1.Preclinical pharmacokinetics and tissue distribution of a polyhexamethylene guanidine derivative after ocular mucosal administration
Ivan IVANOV ; Denis SHATALOV ; Daria KIRILLOVA ; Danila PETRUSEVICH ; Sergei BELIAKOV ; Stanislav KEDIK
Environmental Analysis Health and Toxicology 2025;40(4):e2025027-
Antibiotic resistance is a critical medical issue. Antiseptics, which play a key role in treating and preventing eye infections and inflammations, have the potential to induce resistance in pathogenic microorganisms despite their broad antimicrobial spectrum. When introducing new active substances into ophthalmic treatments, it is crucial to assess the risk of side effects caused by the systemic action of the active compound. The succinic salt of polyhexamethylene guanidine derivative (ss-PHMGd) has shown high in vitro activity. This study aimed to evaluate the systemic effects of ss-PHMGd-based eye drops after ocular instillation in a preclinical model. Simple mathematical models were used to calculate pharmacokinetic parameters during instillation in two types of laboratory animals: guinea pigs and chinchilla rabbits. Groups received intravenous injections and ocular treatments. Tritium-labeled ss-PHMGd was used to quantify its concentration in organs and tissues. To test the linearity of the parameter relationships, data from three different doses were compared. Renal excretion was studied by quantifying ss-PHMGd concentrations in urine using radiometric methods. The results showed that ss-PHMGd-based eye drops present a low risk of systemic side effects and exhibit minimal penetration into other organs after instillation. No species-specific differences were found in the ADME parameters of the preclinical models (the guinea pig-to-chinchilla rabbit absorption ratio was 0.7). The AUC-D parameters exhibited a linear relationship for doses ranging from 0.5 of therapeutic dose (TD) to 5TD in guinea pigs. Renal excretion analysis revealed that 5.3% of the administered dose was excreted through the kidneys, indicating significant metabolic transformation or excretion via other pathways. This study enhances the understanding of the pharmacokinetics and safety of polyguanidines, with implications for toxicology and risk assessment.
2.Plant growth-promoting properties of metal-tolerant bacteria isolated from battery wastes dumpsites
Oluwarotimi John JOSEPH ; Adeniyi Adewale OGUNJOBI
Environmental Analysis Health and Toxicology 2025;40(4):e2025028-
Environmental pollution by heavy metals arising from several industrial processes is a major cause for concern globally as these metals disrupt the soil ecosystem and rendering metal-polluted soils unfit for use in agriculture. As such, it is essential to devise means to reclaim these soils to sustain the soil biodiversity and enhance plant growth. This study focused on the determination of plant growth-promoting features of metal-tolerant bacteria (MTB) isolated from metal-polluted soils. Composite soil samples were obtained from three different sites receiving battery wastes. Using atomic absorption spectrophotometry, concentrations of heavy metals (cadmium, nickel, lead, zinc) in the soil samples were determined. Nutrient agar augmented with 50 μg/mL salts of the metals were used to cultivate MTB. Recovered MTB were screened for metal tolerance (100-500 μg/mL). Isolates demonstrating elevated multiple metal tolerance were identified using biochemical tests and identity confirmed using 16S rRNA sequencing, followed by screening for presence of metal-resistance genes (zntA, nreB, cadA, pbrA) using PCR and selected plant growth-promoting (PGP) traits. Statistical analysis of data generated was conducted using descriptive statistics. Of all contaminants, lead was most abundant (2596.8 ± 4.48 mg/kg). A total of 132 MTB were cultivated in pure culture, with 20 (15.15%) demonstrating multi-metal tolerance belonging to the genera Serratia (1), Citrobacter (1), Bacillus (1), Staphylococcus (2), Providencia (2), Mammaliicoccus (2), Pseudomonas (4) and Alcaligenes (7). Genes (pbrA/cadA/zntA) were detected (1/5/12). Nitrogen fixation/potassium/phosphate solubilisation/IAA/siderophores production were demonstrated by 15/10/5/13/17 isolates. Isolates obtained from the different sites exhibited significant multi-metal tolerance and demonstrated significant plant growth features.
