Acute Toxicity of Jinchuan Formula Plum Wine Extract and Its Protective Effect on Mice with Liver Injury

[Objectives]To investigate the acute toxicity and hepatoprotective effect of Jinchuan formula plum wine extract on mice,determine its safety range,and evaluate its hepatoprotective effect.[Methods]The median lethal dose(LD_(50))was determined by acute toxicity test with the toxic reaction and mortality of mice as indexes.Sixty Kunming mice were randomly divided into 6 groups:normal control group,model group(ConA-induced liver injury model),Jinchuan formula plum wine high,medium and low dose groups(1.0,0.5,0.25 g/kg)and silybin group(0.1 g/kg).The levels of ALT,AST,LDH in serum and TG,VLDL in liver were measured.After HE staining,the pathological changes of liver tissue in mice were observed,and the liver protective effect of Jinchuan formula plum wine extract was analyzed and evaluated.[Results]LD_(50)was 11.18 g/kg,and the 95%confidence limit of LD_(50)was 10.31-12.05 g/kg.The high-dose group of Jinchuan formula plum wine extract could significantly reduce the serum ALT and AST activities of ConA-induced liver injury mice(P<0.05).[Conclusions]Jinchuan formula plum wine extract is relatively safe,and also has a protective effect on liver injury.

Evaluation of the Nutritional Value and Acute Toxicity of the Seeds of the Fruit of Annona muricata L. (Sursop) Consumed in Kinshasa

In this paper, the author aimed to determine the nutritional value of soursop (Annona muricata L. fruit) consumed in Kinshasa as well as the study of the acute toxicity of its seeds. The fruit of Annona muricata L. was sampled according to the ISO 7002 standard for agricultural and food products. The selected fruits were ripe, without physical damage. The usual analytical methods allowed the determination of the nutritional value of the fruit pulp of Annona muricata L. The water content was measured by the method of loss of mass on drying. The total amount of ash was determined by incineration in the oven at 550°C. The mineral elements were determined by inductively coupled plasma spectrometry (ICP0). The determination of acute toxicity was carried out on 25 female mice of the NMRI SUISSE species according to OECD 425 guidelines. For 100 grams of fresh material from the fruit pulp, we noted a very high water content of 84% ± 6%. We also note a particularly high amount of carbohydrates with a rate of 12.2% ± 2%. Protein and lipid content were relatively low at 1% ± 0.01% and 0.7% ± 0.3% respectively. The dietary fiber content was 0.8% ± 0.2%. An energy value of 49.3 Kcal per 100 grams of pulp was determined. The LD 50 obtained was 3320 mg/kg, indicating slight toxicity of soursop seeds. The results of this study show that the white pulp of the fruit of Annona muricata L. consumed in Kinshasa is rich in carbohydrates when we compare it to others biomolecules. It also contains dietary fiber and mineral salts making soursop an excellent constituent of a weight loss diet with a low energy intake.

Acute and sub-acute toxicities of hydroalcoholic extract of Allium affine aerial parts in rats

Objective:To assess the potential toxicity of hydroalcoholic extract of Allium affine(A.affine)aerial parts after acute and sub-acute administration in female and male Wistar rats.Methods:For acute toxicity assay,animals orally received the limit test dose of 2000 mg/kg of A.affine extract and were observed for 2 weeks.For sub-acute toxicity study,rats were orally treated with 125,250,and 500 mg/kg/day of the extract over 28 days,and hematological,biochemical,and histological evaluations were then conducted.Results:All rats were alive with normal body weight gain over 14 days,with LD50˃2000 mg/kg.No abnormality in body weight changes but significant increases in the relative weight of spleen and lung were detected after administration of the highest dose of extract for 28 days in sub-acute assay.Hematological analysis showed prominent elevations in total white blood cells in male rats and neutrophils count in female rats after exposure to 500 mg/kg of A.affine extract.In biochemical evaluations,significant increases in serum creatinine level(female rats,250 and 500 mg/kg)and in aspartate aminotransferase(male and female rate,500 mg/kg)and alanine aminotransferase(male,250 and 500 mg/kg and female,500 mg/kg)activities,however,notable decreases in serum blood glucose(male rats,125 and 500 mg/kg),triglycerides(male rats,500 mg/kg and female rates,250 mg/kg),and low-density lipoprotein cholesterol levels(male,250 mg/kg)were found.Histological examinations presented slight portal inflammation in liver tissue,moderate pneumocyte hyperplasia,congestion and peri-bronchial inflammation in lung tissue,and mild histiocytosis and lymphoid follicular activation in spleen tissue after exposure to 500 mg/kg of A.affine extract in male and female animals.Conclusions:The present investigation reveals the safety of A.affine extract at doses of lower than 250 mg/kg in rats and monitoring of lung,spleen,and liver functions is suggested during excessive and prolonged uses.

