S3: Building AOPs for arsenic-induced developmental outcomes
Building AOPs for arsenic-induced developmental outcomes for improved risk assessment
University of North Carolina
This presentation will detail the development of Adverse Outcome Pathways (AOPs) as they relate to inorganic arsenic exposure in pregnant women and the health of their offspring. In 2012, the Organization for Economic Co-operation and Development (OECD) launched a new program on the development of AOPs. Here we describe the ongoing research that represents an academic-government partnership to develop AOPs as they relate to infant outcomes. These outcomes include lower birth weight, preterm birth and fetal growth restriction relevant to early life exposure to inorganic arsenic. A molecular initiating event (MIE) for these adverse outcomes is the generation of reactive oxygen species. Other key events include inflammation, DNA damage and epigenetic modifications and subsequent transcription related to critical placental and fetal growth-related genes. Linkages across varying levels of biological organization (e.g. molecular, cellular, tissue, organ and organism) will be discussed. AOPs serve a role as a mechanism to integrate mechanistic toxicological data into the risk assessment process in relationship to diverse chemicals in the environment.