The Exposome in Toxicologic Pathology

The “exposome” is an individual’s lifetime spectrum of chemical exposures beginning at conception. An exposome includes general external influences such as pollution and weather; external individual-specific factors (diet, infections, self-selected chemical intake); and internal individual-specific constituents (metabolic byproducts, microbiome derivatives, inflammatory mediators, stress hormones, etc). The exposome paradigm is inherent in animal toxicity testing because laboratory studies are designed so that subjects share a common exposure history encompassing not only exposure(s)/treatment(s) but also other chemical sources (eg, air, bedding, food, water). Toxicologic pathologists should remember that some differences in responsiveness to a test article may reflect subtle differences in individual exposomes of seemingly equivalent test animals. Translation of toxicity data obtained in tests of genetically inbred animals maintained under controlled environmental conditions to produce quasi-identical exposomes at best offers only approximate guidance regarding potential responses in genetically heterogeneous human populations who live in many environmental settings and thus have divergent, complex exposomes.