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Objectives: To establish an enzymatic deconjugation method to separately quantify urinary o‐toluidine (OT), its six metabolites, another six chemicals present in an OT‐processing plant, and one metabolite of p‐toluidine, and to propose optimal urinary biological monitoring items of OT exposure. Methods: Thirty‐six urine samples of an OT‐processing plant's workers were obtained and pretreated by an enzymatic deconjugation method employing β‐glucuronidase/arylsulfatase for 3 hours at 37°C and measured by liquid chromatograph‐mass spectrometry (LC‐MS). An alkaline hydrolytic pretreatment and 1‐chlorobutane extraction procedure was also examined as a widely used urinary OT measurement method. Results: The 14 chemicals were separated by LC‐MS condition set by us and 13 chemicals other than 2‐chloroaniline showed satisfiable linearity and limits of determination. Standard substances of six OT metabolites decomposed after the alkaline heating. In the 36 urine samples, OT, N‐(4‐hydroxy‐2‐methylphenyl) acetamide (NHM), and 4‐amino‐m‐cresol (ACR) accounted for approx. 90% of the total OT and OT metabolites, but inter‐individual variation of the three substance excretion seemed to be wide. Time course of urinary excretion revealed that concentration of the three substances was higher 24 hours after the work shift's end rather than just after the work shift. Conclusions: OT and its six metabolites can each be determined with LC‐MS. The alkaline method is not so optimal for exact biological monitoring. Rather, the sum of urinary OT, NHM, and ACR measured by the enzymatic method is a better index, and "end of the workweek" is a good urine‐sampling time for the biological monitoring of OT exposure. [ABSTRACT FROM AUTHOR]

Background The purpose of this study was to identify plasma and urinary metabolites that can be used to better identify the effects of cadmium exposure than N-acetyl-β-D-glucosaminidase (NAG) using capillary electrophoresis - mass spectrometry (CE-MS). Methods Urinary cadmium (U-Cd) was measured as an indicator of cadmium exposure. Fasting plasma and urine samples were collected from 1,412 men and 2,022 women in Tsuruoka Metabolomics Cohort Study. Charged 94 plasma and 123 urinary metabolites were detected and determined. Regression analysis was performed for urinary NAG, plasma, and urinary metabolites as dependent variables and U-Cd in quartiles as an independent variable. Multivariate regression model included age, SBP, smoke, rice intake, BMI, HbA1c, LDLc, alcohol consumption, physical activity, educational history, dietary energy intake, urinary Na/K ratio, and uric acid. Results The mean U-Cd of the population was 2.65 μg/g creatinine (SD: 1.63). NAG was positively associated with U-Cd, but the association was not significant with lower U-Cd quartiles. In the plasma metabolites, 10 metabolites had significantly negative association with U-Cd in all models and Cd quartiles. Among urinary metabolites, 27 metabolites had significantly positive association with U-Cd. Alanine was negatively associated with U-Cd in urinary metabolites. The trend test also showed significant dose-response trends for 9 plasma and all 28 urinary metabolites (p < 0.05). Conclusions We found that the levels of Cd exposure, which did not cause an increase in NAG, caused changes in plasma and urinary metabolites. Key messages This study indicated that metabolomics might be promising and useful as markers of Cd exposure. [ABSTRACT FROM AUTHOR]