Quantitative Correlation of Chromatographic Retention and Acute Toxicity for Alkyl(1-phenylsulfonyl) Cycloalkane Carboxylates and Their Structural Parameters by DFT

Twenty eight alkyl(1-phenylsulfonyl) cycloalkane carboxylates were computed at the B3LYP/6-31G* level. Based on linear solvation energy theory, two quantitative correlation equations of the molecular structures of alkyl(1-phenylsulfonyl) cycloalkane carboxylate com- pounds to their chromatographic retention (capacity factor lgKW) and the toxicity for photo- bacterium phosphoreum (–lgEC50) were developed by using the molecular structural parameters as theoretical descriptors (r2 = 0.9501, 0.9488). The two quantitative correlation equations were consequently cross validated by leave-one-out (LOO) validation method with q2 of 0.9113 and 0.9281, respectively. The result showed that the two equations achieved in this work by B3LYP/6-31G* are both more advantageous than those from AM1, and can be used to predict the lgKW and –lgEC50 of congeneric organics.

Structural Characterization and Acute Toxicity Prediction of Substituted Aromatic Compounds by Using Molecular Vertexes Correlative Index

A molecular structural characterization （MSC） method called molecular vertexes correlative index （MVCI） was used to describe the structures of 30 substituted aromatic compounds. Through multiple linear regression （MLR） and stepwise multiple regression （SMR）, a quantitative structure-toxicity relationship （QSTR） model with 4 variables was obtained. The correlation coefficient （R） of the model was 0.9467. Through partial least-squares regression （PLS）, another QSTR model with 5 principal components was obtained. The correlation coefficient （R） of the model was 0.9518. Both models were evaluated by performing the cross-validation with the leave-one-out （LOO） procedure and the Cross-Validation （CV） correlation coefficients （Rcv） were 0.9208 and 0.9214, respectively. The results suggested good stability and predictability of the models, and the molecular vertexes correlative index could successfully describe the structures of the substituted aromatic compounds.

Holographic quantitative structure-activity relationship for prediction acute toxicity of benzene derivatives to the guppy(poecilia reticulata)

Holographic quantitative structure activity relationship(HQSAR) is an emerging QSAR technique with the combined application of molecular hologram, which encoded the frequency of occurrence of various molecular fragment types, and the subsequent partial least squares(PLS) regression analysis. In this paper, the acute toxicity data to the guppy( poecilia reticulata) for a series of 56 substituted benzenes, phenols, aromatic amines and nitro aromatics were subjected and this resulted in a model with a high predictive ability. The influence of fragment size and fragment distinction parameters on the quality of HQSAR model was investigated. The robustness and predictive ability of the model were also validated by leave one out (LOO) cross validation procedure and external testing data set.

Predicting the Acute Toxicity of Aromatic Amines by Linear and Nonlinear Regression Methods

In current paper, a quantitative structure-activity relationship （QSAR） study was performed for the prediction of acute toxicity of aromatic amines. A set of 56 compounds was randomly divided into a training set of 46 compounds and a test set of 10 compounds. The electronic and topological descriptors computed by the Scigress package and Dragon software were used as predictor variables. Multiple linear regression （MLR） and support vector machine （SVM） were utilized to build the linear and nonlinear QSAR models, respectively. The obtained models with five descriptors show strong predictive ability. The linear model fits the training set with R2 = 0.71, with higher SVM values of R2 = 0.77. The validation results obtained from the test set indicate that the SVM model is comparable or superior to that obtained by MLR, both in terms of prediction ability and robustness.

QSARS for Acute Toxicity of Halogenated Benzenes to Bacteria in Natural Waters

Objective To measure the acute toxicity of halogenated benzenes to bacteria in natural waters and to study quantitative relationships between the structure and activity of chemicals. Methods The concentration values causing 50% inhibition of bacteria growth （24h-IC50） were determined according to the bacterial growth inhibition test method. The energy of the lowest unoccupied molecular orbital and the net charge of carbon atom of 20 halogenated benzenes were calculated by the quantum chemical MOPAC program. Results The logl/IC50 values ranged from 4.79 for 2,4-dinitrochlorobenzene to 3.65 for chlorobenzene. A quantitative structure-activity relationship model was derived from the toxicity and structural parameters： logl/IC50 =-0.531（ELUMO）＋1.693（Qc）＋0.163（logP）＋3.375. This equation was found to fit well （r^2=0.860, s=0.106）, and the average percentage error was only 1.98%. Conclusion Halogenated benzenes and alkyl halogenated benzenes are non-polar narcotics, and have hydrophobicity-dependent toxicity. The halogenated phenols and anilines exhibit a higher toxic potency than their hydrophobicity, whereas 2,4-dinitrochlorobenzene is electrophile with the halogen acting as the leaving group.

