Toxicity and Antifeedant Activity of Calotropis gigantea L. Leaf Extract Against Plutella xylostella L. (Lepidoptera: Plutellidae)

Many parts of the Calotropis gigantea plant are known to contain bioactive compounds, but leaves contain the most. This study aimed to determine the toxicity and antifeedant activity of C. gigantea leaves against Plutella xylostella. The study was carried out from November 2019 to July 2020. Toxicity was tested using the leaf dipping and spraying methods. Antifeedant activity was tested using a no-choice test and a choice test. Identification of the compound composition of the leaf extract of C. gigantea was carried out at the Integrated Research and Testing Laboratory, Gadjah Mada University. Extract toxicity data obtained were analyzed by Probit analysis. The results showed that the antifeedant activity of C. gigantea leaf extract a no-choice and with choice at each concentration had a significant effect on the consumption of P. xylostella larvae rations. The toxicity (LC50) of the leaf extract of C. gigantea to P. xylostella by the dipping method was 2,958 µgl-1 while the spraying application was 3.944 µgl-1. The composition of chemical compounds contained in the leaf extract of C. gigantea is saponins, alkaloids, flavonoids, tannins, phenols, terpenoids. With the composition of these chemical compounds, the leaf extract of C. gigantea has the potential as a source of vegetable insecticide compounds against P. xylostella.

Novel longitudinal Multiple Overall Toxicity (MOTox) score to quantify adverse events experienced by patients during chemotherapy treatment: a retrospective analysis of the MRC BO06 trial in osteosarcoma

ObjectivesThis study aims at exploring and quantifying multiple types of adverse events (AEs) experienced by patients during cancer treatment. A novel longitudinal score to evaluate the Multiple Overall Toxicity (MOTox) burden is proposed. The MOTox approach investigates the personalised evolution of high overall toxicity (high-MOTox) during the treatment.DesignRetrospective analysis of the MRC-BO06/EORTC-80931 randomised controlled trial for osteosarcoma.SettingInternational multicentre population-based study.ParticipantsA total of 377 patients with resectable high-grade osteosarcoma, who completed treatment within 180 days after randomisation without abnormal dosages (+25% higher than planned).InterventionsPatients were randomised to six cycles of conventional versus dose-intense regimens of doxorubicin and cisplatin. Non-haematological toxicity data were collected prospectively and graded according to the Common Terminology Criteria for Adverse Events (CTCAE).Main outcome measuresThe MOTox score described the overall toxicity burden in terms of multiple toxic AEs, maximum-severity episode and cycle time-dimension. Evolution of high-MOTox was assessed through multivariable models, that investigated the impact of personalised characteristics (eg, achieved chemotherapy dose, previous AEs or biochemical factors) cycle-by-cycle.ResultsA cycle-by-cycle analysis identifies different evolutions of MOTox levels during treatment, detecting differences in patients’ health. Mean MOTox values and percentages of patients with high-MOTox decreased cycle-by-cycle from 2.626 to 1.953 and from 57.8% to 36.6%, respectively. High-MOTox conditions during previous cycles were prognostic risk factors for a new occurrence (ORs range from 1.522 to 4.439), showing that patient’s history of toxicities played an important role in the evolution of overall toxicity burden during therapy. Conventional regimen may be preferred to dose-intense in terms of AEs at cycles 2–3 (p<0.05).ConclusionsThe novel longitudinal method developed can be applied to any cancer studies with CTCAE-graded toxicity data. After validation in other studies, the MOTox approach may lead to improvements in healthcare assessment and treatment planning.Trial registration numberISRCTN86294690; Post-results.

Species Sensitivity Distributions of Benthic Macroinvertebrates in Fludioxonil-Spiked Sediment Toxicity Tests

In China, the fungicide fludioxonil, that accumulates and persists in sediments, has a widespread agricultural use to control various fungal diseases. Its residues may cause toxic effects to benthic aquatic fauna, thereby impacting ecosystem service functions of aquatic ecosystems. To assess the potential environmental effects of fludioxonil in the sediment compartment of edge-of-field surface waters, sediment-spiked single-species toxicity tests with benthic macroinvertebrates were performed. In all experiments artificial sediment was used with an organic carbon content of 2.43% on dry weight basis. The single-species tests were conducted with 8 benthic macroinvertebrates covering different taxonomic groups typical for the Yangtze River Delta, China. The 28d-EC10 and 28-LC10 values thus obtained were used to construct species sensitivity distributions (SSDs). In addition, our data were supplemented with similar fludioxonil-spiked sediment toxicity data for benthic invertebrates from the Netherlands. Based on SSDs constructed with 28d-EC10 values of 8 benthic species from our experiments in China, hazardous concentrations to 5% of the species tested (HC5’s) of respectively 0.57 mg fludioxonil/kg dry weight sediment and 5.4 µg fludioxonil/L pore water were obtained. Supplementing our data from China with 8 similar toxicity data for other benthic species from the Netherlands, these HC5 values became respectively 1.2 mg fludioxonil/kg dry weight sediment and 11 µg fludioxonil/L pore water.

