June 1, 2001
Journal Article

Development of an Integrated Micro-Analytical System for Lead in Saliva and Linkage to a Physiologically Based Pharmacokinetic Model Describing Lead Saliva Secretion

Abstract

There is a need to develop reliable portable analytical instruments for real-time monitoring of trace metals, such as lead (Pb) utilizing readily available non-invasive fluids like saliva. To interpret saliva results, an understanding of the pharmacokinetics of Pb secretion into the saliva is needed. A portable microfluidics/electrochemical device was developed for the rapid analysis of Pb based on square wave anodic stripping voltammetry, where a saliva sample flows over an electrode surface, Pb2+ is chemically reduced, accumulated, and the electric potential of the electrode scanned. To evaluate the relationship between saliva and blood Pb, rats were treated with single oral doses ranging from 20 to 500 mg Pb/kg of body weight, and 24 hours later salivation was induced by administering pilocarpine, a muscarinic agonist. Blood and saliva were collected and analyzed for Pb by inductively coupled plasma-mass spectrometry (ICP-MS) and by the micro-analytical system. The micro-analytical system was slightly less responsive (~75-85%) than ICP-MS, however the response was linear over a concentration range of 1-2000 ppb suggesting that it can be utilized for the quantitation of salivary Pb. To relate saliva levels to internal dose of Pb (e.g. blood) and to total body burden, a physiologically based pharmacokinetic (PBPK) model for Pb was modified to incorporate a salivary gland compartment. The model was capable of predicting blood and saliva Pb concentration based on a limited data set. These preliminary results are encouraging and suggest that a fully developed, micro-analytical system can be utilized as an important tool for real-time biomonitoring of Pb for both occupational and environmental exposures.

Revised: April 17, 2002 | Published: June 1, 2001

Citation

Timchalk C., T.S. Poet, Y. Lin, K.K. Weitz, R. Zhao, and K.D. Thrall. 2001. Development of an Integrated Micro-Analytical System for Lead in Saliva and Linkage to a Physiologically Based Pharmacokinetic Model Describing Lead Saliva Secretion. American Industrial Hygiene Association Journal 62, no. 3:295-302. PNNL-SA-32610.