Poisoning Research Articles

Evaluation of wound healing activities of Vitex doniana (Black Plum) ethanol fruit extract

In this study, the folkloric use of Vitex doniana fruit extract for the treatment of wounds was evaluated. The mesocarps of the fresh fruits were removed, oven-dried at 40°C and pulverized. The powdered material (800 g), was exhaustively macerated in 80 % ethanol, filtered and dried in a water bath at 40°C. Phytochemical screening and acute dermal toxicity of the extract were investigated. Herbal ointments (10 and 50 %w/w) were formulated using soft paraffin base. The wound-healing effect of the extract was carried out using twenty albino rats divided into four groups (n=5). Groups I (soft paraffin) and II (10 %w/w Povidone-iodine) served as negative and positive controls, respectively. Groups III and IV were topically treated with 10 %w/w and 50 %w/w of the herbal ointment respectively. Treatments and wound grading were assessed once daily and every 4 days, respectively, as well as the timeframe for percentage wound contraction and epithelialization Both the 10 %w/w and 50 %w/w herbal ointments exhibited a concentration-related significant (P<0.05) wound contraction when compared to the control. Epithelialization period of 50 %w/w extract was less than that of the standard drug. The wound closure area of 50 %w/w extract was >positive control >10 %w/w extract > negative control. Histological study of the wounds on the 16th day indicated no sign of dermal toxicity. Some secondary metabolites such as alkaloids and tannins were present. In conclusion, the folkloric use of the fruit extract of V. doniana for the treatment of wounds may therefore be justified

Clinical results of helical tomotherapy for high-grade gliomas

Introduction Radiotherapy-related damage of normal tissue inevitably influences the treatment outcomes in the context of high-grade gliomas (HGGs) treatment. We reported the survival outcomes and toxicities of patients with HGG treated with helical tomotherapy (HT) and the prognostic factors were analyzed. Materials and methods A total of 67 patients (29 had grade III and 38 had grade IV HGGs) who received HT between January 2016 and June 2020 were analyzed. Overall survival (OS) and progression-free survival (PFS) from the beginning of HT and OS from surgery were assessed, and toxicity and disease control were described briefly. Results For patients with grade III HGGs, median OS (mOS) and median PFS (mPFS) from the beginning of HT were 68.933 and 62.967 months, respectively. For patients with grade IV HGGs, mOS and mPFS from the beginning of HT were 19.667 and 7.23 months, respectively. No grade ≥3 acute or late nonhematologic toxicities were observed. Multivariable Cox regression analysis showed that methylguanine methyltransferase (MGMT) methylated status, age, number of lesions, WHO grade, and monocyte count for PFS were significant. Age, monocyte count, and isocitrate dehydrogenase (IDH) status for OS. Conclusion Treatment of HGGs with HT appears to be potentially effective and safe. HT is promising for glioblastomas (GBM), especially complex cases with infratentorial involvement or multiple lesions. This study highlighted the potential clinical significance of systemic inflammation indicators in predicting survival and disease progression.

Survival and Toxicity Outcomes with Radiotherapy Technique and Timing in the Management of Wilms Tumor: a Systematic Review to Inform a National Clinical Practice Guideline Development

Purpose: Wilms tumor (WT) management has evolved into a multimodality paradigm that includes radiotherapy (RT), usually as an adjuvant or consolidative modality. Protocols are refined to maximize cure and compliance while minimizing acute toxicity and long-term effects. RT technique and timing are two factors that could improve these outcomes. We reviewed the evidence on survival and toxicity outcomes among WT patients with conventional versus advanced RT techniques and early versus delayed RT to inform a Department of Health (DOH) commissioned guideline. Materials and Methods: We systematically searched PubMed, EuropePMC, EBSCOHost, HERDIN, systematic review and clinical trial registries and official websites of scientific societies for relevant publications and grey literature. Eligibility screening, risk-of-bias assessment and data extraction were performed using a single-reviewer approach. Given the study and data heterogeneity, only a qualitative synthesis was performed. Certainty of evidence assessment was done using the GRADE approach. Results: We screened 314 studies and included seven in the review, including a phase 1/2 trial and six retrospective studies, all from first-world countries (US, France, Netherlands), except one from a newly industrialized country (Brazil). The certainty of evidence on the survival and toxicity outcomes with advanced RT techniques was very low. Moderate-certainty evidence supports that giving RT >14 days after surgery leads to increased mortality. Conclusion: Current evidence does not support the routine use of advanced RT techniques; proper contextualization is necessary. Tertiary centers managing WT should strive to administer RT within 14 days after surgery whenever possible. Keywords: Wilms tumor, nephroblastoma, radiotherapy, intensity-modulated radiotherapy, survival, toxicity