3.Assessing the carcinogenic and non-carcinogenic health risks associated with potentially toxic elements (PTEs) in vegetables from Gombe Markets, Northern Nigeria
Mohammad Bashir SULAIMAN ; Aishatu Maigari UMAR ; Ahmad Bilyaminu RAFI ; Ismail Maigari ADAMU ; Aliyu Tijjani FADAWA ; Taibatu Idris UMAR ; Amina Muhammad BELLO
Environmental Analysis Health and Toxicology 2025;40(4):e2025031-
Vegetables are essential for human nutrition due to their low fat content and high levels of vitamins, minerals, and dietary fiber. However, studies have shown that vegetables are vulnerable to PTE contamination as a result of anthropogenic activities. This study determined the concentrations and health impacts associated with potentially toxic elements (PTEs) in specific vegetables (green beans, spinach, green pepper, carrots, and onions). A total of 90 vegetable samples were randomly selected and purchased from local markets and analyzed for potentially toxic elements (PTEs) (Cd, Fe, Cr, Pb, Cu, Zn, Co, and Ni) using an atomic absorption spectrophotometer (AAS). The mean concentrations (mg·kg-1) of PTEs ranged from 0.006 - 0.021 for Cd, 2.27 - 12.32 for Fe, 0.05 - 0.150 for Cr, 0.087 - 0.254 for Pb, 0.035 - 0.062 for Cu, 2.65 - 15.61 for Zn, 0.010 - 0.050 for Co, and 0.012 - 0.058 for Ni. The abundance of PTEs was found to be in the following declining order: Zn >Fe >Cu >Cr >Ni >Co >Pb >Cd. The hazard index (HI) for both children and adults was <1, suggesting that there is no likely non-carcinogenic effect from consuming these vegetables. Similarly, the carcinogenic risk was below the acceptable value range of 1.0 × 10-6 - 1.0 × 10-4. Based on the results of this study, it is unlikely that the vegetables analyzed pose a health risk to consumers. However, monitoring and continuous stringent regulations of PTEs on foodstuff for public health protection.
4.Health risk assessment of benzene exposure among workers in gasoline stations in Northeastern Thailand
Laksanee BOONKHAO ; Narueporn KAEWKOON ; Ploywan KANHABUT ; Weerayuth PRANAI ; Pongsak RATTANACHAIKUNSOPON ; Sanga TUBTIMHIN
Environmental Analysis Health and Toxicology 2025;40(4):e2025026-
Benzene exposure affects gasoline station personnel, and prior studies have shown that working at gasoline stations has a greater effect on neurological symptoms. This study aims to examine the risk of benzene exposure and evaluate workers’ knowledge and preventive practices regarding benzene at gasoline stations in Northeastern Thailand. A questionnaire was utilized to collect data on general knowledge and preventive practices from 82 employees across 57 gasoline stations. Twelve specific benzene samples were collected, with two samples obtained from each of six gasoline stations: one from the gasoline refueling zone and one from the office area. Sampling adhered to the NIOSH-1501 standard using personal pumps. A gas chromatograph (GC) equipped with a flame ionization detector (FID) was employed to detect benzene. Descriptive statistical analysis was conducted to determine frequency, percentage, mean, maximum, and minimum values. Our findings revealed that benzene concentrations in all samples were below the detection threshold (0.001 mg/kg) during the 8-hour work shift. Strikingly, despite this low measured exposure and acceptable non-cancer risk levels, every work group was still classified as having a significant cancer risk according to the risk assessment models. The study also indicated that 50.0% of workers had a moderate understanding of benzene, whereas 45.1% had a low level of knowledge. Moreover, self-protective measures were inadequate, with workers neglecting to wear protective gloves while handling benzene, delaying gasoline removal until task completion, and consuming food and beverages in the workplace. Our findings provide more evidence about the health risk associated with benzene exposure among gasoline station workers. Therefore, organizations and relevant agencies must prioritize improving workers’ understanding of safe chemical management to ensure proper handling and minimize exposure to carcinogenic substances that may increase cancer risk.
