Dataset Information

Predicting low-concentration effects of pesticides.

ABSTRACT: We present a model to identify the effects of low toxicant concentrations. Due to inadequate models, such effects have so far often been misinterpreted as random variability. Instead, a tri-phasic relationship describes the effects of a toxicant when a broad range of concentrations is assessed: i) at high concentrations where substantial mortality occurs (LC₅₀), we confirmed the traditional sigmoidal response curve (ii) at low concentrations about 10 times below the LC₅₀, we identified higher survival than previously modelled, and (iii) at ultra-low concentrations starting at around 100 times below the LC₅₀, higher mortality than previously modelled. This suggests that individuals benefit from low toxicant stress. Accordingly, we postulate that in the absence of external toxicant stress individuals are affected by an internal "System Stress" (SyS) and that SyS is reduced with increasing strength of toxicant stress. We show that the observed tri-phasic concentration-effect relationship can be modelled on the basis of this approach. Here we revealed that toxicant-related effects (LC₅) occurred at remarkably low concentrations, 3 to 4 orders of magnitude below those concentrations inducing strong effects (LC₅₀). Thus, the EC_x-SyS model presented allows us to attribute ultra-low toxicant concentrations to their effects on individuals. This information will contribute to performing a more realistic environmental and human risk assessment.

SUBMITTER: Liess M

PROVIDER: S-EPMC6813311 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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Predicting low-concentration effects of pesticides.

Liess Matthias M Henz Sebastian S Knillmann Saskia S

Scientific reports 20191024 1

We present a model to identify the effects of low toxicant concentrations. Due to inadequate models, such effects have so far often been misinterpreted as random variability. Instead, a tri-phasic relationship describes the effects of a toxicant when a broad range of concentrations is assessed: i) at high concentrations where substantial mortality occurs (LC<sub>50</sub>), we confirmed the traditional sigmoidal response curve (ii) at low concentrations about 10 times below the LC<sub>50</sub>, w ...[more]

PMID: 31649283

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Project description:BackgroundLow socioeconomic status (SES) residents living in social housing, which is subsidized by government or government-funded agencies, may have higher exposures to pesticides used in indoor residences since pesticides are applied due to structural deficiencies, poor maintenance, etc. OBJECTIVE: To estimate exposure of residents in low-SES social housing built in the 1970s to legacy and current-use pesticides and to investigate factors related to exposures.MethodsTwenty-eight particle-phase pesticides were measured in the indoor air of 46 units in seven low-income social housing, multi-unit residential buildings (MURBs) in Toronto, Canada using portable air cleaners deployed for 1 week in 2017. Pesticides analyzed were legacy and current use in the classes: organochlorines, organophosphates, pyrethroids, and strobilurins.ResultsAt least one pesticide was detected in 89% of the units with detection frequencies (DF) for individual pesticides of up to 50%, including legacy organochlorines and current-use pesticides. Current-use pyrethroids had the highest DF and concentrations, with the highest particle-phase concentration for pyrethrin I at 32,000 pg/m3. Heptachlor, restricted for use in Canada in 1985, had the highest estimated maximum total air (particle plus gas phase) concentration of 443,000 pg/m3. Heptachlor, lindane, endosulfan I, chlorothalonil, allethrin, and permethrin (except in one study) had higher concentrations than those measured in low-income residences reported elsewhere. In addition to the intentional use of pesticides to control pests and their use in building materials and paints, tobacco smoking was significantly correlated with the concentrations of five pesticides used on tobacco crops. The distribution of pesticides with high DF in individual buildings suggested that pest eradication programs by the building management and/or pesticide use by residents were the major sources of measured pesticides.ImpactLow-income social housing fills a much-needed demand, but the residences are prone to pest infestation and hence pesticide use. We found exposure to at least 1 of 28 particle-phase pesticides in 89% of all 46 units tested, with the highest DF and concentrations for current-use pyrethroids and long-banned organochlorines (e.g., DDT, heptachlor) due to very high persistence indoors. Also measured were several pesticides not registered for use indoors, e.g., strobilurins used to treat building materials and pesticides used on tobacco crops. These results, which are the first Canadian data for most pesticides indoors, show widespread exposure to numerous pesticides.

