Background: Adipose tissue (AT) is involved in several physiological functions, including metabolic regulation, energy storage, and endocrine functions.Objectives: In this review we examined the evidence that an additional function of AT is to modulate persistent organic pollutant (POP) toxicity through several mechanisms.Methods: We reviewed the literature on the interaction of AT with POPs to provide a comprehensive model for this additional function of AT.Discussion: As a storage compartment for lipophilic POPs, AT plays a critical role in the toxicokinetics of a variety of drugs and pollutants, in particular, POPs. By sequestering POPs, AT can protect other organs and tissues from POPs overload. However, this protective function could prove to be a threat in the long run. The accumulation of lipophilic POPs will increase total body burden. These accumulated POPs are slowly released into the bloodstream, and more so during weight loss. Thus, AT constitutes a continual source of internal exposure to POPs. In addition to its buffering function, AT is also a target of POPs and may mediate part of their metabolic effects. This is particularly relevant because many POPs induce obesogenic effects that may lead to quantitative and qualitative alterations of AT. Some POPs also induce a proinflammatory state in AT, which may lead to detrimental metabolic effects.Conclusion: AT appears to play diverse functions both as a modulator and as a target of POPs toxicity.

Experimental studies investigating the effects of endocrine disruptors frequently identify potential unconventional dose-response relationships called non-monotonic dose-response (NMDR) relationships. Standardized approaches for investigating NMDR relationships in a risk assessment context are missing. The aim of this work was to develop criteria for assessing the strength of NMDR relationships. A literature search was conducted to identify published studies that report NMDR relationships with endocrine disruptors. Fifty-one experimental studies that investigated various effects associated with endocrine disruption elicited by many substances were selected. Scoring criteria were applied by adaptation of an approach previously used for identification of hormesis-type dose-response relationships. Out of the 148 NMDR relationships analyzed, 82 were categorized with this method as having a “moderate” to “high” level of plausibility for various effects. Numerous modes of action described in the literature can explain such phenomena. NMDR can arise from numerous molecular mechanisms such as opposing effects induced by multiple receptors differing by their affinity, receptor desensitization, negative feedback with increasing dose, or dose-dependent metabolism modulation. A stepwise decision tree was developed as a tool to standardize the analysis of NMDR relationships observed in the literature with the final aim to use these results in a Risk Assessment purpose. This decision tree was finally applied to studies focused on the effects of bisphenol A.

ObjectiveIn this study we reviewed the half-life data in the literature for the 29 dioxin, furan, and polychlorinated biphenyl congeners named in the World Health Organization toxic equivalency factor scheme, with the aim of providing a reference value for the half-life of each congener in the human body and a method of half-life estimation that accounts for an individual’s personal characteristics.Data sources and extractionWe compared data from > 30 studies containing congener-specific elimination rates. Half-life data were extracted and compiled into a summary table. We then created a subset of these data based on defined exclusionary criteria.Data synthesisWe defined values for each congener that approximate the half-life in an infant and in an adult. A linear interpolation of these values was used to examine the relationship between half-life and age, percent body fat, and absolute body fat. We developed predictive equations based on these relationships and adjustments for individual characteristics.ConclusionsThe half-life of dioxins in the body can be predicted using a linear relationship with age adjusted for body fat, smoking, and breast-feeding. Data suggest an alternative method based on a linear relationship between half-life and total body fat, but this approach requires further testing and validation with individual measurements.

Nanoparticles' health risks depend on their biodistribution in the body. Phagocytosis may greatly affect this distribution but has not yet explicitly accounted for in whole body pharmacokinetic models. Here, we present a physiologically based pharmacokinetic model that includes phagocytosis of nanoparticles to explore the biodistribution of intravenously injected polyethylene glycol-coated polyacrylamide nanoparticles in rats. The model explains 97% of the observed variation in nanoparticles amounts across organs. According to the model, phagocytizing cells quickly capture nanoparticles until their saturation and thereby constitute a major reservoir in richly perfused organs (spleen, liver, bone marrow, lungs, heart and kidneys), storing 83% of the nanoparticles found in these organs 120 h after injection. Key determinants of the nanoparticles biodistribution are the uptake capacities of phagocytizing cells in organs, the partitioning between tissue and blood, and the permeability between capillary blood and tissues. This framework can be extended to other types of nanoparticles by adapting these determinants.