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Making research data findable, accessible, interoperable and reusable (FAIR) is typically hampered by a lack of skills in technical aspects of data management by data generators and a lack of resources. We developed a Template Wizard for researchers to easily create templates suitable for consistently capturing data and metadata from their experiments. The templates are easy to use and enable the compilation of machine-readable metadata to accompany data generation and align them to existing community standards and databases, such as eNanoMapper, streamlining the adoption of the FAIR principles. These templates are citable objects and are available as online tools. The Template Wizard is designed to be user friendly and facilitates using and reusing existing templates for new projects or project extensions. The wizard is accompanied by an online template validator, which allows self-evaluation of the template (to ensure mapping to the data schema and machine readability of the captured data) and transformation by an open-source parser into machine-readable formats, compliant with the FAIR principles. The templates are based on extensive collective experience in nanosafety data collection and include over 60 harmonized data entry templates for physicochemical characterization and hazard assessment (cell viability, genotoxicity, environmental organism dose-response tests, omics), as well as exposure and release studies. The templates are generalizable across fields and have already been extended and adapted for microplastics and advanced materials research. The harmonized templates improve the reliability of interlaboratory comparisons, data reuse and meta-analyses and can facilitate the safety evaluation and regulation process for (nano) materials., (© 2024. Springer Nature Limited.)

Graphene-based conductive inks offer attractive possibilities in many printing technology applications. Often, these inks contain a mixture of compounds, such as solvents and stabilizers. For the safe(r) and sustainable use of such materials in products, potentially hazardous components must be identified and considered in the design stage. In this study, the hazards of few-layer graphene (FLG)-based ink formulations were tested in fish using in vitro (RTL-W1 cell line) and in vivo aquatic ecotoxicity tests (OECD TG 203). Five ink formulations were produced using different processing steps, containing varying amounts of solvents and stabilizers, with the end products formulated either in aqueous solutions or in powder form. The FLG ink formulations with the highest contents of the stabilizer sodium deoxycholate showed greater in vitro cytotoxic effects, but they did not provoke mortality in juvenile rainbow trout. However, exposure led to increased activities of the cytochrome P450 1a (Cyp1a) and Cyp3a enzymes in the liver, which play an essential role in the detoxification of xenobiotics, suggesting that any effects will be enhanced by the presence of the stabilizers. These results highlight the importance of an SSbD approach together with the use of appropriate testing tools and strategies. By incorporating additional processing steps to remove identified cytotoxic residual solvents and stabilizers, the hazard profile of the FLG inks improved, demonstrating that, by following the principles of the European Commission's safe(r) and sustainable by design (SSbD) framework, one can contribute to the safe(r) and sustainable use of functional and advanced 2D materials in products.

This study was focused to determine an individual and combined effect of mycotoxin citrinin (CIT) and two compounds of the stilbene family- resveratrol (RES) and his dimethyl ether analogue pterostilbene (PTE) which have many health benefits. As a model the human adenocarcinoma cell line HT-29 was used which may exhibits the properties of small intestine cells. Viability, plasma membrane integrity, lysosomal functionality, intracellular production of superoxide anions and superoxide dismutase activity were examined. The results indicate that concentrations of 50 and 100 μg/mL of the tested compounds were cytotoxic in mostly monitored parameters and probably caused apoptosis. HT-29 cells were more sensitive to PTE than to RES with a higher antioxidant effect of PTE than RES, which may be caused by its chemical structure. Both stilbenes at medium doses act as effective superoxide anions scavengers leading to reduction of oxidative stress and consequent cell damage. The nontoxic concentration of RES (25 µg/mL) protects the HT-29 cell line faced to the toxicity of CIT at 25 µg/mL by increasing viability of cells and by reducing the superoxide production induced by CIT concentrations of 12.5 µg/mL and 25 µg/mL.

Among all classes of nanomaterials, silver nanoparticles (AgNPs) have potentially an important ecotoxicological impact, especially in freshwater environments. Fish are particularly susceptible to the toxic effects of silver ions and, with knowledge gaps regarding the contribution of dissolution and unique particle effects to AgNP toxicity, they represent a group of vulnerable organisms. Using cell lines (RTL-W1, RTH-149, RTG-2) and primary hepatocytes of rainbow trout (Oncorhynchus mykiss) as in vitro test systems, we assessed the cytotoxicity of the representative AgNP, NM-300K, and AgNO3 as an Ag+ ion source. Lack of AgNP interference with the cytotoxicity assays (AlamarBlue, CFDA-AM, NRU assay) and their simultaneous application point to the compatibility and usefulness of such a battery of assays. The RTH-149 and RTL-W1 liver cell lines exhibited similar sensitivity as primary hepatocytes towards AgNP toxicity. Leibovitz's L-15 culture medium composition (high amino acid content) had an important influence on the behaviour and toxicity of AgNPs towards the RTL-W1 cell line. The obtained results demonstrate that, with careful consideration, such an in vitro approach can provide valuable toxicological data to be used in an integrated testing strategy for NM-300K risk assessment.

