Subchronic Toxicity Experiments Research Articles

Aristolochia bracteolata Lam’s Toxicity Profile and Neuroprotective Effects in Mice with Memory Impairment Triggered by Scopolamine

Aim The present study aims to investigate the toxicity profile and neuroprotective effect of ethanol crude extract of Aristolochia bracteolata (EEAB) leaves in mice. Materials and Methods EEAB was subjected to preliminary phytochemical screening and gas chromatography–mass spectrometry (GC–MS) analysis. To determine the toxicity profile in Swiss albino mice, acute and subchronic toxicity experiments were performed according to Organisation for Economic Co-operation and Development criteria. A behavioral test in mice with drug-induced learning and memory impairment was performed to determine neuroprotective effects. Results In the study GC–MS, 19 compounds were detected. Compared to the control group, no clinical signs of toxicity were detected in the plant-treated group in both the acute and subchronic toxicity experiments at the highest dose of 2,000 mg/kg. It was calculated that the mean oral lethal dose (LD50) > was 2,000 mg/kg. Scopolamine-induced cognitive deficits in mice were greatly reduced after pretreatment with the EEAB at a dose of 100 mg/kg p.o. This was demonstrated by the reversal of the improvement in spontaneous alternation in the Y-maze task and by the significant improvement in latency in the passive avoidance task. Conclusion Based on the results, EEAB might contain potent secondary metabolites that would primarily enhance the neuroprotective effects and cognitive deficits induced by cholinergic dysfunction.

Red Amaranth (Amaranthus tricolor L.) Irrigated with Domestic Sewage Wastewater as a Source of Irrigation: Environmental Food Security and Safety Assessment Perspectives through Acute and Sub- Acute Toxicity Study

Water deficiency is one of the main factors for limiting sustainable agricultural development in most arid and semi-arid regions. There is a gradual decline in the availability of fresh water to be used for irrigation in developing countries like India. Sewage farming is quite common in all urban areas in India. The effect of its direct and long-term use for irrigation needs a thorough study. However, there is increasing concern about food safety and health risks, hence, a case study was undertaken to understand the long-term effect of domestic sewage wastewater irrigation on heavy metal concentrations in soil and plants. The study reveals the mineral and heavy metal composition of irrigated domestic sewage wastewater and it has been compared with the well water irrigated in the rural area, soil parameters and also the mineral and heavy metal composition of a cultivated plant, Amaranthus tricolor L. Transfer factor (TF) was calculated to understand the extent of risk and associated hazard due to wastewater irrigation and the consequence of heavy metals accumulation in the edible portion of experimented vegetables. The present study was carried out to assess the potential toxicity of acetone extract of A. tricolor with some essential parameters such as haematological and biochemical parameters, liver and kidney weight and their histopathological study. After conducting in vivo acute and subchronic toxicity experiments using the rat model, there was no toxicity or mortality observed between domestic sewage water and well water irrigated to red amaranth, A. tricolor.

Toxicological Safety Evaluation in Acute and 21-Day Studies of Ethanol Extract from Solanum lyratum Thunb.

Solanum lyratum (Solanaceae) is a traditional Chinese medicine widely used to remedy cold fever, damp-heat jaundice, herpes, and nephritis dropsy. Despite its obvious therapeutic advantages, few toxicological studies have involved the efficacy and safety of its long-term treatment. To investigate the acute and subchronic toxicity of the extract of 75% ethanol extract of whole Solanum lyratum (ESL) after oral administration in mice. In acute toxicity experiment, mice were intragastric administration with ESL at doses of 1000, 2000, 3000, 4000, or 5000 mg/kg for 1 day. In a subchronic toxicity experiment, mice were intragastrically administration with ESL at doses of 180, 360, and 720 mg/kg and 0.9% saline for 21 days. Weight gain, hematological, biochemical, and histopathological analysis of vital organs were evaluated. The presence of aristolochic acid I in ESL was studied using UPLC-QTOF-MS. Phytochemical analysis indicated that the presence of aristolochic acid I in ESL was 0.0025 mg/g. This relatively low concentration is not enough to cause toxicity. In the acute toxicity experiment, neither mortality nor clinical alterations were shown, except for the mild transient diarrhea at 5000 mg/kg. So the LD50 value of ESL was assessed to be more than 5000 mg/kg. In the subchronic toxicity experiment, neither mortality nor treatment-related clinical signs were observed. There was a significant increase in body weight, hemoglobin (HB), and urea nitrogen (BUN) after administration with ESL at 180 mg/kg. In addition, the weight of the stomach was increased and the hematocrit (HCT) was decreased after administration with ESL at 360 mg/kg. The changes were not considered treatment-related toxicological effects because the toxicity and histopathological analysis indicate that the extracts are safe for oral administration.