Comparison of T-2 Toxin and HT-2 Toxin Distributed in the Skeletal System with That in Other Tissues of Rats by Acute Toxicity Test

Twelve healthy rats were divided into the T-2 toxin group receiving gavage of 1 mg/kg T-2 toxin and the control group receiving gavage of normal saline. Total relative concentrations of T-2 toxin and HT-2 toxin in the skeletal system（thighbone, knee joints, and costal cartilage） were significantly higher than those in the heart, liver, and kidneys（P 〈 0.05）. The relative concentrations of T-2 toxin and HT-2 toxin in the skeletal system（thighbone and costal cartilage） were also significantly higher than those in the heart, liver, and kidneys. The rats administered T-2 toxin showed rapid metabolism compared with that in rats administered HT-2 toxin, and the metabolic conversion rates in the different tissues were 68.20%-90.70%.

Quantitative Correlation of the Acute Toxicity of Phenylthio-carboxylates with Their Structural and Thermodynamic Parameters by DFT Calculation

Phenylthio-carboxylates were computed at the B3LYP/6-31G* level with DFT method. Based on linear solvation energy theory, the structural parameters were firstly taken as theoretical descriptors, and the corresponding linear solvation energy relationship (LSER) equation (r = 0.8989) to the toxicity of photobacterium phosphoreum (–lgEC50) was thus obtained. Then the structural and thermodynamic parameters were taken as theoretical descriptors, and as a result the other corresponding correlation equation (r = 0.9274) relating to –lgEC50 was provided. The two equations achieved in this work by B3LYP/6-31G* are both more advantageous than that from AM1.

Large-scale Purification and Acute Toxicity of Hygromycin B PhoSphotransferase

Objective To provide the acute toxicity data of hygromycin B phosphotransferase （HPT） using recombinant protein purified from E. coli. Methods Recombinant HPT protein was expressed and purified from E. coli. To exclude the potential adverse effect of bacteria protein in recombinant HPT protein, bacterial control plasmid was constructed, and bacteria control protein was extracted and prepared as recombinant HPT protein. One hundred mice, randomly assigned to 5 groups, were administrated 10 g/kg, 5 g/kg, or 1 g/kg body weight of HPT or 5 g/kg body weight of bacterial control protein or phosphate-buffered saline （PBS） respectively by oral gavage. Results All animals survived with no significant change in body weight gain throughout the study. Macroscopic necropsy examination on day 15 revealed no gross pathological lesions in any of the animals. The maximum tolerated dose （MTD） of HPT was 10 g/kg body weight in mice and could be regarded as nontoxic. Conclusion HPT protein does not have any safety problems to human health.

Acute Toxicity of Four Drugs to Larvae of Channa argus

The acute toxicity of 4 drugs, dipterex, potassium permanganate, copper sulfate and formaldehyde to larvae of black-spot hybrid snakehead was tested with the semi hydrostatic test method under water temperature of （28.3± 1.5）℃, pH of（8.01 ±0.12） and dissolved oxygen of （4.6 ±0.5） mg/L. The results showed that 96 h median-lethal concentration （LCso） of copper sulphate was the lowest, 1. 586 mg/L, while 96 h LC50 of formaldehyde was the highest, 115. 159 mg/L. The toxicity of the 4 drugs ranked in the order of copper sulphate, dipterex, potassium permanganate and formaldehyde from high to low. The safe concentrations（SCs） of the 4 drugs were in order of formaldehyde （35. 529 mg/L）, potassium permanganate （ 1. 277 mg/L）, dipterex （ 1. 450 mg/L） and copper sulphate （0.882 mg/L）. According to the rosults,the SCs of dipterex, formaldehyde and copper sulphate were higher than the conventional dosage, they were safe to be used for control of corresponding diseases of Channa argus by the conventional dosage. The SC of potassium permanganate was in the conventional dosage range, so it could be used for control of diseases in accordance with the SC of C. argus to the drug in production.

