Small plastic particles in the human foetal environment: novel studies on exposure and hazard

The potential adverse effects of exposure to small plastic particles (SPPs) during human development are largely unexplored. Chemicals associated with plastics, such as bisphenols and phthalates, are known to pass the placenta and have been detected in amniotic fluid. Exposure to these plastic-associated chemicals may disrupt the development of the foetus. Experimental studies with human ex vivo placental perfusion models indicate that SPPs, in particular particles in the low micro- and nanometre range, will accumulate in the placenta when added directly to placental cultures. Studies in rodents suggest that relatively high doses of SPPs result in placental uptake. However, the presence of SPPs in real human placental samples has never been confirmed, and the cross-placental transport of SPPs into foetal amniotic fluid has never been studied. Using real-life samples of human placenta and amniotic fluid, this proposal aims to characterize the exposure of the human foetal environment to SPPs in the low micro- (<20 µm) and nanometre (<500 nm) range. It will also examine the potential hazard of SPPs and associated chemicals to the developing placenta. To this end, we will determine the exposure of SPPs in human placenta and AF. In a collaborative study between the Netherlands and the U.S., we will compare analytical methods, including digestion of tissue (for placenta) and large biomolecules such as proteins (for amniotic fluid) followed by microscopy, pyrolysis-gas chromatography-mass spectrometry (pyrGC-MS) and alkali-assisted thermal hydrolysis for depolymerization of SPPs with measurement by ultra-high-resolution mass spectrometry (HRM). Based on the untargeted profiles acquired by HRM, microscopy, and pyrGC-MS, we will extend recent work with environmental samples and build supervised-cluster analyses to obtain novel chemical classifiers for SPPs in human placenta. To examine the hazard of SPPs and associated compounds in human placental cells, we will use the human BeWo b30 placental syncyiotrophoblast cell line. Toxicity testing will be performed with SPPs of the same size range as expected in placenta, using both fluorescent commercially available SPPs as well as novel environmentally relevant SPPs prepared by weathering particles of various types and shapes. SPPs that have been stripped of chemicals will be compared to weathered particles, to elucidate sources of toxicity, i.e. particle vs chemical toxicity. This multidisciplinary project represents an important first attempt to detect SPPs in real human placenta samples. It also the first study to examine the effects of environmentally relevant SPPs on uptake and toxicity in placenta cells. This project has significant potential impact in terms of providing a ‘proof of principle’ that SPPs are a health risk during human development. It provides a solid foundation in terms of novel analytical, statistical and toxicological approaches for further research in this growing field.