The accumulation and toxicity of ZIF-8 nanoparticles in Corbicula fluminea

Metal-organic frameworks (MOFs) are promising new materials that have been intensively studied and possibly applied to various environmental remediation. However, little is known about the fate and risk of MOFs to living organisms in the water environment. Here, the toxic effects of ZIF-8 nanoparticles (NPs) on benthic organisms were confirmed by sub-chronic toxicity experiments (7 and 14 days) using Corbicula fluminea as the model organism. With exposure doses ranging from 0 to 50 mg/L, ZIF-8 NPs induced oxidative stress behaviors similar to the hormesis effect in the tissues of C. fluminea. The oxidative stress induced by ZIF-8 NPs and the released Zn2+ was the crucial cause of the toxic effects. Besides, we also found that the ZIF-8 NPs and dissolved Zn2+ may result in different mechanisms of toxicity and accumulation depending on the dosages. The Zn2+ release rate of ZIF-8 NPs was high at low dosages, leading to a higher proportion of Zn2+ taken up by C. fluminea than the particulate ZIF-8. Conversely, at high dosages, C. fluminea mainly ingested the ZIF-8 NPs and resulted in increased mortality. The results have important implications for understanding the fate and biological effects of ZIF-8 in natural aquatic environments.

Toxicity of Cypermethrin-chlorpyrifos and Butachlor to Tadpole of Quasipaa boulengeri

The tadpole of Quasipaa boulangeri was taken as the research object in this paper. The toxic effects of cypermethrin-chlorpyrifos and butachlor on tadpole of Q.boulangeri were studied by acute toxicity experiment and subchronic toxicity experiment in order to master the toxicity of different types of pesticides on tadpole of Q.boulangeri and provide scientific basis for amphibian protection. The results of acute toxicity experiment were analyzed by the method of probability unit regression analysis. The results of the acute toxicity experiment were analyzed by means of the probability-unit regression analysis method, and the LC50 of cypermethrin-chlorpyrifos and butachlor to the 2-month-old frog tadpoles at 24h, 48h, 72h and 96h were 0.419, 0.357, 0.346L, 0.332 and 1.183, 1.108, 0.925 and 0.876(mg/L), respectively. In the subchronic toxicity experiment, we observed the accumulation effect of different concentrations of pesticides on tadpoles through the statistics of the growth and development of tadpoles exposed to the drugs for a long time. The results suggested that the body length and body weight of tadpoles increased slowly with the increase of time and concentration of pesticide in the solution during the experiment.

Subchronic Toxicity Assessment of Orally Administered Methanol (70%) Seed Extract of Abrus precatorius L. in Wistar Albino Rats.

Abrus precatorius L. is a famous medicinal plant of the family Fabaceae and is widely used in traditional medicine for the treatment of various ailments. However, there are limited toxicological data available regarding its safety following repeated exposure; therefore, the present study was designed to evaluate the 28-day subchronic toxicity of methanol (70%) crude extract of A. precatorius seeds in adult Wistar albino rats. A subchronic toxicity experiment was conducted by oral administration of graded doses (200 mg/kg and 400 mg/kg) of test extract daily for 28 days. Signs of toxicity, food and water consumption, body weight, and gross pathology as well as relative organ weight were evaluated. The toxic effects were also assessed using hematological and biochemical data followed by histopathological examination of various internal organs. All data collected were expressed as mean ± standard deviation. ANOVA followed by the Bonferroni test was used for data interpretation and p<0.05 was considered significant. No deaths or evident toxic signs were found during the experimental period. There were no significant differences in body weight, gross pathology, organ weight, or food and water consumption between the control and the treated groups. There were no treatment-related differences in hematological or biochemical indices. Moreover, no gross abnormalities or histological alterations were observed. The methanol extract of A. precatorius seeds was nontoxic in subchronic intake at the dosages tested. Thus, this study is expected to be beneficial for clinical and traditional applications for safe consumption and to utilize A. precatorius as a remedy at a recommended dosage.

