UC Berkeley

Despite their ubiquity in modern life, industrial chemicals are poorly regulated in the United States. Statutory law defines industrial chemicals as chemicals that are not foods, drugs, cosmetics, nor pesticides, but may be used in consumer products, and this distinction places them under the purview of the Toxic Substances Control Act (TSCA), which received a substantial update when the US congress passed a revision of the act in 2016. The revised law, the Frank R. Lautenberg Chemical Safety for the 21st Century Act addresses many but not all of TSCA’s failings, and rightfully emphasizes the development and adoption of high throughput screens, in vitro, and alternative assays to improve the process for registering new chemicals and to address the tens of thousands of untested chemicals currently in the TSCA inventory. As the discipline of toxicology gradually shifts from its’ history as a reactive science (responding to problems after they’ve occurred) to a proactive science (attempting to predict and circumvent dangers to human and environmental health), two things become clear: 1.) traditional low throughput toxicological testing methodologies are inadequate to address both the volume of chemicals of interest and the pace of research; and 2.) the modern industrial chemical ecosystem is complex and no single testing solution will be appropriate for all the actors that populate that ecosystem.

To address these challenges, three interventions are proposed, each of which targets a different population within the industrial chemical ecosystem. The first intervention is a suite of computational toxicology methods targeted towards chemists in the initial phases of chemical design and development. The second intervention is an alternative assay, the yeast functional toxicogenomic assay, permits industrial or government labs to rapidly investigate differences in cytotoxic mechanism between different chemicals – even if they are structurally very similar. The third intervention explored in this work is a method for enhancing the metabolic capacity of cell lines currently used by regulators for high throughput cytotoxicity testing. These interventions individually are not necessarily appropriate for all actors across the US industrial chemicals ecosystem, but as bespoke solutions they may be quite useful, and, it is hoped, support a larger exploration of where and how similar efforts may be spent most effectively to reduce industrial chemical hazard.