Chronic Toxicity Research Articles

Clinical Evaluation of the Cannabis-UsingPatient: A Moving Target.

The prevalence of cannabis use has been increasing among both adolescents and adults worldwide. New trends in cannabis legalization and enhanced social media marketing have led to the availability of multiple high-potency cannabis products with hundreds of new and powerful delivery systems. Over the last decade, there have been drastic changes in cannabis formulations, potency, routes of consumption, and device technology, with increased complexity and sophistication among growers, suppliers, and consumers. Patterns of cannabis use among patients can have important clinical implications, including acute neurocognitive effects, chronic multiorgan toxicity, psychiatric, behavioral, social, and economic impact. However, assessment of medical or surgical patients who use cannabis either recreationally or problematically has become challenging for the clinician due to the changing patterns of cannabis consumption. This review provides information on the clinical evaluation of patients who use cannabis in a problematic fashion, with the focus on tetrahydrocannabinol. It provides the clinician with knowledge regarding cannabis terminology, sources, pharmacology, routes of administration, formulations, dosing, and toxicities. Using these components, an assessment approach for diagnosing cannabis use disorder is synthesized at the conclusion of the article.

Residual Assessment of Emerging Pesticides in Aquatic Sinks of Lahore, Pakistan

In recent decades, the use of pesticides has become fundamental to agricultural growth. However, the persistent and toxic nature of pesticides has led to significant concerns regarding their ecological and human health consequences. Therefore, for a better understanding of pesticide contamination and its potential risks, here we assessed the levels of five emerging pesticides—acetochlor, imidacloprid, MCPA, atrazine, and allethrin—in soil samples from ponds used for irrigation and in drinking water samples from nearby areas in Lahore, Pakistan. Our findings revealed that 100% of the samples were contaminated, posing substantial ecological and human health risks. Based on the toxic units (TUsum), all the soil samples showed higher toxic pressure, exceeding acute and chronic toxicity thresholds for earthworms, while 100% of water samples posed chronic toxicity risks to crustaceans and 10% to algae. Pollution index (PI) analysis further classified 100% of the soil samples and 10% of the water samples as highly polluted. These findings show high-pesticide residues in both soil and water and highlight immediate risk assessment and mitigation measures to protect non-target organisms. This preliminary information can be used to adopt risk assessment monitoring programmes and help higher authorities in making policies and guidelines to mitigate the escalating risk for ecology and humans.

A systematic review on the role of interventional radiotherapy for treatment of anal squamous cell cancer: multimodal and multidisciplinary therapeutic approach.

Aim was to compare the efficacy of interventional radiotherapy (IRT) boost vs. external beam radiotherapy (EBRT) boost after chemoradiation (CCRT) in patients with anal cancer (AC). The P.I.C.O. framework was: in patients with AC [P], is IRT boost [I] superior to EBRT boost [C] in terms of local control (LC), cancer specific survival (CSS), overall survival (OS), distant meta-static free Survival (DMFS), colostomy free survival (CFS) and toxicity [O]? 651 patients were analyzed. The median 5-year locoregional control rates was 87.8% in the IRT boost group versus 72.8% in the EBRT boost group. The 5-year cancer-specific survival rate was 91% in the IRT boost group versus 78% in the EBRT boost group. 5-years overall survival was 74.6% in IRT boost versus 67.7% in the EBRT boost. 5-years disease metastasis-free survival rate was 92.9% in IRT boost group vs. 85.6% for the EBRT boost group. Cancer-free survival rate was 76.8% in the IRT group vs. 63.1% in the EBRT boost group. Acute toxicity above grade 2 was less common in the IRT boost group while chronic toxicity was similar between both groups. IRT boost after CCRT could lead to better outcomes than EBRT boost in treating AC.

Biodegradable ICG-Conjugated Germanium Nanoparticles for In Vivo Near-Infrared Dual-Modality Imaging and Photothermal Therapy.

