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Results for “Toxicology in Vitro”

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45 records · Page 3Linked to original sources
USGS2003

Effects of brevetoxins on murine myeloma SP2/O cells: Aberrant cellular division

Massive deaths of manatees (Trichechus manatus latirostris) during the red tide seasons have been attributed to brevetoxins produced by the dinoflagellate Karenia brevis (formerly Ptychodiscus breve and Gymnodinium breve). Although these toxins have been found in macrophages and lymphocytes in the lung, liver, and secondary lymphoid tissues of these animals, the molecular mechanisms of brevetoxicosis have not yet been identified. To investigate the effects of brevetoxins on immune cells, a murine myeloma cell line (SP2/O) was used as a model for in vitro studies. By adding brevetoxins to cultures of the SP2/O cells at concentrations ranging from 20 to 600 ng/ml, an apparent increase in proliferation was observed at around 2 hours post challenge as compared to the unchallenged cell cultures. This was followed by a drop in cell number at around 3 hours, suggesting an aberrant effect of brevetoxins on cellular division, the cells generated at 2 hours being apparently short-lived. In situ immunochemical staining of the SP2/O cells at 1 and 2 hour post challenge showed an accumulation of the toxins in the nucleus. A 21-kDa protein was subsequently isolated from the SP2/O cells as having brevetoxin-binding properties, and immunologically identified as p21, a nuclear factor known to down-regulate cellular proliferation through inhibition of cyclin-dependent kinases. These data are the first on a possible effect of brevetoxins on the cell cycle via binding to p21, a phenomenon that needs to be further investigated and validated in normal immune cells.

International Journal of Toxicology↗
USGS1992

Polychlorinated biphenyl residues and egg mortality in double-crested cormorants from the Great Lakes

We evaluated the overall potency of polychlorinated biphenyl (PCB)-containing extracts from double-crested cormorant ( Phalacrocorax auritis ) eggs with an in vitro bioassay system, the H4IIE rat hepatoma cell bioassay. Results from the H4IIE bioassay were strongly correlated with the hatching success of eggs in the colonies, whereas conventional methods of PCB analysis correlated poorly with hatching success of eggs from the same colonies. These observations suggest that even though concentrations of total PCB residues have declined in almost all compartments of the environment, their effects are still being observed. The significance of this observation is that the adverse symptoms presently observed in certain Great Lakes fish-eating waterbird populations do not appear to be caused by some as yet unidentified industrial chemical or chemicals and seem not to be the result of pesticides, but rather to the dioxin-like activity of PCBs. Evidence is presented to suggest that the relative enrichment of the potency of PCBs in the environment may play a role in the persistence of the observed adverse symptoms.

Environmental Toxicology and Chemistry↗
USGS2025

Derivation and characterization of environmental hazard concentrations for chemical prioritization: A case study in the Great Lakes tributaries

Ongoing anthropogenic activities and analytical advancements yield continuously expanding lists of environmental contaminants. This represents a challenge to environmental managers, who must prioritize chemicals for management actions (e.g., restriction, regulation, remediation) but are often hindered by resource limitations. To help facilitate prioritization efforts, this study presents several strategies for deriving environmental hazard concentrations using publicly accessible data and open-source computational tools. Using a Great Lakes tributaries aquatic monitoring dataset as a case study, environmental hazard concentrations were obtained or derived for 334 organic chemicals. These concentrations were based on (1) current water quality guidelines; (2) apical screening values; (3) apical and (4) nonapical effect concentrations from the ECOTOXicology Knowledgebase; (5) in vitro effect concentrations from the ToxCast database; (6) cytotoxic burst concentrations collated from the Comptox Dashboard; (7) “estimated screening values” derived from modeled or estimated data and available from various regulatory and nonregulatory agencies; (8) pharmaceutical potency estimates from the MaPPFAST database; and (9) quantitative structure-activity relationship (QSAR)–derived acute toxicity estimates. Environmental fate data included aquatic half-lives and bioconcentration factors collated from the Comptox Dashboard or estimated using QSARs. To identify patterns that could be used for characterization, availability of ecotoxicological concentrations and environmental fate data were evaluated. Furthermore, exceedances of hazard concentrations were evaluated and compared across diverse ecotoxicological data types. Altogether, by providing detailed methodology and practical examples generated with real monitoring data, this study demonstrated that these hazard concentration derivation strategies can be efficiently and effectively used with large, complex datasets and identified critical considerations for future prioritization efforts.

