Journal of Toxicology最新文献

Background: Herbal formulations with antimicrobial and anti-inflammatory properties are commonly used in traditional medicine for oral hygiene. Despite growing popularity, little or no research exists on the safety profile of these products to confirm their long-term safety. An ayurvedic dentifrice formulation was analyzed in Wistar albino rats for acute and subacute oral toxicity, with emphasis on the toxic effects of the product on physiological, hematological, biochemical, and histopathological parameters. Methods: Wistar rats (n = 6) were administered a single dose of the test formulation above 2000 mg/kg body weight and were kept on a 14-day observation period for acute toxicity. Subacute toxicity was induced by daily oral administration of 300, 600, and 1000 mg/kg of the test formulation to male (n = 30) and female (n = 30) rats for 28 days. A 14-day recovery period in the high-dose group was then carried out. Clinical signs, including mortality, food and water intake, body weight, hematological and biochemical parameters, vital organ weights, and histopathological alterations, were assessed. Results: Acute and subacute toxicity studies did not reveal any mortality or significant clinical signs. At 2000 mg/kg body weight, the hepatic changes were minor and reversible. The no-observed-adverse-effect level (NOAEL) was determined to be 1000 mg/kg body weight, as there were no significant changes in biochemical, hematological, and histopathological parameters until this dose. Conclusions: In Wistar albino rats, the tested Ayurvedic dentifrice formulation tapered with quiescent toxicity can be considered safe for oral use. Long-term studies in the form of clinical trials are recommended for human use.

Insecticides are widely used to protect agricultural and plantation products from pests and plant-disrupting organisms. Prior to market distribution, pesticide-containing products must undergo safety evaluations, including assessments of potential skin and eye irritation and allergic responses. In this study, we conducted one of the first comparative in vivo evaluations of commercial insecticidal formulations containing cypermethrin (Gusano 300 EC), pymetrozine (Vorum 50 WG), and indoxacarb-emamectin benzoate (Endorse Plus 160/20 OD) using internationally recognized protocols based on OECD 404 (skin irritation), OECD 405 (eye irritation), and OECD 406 (skin sensitization). The results showed that the cypermethrin formulation caused minimal skin irritation, mild eye irritation, and skin sensitization. The pymetrozine formulation did not cause skin irritation or sensitization but induced mild eye irritation. The indoxacarb-emamectin Benzoate formulation caused mild eye irritation and skin sensitization, with minimal skin irritation. These findings contribute novel data to the toxicological profile of these pesticide formulations and support future safety evaluations and regulatory assessments.

Previous studies have identified early life as a sensitive window for BPA exposure that may increase the risk of metabolic disease in adulthood. However, less attention has been paid to the effects of early-life BPA exposure on the pancreas and its relationship to the development of metabolic diseases. In this study, we exposed females to 50 μg/kg/d BPA in drinking water from 6 days of gestation to weaning of offspring mice and administered a high-fat diet after weaning of offspring mice. We found that early-life BPA-exposed male mice gained body weight, had downregulated pancreatic Ins1, Pdx1, and NeuroG3 gene expression, reduced β-cell mass, and resulted in abnormalities in glucose tolerance and insulin tolerance, whereas no significant alterations were observed in females. Lipidomic analyses of mouse pancreas using high-resolution mass spectrometry showed that early-life BPA exposure significantly altered the pancreas of offspring males. Lipid profiles of mouse pancreatic ceramidase gene mRNA expression were upregulated, enzyme activity was enhanced, and pancreatic ceramides, especially long-chain ceramides, were increased in abundance, the latter of which was closely correlated with the increased pancreatic MDA content as well as the decreased SOD enzyme activity. Taken together, our results suggest that early-life BPA exposure may increase the susceptibility of mice to a high-fat diet by altering pancreatic lipid metabolism in mice and that there are significant sex differences in this effect.