Theranostics, by integrating diagnosis and therapy on a single platform, enables real-time monitoring of tumors during treatment. To improve the accuracy of tumor diagnosis, the fluorescence and photoacoustic imaging modalities can complement each other to achieve high resolution and a deep penetration depth. Despite the superior performance, the biodegradability of theranostic agents plays a critical role in enhancing nanoparticle excretion and reducing chronic toxicity, which is essential for clinical applications. Herein, we synthesize biocompatible and biodegradable indocyanine green (ICG)-conjugated germanium nanoparticles (GeNPs) and investigate their biodistributions in nude mice and 4T1 tumor models after intravenous injections using near-infrared (NIR) dual-modality fluorescence and photoacoustic imaging. The ICG-conjugated GeNPs have strong NIR absorption due to the NIR-absorbing ICG and Ge in combination, emit strong NIR fluorescence due to the multilayered ICG coatings, and exhibit very low in vitro and in vivo toxicity. After tail vein injections, the ICG-conjugated GeNPs mainly accumulate in the liver and spleen as well as the tumor with the help of the enhanced permeability and retention effect. The tumor's fluorescence signal is much stronger than that of the control group injected with pure ICG solution, as the GeNPs can function as biodegradable carriers for efficiently delivering the ICG molecules to the tumor. Lastly, the ICG-conjugated GeNPs accumulated in the tumor can also be utilized for photothermal treatment under NIR laser irradiation, after which the tumor volume almost diminishes after 14 days. The experimental findings in this work demonstrate that the ICG-conjugated GeNPs are promising theranostic agents with exceptional biodegradability for in vivo NIR dual-modality imaging and photothermal therapy.

Biochemical and Histopathological Analysis of Aqueous Extract of an Aphrodisiac Formulation against Acetaminophen Induce Hepatocyte Injuries in Wistar Rats

The aimed of this study was to examine the biochemical parameters and histopathological effects of aqueous extract of an aphrodisiac formulation against acetaminophen induce hepatocyte injuries in Wistar rats. Zainacin Dadin duniya (aphrodisiac herbs) extract was prepared by cold maceration. The animal study was done using 30 adult both male and female Wistar rats was grouped into 5 groups (n=6) and orally administered with five different treatments (saline, liver drug, acetaminophen, extract and extract/ acetaminophen) for the period of 28days. The blood is collected from each grouped rat for biochemical parameters test and all rats were later sacrificed for histologically processed investigation. The results showed that the oral administration of the acetaminophen in group 3 treated rats causes a significant (P<0.05) increased in the activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP), but, when administered with the extract in group 4 rats, there was a significantly (p<0.05) decreased in the activities of ALT, AST and ALP. Significantly (p<0.05) increased in the Kidney Function Markers (Creatinine, and Urea) and decreased in Glucose level in the group 3 rats treated with acetaminophen, when compared with the group 4 rats treated with the extract, there was a significant (p<0.05) decreased in Creatinine, and Urea level and increased in the Glucose level. The serum total protein, Albumin, and Globulin significantly (p<0.05) decreased in the group 3 rats treated with acetaminophen while the bilirubin increased significantly. While group 4 rats showed significant increase in the total protein, Albumin, and Globulin and decreased in the bilirubin levels. The Results of Histopathology findings revealed hepatic tissue with distorted hepatocytes, portal vein, and sinusoids accompanied with massive necrosis in the liver of the group 3 rats treated with acetaminophen. While the liver of the group 4 rats showed, hepatic tissue with preserved architecture composed of cords of normal hepatocytes, normal portal vein, and sinusoids. There are no features of acute or chronic damage. The histologically Results of the small intestines of the all five (5) grouped rats showed preserved layers of muscosa, submucosa, muscularis externa, and serosa. There are no features of acute or chronic toxicity. Conclusively, the prolonged oral consumption of acetaminophen in animals resulted in hepatocellular deleterious effects and may be of a similar hazard in humans. Overall, administration of the extract in rats has significant ameliorative effect on the rats; this may be of immense benefits in the management of hepatocytes, necrosis in the liver and its associated biomarkers complications. Improved liver functions as well as improved antioxidant status are beneficial in the management of chronic diseases such as liver failure.

