Skip to main content
. 2020 Jan 17;128(1):015001. doi: 10.1289/EHP6104

Figure 3.

Figure 3A is a flow diagram with eight steps, which, from the top to bottom, are as follows: 1. Exposures, 2. Molecular changes, 3. Cell-level changes, 4. Tissue-level changes, 5. Individual health effects, 6. Transgenerational effects and 7. Early life effects, and 8. Population health effects. In silico, in vitro experiments, in vivo experiments, and cohort studies travel from top to bottom, covering the range till 2. molecular changes, 3. cell level changes, 6. transgenerational and early life effects, and 8. Population health effects, respectively. Case control studies from the bottom to the top, covering the range till either 2. molecular changes or 1. exposures. Adverse outcomes pathways move both from the top to the bottom and from the bottom to the top, covering different ranges. Figure 3B shows that Tier 1 screen and mixtures of the HTS screen cover the range till 2. molecular changes. Tier 1 screen extends to tier 2 screen and mixtures extend, both covering the range till 4. tissue-level changes. Systems toxicology covers the entire range, moving both from the top to the bottom and from the bottom to the top.

An integrative method for investigating the impact of environmental chemicals on the epigenome and a proposed approach for toxico-epigenomic screening. (A) Comparison of in silico, in vitro, in vivo, population-based, and integrative methods in fully understanding the potential effects of environmental chemicals on the epigenome. Dotted arrows indicate situations where evidence can be inferred but not directly proved by the described methods. (B) An illustration of a proposed approach for toxicoepigenomic screening. A high-throughput screen (HTS) using in vitro and in silico methods can be conducted using single compounds and mixtures. Hits identified from the Tier 1 screen can be characterized more extensively using relevant in vitro and in vivo experiments. Finally, a systems toxicology approach could be used to integrate all data, including human data, to generate a complete profile of epigenotoxicology.