Scientific Challenges in the Update of an Assessment of Methylmercury Neurotoxicity
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The US EPA is currently updating the reference dose (RfD) for Methylmercury developmental neurotoxicity (DNT; assessment plan and systematic review protocols were publicly released in 2019-20). Multiple health agencies (Health Canada, 2007; UNEP, 2002; US EPA, 2001, 1997; ATSDR, 1999) and the US National Academy of Sciences (NRC, 2000) have established that prenatal oral exposure to methylmercury in humans causes DNT. The existing US EPA quantitative risk assessment of methylmercury was finalized by the IRIS (Integrated Risk Information System) program in 2001. That assessment established RfD based on DNT effects in children following prenatal exposure using information from 3 epidemiological cohorts (Faroe Islands, Seychelles, New Zealand). The RfD of 0.1 µg/kg-day was derived from multiple DNT outcomes related to cord blood concentrations of 46–79 µg/L, which the assessment estimated corresponded to maternal daily intakes of methylmercury during pregnancy of 0.86–1.47 µg/kg-day. Since 1998, more than 200 epidemiological studies have been published with dose-response information on DNT of methylmercury exposure pre- and/or postnatally, based on dozens of cohorts, including the 3 original cohorts considered in the 2001 IRIS assessment. Updating the risk assessment with this collection of new studies presents several scientific issues that must be considered, including what biomarkers of exposure are most appropriate for deriving the RfD and how different studies account for potential confounding, including such factors as selenium and fish consumption.