URINARY PORPHYRIN PROFILES AS A BIOMARKER OF MERCURY EXPOSURE - STUDIES ON DENTISTS WITH OCCUPATIONAL EXPOSURE TO MERCURY-VAPOR

Porphyrins are formed as intermediates in the biosynthesis of heme. In humans and other mammals, porphyrins with eight, seven, six, five, and four carboxyl groups are excreted in the urine in a well-established pattern. Mercury selectively alters porphyrin metabolism in kidney proximal tubule cells, leading to an altered urinary porphyrin excretion pattern. Previous studies in rats have shown that changes in the urinary porphyrin profile during exposure to mercury as methylmercury hydroxide are uniquely characterized by highly elevated (20- to 30-fold) levels of four- and five-carboxyl porphyrins and by the excretion of an atypical porphyrin (precoproporphyrin), which elutes on high performance liquid chromatography (HPLC) approximately midway between penta- and coproporphyrins. Changes in the urinary porphyrin profile are highly correlated with the dose and duration of mercury exposure and persist for up to 20 wk following cessation of mercury treatment. In the present studies, the utility of urinary porphyrin profile changes as a biomarker of mercury exposure in human subjects was evaluated. Urinary porphyrin concentrations were measured in dentists participating in the Health Screening Programs conducted during the 1991 and 1992 annual meetings of the American Dental Association and compared with urinary mercury levels measured in the same subjects. Among dentists with no detectable urinary mercury, mean concentrations of urinary porphyrins were within the established normal ranges for male human subjects. In contrast, among dentists with urinary mercury in excess of 20 mug/L, mean urinary concentrations of four- and five-carboxyl porphyrins as well as of precoproporphyrin were elevated three to four times those of unexposed subjects. Significant differences in urinary porphyrin concentrations remained when porphyrin concentrations in spot urine samples were adjusted for creatinine levels. These findings suggest that urinary porphyrin profiles may serve as a useful biomarker of mercury exposure in clinical or epidemiologic studies of mercury-related human health risks.