Project description:ObjectiveThe role of Quercetin in ovarian cancer treatment remains controversial, and the mechanism is unknown. The aim of this study was to investigate the therapeutic effects of Quercetin in combination with Cisplatin and other anti-neoplastic drugs in ovarian cancer cells both in vitro and in vivo, along with the molecular mechanism of action.MethodsQuercetin treatment at various concentrations was examined in combination with Cisplatin, taxol, Pirarubicin and 5-Fu in human epithelial ovarian cancer C13* and SKOV3 cells. CCK8 assay and Annexin V assay were for cell viability and apoptosis analysis, immunofluorescence assay, DCFDA staining and realtime PCR were used for reactive oxygen species (ROS)-induced injury detection and endogenous antioxidant enzymes expression. Athymic BALB/c-nu nude mice were injected with C13*cells to obtain a xenograft model for in vivo studies. Immunohistochemical analysis was carried out to evaluate the ROS-induced injury and SOD1 activity of xenograft tumors.ResultsContrary to the pro-apoptotic effect of high concentration (40 µM-100 µM) of Quercetin, low concentrations (5 µM-30 µM) of Quercetin resulted in varying degrees of attenuation of cytotoxicity of Cisplatin treatment when combined with Cisplatin. Similar anti-apoptotic effects were observed when Quercetin was combined with other anti-neoplastic agents: Taxol, Pirarubicin and 5-Fluorouracil (5-Fu). Low concentrations of Quercetin were observed to suppress ROS-induced injury, reduce intracellular ROS level and increase the expression of endogenous antioxidant enzymes, suggesting a ROS-mediated mechanism of attenuating anti-neoplastic drugs. In xenogeneic model, Quercetin led to a substantial reduction of therapeutic efficacy of Cisplatin along with enhancing the endogenous antioxidant enzyme expression and reducing ROS-induced damage in xenograft tumor tissue.ConclusionTaken together, these data suggest that Quercetin at low concentrations attenuate the therapeutic effects of Cisplatin and other anti-neoplastic drugs in ovarian cancer cells by reducing ROS damage. Quercetin supplementation during ovarian cancer treatment may detrimentally affect therapeutic response.

Project description:There is currently a growing interest in the so-called emerging pollutants, such as pesticides, pharmaceuticals, personal hygiene care products, drugs, etc., whose presence in natural ecosystems is not necessarily recent, but the development in latest years of new and more sensitive methods of analysis has allowed their detection. They can be present in the natural environment, food, and many products of everyday origin, which suggests that human exposure to them is massive and universal. Therefore, the study of this type of substances is becoming one of the priority lines of research of the main agencies dedicated to the protection of public and environmental health, such as the World Health Organization (WHO), United States Environmental Protection Agency (USEPA) or European Union (EU). In this sense, it is of vital importance to know the nature and quantity of this type of contaminants, to establish preventive mechanisms that minimize its presence in aquatic systems, with special requirements for human consumption. This study aimed to describe a protocol for a systematic review and meta-analysis to assess the status of pesticides in European waters. We will search for original studies in the PubMed/Medline, Scopus, Web of Science, EMBASE, ScienceDirect databases. Prevalence studies of emerging contaminants (pesticides) in water resources (watersheds, aquifers, rivers, marine and springs), wastewaters (influent and effluent), and drinking water should be included. Two reviewers will independently screen and assess the included studies, with any disagreements being resolved by a third reviewer. We will summarize the findings using a narrative approach and, if possible, conduct a quantitative synthesis (meta-analysis). We will conduct the protocol following the Preferred Reporting Items for Systematic Review and Meta-Analyses Protocols (PRISMA-P) guidelines. The review will summarize the current evidence on the presence of pesticides in European waters such as glyphosate, chlorpyrifos, pyrethroid pesticides, neonicotinoid pesticides, and/or fungicides, in samples of different water resources like wastewaters and drinking water. We expect that this systematic review will establish preventive mechanisms that minimize the presence of pesticides in water in the environment.

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Predicting low-concentration effects of pesticides.

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Predicting low-concentration effects of pesticides.

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