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PBPK-MODEL ESTIMATES OF BROMODICHLOROMETHANE (BDCM) DELIVERY TO THE HUMAN URINARY BLADDER
Citation:
Kenyon, E., C. Eklund, R. Pegram, AND J. Simmons. PBPK-MODEL ESTIMATES OF BROMODICHLOROMETHANE (BDCM) DELIVERY TO THE HUMAN URINARY BLADDER. Gordon Research Conference, Mt Holyoke, Massachusetts, July 30 - August 04, 2017.
Impact/Purpose:
These data indicate the potential for bromodichloromethane delivery to bladder in both urine and blood as important contributors to urothelial exposure and suggests the value of urinary BDCM as a toxicologically relevant measure of dose to target tissue.
Description:
Recent data indicate that noningestion exposure to trihalomethanes (THMs), including BDCM is highly correlated with urinary THM levels. Characterizing urinary levels of drinking water disinfection byproducts (DBPs) will likely be important for understanding DBP-associated bladder cancer. Non-oral exposures contribute significantly to the amount of BDCM available for distribution to target tissues (e.g., bladder urothelium). We refined our multi-route human BDCM PBPK model to include urine production in the kidney, urine retention in bladder lumen and delivery to the bladder via both blood and urine. The revised model was able to adequately predict urinary BDCM concentrations from water use studies in the published literature. The predicted internal dose metric most relevant for bladder exposure is area under the curve (AUC) for BDCM in blood flow to bladder tissue and BDCM delivered via the urine. This metric was compared for showering, bathing and oral exposures to water containing 10 ppb BDCM. For all metrics, noningestion exposure (showering, bathing, floor mopping, dish washing) resulted in 25- to 35-fold higher values compared to ingestion indicating the importance of dermal and inhalation routes of exposure as potential contributors to bladder tissue BDCM exposure. For a 10-minute shower and 20-minute bath, AUC was 2-fold and 3-fold higher, respectively for BDCM delivered in blood compared to BDCM delivered in urine to bladder tissue. When a liter of water is ingested over a 10-minute period, AUC was 4-fold higher for BDCM in blood compared to urine-delivered BDCM. These data indicate the potential for BDCM delivery to bladder in both urine and blood as important contributors to urothelial exposure and suggests the value of urinary BDCM as a toxicologically relevant measure of dose to target tissue. (This abstract does not reflect Agency policy).