On the basis of web databases, 111 compounds with nephrotoxicity and 90 compounds without nephrotoxicity were collected as data set of nephrotoxicity discrimination model, 39 compounds with tubular necrosis and 39 compounds without tubular necrosis were collected as data set of tubular necrosis discrimination model. The 6 122 molecular descriptors, including physicochemical, charge distribution and geometrical descriptors were calculated to characterize the molecular structure of the above-mentioned compounds. CfsSubsetEval valuation method and BestFirst-D1-N5 searching method were used to select molecular descriptors. Two models with high accuracy were built based on the support vector machine (SVM) approach, respectively. Accuracy, sensitivity, specificity and matthew's correlation coefficient of the two models were all above 70%. By using 22 nephrotoxicity compounds of Chinese medicine, the nephrotoxicity discrimination model was further verified with an accuracy of 72.73%. Using the tubular necrosis discrimination model, 10 potential compounds which can cause tubular necrosis were screened from the positive results of nephrotoxicity discrimination model, 6 of them have been verified by literatures. The results demonstrated that the discrimination models can be applied to screen nephrotoxic compounds from Chinese medicinal materials, and they also offer a new research idea for the further studies on the mechanism of nephrotoxicity.
Drugs, Chinese Herbal ; toxicity ; Nephrons ; drug effects ; Support Vector Machine ; Toxicity Tests ; instrumentation ; methods

To discuss IC50 application in cytotoxicity tests of medical devices, we firstly investigated the vibrating condition and endpoint of MTT method specified in ISO 10993-5: 2009. Furthermore, we demonstrated the application of IC50 in the result evaluation of MTT method. The experimental results show that usage of IC50 in quantitative evaluation of MTT method is feasible.
Equipment and Supplies ; adverse effects ; standards ; Inhibitory Concentration 50 ; Toxicity Tests ; methods

OBJECTIVEThis study aims to establish and evaluate the methodology of isolated rabbit eye (IRE) test.

METHODSIRE test was performed according to modifications of the in vitro toxicology (INVITTOX) Protocol No.85: Rabbit enucleated eye test by European Centre for the Validation of Alternative Methods (ECVAM), and then 26 chemicals and 26 cosmetic products were tested in both in vitro IRE and in vivo Draize tests. A statistical analysis was conducted to determine the relevance of the IRE test to the data generated in the Draize test.

RESULTSIRE test was established successfully in our laboratory. It was shown that ranking correlation and class concordance were fairly well between the IRE test and the Draize test for 26 reference chemicals (Fisher's Exact Test χ(2)=51.314, P<0.001; McNemar P=0.261; Gamma=0.960, P<0.001; Kappa=0.843, P<0.001) and 26 cosmetic products (Fisher's Exact Test χ(2)=15.522, P<0.001; McNemar P=0.311; Gamma=0.967, P<0.001; Kappa=0.611, P<0.001).

CONCLUSIONIRE test was established successfully for in vitro testing of eye irritation as an alternative to Draize test.

Animal Testing Alternatives ; Animals ; Cosmetics ; toxicity ; Eye ; drug effects ; Irritants ; toxicity ; Rabbits ; Toxicity Tests ; methods

Hyaluronan acid sodium gels are used in ophthalmic surgery, orthopedic treatment and cosmetic surgery. In 2009,there were 12 domestic manufacturers in China producing 33 kinds of products. 23 kinds of imported products were allowed by SFDA to sale in the meantime. Since manufacturers use different production processes, product performances are quite different. According to the GB/T 16886. 1-2001, we designed a pilot program to evaluate the sodium hyaluronate gel products comprehensively in this paper. The results showed that, except chromosome aberration test of gel A and subchronic systemic toxicity of gel C appeared positive, the remaining samples of the test results were negative. This article provides a reference to write standard of cross-linked hyaluronic sodium gel and the revision of standard YY0308-2004.
Animals ; Biocompatible Materials ; standards ; Cross-Linking Reagents ; chemistry ; Gels ; Hyaluronic Acid ; standards ; Mice ; Pilot Projects ; Quality Control ; Rabbits ; Rats ; Rats, Sprague-Dawley ; Toxicity Tests ; methods

OBJECTIVETo explore new toxicity-reducing methods of Pinellia Rhizoma prepared by ethanol and the latest technical parameters.

