Desynchronized circadian clock and exposures to xenobiotics are associated with differentiated disease phenotypes: The interface of desynchronized circadian clock and exposures to xenobiotics would lead to adverse response and recovery.

A paradigm shift in the human chronotoxicity of xenobiotics would study two-sided desynchronized phenomena of interfacial interactions between cyclic or periodic environmental insults and the endogenous response and recovery profile. These systems-based networks are under the influence of well-synchronized biological clocks and their metabolic regulators. This perspective argues in favor of addressing the concept of synchronization in studies involving critical life windows of susceptibility, or circadian rhythms, or 24-hour (periodic) diurnal rhythms and answering whether these disruptions in synchronization would affect response and recovery or disease phenotypes associated with environmental insults, e.g., xenobiotics. Synchronization or synchrony is defined as the totality of elements that appear during the same time period within a system, including the network of interactions between the system's elements. Desynchronized interfaces during critical life windows or in time-repeated exposure events would likely lead to initiating a cascade of adverse health effects associated with differentiated disease phenotypes.

The Need for an Alternative Health Claim Process for Foods Based on Both Nutrient and Contaminant Profiles.

Most authorized health claims on foods have been established on the basis of single dietary components, mainly micronutrients, such as vitamins, minerals, and possibly bioactives. Failure to sufficiently define and characterize the nutritional profile of a food product is one of the main reasons for rejection or incomplete status for thousands of health claim applications, whereas the food's contaminant profile is simply not accounted for. The objective of this work was to highlight the accumulating scientific evidence supporting a reform of the health claim evaluation process for foods toward more holistic approaches. This would entail the characterization of multiple nutrient-contaminant pairs and contaminant mixture profiles at contaminant levels currently considered "safe," including their interactions that would impact human health outcome(s) in a net positive or negative direction. The notion of a stable nutritional profile in food commodities has been challenged by studies reporting a variable food contaminant content and a declining content of proteins/micronutrients in crops due to anthropogenic greenhouse gas emissions. A holistic approach in the health claim process for foods would entail the incorporation of cumulative risk assessment and/or risk-benefit protocols that effectively combine health risks and benefits associated with multiple nutritional and contaminant attributes of the food/diet under evaluation.