Fouling-Resistant Voltammetric Xylazine Sensors for Detection of the Street Drug “Tranq”

As the opioid crisis continues to wreak havoc on a global scale, it is increasingly critical to develop methodologies to detect the most dangerous drugs such as fentanyl and its derivatives, which have orders of magnitude higher potency than morphine. The scientific challenge for chemical detection of fentanyl and its derivatives is complicated by both the constantly increasing synthetic variations of the drug as well as the expanded use of adulterants. One tragically consequential example is the nocuous street drug known as “Tranq”, which combines fentanyl or a fentanyl derivative with the veterinary sedative Rompun®, chemically identified as xylazine (XYL). This pervasive street cocktail is exacerbating the already staggering number of fentanyl-related deaths as its acute toxicity poses a danger to medical first-responders and complicates their initial assessment and treatment options for overdose victims. Given the widespread use of XYL as an adulterant, an electrochemical XYL sensor capable of on-site operation by non-experts as a fast-screening tool is a notable goal. This work presents a voltammetry-based sensor featuring carbon electrodes modified with carboxylic-acid functionalized multi-walled carbon nanotubes layered with cyclodextrin and polyurethane membranes for sensitivity and selectivity enhancements. The sensor has critical and robust fouling resistance while providing sensitivity at 950 μA/mM∙cm2, a low limit of detection (~5 ppm), and the ability to detect XYL in the presence of fentanyl and/or other non-fentanyl stimulants like cocaine. The demonstrated sensor can be applied to promote public health with its ability to detect and indicate XYL in the presence of opioids, serving to protect drug-users, first responders, medical examiners, and on-site forensic investigators from exposure to these dangerous mixtures.

Assessment of sedative and anxiolytic activities of fruit extract of Vitex doniana (black plum)

This research study was aimed at investigating the common folkloric use of Vitex doniana fruit extract for induction of sleep. Extraction of the fruit extract was carried out with 80 %v/v ethanol. Acute toxicity study and qualitative phytochemical screening of the extract were also done. Twenty-five adult mice divided into five groups (n=5) were used for both the anxiolytic study and the phenobarbital-sleeping time analysis tests. Groups I and II served as negative (distilled water 10 ml/kg) and positive (diazepam 1 mg/kg i.p.) controls, respectively. Groups III, IV and V received the extracts of 250, 500 and 1000 mg/kg p.o., respectively. The effect of extract on time spent in and number of entries into the open arms and closed arms when compared to control were noted. The effect on onset and duration of sleep -were also noted. The extract was found to be relatively safe. Secondary metabolites like tannins and flavonoids were present. There was a dose-related significant (p < 0.05) increase in time spent on the open arm and a decrease in time spent on closed arm when compared to the negative control. Dose-related significant (p < 0.05) decrease in time for sleep onset and increase in duration of sleep when compared to negative control were also observed. From the results of this study, the folkloric use of this fruit extract for the induction of sleep and relaxation seem to be justified.

