Journal
TOXICOLOGICAL SCIENCES
Volume 161, Issue 2, Pages 443-453Publisher
OXFORD UNIV PRESS
DOI: 10.1093/toxsci/kfx226
Keywords
methylmercury; elimination; metabolism; biotransformation; half-life; toxicokinetics; laser ablation ICP-MS
Categories
Funding
- National Institute of Environmental Health Sciences (NIEHS) at the NIH [R21-ES024859]
- University of Rochester Environmental Health Science Center [P30 ES001247]
- NIH/NIEHS [P42 ES007373, 1UG3OD023275-01, P01ES022832]
- NIH/NCI [P30CA023108]
- EPA [RD83544201]
- NATIONAL CANCER INSTITUTE [P30CA023108] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES [R21ES024859, P42ES007373, P30ES001247, P01ES022832] Funding Source: NIH RePORTER
- OFFICE OF THE DIRECTOR, NATIONAL INSTITUTES OF HEALTH [UG3OD023275] Funding Source: NIH RePORTER
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Evaluating the potential for methylmercury (MeHg) toxicity relies on accurately predicting the mercury (Hg) body burden that results from eating fish. Hg body burden is directly determined by the slow elimination kinetics of MeHg in the human body (k(el) = 0.014 days(-1) or t(1/2) = 50 days). Existing studies on MeHg half-life in humans demonstrate a wide range values (t(1/2) = 30 to > 150 days) and has lead to uncertainty in the derivation of a regulatory standard for acceptable daily oral intake. The causes of variation in MeHg toxicokinetics in humans remain little explored. Here we characterize variation in human MeHg metabolism and elimination rate (kel) in 37 adult volunteers who consumed 3 fish meals. We determined MeHg elimination rates via longitudinal Hg analysis in single hairs using laser ablation inductively coupled plasma mass spectrometry. We also measured MeHg metabolism(biotransformation) via speciation of fecal Hg. We find an average k(el) = 0.0157 days(-1) (t(1/2) = 44 days) amongst a more than 2-fold variation in kel across the cohort (0.0248-0.0112 days(-1); t(1/2) = 28-62 days). Although MeHg biotransformation varied widely between individuals, it showed a positive association with elimination rates across the cohort. A more than 2-fold change in kel over a period of 2 years was seen in some individuals. In 2 individuals, who received antibiotic for unrelated health issues, elimination rate was seen to slow significantly. Associations of kel with age, body mass index, gender, and fish eating habits were not observed. We establish that a measure of methylmercury metabolismand eliminaiton status (MerMES) can reduce uncertainty in determining an individual's MeHg toxicokinetics subsequent to eating fish.
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