Great Lakes region↗
USGS2020

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↗
USGS2025

Prioritizing chemicals of emerging concern in the Great Lakes Basin using covariance of chemical concentrations and diverse biological responses from a variety of species

The Great Lakes Restoration Initiative aims to protect and restore the nation’s largest freshwater resource, in part, by furthering our understanding of the effects of contaminants of emerging concern (CECs) and chemical mixtures on aquatic and terrestrial organisms. To address this goal, an interagency team conducted field studies at sites along the Maumee River in Ohio, USA, in 2016–2017, monitoring CEC levels along with diverse in vitro and in vivo biological effects in ecologically relevant species (fathead minnows, tree swallows, and golden clams). The objective of the present work was to prioritize the CECs in these studies for further monitoring and assessment by determining if there are patterns in chemical–bioeffect relations across data sets, species, and response types that indicate relatively high or low hazard to aquatic life from CEC exposure. Of the 748 monitored chemicals, 425 were detected and were analyzed for covariance with bioeffects. All 748 chemicals were placed into 10 bins based on their frequencies of monitoring, detection, and covariance with bioeffects across studies and species. We describe how chemicals can be prioritized across bins to aid monitoring and assessment efforts. Our approach using effects-based monitoring data is especially useful for prioritizing chemicals with little or no traditional toxicity testing data. Similar evidence-based prioritizations will allow agencies to more efficiently allocate limited resources to improve the ability to protect aquatic and terrestrial organisms from adverse impacts due to contaminant exposure.

Ohio↗
USGS2022

A critical review of bioaccumulation and biotransformation of organic chemicals in birds

A literature review of bioaccumulation and biotransformation of organic chemicals in birds was undertaken, aiming to support scoping and prioritization of future research. The objectives were to characterize available bioaccumulation/biotransformation data, identify knowledge gaps, determine how extant data can be used, and explore the strategy and steps forward. An intermediate approach balanced between expediency and rigor was taken given the vastness of the literature. Following a critical review of > 500 peer-reviewed studies, > 25,000 data entries and 2 million information bytes were compiled on > 700 organic compounds for ~ 320 wild species and 60 domestic breeds of birds. These data were organized into themed databases on bioaccumulation and biotransformation , field survey , microsomal enzyme activity , metabolic pathway , and bird taxonomy and diet . Significant data gaps were identified in all databases at multiple levels. Biotransformation characterization was largely fragmented over metabolite/pathway identification and characterization of enzyme activity or biotransformation kinetics. Limited biotransformation kinetic data constrained development of an avian biotransformation model. A substantial shortage of in vivo biotransformation kinetics has been observed as most reported rate constants were derived in vitro. No metric comprehensively captured all key contaminant classes or chemical groups to support broad-scope modeling of bioaccumulation or biotransformation. However, metrics such as biota-feed accumulation factor, maximum transfer factor, and total elimination rate constant were more readily usable for modeling or benchmarking than other reviewed parameters. Analysis demonstrated the lack of bioaccumulation/biotransformation characterization of shorebirds, seabirds, and raptors. In the study of bioaccumulation and biotransformation of organic chemicals in birds, this review revealed the need for greater chemical and avian species diversity, chemical measurements in environmental media, basic biometrics and exposure conditions, multiple tissues/matrices sampling, and further exploration on biotransformation. Limitations of classical bioaccumulation metrics and current research strategies used in bird studies were also discussed. Forward-looking research strategies were proposed: adopting a chemical roadmap for future investigations, integrating existing biomonitoring data, gap-filling with non-testing approaches, improving data reporting practices, expanding field sampling scopes, bridging existing models and theories, exploring biotransformation via avian genomics, and establishing an online data repository.

Reviews of Environmental Contamination and Toxicol↗
USGS1998

Rapid toxicity assessment of sediments from estuarine ecosystems: A new tandem in vitro testing approach

