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.

Determination of the Mineral Composition of the Pulp and Evaluation of the Acute Toxicity of the Seeds of Carica papaya L. Consumed in Lubumbashi and Kinshasa in the Democratic Republic of the Congo

This work aimed, on the one hand, to determine the mineral and phytochemical composition of Carica papaya in order to guarantee the food safety of consumers and on the other hand, to evaluate the acute toxicity of papaya seeds. The papayas were bought at the Mzée market in Lubumbashi and Selembao in Kinshasa. Fruit sampling was done according to the ISO 7002 standard on agricultural and food products;the papayas were firm, mature, and without stains or physical damage. The analysis results of the papaya pulp showed both for the samples from the city of Lubumbashi and for the city province of Kinshasa that it contains respectively 85.87% and 84.46% water, 0.59% and 0.53% ash content. The mineral evaluation of our two samples presented a potassium content of 200 ± 8 mg, magnesium 13.12 ± 3 mg, calcium 22.15 ± 2 mg, sodium 3 mg ± 0.5 for the sample from Lubumbashi and 192.32 ± 8 mg of potassium, 14.458 ± 3 mg of magnesium, 20.58 ± 2 mg of calcium and 3.58 ± 0.5 mg of sodium for the sample from Kinshasa in macroelements. Concerning the trace elements, after analysis, we found zinc content (0.29 ± 0.1 mg and 0.12 ± 0.1 mg), copper (0.02 ± 0.01 mg and 0.14 ± 0.01 mg), and iron (2.22 ± 0.5 mg and 2.04 ± 0.5 mg) respectively for Lubumbashi and Kinshasa. The chemical screening indicates the presence of alkaloids, saponosides, tannins catechics, flavonoids and anthocyanins in the palm wine and ethanolic extract of the seeds of Carica papaya and an absence of cyanogenic glycosides and gallic tannins. With mild toxicity, the seeds of the fruit of Carica papaya L. can be used with moderate risk by the population.

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-Chronic Toxicity Evaluation of the Crude Methanolic Bark Extract of Bridelia micrantha (Hochst.) Baill. (Phyllanthaceae) and Its Fraction

Bridelia micrantha, commonly known as coastal golden leaf, is a member of the family Phyllanthaceae. In preliminary studies nine fractions, named F1 - F9, were obtained by fractionating the crude methanol extract of the stem bark of Bridelia micrantha using column chromatographic techniques. The fraction F6 was the most active when tested for antibacterial activity. Thus, toxicity of this fraction was investigated for further use. The present study evaluated the acute and sub-chronic toxicity of the crude methanolic bark extract of Bridelia micrantha and its fraction. The acute toxicity was carried out according to the experimental protocol of Organization for Economic Co-operation and Development (OECD). The plant extract or the fraction F6 was administered orally to female mice at a single dose of 2000 mg/kg and the animals were observed for any behavioral changes or mortality for 14 days. In the sub-chronic toxicity study, the extract and fraction were administered orally at 200, 400 and 800 mg/kg bw/day for 28 days to healthy Wistar rats. The general behavior and body weight of the rats were recorded daily. At the end of the experimental period, hematological and biochemical analyses, changes in vital organ weight (liver, lung, heart, spleen and kidney), and histopathological examination of the liver and kidney were performed. No mortality or adverse effects were noted at the 2000 mg/kg dose during the oral acute toxicity test. In the sub-chronic study, the crude methanolic bark extract of Bridelia micrantha and the fraction F6 induced no mortality or treatment-related adverse effects on body weight, general behavior, relative organ weights, hematological and biochemical parameters. Histopathological examination of the liver and kidney showed normal architecture suggesting no morphological alterations. In conclusion, the oral administration of the crude methanolic bark extract of Bridelia micrantha and the fraction F6 for 28 days at a dosage of up to 800 mg/kg did not induce toxicological damage in rats. From acute toxicity study, the median lethal dose (LD50) of the crude methanolic bark extract of Bridelia micrantha and the fraction F6 was estimated to be more than 2000 mg/kg.

Acute Oral Toxicity Test of Radix aconiti lateralis preparata in Kunmin Mice

[Objective] This study aimed to investigate the acute oral toxicity of crude monkshood （Radix aconiti lateralis preparata）. [Method] Monkshood alcohol extract was prepared using soxhlet extractor. The maximum drug dose, which was the minimum dose causing 100% lethally rate in the preliminary test, was diluted into seven con- centrations in formal test. Then every mouse was orally administrated with 0.04 ml/g of the monkshood solution at single time for 7 d. Median lethal dose （LD50） and 95% confidence limit were calculated by the improved Karber method formulas. [Result] LD50 of monkshood ethanol extract was 230.12 mg/kg and 95% confidence limit of LD50 was 80.39-658.57 mg/kg. [Conclusion] Crude monkshood alcohol extract can quickly induce acute toxicity in mice.

