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

Abstract

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.

The Human Early-Life Exposome (HELIX): Project Rationale and Design

“…PBPK models describe the fate of chemicals in the body using individual-specific information about the physiology (age, sex, weight) and the biochemistry (enzyme content) of the individual as well as information on the individual’s behavior (breastfeeding, physical activity, diet) (Beaudouin et al 2010). In the context of population (epidemiological) studies, PBPK models can be used to simulate exposure during critical time periods in between biomarker measurement points (e.g., Gascon et al 2013b; Lyons et al 2008; Ulaszewska et al 2012). To be relevant, this approach requires detailed input data on individual characteristics and behaviors to minimize assumptions and uncertainties.…”

Added value of human biomonitoring in assessment of general population exposure to xenobiotics

“…Modelling approaches from HBM data could be used for generating consistent input data for human exposure assessment. For example, Ulaszewska et al (22) used HBM data of PCB levels in breast milk from Italian women and PBPK models to determine the most probable scenario of exposure: for each congener, the authors determined the most probable long-term history of PCB emission in air as well as concentrations in environmental receptor media and food, and estimated the time evolution of daily intakes over a lifetime. As a result, they were able to accurately reconstruct exposure and supplement the data gaps on environmental concentrations over a period of decades.…”

Development and Application of a Probabilistic Risk–Benefit Assessment Model for Infant Feeding Integrating Microbiological, Nutritional, and Chemical Components

“…Initial level of dl-PCB, N dl-PCB 0 (k = PIF), was based on European data (including French). (83) A uniform distribution was implemented between half of the (94) Uncertainty Note: The "Category" column indicates the kind of dispersion, which reflects the distribution of inputs: variability or uncertainty. When none is considered, a deterministic value is used, D.…”

“…In addition, it needs to be taken into account that levels of chemicals in BM could decrease according to the lactation duration due to a depuration phenomenon, in average this decrease is around 0.17% per week. (94) Nevertheless, this depuration phenomenon remains discussed (95,96) so a uniform distribution was implemented between 0 up to 1.7% per week. The daily exposure of breast-fed infants was thus estimated with Equation (21) adapted from Ulaszewska et al: (84)…”