Registration Dossier

Toxicological information

Basic toxicokinetics

Currently viewing:

Administrative data

Endpoint:
basic toxicokinetics in vivo
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: sufficient documented and scientifically acceptable

Data source

Reference
Reference Type:
publication
Title:
Toxicokinetic study of 2-mercaptobenzimidazole (MBI) and its methylated derivative (MMBI) in rats treated by repeated oral administration - metabolism and urinary excretion
Author:
Tsuda M, Sakemi K, Ito R, Usami M, Ohno Y
Year:
1997
Bibliographic source:
J Toxicol Sci 22, 348

Materials and methods

Objective of study:
toxicokinetics
Principles of method if other than guideline:
Male Wistar rats were treated with 0.3 mmol/kg of MBI (2-mercaptobenzimidazole) or MMBI (2mercaptomethylbenzimidazole) by gavage for 15 days. 24h-urine samples were collected on day(s) 1, 8 and 15. Urinary amounts of MBI and MMBI, and their metabolites were determined.
GLP compliance:
not specified

Test material

Constituent 1
Chemical structure
Reference substance name:
1,3-dihydro-4(or 5)-methyl-2H-benzimidazole-2-thione
EC Number:
258-904-8
EC Name:
1,3-dihydro-4(or 5)-methyl-2H-benzimidazole-2-thione
Cas Number:
53988-10-6
Molecular formula:
C8H8N2S
IUPAC Name:
1,3-dihydro-4(or 5)-methyl-2H-benzimidazole-2-thione
Details on test material:
MMBI (methylated derivative of 2-mercaptobenzimidazole), no further data
Radiolabelling:
no

Test animals

Species:
rat
Strain:
Wistar
Sex:
male

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
not specified
Duration and frequency of treatment / exposure:
15 days
Doses / concentrations
Remarks:
Doses / Concentrations:
0.3 mmol/kg = 49.27 mg
No. of animals per sex per dose / concentration:
no data
Control animals:
not specified

Results and discussion

Preliminary studies:
no data

Metabolite characterisation studies

Metabolites identified:
yes
Details on metabolites:
In the MMBI treatment, the urinary amounts were MMBI < MBI (methylbenzimidazoles) (4 fold in day 1) and this ratio was not changed significantlly in days 8 and 15. The 2 isomeres of MMBI were desulfurized and excreted in different extent.

Any other information on results incl. tables

In the MMBI treatment the, the urinary amounts were MMBI < MBI (4 fold in day 1) and this ratio was not changed significantly in days 8 and 15. The 2 isomers of MMBI were desulfurized and excreted in different extend.

The effective desulfurization in MMBI may be a causal factor for the lack of thyroid toxicity

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): no bioaccumulation potential based on study results
Executive summary:

Wistar male rats were treated with 0.3 mmol/kg of MBI (2-mercaptobenzimidazole) or MMBI (methylated derivative of 2-mercaptobenzimidazole) by gavage for 15 days and collected 24h-urine samples (n=3) in day(s) 1, 8, and 15. Urinary amounts of MBI and MMBI, and their metabolites were determined.

In the MMBI treatment, the urinary amounts were MMBI < MBI (methylbenzimidazoles) (4 fold in day 1) and this ratio was not changed significantlly in days 8 and 15. The 2 isomeres of MMBI were desulfurized and excreted in different extent. The effective desulfurization in MMBI may be a causal factor for the lack of thyroid toxicity