Bioaerosols and VOC emissions from landfill leachate treatment processes: Regional differences and health risks

The landfill leachate treatment process (LLTP) is a crucial anthropogenic source of bioaerosols and volatile organic compounds (VOCs) with potential environmental impacts and on-site health risks to plant workers. However, factors influencing microbial aerosol and VOC emissions remain poorly understood. We sampled and analyzed bioaerosols and VOCs in two process sections (oxidation ditch [OD] and reverse osmosis membrane [RO]) of LLTPs in northern (NLF) and southern (SLF) China. Bioaerosol concentrations were highest in OD, and particle size predominantly ranged from 0.654.7 µm. Microbial community analysis revealed distinct differences between geographical locations and process sections, with 332 genera identified. Genera such as Paenibacillus, Bacillus, and Pseudomonas were prevalent at all sampling sites. Oxygen-containing compounds (e.g., acetophenone and propionic acid) were the dominant VOCs, particularly in SLF-OD. Network analysis showed complex interactions, with Sphingomonas and ketones playing central roles in microbial and VOC communities, respectively. Partial least squares (PLS) modeling indicated a significant correlation between bioaerosols and VOCs. Specific microorganisms, such as TK10, Adhaeribacter, and Lachnospiraceae, were major contributors to emissions of hazardous VOCs (e.g., toluene and styrene). The ozone-generation potential and olfactory effect of the OD were significantly higher than those of RO; and those of SLF were higher than those of NLF. Health risk assessments indicated potential chronic toxicity and cancer risks associated with VOC exposure to specific compounds, such as trichloroethylene. Bioaerosol exposure occurred primarily through inhalation, particularly in male workers. This study establishes a theoretical foundation for the prevention and control of air-phase pollutant risks associated with LLTPs.

Aquatic toxicity and ecological risk of bisphenol B, and comparison with those of bisphenol A

2,2-bis(4-hydroxyphenyl)butane (BPB), one of the 2,2-bis(4-hydroxyphenyl)propane (BPA) alternatives, has not received sufficient attention so far due to the limited environmental concentration and toxicological data available. In this study, the acute toxicity of BPB was investigated using three aquatic organisms, i.e., Tetradesmus obliquus, Daphnia magna and Danio rerio. It was showed that Daphnia magna was the most sensitive organism with a half effective concentration of 3.93 mg/L. Subsequently, Daphnia magna was exposed to BPB solutions for 21 days to explore its chronic toxicity. Results indicated that BPB restricted the body length of parent Daphnia magna and reduced the total number of broods and neonates. The no-observed effect concentration of BPB to Daphnia magna was as low as 0.01 mg/L, which was two orders of magnitude lower than that of BPA (0.86–5.00 mg/L). Furthermore, the ecological risk of BPB was quantitatively assessed using a risk quotient (RQ) method. The RQ values of BPB ranged from 0.003 to 0.914, with the mean of 0.197. BPB posed a moderate risk at most sampling sites, while BPA posed a low ecological risk with RQ < 0.1 at nearly all the sampling sites. Hence, environmental monitoring and management should also be focused on BPB contamination.

Assessing the chronic toxicity of climbazole to Daphnia magna: Physiological, biochemical, molecular, and reproductive perspectives

The widespread use of climbazole (CBZ) has led to its increased presence in aquatic environments, potentially threatening freshwater ecosystems. However, evidence regarding the harmful effects of CBZ on aquatic organisms remains limited. In this study, Daphnia magna was exposed to CBZ at concentrations of 0, 0.2, 20, and 200 μg/L for 21 days to evaluate its chronic toxicity through assessment of life-history traits, physiological parameters, biochemical analyses, and gene expression. The results indicated that CBZ exposure delayed the days to the first brood, reduced the frequency of molting per adult, decreased the offspring number at first brood, diminished the body length, and decreased both the total number of broods per female and the total number of offspring per female. Additionally, CBZ inhibited the swimming speed, filtration rate, and ingestion rate. Moreover, CBZ altered the levels of superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH), while increasing malondialdehyde (MDA) levels. Gene expression analysis revealed varied responses in mRNA levels related to metabolic detoxification (cyp360a8, gst, and p-gp), digestive enzymes (α-amylase, α-esterase, and trypsin), energy (ak), oxygen transport (dhb), and reproduction (nvd, cyp314, ecr, vtg, and jhe) following CBZ exposure. These results indicate that the presence of CBZ in aquatic environments can induce toxicity by altering energy acquisition, supply, and metabolism; impairing metabolic detoxification pathways; eliciting oxidative stress; and causing reproductive toxicity in D. magna.

