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APPLICATION OF A MULTIROUTE HUMAN PBPK MODEL FOR BROMODICHLOROMETHANE (BDCM)
Citation:
KENYON, E. M., T. L. Leavens, C. Eklund, AND R. A. PEGRAM. APPLICATION OF A MULTIROUTE HUMAN PBPK MODEL FOR BROMODICHLOROMETHANE (BDCM). Presented at Society of Toxicology (SOT) Annual Meeting, Washington, DC, March 06 - 10, 2011.
Impact/Purpose:
These data indicate the need to consider the contribution of multiple routes of exposure when evaluating risk.
Description:
Due to its presence in water as a volatile disinfection byproduct, BDCM poses a risk for exposure via multiple routes. Mechanistic data suggest target tissue metabolism could be important for some types of BDCM-induced toxicity. Utilizing our refined PBPK model for BDCM, the impact on internal dose of BDCM from dermal and inhalation exposure during showering and bathing was compared with oral exposure from drinking water. Dose metrics evaluated were maximum blood concentration (Cmax), area under the curve (AUC) for blood BDCM, and amount metabolized in liver per hour (AML). Compartments in the model were skin, liver, gut, fat, kidney, and slowly and rapidly perfused tissue groups. Tissue transport was blood-flow limited. Metabolism occurred in the liver via two pathways (cytochrome P450, glutathione S-transferase). Chemical-specific parameters for tissue solubility and physiological parameters were obtained from the literature; metabolism parameters were estimated on the basis of our in vivo and in vitro human data. The model adequately predicted data from the published literature for oral, dermal, inhalation, and combined exposures. To produce by oral exposure (assuming a single 1/4 L drink), the same internal doses that resulted from a l0-minute dermal-only exposure to water containing 10 ppb BDCM, would require the drinking water to contain 200,470 and 7.6 ppb BDCM for Cmax, AUC, and AML, respectively. For a la-minute, inhalation-only exposure to BDCM volatized from 10 ppb BDCM in water (estimated air concentration 2.6 ppb), the oral equivalent water concentrations were 50, 100 and 2.4 ppb for Cmax, AUC and AML, respectively. These results suggest a large contribution of inhalation and dermal exposure (e.g. from showering) to internal dose of parent BDCM reaching the systemic circulation to be available for extrahepatic metabolism These data indicate the need to consider the contribution of multiple routes of exposure when evaluating risk. (This abstract does not necessarily reflect Agency policy).