Phytochemical constituents, antioxidant activity and safety evaluation of Kei-apple fruit (Dovyalis caffra)

Present study was conducted to determine phytochemical constituents of Kei-apple fruit grown in Egypt, to evaluate antioxidant activity of the fruit extracts, and assess the safety of whole fruit extract (WFE) in acute and sub-chronic toxicity experiments using rats model. Chlorogenic acid and pyrogallol were the main identified phenolic compounds in dry fruits. Malic acid was the most abundant organic acid. The whole fruit extract exhibited higher antioxidant activity than the flesh extract (FE). The fatal dose of the extract is more than 6000 mg/kg b.w. In sub-chronic experiment, hemoglobin, red blood cells, total white blood cells and mean cell hemoglobin values did not significantly alter when male and female rats ingested 1000 mg/kg D. caffra WFE. Biochemical analysis showed some significant changes especially in female rats.

Pyrolysis of Arundo donax L. to produce pyrolytic vinegar and its effect on the growth of dinoflagellate Karenia brevis

Harmful algal blooms (HABs) have become global environmental issues, and the demand for alternative algaecides is urgent. Pyrolytic vinegars (PVs) were pyrolyzed from giant reed at 300–600°C to investigate the underlying mechanisms of their inhibitory effect on the red tide dinoflagellate Karenia brevis by sub-chronic toxicity experiments. The major components of PVs were acetic acid, phenols, aldehyde, ketone, and esters. The 96h median effective concentration (96h-EC50) values of PVs were 0.65–1.08mLL−1, and PV300 showed the strongest inhibitory effect. The increased contents of reactive oxygen species (ROS) and malondialdehyde, antioxidant enzymes activities indicated that K. brevis cells were suffering from oxidative stress, leading to lipid oxidation and cell structure damage. The sites of ROS accumulation in the treated cells were chloroplasts and mitochondria. These results suggest the suitability of PVs as potential algaecides for HAB control, and also provide a new direction for biomass valorization.

Safety pharmacology and subchronic toxicity of jinqing granules in rats

BackgroundJinqing granules which are made of a mixture extract that contains Radix Tinosporae and Canarii fructus in proportions according to a longstanding formula have a good effect on the prevention and treatment of gastric ulcer disease. It has not been through safety through systematic toxicological studies, however. To provide basis for clinical application, we performed safety pharmacology and subchronic toxicity experiments in specific pathogen-free Sprague-Dawley rats.ResultsIn safety pharmacology experiments, Jinqing granules had no evident adverse effects on the central nervous, cardiovascular, or respiratory systems. In subchronic toxicity study, 2–8 g/kg of Jinqing granules induced no evident adverse effects on Clinical signs, body weight changes, food and water intake, death daily, indicators of urine, hematological assay, serum biochemistry, organ coefficient and histopathological examination. However, the 16 g/kg dose was associated with slightly slowed weight growth, decreased number of sperm in seminiferous tubules and increased values of serum aspartate aminotransferase and bilirubin. During the 30-day feeding test, 3 rats that received the 16 g/kg dose died, but the deaths were most likely due to trauma of oral gavage, not to drug toxicity.ConclusionJinqing granules given to Sprague-Dawley rats orally for 30 days at a dose of 8 g/kg or less appears safe, but higher doses were not proven safe. The significance of these observations with respect to animal usage of Jinqing granules deserves thorough investigation.

