Safe and Sustainable Alternatives Research Program

National Institute Of Environmental Health Sciences

Investigators

Linked publications, trials & patents

Abstract

In FY22-23, the SSA program of the DTT has continued to advance research within the project portfolio to achieve the aspirations of state objectives. Central to these efforts has been the completion of the PFAS/AFFF in vitro hepatocyte screening manuscript, which was submitted to, and cleared, in-house reviews. This manuscript will be submitted as a high impact article into the journal Environmental Science and Technology, and will describe the research teams exploration of PFAS toxicity mechanisms in human liver cell cultures established to predict the potencies of human liver injury. The team contextualized biological-response similarity relationships among PFAS-containing complex mixtures and individual chemical. Moreover, the hepatocyte transcriptomics platform successfully predicted in vivo liver weight change potencies from in vitro data. The team is re-focusing on the in vivo bioaccumulation manuscript for FY23-24. In addition, for FY22-23, the AFFF team led the creation of a first-in-class decision framework that integrated in vivo and in vitro data streams into a product prioritization metric to identify safer products for military use. This framework will be published with the US Department of Defense in FY23-24. Central to this framework, and tuned to the unique challenges of PFAS toxicity, is the inclusion of innovative study designs to address PFAS bioaccumulation from complex mixtures exposures (i.e., Aqueous film-forming foams). A critical gap identified by the SSA with PFAS and PFAS mixtures was a need to foster development of rapid approaches to proactive identify chemical constituents that build up in our bodies upon extended/repeated exposure periods. Thus, the teams have initiated efforts to identify computational, in vitro screening, and advanced microphysiological systems for prospective identification of bioaccumulating PFAS and other environmental chemicals. Preliminary data indicate a clear opportunity for effectively addressing this critical research need for environmental toxicology research. The SSA Program is primarily oriented toward responsive research needs identified in partnership with external stakeholders. The designs seek to provide quantitative/actionable methods and information with efficient and timely delivery. Building on the DTT 's strong "brand" of trusted science in support of decision-making with environmental chemicals and 21st Century toxicology screening, the SSA Program has facilitated green chemistry approaches that contextualize hazards and identify safer alternatives through innovative tools and approaches. Ultimately, facilitating prevention of hazardous substances being introduced into the marketplace through advances in environmental toxicology can help to break the historical cycles of regrettable substitutions and genuinely provide safer and sustainable alternatives. For FY22-23, the SSA program has partnered with the A4 alternatives association to host a workshop to engage with the public and identify opportunities for collaborative breakthroughs in the science of mixtures assessments and engagement on opportunities to enable greener chemistry.