Trichloroethylene hypersensitivity syndrome (THS), referred to as occupational medicamentosa-like dermatitis (OMDT) in China, typically manifests several days after exposure to trichloroethylene (TCE) in certain workers. Although our previous research has demonstrated that poly I:C exacerbates TCE-caused hepatitis in mice, the crucial role of poly I:C in THS renal injury remains largely unknown. In the current study, we focus on renal endothelial cell (EC) dysfunction after poly I:C treatment using a TCE-sensitized mouse model. Renal injury was evaluated in mice pretreated with poly I:C and compared to those without pretreatment, and the acetylation of high-mobility group box protein 1 (HMGB1) was also examined. Our results demonstrated that pretreatment with poly I:C worsened TCE-caused histological damage and functional impairment of mice kidneys. Notably, renal EC injury was identified as a key contributor to kidney damage, with poly I:C pretreatment amplifying these effects in the context of TCE sensitization. Moreover, our data showed that poly I:C, through its interaction with toll-like receptor 3 (TLR3), enhanced HMGB1 acetylation and subsequent release from renal ECs. Therefore, these key findings highlight a distinctive role of poly I:C in exacerbating TCE-caused renal EC injury. This study sheds new light on the complex interplay between viral mimicry and chemical sensitization, offering potential mechanistic explanations for THS pathogenesis. Our findings may help shape advanced strategies to prevent viral infections and address renal damage related to TCE exposure, with implications for clinical practice.

Background: Acute intoxications are a critical yet underexplored area in intensive care. Poisoning ranks among the leading causes of injury-related death, but limited data and the lack of clinical guidelines hinder prompt recognition and effective management. This study aims to describe intensive care unit (ICU) admissions for acute intoxications at an Italian tertiary hospital and to identify key factors associated with patient outcomes. Methods: We conducted a retrospective cohort study of patients admitted for confirmed acute intoxication to the ICUs (general, cardiac, and neuro) at Fondazione IRCCS San Gerardo dei Tintori Hospital, Monza, from January 2009 to May 2024. Data included demographics, substance type, intoxication severity, treatments, and outcomes. Results: Among 117 patients (126 intoxication episodes), intentional self-poisoning, often involving psychotropic drugs, was most prevalent. Multiple-substance intoxications made up 55.6% of cases, typically involving medications and ethanol, and were associated with shorter ICU stays and lower mortality than single-substance cases, where toxic agents like cocaine and household/industrial agents led to more severe outcomes. The overall ICU mortality rate was 5.1% (hospital mortality 6%) with a median ICU length of stay of 3 days. Early recognition of intoxication was associated with higher hospital survival rates, whereas lower pH and higher lactate levels were associated with increased hospital mortality. Conclusions: Prompt identification of acute intoxications significantly impacts ICU and hospital outcomes. The findings suggest that early intervention, along with standardized treatment protocols, is crucial to improving patient prognosis and reducing mortality.

The vitamin E derived from palm oil, known as the tocotrienol-rich fraction (TRF), has been reported to possess potent anticancer and immunomodulatory effects in numerous cell-based and animal models of breast cancer (BC). However, only a low dose of TRF (50 mg/kg, equivalent to 1 mg/day) has been tested, which resulted in incomplete effects in a mouse model of BC. In addition, there are no scientific data on the toxic effects of TRF on the internal organs. This study aimed to evaluate the effects of supplementing higher doses of TRF on biochemical parameters and histology of internal organs in female BALB/c mice. In brief, 30 female BALB/c mice were randomly assigned to one of the six study groups (five mice/group). The mice were fed daily with vehicle (control), 50, 100, 150, 200, or 250 mg/kg of TRF for 28 days by oral gavage. The results show that the subacute exposure of TRF showed no toxic effects in the animals from all the groups, as evaluated through some biochemical tests (alanine transaminase (ALT), alkaline phosphatase (ALP), creatine, and urea) and histology of the liver. In conclusion, female BALB/c mice fed daily with 250 mg/kg of TRF showed no signs of distress or adverse effects.