Microtox® and Mutatox® were used to evaluate the acute toxicity and genotoxicity, respectively, of organic sediment extracts from Pensacola Bay and St. Andrew Bay, two estuaries that cover about 273 and 127 km 2 , respectively, along the Gulf coast of Florida, USA. The sensitivity and selectivity of these two bioluminescent toxicity assays were demonstrated in validation studies with over 50 pesticides, genotoxins, and industrial pollutants, both as single compounds and in complex mixtures. The 50% effective concentration (EC50) values of insecticides, petroleum products, and polychlorinated biphenyls determined by Microtox all tended to group around the mean EC50 value of 1.2 (0.8) mg/L. The polycyclic aromatic hydrocarbon sensitivity of Mutatox was in general similar to that reported in the Ames test. Surficial sediment samples were collected, extracted with dichloromethane, evaporated and concentrated under nitrogen, dissolved in dimethyl sulfoxide, assayed for acute toxicity and genotoxicity, and compared with reference sediments. Samples with low EC50 values, and determined to be genotoxic, were detected in Massalina Bayou, Watson Bayou, East Bay, and St. Andrew Bay–East in St. Andrew Bay as well as Bayou Grande, Bayou Chico, and Bayou Texar in Pensacola Bay. An overview of these data sets analyzed by Spearman rank correlation showed a significant correlation between acute toxicity and genotoxicity ( p < 0.05). Microtox and Mutatox in tandem was a sensitive, cost‐effective, and rapid (<24 h) screening tool that identified troublesome areas of pollution and assessed the potential sediment toxicity of lipophilic contaminants in aquatic ecosystems.

Environmental Toxicology and Chemistry↗
USGS2025

Retrospective stepwise prioritization of chemicals detected in Great Lakes tributaries (2008–2018)

Through the U.S. Great Lakes Restoration Initiative, a 10-year, multiagency chemical monitoring effort was undertaken across the Great Lakes. In this effort, 586 chemicals were monitored and 334 were detected in grab/composite water samples. To help inform potential future actions, a stepwise prioritization framework was used to identify compounds for which publicly accessible water quality guidelines or effects information suggested there was potential aquatic ecotoxicity. Because water quality guidelines were only available for some chemicals, this framework used apical toxicity data collated from publicly accessible databases (e.g., the ECOTOXicology Knowledgebase) and alternative data, including literature-derived non-apical effect concentrations, in vitro bioactivities from high-throughput screening, and modeled ecotoxicity. To account for the diverse levels of confidence in these data, chemicals were prioritized within specific action categories, which suggested potential management or experimental activities that may be considered based on the types of data available for each compound. Overall, 11 detected chemicals were identified as high priority in different action categories. This included four chemicals prioritized for environmental management or targeted risk assessment, three chemicals prioritized for effects-based monitoring, one chemical prioritized for apical effects assessment, and three chemicals targeted for non-apical effects evaluation. This framework also identified 164 low-priority chemicals, among which more than 50% were prioritized based on water quality guidelines or apical effect concentrations (thus could be considered low priority for future risk assessment or management activities). Results aim to help regulatory agencies, environmental managers, and other stakeholders focus available resources on carrying out monitoring, experimental, and risk assessments for the chemicals that display the greatest potential to adversely impact Great Lakes ecosystems.

Great Lakes↗
USGS1998

Overview of a workshop on screening methods for detecting potential (anti-) estrogenic/androgenic chemicals in wildlife

The U.S. Congress has passed legislation requiring the U.S. Environmental Protection Agency (U.S. EPA) to develop, validate, and implement screening tests for identifying potential endocrine-disrupting chemicals within 3 years. To aid in the identification of methods suitable for this purpose, the U.S. EPA, the Chemical Manufacturers Association, and the World Wildlife Fund sponsored several workshops, including the present one, which dealt with wildlife species. This workshop was convened with 30 international scientists representing multiple disciplines in March 1997 in Kansas City, Missouri, USA. Participants at the meeting identified methods in terms of their ability to indicate (anti-) estrogenic/androgenic effects, particularly in the context of developmental and reproductive processes. Data derived from structure-activity relationship models and in vitro test systems, although useful in certain contexts, cannot at present replace in vivo tests as the sole basis for screening. A consensus was reached that existing mammalian test methods (e.g., with rats or mice) generally are suitable as screens for assessing potential (anti-) estrogenic/ androgenic effects in mammalian wildlife. However, due to factors such as among-class variation in receptor structure and endocrine function, it is uncertain if these mammalian assays would be of broad utility as screens for other classes of vertebrate wildlife. Existing full and partial life-cycle tests with some avian and fish species could successfully identify chemicals causing endocrine disruption; however, these long-term tests are not suitable for routine screening. However, a number of short-term tests with species from these two classes exist that could serve as effective screening tools for chemicals inducing (anti-) estrogenic/androgenic effects. Existing methods suitable for identifying chemicals with these mechanisms of action in reptiles and amphibians are limited, but in the future, tests with species from these classes may prove highly effective as screens. In the case of invertebrate species, too little is known at present about the biological role of estrogens and androgens in reproduction and development to recommend specific assays.

Environmental Toxicology and Chemistry↗