Registration Dossier

Administrative data

Endpoint:
basic toxicokinetics
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 scientif principles

Data source

Reference
Reference Type:
publication
Title:
Metabolism of 2-thiobenzothiazoles in the rat, urinary fecal and billary metabolites of 2-benzothiazyl sulfenamides
Author:
Fukuoka, M.; et al.
Year:
1995
Bibliographic source:
Arch. Toxicol., 70, 1-9

Materials and methods

Objective of study:
excretion
metabolism
Principles of method if other than guideline:
other: evaluation of excretion and metabolism
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
N-oxydiethylene-2-[14C]-benzothiazyl sulfenamide
Radiolabelling:
yes
Remarks:
14C-ODBS

Test animals

Species:
rat
Strain:
Wistar

Administration / exposure

Route of administration:
oral: unspecified
Vehicle:
DMSO
Doses / concentrations
Remarks:
Doses / Concentrations:
250 mg/kg
No. of animals per sex per dose:
3 or 5 male rats
Control animals:
not specified

Results and discussion

Preliminary studies:
no data

Toxicokinetic / pharmacokinetic studies

Details on excretion:
The compound given orally to rats, was rapidly excreted in the urine and feces

Metabolite characterisation studies

Metabolites identified:
yes
Details on metabolites:
five urinary metabolites: 2-mercaptobenzothiazole (MBT), its three conjugates, mercapturate, glucuronide and sulfate, 2-mercaptobenzothiazole disulide

Any other information on results incl. tables

The metabolic fate of the test article in rats was studied using tracer techniques. The compound given orally to rats, was rapidly excreted in the urine and feces. Five urinary metabolites, (2-mercaptobenzothiazole, its three conjugates mercapturate, glucuronide and sulfate, and 2 -mercaptobenzothiazole disulfide) were confirmed. 2-mercaptobenzothiazole disulfide was also found as a fecal metabolite. The test compound was partially transformed in the stomach to 2-mercaptobenzothiazole disulfide,which was predominately excreted into feces. In the liver, the test compound was mainly transformed to 2-mercaptobenzothiazole and its conjugates. The S-glucuronide and S-sulfate conjugates were predominately excreted into bile.

14C was rapidly absorbed , as indicated blood peak levels at 15 to 30 min after administration and undergo enterohepatic circulation

Applicant's summary and conclusion