METHODPinellia Rhizoma is prepared with ethanol. The orthogonal experimental design was adopted for investigating amount of ethanol, preparing time, ethanol concentration and preparing temperature. The optimal technology was determined by the comprehensive score of toxicological indicators of PGE2 content of rat celiac percolate, with the rabbit conjunctival irritation test as the intuitive validation on toxicology reduction. The pharmacodynamics validation was used to determine the reasonability of the preparation process.

RESULTThe optimal technology was that Pinellia Rhizoma was prepared by 75% ethanol at the temperature of 60 degrees C by 4 days, and then dried. The effect of relieving cough, reducing sputum and anti-inflammatory of Pinellia Rhizoma is not reduced after prepared by ethanol.

CONCLUSIONThe optimal technology of Pinellia Rhizoma prepared by ethanol is simple and reasonable that it can be used as the new method to reduce toxicity and keep efficacy of Pinellia Rhizoma.

Animals ; Anti-Inflammatory Agents ; chemistry ; isolation & purification ; pharmacology ; Cough ; drug therapy ; Desiccation ; Drugs, Chinese Herbal ; chemistry ; isolation & purification ; pharmacology ; Ethanol ; chemistry ; Female ; Hot Temperature ; Male ; Mice ; Mice, Inbred ICR ; Pinellia ; chemistry ; toxicity ; Plants, Medicinal ; chemistry ; toxicity ; Rabbits ; Rats ; Rats, Sprague-Dawley ; Rhizome ; chemistry ; toxicity ; Sputum ; drug effects ; Technology, Pharmaceutical ; methods ; Time Factors ; Toxicity Tests

OBJECTIVETo observe dynamic changes of blood lead concentration in rats with long-term toxicity test with Goupi Gao by the flame atomic absorption spectrometry, in order to provide reference for safe administration of Goupi Gao.

METHODThe rats were administered with Goupi Gao by high-dose (7 g x kg(-1)), medium-dose (3.5 g x kg(-1)), low-dose (1.75 g x kg(-1)) by external use for consecutively 90 days. Then, the blood samples were collected from the rats before the administration and at 10, 30, 45, 52, 60, 90 d after the administration respectively, as well as 16 d and 28 d after the drug withdrawal. The samples were dispelled with microwave digestion system and then were determined by graphite furnace atomic absorption spectrometry for blood lead levels.

RESULTAccording to methodological study, the standard curve regression equation in this experiment was A = 0.004 9X + 0. 017, r = 0.999 5, with the detection limit up to 0. 380 microg x L(-1). The RSD was 1.4% by precision checks. Blood lead level of mixed blood samples was 175.77 microg x L(-1), whose RSD was 6. 0%. Blood lead concentration gradually increased after low-dose and medium-dose administration to rats and became stable at the 10th day and the 30th day by high-dose. Dose is directly related to blood lead concentration. Meanwhile, the blood lead concentration decreases after the drug withdrawal.

CONCLUSIONThe method of determination in this experiment is so accurate and reliable that it can be used for the determination of blood lead. Long-term and high-dose external use of Goupi Gao can increase blood lead.

Animals ; Dose-Response Relationship, Drug ; Drugs, Chinese Herbal ; administration & dosage ; toxicity ; Female ; Lead ; blood ; Male ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Spectrophotometry, Atomic ; methods ; Time Factors ; Toxicity Tests

Humans ; Lymphocytes ; cytology ; drug effects ; Micronucleus Tests ; Occupational Exposure ; prevention & control ; Polycyclic Aromatic Hydrocarbons ; toxicity ; Population Surveillance ; methods