The Acute and Subchronic Toxicity Evaluation of methanol leaf Extracts Of Bombaxbuonopozense

Natural products serve as the foundation for conventional medicine and are significant sources of lead compounds for medication research. One of the underutilized plants in West Africa is Bombax buonopozense. West African populations use the majority of its parts for nutritional and therapeutic purposes. The research was aimed at evaluation of the Acute and subchronic oral toxicity of Bombaxbuonopozense leaves extract in rats.In the acute toxicity study, female rats received oral doses of 2000 mg/kg of Bombaxbuonopozense extract (n = 5/group). Abnormal behavior, toxic symptoms, weight changes, and mortality were monitored for 14 consecutive days to evaluate acute toxicity. For the sub-chronic toxicity study, the extract was orally administered to Wistar rats at doses of 800 and 1600 mg/kg (n = 5/group) daily for 28 days. Daily observations were made on the general behavior and body weight of the rats. Biochemical and hematological analyses were performed at the end of the treatment period. Following acute oral administration, the LD50 of Bombaxbuonopozens leaves extract was found to be greater than 2000 mg/kg in the evaluation of acute oral toxicity. Administration of Bombaxbuonopozense extract to rats did showed significantly increase in platelate in the treated group (362.00±23.67*) when compared to the control group (451.67±30.77) at (p>0.05). The liver enzymes, An increase (P>0.05) was seen in ALP concentration on the treated group (216.59±44.29*) In the subchronic oral toxicity assessment at doses of 800 and 1600 mg/kg/day for 28 days, no significant changes were observed in food consumption, body weight gain, organ weights, and biochemical parameters. Treatment of rats with Bombaxbuonopozense extract showed a significant increase in ALP on the group treated with 1600 mg/kg (216.59±44.29*) compared to the control (98.70±13.32) and significant increase in LDL for the treated groups 800 mg/kg (70.76±8.19*) and 1600 mg/kg (71.40±13.17*) were observed when compared with.The current research demonstrated that administration of Bombaxbuonopozense extract orally for 28 days, at doses of up to 1600 mg/kg, did not cause any toxic effects. Based on the acute toxicity study, the estimated median lethal dose (LD50) of the extract was more than 2000 mg/kg.

Acute Fluoride Toxicity Due to Intentional Ingestion of Hydrofluoric Acid Commercial Product.

Hydrofluoric (HF) acid, an irritating and corrosive acid, is commonly found in cleaning supplies. Fatal HF acid ingestion has been documented, although relatively rare. We report a case of acute fluoride toxicity suicide due to the ingestion of a commercial product containing HF acid and ammonium bifluoride. To our knowledge, this is the first to describe the associated gastrointestinal histopathology in detail.A 56-year-old woman was found deceased near a rust remover product and a notebook containing suicide methods via chemical ingestion. Gross autopsy findings included laryngeal mucosal petechial hemorrhages; patchy esophageal mucosal denudation; and autolyzed, red-black discolored gastric mucosa. Histology of the esophagus demonstrated superficial mucosal ulceration with necrosis of the squamous mucosa, vascular congestion, and lymphoid aggregates in the lamina propria; muscularis mucosae and muscularis propria were unperturbed. The stomach showed superficial coagulative necrosis of the oxyntic crypts, with fresh microhemorrhage dissecting the glandular mucosa away from the muscularis mucosae; muscularis mucosae, submucosa, muscularis propria, and serosa were all spared.Toxicology revealed an elevated fluoride ion concentration (20 mg/L). Death was attributed to acute fluoride toxicity due to intentional ingestion of a commercial product containing HF acid and ammonium bifluoride, and the manner was suicide.

Potential hepatoprotective properties of synthetic derivatives of thiourea — 2-aminobenzothiazole and IEM-2320