Therapeutic strategies for mobile spine chordoma: en bloc Versus intralesional surgery with adjuvant charged-particle therapy.

The aim of this retrospective study is to analyze the impact of en bloc resection with negative margins versus intralesional resection plus adjuvant hadron-therapy (HT) on local control (LC) and overall survival (OS) in patients with mobile spine chordomas. Mechanical complications incidence as well as risk factors, and outcome differences are investigated as secondary endpoints. 33 patients in a period from January 2013 to December 2021 were enrolled for the final analysis. The inclusion criteria were: lesions located in the mobile spine (C1-L5), age ≥ 15 years, minimum follow-up of 2 years, en bloc or intralesional surgical resection, virgin or recurrent chordomas, with only one previous surgical treatment. No difference was found in terms of LC between the two groups. The presence of pathologic fracture at pre-operative imaging and the presence of macroscopic residual tumor after surgery, independently from its entity, seemed to be associated with an increased risk of LR. No difference was found between planned en bloc and planned intralesional surgery in terms of mechanical complications occurrence. Eight patients (24.24%) had mechanical complications during the follow up period: male sex, presence of pathologic fracture at baseline, a combined surgical approach, the use of carbon fiber-only hardware appeared to be associated with an increased risk of mechanical complications after the primary surgery. En bloc resection, whenever possible, is always to be preferred for its widely recognized potential in LC and OS improvement. However, technology advances in high-dose conformal charged-particle therapy have allowed improvement of local control rates as an adjuvant therapy of intralesional surgery for mobile spine chordoma, with acceptable acute and chronic toxicity.

Co-Delivery of Renal Clearable Cerium Complex and Synergistic Antioxidant Iron Complex for Treating Sepsis.

The mononuclear phagocytic system clears the circulating inorganic nanomaterials from the bloodstream, which raises concerns about the chronic toxicity of the accumulated metal species. A better understanding of the behavior of each metal after systemic injection is thus required for clinical translations. This study investigates the significance of the metal-ligand interaction on the accumulation of cerium and demonstrates that only the form in which cerium is coordinated to a multidentate chelator with a strong binding affinity does not accumulate in major organs. Specifically, cerium complexed with diethylenetriamine pentaacetic acid (DTPA) forms renally excretable nanoparticles in vivo to circumvent the leaching of cerium ions, whereas weakly coordinated cerium-based nanomaterials produce insoluble precipitates upon encountering physiological phosphate anions. Ceria-based renally clearable nanoparticles (CRNs) derived from cerium-DTPA are utilized as the antioxidant pair with iron-DTPA, in which their combination leverages the Fenton reaction to synergistically scavenge hydrogen peroxide. This reduces the gene expression of pro-inflammatory factors in the macrophages activated with lipopolysaccharide as well as improves the survival rate of septic mice by alleviating the systemic inflammatory response and its downstream tissue injury in the liver, spleen, and kidneys. This study demonstrates that CRNs combined with iron-DTPA can be utilized as nonaccumulative nanomedicines for treating systemic inflammation, thereby overcoming the limitations of conventional ceria nanoparticle-based treatments.

Poor Survival Rate of Eastern Gray Kangaroos (Macropus giganteus) Affected by Chronic Phalaris Toxicity.

Chronic phalaris toxicity (CPT) is a neurological disease caused by animals ingesting toxins produced by early growth stages of Phalaris aquatica, a pasture plant introduced to the southeastern regions of Australia post colonization. Little is known about the clinical progression of CPT in wildlife, as incidents are sporadic and predominantly reported when animals are in the end stages of disease and in a poor welfare state. We studied a cohort of 35 eastern gray kangaroos (Macropus giganteus) affected by CPT to clarify clinical prognosis and survival rates. Kangaroos were captured in May, June, and July of 2022 at Plenty Gorge Parklands, Victoria, Australia. Each animal was radiotracked for 180 d, clinical progression and disease outcomes monitored twice a week. By the conclusion of the study, 24 animals had died (19 by euthanasia due to deterioration, five found dead). Ten animals survived, with two demonstrating a reduction in clinical signs and eight showing full resolution of clinical signs. One animal was disqualified from the study. The overall survival rate was 29.4% (95% confidence interval 17.5-49.5%). The survival duration of animals that died ranged from 5 to 133 d. There was no difference in survival rate based on sex (P=0.2), age class (P=0.49) or the month of capture (P=0.49). These results suggest that CPT is an important health and welfare concern for at-risk macropod populations, with high case-fatality rates and prolonged clinical durations. Further research to manage the disease via methods such as reducing Phalaris aquatica plant coverage and preventative treatments for animals is warranted to reduce disease incidences and improve disease outcomes in wildlife populations.

