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In 2012, a controversial study on the long-term toxicity of a Roundup herbicide and the glyphosate-tolerant genetically modified (GM) maize NK603 was published. The EC-funded G-TwYST research consortium tested the potential subchronic and chronic toxicity as well as the carcinogenicity of the glyphosate-resistant genetically modified maize NK603 by performing two 90-day feeding trials, one with GM maize inclusion rates of 11 and 33% and one with inclusion rates of up to 50%, as well as a 2-year feeding trial with inclusion rates of 11 and 33% in male and female Wistar Han RCC rats by taking into account OECD Guidelines for the testing of chemicals and EFSA recommendations on the safety testing of whole-food/feed in laboratory animals. In all three trials, the NK603 maize, untreated and treated once with Roundup during its cultivation, and the conventional counterpart were tested. Differences between each test group and the control group were evaluated. Equivalence was assessed by comparing the observed difference to differences between non-GM reference groups in previous studies. In case of significant differences, whether the effects were dose-related and/or accompanied by changes in related parameters including histopathological findings was evaluated. It is concluded that no adverse effects related to the feeding of the NK603 maize cultivated with or without Roundup for up to 2 years were observed. Based on the outcome of the subchronic and combined chronic toxicity/carcinogenicity studies, recommendations on the scientific justification and added value of long-term feeding trials in the GM plant risk assessment process are presented.

Erythrina fusca Lour. is a medicinal plant traditionally used in herbal medicine; however, there are no records of toxicity associated with the ethanol extract of E. fusca fruit (EtEF). The objective of this study was to assess the safety of EtEF through toxicity testing. Four groups of Swiss albino mice were employed, including a control group and three groups administered EtEF at doses of 1000, 3000, and 5000 mg/kg (single dose) and 100, 300, and 500 mg/kg (administered repeatedly for 90 days). Various parameters, including body weight, food and water consumption, hematological and biochemical parameters, relative organ weight, urine composition, and histopathology, were evaluated. No significant differences were observed in the tested groups compared to the control group, and there was no evidence of morphological or histopathological damage in the organs of mice treated with EtEF. This study affirms the safety of EtEF and establishes a foundation for further investigations into its utilization in traditional medicine.

Neonicotinoid insecticides are successfully applied to control pests in a variety of agricultural crops; however, they may not only affect pest insects but also non-target organisms such as pollinators. This review summarizes, for the first time, 15 years of research on the hazards of neonicotinoids to bees including honey bees, bumble bees and solitary bees. The focus of the paper is on three different key aspects determining the risks of neonicotinoid field concentrations for bee populations: (1) the environmental neonicotinoid residue levels in plants, bees and bee products in relation to pesticide application, (2) the reported side-effects with special attention for sublethal effects, and (3) the usefulness for the evaluation of neonicotinoids of an already existing risk assessment scheme for systemic compounds. Although environmental residue levels of neonicotinoids were found to be lower than acute/chronic toxicity levels, there is still a lack of reliable data as most analyses were conducted near the detection limit and for only few crops. Many laboratory studies described lethal and sublethal effects of neonicotinoids on the foraging behavior, and learning and memory abilities of bees, while no effects were observed in field studies at field-realistic dosages. The proposed risk assessment scheme for systemic compounds was shown to be applicable to assess the risk for side-effects of neonicotinoids as it considers the effect on different life stages and different levels of biological organization (organism versus colony). Future research studies should be conducted with field-realistic concentrations, relevant exposure and evaluation durations. Molecular markers may be used to improve risk assessment by a better understanding of the mode of action (interaction with receptors) of neonicotinoids in bees leading to the identification of environmentally safer compounds.

In this study, eleven commonly used antibiotics including sulfonamides, tetracyclines, aminoglycosides, fluoroquinolones, and beta-lactams were evaluated for their acute and chronic aquatic toxicities using standard test organisms e.g., Vibrio fischeri, Daphnia magna, Moina macrocopa , and Oryzias latipes . Among the antibiotics tested for acute toxicity, neomycin was most toxic followed by trimethoprim, sulfamethoxazole and enrofloxacin. Sulfamethazine, oxytetracycline, chlortetracycline, sulfadimethoxine and sulfathiazole were of intermediate toxicity, while ampicillin and amoxicillin were least toxic to the test organisms. There were no trends in sensitivity among test organisms or among different classes of the antibiotics. Only the beta-lactam class was the least toxic. In chronic toxicity test, neomycin affected reproduction and adult survival of D. magna and M. macrocopa with low mg/l levels exposure. Predicted no effect concentrations (PNECs) were derived from the acute and chronic toxicity information gleaned from this study and from literature. When the PNECs were compared with measured environmental concentrations (MECs) reported elsewhere for the test compounds, hazard quotients for sulfamethoxazole, sulfathiazole, chlortetracycline, oxytetracycline, and amoxicillin exceeded unity, which suggests potential ecological implication. Therefore, further studies including monitoring and detailed toxicological studies are required to assess potential ecological risk of these frequently used veterinary antibiotics.