BACKGROUND: Toxic hepatitis is characterized by a significant severity of the course and by high mortality. So, search for effective means of correcting this condition seems to be relevant. It has previously been shown that some thiazolo[5,4-b]indole derivatives are capable to prevent experimental toxic liver damage in laboratory animals. In continuation of this direction, the study of the hepatoprotective properties of synthetic derivatives of thiourea 2-aminobenzothiazole and IEM-2320 was undertaken. AIM: To study the potential hepatoprotective properties of 2-aminobenzothiazole and IEM-2320 in acute carbon tetrachloride poisoning. MATERIALS AND METHODS: Experiments were carried out on 30 male white outbred rats (150–270 g). On a model of carbon tetrachloride poisoning (50% solution of CCl4 in vaseline oil, 0.2 ml/100 g of body weight), the potential hepatoprotective properties of 2-aminobenzothiazole (32 mg/kg) and IEM-2320 (20 mg/kg) were investigated. Ademethionine (Heptral, AbbVie, S.r.L, Italy) at a dose of 20 mg/kg was used as a comparison drug. The studied drugs were administered intraperitoneally 4 times: one hour before the introduction of CCl4, and then — for three subsequent days after the poisoning with CCl4. The results were compared with those of 2 control groups. Animals of the 1st control group were not exposed to CCl4, instead of the studied drugs, they were injected with an equivalent volume of saline solution (0.2 ml/100 g of body weight). Animals of the 2nd control group did not receive any treatment after the CCl4 poisoning. Blood was taken on the seventh day of the experiment. The total contents of protein, glucose, and total cholesterol in blood serum were determined, and the activities of alanine aminotransferase and aspartate aminotransferase were evaluated. RESULTS: Under the CCl4 poisoning, the administration of 2-aminobenzothiazole led to a significant decrease in the concentrations of glucose, total protein, total cholesterol and alanine aminotransferase activity. When IEM-2320 was administered under the condition of poisoning, a decrease in the concentrations of total protein, glucose, urea, total cholesterol, and the alanine aminotransferase activity was observed. CONCLUSIONS: A significant decrease in the biochemical parameters of blood serum after administration of 2-aminobenzothiazole and IEM-2320 under the condition of CCl4 poisoning demonstrates thir potential hepatoprotective properties under acute hepatotropic poisonings.

Crop growth scenario-based pH/temperature dual-responsive degradable polyurea nano/microcapsules: Smart pesticide delivery and sustainable control of Fusarium crown rot in wheat

Designing smart pesticide delivery systems in response to the environmental factors of disease occurrence is critical to achieving targeted pesticide delivery, improving effective pesticide utilization and reducing environmental pollution. Herein, we prepared a novel chemically degradable pH/temperature dual-responsive polyurea capsule (Pyr@PU). The Pyr@PU was based on the diamine cross-linking agent 2,2-diethoxypropane (DAKT) containing acetal groups unstable to acids and isophorone diisocyanate (IPDI), and the phase change material methyl myristate (melting point: 18°C) was used as the oil phase. Owing to the acetal structure in the capsular shell and methyl myristate in the core, Pyr@PU has excellent acidic pH responsiveness and temperature sensitivity. 95.0 % of the fungicidewas released within 48 h at a weakly acidic condition (pH = 5.0), and the fungicide release rate at 35°C was 3.6 and 10.4 times higher than that at 25°C and 15°C, respectively. Bioactivity assays showed a longer duration of Pyr@PU compared to the commercial emulsion (Pyr EC). The degradation rate of Pyr@PU microcapsules (Pyr@PU-Micro) (64.5 %) was significantly lower than Pyr EC (98.6 %) after 24-h UV irradiation. In the 96-h acute toxicity test, Pyr@PU-Micro (LC50 = 0.695 mg·L−1) exhibited a lower toxicity to zebrafish than the Pyr (LC50 = 0.076 mg·L−1), Pyr EC (LC50 = 0.108 mg·L−1), and commercialized microcapsules (Pyr CS) (LC50 = 0.209 mg·L−1). In summary, the new chemically degradable polyurea microcapsules improved the stability and duration of fungicide efficacy and provided a new solution for the effective control of Fusarium crown rot and the reduction of environmental pollution caused by microplastics.

Evaluating the impact of the combined acute toxicity of iron (Fe) and microplastics on Namalycastis jaya