Acute and Sub-chronic Toxicity Analyses of Hot-Water Extract of Isaria japonica from Silkworm (Bombyx mori) Pupae

Medicinal combinations of Isaria japonica (Paecilomyces tenuipes, Paecilomyces japonica, and Isaria tenuipes) and the silkworm Bombyx mori are commercially available in Japan, China, and Korea. Isaria japonica exhibits host specificity for lepidopteran insects and can be cultured in the insect’s body. Recently, a hot-water extract of an I. japonica product (“IJE”) was shown to prevent brain function decline in aging mice. Therefore, evaluating the safety profile of IJE is worthwhile. Acute toxicity experiments were performed on adult female ICR mice (8-10 weeks old; 25-35 g). Sub-chronic toxicity experiments on adult female Wistar rats (8-10 weeks old; 130-150 g) assessed general behavior, mortality, body weight, food + water consumption, hematology, blood chemistry, relative organ weights and histopathology. IJE caused neither significant visible signs of toxicity nor mortality in ICR mice. In the sub-chronic toxicity analysis, administration of IJE to Wistar rats at doses of 25 and 500 mg/kg for 28 consecutive days did not cause mortality. No significant differences were found in food or water consumption, hematological parameters, or relative organ weights between the treated and control groups. IJE appears to be safe when administered orally. Keywords: Acute toxicity, Animals, Biochemical parameters, Hot-water extract, Isaria japonica, subchronic toxicity.

Effects of genetically modified T2A-1 rice on the GI health of rats after 90-day supplement

Bacillus thuringiensis insecticidal toxin (Bt) rice will be commercialized as a main food source. Traditional safety assessments on genetically modified products pay little attention on gastrointestinal (GI) health. More data about GI health of Bt rice must be provided to dispel public' doubts about the potential effects on human health. We constructed an improved safety assessment animal model using a basic subchronic toxicity experiment, measuring a range of parameters including microflora composition, intestinal permeability, epithelial structure, fecal enzymes, bacterial activity, and intestinal immunity. Significant differences were found between rice-fed groups and AIN93G-fed control groups in several parameters, whereas no differences were observed between genetically modified and non-genetically modified groups. No adverse effects were found on GI health resulting from genetically modified T2A-1 rice. In conclusion, this study may offer a systematic safety assessment model for GM material with respect to the effects on GI health.

3, 4- dinitro-furazan-based oxidation furazan acute and subchronic toxicity studies

To study the 3, 4- dinitro-furazan-based oxidation furazan (DNTF) of sub-acute toxicity and chronic toxicity, to determine the acute toxicity classification DNTF, the nature of toxic effects and major target organ for the development provide the basis for occupational exposure limits. ( 1) Acute toxicity: The oral gavage method once infected, symptoms of poisoning of animals observed to calculate the LD50DNTF and 95% confidence limits. ( 2) sub-chronic experiment: selection of 96 healthy SD rats were randomly divided into four groups, doses of 25, 56.2, 125 mg/kg and the negative control group, Exposure for ninety days,five days a week, once a day, The rats were killed at end of Exposure, heart, liver, spleen, lung, kidney, brain,testis, uterus were taken to observe the pathological changes. ( 1) Acute oral toxicity test results indicate that DNTF rat oral LD50 greater than 5000 mg/kg, DNTF mice treated by oral LD50 4589 mg/kg, 95%confidence limit for the 4026-5230 mg/kg, Acute toxicity grade level is low toxicity compounds. (2) Sub-chronic toxicity experiment, the high-dose male rats, high, medium and low-dose group female rats weight gain than the negative control group, compared with the control group, the difference was statistically significant (P<0.05).125 mg/kg of serum alanine aminotransferase, aspartate aminotransferase was significantly higher. 125 mg/kg dose groups, liver, kidney, lung, testicular factor was significantly higher. Liver, kidney, lung histological examination showed obvious morphological changes. Acute toxicity grade DNTF low toxicity level compounds, target organ toxicity of liver, kidney and lung.

