Toxicology Reports最新文献

Aquatic environments, including marine and freshwater ecosystems, are vital for ecological balance and biodiversity. The rising global demand for aquaculture products necessitates increased production, with intensified aquaculture practices posing significant environmental risks. This review explores the pathways through which chemical pollutants, heavy metals, pharmaceuticals, and environmental stressors induce teratogenic effects in aquatic species. The review highlights the impact of pesticide include triazine herbicides, organophosphate and organochlorine insecticides, and carbamates on aquatic life, emphasizing their interference with endocrine systems and developmental processes. Heavy metals like mercury, lead, cadmium, arsenic, and chromium are noted for their persistence and bioaccumulative properties, disrupting cellular and hormonal functions. Pharmaceuticals, including NSAIDs, antibiotics, and chemotherapeutic agents, exert teratogenic effects by disrupting physiological and developmental pathways. Environmental stressors includes temperature fluctuations, salinity variations, pH changes, and oxygen level imbalances exacerbate the teratogenic impact of pollutants. This review highlights the importance of comprehensive environmental management and understanding these complex interactions is essential for formulating efficient strategies to safeguard the effective measures to protect aquatic ecosystems and the biodiversity.

The governing laws mandate animal testing guidelines (TG) to assess the developmental and reproductive toxicity (DART) potential of new and current chemical compounds for the categorization, hazard identification, and labeling. In silico modeling has evolved as a promising, economical, and animal-friendly technique for assessing a chemical's potential for DART testing. The complexity of the endpoint has presented a problem for Quantitative Structure-Activity Relationship (QSAR) model developers as various facets of the chemical have to be appropriately analyzed to predict the DART. For the next-generation risk assessment (NGRA) studies, researchers and governing bodies are exploring various new approach methodologies (NAMs) integrated to address complex endpoints like repeated dose toxicity and DART. We have developed four hybrid computational models for DART studies of rodents and rabbits for their adult and fetal life stages separately. The hybrid models were created by integrating QSAR features with similarities-derived features (obtained from read-across hypotheses). This analysis has identified that this integrated method gives a better statistical quality compared to the traditional QSAR models, and the predictivity and transferability of the model are also enhanced in this new approach.

Nut products are susceptible to contamination with mycotoxin, especially aflatoxins, which results of mold growth during harvest or storage. This study aimed to evaluate the occurrence of aflatoxins in peanut products from the Saudi market. A total of 472 samples of peanut and peanut butter imported from various countries were collected in the period from 2015 to 2020. All samples were analyzed by High-Performance Liquid Chromatography (HPLC). Total aflatoxins (B1, B2, G1, G2) were found to exceed the maximum level (ML) in 38 samples (8.1 %) with a concentration range of 15.56-973.21 µg/kg, while 434 samples were below ML (91.9 %). Specifically, in Peanut butter samples, 27 out of 333 were contaminated with Aflatoxins (8.8 %), and 11 out of 139 peanut samples were contaminated with aflatoxins (8.6 %). The results show that the percentage of Aflatoxins contamination was reduced in the period (2019 - 2020) compared to (2015 - 2018), due to the control of mycotoxins in Saudi Arabia which played an important role in reducing the contamination of AFs in peanut products.

Heavy metal contamination in the environment, often resulting from industrial activities, mining, and improper waste disposal, leads to the accumulation of heavy metals in soil, water, air, drinks and food. Prolonged exposure to these metals can cause serious health issues in humans, including neurological damage, kidney failure, respiratory problems, and an increased risk of cancer. High levels of heavy metals in food are hazardous to human health. Heavy metals can find their way into beer at different stages, including through raw materials, the brewing process, equipment, bottling, and storage. This study examined the presence of Cu, Cd, Pb, Cr, Fe, and Zn in ten of the most consumed beer brands in Tanzania using an atomic absorption spectrometer (AAS). The results showed that the concentration of heavy metals in the beer samples increased in the order of Zn < Cu < Fe < Cr. Cd and Pb were not detected in any beer samples. Compared to WHO guidelines, the levels of Zn and Cu were below the limit, while Fe and Cr exceeded it. Estimated daily intake (CDI), hazard quotient (HQ), hazard index (HI), and incremental lifetime cancer risk (ILCR) were used to evaluate the potential human health risks. The EDI values of Fe and Zn were lower than the provisional maximum tolerable daily intake (PMTDI) set by the FAO/WHO. However, the mean EDI for Cr surpassed the recommended value, posing a potential risk for moderate and high beer consumers. The HQ and HI values for Zn and Fe were below 1, signifying no non-carcinogenic health concerns. In contrast, Cr had HQ and HI values greater than 1, indicating a notable non-carcinogenic health risk through beers consumption. ILCR due to Cr ranged from 0.029 to 0.695. These ILCR values for Cr in all beer samples are above range of ${10}^{-6}-{10}^{-4}$ recommended by USEPA, suggesting a potential carcinogenic risk linked to this toxic metal and, consequently, a possible cancer risk for beer consumers. Therefore, beer manufacturers should continuously work to minimize public health risks. Additionally, further research involving a larger variety of beer brands and the implementation of policy interventions is needed.