The rising concern over heavy metals (HMs) and microplastics (MPs) pollution in marine ecosystems, primarily driven by anthropogenic activities, poses significant threats to ecological health. Understanding the combined exposure of HMs and MPs aids in toxicity assessment. In this study, we examined the combined effects of polystyrene microplastics (MPs) and iron (Fe) on oxidative stress, bioaccumulation, histopathology, and genotoxicity in Namalycastis jaya. Oxidative stress was assessed by analyzing the levels of Superoxide dismutase (SOD), Catalase (CAT), Peroxidase (POD), Malondialdehyde (MDA), and Bicinchoninic acid (BCA), while genotoxicity was evaluated using the comet assay. Bioaccumulation analysis, conducted via Inductively coupled plasma-optical emission spectrometry (ICP-OES), indicated that the highest values (4.790 µg/ml) were observed in combined exposure, emphasizing the significant increase in iron (Fe) accumulation in polychaetes facilitated by MPs. Biochemical analysis revealed that oxidative damage in polychaetes became evident within 48 h of exposure to individual contaminants. However, in the case of combined exposures, elevated stress levels were observed within just 24 h. The genotoxic assay further demonstrated a higher degree of DNA damage in the combined exposure compared to individual exposures. Similarly, histopathology revealed mild alterations in the gut epithelium in combined exposures. It is evident that MPs intensify both oxidative and DNA damage induced by Fe in polychaetes. The insights gained from this study provide valuable information for the risk assessment of Fe and MPs in environmental safety, contributing to our understanding of the complex interactions between these pollutants in marine ecosystems.

Metal‐Organic Framework (Cu@ZIF) for Photocatalytic Reduction of p‐Nitrophenol and its Toxicological Evaluation using Zebrafish (Danio Rerio)

AbstractGlobal food security depends on agricultural development, yet excessive fertilizer and pesticide usage is harmful to the environment. These substances have a role in human health problems, environmental changes, and erosion of the soil. Although p‐nitrophenol, an organic pollutant and other organophosphorous compounds are utilised in agriculture, their usage raises major health and environmental issues. These synthetic pesticides are quite effective at getting rid of pests, but they have also been linked to serious health problems for people and animals, degraded soil, and contaminated water. One typical persistent pollutant present in industrial wastewater is the organic pollutant, which is produced by organophosphorous compounds. The primary objective of this work is to use Cu@ZIF for photoreduction of p‐nitrophenol (PNP). A UV‐visible spectrophotometer test revealed that the deterioration peak after 60 mins. An analyzer for total organic carbon (TOC) was utilised to assess the PNP mineralization. The catalyst remained same and continued in the same behaviour even after four cycles. This study evaluated the acute toxicity of PNP on the development of early‐stage zebrafish, paying particular attention to the embryonic developmental deformities. The technique of photocatalytic decontamination is safe for the environment, financially practical, and technically achievable.

Sensitivity of Daphnia magna: Acute Toxicity Evaluation of 22 Metals

Introduction: All potentially toxic metals in the environment can be discharged in the aquatic ecosystems. Daphnia magna is one of the most sensitive species to toxic chemicals in water and is frequently used in toxicological research and environmental monitoring. Material and Methods: Acute toxicity test for twenty-two metals (Pb, Cd, Ni, Hg, Cu, Fe, Co, As, Cr, Mn, Zn, Al, Pd, Na, K, Mo, Mg, Ca, W, Ir, Ti, Ag) was carried out for Daphnia magna. These elements were checked and ranked in terms of decreased immobilization (EC50) after 24Hr and 48Hr and compared with previous studies. Results: The results were categorized into four groups by the 48Hr EC50s values: highly toxic groups (Ag, Hg, Cu, Cd, Pd) [EC50 < 100 μg.l-1], moderately toxics groups Cr, Fe, Ni, Zn and Pb) [100 μg.l-1<EC50 < 1 000 μg.l-1], low toxic groups (Al, Mn, As, Ti, Co, W and Ir) [1000 μg.l-1<EC50 < 100000 μg.l-1], and minimally toxic groups (Na, Mg, K, Ca, and Mo) [EC50 > 100 000 μg.l-1]. Correlation coefficients (r) between EC values and eight physicochemical properties were also examined. The results obtained in this study were weak. Conclusion: This work adds and confirm data about the toxicities of metals in aquatic ecosystems by using a rapid biomonitoring test.

Site-Selective Zwitterionic Poly(caprolactone-carboxybetaine)-Growth Hormone Receptor Antagonist Conjugate: Synthesis and Biological Evaluation.

