The Impact Of Short-Term Exposure To Disinfection By-Products On The Metabolome A Metabolome-Wide Association Study

Karin VAN VELDHOVEN, Imperial College London, United Kingdom
KOGEVINAS M. 2 , FONT-RIBERA L. 2 , VILLANUEVA C. 2 , GUIDA F. 1 , CHADEAU-HYAM M. 1 , VINEIS P. 1,3 , KESKI-RAHKONEN P. 4 , SCALBERT A. 4 , BARUPAL D. 4

1 MRC-PHE Centre for Environment and Health, School of Public Health, Dept. of Epidemiology and Biostatistics, Imperial College London, London, UK
2 Centre for Research in Environmental Epidemiology - CREAL), Barcelona, Spain
3 HuGeF, Human Genetics Foundation, Torino, Italy.
4 International Agency for Research on Cancer - IARC, Lyon, France

Purpose
Exposure to disinfection by-products (DBPs), found in drinking water and swimming pools, has been associated with adverse health outcomes such as bladder cancer and impaired respiratory health. The underlying biological mechanisms are still unknown and therefore the aim of this study was to investigate the impact of DBPs on the metabolome.

Methods
We used data from the experimental PISCINA-II study, which was performed in an indoor chlorinated pool where 60 volunteers (18-40y non-smokers) swam for 40 minutes. Questionnaires about lifestyle factors and physical activity were completed, heart rate was monitored, and exhaled breath and blood samples were collected before and 2 hours after swimming. Exposure to DBPs was assessed using measurements of chloroform, bromodichloromethane, dibromochloromethane and bromoform in exhaled breath and pool water. Untargeted metabolomics of plasma samples was conducted using a UHPLC-QTOF mass spectrometer operated in ESI positive mode. PLS-DA was performed and the association between DBP-exposure and levels of metabolites was analysed using confounder adjusted linear mixed models (FWER 5%). 

Results
All exposures were significantly higher after the experiment. PLS-DA suggested that samples obtained before swimming can be distinguished from samples obtained after swimming. Linear mixed models showed an association between chloroform, bromoform and total trihalomethanes concentrations measured in exhaled breath and levels of 15, 1, and 3 metabolites, respectively. For exposures measured in pool water, additional associations were found for bromodichloromethane and the brominated species. 

Conclusions
After annotation of the metabolites, our work will provide insights into metabolic changes induced by DBP exposure, shedding light on biological pathways affected by these exposures, and in-turn impacting future risk of adverse health outcomes.
 
Funding source
EXPOsOMICS project