Transcriptomic Analysis of the Differential Nephrotoxicity of Diverse Brominated Flame Retardants in Rat and Human Renal Cells.

Brominated flame retardants (BFRs) are environmentally persistent, are detected in humans, and some have been banned due to their potential toxicity. BFRs are developmental neurotoxicants and endocrine disruptors; however, few studies have explored their potential nephrotoxicity. We addressed this gap in the literature by determining the toxicity of three different BFRs (tetrabromobisphenol A (TBBPA), hexabromocyclododecane (HBCD), and tetrabromodiphenyl ether (BDE-47)) in rat (NRK 52E) and human (HK-2 and RPTEC) tubular epithelial cells. All compounds induced time- and concentration-dependent toxicity based on decreases in MTT staining and changes in cell and nuclear morphology. The toxicity of BFRs was chemical- and cell-dependent, and human cells were more susceptible to all three BFRs based on IC50s after 48 h exposure. BFRs also had chemical- and cell-dependent effects on apoptosis as measured by increases in annexin V and PI staining. The molecular mechanisms mediating this toxicity were investigated using RNA sequencing. Principal components analysis supported the hypothesis that BFRs induce different transcriptional changes in rat and human cells. Furthermore, BFRs only shared nine differentially expressed genes in rat cells and five in human cells. Gene set enrichment analysis demonstrated chemical- and cell-dependent effects; however, some commonalities were also observed. Namely, gene sets associated with extracellular matrix turnover, the coagulation cascade, and the SNS-related adrenal cortex response were enriched across all cell lines and BFR treatments. Taken together, these data support the hypothesis that BFRs induce differential toxicity in rat and human renal cell lines that is mediated by differential changes in gene expression.

Implications of Insecticide-Treated Mosquito Net Fishing in Lower Income Countries.

INTRODUCTION: Insecticide-treated mosquito nets (ITNs) are highly effective for the control of malaria. Yet widely distributed ITNs have been repurposed as fishing nets throughout the world. OBJECTIVES: Herein we present a synthesis of the current knowledge of ITN fishing and the toxicity of pyrethroids and discuss the potential implications of widespread fishing with ITNs. We further review effective management strategies in tropical fisheries to explore a framework for managing potential ITN fishing impacts. DISCUSSION: Pyrethroids are toxic to fish and aquatic environments, and fishing with ITNs may endanger the health of fisheries. Furthermore, although human toxicity to the pyrethroid insecticides that impregnate ITNs is traditionally thought to be low, recent scientific advances have shown that pyrethroid exposure is associated with a host of human health issues, including neurocognitive developmental disorders, diabetes, and cardiovascular disease. Although it is known that ITN fishing is widespread, the implications for both fisheries and human communities is understudied and may be severe. https://doi.org/10.1289/EHP7001.