Biological monitoring of methylhexahydrophthalic anhydride by determination of methylhexahydrophthalic acid in urine and plasma from exposed workers

Objective: To investigate whether methylhexahydrophthalic acid (MHHP acid) in urine and plasma can be used as a biomarker for exposure to methylhexahydrophthalic anhydride (MHHPA). Methods: MHHPA in air was sampled by Amberlite XAD-2 and analysed by gas chromatography (GC) with flame ionisation detection. MHHP acid in urine and plasma was analysed by GC with mass spectrometric detection. Workers occupationally exposed to MHHPA were studied. Air levels of MHHPA were determined by personal sampling in the breathing zone. Urinary levels of MHHP acid, a metabolite of MHHPA, were determined in 27 workers. In eight workers all urine was collected at intervals during 24 h. Plasma levels of MHHP acid were determined in 20 workers. Results: The time-weighted average (TWA) air levels ranged from 5 to 60 μg MHHPA/m³ during 8-h work-shifts. The urinary levels of MHHP acid increased during exposure and decayed after the end of exposure with an estimated half-life of about 6 h. A correlation was found between the TWA air levels of MHHPA and creatinine-adjusted MHHP acid levels in urine collected during the last 4 h of exposure. A correlation was also seen between the TWA air levels of MHHPA and the plasma concentrations of MHHP acid. An exposure to 20 μg MHHPA/m³ corresponded to about 140 nmol MHHP acid/mmol creatinine and about 40 nmol MHHP acid/l plasma. Conclusion: The results indicate that MHHP acid in urine or plasma may be used for biological monitoring of the exposure to MHHPA. Received: 4 October 1996 / Accepted: 2 January 1997