Combined toxicity of perfluoroalkyl substances and microplastics on the sentinel species Daphnia magna: Implications for freshwater ecosystems

Persistent chemicals from industrial processes, particularly perfluoroalkyl substances (PFAS), have become pervasive in the environment due to their persistence, long half-lives, and bioaccumulative properties. Used globally for their thermal resistance and repellence to water and oil, PFAS have led to widespread environmental contamination. These compounds pose significant health risks with exposure through food, water, and dermal contact. Aquatic wildlife is particularly vulnerable as water bodies act as major transport and transformation mediums for PFAS. Their co-occurrence with microplastics may intensify the impact on aquatic species by influencing PFAS sorption and transport. Despite progress in understanding the occurrence and fate of PFAS and microplastics in aquatic ecosystems, the toxicity of PFAS mixtures and their co-occurrence with other high-concern compounds remains poorly understood, especially over organisms’ life cycles.Our study investigates the chronic toxicity of PFAS and microplastics on the sentinel species Daphnia, a species central to aquatic foodwebs and an ecotoxicology model. We examined the effects of perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA), and polyethylene terephthalate microplastics (PET) both individually and in mixtures on Daphnia ecological endpoints. Unlike conventional studies, we used two Daphnia genotypes with distinct histories of chemical exposure. This approach revealed that PFAS and microplastics cause developmental failures, delayed sexual maturity and reduced somatic growth, with historical exposure to environmental pollution reducing tolerance to these persistent chemicals due to cumulative fitness costs. We also observed that the combined effect of the persistent chemicals analysed was 59% additive and 41% synergistic, whereas no antagonistic interactions were observed. The genotype-specific responses observed highlight the complex interplay between genetic background and pollutant exposure, emphasizing the importance of incorporating multiple genotypes in environmental risk assessments to more accurately predict the ecological impact of chemical pollutants.

MQ232, A Snake Toxin Derivative for Treatment of Hyponatremia and Polycystic Kidney Diseases

Background: Vaptans were developed at the end of the previous century as V2R antagonists. Tolvaptan is the most prescribed vaptan for hyponatremia and the autosomal polycystic kidney disease (ADPKD). However, its use is not as widespread as it should be due to price issues, a narrow therapeutic window and some side effects. With the aim of discovering new efficient and safer V2R antagonists, we screened animal venoms and identified several interesting peptide toxins. Among them, MQ1 displayed such unique biological properties in that regard that it was the starting point for the development of a potential drug candidate. Methods: Human T-cell assays and bioinformatics was used to mitigate MQ1 immunogenicity risk. The MQ232 biodistribution in mice was done by positron emission tomography (PET). Pharmacodynamics, pharmacokinetics, acute and chronic toxicity tests were performed on control rats. A rat experimental model of dDAVP-induced hyponatremia, an ex vivo mice model of renal cysts and a mice orthologous model of ADPKD were used to validate MQ232 efficacy in these pathologies. Results: Three mutations were introduced in MQ1 to mitigate its immunogenicity risk. A fourth gain-of-function mutation was added to generate MQ232. MQ232’s safety was demonstrated by a first toxic dose as high as 3,000 nmol/kg and a strong kidney organ selectivity by PET imaging, while showing almost no interaction with the liver. MQ232’s efficacy was first demonstrated with an effective dose of 3 nmol/kg in a hyponatremic model, and then in polycystic kidney models on which MQ232 significantly reduced cyst growth. Conclusions: We demonstrated, employing diverse translational techniques and minimizing animal use, MQ232's safety and efficacy in several rodent models of hyponatremia and ADPKD.