Acute Toxicity and Cardio-Respiratory Effects of 2-Deoxy-D-Glucose: A Promising Radio Sensitiser

Objective To evaluate the acute toxicity of 2-deoxy-D-glucose （2DG） by oral （p.o.） and intravenous （i.v.） routes, and also the cardio-respiratory effects following high doses of 2DG in animal models. Methods The LD50 of 2DG （in water） was determined in rats and mice by p.o. route and in mice by i.v. route. The effect of 2-DG （250 mg/kg, 500 mg/kg, and 1000 mg/kg, i.v.） was studied on various cardio-respiratory parameters viz., mean arterial blood pressure, heart rate and respiratory rate in anaesthetised rats. The effect of 2DG （500 mg/kg, 1000 mg/kg, and 2000 mg/kg, p.o.） was also studied on various respiratory parameters viz., respiratory rate and tidal volume in conscious rats and mice using a computer program. Results The p.o. LD50 of 2DG was found to be 〉8000 mg/kg in mice and rats, and at this dose no death was observed. The LD50 in mice by i.v. route was found to be 8000 mg/kg. At this dose 2 out of 4 mice died and the death occurred within 6 h. A significant increase in the body weight was observed after p.o. administration of 2DG in rats at 500 mg/kg, 1000 mg/kg, and 2000 mg/kg doses. There was no significant change in the body weight at 4000 mg/kg and 8000 mg/kg by the p.o. route in rats and up to 8000 mg/kg by p.o. as well as i.v. routes in mice. Intravenous administration of 2DG （250 mg/kg, 500 mg/kg, and 1000 mg/kg） in anaesthetised rats showed a time-dependent decrease in the mean arterial blood pressure. There was no change in the heart rate in any of the treatment groups. The tidal volume was not changed significantly by p.o administration in conscious rats, but a significant decrease in the respiratory frequency at 500 mg/kg and 1000 mg/kg doses was observed. In the mice also there was no change in the tidal volume after p.o, administration, but the respiratory frequency decreased significantly at 2000 mg/kg dose. Conclusion 2DG is a safe compound but can cause a fall in the blood pressure and a decrease in respiratory frequency at high doses.

Preparation and Acute Toxicology of Nano-Magnetic Ferrofluid

The nano-magnetic ferrofluid was prepared by chemical coprecipitation and its acute toxicology was investigated. The effective diameter (Eff. Diam.) of the magnetic particles was about 19.9 nm, and the concentration of the ferrofluid was 17.54 mg/ml. The acute toxic reaction and the main viscera pathological morphology of mice were evaluated after oral, intravenous and intraperitoneal administration of the nano-magnetic ferrofluid of different doses respectively. Half lethal dose (LD 50)>2104.8 mg/kg,maximum non-effect dose (ED 0)=320.10mg/kg with oral; LD 50>438.50 mg/kg, ED 0=160.05 mg/kg with intravenous route; and LD 50>1578.6 mg/kg, ED 0=320.10 mg/kg with intraperitoneal administration. Degeneration and necrosis of viscera were not found. So the nano-magnetic ferrofluid, of which toxicity is very low, may be used as a drug carrier.

Acute toxicity of DMAH to Oryzias latipes as modified by some influential factors

As a new insecticide,less information about the aquatic biological toxicity of DMAH [N-(2,4-dimethylphenyl)-N'-methylamidine hydrochloride]is known.Acute 96h static bioassays were conducted with Oryzias latipes to assess the toxicity of DMAH and the influence of environ- mental factors.The results indicated that,at 23℃,the 24h,48h and 96h LC_(50)are 14.6 mg/L,13. 06 mg/L and 12.39 mg/L,respectively,the safe concentration(SC)of DMAH to Oryzias latipes is 1.16-1.32 mg/L.The changes of temperature,pH value and hardness of water will significantly influence the toxicity of DMAH to fish.

Acute toxicity and chromosomal aberration toxicity of insect wax and its policosanol

An acute toxicity test in Sprague Dawley(SD)rats and a chromosomal aberration toxicity test in Chinese hamster lung(CHL)fibroblasts were conducted to promote the application of insect wax and its policosanol.Results of oral acute toxicity test showed that the LD;values of insect wax and its policosanol were higher than 5000 mg/kg.The rats showed no obvious toxic symptoms and survived,suggesting that these substances were not toxic.The chromosomal aberration rates of the CHL cells incubated with insect wax for 3-6 h under metabolic activation conditions and for 3-6 h and 24 h under non-metabolic activation conditions were lower than 5%.No significant difference was found compared with the negative control group.Also,no significant difference in chromosomal aberration rates was found between each dose group of policosanol under metabolic or non-metabolic activation conditions and the negative control group.Therefore,the chromosomal aberration rates of CHL cells treated with insect wax and its policosanol were negative regardless of metabolic activation conditions.These results indicate the absence of acute toxicity and potential chromosomal aberration in the tested dose range of insect wax and its policosanol.

