Adverse birth outcomes are a critical global public health concern, with substantial health and financial impacts on mothers, babies, families and communities-at-large. Exposures to environmental pollutants are increasingly thought to contribute to pregnancy complications, adverse birth outcomes and/or developmental effects. For example, over the last half-century, there has been a large body of scientific evidence associating maternal both firsthand and secondhand smoke exposure with a multitude of pregnancy complications involving the placenta, adverse birth outcomes and developmental effects. Despite strong evidence linking firsthand and secondhand smoke exposure to offspring health effects, little is known about pregnancy health effects of maternal exposure to thirdhand smoke (THS), the chemical residues from secondhand smoke that accumulate on hard surfaces as dust-like particles and embed in soft surfaces over time. We plan to use two parallel in vitro models to investigate the toxic effects of thirdhand smoke collected from house dust samples on placenta using a placental cell line HTR-8/SVneo, and on fetal development using zebrafish. We will assess cell viability, cytotoxicity and proliferation in placental cells and embryonic survival, morphology (structural defects), and hatching success in zebrafish. In both models, mechanisms of toxicity will be assessed using fluorometric reporters of detoxification mechanisms and qPCR of important enzymes in xenobiotic response. Our research will provide crucial toxicological data for THS toxicity during pregnancy, which is currently unavailable. This data will be communicated with regulatory toxicologists and can be used to inform federal, state and local policies around smoking.