Study on the Acute Toxicity and Genetics Toxicity of Bensulfuronk-methyl on Danio rerio

[Objective] The aim was to study the effect of bensulfuron-methyl herbicide on acute toxicity and genetics toxicity of Danio redo. [ Method] Median lethal concentration was calculated by acute toxicity test, and analyzing the herbicide whether existing in potential toxicity to aquatic organisms or not. Based on the study of acute toxicity, genetics toxicity was carried out, by calculating the micronucleus rate to judge bensulfuron-methyl herbicide whether existing in potential toxicity or not. [ Result ] The LD5o （24 h and 48 h） of bensulfuron-methyl herbicide are 0.698 ml/L and 0.637 ml/L respectively, the safe concentration was 0.159 ml/L. The results on the effects of micronucleus （MN） in erythrocytes of Danio redo induced by bensulfuron-methyl at different times and different concentrations showed that the MN rate of control group was 0.010 3%, the highest MN rate of experimental group reached to 0. 372%, it also indicated that bensulfuron-methyl herbicide had genetics toxicity to Danio redo. At the same detection time, there was dose-effect relationship of MN rate in erythrocytes between treatment and control groups with different concentrations. In the same treatment group, the MN rate in erythrocytes reached to peak value at 24 h, and decreased at 48 h and 72 h with the infection time was prolonged. [ Conclusion ] The study provides some basis for scientifically selecting and reasonably using herbicide.

Acute Toxicity Test of Chinese Herbal Compound Tongmai Tangyanming Capsule

[Objective] This study was conducted to determine the safe dose of Tongmai Tangyanming capsule in clinic by evaluating its acute toxicity, so as to ensure clinical medication safety. [Method] The test was designed according to ＂Technique Requirements of Research of New Chinese Medicine＂ and ＂Guide for Research of New Chinese Medicine＂, mice were intragastrically administrated with Tongmai Tangyanming capsule at a maximum concentration and a maximum volume, and the acute toxic response of mice was observed, so as to determine medi- na lethal dose （LDso） and maximum administration dosage of Tongmai Tangyanming capsule. [Result] The LD^o could not be detected in the test, and the maximum administration dosage of mouse was calculated to be 112.104 g of dried herbs/（kg.d）, equivalent to 260 times of clinical dose of adult. [Conclusion] Chinese herbal compound Tongmai Tangyanming capsule has low acute toxicity, and its clinical dose is safe and reliable.

Acute Toxicity of Two Pyrethroids Insecticides on Brachionus calyciflorus

[ Objective] The paper was to study the 24 and 48 h acute toxicity of common pyrethroid insecticides of eypermethrin and deltamethrin on Brachionus calyciflorus. [ Method ] With Guangzhou strain of B. colyciflorus as test animal, the standard toxicity test method was used to carry out acute toxicity test, and LC50 of cypermethrin and deltamethrin on rotifer was determined using probit method. [ Result ] LC50 of cypermethrin on rotifer was 3 376.87 and 5.87 μg/L at 24 and 48 h, respectively, and those of deltamethrin on rotifer was 594.56 and 74.17 μg/L, respectively. [Condusion] Acute toxicity of cypermethrin and dehamethrin on rotifer at 24 and 48 h was different, LC50 of cypermethrin and deltamethrin on rotifer at 48 h was more sensitive to monitor the chemical pollutants in water body than LC50 at 24 h.

Acute Toxicity of Oxytropis Kansuensis Bunge on Rats

[ Objective] The paper was to study the acute toxicity of Oxytropis Kansuensis Bunge on rats. [ Method ] Forty rats were randomly divided into two gToups： control group （distilled water） and trial group （water extract of 0. Kansuens/s） to carry out the acute toxicity experiment. The trial group was supplied with the maximum dose （6.0 g/ml,0.8 ml/20 g） twice per day for continuous 7 d. [Result] The maximal tolerance dose of rats to water extract of O. Kansuens/s was more than 480 g/kg. Feeding rats with O. Kansuens/s would not lead to the death of rats within short time （7 d） and no obvious macroscopic pathological changes in the viscera of rats could be seen in naked eyes. [Condusion] The study provided theoretical basis for full use of O. Kansuens/s resources.

