Combined fugacity-based exposure and PBPK modelling for human health risk assessment and risk management of trihalomethanes in indoor swimming pools

The chlorination of swimming pool water creates disinfection byproducts (DBPs) which can have negative impacts on human health. Toxicological and epidemiological studies have identified health effects caused by disinfection byproducts including cancer (kidney, liver, intestinal, and bladder), as well as respiratory and reproductive effects. Among the most prevalent and studied DBPs are trihalomethanes (THMs): chloroform, bromodichloromethane, dibromochloromethane, and bromoform. Risk assessment and management is necessary to reduce the inhalation and dermal contact exposures to swimmers. Past research has focussed on chloroform, rather than the more genotoxic brominated THMs, household rather than swimming pool exposures, and the amount of THMs at the interface between the environment and the individual. Physiologically based pharmacokinetic (PBPK) models offer a more detailed way to assess human health risk. By modelling the absorption, distribution, metabolism and excretion of THMs, we can better predict the doses delivered to the most sensitive organs where the toxic effects occur. Few mechanistic models exist which can accurately predict delivered doses of all four THMs while incorporating pool design and operating conditions (e.g. layout and air recirculation), and swimmer characteristics (e.g. exercise intensity). There is a need for enhanced modelling and risk assessment of THMs in indoor swimming pools to propose risk management solutions that reduce the impact of DBPs on swimmers. This research presents a novel approach to exposure modelling, PBPK modelling, human health risk assessment, and risk management. The concept of fugacity was used to combine exposure and PBPK models. Delivered doses to target organs were estimated from water concentrations of THMs without the need for sampling ambient air, alveolar air, blood, or urine. Biomonitoring equivalents for THMs at the toxicological reference values were compared with model results to assess swimmer risk. The utility of the model was further demonstrated by using risk assessment to evaluate risk management strategies. Uncertainty analysis included Monte Carlo simulations and fuzzy techniques. By considering all four THMs, multiple complex pool environments, swimmer exercise intensity and risk management alternatives, this research advances DBP modelling for the management of swimmer risks and lays the groundwork for future development of guidelines for THMs in swimming pools.