“…In the U.S. and Canada, laboratory data show that exposure to FPW inhibits the survival, growth, and reproduction of aquatic animals (see the Supporting Information for detailed results of these toxicity studies), ,− causing functional and morphological impairment in exposed animals (Supporting Information, Figure S4) − and changing the expression of a battery of genes, including those responsible for biotransformation (cytochrome p450 families), detoxification ( udpgt and gst ), oxidative stress ( sod , gpx , cat ), and embryonic development ( atp2a2a , tnnt2a , and nkx2.5 ). ,, Many of these changes in gene expression are believed to be associated with impaired performance and metabolism (e.g., organic toxicant metabolism), along with sublethal toxicity levels. ,− Endocrine-disruptive properties are among the most extensively studied adverse impacts regarding the toxicity of chemicals used in HF activities, contaminated water associated with HF, and field-collected FPW samples from the U.S. and Canada . On the basis of a quantitative overview relying on voluntary disclosures to FracFocus, more than 1,000 chemicals used throughout the HF process are of concern, including many known or suspected endocrine-disrupting chemicals (EDCs). , The current evidence from the study of HF chemical additives, contaminated water associated with HF activities, and FPW samples suggests that accidental spills and/or inappropriate disposal of FPW may cause significant endocrine-mediated health impacts on animals (see the Supporting Information for a detailed discussion of findings regarding EDCs). , …”