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Jason P. Berninger

Publications and source records attributed to Jason P. Berninger.

8 recordsLinked to original sources

Response to Gard et al.'s (2021) Comments on the Critical Review “Polychlorinated Biphenyl Tissue-Concentration Thresholds for Survival, Growth, and Reproduction in Fish”

This response is offered to the critique by Gard et al. ( 2021 ) of our meta-analysis of polychlorinated biphenyl (PCB)-induced toxicity data in fish (Berninger and Tillitt 2019 ). Gard et al. ( 2021 ) offered numerous comments, the most substantive suggesting that 1) we should have added no-observable–adverse effect residue (NOAER) data from additional studies and all data points from selected studies, and 2) the uncertainty of aggregating data from different PCB mixtures, different species, and different life stages is too great based on a limited data set. The additional studies Gard et al. suggested either were not designed to produce toxicological data, had experimental design issues, were confounded by co-contaminants, or did not contain paired exposure–effects data and as such were not appropriate to add to the data set. Lowest-observable–adverse effect residue (LOAER) values were selected for our analysis because they represent population sensitivities from the central portions of a frequency distribution (the linear portion of dose–response curves). As a consequence, there is less uncertainty in these input data (LOAER values) and greater confidence that they accurately represent the response of fish populations tested. Modeling NOAER values is in the extrapolation portion of a dose–response relationship and subject to enhanced uncertainty. The Gard et al. ( 2021 ) critique ignores this fundamental principle of toxicology and adds/deletes data points from our data set without clear selection criteria, which artificially enhances the uncertainty of their models that ultimately are not useful. We reject the premise that it is better to use individual study data as opposed to aggregation of PCB-induced toxicity thresholds in fish.

Environmental Toxicology and Chemistry

Effects of early life stage exposure of largemouth bass to atrazine or a model estrogen (17α-ethinylestradiol)

Endocrine disrupting contaminants are of continuing concern for potentially contributing to reproductive dysfunction in largemouth and smallmouth bass in the Chesapeake Bay watershed (CBW) and elsewhere. Exposures to atrazine (ATR) have been hypothesized to have estrogenic effects on vertebrate endocrine systems. The incidence of intersex in male smallmouth bass from some regions of CBW has been correlated with ATR concentrations in water. Fish early life stages may be particularly vulnerable to ATR exposure in agricultural areas, as a spring influx of pesticides coincides with spawning and early development. Our objectives were to investigate the effects of early life stage exposure to ATR or the model estrogen 17α-ethinylestradiol (EE2) on sexual differentiation and gene expression in gonad tissue. We exposed newly hatched largemouth bass (LMB, Micropterus salmoides ) from 7 to 80 days post-spawn to nominal concentrations of 1, 10, or 100 µg ATR/L or 1 or 10 ng EE2/L and monitored histological development and transcriptomic changes in gonad tissue. We observed a nearly 100% female sex ratio in LMB exposed to EE2 at 10 ng/L, presumably due to sex reversal of males. Many gonad genes were differentially expressed between sexes. Multidimensional scaling revealed clustering by gene expression of the 1 ng EE2/L and 100 µg ATR/L-treated male fish. Some pathways responsive to EE2 exposure were not sex-specific. We observed differential expression in male gonad in LMB exposed to EE2 at 1 ng/L of several genes involved in reproductive development and function, including star , cyp11a2 , ddx4 (previously vasa ), wnt5b , cyp1a and samhd1 . Expression of star , cyp11a2 and cyp1a in males was also responsive to ATR exposure. Overall, our results confirm that early development is a sensitive window for estrogenic endocrine disruption in LMB and are consistent with the hypothesis that ATR exposure induces some estrogenic responses in the developing gonad. However, ATR-specific and EE2-specific responses were also observed.

