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 (Cblood ss ) 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 Cblood ss were computed for Scenario 3 over Scenario 1. Ratios >1, demonstrating an exceedance of the RfD‐equivalent Cblood ss by Scenario 3, are obtained at mean and 97.5 th 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 97.5 th percentile. Nine VOCs exhibited such exceedance in children (ranges: 0.34–36 at the mean; 0.38–57 at the 97.5 th 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.