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EC number: 258-904-8
CAS number: 53988-10-6
Short description of key information on bioaccumulation potential result:
MBI (2-Mercaptobenzimidazole) and the MMBIs [4-methylated MBI (4-MMBI)
and 5-methylated MBI (5-MMBI), and a 1:1 mixture of these 4- and
5-methylated isomers (MMBI mix)] suspended in corn oil were repeatedly
administered (at 0.3–0.6 mmol/ kg) to male Wistar rats by gavage once
daily for 2 weeks. After the first and last administrations, blood and
urine samples were collected, and the levels of unchanged compounds and
their desulfurated metabolites were determined.
The toxicokinetik of 2-mercaptomethylbenzimidazole (MMBI) in rats was
examined in several studies and compared with the toxikokinetik profile
of 2-mercaptobenzimidazole (MBI).Additionally the metabolites of MMBI
and MBI were examined in urine.
MMBI in serum disappeared faster than MBI, being undetectable even at 12
hr at 50 mg/kg. When 4-MMBI and 5-MMBI were determined separately after
oral administration of MMBI at 50 mg/kg, the former disappeared slower
than the latter, indicating the apparent effect of the position of
methyl substituent on the toxicokinetics of MMBI.
MBI and MMBI (2-mercaptomethylbenzimidazole) showed similar Cmax values,
but the former disappeared slower in the serum than the latter and
resulted in its larger AUC values. Analyses of MBI, MMBI and their
desulfurated metabolites in urine suggested that these differences were
due to their metabolic elimination rates. As desulfurated metabolites of
MMBI the 5-MeBI (5-methylbenzimidazole) and 4-MeBI
(4-methylbenzimidazole) were identified.
Discussion on bioaccumulation potential result:
After repeated oral administration (roa), the Cmax and area under
concentration-time curve (AUC) of MBI were markedly increased, while the
MMBIs essentially were cleared from the blood within 10 h. After roa,
the Cmax and AUC of 4-MMBI decreased markedly, suggesting metabolic
enzyme induction. However, the toxicokinetic parameters of 5-MMBI were
not markedly altered by roa.
After roa of 0.6 mmol/kg of the MMBI mix, urinary excretion of unchanged
compounds, 4-MMBI and 5-MMBI, on day 15 increased markedly (7-fold and
2-fold of those amounts on day 1, respectively). In contrast, the
urinary excretion of their desulfurated metabolites was not altered
significantly. Roa of the lower dose (0.3 mmol/kg) did not affect
urinary excretion patterns. The sum of the urinary excretions of
unchanged compounds and their desulfurated metabolites during the 24 h
following oral administration of these thioureylene compounds was less
than 10% of the administered amounts. When administered each isomer
separately, urinary excretion of the desulfurated metabolite, 4-MeBI, on
day 14 was increased 2-fold (P<0.01) by roa of 4-MMBI compared with that
on day 1. However, in the case of 5-MMBI, urinary excretion of both the
unchanged compound and the desulfurated metabolite, 5-MeBI, were not
altered by roa.
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