Chronic oral toxicity protocol for adult solitary bees (Osmia bicornis L.): Reduced survival under long-term exposure to a “bee-safe” insecticide

Pollinators are essential for crop productivity. Yet, in agricultural areas, they may be threatened by pesticide exposure. Current pesticide risk assessments predominantly focus on honey bees, with a lack of standardized protocols for solitary bees. This study addresses this gap by developing a long-term oral exposure protocol tailored for O. bicornis. We conducted initial trials to determine optimal container sizes and feeding methods, ensuring high survival rates and accurate syrup consumption measurements. A validation test involving five laboratories was then conducted with the insecticide Flupyradifurone (FPF). Control mortality thresholds were set at ≤ 15% at 10 days. Three laboratories achieved ≤10%, demonstrating the protocol's effectiveness in maintaining healthy test populations. The seasonal timing of experiments influenced control mortality, underscoring the importance of aligning tests with the natural flight period of the population used. Our findings revealed dose-dependent effects of FPF on syrup consumption, showing stimulatory effects at lower concentrations and inhibitory effects at higher ones. The 10-day median lethal daily dose (LDD50) of FPF for O. bicornis (531.92 ng/bee/day) was 3.4-fold lower than that reported for Apis mellifera (1830 ng/bee/day), indicating Osmia's higher susceptibility. Unlike other insecticides, FPF did not exhibit time-reinforced toxicity. This study introduces a robust protocol for chronic pesticide exposure in solitary bees, addressing a critical gap in current risk assessment. Based on its low risk to honey bees and bumblebees, FPF is approved for application during flowering. However, our results suggest that it may threaten Osmia populations under realistic field conditions. Our findings underscore the need for comparative toxicity studies to ensure comprehensive protection of all pollinators and the importance of accounting for long term exposure scenarios in risk assessment. By enhancing our understanding of chronic pesticide effects in solitary bees, our study should contribute to the development of more effective conservation strategies and sustainable agricultural practices.

A test method for assessing chronic oral toxicity of a pesticide to solitary nesting orchard bees, Osmia spp. (Hymenoptera: Megachilidae).

Orchard bees of the genus Osmia Panzerare important pollinators of fruit trees in various regions of the world, with some species commercially available in the United States and Europe. In addition to their pollination services, Osmia lignaria, Osmia cornifrons, Osmia bicornis, and Osmia cornuta have been identified as potential model species for solitary bees in pesticide risk assessment and have been used for the development of new methods to test acute lethal effects via contact and oral routes of exposure. Our goal was to expand the available methodology to characterize the toxicity of pesticides for these solitary bees through a chronic oral test for adult bees. Chronic oral toxicity of pesticides to orchard bees has been reported, but methods differ among research groups. In our study, O. lignaria, O. cornifrons, O. bicornis, and O. cornuta female bees had access to sucrose solution ad libitum in separate, species-specific 10-day tests. Mean body mass, mean daily consumption, and survival differed among the studied bee species. The dose-response test design was validated with dimethoate, a reference toxic compound, and chronic toxicity endpoints were estimated for the 4 Osmia species. The median lethal daily doses normalized by weight for O. lignaria, O. bicornis, O. cornuta, and O. cornifrons were within the same order of magnitude at 0.23, 0.26, 0.49, and 0.61 µg dimethoate/g bee/day, respectively. The methodology described here was aligned as much as possible with the available honey bee and bumble bee standard methods to facilitate the comparison of chronic toxicity profiles among bee species.

Evaluation of the chronic oral toxicity of the classical ancient prescription Kai-Xin-San

