Interindividual Variation in Source‐Specific Doses is a Determinant of Health Impacts of Combined Chemical Exposures

Abstract

All individuals are exposed to multiple chemicals from multiple sources. These combined exposures are a concern because they may cause adverse effects that would not occur from an exposure recieved from any single source. Studies of combined chemical exposures, however, have found that the risks posed by such combined exposures are almost always driven by exposures from a few chemicals and sources and frequently by a single chemical from a single source. Here, a series of computer simulations of combined exposures are used to investigate when multiple sources of chemicals drive the largest risks in a population and when a single chemical from a single source is responsible for the largest risks. The analysis found that combined exposures drive the largest risks when the interindividual variation of source-specific doses is small, moderate-to-high correlations occur between the source-specific doses, and the number of sources affecting an individual varies across individuals. These findings can be used to identify sources with the greatest potential to cause combined exposures of concern.

Sanitary, Hygienic and Organizational Criteria for Reducing the Risk of COVID-19

“…It is clear that during the spread of coronavirus infection, determining the environment is a priority to clarify the exposure scenario that describes the movement path from the place of formation to the point of exposure [34].…”

Opportunities and challenges related to saturation of toxicokinetic processes: Implications for risk assessment

“…Another concern that was raised, that is not directly addressed by the case studies presented here or in the companion paper ( Lowe, 2021 ), is related specifically to cumulative exposure; that is, people can be exposed to several substances at the same time and that when these substances have a similar mode of action, it is the accumulated exposure, not the exposure to a single substance, that should be compared to the top dose in a toxicity study. In a recent paper ( Price, 2020 ), an analysis was conducted to investigate a common observance, following the Pareto principle, 4 that risks posed by combined exposures from multiple chemicals are typically driven by exposures from a few chemicals/sources and also that individuals with the highest exposures were driven by a single chemical from a single source. The paper identifies characteristics of those cases where cumulative exposure is driven by a limited set of chemicals/sources and proposes that it may be possible to develop criteria to predict if risks from combined exposures would exceed the risks from separate exposures to individual chemicals.…”