Citation:

Collette, T., D. Ekman, H. Zhen, H. Nguyen, P. Bradley, AND Q. Teng. Cell-Based Metabolomics for Untargeted Screening and Prioritization of Vertebrate-Active Stressors in Streams Across the United States. ENVIRONMENTAL SCIENCE & TECHNOLOGY. American Chemical Society, Washington, DC, 53(15):9232-9240, (2019). https://doi.org/10.1021/acs.est.9b02736

Impact/Purpose:

Many anthropogenic chemicals are detected - often as components in highly complex mixtures - in streams that are impacted by urban, commercial, and/or agricultural activity. While it is widely accepted that some of these anthropogenic chemicals are detrimental to ecosystem health, there is rarely evidence to suggest which chemicals, chemical classes, or defined mixtures are most biologically harmful. To help address these needs, the USGS and the EPA partnered to carry out an extensive field study of 38 stream sites across the US. The USGS conducted an exhaustive chemical analysis on these water samples, and in this manuscript, we report results from metabolomic assessment of zebrafish liver (ZFL) cells exposed to water collected from these sites. Further, we used regression analysis to help assess which of the detected chemicals was most likely responsible for the biological responses measured with the ZFL cells. The results showed that, while chemicals of emerging concern (pharmaceuticals, personal care products, etc.) were often associated with biological impacts, certainly legacy contaminants, such as PCBs, were even more strongly associated. This suggests that chemical risk assessors should continue to give high priority to toxic and persistent legacy contaminants such as PCBs alongside contaminants of emerging concern.

Description:

The U.S. Geological Survey and the U.S. Environmental Protection Agency partnered to assess contaminants in 38 streams across the U.S., using an extensive suite of chemical analysis methods (916 total analytes) along with a variety of biological effects-based tools. Here we report zebrafish liver (ZFL) cell-culture based NMR metabolomic analysis of these split stream samples. We used this untargeted effects-based approach to rank the 38 sites according to overall impact on the ZFL metabolome and found that neither the total number of organics detected at the sites, nor their cumulative concentrations, were good predictors of the observed biological impacts. Further, we used partial-least squares regression to compare relative abundances of ZFL endogenous metabolites to values for all 455 stressors that were measured in these water samples, which included concentrations of 406 unique organic and 37 inorganic chemicals, along with 12 physical properties / measurements (e.g., pH, DO, etc.). Endogenous metabolite profiles covaried with at most 280 of these stressors, which were coarsely ranked into quartiles based on the strength of their covariance. While contaminants of emerging concern (CECs) that are designed-bioactive chemicals were well represented in the top, most strongly covarying quartile, there was also a strong presence of legacy contaminants (e.g., PCB congeners) and other chemicals that have long been recognized as environmental concerns. Neither the chemicals that were most frequently detected nor the chemicals that were detected at the highest concentrations were well represented in this top quartile, which emphasizes the value of an untargeted effects-based tool used alongside targeted stressor analysis for assessing the risk of contaminants in aquatic ecosystems.

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