Collaborative Research: CAS: Filling Gaps in the Environmental Fate of Lubabegron, an Emerging use Beta-adrenergic Receptor Agonist/Antagonist Proposed for Sustainable Agriculture

With support from the Environmental Chemical Sciences Program in the Division of Chemistry, Nicholas C. Pflug at the SUNY College of Environmental Science and Forestry, David M. Cwiertny at the University of Iowa, and Dalma Martinovic-Weigelt at the University of St. Thomas will collaboratively investigate how a chemical that is widely used in animal agriculture known as lubabegron behaves in the environment. The risks to the environment and people that may be exposed to lubabegron from its use in beef production will also be determined. The research team will explore how lubabegron, which is applied as an animal feed, is broken down by beef cattle, helping to better understand the forms of the chemical that are released to the environment in animal waste. Common pathways by which lubabegron breaks down in the environment will be established and additional studies will assess the toxicity of lubabegron and its major break down products that are identified through experimental investigations. In addition to training of graduate and undergraduate students, the research team will engage in several activities that will promote awareness of lubabegron and its use among the research and environmental policy community, promote additional study of its environmental occurrence, and help to ensure a safe food system for humans and the environment. This highly collaborative project aims to produce fundamental chemical insights into the application of lubabegron in animals through microsomal metabolism studies. These studies will also probe the environmental fate of lubabegron in surface waters and soils through photolysis and soil partitioning studies. The team will conduct bioeffects assays to assess the ecological and human health hazards associated with exposure to lubabegron, its metabolites, and environmental transformation products. The project will use advanced analytical chemical tools (e.g., liquid chromatography with high resolution tandem mass spectrometry, preparatory column separations, and nuclear magnetic resonance (NMR) spectroscopy) to isolate and characterize lubabegron metabolites and transformation products. Analytical methods development for the separation and detection of lubabegron in complex mixtures will allow a subset of experiments to be conducted at environmentally relevant concentrations in authentic environmental matrices. Bioactivity testing will use commercially available, high throughput transcription factor, nuclear receptor, and G-protein coupled receptor assays, complemented by targeted characterization of select biological endpoints using traditional in vitro approaches. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.