The phlorotannin-polycaprolactone-coated endotracheal tube (PP tube) has been developed with the aim of preventing tracheal stenosis that can result from endotracheal intubation, a factor that can lead to a serious airway obstruction. Its preventive efficacy has been assessed through both in vitro and in vivo investigations. However, there is a lack of studies concerning its biocompatibility and sub-chronic toxicity in animal models, a crucial factor to ensure the safety of its usage as a functional endotracheal tube. Thus, this study aimed to evaluate the biocompatibility and sub-chronic (13 weeks) toxicity of the PP tube through L929 cell line and diverse in vivo models. The cytotoxicity testing was performed using the extracts of PP tube on L929 cells for 72 h. Furthermore, other tests conducted on animal models, including ICR mice (acute systemic toxicity), New Zealand white rabbit (intradermal reactivity and pyrogen tests), guinea pig (maximization sensitization), and Sprague Dawley rats (sub-chronic toxicity). In both biocompatibility and sub-chronic toxicity analyses, no significant adverse effects are observed in the groups exposed to the PP tube, when compared to control group. Altogether, the findings suggested that the PP tube exhibits relative non-toxic and safety, supporting its suitability for clinical usage. However, extended periods of intubation may produce mild irritant responses, highlighting the clinical caution of limiting intubation duration to less than 13 weeks.

Although the fruit extract of Dolichandrone genus was shown to inhibit spermatogenesis, the reproductive toxicity of Dolichandrone serrulata flowers (DSFs) is not documented. Recent study aimed to evaluate the sub‐chronic toxicity of DSF on male reproductive system. Antioxidant capacity and total phenolic contents of DSF extract were determined using Folin–Ciocalteu's, 2,2‐diphenyl‐1‐picrylhydrazyl and ferric reducing antioxidant power assays. The terpenoid components were determined using nuclear magnetic resonance spectrum. Adult male rats were treated orally with DSF (100, 300 or 600 mg/kg) for 48 days. Histopathology of testis and epididymis was observed. Sperm concentration, viability, acrosome status and morphology were also examined. Expressions of heat shock protein 70 (Hsp70), tyrosine‐phosphorylated (TyrPho) proteins, androgen receptor (AR) and steroidogenic acute regulatory (StAR) protein in testis were investigated. Results showed that DSF contained phenolic compounds and terpenoids (phytoandrogens; rengyolone and cleroindicin B). No reproductive histopathology was observed in DSF‐treated rats. Although DSF decreased the serum testosterone level, the sperm qualities were not affected. Particularly, sperm concentration of DSF‐treated animals was significantly increased. DSF changed the testicular TyrPho proteins but the expression of AR, StAR or Hsp70 was not altered. In conclusion, DSF possesses antioxidant capacity with no toxicity on male reproductive system.

Background Quercetin is an organic flavonoid present in several fruits and vegetables. The anti-inflammatory, antiviral, antioxidant, cardio-protective, anti-carcinogenic and neuroprotective properties demonstrated by this dietary supplement endorses it as a possible treatment for inflammatory diseases and cancer. Unfortunately, conflicting research has cast uncertainties on the toxicity of quercetin. The main purpose of this study was to determine if quercetin has any toxic properties in mice at doses that have shown efficacy in pre-clinical studies regarding cancer, cancer therapy, and their off-target effects. Methods A sub-chronic toxicity study of quercetin was examined in male and female CD2F1 mice. Three different doses of quercetin (62, 125, and 250 mg/kg of diet) were infused into the AIN-76A purified diet and administered to mice ad libitum for 98 days. Body weight (BW), food consumption, water intake, body composition, blood count, behavior, and metabolic phenotype were assessed at various timepoints during the course of the experiment. Tissue and organs were evaluated for gross pathological changes and plasma was used to measure alkaline phosphatase (AP), aspartate transaminase (AST), and alanine transaminase (ALT). Results We found that low (62 mg/kg of diet), medium (125 mg/kg of diet), and high (250 mg/kg of diet) quercetin feeding had no discernible effect on body composition, organ function, behavior or metabolism. Conclusions In summary, our study establishes that quercetin is safe for use in both female and male CD2F1 mice when given at ~ 12.5, 25, or 50 mg/kg of BW daily doses for 14 weeks (i.e. 98 days). Further studies will need to be conducted to determine any potential toxicity of quercetin following chronic ingestion.

