The fate of¹⁴C-carbendazim in rat

Abstract

The disappearance of 14C-carbendazim in rat (i.v. 12 mg/kg) followed the kinetics of a two-compartment open-system model. Half-lives of the alpha-phase were 0.1 h (blood), 0.16 h (liver), 0.25 h (kidney), and of the beta-phase: 2.15 h, 6.15 h, respectively. Two metabolites: methyl 5-hydroxy-2-benzimidazolecarbamate (5-HBC) and 2-aminobenzimidazole (2-AB) were formed very rapidly. Their peak concentrations in liver and kidney were 15 min after i.v. injection. Unchanged carbendazim was found in highest concentrations in blood. 5-HBC prevails in organs. 2-AB was present only in minor amounts. The extent of bioavailability in orally administered 14C-carbendazim (12 mg/kg) was about 85%. The disposition of radioactivity in subcellular fractions was not uniform, its highest concentration was in cytosol, the lowest in microsomes. The elimination of 14C-carbendazim in urine is biphasic. Half-lives of the alpha-phase were 1.4 h (i.v.) and 2.5 h (oral), and of the beta-phase 11.2 h and 12.1 h, respectively. Irrespective of the route of administration, 95% of the radioactivity in urine was composed of 5-HBC. The concentration of unchanged carbendazim in blood and of 5-HBC in urine may be of diagnostic value in acute poisoning with carbendazim.

Testicular Damage after Exposure to Carbendazim Depends on the Number of Patent Efferent Ductules

“…These facts may account for the early temporal increase of seminiferous tubules that had abnormal germ cells. However, MBC is rapidly excreted and does not accumulate in animal tissues [4,10,13]. Therefore, it is likely that germ cells that are not susceptible to MBC develop normally, reconstruct the seminiferous epithelium, and contribute to the greater number of normal seminiferous tubules after a longer follow-up interval unless the EFDs are severely occluded.…”

Role of Testis Exposure Levels in the Insensitivity of Prepubertal Rats to Carbendazim-Induced Testicular Toxicity

“…These compounds are unlikely to play a role in CBZ-induced testicular toxicity. Levels of 5-HBC and 2-AB, however, were detected by other investigators, in blood, liver, and kidneys when [ I4 C]CBZ was administered intravenously (Krechniak and Klosowska, 1986). While unchanged CBZ was found in highest concentrations in blood, 5-HBC was readily detected in liver and kidneys, with minor amounts of 2-AB also present.…”

“…Liver and kidneys were the only organs examined. Since hydroxylation of CBZ to 5-HBC occurs enzymatically and is catalyzed by a hepatic microsomal mixed-function oxidase system, most likely cytochrome P450 (Krechniak and Klosowska, 1986;Dalvi, 1992;Douch, 1973), the presence of 5-HBC predominantly in the liver is not surprising. Although testis Leydig cells contain some cytochrome P450, the testicular isozymes may not catalyze the formation of 5-HBC.…”

“…Although testis Leydig cells contain some cytochrome P450, the testicular isozymes may not catalyze the formation of 5-HBC. Hydrolytic enzymes located in blood plasma and cytosol fractions of different organs are capable of metabolizing CBZ to 2-AB (Krechniak and Klosowska, 1986), but only small amounts of this metabolite are formed.…”

Inhibitors of DNA Biosynthesis-Mitosis: Benzimidazoles—The Benzimidazole Fungicides Benomyl and Carbendazim

“…Carbendazim then undergoes aryl hydroxylation-oxidation of the benzimidazole ring at the 5 and 6 positions followed by sulfate or glucuronide conjugation as the primary metabolic pathway in 77.4 Absorption, Distribution, Metabolism, and Excretion 1677 dogs and rats (Anderson, 1999). The hydrolysis of carbendazim to 2-aminobenzimidazole is another significant pathway in rats (Krechniak and Klosowska, 1986). Krupka (1974) has shown that benomyl does not inhibit either acetyl or butyryl cholinesterase in vitro, as did Belasco (1979a), who examined in vitro inhibition of acetylcholinesterase using bovine red blood cells.…”