Ethnopharmacological relevanceThe Kai-Xin-San (KXS), as an ancient classic prescription, has been used for the treatment of amnesia for thousands of years. Modern clinical and non-clinical pharmacological studies have found that it has significant therapeutic effects on dementia and depression, but there are relatively few studies on its safety. Aim of the studySubacute and chronic toxicity studies were conducted to investigate the symptoms, severity, target organs, development and recovery of toxic reactions, as well as the toxic dose. These studies provide technical data for ensuring the safety of KXS. Materials and methodsIn the sub-acute toxicity study, rats were orally administered KXS at doses of 0.80, 1.61, 3.22, and 6.43 g/kg body weight for a duration of 4 weeks. In the chronic toxicity study, rats were orally administered KXS at doses of 0.27, 0.81, and 2.43 g/kg body weight for a duration of 26 weeks, and a withdrawal study was conducted for a period of 4 weeks after the treatment.The rats were observed daily for clinical signs and mortality. Changes in body weight, food consumption, and water consumption were periodically monitored. Additionally, urinalysis results, hematological and biochemical parameters, relative organ weights, and pathology were monitored at specific observation time points. ResultsIn the sub-acute toxicity study, necropsy of dead and moribund rats revealed evident distension and swelling of the gastrointestinal tract, as well as thinning of the intestinal wall. The main adverse reactions observed included flatulence, piloerection, abnormal breathing sounds, and emaciation. Doses of 1.61 g/kg and below did not cause animal death. The gastrointestinal system is the main target organ of toxicity. In the chronic toxicity study, the no-observed-adverse-effect-level (NOAEL) of KXS was 0.27 g/kg, and its toxic effects were primarily concentrated in the gastrointestinal system. This led to secondary pathological changes in the immune system, hematopoietic system, and heart, suggesting that relevant indicators should be monitored when large doses are used clinically for an extended period of time. ConclusionsDuring the rodent toxicity evaluation, severe gastrointestinal damage was observed when KXS, powdered with crude drugs, was administered. The NOAEL for rats was found to be 0.27 g/kg/day.

Toxicodynamics of cadmium in the green mussel Perna viridis (Linnaeus, 1758) using bioenergetic and physiological biomarkers.

This study evaluated the toxicity of cadmium (Cd) on the green mussel Perna viridis, aiming to identify toxicological endpoints and investigate its responses across physiological, bioenergetic, and biochemical parameters. The 96-hour LC50 value for Cd in P. viridis was 3.03 ± 0.12 mg L-1, with a 95% confidence interval of 2.35-3.91 mg L-1. Chronic toxicity tests revealed a No Observable Effect Concentration (NOEC), Lowest Observable Effect Concentration (LOEC), and chronic toxicity values of 0.20, 0.37, and 0.29 mg L-1, respectively. Cadmium accumulation in treated mussels increased 46- to 215-fold compared to the control group. Superoxide dismutase, catalase, glutathione S-transferase, and glutathione peroxidase levels in exposed mussels exhibited a significant increase compared to the control group. The redox index ratio, acetylcholinesterase activity, and lysosomal membrane stability decreased with increasing exposure concentrations. Levels of reduced and oxidized glutathione, glutathione reductase, lipid peroxidation, and metallothionein-like proteins increased in exposed mussels. Clearance rate, respiration rate, and excretion rate decreased in a dose-dependent manner. Protein, carbohydrate, and lipid levels decreased with increasing exposure concentration (p < 0.001). Mitochondrial electron transport system activity increased, while cellular energy allocation (p < 0.001) and scope for growth decreased in a dose-dependent manner (p < 0.01). The significant increase in antioxidants suggests heightened oxidative stress in mussels under Cd exposure. The physiological activities of the mussels were severely affected, ultimately leading to a reduced scope for growth. The toxicological data generated in this study contribute to the development of seawater quality criteria for the metal Cd.

Generation and geochemical characteristics of acid rock drainage (ARD) in Barton Peninsula, King George Island (KGI), maritime, Antarctica

