Mechanistic Pharmacokinetic Modeling of the Bioamplification of Persistent Lipophilic Organic Pollutants in Humans during Weight Loss

Environ Sci Technol. 2017 May 16;51(10):5563-5571. doi: 10.1021/acs.est.7b00055. Epub 2017 May 3.

Abstract

Bioamplification means the liberation of persistent lipophilic organic pollutants (PLOPs) into blood from their storage in inert adipose tissue during rapid weight loss. Here, using a modified mechanistic pharmacokinetic model, we investigated how chemical properties and anthropometric parameters interact to influence the bioamplification of various PLOPs in humans. The model succeeds in reproducing literature documented weight loss-induced increments in human blood PLOP concentrations. We simulated the degree of bioamplification, as characterized by the bioamplification factor (BAmF), of hypothetical PLOPs with different combinations of partitioning and biotransformation properties at various rates of lipid loss. We also investigated how BAmF evolves with the duration of weight loss. Results show that bioamplification is expected to occur for any chemical with even moderate lipophilicity (log KOW > 2 and log KOA > 6) as long as the half-life for metabolic elimination is long relative to the time scale of relative lipid loss (e.g., exceeding 104 h in the case of lipid loss of 3 kg month-1 with an initial lipid mass of 40 kg). While BAmF of a chemical is time-variant, whether bioamplification occurs for a chemical or not is independent of the duration of weight loss. The successful application of such a simple model demonstrates that it is the lipid dynamics that predominantly govern the dynamics of PLOPs rather than vice versa.

MeSH terms

  • Adipose Tissue / chemistry*
  • Biotransformation
  • Environmental Pollutants / pharmacokinetics*
  • Half-Life
  • Humans
  • Models, Theoretical
  • Weight Loss*

Substances

  • Environmental Pollutants