Reconstruction of the dynamic exposure to PCBs for Italian population using physiologically based pharmacokinetic (PBPK) model and a complex approach combining human biomonitoring studies and environmental data

Polychlorinated biphenyls (PCBs) are persistent contaminants suspected to cause adverse health effects in humans. Due to their extensive use in the past and persistence in the environment significant amounts are still detectable in environmental media. The major route of human exposure is contaminated food. Since food contamination by PCBs has not been monitored frequently in the past and was rarely congener-specific, human exposure cannot be directly assessed. An alternative to this lack of data is to use exposure models developed for environmental media and to transpose the environmental model outcomes into time-variant dietary intakes. According to the hypotheses assumed, the shape and the magnitude of the modeled intakes are affected by uncertainty leading to several possible exposure scenarios. Here we propose to improve this methodology by integrating actual internal levels in humans (from biomonitoring studies) in order to reduce the uncertainty in the exposure scenario. We propose to model the exposure and the toxicokinetics of PCBs in humans and to analyze breast milk levels of Italian primiparous women in this modeling framework in order to determine the most likely scenario of exposure (i.e. the shape and magnitude). Our approach was applied to most prevalent PCB congeners detected in human milk and fluids: PCB-138 (2,2',3,4,4',5'-hexachlorobiphenyl), PCB-153 (2,2',4,4',5,5'-hexachlorobiphenyl) and PCB-180 (2,2',3,4,4',5,5' -heptachlorobiphenyl). Breast milk concentrations were measured in Italian women for PCB-138, PCB-153 and PCB-180. Forty one healthy primiparous women, not-occupationally exposed to PCBs, were included in biomonitoring study: 15 women from Giugliano in Campania, 18 from Piacenza and 8 from Milan. For each congener, three exposure scenarios were derived and a PBPK model was used to relate the lifetime exposure to the breast milk levels. For the three PCBs, we determined the most probable scenario of exposure. A Bayesian analysis was performed to estimate the magnitude of each exposure scenario for each woman using the breast milk concentrations. The intake estimates are in good agreement with previous exposure assessments based solely on food contamination demonstrating the relevance of our approach to reconstruct accurately the exposure and to fill in data gaps on exposure. The link between the exposure scenario and biomonitoring data was provided by the PBPK model in order to support the adequacy of the models according to the data (e.g., for PCB-180) or to identify possible improvements for the exposure and PBPK models (e.g., for PCB-138 and PCB-153)

Interpreting PCB levels in breast milk using a physiologically based pharmacokinetic model to reconstruct the dynamic exposure of Italian women

Polychlorinated biphenyls (PCBs) are persistent contaminants suspected to cause adverse health effects in humans. As PCBs levels in food have not been monitored frequently in the past, modeling approaches based on environmental data have been proposed to predict the human dietary intake. In this work, we propose to improve these approaches by taking into account internal levels of PCBs in humans. This methodology is based on the analysis of biomonitoring data using exposure and physiologically based pharmacokinetic (PBPK) modeling to determine the most probable scenario of exposure. Breast milk concentrations were measured in Italian women for PCB-138, PCB-153 and PCB-180. For each congener, three exposure scenarios were derived and a PBPK model was used to relate the lifetime exposure to the breast milk levels. For the three PCBs, we determined the most probable scenario of exposure. Our results support the adequacy of the exposure and the PBPK models for PCB-180 and PCB-153, whereas we observed discrepancies between the models and the biomonitoring data for PCB-138. Our intake estimates are in good agreement with previous exposure assessments based solely on food contamination demonstrating the relevance of our approach to reconstruct accurately the exposure and to fill in data gaps on exposure. \ua9 2012 Nature America, Inc. All rights reserved