We examined the biocompatibility and the safety of a-calcium sulfate hemihydrate (CSH)/multi-walled carbon nanotube (MWCNT) composites for bone reconstruction application. The biocompatibility of the CSH/MWCNT composites was evaluated by the measures which taking L929 fibroblast cells cultured in the extracted liquid of the composite soaking solution and putting bone marrow stromal cells planted on the composite pellets in vitro, respectively. The cell proliferation was evaluated by MTT test and further observed using an inverted optical microscope and a scanning electric microscope. The toxicity of the composites was evaluated by acute and subacute systemic toxicity test. Long-term muscle and bone implantation in vivo tests were also conducted. L929 fibroblast cells grew well in the extracted liquid, as well as bone marrow stromal cells that could adhere on the surface of sample pellets and proliferated rapidly. MTT test showed that there were no significant differences between the experimental and control groups (P > 0.05). In vivo test manifested that the composites were no toxicity, no irritation to skin and good for bone defect reconstruction. It was proved that a-calcium sulfate hemihydrate (CSH)/multi-walled carbon nanotube (MWCNT) composites exhibited excellent biocompatibility for the potential application in bone tissue engineering.
Animals ; Biocompatible Materials ; chemistry ; Bone Marrow Cells ; cytology ; Bone Substitutes ; chemical synthesis ; chemistry ; Calcium Sulfate ; chemistry ; Cell Line ; Cell Proliferation ; Fibroblasts ; cytology ; Materials Testing ; Nanotubes, Carbon ; chemistry ; Rabbits ; Stromal Cells ; cytology ; Tissue Engineering ; methods ; Toxicity Tests

OBJECTIVETo establish a cell-based detection method of ciguatoxin using fluorescence assay.

METHODSMouse neuroblastoma N-2A cells were exposed to ouabain and veratridine and different concentrations of standard ciguatoxin samples (P-CTX-1) to establish the curvilinear relationship between the toxin dosage and fluorescence intensity using the sodium fluorescence probe CoroNaTM Green. The toxicity curvilinear relationship was also generated between the toxin dosage and cell survival using CCK-8 method. Based on these standard curves, the presence of ciguatoxin was detected in 33 samples of deep-sea coral fish.

RESULTSA correlation was found between the detection results of cell-based fluorescence assay and cytotoxicity assay, whose detection limit reached 103 g/ml and 1012 g/ml, respectively. The cell-based fluorescent assay sensitivity showed a higher sensitivity than cytotoxicity assay with a 2-4 h reduction of the detection time.

CONCLUSIONSThe cell-based fluorescent assay can quickly and sensitively detect ciguatoxin and may serve as a good option for preliminary screening of the toxin.

Animals ; Cell Line, Tumor ; Ciguatoxins ; toxicity ; Cytotoxicity Tests, Immunologic ; methods ; Fishes ; Fluorescent Dyes ; Mice ; Sodium

OBJECTIVETo investigate the fetotoxicity of retrorsine.

METHODMouse whole embryo culture (WEC) was applied. Post-implantation (8.5 d) mouse embryos were isolated from their mothers and put into the medium of immediately centrifuged serum (ICS) prepared from rats. Different concentrations of retrorsine (12.5, 25, 50, 100 mg x L(-1)) were added into the WEC culture. Development (yolk sac diameter, crown-rump length, head length, somite number) and organic morphodifferentiation (yolk sac circulation, allantois, embryonic flexion, heart, brain, optic-otic-olfactory organ, branchial arch, maxillary, mandible, bud) of embryos were observed at 48 h after treatment.

RESULTObvious fetotoxicity could be observed in various retrorsine treatment groups in a dose-dependent manner. Development of embryos was delayed significantly at dose 12.5-100 mg x L(-1). Malformations were shown in all organic morphodifferentiation indexes, especially in otic-olfactory organ, branchial arch, maxillary, mandible, bud.

CONCLUSIONRetrorsine had obvious fetotoxicity in vitro WEC culture, indicating that exposure of pregnant mice to retrorsine may have potential risk on fetals.

Animals ; Dose-Response Relationship, Drug ; Embryo, Mammalian ; drug effects ; Female ; Male ; Mice ; Pregnancy ; Pyrrolizidine Alkaloids ; toxicity ; Rats ; Toxicity Tests ; methods