Developing the Regulatory Utility of the Exposome: Mapping Exposures for Risk Assessment through Lifestage Exposome Snapshots (LEnS)

Abstract

Background: Exposome-related efforts aim to document the totality of human exposures across the lifecourse. This field has advanced rapidly in recent years but lacks practical application to risk assessment, particularly for children's health.

Objectives: Our objective was to apply the exposome to children's health risk assessment by introducing the concept of Lifestage Exposome Snapshots (LEnS). Case studies are presented to illustrate the value of the framework.

Discussion: The LEnS framework encourages organization of exposome studies based on windows of susceptibility for particular target organ systems. Such analyses will provide information regarding cumulative impacts during specific critical periods of the life course. A logical extension of this framework is that regulatory standards should analyze exposure information by target organ, rather than for a single chemical only or multiple chemicals grouped solely by mechanism of action.

Conclusions: The LEnS concept is a practical refinement to the exposome that accounts for total exposures during particular windows of susceptibility in target organ systems. Application of the LEnS framework in risk assessment and regulation will improve protection of children's health by enhancing protection of sensitive developing organ systems that are critical for lifelong health and well-being. https://doi.org/10.1289/EHP1250.

Figure 1.

Contrast between previous discussions of the exposome (top), focusing on total lifetime exposures in relation to cancer or other chronic diseases, and new framework for the Lifestage Exposome Snapshots (LEnS) (bottom), based on sensitive periods of development defined by health endpoints of interest. The LEnS approach may be more feasible to implement because the exposure snapshots of interest represent shorter periods of time, compared with the whole lifetime as envisioned in the traditional exposome approach.

Figure 2.

Illustration of multiple environmental exposures during critical periods of brain development. The LEnS approach focuses on lifestage-specific exposures for target systems of interest. Timeline of brain development (bottom) adapted from Bernal (2007), reproduced with permission. Depiction of multiple exposures over time (top) adapted from Robinson and Vrijheid (2015), reproduced with permission.

Figure 3.

Current pesticide risk assessment requires aggregate and cumulative assessment by mode of action (MOA) and therefore ignores the impact of cumulative exposures to multiple compounds acting by different mechanisms to disrupt the same organ system.

Figure 4.

Comparison between (A) traditional single chemical risk assessment, (B) FQPA risk cup determination, (C) LEnS risk assessment based on critical windows.