Background: Carbamazepine is one of the most widely used antiepileptic drugs. Carbamazepine has been shown to be toxic to cells. Cilostazol, an antiplatelet agent, has known antioxidant, antiproliferative, anti-inflammatory, and anti-tumor effects.

Objective: This study aimed to explore whether carbamazepine and cilostazol exert genotoxic and/or cytotoxic effects in human cultured blood lymphocytes and the impact of combining both drugs on such effects.

Methods: Genotoxicity was examined using sister chromatid exchange (SCE) assay, while cytotoxicity was evaluated by cell kinetic assays (mitotic and proliferative indices).

Results: Study findings have revealed that carbamazepine markedly increased SCEs (p<0.01), while cilostazol significantly decreased their frequencies (p<0.01). In addition, the frequency of SCEs of the combination of both drugs was similar to that of the control group (p>0.05). Carbamazepine increased the cell proliferative index (p<0.01) while cilostazol decreased it (p<0.01). The proliferative index was normalized to the control level when both drugs were combined.

Conclusion: We suggest that cilostazol has the potential to protect human lymphocytes from carbamazepine-induced toxic effects.

Perampanel (Fycompa®) is a non-competitive alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) glutamate receptor antagonistic antiepileptic medication used to treat generalized seizure disorders. Very little is known about the management of patients following perampanel overdose, particularly in the pediatric population. We report a case of a pediatric patient, initially presenting with increased aggression and erratic behavior, who quickly developed severe respiratory failure and prolonged coma following an intentional ingestion of between 80 and 216 mg of perampanel (1.64-4.43 mg/kg of body weight). Phenobarbital was initiated to increase the metabolism of perampanel and for seizure prophylaxis. Perampanel toxicity has been associated with a range of symptoms including bradycardia, hypotension, hyponatremia, central nervous system depression, prolonged coma, hypercoagulable state, and erratic, aggressive "zombie-like" behavior. With a reported half-life of 105 hours, no known reversal agent, and limited evidence-based management, clinicians should be prepared for prompt resuscitation and prolonged management of patients with suspected perampanel intoxication.

Educational objectives: 1.Identify symptoms of perampanel overdose and consider early intubation and resuscitation for prolonged coma and respiratory failure.2.Describe alternative methods to increase metabolization of medications with prolonged half-life.

The pathophysiology of hepatic and cerebral damage includes various molecular and signalling pathways. Assessment of inflammation-induced DNA damage is one of the principal issues for investigating organ distortion and mutation. The current study was premeditated to discover the prophylactic role of 5-Methoy-N-acetyltryptamine (5-MNAT) and/or Quercetin (QR) versus sodium nitrite (NaNO₂) induced liver and brain injury in a rat model, as well as to clarify the different cross-linked inflammatory pathways and neurotransmitters. Pre-treatment with QR and 5-MNAT was followed with NaNO₂ administration in a dose of (75 mg/kg BW). NaNO₂-intoxication significantly caused alleviation in inflammatory biomarkers including C-reactive protein (CRP) and interleukin-6 (IL-6). The above-mentioned antioxidants noticeably amended the altered inflammatory biomarkers signalling pathways and liver function biomarkers including alanine aminotransferase (ALT) and lactate dehydrogenase (LDH). Furthermore, they modulated brain neurotransmitters including, GABA and serotonin in brain tissue. Likewise, the COMET assay revealed that these antioxidants successfully modified NaNO₂-induced liver and brain DNA damage. In conclusion, treatment with both QR and 5-MNAT revealed the most effective therapeutic index in improving NaNO₂-induced liver and brain injury, confirming the effectiveness of this combination as a powerful treatment for brain hypoxia. Nevertheless, this was confirmed with histopathological investigation.