This study deals with the generation, geochemical characteristics, and environmental impacts of acid rock drainage (ARD), a global environmental problem, on the Barton Peninsula. To elucidate the governing processes and to assess the environmental hazards of ARD, we present chemical data from lakes, ponds, and creeks with a wide range of pH values. We also provide mineralogical and geochemical compositions of sediments and bedrocks. Compared to weak-acidic and neutral waters, waters that display typical characteristics of ARD with low pH (3.7 to 4.2), high sulfate (46 to 92 mg/L), and Fe (0.8 to 16.5 mg/L) occur in the northern tip of the peninsula. Acidic waters with the highest cation (e.g., K, Na, Si, and Ca) and anion (e.g., SO4) compositions indicate ARD-enhanced rock weathering in the peninsula. Consistently, quantifying of chemical weathering degree yields the highest chemical index of alteration (CIA) and the mafic index of alteration (MIA) with the lowest ICV values for sediments from the acidic waters. Enrichment factors (EFs) calculated for As, Co, Cd, Cu, Pb, Zn, and Ni indicate severe to minor enrichment for As and Pb metals, respectively in the acidic water-associated sediments. Heavy metal concentrations of acidic waters also display the highest values for the peninsula, with Fe, Cu, and Cd metals exceeding the chronic aquatic toxicity limit (CAT). Therefore, geochemical records of acidic waters and sediments, especially lakes, may help in tracing the long-term environmental impacts of ARD, while sediments obtained from the weak acidic and near-neutral waters, together with water chemistry data, may provide a better representative composition of the bedrocks with neutralizing potential. The data presented here may contribute to predicting the source/s, and extent of future ARD generation in the peninsula, which is likely to be enhanced by increased chemical weathering due to climate warming.

Ecotoxicological risk assessment of active pharmaceutical ingredients (APIs) against different aquatic species leveraging intelligent consensus prediction and i-QSTTR modeling

The increasing presence of active pharmaceutical ingredients (APIs) in aquatic ecosystems, driven by widespread human use, poses significant risks, including acute and chronic toxicity to aquatic species. However, the scarcity of experimental toxicity data on APIs and related compounds due to the high costs, time requirements, and ethical concerns associated with animal testing hinders comprehensive risk assessment. In response, we developed quantitative structure-toxicity relationship (QSTR) and interspecies quantitative structure toxicity-toxicity relationship (i-QSTTR) models for three key aquatic species: zebrafish, water fleas, and green algae, using NOEC as an endpoint, following OECD guidelines. Algae, daphnia, and fish, recognized as standard organisms in toxicity testing, are crucial bio-indicators due to their size, transparency, adaptability, and regulatory acceptance. We used partial least squares (PLS) and multiple linear regression (MLR) methods for model development alongside machine learning techniques such as Random Forest (RF), Support Vector Machines (SVM), K-nearest Neighbor (kNN), and Neural Networks (NN) to enhance the predictivity. Lipophilicity, electronegativity, unsaturation, a molecular cyclized degree in molecular structure, large fragments, aliphatic secondary C(sp2), and R–CR–R groups were identified as critical biomarkers for API toxicity. Screening of the PPDB (pesticide properties databases) and DrugBank validated the practical application of these models, offering valuable tools for regulatory decisions, safer API design, and the preservation of aquatic biodiversity.

Environmental pollution impact on the severity of some rheumatic diseases: a comparative analytical study on inflammatory and non-inflammatory samples

ObjectiveEnvironmental pollution of heavy metals is increasingly a problem and has become of great concern due to the adverse effects it causes worldwide. Heavy metal exposure has been implicated in health problems, including fibromyalgia and rheumatoid arthritis. We aim to evaluate the rule of chronic heavy metals toxicity on the induction of vitamin D3 (VD) deficiency and parathyroid hormone (PTH) disturbances in an inflammatory disease like rheumatoid arthritis (RA) and non-inflammatory disease like fibromyalgia syndrome (FMS).MethodsThis comparative analytical study was conducted on sixty adults (age ≥ 18 years). Participants were divided into three groups. Group I: twenty patients diagnosed with RA according to the specific ACR/EULAR criteria for RA. Group II: twenty patients diagnosed with FMS according to the specific 2010 (ACR) criteria for FMS. Group III: twenty healthy adults. All patients and controls were subjected to routine laboratory tests as well as the measurement of PTH, VD and estimation of serum levels of lead, cadmium, and chromium.ResultsVD was significantly inversely correlated to PTH, lead, cadmium, chromium, and activity scores in the RA and FMS groups. Lead, Cadmium and Chromium had a significant independent risk on the VD level in RA patients, while lead had a significant independent risk on the VD level in FMS patients.ConclusionHeavy metals may affect VD synthesis, leading to hypovitaminosis D and secondary hyperparathyroidism in RA and FMS patients. Heavy metals play a key role in the pathogenesis of RA, FMS, and their disease activity.