Zwitterionic polymers have been found to be biocompatible alternatives to poly(ethylene glycol) (PEG) for conjugation to proteins. This work reports the site-selective conjugation of poly(caprolactone-carboxybetaine) (pCLZ) to human growth hormone receptor antagonist (GHA) B2036-alkyne and investigation of safety, activity, and pharmacokinetics. Azide-end-functionalized pCLZs were synthesized and conjugated to GHA B2036-alkyne via copper-catalyzed click reaction. The resulting inhibitory bioactivity concentration responses in Ba/F3-GHR cells were compared to those of PEGylated GHA B2036. IgG and IgM antibody production was tested in mice, and no measurable antibody or cytokine production was detected for the pCLZ conjugate. Using 18F-labeled PET/CT imaging, the pCLZ conjugate showed an increase in circulation time compared to that of GHA B2036. Acute toxicity of the polymer was investigated in vivo and found to be nontoxic. Ex vivo degradation of the polymer on the conjugate was investigated. The results suggest that pCLZ-GHA is a potentially safe alternative to PEG-GHA.

5.Y.2. Alcohol intoxication among adolescents in Italy, Belgium and The Netherlands

Abstract Excessive drinking behavior poses a significant risk to the health of adolescents and contributes to high social and health costs. It is also well-documented that engaging in risky drinking behavior at a young age increases the likelihood of developing alcohol use disorders and other mental health disorders later in life. Therefore, the timely development of adequate interventions to prevent and reduce such behavior is an important public health task. The initial step here is to gather comprehensive data on the phenomenon. Studying alcohol intoxication data among adolescents is an important source in this context. In the Netherlands, data on alcohol intoxication in adolescents have been routinely collected for several years, leading to a successful transmural framework aimed at supporting these young individuals and their parents. As countries are at varying stages in addressing this issue, the objective of this workshop is to facilitate mutual learning about effective prevention initiatives targeting problematic alcohol use in young people. The workshop will feature presentations from four studies representing three countries: Italy, Belgium, and the Netherlands. Allegra Ferrari from Italy will discuss alcohol-related emergencies among adolescents admitted to an emergency department in Genoa, emphasizing the importance of urgent interventions to mitigate adolescent alcohol use. Hanna van Roozendaal from Belgium will present data from both retrospective and prospective studies on adolescents with acute alcohol intoxication in Antwerp hospitals, exploring the feasibility of follow-up interventions. Louise Pigeaud from the Netherlands will share data from a cohort of individuals under 18 years presented with acute alcohol intoxication symptoms at an emergency department between 2015-2023 to monitor trends in admission characteristics. Finally, Guido van Hal will focus more in depth on the differences and similarities in adolescents accessing emergency care for acute alcohol intoxication in Italy, Belgium and The Netherlands. The workshop will conclude with an open discussion on topics such as the necessary data to be registered for minors with acute alcohol intoxication, the most effective methods for preventing/reducing alcohol intoxication in these age groups, and the potential transferability of the successful Dutch transmural framework to other countries. Key messages • Acute alcohol intoxication and problematic alcohol use in minors can lead to significant alcohol-related issues in adulthood. • Collecting and analyzing high-quality data can facilitate the development of interventions aimed at reducing and preventing alcohol-related issues in adolescents.

Characteristics of adolescents with acute alcohol intoxication accessing emergency care in The Netherlands

Abstract Background Prevent alcohol consumption amongst minors is a major concern for national governments. Collecting comprehensive data on adolescent drinking patterns is crucial for developing effective prevention strategies. Therefore, the aim of this study is to give an overview of demographic and clinical characteristics of adolescents with an acute alcohol intoxication in the Netherlands. Methods This study was conducted using a cohort of adolescents aged 14-17 years presenting with acute alcohol intoxication symptoms at the emergency department from 2015-2023. Data were collected at the Reinier de Graaf Gasthuis in Delft in order to monitor trends in admissions for acute alcohol intoxication. Data on patients age, blood alcohol concentration, sex, combined drug use and reason of admission were collected. Results A total of 505 patients who presented themselves with symptoms of acute alcohol intoxication at the Reinier de Graaf Gasthuis were included. The mean age of patients was 15.7 years old. The mean blood alcohol concentration was 2.0‰. During the COVID-lockdown period there were statistically significant less admissions with alcohol intoxication. The distribution of sex was nearly equal with 50.3% females and 49.7% males. Combined drug use was present in 13.4% of all cases, with cannabis as the most frequent type of drugs found. The most common known reason for admission was ‘reduced consciousness’ (35.9%). Conclusions These findings are relevant for both the central government’s ongoing prevention initiatives and treatment strategies within hospitals. In the future, more countries should evaluate data on adolescent drinking patterns.

