Determination of urinary 2-mercaptobenzothiazole (2-MBT), the main metabolite of 2-(thiocyanomethylthio)benzothiazole (TCMTB) in humans and rats

Abstract

A method for biological monitoring of urinary 2-(thiocyanomethylthio)benzothiazole (TCMTB), a wood preservative and an industrial chemical, was developed. Three different doses of TCMTB in olive oil were given to male rats by gavage for 3 weeks. Urine was collected daily and the metabolites were analysed as thioethers by derivatization with pentafluorobenzyl-bromide by gas chromatography-mass spectrometry. The parent chemical was not detected in urine samples, but two metabolites of TCMTB were identified. 2-Mercaptobenzothiazole (2-MBT) was the main metabolite, and its excretion varied according to the dose. The second metabolite was 2-(mercaptomethylthio)benzothiazole. The amount of 2-MBT excreted in rat urine was 66 +/- 12% (SD), 51 +/- 20% and 44 +/- 9% for TCMTB doses of 15, 75 and 150 mg/kg, respectively. Two doses, 75 and 150 mg/kg, caused diuresis in rats during the 1 week of dosing. During the 3-week TCMTB treatment, rat liver microsomal CYP enzyme profile was not significantly changed. Urine samples of sawmill workers exposed to TCMTB were collected after their work shifts for exposure assessment. TCMTB could not be detected in the urine samples of exposed workers. Most concentrations of 2-MBT were below the limit of the detection, 0.12 mumol/l, the concentrations were 0.12-0.15 mumol/l only in few cases. The determination of 2-MBT in urine, when a sample is taken immediately after a work shift, is a suitable indicator of workers' exposure to TCMTB.

Allergenicity Evaluation of N-(1-Methylheptyl)-N'-Phenyl-p-Phenylenediamine and 2-(Thiocyanomethylthio) Benzothiazole by the Guinea Pig Maximization Test.

“…Although MTBT and MBT exhibited cross-reactivity to TCMTB-sensitized animals after topical application, the degree of skin reactions caused by these compounds was far weaker compared to that by TCMTB, despite the use of a 100-fold concentration in the topical application. Although MBT is a major metabolite of TCMTB in rats, 8) the animals seemed to be sensitized by TCMTB itself and not by the metabolites.…”

“…On the other hand, TCMTB may produce 2-mercaptobenzothiazole (MBT), a rubber vulcanizing agent and a typical rubber allergen, 6,7) as its major metabolite. 8) In the process of risk assessment of a chemical, hazard identification should be followed by doseresponse evaluation. In this study, we evaluated the dose-response profiles of MHPPD-and TCMTBallergenicity by varying both induction and challenge doses in the GPMT.…”

Preventing decomposition of 2-mercaptobenzothiazole during gas chromatography analysis using programmable temperature vaporization injection

“…As a result, MBT was identified as S-methylated product. Shinohara et al 18 methylated MBT prior to GC-FPD analysis using dimethyl formamide diacetal as methylation reagent, and Manninen et al 19 derivatized samples with pentafluorobenzyl bromide. Rennie 30 used HPLC for determination of MBT instead of gas chromatography because of degradation problems.…”

“…Prior to LC determination, no derivatization of MBT is necessary. Some researchers derivatized MBT to thioethers prior to GC analysis, [18][19][20] while others carried out analysis without derivatization. 21,22 Main reason for derivatization of MBT, prior to GC analysis, is the reactivity of the thiol group inside of a gas chromatograph.…”

“…21,22 Main reason for derivatization of MBT, prior to GC analysis, is the reactivity of the thiol group inside of a gas chromatograph. 19 Other methods have also been reported for analys of MBT, including voltammetry and spectrophotometry. 23,24 Most of the researchers determined MBT simultaneously with other related chemical compounds.…”