Ozonolysis efficiency and safety evaluation of aflatoxin B1 in peanuts

Ozonolysis efficiency of aflatoxin-contaminated peanuts (ACPs) was investigated, and the safety of ACPs untreated/treated by ozone was evaluated after 28-day intragastrically administration in male and female Wistar rats. 89.40% of aflatoxin B1 (AFB1) in peanuts was decomposed by ozone with a concentration of 50mg/L, flow rate of 5L/min for 60h. After 60h, the ozonolysis efficiency of AFB1 was not further improved. In the subchronic toxicity experiment, all rats did not have unusual changes in behavior, and no signs of intoxication were observed except for several dead rats due to inappropriate gavage or anesthesia. The results of subchronic toxicity indicated that rats fed on ACPs alone had significantly decreased in body weight gain and feed conversion efficiency. Most serum biochemical indexes of rats had apparently changed compared with those in the negative control, and gender difference significantly affected most indexes of subchronic toxicity except for the ratios of organ to body weight and histopathological observation. Rats fed on ACPs treated by ozone showed significant beneficial health effects. All the results suggested that the deleterious effects of AFB1 could be highly reduced by ozone, and ozone itself did not show any toxic effects on animals in this processing.

오공약침(蜈蚣藥鍼)에 대한 연구현황분석(硏究現況分析)과 치료법(治療法)에 관한 연구(硏究)

Objectives : We review a result of studies until the present and suggest the method of medical treatment for the clinical treatment of Scolopendrid Herbalacupuncture. Methods : We analysis the paper of the bibliographic studies, the experiment studies and the clinical studies from 2001 developed Scolopendrid Herbalacupuncture and grope for the course of studies. Results : 1. Scolopendrid Herbalacupuncture is proved the clinical safety by the aninmal and human tests. 2. The pharmacological action of Scolopendra subspinipes mutilans L. Koch is anti-convulsive action, analgesic action, lowering blood pressure, anti-inflammatory action, anti-tumor action and microbe inhibition 3. Scolopendrid Herbalacupuncture has been a fine effect to the entrapment neuropathy and inflammatory. 4. Scolopendrid Herbalacupuncture was thought effective on a acute phase and to the excessive symptoms. The Sub-chronic toxicity experiment observing the response after hypodermic medication over 90 days, The Genetic-mutagenic toxity experiment and the clinical effect studies are necessary.

Dynamics of microcystins-LR and -RR in the phytoplanktivorous silver carp in a sub-chronic toxicity experiment

A sub-chronic toxicity experiment was conducted to examine tissue distribution and depuration of two microcystins (microcystin-LR and microcystin -RR) in the phytoplanktivorous filter-feeding silver carp during a course of 80 days. Two large tanks (A, B) were used, and in Tank A, the fish were fed naturally with fresh Microcystis viridis cells (collected from a eutrophic pond) throughout the experiment, while in Tank B, the food of the fish were M. viridis cells for the first 40 days and then changed to artificial carp feed. High Performance Liquid Chromatography (HPLC) was used to measure MC-LR and MC-RR in the M. viridis cells, the seston, and the intestine, blood, liver and muscle tissue of silver carp at an interval of 20 days. MC-RR and MC-LR in the collected Microcystis cells varied between 268–580 and 110–292 μg g −1 DW, respectively. In Tank A, MC-RR and MC-LR varied between 41.5–99.5 and 6.9–15.8 μg g −1 DW in the seston, respectively. The maximum MC-RR in the blood, liver and muscle of the fish was 49.7, 17.8 and 1.77 μg g −1 DW, respectively. No MC-LR was detectable in the muscle and blood samples of the silver carp in spite of the abundant presence of this toxin in the intestines (for the liver, there was only one case when a relatively minor quantity was detected). These findings contrast with previous experimental results on rainbow trout. Perhaps silver carp has a mechanism to degrade MC-LR actively and to inhibit MC-LR transportation across the intestines. The depuration of MC-RR concentrations occurred slowly than uptakes in blood, liver and muscle, and the depuration rate was in the order of blood>liver>muscle. The grazing ability of silver carp on toxic cyanobacteria suggests an applicability of using phytoplanktivorous fish to counteract cyanotoxin contamination in eutrophic waters.