Evaluation of Pharmacokinetic Models for the Disposition of Lead (Pb) in Humans, in Support of Application to Occupational Exposure Limit Derivation
Technical Report,01 Mar 2015,30 Oct 2015
Naval Medical Research Unit Dayton Wright-Patterson Air Force Base
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The National Research Council NRC issued a report on the exposure of Department of Defense DOD personnel to lead Pb at firing ranges NRC, 2013. In this report, they expressed the opinion that the current Occupational Safety and Health Administration OSHA Permissible Exposure Limit PEL was not sufficiently protective of DOD firing range personnel. A need has been identified by the Office of the Deputy Under Secretary of Defense Installations and Environment to derive of airborne Pb levels corresponding to the blood Pb levels BLL associated with various levels of concern identified by U.S. Army Public Health Command USAPHC, 2014. Mechanistic models for prediction of blood Pb, such as biokinetic or physiologically-based pharmacokinetic PBPK models, are appropriate tools for such a task. The two models under consideration were similar in their ability to simulate BLL measured in the selected studies. The OFlaherty model, however, more accurately described urinary vs. biliary clearance of Pb than the Leggett model, indicating that the OFlaherty model will more accurately predict BLL in subpopulations with impairments in either mode of clearance. The OFlaherty model, therefore, is recommended for use in future DOD applications to derive occupational exposure limits for Pb.