Bayesian analysis of a PBPK model to reconstruct the exposure of Italian women to PCB-153 via breast milk concentrations

Polychlorinated biphenyls (PCBs) are persistent organic pollutants that induce numerous toxic effects on humans (for example, cancer, liver damage, or neurological and motor control problems for in utero exposure). Despite the banning to produce PCBs, these chemicals continue to be a human health concern through bioaccumulation. PCBs have been detected in different human media, such as blood, adipose tissues and for pregnant and lactating women in placenta, cord blood and breast milk. Breast milk samples are usually used to predict the exposure of breastfed infants, but information contained in these samples about the history of the women exposure is rarely used. In this work, we propose to perform the reverse dosimetry methodology with the breast milk concentrations. In other words, we propose to model the toxicokinetics of a PCB of interest in humans in order to simulate the internal levels and then to use the breast milk concentrations to reconstruct the exposure of women to PCBs. PCB-153 was selected for this study. PCB-153 is one of the most prevalent PCB congener detected in human tissue, and it has been suggested as a valuable indicator for PCBs in the food of animal origin (i.e. fish). Its presence in breast milk was also found to be a biomarker of total sum TEQ concentrations. Human biomonitoring of breast milk was conducted in Italy in 2008-2009 on 60 women living in 3 different areas (agricultural or industrial area). A stochastic physiologically based pharmacokinetic (PBPK) model has been recently developed to assess the tissue dosimetry of different chemicals over the human lifespan, including the pregnancy and lactation periods. This model was parameterized to simulate the PCB-153 internal levels in the Italian women. Instead of defining a constant intake through the entire life, data obtained from national food consumption studies and food contamination in Italy were used to derive the tendency of the intake of PCB-153 in the Italian population. A Bayesian analysis of the PBPK model was then performed to estimate the exposure dose of mothers during their lifetime