In this paper, a possible use of white sweet clover (Melilotus albus Med.) for phytoremediation was assessed. The plants were grown on soils with naturally occurring concentrations of potentially toxic elements (PTEs). First, the content of PTEs was determined in plant biomass and in soil samples using: (a) Optical emission spectrometry with inductively coupled plasma to determine Sb, As, Cd, Cu, Ni, Pb, and Se, and (b) thermal decomposition, amalgamation, and atomic absorption spectrometry to determine Hg. The effectiveness of Melilotus albus Med. (M. albus) for phytoremediation was evaluated using the bioconcentration factor (BCF). The phytoextraction potential of M. albus was determined using bioaccumulation factor (BAC) and translocation factor (TF) values. The highest concentration of PTEs in roots was detected for zinc (10.56 mg/kg of dry weight, DW) and copper (5.128 mg/kg of DW). Similarly, the highest concentration in above-ground parts of the plant was detected for zinc and copper (12.638 and 4.0 mg/kg of DW, respectively). Although the values were relatively high, the effectiveness of the absorption of these PTEs by plant biomass from the soil was relatively very low. BAC and BCF were always lower than 1. On the other hand, the results suggested that M. albus effectively transports PTEs (only for Zn, Pb and Hg) from roots to shoots, because TF was always higher than 1. However, the accumulation of PTEs from soils with a natural abundance of PTEs was not excessive in comparison to conventional maize silage. Therefore, there is no potential risk of biomethane production in biogas plants when biomass from M. albus is used. Full article

Polycyclic aromatic hydrocarbons (PAHs) and polychlorinated biphenyls (PCBs) are groups of chemical substances commonly found in the environment. Because of large differences in the concentrations of PAHs and PCBs in the materials tested, separate analytical methods specific to each group of compounds are usually used. The aim of this study was to compare methods for the determination of PAHs and PCBs that permit the simultaneous determination of these compounds from one solvent extract. The analysis of the content of 15 PCB congeners and 16 PAHs was conducted using dried fruits. The analyses were performed with gas chromatography coupled with mass spectrometry. PAHs and PCBs were determined separately in each fruit sample using specific extraction and cleanup procedures for the respective groups of compounds. Analyses were also performed with two methods that permitted the simultaneous analysis of PAHs and PCBs in one solvent extract. The integrated methods did not provide adequate extract cleanup of interfering substances; consequently, the results of determinations of PAHs and PCBs using these methods were significantly different from the values obtained with proven determination methods for PAHs and PCBs. Full article

(1) Background: The aim of this study was to identify the degradation product of ramipril (RAM) formed under dry air and to verify its potential modes of carcinogenicity. We intended to check whether its formation and presence in final dosage forms could pose a cancer risk to humans who are treated with RAM due to cardiological indications. The carcinogenicity of this compound was evaluated with respect to two mechanisms: a potential direct DNA-damage and indirect toxicity, secondary to forming mutagenic N-nitroso metabolites. (2) Methods: Firstly, a forced ageing test under dry air was conducted for pure RAM in order to induce its degradation. The validated HPLC system was used to describe the kinetic order of this reaction. The emerging degradation impurity was identified by HPLC-MS. In the second stage, the cancer risk of the identified RAM degradant was predicted using a structure-based assessment by in silico QSAR model, employing three endpoints: carcinogenicity, genotoxicity and mutagenicity. In the third stage, the obtained QSAR results were experimentally verified. To verify genotoxicity prediction, in vitro micronucleus assay was employed. It enabled us to assess the potential direct DNA-damaging properties of RAM degradant at high concentrations (as screening series) and at concentrations usually observed in human blood (to mimic the clinical scenario). To verify the QSAR mutagenicity prediction, an in vitro Ames test was carried out. It was designed so as to detect two mechanisms of mutagenicity: a direct one (for pure degradant) and an indirect one (via N-nitroso-metabolites formation). N-nitroso-metabolites for mutagenicity assessment were obtained using NAP test. (3) Results: The kinetic mechanism of RAM degradation was first-order, the degradation rate constant was k = 1.396 ± 0.133 × 10⁻⁵ s⁻¹ (T = 373 K), thus the formation of impurity was rapid. Energy of activation was 174.12 ± 46.2 kJ/mol, entropy was positive, thus reaction was bimolecular and favored; enthalpy was 171.65 ± 48.7 kJ/mol, thus reaction was endothermic. Only one degradation impurity was formed, and it was identified as RAM diketopiperazine derivative (DKP). QSAR simulation predicted that DKP could be carcinogenic and genotoxic, but this result had only moderate reliability. DKP was also predicted to be non-mutagenic and this prediction was strong (endpoint score 0.2). The confirmatory micronucleus experiment for genotoxicity prediction suggested that DKP was cytotoxic and it could be also aneugenic at a high concentration (0.22 mg/mL), evidenced by a three-fold increase in micronuclei relative to the control (11.86:33.33%, p = 0.0184). At physiologic concentrations, its cytotoxicity and genotoxicity did not occur. This means that the genotoxicity of DKP was limited by a threshold mechanism. In the mutagenicity in vitro assessment, pure DKP was not mutagenic, but its nitrosation product induced base substitutions mutations in test bacteria TA100 following metabolic activation at a concentration of 4.5 mg/mL, confirming its mutagenicity. (4) Conclusions: RAM rapidly cyclizes to diketopiperazine derivative under dry air. This impurity resides in drugs administered to patients. DKP is potentially aneugenic and cytotoxic at high concentrations, yet at concentrations typically occurring in human blood, this effect is unlikely. The exposure of patients to high concentrations of DKP, exceeding the typical blood level and standard RAM dosing, could lead to cancer development, thus the safe threshold for human exposure to DKP must be verified in follow-up in vivo experiments. Based on our results, it is impossible to establish the maximum safe dose of pure DKP to humans. Furthermore, DKP itself is not mutagenic, but it is liable to the formation of mutagenic nitroso-metabolites in vivo. Nitroso-derivatives of DKP are in vitro mutagens and their real-life impact on humans must be further evaluated in in vivo studies. Until this is carried out, RAM should not be formulated by manufacturers using dry procedures to minimize DKP formation and reduce risk of human carcinogenesis, since DKP could cause cancer via two independent mechanisms: direct genotoxicity when the exposure over standard RAM dosing occurs, and indirect mutagenicity via in vivo N-nitrosamine formation. Full article

