Methyltetrahydrophthalic acid in urine as an indicator of occupational exposure to methyltetrahydrophthalic anhydride

Objective: To investigate whether methyltetrahydrophthalic acid (MTHP acid) in urine can be used as a biomarker for exposure to methyltetrahydrophthalic anhydride (MTHPA). Methods: Workers occupationally exposed to MTHPA were studied in combination with one of the authors, who was experimentally exposed to MTHPA. Air levels of MTHPA were determined by personal sampling in the breathing zone. The MTHPA in air was sampled by silica gel and analyzed by gas chromatography (GC) with electron-capture detection. Urinary levels of MTHP acid, a metabolite of MTHPA, were determined in 15 subjects in total. Urine was collected from 14 workers immediately before the start of the work shift and then after 4 and 8 h, and from one of the authors at intervals during 24 h. MTHP acid in urine was analyzed by GC with mass spectrometric detection. Results: The time-weighted average (TWA) air levels ranged from 1.0 μg to 200 μg MTHPA/m³ during 8 h work shifts. The urinary levels of MTHP acid increased during exposure and decayed after the end of exposure, with an estimated half-time of about 3 h. A close correlation was found between the TWA air levels of MTHPA and creatinine-adjusted MTHP acid levels in urine collected at the end of the shift (r=0.955; P<0.0001). The current occupational exposure limit of 50 μg MTHPA/m³ (Japan Society for Occupational Health) corresponded to about 1300 μg MTHP acid/g creatinine, which was equivalent to about 900 nmol/mmol creatinine in the International System of Units (SI). Conclusions: These results indicate that the determination of MTHP acid in urine is suitable for use in the biological monitoring of MTHPA exposure.