The Comparative Toxicogenomics Database (CTD; http://ctdbase.org/) harmonizes cross-species heterogeneous data for chemical exposures and their biological repercussions by manually curating and interrelating chemical, gene, phenotype, anatomy, disease, taxa, and exposure content from the published literature. This curated information is integrated to generate inferences, providing potential molecular mediators to develop testable hypotheses and fill in knowledge gaps for environmental health. This dual nature, acting as both a knowledgebase and a discoverybase, makes CTD a unique resource for the scientific community. Here, we report a 20% increase in overall CTD content for 17 100 chemicals, 54 300 genes, 6100 phenotypes, 7270 diseasesand 202 000 exposure statements. We also present CTD Tetramers, a novel tool that computationally generates four-unit information blocks connecting a chemical, gene, phenotype, and disease to construct potential molecular mechanistic pathways. Finally, we integrate terms for human biological media used in the CTD Exposure module to corresponding CTD Anatomy pages, allowing users to survey the chemical profiles for any tissue-of-interest and see how these environmental biomarkers are related to phenotypes for any anatomical site. These, and other webpage visual enhancements, continue to promote CTD as a practical, user-friendly, and innovative resource for finding information and generating testable hypotheses about environmental health.