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Transcriptomic-based effects monitoring for endocrine active chemicals: Assessing relative contribution of treated wastewater to downstream pollution
Citation:
Martinovic-Weigelt, D., A. Mehinto, G. Ankley, N. Denslow, L. Barber, K. Lee, R. King, H. Schoenfuss, AND Dan Villeneuve. Transcriptomic-based effects monitoring for endocrine active chemicals: Assessing relative contribution of treated wastewater to downstream pollution. ENVIRONMENTAL SCIENCE AND TECHNOLOGY. John Wiley & Sons, Ltd., Indianapolis, IN, 48(4):2385-2394, (2014).
Impact/Purpose:
One of the major challenges the Agency continues to face relative to evaluating chemical safety and sustainability is that of detecting and identifying hazards associated with chemicals that are already present in the environment. Traditional risk assessment paradigms focused on chemical-specific exposure and hazard assessment are challenged by the reality that exposures in the ambient environment are typically to mixtures whose composition is generally only partially defined, if known at all. This can make selection of appropriate endpoints for effects-based hazard monitoring highly challenging and introduces the possibility that important pathway-based effects, particularly those that may lead to chronic or sublethal adverse outcomes may be missed. Transcriptomics and other types of unsupervised, high content, approaches have the potential to greatly broaden the scope of biological pathways that can be evaluated in effects-based monitoring studies. However, demonstrations of application and case studies are needed to demonstrate and evaluate the effectiveness of such approaches, identify limitations, and determine how best to deploy these approaches as part of an overall strategy for pathway-based environmental monitoring and surveillance. This manuscript supports the research objectives of CSS task 2.1.1 (AOP-based effects monitoring and exposure reconstruction) by evaluating the utility of hepatic transcriptomics in small fish as an unsupervised effects-based monitoring approach for evaluating the impacts of treated wastewater discharges, a known source of contaminants of emerging concern, on receiving waters. This paper is the first in a series of three investigations that employed unsupervised, “omics” approaches to characterize the relative biological impacts of wastewater discharges at three distinct sites in MN, USA, representing watersheds with differing land-use patterns, population densities, and treatment types. This work leverages and builds upon analytical chemistry-based characterizations of these same sites by USGS and the Minnesota Pollution Control Agency.
Description:
The present study investigated whether combining of targeted analytical chemistry methods with unsupervised, data-rich methodologies (i.e. transcriptomics) can be utilized to evaluate relative contributions of wastewater treatment plant (WWTP) effluents to biological effects. The effects of WWTP effluents on fish exposed to ambient, receiving waters were studied at three locations with distinct WWTP and watershed characteristics. At each location, 4-day exposures of male fathead minnows to the WWTP effluent and upstream and downstream ambient waters were conducted. Transcriptomic analyses were performed on livers using a 15,000 feature microarrays, followed by canonical pathway and gene set enrichment analyses. Enrichment of gene sets indicative of teleost brain-pituitary-gonadal-hepatic (BPGH) axis functioning indicated that WWTPs serve as an important source of endocrine active chemicals (EACs) that disrupt the BPGH axis (e.g., cholesterol and steroid metabolism was altered). The results indicated that transcriptomics can be a powerful approach for pinpointing pertinent biological effects, and groups of chemicals (EACs in particular) that preselected chemical analytes and biomarkers may miss. Transcriptomics-based effects monitoring data was capable of discerning sites and it reflected chemical pollution gradients, thus holding promise for assessment of relative contributions of point sources to pollution and the efficacy of pollution remediation.
