{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T05:58:20Z","timestamp":1790834300101,"version":"4.1.0"},"reference-count":51,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2021,1,22]],"date-time":"2021-01-22T00:00:00Z","timestamp":1611273600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/100000066","name":"National Institute of Environmental Health Sciences","doi-asserted-by":"publisher","award":["R21ES024859"],"award-info":[{"award-number":["R21ES024859"]}],"id":[{"id":"10.13039\/100000066","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000066","name":"National Institute of Environmental Health Sciences","doi-asserted-by":"publisher","award":["R01ES025721"],"award-info":[{"award-number":["R01ES025721"]}],"id":[{"id":"10.13039\/100000066","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000066","name":"National Institute of Environmental Health Sciences","doi-asserted-by":"publisher","award":["P30ES001247"],"award-info":[{"award-number":["P30ES001247"]}],"id":[{"id":"10.13039\/100000066","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,2,26]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The biological half-life (t1\/2) of methylmercury (MeHg) shows considerable individual variability (t1\/2 &amp;lt; 30 to &amp;gt; 120\u2009days), highlighting the importance of mechanisms controlling MeHg metabolism and elimination. Building on a prior physiologically based pharmacokinetic (PBPK) model, we elucidate parameters that have the greatest influence on variability of MeHg t1\/2 in the human body. Employing a dataset of parameters for mean organ volumes and blood flow rates appropriate for man and woman (25\u201335 years) and child (4\u2009\u2212\u20096 years), we demonstrate model fitness by simulating data from our prior controlled study of MeHg elimination in people. Model predictions give MeHg t1\/2 of 46.9, 38.9, and 31.5\u2009days and steady-state blood MeHg of 2.6, 2.6, and 2.3\u2009\u00b5g\/l in man, woman, and child, respectively, subsequent to a weekly dose of 0.7\u2009\u00b5g\/kg body weight. The major routes of elimination are biotransformation to inorganic Hg in the gut lumen (73% in adults, 61% in child) and loss of MeHg via excretion within growing hair (13% in adults, 24% in child). Local and global sensitivity analyses of model parameters reveal that variation in biotransformation rate in the gut lumen, and rates of transport between gut lumen and gut tissue, have the greatest influence on MeHg t1\/2. Volume and partition coefficients for skeletal muscle (SM) and gut tissue also show significant sensitivity affecting model output of MeHg t1\/2. Our results emphasize the role of gut microbiota in MeHg biotransformation, transport kinetics at the level of the gut, and SM mass as moderators of MeHg kinetics in the human body.<\/jats:p>","DOI":"10.1093\/toxsci\/kfaa192","type":"journal-article","created":{"date-parts":[[2021,1,9]],"date-time":"2021-01-09T18:49:15Z","timestamp":1610218155000},"page":"26-37","source":"Crossref","is-referenced-by-count":23,"title":["Variation in Methylmercury Metabolism and Elimination in Humans: Physiological Pharmacokinetic Modeling Highlights the Role of Gut Biotransformation, Skeletal Muscle, and Hair"],"prefix":"10.1093","volume":"180","author":[{"given":"Quintin","family":"Pope","sequence":"first","affiliation":[{"name":"Department of Environmental Medicine, School of Medicine and Dentistry, University of Rochester, Rochester, New York 14642, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew D","family":"Rand","sequence":"additional","affiliation":[{"name":"Department of Environmental Medicine, School of Medicine and Dentistry, University of Rochester, Rochester, New York 14642, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,1,22]]},"reference":[{"key":"2021022816094778700_kfaa192-B1","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1080\/00039896.1969.10666872","article-title":"Metabolism of methyl mercury (203Hg) compounds in man","volume":"19","author":"Aberg","year":"1969","journal-title":"Arch. 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