An exposure:activity profiling method for interpreting high-throughput screening data for estrogenic activity—Proof of concept

Becker, Richard A.; Friedman, Katie Paul; Simon, Timothy M.; Marty, M. Sue; Patlewicz, Grace; Rowlands, J. Craig

doi:10.1016/j.yrtph.2015.01.008

Cited by 48 publications

(73 citation statements)

References 78 publications

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“…However, development of high-throughput, predictive, and mechanism-based assays for evaluating the potential toxicity of nanomaterials that humans are exposed to, but for which little toxicity information is available, is important and desirable. 34 The unique physical and chemical properties of nanomaterials drive the need to develop and validate in vitro tests to assess their potential toxicity. The exposure-effect relationship results determined by in vitro models may be predictive of the toxicological and pharmacological activities in vivo 35,36 provided they are appropriately validated.…”

Section: Characterization Of Nanomaterialsmentioning

confidence: 99%

Toxicity of nanomaterials found in human environment

Sahu

Hayes

2017

Toxicology Research and Application

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The US National Nanotechnology Initiative (NNI) defines nanotechnology as "the understanding and control of matter at dimensions between approximately 1 and 100 nm, where unique phenomena enable novel applications." Recent scientific reports available in the literature clearly demonstrate the potential benefits of nanotechnology in consumer and industrial products. More and more nanomaterials are expected to be used in consumer products. This is expected to lead to increased human exposure to nanomaterials in their daily lives. Therefore, the effect of nanomaterials present in human environment is an area of increasing scientific interest. The information presented in this review is obtained from the current literature. It indicates that nanomaterials found in human environment may have potential for toxicological effects. However, the current literature on toxicological effects of nanomaterials is diverse. The current data are presented from studies without harmonization. These studies have used different in vitro and in vivo test models, different sources of test nanomaterials, different methods for nanomaterial characterization, and different experimental conditions. Therefore, these data are hard to interpret. More research on nanomaterial characterization, biological interaction, toxicity, and health effects is needed. The test methods need to be validated. Positive and negative controls for nanotoxicity need to be identified. Toxicity data harmonization needs to be done. Therefore, general information is not currently available for risk evaluation of certain nanomaterials that might be present in consumer products or that may enter into the market in future. Standardized and validated methods are necessary for toxicity assessment of nanomaterials. Therefore, in the absence of standardized validated methods any specific regulatory testing requirements for nanomaterials are currently premature. We conclude that the benefits of nanomaterials found currently in human environment are many, but their overall adverse effects on human health are limited.

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Section: Characterization Of Nanomaterialsmentioning

confidence: 99%

Toxicity of nanomaterials found in human environment

Sahu

Hayes

2017

Toxicology Research and Application

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“…The AC50 is the concentration at which a chemical induces a 50% increase in activity compared with a reference. To determine if a detected environmental chemical is at a concentration necessary to elicit an observed biological activity, an exposure–activity ratio can be used (Figure B) . Exposure–activity ratios compare the concentration of a chemical detected in an environmental sample to the AC50 concentration for that particular chemical to determine if the concentration measured in the environment may be high enough to cause a biological activity.…”

Section: The Next Frontier For High‐throughput Toxicologymentioning

confidence: 99%

Environmental surveillance and monitoring—The next frontiers for high‐throughput toxicology