New York, Pennsylvania, Maryland, West Virginia, V

Factors affecting sampling strategies for design of an effects‐directed analysis for endocrine‐active chemicals

Effects‐directed analysis (EDA) is an important tool for identifying unknown bioactive components in a complex mixture. Such an analysis of endocrine‐active chemicals (EACs) from water sources has promising regulatory implications but also unique logistical challenges. We propose a conceptual EDA (framework) based on a critical review of EDA literature and concentrations of common EACs in waste and surface waters. Required water volumes for identification of EACs under this EDA framework were estimated based on bioassay performance (in vitro and in vivo bioassays), limits of quantification by mass spectrometry (MS), and EAC water concentrations. Sample volumes for EDA across the EACs showed high variation in the bioassay detectors, with genistein, bisphenol A, and androstenedione requiring very high sample volumes and ethinylestradiol and 17β‐trenbolone requiring low sample volumes. Sample volume based on the MS detector was far less variable across the EACs. The EDA framework equation was rearranged to calculate detector “thresholds,” and these thresholds were compared with the literature EAC water concentrations to evaluate the feasibility of the EDA framework. In the majority of instances, feasibility of the EDA was limited by the bioassay, not MS detection. Mixed model analysis showed that the volumes required for a successful EDA were affected by the potentially responsible EAC, detection methods, and the water source type, with detection method having the greatest effect on the EDA of estrogens and androgens. The EDA framework, equation, and model we present provide a valuable tool for designing a successful EDA.

Environmental Toxicology and Chemistry

Predictive analysis using chemical-gene interaction networks consistent with observed endocrine activity and mutagenicity of U.S. streams

In a recent U.S. Geological Survey/U.S. Environmental Protection Agency study assessing >700 organic compounds in 38 streams, in vitro assays indicated generally low estrogen, androgen, and glucocorticoid receptor activities, but identified 13 surface waters with 17β estradiol equivalent (E2Eq) activities greater than the 1 ng/L level of concern for feminization of male fish. Among the 36 samples assayed for mutagenicity in the Salmonella bioassay (reported here), 25% were considered mutagenic (statistically significant slope and at least a two-fold increase in revertants/plate). Endocrine and mutagenic activities of the water samples were well correlated with each other and with the total number and cumulative concentrations of detected chemical contaminants. To test the predictive utility of knowledgebase-leveraging approaches, site-specific predicted chemical-gene (pCGA) and predicted analogous pathway-linked (pPLA) association networks identified in the Comparative Toxicogenomics Database were compared with observed endocrine/mutagenic bioactivities. We evaluated pCGA/pPLA patterns among sites by cluster analysis and principal component analysis and grouped the pPLA into broad mode-of-action classes. Measured E2Eq and mutagenic activities correlated well with predicted pathways. The pPLA analysis also revealed correlations with signaling, metabolic, and regulatory groups, suggesting that other effects pathways may be associated with chemical contaminants in these waters and indicating the need for broader bioassay coverage to assess potential adverse impacts.

Environmental Science & Technology

Mixed-chemical exposure and predicted effects potential in wadeable southeastern USA streams

Complex chemical mixtures have been widely reported in larger streams but relatively little work has been done to characterize them and assess their potential effects in headwaterstreams. In 2014, the United States Geological Survey (USGS) sampled 54 Piedmont streams over ten weeks and measured 475 unique organic compounds using five analytical methods. Maximum and median exposure conditions were evaluated in relation to watershed characteristics and for potential biological effects using multiple lines of evidence. Results demonstrate that mixed-contaminant exposures are ubiquitous and varied in sampled headwater streams. Approximately 56% (264) of the 475 compounds were detected at least once across all sites. Cumulative maximum concentrations ranged 1,922–162,346 ng L −1 per site. Chemical occurrence significantly correlated to urban land use but was not related to presence/absence of wastewater treatment facility discharges. Designed bioactive chemicals represent about 2/3rd of chemicals detected, notably pharmaceuticals and pesticides, qualitative evidence for possible adverse biological effects. Comparative Toxicogenomics Database chemical-gene associations applied to maximum exposure conditions indicate >12,000 and 2,900 potential gene targets were predicted at least once across all sites for fish and invertebrates, respectively. Analysis of cumulative exposure-activity ratios provided additional evidence that, at a minimum, transient exposures with high probability of molecular effects to vertebrates were common. Finally, cumulative detections and concentrations correlated inversely with invertebrate metrics from in-stream surveys. The results demonstrate widespread instream exposure to extensive contaminant mixtures and compelling multiple lines of evidence for adverse effects on aquatic communities.

