Addressing Urgent Questions for PFAS in the 21st Century.

Despite decades of research on per- and polyfluoroalkyl substances (PFAS), fundamental obstacles remain to addressing worldwide contamination by these chemicals and their associated impacts on environmental quality and health. Here, we propose six urgent questions relevant to science, technology, and policy that must be tackled to address the "PFAS problem": (1) What are the global production volumes of PFAS, and where are PFAS used? (2) Where are the unknown PFAS hotspots in the environment? (3) How can we make measuring PFAS globally accessible? (4) How can we safely manage PFAS-containing waste? (5) How do we understand and describe the health effects of PFAS exposure? (6) Who pays the costs of PFAS contamination? The importance of each question and barriers to progress are briefly described, and several potential paths forward are proposed. Given the diversity of PFAS and their uses, the extreme persistence of most PFAS, the striking ongoing lack of fundamental information, and the inequity of the health and environmental impacts from PFAS contamination, there is a need for scientific and regulatory communities to work together, with cooperation from PFAS-related industries, to fill in critical data gaps and protect human health and the environment.

Using Chicken Embryo as a Powerful Tool in Assessment of Developmental Cardiotoxicities.

Chicken embryos are a classical model in developmental studies. During the development of chicken embryos, the time window of heart development is well-defined, and it is relatively easy to achieve precise and timely exposure via multiple methods. Moreover, the process of heart development in chicken embryos is similar to mammals, also resulting in a four-chambered heart, making it a valuable alternative model in the assessment of developmental cardiotoxicities. In our lab, the chicken embryo model is routinely used in the assessment of developmental cardiotoxicities following exposure to various environmental pollutants, including per- and polyfluoroalkyl substances (PFAS), particulate matter (PMs), diesel exhaust (DE) and nano materials. The exposure time can be freely selected based on the need, from the beginning of development (embryonic day 0, ED0) all the way to the day prior to hatch. The major exposure methods include air-cell injection, direct microinjection, and air-cell inhalation (originally developed in our lab), and the currently available endpoints include cardiac function (electrocardiography), morphology (histological assessments) and molecular biological assessments (immunohistochemistry, qRT-PCR, western blotting, etc.). Of course, the chicken embryo model has its own limitations, such as limited availability of antibodies. Nevertheless, with more laboratories starting to utilize this model, it can be used to make significant contributions to the study of developmental cardiotoxicities.

Assessment of recent developmental immunotoxicity studies with bisphenol A in the context of the 2015 EFSA t-TDI.

Humans are exposed to bisphenol A (BPA) mainly through the diet, air, dust, skin contact and water. There are concerns about adverse health effects in humans due to exposure to bisphenol A (BPA). The European Food Safety Authority (EFSA) has extensively reviewed the available literature to establish a temporary Tolerable Daily Intake (t-TDI). This exposure level was based on all available literature published before the end of 2012. Since then, new experimental animal studies have emerged, including those that identified effects of BPA on the immune system after developmental exposure. These studies indicate that developmental immunotoxicity might occur at lower dose levels than previously observed and on which the current EFSA t-TDI is based. The Dutch National Institute for Public Health and the Environment (RIVM) organized an expert workshop in September 2015 to consider recently published studies on the developmental immunotoxicity of bisphenol A (BPA). Key studies were discussed in the context of other experimental studies. The workshop concluded that these new experimental studies provide credible evidence for adverse immune effects after developmental exposure to BPA at 5µg/kg BW/day from gestation day 15 to postnatal day 21. Supportive evidence for adverse immune effects in similar dose ranges was obtained from other publications that were discussed during the workshop. The dose level associated with adverse immune effects is considerably lower than the dose used by EFSA for deriving the t-TDI. The workshop unanimously concluded that the current EFSA t-TDI warrants reconsideration in the context of all currently available data.

Associating Changes in the Immune System with Clinical Diseases for Interpretation in Risk Assessment.

This overview is an update of the unit originally published in 2004. While the basic tenets of immunotoxicity have not changed in the past 10 years, several publications have explored the application of immunotoxicological data to the risk assessment process. Therefore, the goal of this unit is still to highlight relationships between xenobiotic-induced immunosuppression and risk of clinical diseases progression. In immunotoxicology, this may require development of models to equate moderate changes in markers of immune functions to potential changes in incidence or severity of infectious diseases. For most xenobiotics, exposure levels and disease incidence data are rarely available, and safe exposure levels must be estimated based on observations from experimental models or human biomarker studies. Thus, it is important to establish a scientifically sound framework that allows accurate and quantitative interpretation of experimental or biomarker data in the risk assessment process.