Doxorubicin, an effective antineoplastic agent, is often prescribed for the treatment of various carcinomas. However, the use of doxorubicin becomes limited due to its adverse effects like cardiotoxicity, dysmenorrhea, and leucopenia. Cardiogrit Gold (CG) is a herbo-mineral Ayurvedic medicine prescribed for the treatment of various cardiovascular ailments. The current study aimed to investigate the therapeutic potential of CG in imparting protection against doxorubicin-induced cardiotoxicity. Wild-type (N2) and genetically modified Caenorhabditis elegans(SJ4005 and DA597) were used as model organisms to assess the bioactivity of CG against doxorubicin-induced cardiotoxicity. Chemical characterization of CG was performed by HPLC-based analysis. Calcium, a key mineral component of CG, was measured in CG-treated C. elegans using inductively coupled plasma mass spectrometry (ICP-MS) analysis, as the marker of CG internalization in C. elegans. Toxicity induced by doxorubicin and its recovery upon CG treatment was determined by various toxicologically important endpoints. CG treatment rescued N2 C. elegans from doxorubicin-induced reduction in their growth, reproduction, locomotory behavior, pharyngeal pumping, feeding ability, and increased ROS generation. CG treatment modulated the expression of hsp-4 in SJ4005 C. elegans suggestive of decreased ER stress and normalized the pharyngeal grinder damage in DA597 C. elegans, indicating a robust induction of cardio-normalcy. Novel analytical methods were developed to detect and quantify doxorubicin in C. elegans on HPLC and UPLC/QToF-MS platforms. Interestingly, CG treatment decreased bioaccumulation of doxorubicin in C. elegans, robustly correlating with the observed cardioprotective effects. Taken together, CG has a strong cardioprotective profile against doxorubicin-induced damages and could be taken for further preclinical and clinical assessments.

[This corrects the article DOI: 10.1155/jt/9857933.].

In response to the COVID-19 pandemic and following the World Health Organization's call for action, several traditional medicine recipes were used without any scientific prerequisites concerning their safety. The current study investigated several short-term toxicity parameters of SAYE PLUS, an antimalarial phytomedicine used in COVID-19 patients in Burkina Faso. Following the guidelines of the Organisation for Economic Co-operation and Development (OECD), the safety profile of SAYE PLUS was investigated in a battery of tests in rats and mice. In an acute toxicity study, male and female rats received a single oral dose of 2000 mg/kg b.w. of the test substance. For the subacute toxicity test, male and female rats received daily oral doses of 250, 500, and 1000 mg/kg b.w. for 28 days. Acute and subacute toxicity tests were accompanied by food and water intake, body and organ relative weight, and blood chemistry of animals recording. In mutagenicity, sperm quality, and lipid peroxidation tests, mice were orally exposed to daily oral doses of 500, 1000, and 2000 mg/kg for seven days. Single dose of 2000 mg/kg b.w. of SAYE PLUS did not cause rats mortality. The LD₅₀ is more than 2000 mg/kg b.w. Daily administration of SAYE PLUS for 28 days did not induce any significant change in the water or food intake and the body or organ relative weights of animals. Furthermore, no significant change was observed in biochemical parameters. In the test conditions, the recipe did not induce an increase of micronucleus or changes in sperm motility and number. However, all tested doses of SAYE PLUS induced a significant increase in MDA levels in mice serum. These results show that SAYE PLUS did not induce negative impacts on studied parameters, but the possible lipidic peroxidation observed must be further investigated for its mechanism and effects.

Copra meal hydrolysate (CMH) with high protein and mannooligosaccharides (MOS) was derived by β-mannanase hydrolysis. CMH has been shown to elicit health benefits via prebiotic properties. However, a systematic examination of its safety is required before effective utilization. This study assessed CMH oral acute toxicity at a single dose of 2000 mg/kg for 14 consecutive days, while a subacute toxicity test was conducted by daily oral administration of CMH at doses of 0.25, 0.5 and 1.0 mg/kg for 90 days using Sprague Dawley rats and following OECD guidelines 423 and 408. The acute toxicity study showed that the LD₅₀ of CMH was over 2000 mg/kg since no mortality or abnormal clinical signs were observed at this dose. The subacute toxicity results showed that CMH did not induce any abnormalities in body weight, food and water consumption, clinical signs, haematology, clinical chemistry, organ weight and necropsy. Significant changes in some of the parameters were observed but most were not treatment-related and had no effect on animal health. No toxicity-related microscopic findings were recorded in the examined tissues (lung, heart, liver, spleen and kidneys). Oral administration of CMH had a 'no observed adverse effect level (NOAEL)' of 1.0 mg/kg for both male and female Sprague Dawley rats. CMH demonstrated a high level of safety in animal studies and can be considered a safe prebiotic substance for use in the food and nutraceutical industries.