Acute Toxicity of Recombinant Porcine Interferon-alpha

To observe the acute toxicity of recombinant porcine interferen-alpha （IFN-alpha） in mice and thus provide a basis for the clinical safety. [Method] According to the principles of acute toxicity, all the mice were divided into two major groups （intraperitoneally injected group and intramuscularly injected group） respectively at high dose, moderate dose and low dose. And the normal control group was also set up. Within 14 d after administration, the behavior of mouse and the degree of toxicity were continuously observed. The hematological indexes and biochemical indexes of blood were detected to obtain the preliminary toxicity data of the recombinant porcine IFN-alpha. And at the end of the experiment, mice were sacrificed for autopsy. [ Result] There was not significant difference in external performance, behavioral characteristics, body temperature, weight, pathological anatomy of visceral organs, hematological indexes and biochemical indexes between the experimental groups and the control group. [ Conclusion] The highest dose of porcine interferon （5.0 x 10s IU per mouse） in this experiment or the dose lower than this dosage should not have significant toxic effects on mice, and the recombinant porcine IFN-alpha is safe in clinical application.

Acute toxicity of live and decomposing green alga Ulva (Enteromorpha) prolifera to abalone Haliotis discus hannai

From 2007 to 2009, large-scale blooms of green algae (the so-called "green tides") occurred every summer in the Yellow Sea, China. In June 2008, huge amounts of floating green algae accumulated along the coast of Qingdao and led to mass mortality of cultured abalone and sea cucumber. However, the mechanism for the mass mortality of cultured animals remains undetermined. This study examined the toxic effects of Ulva (Enteromorpha) prolifera, the causative species of green tides in the Yellow Sea during the last three years. The acute toxicity of fresh culture medium and decomposing algal effluent of U. prolifera to the cultured abalone Haliotis discus hannai were tested. It was found that both fresh culture medium and decomposing algal effluent had toxic effects to abalone, and decomposing algal effluent was more toxic than fresh culture medium. The acute toxicity of decomposing algal effluent could be attributed to the ammonia and sulfide presented in the effluent, as well as the hypoxia caused by the decomposition process.

Experimental Study on Acute Toxicity of Yusheng Xiaoyang Lotion in Mice

[Objective] This study was carried out to provide toxicological basic data for the development and research of Yushen Xiaoyang Lotion.[Method]SPF SD mice, half male and half female, were divided into a blank control group and a Yusheng Xiaoyang Lotion group randomly. The percutaneous acute toxicity of Yusheng Xiaoyang Lotion was observed by one time limited dose method, and ap-parent sign changes and death condition of mice after administration of the drug were recorded. After the test, all the animals were weighed and subjected to gross anatomy, and if there were abnormal phenomena, further histopathological examina-tion of should be done. Animals died during the test should be subjected to anato-my. [Result] All the mice survived and exhibited normal behavior,glossy hair and increase of body weight in accordance with growth law.No local and systematic toxicity responses on skin were observed. In visual observation after dissection, no pathologic changes on heart, liver, spleen, lung and kidney were observed. There were no significant differences in body weight between the Yusheng Xiaoyang Lo-tion group and the blank control group before administration,the 7th d after adminis-tration and the 14th after administration （P〉0.05）. [Conclusion] In the transdermaldrug delivery acute toxicity test of Yusheng Xiaoyang Lotion on mice, no obvious toxic responses were observed under the total dose of 89.70 g/kg （equivalent to 120 times of the clinical daily dose for adults）.

Acute Toxicity of Clethodim, Cypermethrin and 2,4-D-butylate to the Larva of Chironomus sinicus

[Objective] The aim of this study was to detect the acute toxicity of clethodim, cypermethrin and 2,4-D-butylate. [Method] Chironomus sinicus larvae were exposed to different concentrations of clethodim, cypermethrin and 2,4-D-butylate. Survival rate, lethal concentration 50 （LC50） and superoxide dismutase （SOD） activity in the homogenate of the larvae were monitored to detect the toxicity of the pesti- cides. [Result] The survival rates of C. sinicus larvae exposed to cypermethrin and 2,4-D-butylate for 12 h were almost unchanged at different concentrations, but de- creased with concentration increasing 48 h later. For each pesticide, the differences in survival rates of C. sinicus larvae at 48 h were significant. The 48 h LC50 of clethodim, cypermethrin and 2,4-D-butylate to C. sinicus larvae were 1.842, 0.150 and 1.999 mg/L, respectively. The acute toxicity of cypermethrin was the highest a- mong the three pesticides and that of 2,4-D-butylate was the lowest. Clethodim sig- nificantly reduced the SOD content in a dose-dependent manner. 2,4-D-butylate also reduced SOD content in C. sinicus larvae, but the reduction was not significantly re- lated to its dosage. However, cypermethrin showed no significant effect on SOD ac- tivity in C. sinicus larvae.