Schroeder

Ankley

Houck

et al. 2016

Enviro Toxic and Chemistry

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High-throughput toxicity testing technologies along with the World Wide Web are revolutionizing both generation of and access to data regarding the biological activities that chemicals can elicit when they interact with specific proteins, genes, or other targets in the body of an organism. To date, however, most of the focus has been on the application of such data to assessment of individual chemicals. The authors suggest that environmental surveillance and monitoring represent the next frontiers for high-throughput toxicity testing. Resources already exist in curated databases of chemical-biological interactions, including highly standardized quantitative dose-response data generated from nascent high-throughput toxicity testing programs such as ToxCast and Tox21, to link chemicals detected through environmental analytical chemistry to known biological activities. The emergence of the adverse outcome pathway framework and the associated knowledge base for linking molecular-level or pathway-level perturbations of biological systems to adverse outcomes traditionally considered in risk assessment and regulatory decision-making through a series of measurable biological changes provides a critical link between activity and hazard. Furthermore, environmental samples can be directly analyzed via high-throughput toxicity testing platforms to provide an unprecedented breadth of biological activity characterization that integrates the effects of all compounds present in a mixture, whether known or not. Novel application of these chemical-biological interaction data provides an opportunity to transform scientific characterization of potential hazards associated with exposure to complex mixtures of environmental contaminants.

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“…With the AC50 and chemical concentration information, an exposure-activity ratio (EAR) can be calculated. The EAR is defined as the measured chemical concentration in the water sample, divided by the in vitro AC50 values (Becker et al, 2015):…”

Section: Bio-effects Predictionmentioning

confidence: 99%

An integrated approach for identifying priority contaminant in the Great Lakes Basin – Investigations in the Lower Green Bay/Fox River and Milwaukee Estuary areas of concern

Villeneuve

Berninger

et al. 2017

Science of The Total Environment

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Environmental assessment of complex mixtures typically requires integration of chemical and biological measurements. This study demonstrates the use of a combination of instrumental chemical analyses, effects-based monitoring, and bio-effects prediction approaches to help identify potential hazards and priority contaminants in two Great Lakes Areas of Concern (AOCs), the Lower Green Bay/Fox River located near Green Bay, WI, USA and the Milwaukee Estuary, located near Milwaukee, WI, USA. Fathead minnows were caged at four sites within each AOC (eight sites total). Following 4d of in situ exposure, tissues and biofluids were sampled and used for targeted biological effects analyses. Additionally, 4d composite water samples were collected concurrently at each caged fish site and analyzed for 132 analytes as well as evaluated for total estrogenic and androgenic activity using cell-based bioassays. Of the analytes examined, 75 were detected in composite samples from at least one site. Based on multiple analyses, one site in the East River and another site near a paper mill discharge in the Lower Green Bay/Fox River AOC, were prioritized due to their estrogenic and androgenic activity, respectively. The water samples from other sites generally did not exhibit significant estrogenic or androgenic activity, nor was there evidence for endocrine disruption in the fish exposed at these sites as indicated by the lack of alterations in ex vivo steroid production, circulating steroid concentrations, or vitellogenin mRNA expression in males. Induction of hepatic cyp1a mRNA expression was detected at several sites, suggesting the presence of chemicals that activate the aryl hydrocarbon receptor. To expand the scope beyond targeted investigation of endpoints selected a priori, several bio-effects prediction approaches were employed to identify other potentially disturbed biological pathways and related chemical constituents that may warrant future monitoring at these sites. For example, several chemicals such as diethylphthalate and naphthalene, and genes and related pathways, such as cholinergic receptor muscarinic 3 (CHRM3), estrogen receptor alpha1 (esr1), chemokine ligand 10 protein (CXCL10), tumor protein p53 (p53), and monoamine oxidase B (Maob), were identified as candidates for future assessments at these AOCs. Overall, this study demonstrates that a better prioritization of contaminants and associated hazards can be achieved through integrated evaluation of multiple lines of evidence. Such prioritization can guide more comprehensive follow-up risk assessment efforts.

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An exposure:activity profiling method for interpreting high-throughput screening data for estrogenic activity—Proof of concept

Cited by 48 publications

References 78 publications

Toxicity of nanomaterials found in human environment

Toxicity of nanomaterials found in human environment

Environmental surveillance and monitoring—The next frontiers for high‐throughput toxicology

An integrated approach for identifying priority contaminant in the Great Lakes Basin – Investigations in the Lower Green Bay/Fox River and Milwaukee Estuary areas of concern

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