A QSAR–ICE–SSD Model Prediction of the PNECs for Per- and Polyfluoroalkyl Substances and Their Ecological Risks in an Area of Electroplating Factories

Per- and polyfluoroalkyl substances (PFASs) are a class of highly fluorinated aliphatic compounds that are persistent and bioaccumulate, posing a potential threat to the aquatic environment. The electroplating industry is considered to be an important source of PFASs. Due to emerging PFASs and many alternatives, the acute toxicity data for PFASs and their alternatives are relatively limited. In this study, a QSAR–ICE–SSD composite model was constructed by combining quantitative structure-activity relationship (QSAR), interspecies correlation estimation (ICE), and species sensitivity distribution (SSD) models in order to obtain the predicted no-effect concentrations (PNECs) of selected PFASs. The PNECs for the selected PFASs ranged from 0.254 to 6.27 mg/L. The ΣPFAS concentrations ranged from 177 to 983 ng/L in a river close to an electroplating industry in Shenzhen. The ecological risks associated with PFASs in the river were below 2.97 × 10−4.

Deep Eutectic Solvents: Are They Safe?

Deep eutectic solvents (DESs) are a relatively new type of solvent that have attracted the attention of the scientific community due to their environmentally friendly properties and their versatility in many applications. Many possible DESs have been described and, thus, it is not easy to unequivocally characterize and generalize their properties. This is especially important in the case of the (eco)toxicity information that can be found for these mixtures. In this review, we collect data on the human and environmental toxicity of DESs, with the aim of gathering and exploring the behavioral patterns of DESs. The toxicity data found were analyzed attending to different factors: hydrogen bond donors or acceptors that form part of the eutectic mixture, pH, and the presence of organic acids in the DES molar ratio of the components, or interactions with natural compounds. In the case of ecotoxicity, results generally depend on the biomodel studied, along with other factors that have been also revised. Finally, we also carried out a revision of the biodegradation of DESs.

Do Lipid-Based Nanoparticles Hold Promise for Advancing the Clinical Translation of Anticancer Alkaloids?

Since the commercialization of morphine in 1826, numerous alkaloids have been isolated and exploited effectively for the betterment of mankind, including cancer treatment. However, the commercialization of alkaloids as anticancer agents has generally been limited by serious side effects due to their lack of specificity to cancer cells, indiscriminate tissue distribution and toxic formulation excipients. Lipid-based nanoparticles represent the most effective drug delivery system concerning clinical translation owing to their unique, appealing characteristics for drug delivery. To the extent of our knowledge, this is the first review to compile in vitro and in vivo evidence of encapsulating anticancer alkaloids in lipid-based nanoparticles. Alkaloids encapsulated in lipid-based nanoparticles have generally displayed enhanced in vitro cytotoxicity and an improved in vivo efficacy and toxicity profile than free alkaloids in various cancers. Encapsulated alkaloids also demonstrated the ability to overcome multidrug resistance in vitro and in vivo. These findings support the broad application of lipid-based nanoparticles to encapsulate anticancer alkaloids and facilitate their clinical translation. The review then discusses several limitations of the studies analyzed, particularly the discrepancies in reporting the pharmacokinetics, biodistribution and toxicity data. Finally, we conclude with examples of clinically successful encapsulated alkaloids that have received regulatory approval and are undergoing clinical evaluation.

Development of the SciRAP Approach for Evaluating the Reliability and Relevance of in vitro Toxicity Data

Efficient and successful integration of data generated from non-animal test methods must rely on reliable and relevant data. It is important therefore to develop tools and criteria that facilitate scientifically sound, structured, and transparent evaluation of reliability and relevance of in vitro toxicity data to efficiently inform regulatory hazard and risk assessment. The Science in Risk Assessment and Policy (SciRAP) initiative aims to promote such overarching goals. We present the work to develop and refine the SciRAP tool for evaluation of reliability and relevance of in vitro studies for incorporation on the SciRAP web-based platform (www.scirap.org). In the SciRAP approach, reliability evaluation is based on criteria for reporting quality and methodological quality, and is explicitly separated from relevance evaluation. The SciRAP in vitro tool (version 1.0) was tested and evaluated during an expert test round (April 2019-September 2020) on three in vitro studies by thirty-one experts from regulatory authorities, industry and academia from different geographical areas and with various degree of experience in in vitro research and/or human health risk assessment. In addition, the experts answered an online survey to collect their feedback about the general features and desired characteristics of the tool for further refinement. The SciRAP in vitro tool (version 2.0) was revised based on the outcome of the expert test round (study evaluation and online survey) and consists of 24 criteria for evaluating “reporting quality” (reliability), 16 criteria for “methodological quality” (reliability), and 4 items for evaluating relevance of in vitro studies. Participants were generally positive about the adequacy, flexibility, and user-friendliness of the tool. The expert test round outlined the need to (i) revise the formulation of certain criteria; (ii) provide new or revised accompanying guidance for reporting quality and methodological quality criteria in the “test compounds and controls,” “test system,” and “data collection and analysis” domains; and (iii) provide revised guidance for relevance items, as general measures to reduce inter-expert variability. The SciRAP in vitro tool allows for a structured and transparent evaluation of in vitro studies for use in regulatory hazard and risk assessment of chemicals.

Study of the toxicity of nanoparticles of various nature

Nanoparticles of various nature are increasingly being subjected to extensive research in recent years, in particular, studies of toxicity. This review article briefly systematizes and summarizes the available toxicity data of nanoparticles of various nature.