5.Purinergic system dysregulation and depression: The neuroinflammatory impact of silica nanoparticles
Khadija BOUKHOLDA ; Bakhta AOUEY ; Melania GUERRERO-HUE ; Eman ELBAYOUMI ; Fatma BOUKHOLDA ; Yassine CHTOUROU ; Bernd L. FIEBICH ; Juan Antonio MORENO ; Hamadi FETOUI
Environmental Analysis Health and Toxicology 2025;40(4):e2025030-
Major depressive disorder (MDD) is a neuropsychiatric condition linked to neurotransmitter imbalances, neuroinflammation, and purinergic signaling dysregulation. Emerging evidence suggests that environmental pollutants, such as silica nanoparticles (SiNPs), contribute to neuroinflammatory responses and depressive-like behaviors, though the mechanisms remain unclear. This study investigates the effects of repeated SiNP exposure on depressive-like behaviors and purinergic signaling in the hippocampus of adult male rats. Thirty-six Wistar rats were divided into three groups (control, low-dose SiNP, high-dose SiNP) and received intraperitoneal injections for 28 days. Depressive-like behaviors were assessed using the Forced Swimming Test (FST) and Tail Suspension Test (TST), while the enzymatic activities of ectonucleotidases (E-NTPDase, E-NPP, and ecto-5′-nucleotidase) and ATPase function were measured in hippocampal tissue. Gene expression of purinergic receptors (A2A, P2X7, P2Y2) and ectonucleotidases (CD73, NTPDase 1–3) was analyzed via RT-qPCR, with immunohistochemistry and immunofluorescence assessing CD73 and CD90 protein levels. SiNP exposure significantly increased immobility time in both behavioral tests, indicating depressive-like behavior. It also upregulated ectonucleotidase activity, purinergic receptors (A2A, P2X7, P2Y2), and CD73/CD90 expression, while disrupting ATPase function by decreasing both Na⁺/K⁺-ATPase and Ca²⁺-ATPase activities. These findings suggest that SiNPs induce depressive-like behavior through purinergic pathway dysregulation, promoting neuroinflammation and neurotransmission alterations. Further studies are needed to explore purinergic signaling as a potential therapeutic target in depression.
6.Effect of fluazifop-P-butyl herbicide on growth, pigment, and ultrastructure of Auxenochlorella pyrenoidosa and Raphidocelis subcapitata
Manal Mohamed Mostafa EL-ABASY ; Mohamed Saad ABDEL-KAREEM ; Khaled Yassin ABDEL-HALIM ; Soad Mohamed Mohy EL-DIN ; Elsayed Mohamed IBRAHIM
Environmental Analysis Health and Toxicology 2025;40(4):e2025029-
The terrible intensification in global food demand predictably results in an increase in agricultural practices, with a focus on the usage of herbicides. Hence, a deeper understanding of the impact of this herbicide on aquatic ecosystems is required. The characterization of nano-emulsion of fluazifop-P-butyl (FL) and the toxic effects in both traditional and nanoforms on the growth, pigmentation and ultrastructure of the freshwater microalgae: Auxenochlorella pyrenoidosa and Raphidocelis subcapitata were studied. The prepared nano-emulsion has a particle size of 52-94 nm by transmission electron microscopy (TEM). Zeta potential recorded (38.5 mV) and polydispersity index recorded (0.394). Traditional fluazifop-P-butyl (TFL) in the case of A. pyrenoidosa exhibited median effective concentration (EC50) (10.909 ± 3.635 mg/L) (P= 0.235), while nano fluazifop-P-butyl (NFL) recorded EC50 (14.281 ± 6.251 mg/L) (P= 0.205). In the case of R. subcapitata, TFL recorded EC50 (1.174 ± 0.501 mg/L) (P= 0.105), while NFL exhibited EC50 (4.757 ± 1.755 mg/L) (P= 0.150). Exposure of R. subcapitata cells to 0.117 mg/L of TFL significantly decreased chlorophyll a level by (-)15.51% (P= 0.002) relative to control. Also, chlorophyll b content in A. pyrenoidosa cells significantly decreased upon treatment with 1.43 mg/L of NFL by (-)67.16% (P= 0.001). Carotenoid content in A. pyrenoidosa cells significantly increased after exposure to 1.09 mg/L of TFL by 108.88% (P= 0.001) compared to the control. Likewise, exposure of R. subcapitata cells to 0.117 mg/L of TFL elevated carotenoid levels by 200.57% (P < 0.001). Destroyed chloroplasts and compacted cell walls were observed through TEM when A. pyrenoidosa was exposed to 1.09 mg/L of TFL and 1.43 mg/L of NFL. Likewise, R. subcapitata cells were exposed to 0.117 mg/L of TFL and 0.476 mg/L of NFL. This study demonstrates that both conventional and nano-forms of FL endanger the integrity of the ecosystem and have adverse impacts on non-target organisms. Thus, it's crucial to follow biosafety protocols concerning non-target species before deciding to use this herbicide.
