This study predicted dapaconazole clinical drug–drug interactions (DDIs) over the main Cytochrome P450 (CYP) isoenzymes using static (in vitro to in vivo extrapolation equation, IVIVE) and dynamic (PBPK model) approaches. The in vitro inhibition of main CYP450 isoenzymes by dapaconazole in a human liver microsome incubation medium was evaluated. A dapaconazole PBPK model (Simcyp version 20) in dogs was developed and qualified using observed data and was scaled up for humans. Static and dynamic models to predict DDIs following current FDA guidelines were applied. The in vitro dapaconazole inhibition was observed for all isoforms investigated, including CYP1A2 (IC₅₀ of 3.68 µM), CYP2A6 (20.7 µM), 2C8 (104.1 µM), 2C9 (0.22 µM), 2C19 (0.05 µM), 2D6 (0.87 µM), and 3A4 (0.008–0.03 µM). The dynamic (PBPK) and static DDI mechanistic model-based analyses suggest that dapaconazole is a weak inhibitor (AUCR > 1.25 and 2 and <5) of CYP2C8 and CYP2D6, and a strong inhibitor (AUCR ≥ 5) of CYP2C19 and CYP3A, considering a clinical scenario. The results presented may be a useful guide for future in vivo and clinical dapaconazole studies.

Metformin (MET), an antidiabetic compound, has received increasing attention, as it cannot be effectively removed during conventional wastewater treatment processes and may act as an endocrine disruptor. Electron beam irradiation (EBI) is an eco-friendly process able to degrade and neutralize biohazardous pollution almost instantly. In this context, this study applied EBI to MET degradation and detoxification in aqueous solutions. A 98% MET degradation rate and TOC removal of 19.04 ± 1.20% at a 1.0 kGy EBI dose was obtained, with up to 65% mineralization reached at 5.0 kGy. Toxicity assays were performed with Vibrio fischeri, Saccharomyces cerevisiae, and Daphnia similis, and the findings indicate that generated byproducts were only more toxic to D. similis. This reveals the need to assess organisms belonging to different trophic levels. A cytotoxic assessment employing Allium cepa roots demonstrated no toxic effects concerning untreated and irradiated samples.

Technological advances have promoted improvements in several science fields, especially related to environmental and analytical areas with the improvement of detection and development of environmentally friendly extraction techniques. This study applied Quick, Easy, Cheap, Effective, Rugged and Safe method (QuEChERS) for soil extraction and assessed its performance through a validation study using samples from the soil of a contaminated area in Caieiras, SP, Brazil. Nine organochlorine pesticides, including the isomers alpha, beta, gamma and delta- hexachlorocyclohexane; cis- and trans-heptachlor epoxide; cis- and trans-chlordane and heptachlor were analyzed by gas chromatography coupled to electron capture detector. The method was validated according to ISO 5725-4 (2020), EURACHEM (2014) and DOQ-CGCRE-008 (2016). The limits of detection and quantification of the method for the nine organochlorines were α-HCH (1.2 and 12.6 µg kg⁻¹), β-HCH (1.7 and 12.0 µg kg⁻¹), γ-HCH (1.5 and 11.6 µg kg⁻¹), δ-HCH (0.8 and 11.6 µg kg⁻¹), heptachlor (1.0 and 10.8 µg kg⁻¹), cis-heptachlor epoxide (0.9 and 11.5 µg kg⁻¹), trans-heptachlor epoxide (0.9 and 11.5 µg kg⁻¹), cis-chlordane (0.4 and 7.9 µg kg⁻¹) and trans-chlordane (0.5 and 10.9 µg kg⁻¹), respectively, and all of them were within the maximum limits recommended by the EPA for the compounds α-HCH (86.0 and 360.0 µg kg⁻¹), β-HCH (300.0 and 1.3 × 10³ µg kg⁻¹), γ-HCH (570.0 and 2.5 × 10³ µg kg⁻¹), δ-HCH (not defined), heptachlor (130.0 and 630.0 µg kg⁻¹), cis-/trans-heptachlor epoxide (7.0 and 330.0 µg kg⁻¹), cis-/trans-chlordane (1.77 × 10³ and 7.7 × 10³ µg kg⁻¹) in residential and industrial soil, respectively. Recovery results were between 65% and 105% for almost all compounds, which is an optimum result for multi-residue analytical methods, considering the complexity of the matrix used in the study. Caieiras presented contamination levels of α-HCH in the range of 2.0 to 66.0 µg g⁻¹, which was higher than the limits established by EPA, corresponding to 0.077 µg g⁻¹ for residential soil and 0.27 µg g⁻¹ for industrial soil. According to the validation study, the analytical method proposed was reliable for organochlorine quantification, and the QuEChERS was considered efficient for organochlorine extraction from soil.