The presence of anthracene (ANT) in coastal waters is increasingly being reported and profoundly impacts the marine biota. However, toxicity data for ANT on marine organisms are scarce to develop numerical water quality criteria to protect marine life. Therefore, for the first time, this study derived the seawater quality criteria (SWQC) of ANT are based on the toxicity values of five marine organisms. Acute and chronic toxicity values of ANT were derived on diatoms ( Thalassiosira subtilis and Endomoneis paludosa ), copepods ( Oithona similis and Tisbe furcata ), and shrimp ( Litopenaeus vannamei ). 96 h-EC 50 and 96 h-LC 50 were ranged between 23.98 ± 2.4 and 1730 ± 330 μg/L. Chronic toxicity values such as no observed effect concentration (NOEC), lowest observed effect concentration (LOEC), and chronic values ranged from 2.1 ± 0.6 to 267 ± 58 µg/L, 2.5 ± 0.8 to 400 ± 7 µg/L, and 2.4 ± 0.8 to 327 ± 71 µg/L, respectively. Seawater quality criteria, viz . predicted no effect concentration (PNEC), criterion continuous concentration (CCC), and criterion maximum concentration (CMC) were derived using NOECs, chronic values, and acute data. The criterion concentrations PNEC, CCC, and CMC can apply to sensitive/protected waters across the coastal waters and accidental spill/outfalls/discharge points in enclosed waters, respectively. The PNEC, CCC, and CMC are derived as 2.7, 8.8, and 17 µg/L, respectively, from the Australian Burrlioz SSD, whereas the USEPA SSD resulted in 3.89 µg/L of PNEC, 10.7 µg/L of CCC, and 26.7 µg/L of CMC. The Australian Burrlioz SSDs delivered sensitive SWQCs, which may ensure the protection of marine life from ANT pollution.

Although considered safe and widely used, some natural remedies are responsible for health ailments to their users that deserve to be investigated. SAYE PLUS is one of the most widely used traditional recipes as antimalaria for decades and recently against Covid-19 in Burkina Faso and beyond, and is commonly regarded as safe to use. In the present study, sub-chronic toxicity tests were performed orally in Wistar rats at daily doses of 250, 500, and 1000 mg/kg for 90 days, following the guidelines of the Organization for Economic Cooperation and Development (OECD). The results revealed neither symptoms of toxicity nor mortality. Depending on the dose, time frame, or animal sex, compared with the control, SAYE PLUS powder caused a statistically significant reduction in the water and food consumption of the treated rats. Significantly increases in serum creatinine, total protein, hydrogen phosphate ion (PO 4 2 ), and potassium ion (K + ) levels were detected in females at all doses. Compared to control values, the male rats’ glucose decreased while its PO 4 2- increased significantly at the daily dose of 1000 mg/kg of SAYE PLUS. Histopathological analysis revealed that the rat heart, lungs, liver, kidneys, and spleen histostructure were unaffected by sub-chronic exposure to SAYE PLUS up to 1000 mg/kg/d. The Findings provide some scientific information on the toxicological profile of the phytomedicine SAYE PLUS when administered in repeated doses for 90 days. However, they are limited by the absence of analysis of the animals’ hematological parameters. Nevertheless, results show that for patient safety, it is not advisable to use SAYE PLUS for more than two consecutive weeks. Furthermore, herbal remedies need careful evaluation before or during their human use, especially when a new form of use other than the traditional one is proposed. Further long-term studies focusing on the hematological parameters and certain kidney and liver functional indicators will add the scientific merit and interest of the present work.

While it has been well established that increasing chloride concentration in water reduces the toxicity of nitrite to freshwater species, little work has been done to investigate the effect of chloride on nitrate toxicity. We conducted acute and chronic nitrate (as sodium nitrate) toxicity tests with the cladoceran Ceriodaphnia dubia and the amphipod Hyalella azteca (chronic tests only) over a range of chloride concentrations spanning natural chloride levels found in surface waters representative of watersheds of the Great Lakes Region. Chronic nitrate toxicity test results with both crustaceans were variable, with H. azteca appearing to be one of the more sensitive invertebrate species tested and C. dubia being less sensitive. While the variability in results for H. azteca were to an extent related to chloride concentration in test water that was distinctly not the case for C. dubia . We concluded that the chloride dependent toxicity of nitrate is not universal among freshwater crustaceans. An additional sodium chloride chronic toxicity test with the US Lab strain of H. azteca in the present study suggested that when present as predominantly sodium chloride and with relatively low concentrations of other ions, there is a narrow range of chloride concentrations over which this strain is most fit, and within which toxicity test data are reliable.