7.Levels of OH-PAHs and markers of oxidative stress in urine of taxi drivers and controls
Na-Youn PARK ; Geurim SONG ; Kyungmu LEE ; Younglim KHO
Environmental Analysis Health and Toxicology 2024;39(4):e2024027-
Polycyclic aromatic hydrocarbons are pervasive in the atmosphere, originating from sources like vehicle emissions and incomplete combustion. Exposure to PAHs occurs through diet, tobacco smoke, and air pollutants, and they are recognized as carcinogens. This study, conducted from July to October 2021 in Seoul, Gyeonggi, and Ulsan regions, focused on taxi drivers, a group with elevated PAH exposure due to prolonged vehicle use. The study involved 19 male taxi drivers and 46 control participants (18 male, 28 female). LC-MS/MS analysis was employed to quantify urinary levels of 18 hydroxy-PAHs, oxidative damage markers (MDA, 8-OHdG), and cotinine. The detection rates of OH-PAHs were 1-naphthol (96.9 %), 2-naphthol (90.8 %), 2-hydroxyfluorene (86.2 %), and 1-hydroxypyrene (80.0 %). Compared to the male controls, taxi drivers showed higher median concentrations of 2-OH-Na (1.698 ng/mL), 1-OH-Na (0.666 ng/mL), 2-OH-Flu (0.067 ng/mL), and 1-OHP (0.045 ng/mL). Similarly, significant differences were observed between taxi drivers and female controls for 1-OH-Na, 2-OH-Na, 2-OH-Flu, 3-OH-Phe, and 1-OHP. MDA and 8-OHdG were detected in over 90% of all groups, with significant differences between taxi drivers. Strong positive correlations were revealed between urinary OH-PAHs, MDA, and 8-OHdG (r ranging from 0.589 to 0.770, p<0.01). The findings suggest that taxi drivers, due to prolonged exposure to traffic-related air pollutants, have elevated levels of PAH metabolites and oxidative stress, especially among smokers. Further studies with larger sample sizes are recommended to validate these results and explore the long-term health implications of occupational PAH exposure in urban transportation workers..
8.A comparative neuro-study of solo or accompanied low and high boric acid doses with date molasses in adult male albino rats
Environmental Analysis Health and Toxicology 2024;39(4):e2024026-
Boric acid (BA) is a weak acid and the simplest compound resulting from the dissolution of boron in water. There is great competition to determine whether boron is an essential or nonessential nutrient. Date molasses is a potent type of sweetener with valuable components, such as flavonoids and phenolics, and has significant health benefits. This study investigated the neuro-essentiality and neurotoxicity of boric acid boron in adult male albino rat cortex and cerebellum brain areas and the impact of date molasses treatment. Animals were grouped into the following groups: control, low and high boric acid doses, 10 and 500 mg/kg, respectively, with or without 250 mg/kg date molasses. The results revealed the ability of BAs to cross the blood–brain barrier and accumulate in the cerebellum and cortex, revealing the ability of date molasses to decrease BA accumulation at different time intervals. Additionally, the results varied between a nonsignificant increase or decrease in calcium ion content, monoamines (norepinephrine, dopamine, and serotonin), glucose, adenosine triphosphate, malondialdehyde and glutathione, depending on the BA dose. Moreover, date molasses mitigated any unwanted BA results. In conclusion, boric acid, which is within a permissible limit, could be essential and have a neuroprotective effect, whereas at a sublethal level, it could have a neurotoxic effect. Additionally, Date molasses can have neuroprotective effects and antagonize the neurotoxic effects of boric acid through its antioxidant and scavenging effects.
