of rabbits after administration of the test material by stomach tube
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): 2,3- Dichloronitrobenzene
- Analytical purity: no data
- Source: Bayer Products Ltd.
Radiolabelling:
no

Test animals

Species:
rabbit
Strain:
not specified
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 2-3 kg

Administration / exposure

Route of administration:
other: stomach tube
Vehicle:
water
Duration and frequency of treatment / exposure:
no data
Doses / concentrations
Remarks:
Doses / Concentrations:
100 mg/kg bw
No. of animals per sex per dose:
6
Control animals:
no

Results and discussion

Metabolite characterisation studies

Metabolites identified:
yes
Details on metabolites:
The main products excreted in urine were phenols, conjugated with glucuronic and sulphuric acids, and dichloroanilines. The phenols detected were: 2-Amino-3,4-dichlorophenol, 3-Amino-4,5-dichlorophenol, 4-Amino-2:3-dichlorophenol and 4,5-Dichloro-3-nitrophenol. No mercapturic acids were detected in the urines.

Any other information on results incl. tables

About 5% of a dose of 2,3 -dichloronitrobenzene is unabsorbed, the greater part of the unabsorbed material being reduced to the aniline. The test substance was not found in urine in the form of mercapturic acid. A large proportion of the dose was excreted as glucosiduronic acid and ethereal sulphate, indicating hydroxylation of the test substance. The ethereal sulphate is presumably formed from amino or nitro-dichlorophenols. With 2,3 -dichloronitrobenzene considerable reduction occurred and most of the base was excreted as such. From 2:3 -Dichloronitrobenzene significant amounts of the aniline were excreted combined.

Hence, the main metabolic pathways of 2,3 -dinitrochloronitrobenzene are reduction and hydroxylation, leading to the formation of 2-Amino-3,4-dichlorophenol, 3-Amino-4,5-dichlorophenol, 4-Amino-2:3-dichlorophenol and 4,5-Dichloro-3-nitrophenol and subsequent glucoronidation and sulfatation.

Applicant's summary and conclusion