The potential cytotoxic effects of the compounds 8-quinolinol, chloramine-T and natamycin have been studied in isolated pig hepatocytes. The relative cytotoxicity of these compounds was evaluated on the basis of the leakage of cytosolic lactate dehydrogenase (LDH), 3-(4,5 dimethyl)thiazol-2-yl,-2,5-diphenyl tetrazolium bromide (MTT) reduction by mitochondrial dehydrogenases, uptake of neutral red (NR) by cytosolic lysosomes, glutathion (GSH) depletion and oxidized glutathion (GSSG) efflux after 24 h exposure. Evaluation of the 20%, 50% and 80% reduced absorbance data obtained from the parameters NR20, NR50, and NR80, and MTT20, MTT50 and MTT80 enabled us to rank these compounds in decreasing order of cytotoxicity: 8-quinolinol > natamycin > chloramine-T. Also for the parameters LDH and GSH, chloramine-T appears to be less cytotoxic than natamycin and 8-quinolinol. Our study demonstrated that pig hepatocytes may be a useful model for examining cytotoxic events of drugs to be used in pigs, therefore avoiding possible extrapolation problems due to species differences.

The kinetics of fumonisin B1 (FB1) after single doses of 10 mg FB1/kg (po) or 2 mg FB1/kg (i.v.) were studied in male Wistar rats. Serial blood samples were obtained after p.o and i.v. administration. Liver and kidney tissue samples were also obtained after p.o administration. Plasma, liver and kidney concentrations of FB1 were determined by a reversed-phase high-performance liquid chromatographic assay using precolumn 0-phthaldialdehyde derivatisation with fluorescence detection. The FB1 plasma profile could be adequately described by a 2-compartment open model. For FB1, the elimination half-life from plasma was 1.03 h after i.v. and 3.15 h after p.o administration. The apparent volume of distribution and volume of distribution at steady state for FB1 were 0.11 and 0.072 L, respectively, after i.v. administration. The total plasma clearance of FB1 was the same for both the p.o and i.v. routes, 0.072 L/h. After the single p.o dose, FB1 was rapidly absorbed with a Tmax of 1.02 h. The maximum plasma concentration of FB1 was 0.18 microgram/mL. The p.o bioavailability of FB1 was 3.5%. The tissue concentration time data for FB1 fit a 1-compartment open model. Considerable concentrations of FB1 were found in the liver and kidney tissues. The elimination half-lives for FB1 were longer for liver (4.07 h) and kidney (7.07 h) than for plasma (3.15 h). Tissue accumulation of FB1 was evidenced by the tissue/plasma area under the concentration-time curve (AUC) ratios; the AUCtissue/AUCplasma for FB1 was 2.03 in liver and 29.89 in kidney.

The effects of repeated exposure to fumonisin B1 (FB1) on hepatic and renal mixed function oxidase activities and peroxisomal proliferation has been examined in rats following intraperitoneal administration at three dose levels (0.125, 0.25, and 2.5 mg/kg) once a day for 6 days. At the two highest doses, FB1 increased the renal and hepatic N-demethylation of erythromycin (CYP3A1) and the hepatic O-deethylation of ethoxyresorufin (CYP1A1). FB1, at the highest dose of 2.5 mg/kg, also increased the renal O-deethylation of ethoxyresorufin. The liver, but not the kidney, was also susceptible to FB1-dependent induction of the 12- and 11-hydroxylation of lauric acid, suggesting induction of the CYP4A subfamily. Immunoblot studies employing solubilized microsomes from FB1-treated rats revealed that FB1, at the two highest doses, increased the apoprotein levels of CYP1A1 and CYP4A1. The same treatment with FB1 increased the beta-oxidation of palmitoyl-coenzyme A (CoA) in liver homogenates, and immunoblot analysis showed an increase in the apoprotein levels of the trans-2-enoyl-CoA hydratase trifunctional protein. The possible implications of these findings to the hepatocarcinogenicity of this mycotoxin are discussed.