Dexmedetomidine (DEX) used for sedation was reported to have organ-protecting effects in ischemia–reperfusion injury model animals. However, no testicular cell-protecting effect was observed with DEX treatment. The effects of DEX on a normal testis in vivo have not been reported. Therefore, DEX was administered to mice for 14 days to investigate the reproductive toxicology of DEX on the testis and the localization of DEX-responsive receptors. The testes, pituitary glands, and serum were examined and analyzed using real-time PCR, immunofluorescence staining, and liquid chromatography–mass spectrometry. In the testis, α2A-adrenergic receptors were observed in the cytoplasm of Leydig cells, while imidazoline receptors were observed in germ cells and Leydig cell cytoplasm. The levels of luteinizing hormone and follicle-stimulating hormone mRNA in the pituitary gland significantly temporarily decreased. Serum DEX could not be detected 26 h after DEX administration. DEX administration did not affect serum testosterone levels, some testicular mRNA related to spermatogenesis, and oxidative stress factors. Therefore, although DEX receptors are present in the testis, DEX is metabolized relatively quickly, and DEX administration has no damaging effects on the testis. This study is the first in vivo report about the effects of DEX administration on the testis. Full article

Therapeutic Deep Eutectic Systems (THEDESs) are a mixture of components, including an active pharmaceutical ingredient, that have recently emerged because of their interesting properties for drug therapies. In general, they have been recognized to increase the solubility and permeability of some drugs, and consequently, their bioavailability. Moreover, they have also been used for novel formulations of pharmaceuticals. Despite the potential benefits of THEDESs, concerns about their safety and toxicity remain. In this review, we summarize previous studies that have investigated the toxicity of THEDESs. These studies evaluate the toxicity of THEDESs using various methods, including cell cultures, animal models, and human trials. The results of previous findings suggest that THEDESs are generally well-tolerated and have low toxicity. However, further research is needed to fully understand the long-term effects of these systems on human health and to identify any potential adverse effects. Full article

Some chemical components in sun cream filters have endocrine-disrupting activity or can be carcinogenic, neurotoxic, bioaccumulative, allergens, or be toxic for human reproduction. It is important that sunscreens have safety requirements. The objective of this work is to compare sun cream filters used in conventional commercial sunscreens and those that are considered natural products, especially focused on endocrine-disrupting effects. In order to achieve the above objective, the compositions of different conventional and natural sun cream filters were evaluated and compared, taking into account the presence of the different sun cream filters whose effects were evaluated on the website specialized in safety and cosmetics, Environmental Working Group (EWG), and in the Register of chemical substances and mixtures in the EU Registration, Evaluation, Authorization and Restriction of Chemicals (REACH) Regulation. The currently available evidence of each sun cream filter and their degree of safety has been summarized. Several organic sun cream filters present a potential risk to health and the environment; however, inorganic sun cream filters such as titanium dioxide and zinc oxide (ZnO and TiO₂) show a very low risk in humans as they are not absorbed through intact or damaged tissues. The legislation does not oblige manufacturers to specify the concentration of each substance, which provides qualitative but not quantitative information for the consumer. Full article