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Effects‐based monitoring frameworks that combine the use of analytical chemistry with in vitro cell bioassays, as well as in vivo whole organism tests offer an integrative approach to broadly screen for chemical contaminants and link their presence with adverse effects on aquatic organisms. California (USA) is currently evaluating the use of such a framework to assess the impact of contaminants of emerging concern (CECs) on biota in urbanized rivers and other waterbodies. In the present study, the occurrence and effects of contaminants found in the Los Angeles River (Los Angeles County, CA, USA) were examined using analytical chemistry and in vitro and in vivo bioassays. Male fathead minnows were deployed in field‐based exposure units and exposed to river water for 21 d. The 2 field sites (above Bull Creek [BLC] and below Glendale Water Reclamation Plant [GWR]) were selected based on their unique characteristics and different contaminant discharge sources. In addition, 2 control units (filtered city water and estrone‐spiked water) were added to the experimental design. Chemical analyses revealed differences in abundance of CECs between the 2 field sites and the controls, with GWR having the highest number and concentrations of CECs and metals. Cell bioassays screening for estrogenic, glucocorticoid, progestin, and dioxin‐like activities were near or below detection limits in all river water samples, indicating a low potential for endocrine‐related toxicity and tissue damage. Cell bioassay results were corroborated by the in vivo analyses. Field‐exposed fish exhibited no changes in plasma hormones (e.g., estradiol), vitellogenin, or gonad maturation, but gene biomarkers of chemical exposure (cytochrome p450 1A and metallothionein) were significantly elevated, confirming exposure of the fish to complex chemical mixtures. The results demonstrate the value of a tiered monitoring approach to assess the sublethal effects of chemical mixtures on aquatic life. Environ Toxicol Chem 2021;40:402–412. © 2020 SETAC [ABSTRACT FROM AUTHOR]

Abstract: High‐throughput cell assays that detect and integrate the response of multiple chemicals acting via a common mode of action have the potential to enhance current environmental monitoring practices. Establishing the linkage between in vitro and in vivo responses is key to demonstrating that in vitro cell assays can be predictive of ecologically relevant outcomes. The present study investigated the potency of 17β‐estradiol (E2), estrone (E1), nonylphenol (NP), and treated wastewater effluent using the readily available GeneBLAzer® estrogen receptor transactivation assay and 2 life stages of the inland silverside (Menidia beryllina). In vitro estrogenic potencies were ranked as follows: E2 > E1 >> NP. All 3 model estrogens induced vitellogenin and choriogenin expression in a dose‐dependent manner in larvae and juveniles. However, apical effects were only found for E2 and E1 exposures of juveniles, which resulted in female‐skewed sex ratios. Wastewater effluent samples exhibiting low in vitro estrogenicity (below the 10% effective concentration [EC10]), did not cause significant changes in M. beryllina. Significant induction of estrogen‐responsive genes was observed at concentrations 6 to 26 times higher than in vitro responses. Gonadal feminization occurred at concentrations at least 19 to 26 times higher than the in vitro responses. These findings indicated that in vitro cell assays were more sensitive than the fish assays, making it possible to develop in vitro effect thresholds protective of aquatic organisms. Environ Toxicol Chem 2018;37:884–892. © 2017 SETAC [ABSTRACT FROM AUTHOR]

ABSTRACT The chemical-specific risk-based paradigm that informs monitoring and assessment of environmental contaminants does not apply well to the many thousands of new chemicals that are being introduced into ambient receiving waters. We propose a tiered framework that incorporates bioanalytical screening tools and diagnostic nontargeted chemical analysis to more effectively monitor for contaminants of emerging concern (CECs). The framework is based on a comprehensive battery of in vitro bioassays to first screen for a broad spectrum of CECs and nontargeted analytical methods to identify bioactive contaminants missed by the currently favored targeted analyses. Water quality managers in California have embraced this strategy with plans to further develop and test this framework in regional and statewide pilot studies on waterbodies that receive discharge from municipal wastewater treatment plants and stormwater runoff. In addition to directly informing decisions, the data obtained using this framework can be used to construct and validate models that better predict CEC occurrence and toxicity. The adaptive interplay among screening results, diagnostic assessment and predictive modeling will allow managers to make decisions based on the most current and relevant information, instead of extrapolating from parameters with questionable linkage to CEC impacts. Integr Environ Assess Manag 2016;12:540-547. © 2015 SETAC [ABSTRACT FROM AUTHOR]