Altered porphyrin metabolism as a biomarker of mercury exposure and toxicity.

Changes in urinary porphyrin excretion patterns (porphyrin profiles) have been described in response to a variety of drugs and chemicals. The present studies were conducted to define the specific changes in the urinary porphyrin profile associated with prolonged exposure to mercury and mercury compounds. In rats, exposure for a prolonged period to mercury as methyl mercury hydroxide was associated with urinary porphyrin changes, which were uniquely characterized by highly elevated levels of 4- and 5-carboxyl porphyrins and by the expression of an atypical porphyrin ("precoproporphyrin") not found in urine of unexposed animals. These distinct changes in urinary porphyrin concentrations were observed as early as 1-2 weeks after initiation of mercury exposure, and increased in a dose- and time-related fashion with the concentration of mercury in the kidney, a principal target organ of mercury compounds. Following cessation of mercury exposure, urinary porphyrin concentrations reverted to normal levels, consistent with renal mercury clearance. In human studies, a comparable change in the urinary porphyrin profile was observed among subjects with occupational exposure to mercury as mercury vapor sufficient to elicit urinary mercury levels greater than 20 micrograms/L. Urinary porphyrin profiles were also shown to correlate significantly with mercury body burden and with specific neurobehavioral deficits associated with low level mercury exposure. These findings support the utility of urinary porphyrin profiles as a useful biomarker of mercury exposure and potential health effects in human subjects.