Abstract

Background Comprehensive environmental risk characterization, encompassing physical, chemical, social, ecological, and lifestyle stressors, necessitates innovative approaches to handle the escalating complexity. This is especially true when considering individual and population-level diversity, where the myriad combinations of real-world exposures magnify the combinatoric challenges. The GeoTox framework offers a tractable solution by integrating geospatial exposure data from source-to-outcome in a series of modular, interconnected steps.

Results Here, we introduce the GeoTox open-source R software package for characterizing the risk of perturbing molecular targets involved in adverse human health outcomes based on exposure to spatially-referenced stressor mixtures. We demonstrate its usage in building computational workflows that incorporate individual and population-level diversity. Our results demonstrate the applicability of GeoTox for individual and population-level risk assessment, highlighting its capacity to capture the complex interplay of environmental stressors on human health.

Conclusions The GeoTox package represents a significant advancement in environmental risk characterization, providing modular software to facilitate the application and further development of the GeoTox framework for quantifying the relationship between environmental exposures and health outcomes.

By integrating geospatial methods with cutting-edge exposure and toxicological frameworks, GeoTox offers a robust tool for assessing individual and population-level risks from environmental stressors. GeoTox is freely available at https://niehs.github.io/GeoTox/.

Competing Interest Statement

The authors have declared no competing interest.

Funding Statement

This work is supported by the National Institute of Environmental Health Sciences, Division of Translational Toxicology, Division of Intramural Research, and the Spatiotemporal Exposures and Toxicology group under project number ZIA ES103368-02.

Author Declarations

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.

Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

Yes

I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.

Yes

Data Availability

The software and package data is open-source. The large data examples from the manuscript are available upon reasonable request to the authors.

https://niehs.github.io/GeoTox/

6 List of AbbreviationsAEPAggregate Exposure PathwayAOPAdverse Outcome PathwaycHTScurated high-throughput screeningGCAGeneralized Concentration Additionhttkhigh-throughput toxicokineticsKCCKey Characteristics of CarcinogensNGRANext Generation Risk AssessmentSNPSingle Nucleotide Polymorphism