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.

Acute and joint toxicity of three agrochemicals to Chinese tiger frog （Hoplobatrachus chinensis） tadpoles

We studied acute and joint toxicity of three different agrochemicals （chlorantraniliprole, flubendiamide-abamectin and penoxsulam） to Chinese tiger frog （Hoplobatrachus chinensis） tadpoles with the method of stability water tests. Results showed that the three agrochemicals increased tadpole mortality. For acute toxicity, the LC50 values after 24, 48 and 72 h of chlorantraniliprole, flubendiamide-abamectin and penoxsulam exposure were 5.37, 4.90 and 4.68 mg/L; 0.035, 0.025 and 0.021 rag/L; 1.74, 1.45 and 1.29 mg/L, respectively. The safety concentrations （SC） of chlorantraniliprole, fiubendiamide-abamectin and penoxsulam to the tadpoles were 1.23, 0.30 and 0.003 mg/L, respectively. Based on these findings, chlorantraniliprole and penoxsulam were moderately toxic, while flubendiamide-abamectin was highly toxic. All pairwise joint toxicity tests showed moderate toxicity. The LCs0 values after 24, 48 and 72 h of exposure were 7.08, 6.61 and 6.03 mg/L for chlorantra- niliprole＋penoxsulam, with corresponding values of 2.455, 2.328 and 2.183 mg/L for chlorantraniliprole＋flubendiamide-abamectin, and 1.132, 1.084 and 1.050 mg/L for penoxsulam＋flubendiamide-abamectin, with safe concentrations of 1.73, 0.63 and 0.30 mg/L, respectively. For toxic evaluations of pairwise combinations of the three agrochemicals, only the joint toxicity of chlorantraniliprole and flubendiamide-abamectin after 24 h was found to be synergistic, whereas all other tests were antagonistic. Our findings provide valuable information on the toxic effects of agrochemicals on amphibians and how various types of agrochemicals can be reasonably used in agricultural areas.

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.

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.

Acute and subchronic toxicity as well as evaluation of safety pharmacology of modified pulsatilla granules

The present study investigated acute and subchronic toxicity and safety pharmacology of modified pulsatilla granules（MPG）to provide a basis for a comprehensive understanding of MPG toxicity.The results of acute toxicity testing showed that the median lethal dose of MPG was more than 5 000 mg kg^-1,suggesting that MPG was considered as practically non-toxic.The subchronic toxicity study for 30 days was conducted by daily oral administration at doses of 375,750 and 1 500 mg kg^-1 in Sprague-Dawley rats.The results of subchronic toxicity study showed that the body weight and relative organ weight were not significantly changed by administration of MPG.The clinical chemistry study showed that MPG could induce kidney and liver damages.In histopathological,mild lesions in liver and kidney were also observed,suggesting that the liver and kidney might be potential target organs of MPG.In the safety pharmacology study,MPG did not exhibited any side effects to rats in cardiovascular system,respiratory system and central nervous system.These results suggested that MPG could be considered safe for veterinary use.

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.

Acute Toxicity Test of Qiangli Bupi Paste

[Objective] The toxicity of Qiangli Bupi Paste was investigated, to provide a test basis for its further development and safe use. [Method] Forty Kunming mice, half male and half female, were selected and divided into the CK group and the Qiangli Bupi Paste group, each of which included 20 mice. The acute toxicity of Qiangli Bupi Paste was observed by the maximum administration dosage method. No mice and abnormal response were observed within 14 d in various groups. The tested animals were also subjected to anatomical observation. [Result] All the tested animals survived in the test, and behaved normally, with glossy hair. Their body weights accorded with the growth regularity. During the anatomy, no important vis- ceral organs showed pathological changes, and there were no significant differences in body weight between the two groups before administration, on the 7~ after ad- ministration and the 14 d after administration （P〉0.05）. [Conclusion] In the acute toxicity test of Qiangli Bupi Paste, the maximum administration dosage was 48 g/kg （equivalent to 96 times of the daily dose of adult in clinic）, and no obvious toxic response was observed.