The toxicokinetics of deltamethrin and its metabolite 4'-HO-deltamethrin after single doses of 26 mg of deltamethrin/kg (oral) or 1.2 mg of deltamethrin/kg (intravenous) were studied in male Wistar rats. Serial blood samples were obtained after oral and intravenous administration. Brain, vas deferens, and anococcygeus tissue samples were also obtained after oral administration. Plasma, hypothalamus, cerebellum, frontal cortex, caudate putamen, hippocampus, medulla oblongata, vas deferens, and anococcygeus concentrations of deltamethrin and 4'-HO-deltamethrin were determined by a high-performance liquid chromatographic assay. The deltamethrin and 4'-HO-deltamethrin plasma profiles could be adequately described by a two-compartment open model. For deltamethrin and 4'-HO-deltamethrin, the elimination half-lives (t1/2 theta) from plasma were 33.0 and 25.67 hr after iv and 38.50 and 30.13 hr after po administration of deltamethrin parent compound. The apparent volume of distribution [V alpha(area)] and volume of distribution at steady state [V d(m)] for deltamethrin were 5.33 and 2.04 liters, respectively, after iv administration, suggesting a considerable diffusion of the pyrethroid into tissue. The total plasma clearance of deltamethrin was the same for both the oral and the iv routes-0.11 liter/hr. After the single oral dose, deltamethrin was rapidly absorbed with a Tmax of 1.83 hr. The maximum plasma concentrations of deltamethrin and 4'-HO-deltamethrin were 0.46 and 0.26 microgram/ml. The maximum plasma concentration of 4'-HO-deltamethrin was achieved at 3.29 hr. The oral bioavailability of deltamethrin was found to be 14.43%. The tissue concentration time data for deltamethrin and its metabolite 4'-HO-deltamethrin were found to fit a one-compartment open model. Considerable concentrations of deltamethrin and 4'-HO-deltamethrin were found in the hypothalamus, cerebellum, frontal cortex, caudate putamen, hippocampus, medulla oblongata, vas deferens, and anococcygeus tissues. The elimination half-lives (t1/2 el) for both deltamethrin and 4'-HO-deltamethrin were somewhat smaller for the cerebellum, frontal cortex, caudate putamen, medulla oblongata, vas deferens, and anococcygeus tissues (range, 18-33 hr for deltamethrin and 15-28 hr for 4'-HO-deltamethrin) than for plasma (t1/2 el, 38.50 and 30.13 hr, respectively). Exceptions were seen for the hypothalamus and hippocampus in which the t1/2et's for deltamethrin were 40.76 and 38.50 hr, respectively. Nervous tissue accumulation of deltamethrin and its metabolite 4'-HO-deltamethrin was evidenced by the tissue/plasma area under the concentration (AUC) versus time curve ratios. The ratios of AUCtissue/AUCplasma for deltamethrin were 2.32 in medulla oblongata, 295.30 in hypothalamus, and intermediate in other tissues.

Amoxicillin was given to two groups of eight chickens at a dose of 10 mg/kg of body weight, intravenously (i.v.) or orally. Plasma concentration was monitored serially for 24 h after each administration. Concentrations of amoxicillin were measured using high-performance liquid chromatography. Pharmacokinetic variables were calculated, using a two-compartment open model. The elimination half-life, and the mean residence time for plasma were 8.17 +/- 0.31 and 10.46 +/- 0.51 h, respectively, after i.v. administration and 9.16 +/- 0.60 and 12.26 +/- 0.81 h, respectively, after oral administration. After single oral administration, amoxicillin was rapidly absorbed, with Tmax, of 1.00 +/- 0.06 h. Maximum plasma concentration was 160.40 +/- 4.67 microg/ml and mean amoxicillin concentrations > 15 microg/ml persisted for 24 h. Oral bioavailability of amoxicillin was found to be 63.00 +/- 4.58%. The results indicate that a dosage of 10 mg/kg administered orally at 24 h intervals should be effective in treating a variety of systemic infections in poultry.

The effects of repeated exposure to the pyrethroid insecticide flumethrin (40 mg/kg intraperitoneally once a day for 6 days) on the activity of cytochrome P450-dependent monooxygenases and UDP-glucuronosyltransferase as well as on antipyrine disposition were investigated in male Wistar rats. Pretreatment with flumethrin decreased the activities of NADPH-cytochrome c reductase (38%), aniline hydroxylase (53%), aminopyrine N-demethylase (54%), and UDP-glucuronosyltransferase (34%), and the content of cytochrome P450 (36%) in hepatic microsomes. Total plasma clearance of antipyrine was decreased by flumethrin pretreatment (54%), while the elimination half-life at beta phase and the mean residence time of antipyrine were increased (96 and 88%, respectively). Urinary excretion of norantipyrine, 4-hydroxyantipyrine, and 3-hydroxymethylantipyrine was decreased by 60, 38, and 33%, respectively, in the 96 hr after flumethrin treatment. In addition, the rate constants for formation of each of these metabolites were decreased by an average of approximately 74%. These findings provide evidence that flumethrin exposure diminishes hepatic enzyme levels and catalytic activities of monooxygenase systems as well as oxidative metabolism of antipyrine.

Doxycycline was given to two groups of eight chickens at a dose of 20 mg/kg of body weight, intravenously (i.v.) or orally. Plasma concentration was monitored serially for 12 h after each administration. Another group of 30 chickens was given 20 mg/kg orally every 24 h for 4 days, and plasma and tissue concentrations determined serially after the last administration. Concentrations of doxycycline were measured using high-performance liquid chromatography. Pharmacokinetic variables were calculated, using a two-compartment open model. The elimination half-life and the mean residence time for plasma were 6.03 +/- 0.45 and 7.48 +/- 0.38 h, respectively, after oral administration and 4.75 +/-0.21 and 2.87 +/-0.11 h, respectively, after i.v. administration. After single oral administration, doxycycline was absorbed rapidly, with T(max) of 0.35 +/- 0.02 h. Maximum plasma concentration was 54.58 +/- 2.44 mu/ml. Oral bioavailability of doxycycline was found to be 41.33 +/- 2.02%. Doxycycline was widely distributed in tissues and considerable concentrations were found following oral administration of 20 mg/kg on four successive days. The results indicate that doxycycline concentrations were cleared slowly and were at or below the accepted drug tolerance levels in the marker tissues within 5 days after dosing.