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Description of key information

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

Key value for chemical safety assessment

Bioaccumulation potential:
no bioaccumulation potential

Additional information

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.