Probabilistic Assessment of the Relative Source Contribution Factor While Accounting for Exposure to Other Regulated Media: A Toxicokinetic Proof-of-Concept for Volatile Drinking Water Contaminants.

Abstract

A relative source contribution factor is applied when deriving noncancer health-based guidance values for drinking water contaminants. The present work aimed at assessing the adequacy of the 20% default value often attributed to this factor while accounting for concomitant inhalation exposure to the reference concentration (RfC). Steady-state toxicokinetic equations were applied to calculate constant blood concentration (Cbloodss) in adults and 1-3-year-old children for 12 volatile organic compounds (VOCs). Three exposure scenarios were considered for each compound, namely, (1) ingestion of the reference dose (RfD) alone; (2) inhalation of the RfC alone; and (3) ingestion of 20% of the RfD combined with inhalation of the RfC. Using Monte Carlo simulations, probabilistic ratios of Cbloodss were computed for Scenario 3 over Scenario 1. Ratios >1, demonstrating an exceedance of the RfD-equivalent Cbloodss by Scenario 3, are obtained at mean and 97.5th percentile value for eight of the chosen VOCs in adults, with range of 0.3-29 at the mean and of 0.32-52 at the 97.5th percentile. Nine VOCs exhibited such exceedance in children (ranges: 0.34-36 at the mean; 0.38-57 at the 97.5th percentile). For eight VOCs, ratios >1 were mainly explained by high RfC-related intake as compared to RfD-related intake. Concluding, steady-state toxicokinetic modeling was successfully used to illustrate the importance of other media's guidance levels-related exposures, in the present case the RfC, to evaluate the magnitude of the relative source contribution factor required when determining health-based guidance values for chemicals in drinking water.