Pharmacokinetics of mercury from dental amalgam

Sammanfattning: PHARMACOKINETICS OF MERCURY FROM DENTAL AMALGAM Gunilla Sandborgh Englund Dept. of Basal Oral Sciences, Karolinska Institutet, S-141 04Huddinge The overall aim of the present work has been to obtain quantitative and qualitativedata on mercury from dental amalgam in humans. The influence of amalgam removal on mercury levels in blood, plasma and urine hasbeen studied in twelve volunteers. All amalgam fillings were removed during one dentalsession. A transient increase of mercury in blood and plasma was observed within48 h after amalgam removal, and sixty days after the mercury levels in all mediahad decreased to about 60% of the pre removal levels. A bi-exponential model wasapplied on mercury in plasma with the median half-time of the second phase being88 days. The kinetics of mercury in urine was fitted to a mono-exponential model,the median half-time being 46 days. The pharmacokinetics of mercury vapor was studied after a single dose exposurein human volunteers. Nine subjects were exposed to 400 µg/m3 mercury vapor for15 min. The retention was on average 67% of the inhaled mercury dose. A rapid absorptionphase was seen in blood and plasma, followed by a bi-exponential decline. In plasmathe median half-time of the second phase was 10 days with a large inter-individualvariation. The estimated total amount of mercury excreted via urine during 30 daysranged from 8% to 41%. Mercury levels in saliva and feces before and after amalgam removal were studied.The fecal mercury concentrations were more than ten times higher in the pre-removalsamples than those found in a reference group with no amalgam fillings. Two daysafter removal, the fecal mercury concentrations increased about 100 times, followedby a significant decrease. Sixty days after amalgam removal, the mercury levels infeces were still slightly higher than in the reference group. In saliva the medianmercury levels declined from the pre-removal level of 200 nmol/kg to 1 nmol/kg sixtydays after amalgam removal. The kidney is a target organ for inorganic mercury and in animal studies decreasedrenal function has been shown after placement of amalgam fillings. The mercury levelsin blood, plasma and urine and the kidney function were studied before and afteramalgam removal. A number of sensitive renal parameters were determined: the glomerularfiltration rate (GFR) and the excretion of N-acetyl-ß glucose aminidase (NAG),ß2-microglobuline and albumin. No signs of kidney dysfunction were detectable. Effects on mercury levels in blood, plasma and urine after 14-days treatment witha chelating agent (DMSA) or placebo were studied in twenty subjects, relating theirsymptoms to mercury exposure from amalgam fillings. In addition, these effects wererelated to possible changes of symptoms. Three cases of generalized hypersensitivereactions were encountered at the end of the treatment period. A significant increasein urinary mercury excretion was apparent during DMSA treatment, and the blood mercurylevels decreased. There was no evidence that chelating therapy alleviated symptomsallegedly attributable to mercury from amalgam fillings. In summary, amalgam fillings constitute a significant source of exposure to mercury.Mercury levels in blood, plasma, urine, saliva and feces decrease considerably afterthe removal of dental amalgam. No adverse effects on the kidney function were observedfrom the mercury exposure in conjunction with amalgam removal. DMSA treatment appearsto mainly affect the mercury excretion from the kidney, and the risk of hypersensitivityreactions is considerable during prolonged treatment. Combined evaluation of thedecline of mercury in plasma after amalgam removal and after the single dose exposureclearly verifies the pharmacokinetics of mercury as at least tri-exponential. Thepharmacokinetic analysis of mercury verifies the daily mercury dose in subjects withan average number of amalgam fillings to be 5-9 µg per day. Key words: Human, dental amalgam, mercury, blood, plasma, urine, saliva, feces,pharmacokinetics, kidney, chelating agents. ISBN 91-628-2791-X