You are here:
PBPK-MODEL ESTIMATES OF BROMODICHLOROMETHANE (BDCM) DISTRIBUTION IN URINE AND BLADDER TISSUE
Citation:
Kenyon, E., C. Eklund, J. Simmons, AND R. Pegram. PBPK-MODEL ESTIMATES OF BROMODICHLOROMETHANE (BDCM) DISTRIBUTION IN URINE AND BLADDER TISSUE. Society of Toxicology, New Orleans, LA, March 12 - 17, 2016.
Impact/Purpose:
These data suggest the potential for BDCM delivery to bladder in the urine as an important contributor to urothelial exposure and suggests the value of measuring 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 bladder tissue in both blood and urine. The revised model was able to adequately predict urinary BDCM concentrations from water use studies in the published literature. Predicted internal dose metrics relevant for bladder exposure are area under the curve (AUC) and maximum concentration (Cmax) for BDCM in arterial blood flow to bladder tissue, in bladder tissue and in urine. These metrics were compared for oral and shower related (inhalation + dermal) exposures to water containing 10 ppb BDCM. For all metrics, noningestion exposure (e.g., showering) 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 exposure. For a 10 minute shower, AUC and Cmax were 40-fold and 100-fold higher, respectively for BDCM in urine compared to bladder tissue. When a liter of water is ingested over a 10 minute period, AUC and Cmax were 45-fold and 130-fold higher, respectively, for BDCM in urine compared to bladder tissue. These data suggest the potential for BDCM delivery to bladder in the urine as an important contributor to urothelial exposure and suggests the value of measuring urinary BDCM as a toxicologically relevant measure of dose to target tissue.