Clay Types Modulate the Toxicity of Low Concentrated Copper Oxide Nanoparticles Toward Springtails in Artificial Test Soils.

Copper oxide nanoparticles (CuO-NPs) can be applied as an efficient alternative to conventional Cu in agriculture. Negative effects of CuO-NPs on soil organisms were found, but only in clay-rich loamy soils. It is hypothesized that clay-NP interactions are the origin of the observed toxic effects. In the present study, artificial Organisation for Economic Co-operation and Development soils containing 30% of kaolin or montmorillonite as clay type were spiked with 1-32 mg Cu/kg of uncoated CuO-NPs or CuCl2 . We performed 28-day reproduction tests with springtails of the species Folsomia candida and recorded the survival, reproduction, dry weight, and Cu content of adults. In a second experiment, molting frequency and the Cu content of exuviae, as well as the biochemical endpoints metallothionein and catalase (CAT) in springtails, were investigated. In the reproduction assay, negative effects on all endpoints were observed, but only in soils containing montmorillonite and mostly for CuO-NPs. For the biochemical endpoints and Cu content of exuviae, effects were clearly distinct between Cu forms in montmorillonite soil, but a significant reduction compared to the control was only found for CAT activity. Therefore, the reduced CAT activity in CuO-NP-montmorillonite soil might be responsible for the observed toxicity, potentially resulting from reactive oxygen species formation overloading the antioxidant system. This process seems to be highly concentration-dependent, because all endpoints investigated in reproduction and biochemical assays of CuO-NP-montmorillonite treatments showed a nonlinear dose-response relationship and were constantly reduced by approximately 40% at a field-realistic concentration of 3 mg/kg, but not at 32 mg/kg. The results underline that clay-CuO-NP interactions are crucial for their toxic behavior, especially at low, field-realistic concentrations, which should be considered for risk assessment of CuO-NPs. Environ Toxicol Chem 2022;41:2454-2465. © 2022 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

Evaluation of electrocardiograms recorded in cynomolgus monkeys with short- and long-term intracardiac lead implantations.

INTRODUCTION: minimally invasive placement of intracardiac (IC) ECG leads in monkeys has greatly improved signal quality and the ability to interpret these ECGs. However, information on characteristics of the ECGs recorded using the IC lead is not available in the literature. There are concerns about the potential impact of IC lead placement on the ECG waveform and cardiac function as a result of potential irritation or trauma resulting from the placement and/or long term residence of the IC lead. The purposes of this study were to characterize IC ECG morphology, to obtain information on the recovery processes after IC ECG lead implantation, and to evaluate the IC ECG model application to safety pharmacology studies. METHODS: the telemetry transmitter, arterial blood pressure catheter and IC ECG lead were implanted in 40 cynomolgus monkeys, two of which were also implanted with subcutaneous (SC) ECG leads. The data of IC ECG, heart rate (HR) and mean arterial blood pressure (MABP) were collected telemetrically for a period of 1-12 months after implantation, and measured using computer softwares. RESULTS: the IC ECG waveforms varied greatly from those of SC ECG. There was no clearly identifiable S-T segment, and T waves were biphasic in the majority of IC ECGs. The morphology of IC ECG was diversified among animals, progressively changed in the first 2 weeks post-surgery and stabilized approximately 3 weeks post-surgery. MABP and HR were elevated after implant surgery, but recovered to the levels comparable to those of SC in approximately 1 and 4 weeks, respectively. The IC ECG values obtained during week 8 to 10 (HR=134+/-25 bpm, PR interval=87+/-13 ms, QRS interval=40+/-7 ms, and QT interval=246+/-30 ms, QTcF=318+/-28 ms) were comparable to those from SC ECG. DISCUSSION: the IC ECG provides a clear ECG signal with values comparable to, and waveforms different from, SC recordings. The complicated surgical procedure with long substantial recovery time, high incidence of IC lead malfunction, and high costs for IC leads may limit application of the IC ECG model in safety pharmacology studies.