ALTERED PORPHYRIN METABOLISM AS A BIOMARKER OF MERCURY EXPOSURE AND TOXICITY

Changes in urinary porphyrin excretion patterns (porphyrin profiles) h ave been described in response to a variety of drugs and chemicals. Th e present studies were conducted to define the specific changes in the urinary porphyrin profile associated with prolonged exposure to mercu ry and mercury compounds. In rats, exposure for a prolonged period to mercury as methyl mercury hydroxide was associated with urinary porphy rin changes, which were uniquely characterized by highly elevated leve ls of 4- and 5-carboxyl porphyrins and by the expression of an atypica l porphyrin (''precoproporphyrin'') not found in urine of unexposed an imals. 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 concentrati on of mercury in the kidney, a principal target organ of mercury compo unds. Following cessation of mercury exposure, urinary porphyrin conce ntrations reverted to normal levels, consistent with renal mercury cle arance. In human studies, a comparable change in the urinary porphyrin profile was observed among subjects with occupational exposure to mer cury as mercury vapor sufficient to elicit urinary mercury levels grea ter than 20 mu g/L. Urinary porphyrin profiles were also shown to corr elate significantly with mercury body burden and with specific neurobe havioral deficits associated with low level mercury exposure. These fi ndings support the utility of urinary porphyrin profiles as a useful b iomarker of mercury exposure and potential health effects in human sub jects.