Invited Review ArticleThe retention time of inorganic mercury in the brain - A systematic review of the evidence

Reports from human case studies indicate a half-life for inorganic mercury in the brain in the order of years-contradicting older radioisotope studies that estimated half-lives in the order of weeks to months in duration. This study systematically reviews available evidence on the retention time of inorganic mercury in humans and primates to better understand this conflicting evidence. A broad search strategy was used to capture 16,539 abstracts on the Pubmed database. Abstracts were screened to include only study types containing relevant information. 131 studies of interest were identified. Only 1 primate study made a numeric estimate for the half-life of inorganic mercury (227-540 days). Eighteen human mercury poisoning cases were followed up long term including autopsy. Brain inorganic mercury concentrations at death were consistent with a half-life of several years or longer. 5 radionucleotide studies were found, one of which estimated head half-life (21 days). This estimate has sometimes been misinterpreted to be equivalent to brain half-life-which ignores several confounding factors including limited radioactive half-life and radioactive decay from surrounding tissues including circulating blood. No autopsy cohort study estimated a half-life for inorganic mercury, although some noted bioaccumulation of brain mercury with age. Modelling studies provided some extreme estimates (69 days vs 22 years). Estimates from modelling studies appear sensitive to model assumptions, however predications based on a long half-life (27.4 years) are consistent with autopsy findings. In summary, shorter estimates of half-life are not supported by evidence from animal studies, human case studies, or modelling studies based on appropriate assumptions. Evidence from such studies point to a half-life of inorganic mercury in human brains of several years to several decades. This finding carries important implications for pharmcokinetic modelling of mercury and potentially for the regulatory toxicology of mercury.