Science of the Total Environment

Polychlorinated biphenyl tissue‐concentration thresholds for survival, growth, and reproduction in fish

Polychlorinated biphenyls (PCBs) have left a legacy of environmental contamination. Even though they were banned from production and active use in the 1970s, they persist in the environment and still have the potential to impact aquatic life. Our objective was to identify data from controlled laboratory studies of PCB‐related adverse effects in fish and to conduct a meta‐analysis on mortality, growth, and reproductive (MGR) threshold responses. For each endpoint type, we compiled data on the lowest‐observed‐adverse effect concentration (LOAEC) and the degree of effect at the LOAEC as a percentage of control. The LOAECs were expressed as tissue concentrations, so the term lowest‐observed‐adverse‐effect residue concentration (LOAER) was used to represent PCB exposures. The lower limit of applicability was set at 0.1 μg/g total PCB tissue concentration, below which adverse MGR effects in fish were not supported by the data. Sensitivity distributions identifying the probability of adverse effects in fish populations or communities predicted that 25% of fish species would be impacted between 0.1 and 7.5 μg/g. Concentration–response threshold regressions were developed from the MGR datasets. For example, a 1 μg/g total PCB tissue concentration would predict effects of 17% mortality, 15% growth, and 39% reproductive. The analysis determined the degree of adverse response, with uncertainty estimates, expected across a broad range of PCB tissue exposure concentrations in fish. Data generated from MGR endpoints were combined to determine an approach for overall effect thresholds for PCB‐related injury in fish. The MGR datasets included only laboratory data; however, responses were compared with field‐observed effects. The present review provides a comprehensive assessment of PCB‐induced injury in fish utilizing a data‐inclusive approach.

Environmental Toxicology and Chemistry

Linking field-based metabolomics and chemical analyses to prioritize contaminants of emerging concern in the Great Lakes basin

The ability to focus on the most biologically relevant contaminants affecting aquatic ecosystems can be challenging because toxicity-assessment programs have not kept pace with the growing number of contaminants requiring testing. Because it has proven effective at assessing the biological impacts of potentially toxic contaminants, profiling of endogenous metabolites (metabolomics) may help screen out contaminants with a lower likelihood of eliciting biological impacts, thereby prioritizing the most biologically important contaminants. The authors present results from a study that utilized cage-deployed fathead minnows ( Pimephales promelas ) at 18 sites across the Great Lakes basin. They measured water temperature and contaminant concentrations in water samples (132 contaminants targeted, 86 detected) and used 1 H-nuclear magnetic resonance spectroscopy to measure endogenous metabolites in polar extracts of livers. They used partial least-squares regression to compare relative abundances of endogenous metabolites with contaminant concentrations and temperature. The results indicated that profiles of endogenous polar metabolites covaried with at most 49 contaminants. The authors identified up to 52% of detected contaminants as not significantly covarying with changes in endogenous metabolites, suggesting they likely were not eliciting measurable impacts at these sites. This represents a first step in screening for the biological relevance of detected contaminants by shortening lists of contaminants potentially affecting these sites. Such information may allow risk assessors to prioritize contaminants and focus toxicity testing on the most biologically relevant contaminants. Environ Toxicol Chem 2016;35:2493–2502.

Environmental Toxicology and Chemistry

Pathway-based approaches for assessment of real-time exposure to an estrogenic wastewater treatment plant effluent on fathead minnow reproduction

Wastewater treatment plant (WWTP) effluents are known contributors of chemical mixtures into the environment. Of particular concern are endocrine-disrupting compounds, such as estrogens, which can affect the hypothalamic-pituitary-gonadal axis function in exposed organisms. The present study examined reproductive effects in fathead minnows exposed for 21 d to a historically estrogenic WWTP effluent. Fathead minnow breeding pairs were held in control water or 1 of 3 effluent concentrations (5%, 20%, and 100%) in a novel onsite, flow-through system providing real-time exposure. The authors examined molecular and biochemical endpoints representing key events along adverse outcome pathways linking estrogen receptor activation and other molecular initiating events to reproductive impairment. In addition, the authors used chemical analysis of the effluent to construct a chemical-gene interaction network to aid in targeted gene expression analyses and identifying potentially impacted biological pathways. Cumulative fecundity was significantly reduced in fish exposed to 100% effluent but increased in those exposed to 20% effluent, the approximate dilution factor in the receiving waters. Plasma vitellogenin concentrations in males increased in a dose-dependent manner with effluent concentration; however, male fertility was not impacted. Although in vitro analyses, analytical chemistry, and biomarker responses confirmed the effluent was estrogenic, estrogen receptor agonists were unlikely the primary driver of impaired reproduction. The results provide insights into the significance of pathway-based effects with regard to predicting adverse reproductive outcomes.

Environmental Toxicology and Chemistry