High-throughput prediction of oral acute toxicity in Rat and Mouse of over 100,000 polychlorinated persistent organic pollutants (PC-POPs) by interpretable data fusion-driven machine learning global models

This study utilized available oral acute toxicity data in Rat and Mouse for polychlorinated persistent organic pollutants (PC-POPs) to construct data fusion-driven machine learning (ML) global models. Based on atom-centered fragments (ACFs), the collected high-throughput data overcame the applicability limitations, enabling accurate toxicity prediction for a wide range of PC-POPs series compounds using only single models. The data variances in the Rat training and test sets were 1.52 and 1.34, respectively, while for the Mouse, the values were 1.48 and 1.36, respectively. Genetic algorithm (GA) was used to build multiple linear regression (MLR) models and pre-screen descriptors, addressing the “black-box” problem prevalent in ML and enhancing model interpretability. The best ML models for Rat and Mouse achieved approximately 90 % prediction reliability for over 100,000 true untested compounds. Ultimately, a warning list of highly toxic compounds for eight categories of polychlorinated atom-centered fragments (PCACFs) was generated based on the prediction results. The analysis of descriptors revealed that dioxin analogs generally exhibited higher toxicity, because the heteroatoms and ring systems increased structural complexity and formed larger conjugated systems, contributing to greater oral acute toxicity. The present study provides valuable insights for guiding the subsequent in vivo tests, environmental risk assessment and the improvement of global governance system of pollutants.

Differences and similarities in adolescents accessing emergency care for acute alcohol intoxication in three urban regions in Italy, Belgium, and The Netherlands

Abstract Background Excessive drinking among adolescents in Western Europe is prevalent, posing significant health risks and societal costs. Early initiation of alcohol use and binge drinking are associated with adult alcohol use disorders. Collecting comprehensive data on adolescent drinking patterns is crucial for developing effective prevention strategies. Methods To gain insight into the demographic and clinical characteristics of acute alcohol intoxication (AAI), we analysed emergency department access data of adolescents aged 14-17 years presenting with AAI symptoms from 2015-2023. Three urban regions were included: the Reinier de Graaf Gasthuis in Delft (The Netherlands), eight combined hospitals in Antwerp (Belgium) and the IRCCS San Martino Hospital in Genoa (Italy). Results A total of 1841 patients with symptoms of AAI were included. The mean age of patients in the Netherlands was statistically significant younger than in Italy and Belgium (15.7 compared to 15.9 and 16.0 years old, respectively). Moreover, the blood alcohol concentration was higher in the Netherlands and Belgium compared to Italy (2.0‰ compared to 1.95‰ and 1.8‰ respectively). The distribution of sex was nearly equal in the Netherlands, while statistically significant differences were observed with a higher proportion of males in Italy (54.8%) and Belgium (56.8%). Combined drug use was lower in Belgium with 10.0%, compared to 13.4% in The Netherlands and 14.7% in Italy. The most common reason for admission was ‘reduced consciousness’ in the total population (45.2%). Conclusions This is one of the first international studies which combines data on AAI in minors. In the future, efforts should be made to establish a common European database where records of AAI can be stored and analysed more efficiently for prevention purposes.