The genus Cyrtopodium, from the Orchidaceae family, is widely used for its therapeutic properties in the treatment of tuberculosis, abscesses, urinary infection, and colds. C. glutiniferum, one of the species of this genus, is endemic in Brazil and largely used in herbal medicine. Thus, it is of great interest to recognize its composition, the properties of the molecules found in it. This study aimed to perform the in silico analysis of the main compounds from C. glutiniferum, on the platforms pKCSM, SwissADME, LAZAR, CLC-pred, ToxTree, DIGEPred, STRING, and Cytoscape. Further than this, the molecular docking was performed. The compounds present in the aqueous extract of C. glutiniferum were identified by UHPLC-MS/MS, finding Arbutin, Caffeic acid 4-O-glucoside, and Dihydroformononetin as the three most abundant molecules. The evaluation of the gastrointestinal absorption of Dihydroformononetin is given as high, also managing to cross the blood-brain barrier, while Arbutin can only be absorbed by the gastrointestinal tract and Caffeic acid 4-O-glucoside had very low absorption. Further analysis showed that Arbutin and Dihydroformononetin are possible leading molecules for drug synthesis, according to the prediction. Toxicological aspects were analysed, and no adverse effects were noted, but there were divergences in the mutagenic prediction of Arbutin and Dihydroformononetin, having different results in the used platforms, demonstrating that a cautious analysis and data insertion is needed in these tools to optimize them. The analysis of the differentially expressed genes predicted that the compounds can regulate several genes, including some genes associated with carcinogenesis and inflammation. The Molecular docking analysis showed high binding affinities of the molecules with different proteins. Therefore, C. glutiniferum demonstrates the potential to be used as a phytotherapeutic. The same was given through the in silico analysis of the three compounds found in the orchid, that show good individual potential.

Abnormal Toxicity Test (ATT) is performed as quality control test by manufacturers and National Control Laboratory (NCL) to ensure safety of biologicals. However, stakeholders are in general consensus that extraneous toxic contaminations are extremely unlikely where Good Manufacturing Practices (GMPs) and consistent production have been established. This test requiring mice and guinea pigs is still a regulatory requirement for the batch release of biologicals in several countries although it has been deleted by some National Regulatory Authorities (NRAs) and Pharmacopoeias while some are still working on its elimination. Therefore, ten years historic data of ATT performed at National Institute of Biologicals (NIB), India on 4813 batches of biologicals including blood and related products, enzymes, hormones and vaccines by using 33637 animals was analyzed. As per Indian Pharmacopeia (IP), 4783 batches of these biologicals passed the test. The test had to be repeated in 30 batches, all of which were blood products and the repetition rate was 0.62 %. Further, after repeat testing, all these 30 batches also passed the test. This data will help the regulatory authorities of countries where ATT is still a requirement, take appropriate decision regarding its deletion. The elimination of ATT from specific monographs of these biologicals will help save many thousands of animals being used globally for this test.

Acute methanol poisoning could be associated with high morbidities and fatalities. Stratifying high-risk patients is crucial in improving their prognosis. Hence, this study aimed to identify patients with methanol poisoning at high risk of in-hospital mortality. Also, the risk factors for blindness were assessed. The study included 180 acutely methanol-poisoned patients who received standard medical care. Out of 180 patients, 52 (28.9 %) patients presented with blindness, and 43 (23.9 %) patients died. The predictive model was based on four significant variables, including blindness, mean arterial pressure, serum bicarbonate, and serum creatinine. The presence of blindness and elevated serum creatinine significantly increased the likelihood of mortality by 14.274 and 5.670 times, respectively. Likewise, decreases in mean arterial pressure and serum bicarbonate significantly increased mortality risk by 0.908 and 0.407 times, respectively. The proposed nomogram exhibited excellent discriminatory power (area under the curve (AUC)=0.978, accuracy=93.3 %), which outperforms the AUCs of individual predictors. The provided nomogram is easily applicable with outstanding discrimination, making it clinically helpful in predicting in-hospital mortality in acutely methanol-poisoned patients. Regarding the risk factors for blindness, multivariable regression analysis revealed that delayed time for admission (OR=1.039; 95 % CI=1.010-1.069; p= 0.009) and elevated anion gap (OR=1.053; 95 % CI=1.007-1.101; p= 0.023) were significant risk factors. The current study assists physicians in identifying methanol-poisoned patients with a high probability of mortality or blindness on admission. Future studies are recommended for external validation of the created nomogram, in addition to follow-up for patients with visual impairment.