Acute Toxicity of Oxyclozanide Suspension in Mice by Oral Administration

The safety of oxyclozanidc suspension was preliminarily evaluated through acute toxicity test in mice. Administration dose, formal trial grouping and group interval were determined in pre-trial using incremental method. Formal test was performed using simplified karber＇s method. Changes in sign of mice after ad- ministration were observed; the mortality rate was statistically calculated, and the time of death was recorded; the median lethal dose （LD50） and 95% confidence limit of oxyclozanide suspension were calculated. The results showed the LD50 of oxyclozanide suspension in mice by oral administration was 1. 679 g/kg, and the 95% confidence interval was 1. 439 - 1. 947 g/kg. According to toxicity grading of chemicals, oxyclozanide suspension was low toxic substance.

Acute Toxicity and Toxicokinetics of Tongguan Powder in Rats

[Objectives]To evaluate the acute toxicity and toxicokinetics of Tongguan Powder in rats,and provide references for clinical safe medication.[Methods]The classical acute toxicity test method was used,rats were given different doses of Tongguan Powder through the mouth and nasal cavity to observe the symptoms of toxicity,and make a record of the food intake,weight changes,and death.After the medication,blood was taken from each group of rats at different time points,and the plasma levels of benzoyl aconitine(BA),benzoyl hypaconine(BH)and benzoyl mesaconine(BM)were determined by the liquid chromatography tandem-mass spectrometry(LC-MS/MS),and the toxicokinetic parameters were fitted with the aid of DAS software.[Results]Rats were given Tongguan Powder 3.75 g/kg(equivalent to 54 times the human daily dose)in the nasal cavity of rats.Rats were observed with reactions such as scratching and sneezing;rats were given Tongguan Powder LD50 and 95%confidence limit of 4.15(3.53-4.71)g/kg through the oral administration,which is equivalent to 60 times the human daily dose,rats showed slow weight gain,decreased food intake,decreased voluntary activities,prone,black stools,etc.One hour after nasal administration of Tongguan Powder,the plasma concentration of benzoyl aconitine and benzoyl hypaconine was below the lower limit of detection,and benzoyl mesaconine could not be detected at any time point;one hour after the oral administration of Tongguan Powder,the plasma concentration of the three components reached the maximum,the exposure level of benzoyl hypaconine was higher than that of benzoyl aconitine and benzoyl mesaconine;there was no gender difference in the kinetic parameters.[Conclusions]The toxicity of Tongguan Powder in nasal administration is much lower than that of intragastric administration.The target organs and mechanism of toxicity need to be further studied.

Estimation of Acute Toxicity of Ammonium Sulphate to the Fresh Water Catfish,Heteropneustes fossilis——Ⅰ.Analysis of LC_(50) Values Determined by Various Methods

The acute toxic effects of ammonium sulphate to fresh-water catfish, Heteropneustes fossilis (H.fossilis) have been studied by determining LC50 values with 95% confidence limits, by the graphic method, the logistic method, the Spearman and Karber method and the trimmed Spearman-Karber method. The trimmed Spearman-Karber method was found the most ideal for ammonium salt toxicity test. The flaws in the trimmed Spearman-Karber method are also discussed.

Acute Toxicity of Aluminium Phosphide Following Oral Administration in Rats

Aluminium phosphide (AlP) is used as a fumigant and also sometimes misused for suicidal attempts in India, due to its easy availability. The effect of phosphine, the gas that is liberated when AlP comes in contact with moisture, is well documented in the literature. However, the effect of AlP in its native form on animal models is not well cited. In this study we examined the acute toxic effect of AlP in rats. Oral LD50 of AlP for male and female rats were found to be 14. 13 and 11. 89mg/kg, respectively. Oral administration of an AlP dose of 0. 80 LD50 resulted in significant increases in the level of plasma glutamic oxaloacetic transaminase,alkaline phosphatase, glucose and urea in rats of both sexes. Hemoglobin level and packed cell volume also increased significantly 6h after administration. Body weight was reduced but the organ to body weight ratio of lung, liver, spleen, kidney and testes remained unchanged.Histopathological changes induced by AlP during 24-48h induced hemorrhage, congestion and mild to moderate atrophy of various cellular components of visceral organs. The study showed that the acute toxic effect of AlP may be due to hypovolemic shock. Female rats were found to be more susceptible than were males.