9.Effect of fluoride-induced testicular alteration in rats fed a high-fat diet
Manuel SÁNCHEZ-GUTIÉRREZ ; Itziar HERNÁNDEZ-MARTÍNEZ ; Eduardo Osiris MADRIGAL-SANTILLÁN ; Kevin Francisco FLORES-ELIZALDE ; Jeannett Alejandra IZQUIERDO-VEGA
Environmental Analysis Health and Toxicology 2024;39(3):e2024023-
Previous research on the well-known environmental pollutant fluoride has demonstrated that fluoride exposure can lead to oxidative stress-related male infertility. Obesity is another public health issue that has a detrimental impact on male fertility. Previously, findings on fluoride toxicity in high-fat diet (HFD) conditions associated with oxidative stress have been evidenced. This study aimed to evaluate the impact of subchronic fluoride exposure (5 mg/kg) plus a HFD on testicular alteration in Wistar rats. Animals were divided into four groups (control, HFD, fluoride, and fluoride 5 mg/kg plus HFD). The HFD contained a 50% kcal increase in fat (saturated fat), after 90 days of co-exposure to fluoride plus HFD, the animals showed a significant decrease in the adiposity index. The co-exposed group showed oxidative damage assessed through decreased glutathione (GSH) concentration (p < 0.0001), increased concentrations of malondialdehyde (MDA) (p < 0.0001), and the oxidation of proteins (p < 0.0001) vs the control group. Finally, testicular histology exhibited a reduction in spermatogonia and spermatocytes. The results of the study indicate that under these conditions, subchronic co-exposure to fluoride under HFD conditions could protect against the accumulation of epididymal fat, however, oxidative alteration at the testicular level is maintained.
10.Quercetin diminishes the apoptotic pathway of magnetite nanoparticles in rats' ovary: Antioxidant status and hormonal profiles
Environmental Analysis Health and Toxicology 2024;39(3):e2024025-
Magnetite nanoparticles have attracted the attention of researchers for biomedical uses, but their impacts on the reproductive system did not report. Here, we have studied the possible attenuation efficiency of quercetin against magnetite nanoparticles-induced apoptosis in ovarian. Forty female rats were divided equally into control, quercetin (100 mg/kg), magnetite nanoparticles (50 mg/kg), and magnetite nanoparticles+quercetin, where all rats received their doses for four weeks. Compared with the control, magnetite nanoparticles significantly reduced the serum hormonal levels (follicle-stimulating hormone, luteinizing hormone, estrogen, and progesterone) along with glutathione and superoxide dismutase in ovarian tissues. Moreover, magnetite nanoparticles markedly increased the ovarian malondialdehyde, and apoptotic gene expressions (Bax and caspase-3), and induced many histopathological changes. Significantly, co-treatment with quercetin markedly alleviated the hormonal profile, antioxidant disturbance, and ovarian apoptotic pathway of magnetite nanoparticles. Furthermore, our docking study revealed that quercetin could act as a caspase-3 inhibitor and allosteric agonist to follicle-stimulating hormone (Met520 and Val53), luteinizing hormone (Met517, Ala589, Ser604, and Lys595), estrogen (Met421, Phe425, and Ala350), and progesterone (Met759 and Met909) receptors. Those records reveal that the antioxidants and antiapoptotic characteristics are acceptable pointers for female infertility defenders of quercetin, especially during nanoparticle exposure.

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