Characteristics of adolescents with acute alcohol intoxication in Belgium

Abstract Background Binge drinking and acute alcohol intoxication (AAI) are common in Belgian adolescents, posing a risk of serious health consequences. To develop cost-effective preventive measures for problematic alcohol use in adolescents in Belgium, more insight into the background of this group is necessary. Methods To gain more insight into the prevalence, medical characteristics and context of AAI, a retrospective multicentre hospital chart study was performed on adolescents aged 10 to 18 years with AAI in Antwerp, Belgium from 2015-2021. Furthermore, a prospective intervention study for adolescents with AAI in Antwerp was set up in 2023, of which the first results were not yet known at the time of submission. However, these results will be presented at the conference, if available. Results Over the study period, a total of 1032 admissions related to alcohol intoxication occurred in 1016 patients, with a median age of 16.6 years old and a median blood alcohol intoxication (BAC) of 1.95 g/L. There was combined drug use in 10% of the cases. Only 17% of the patients received additional care after admission. These findings did not significantly change over the study period. Multiple linear regression analyses indicated that after correcting for covariates, higher age, no combined drug use and decreased consciousness at admission were associated with more severe AAI cases (higher BAC). Conclusions AAI is prevalent among Belgian adolescents. Therefore, better-targeted preventive measures and policies are needed. Our findings could be taken into account when developing preventive measures. However, data addressing the demographics and context of AAI were mostly missing. Therefore, a prospective follow-up study was set up in Antwerp, which started in 2023 and is still ongoing. Furthermore, this study will investigate the feasibility and effectiveness of a follow-up intervention for this group of patients.

Toxicological evaluation of LivLonga®, a polyherbal combination, in rodents

There has been keen interest on herbs and phytoconstituents with hepatoprotective property to help restore healthy liver function. Ayurveda, the ancient Indian traditional system of medicine mentions about Curcuma longa, Garcinia indica and Piper nigrum which are reported to have hepatoprotective activity. Apart from supporting metabolism, liver plays pivotal role in numerous bodily processes, immune functions to digestion, detoxification, and storage of nutrients. Factors such as sedentary lifestyle, viral infections, drugs/chemicals, high calorie diet, excess intake of alcohol etc have adverse impact on normal functioning of liver. Development of novel herbal combination with standards of safety and efficacy can help manage liver ailments and protect liver health. LivLonga® is a polyherbal combination of scientifically validated ingredients- curcuminoids, garcinol and piperine to support healthy liver function. The present work was conducted to evaluate toxicity of LivLonga® using in vivo models when administered orally. The acute, subacute, and subchronic toxicity studies were carried out in accordance with the test guidelines established by the Organization for Economic Cooperation and Development. A single-dose acute oral toxicity produced no toxic effects after 14 days of treatment. Four-week (subacute) and 3-months (subchronic) oral toxicity studies were conducted and observed no abnormal clinical signs, no alterations in the body weight, hematology and biochemical parameters or gross and histopathological changes. Thus, oral administration of LivLonga® showed no signs of toxicity when dosed orally to rats, with a no observed adverse effect level (NOAEL) of 600 mg/kg/day.

Towards better prepared prisons: monitoring and response to the use of new substances inside prison

Abstract The use of new psychoactive substances (NPS) became an emerging issue in prisons in a number of European countries in 2014-2015. Synthetic cannabinoids were the new psychoactive substances most often reported, followed by synthetic cathinones, synthetic opioids and new benzodiazepines. Quantitative qualitative data on prison and drugs provided by 27 European Member States, Norway and Turkey to the EMCDDA (European Monitoring Centre for Drugs and Drug Addiction). An exploratory study conducted in 2017 found signs of NPS use in prison in 22 countries. Based on 2021-2022 data from a few countries, the lifetime prevalence of NPS in prison ranges from <1 to 19%, with large variation by country. Anecdotal information from 2024 referred to the use of new strong synthetic opioids (nitazene) inside prison. A wide range of physical and mental health harms (e.g. psychosis, disorientation, suicidal ideation, aggressiveness to others or self-harm) has been associated with acute intoxication by, and chronic consumption of NPS inside prison. Recent overdoses associated with the use of nitazene were reported in some prisons in Ireland and the UK. Additionally, the use of NPS in prison can have a disturbing impact on prison management, internal violence and bullying. To date, interventions to tackle the problems related to the use of NPS in prison have tended to focus on supply reduction and controls. Health and social interventions have begun to emerge, but they remain limited. Despite signs of increasing challenges posed by the emergence of NPS since several years, prisons remain largely unprepared to monitor and respond to those challenges. A new key task of the revised EMCDDA mandate (EUDA - European Drug Agency from 2nd of July) is to be better prepared to monitor, forecast and respond to new challenges in the drug field. Prisons should be prepared to adequately address the new challenges posed by the NPS to benefit the health and security of people living and working in prison.