PFAS and Potential Adverse Effects on Bone and Adipose Tissue Through Interactions With PPARγ.

Perfluoroalkyl and polyfluoroalkyl substances (PFAS) are a widely dispersed, broad class of synthetic chemicals with diverse biological effects, including effects on adipose and bone differentiation. PFAS most commonly occur as mixtures and only rarely, if ever, as single environmental contaminants. This poses significant regulatory questions and a pronounced need for chemical risk assessments, analytical methods, and technological solutions to reduce the risk to public and environmental health. The effects of PFAS on biological systems may be complex. Each may have several molecular targets initiating multiple biochemical events leading to a number of different adverse outcomes. An exposure to mixtures or coexposures of PFAS complicates the picture further. This review illustrates how PFAS target peroxisome proliferator-activated receptors. Additionally, we describe how such activation leads to changes in cell differentiation and bone development that contributes to metabolic disorder and bone weakness. This discussion sheds light on the importance of seemingly modest outcomes observed in test animals and highlights why the most sensitive end points identified in some chemical risk assessments are significant from a public health perspective.

Evaluation of Fetal Exposures to Metals and Metalloids through Meconium Analyses: A Review.

This paper surveys the existing scientific literature on metals concentrations in meconium. We examine some 32 papers that analyzed meconium for aluminum, arsenic, barium, calcium, chromium, copper, iron, lithium, magnesium, manganese, zinc, lead, mercury, manganese, molybdenum, nickel, phosphorus, lead, antimony, selenium, tin, vanadium, and zinc. Because of the lack of detail in the statistics it is not possible to do a rigorous meta-analysis. What stands out is that almost every study had subjects with seemingly large amounts of at least one of the metals. The significance of metals in meconium is not clear beyond an indication of exposure although some studies have correlated metals in meconium to a number of adverse outcomes. A number of outstanding questions have been identified that, if resolved, would greatly increase the utility of meconium analysis for assessment of long-term gestational metals exposures. Among these are questions of the developmental and long-term significance of metals detected in meconium, the kinetics and interactions among metals in maternal and fetal compartments and questions on best methods for meconium analyses.

Summary of Discussions From the 2019 OECD Conference on RNAi Based Pesticides.

RNA interference (RNAi) is a biological process in which double-stranded ribonucleic acid (dsRNA) molecules inhibit protein expression. In recent years, the application of dsRNA has been used in the development of agricultural products for pest control. The 2019 Organisation for Economic Cooperation and Development (OECD) Conference on RNAi Based Pesticides ("the Conference") brought together academic, industry, and government experts in various aspects of RNAi to discuss the current state of knowledge and topics to help in developing considerations for risk assessment. The Conference focused on environment, with some discussion of human health. Along with presentations on the use of dsRNA-based products in agriculture, government regulation, risk assessment, and a background on the Draft OECD Working Paper on "Considerations for the Environmental Risk Assessment of the Application of Sprayed or Externally Applied dsRNA-Based Pesticides" ("OECD Working Paper"), the Conference included panel discussions from presenters at the end of each session and a larger discussion session with Conference participants on the environmental fate of dsRNA, non-target organism (NTO) risk assessment, and human health risk assessment. This paper summarizes input from presenters and Conference participants during these discussions. Key considerations from these discussions have already been incorporated into the OECD Working Paper, that once finalized and published, will facilitate regulators in evaluating externally applied dsRNA-based products for potential environmental risks.