Animals ; Carcinogenicity Tests ; Cytotoxicity Tests, Immunologic ; Humans ; Mutagenicity Tests ; Soot ; toxicity

OBJECTIVETo study the acute toxicity of C25P polypeptide, a CCR5 antagonist, in mice and its carcinogenic effect in vitro.

METHODSThe acute toxicity of C25P polypeptide in mice was assessed by determining the maximum tolerated dose (MTD). The mice were given C25P at the dose of 3.64 g/kg by tail vein injection, and the control mice received saline (40 ml/kg) injection. The mice were continuously observed for 14 days after the administration and sacrificed on day 14 for routine blood test, examination of the blood biochemistry and pathological examination. The carcinogenicity of C25P polypeptide in vitro was evaluated in cultured cell lines by chromosome aberration test, cell transformation test and non-anchorage dependent growth test.

RESULTSNo mice died following administration of the drug, but 3 mice showed mild adverse reactions. The rats in both groups showed an increase in the body weight at a comparable rate. GPT increased and ALP decreased significantly in C25P polypeptide group (P<0.05). Most of the organs of the rats treated with in C25P polypeptide remained normal, but 3 mice showed pathologies in the lung, spleen and liver. Chromosome aberration test, cell transformation test and non-anchorage-dependent growth test all yielded negative results for C25P polypeptide.

CONCLUSIONC25P polypeptide is a low-toxicity drug that produces no apparent acute toxicity in mice or obvious carcinogenicity in vitro.

Animals ; CCR5 Receptor Antagonists ; Carcinogenicity Tests ; Chemokines ; toxicity ; Female ; Male ; Mice ; Mice, Inbred Strains ; Mutagenicity Tests ; Peptides ; toxicity ; Toxicity Tests, Acute

With the increased use of cell therapy in the veterinary sector, there is a growing demand for the development of cell-based medicinal products and the determination of their safety. Currently, the Korean Animal and Plant Quarantine Agency has established a guideline for evaluating the safety of cell-based medicinal products for animal use. The guideline includes items related to definition, classification, management, manufacturing procedure and quality control (standard and test method), stability testing, toxicity testing, pharmacological testing, and performance of clinical trials. In addition, testing protocols related to safety assessment of animal cell-based products such as chromosome karyotyping, tumorigenicity testing, confirmatory testing of biodistribution and kinetics, and target animal safety testing are described in detail. Moreover, because cell-based medicinal products are novel therapies, deviations from traditional designs may be justified in order to obtain relevant safety information on the treatment. Additionally, this guideline can be amended on the basis of new scientific findings.
Animals ; Carcinogenicity Tests ; Cell- and Tissue-Based Therapy ; Classification ; Karyotyping ; Kinetics ; Plants ; Quality Control ; Quarantine ; Toxicity Tests

OBJECTIVETo study the acute toxicity and mutagenic risk of the water extracts (ERWE) and 70% ethanol extracts (EREE) from the nearly ripe fruit of Evodia rutaecarpa, and provide experimental basis for safety evaluation of ones.

METHODThe ERWE and EREE were prepared from the nearly ripe fruit of E. rutaecarpa by reflux extraction with H2O and 70% ethanol aqueous solution for three times, respectively. According to the terms from "technical standards for test & toxicological assessment of health food" issued by Healthy Ministry of PRC, acute toxicity, and Ames, mouse marrow cell micronucleus and mouse sperm aberration test were performed. Acute toxicity test of ERWE and EREE in mice was studied by the method of Horn to give the median lethal dose (LD50). Forty healthy Kunming strain male and female mice were used and their body weights ranged from 17-22 g. All of them were distributed randomly to 4 different dose groups which each had 10 mice. The ERWE or EREE was administered at the doses of 1.00, 2.15, 4.64 and 10.00 g x kg(-1), respectively, via intragastrical route. The number of animals poisoned and died in each group were noted daily for 7 consecutive days. The Ames test was carried out using the Salmonella typhimurium strain TA97, TA98, TA100 and TA102. In the sperm abnormalities test, 25 healthy adult male Kunming strain mice with a body weights ranged from 25-35 g were distributed randomly to 5 different groups (1 positive control, 1 negative control and 3 treated groups) which each had 5 mice. A single dose of 60 g x kg(-1) of cyclophosphamide was intragastrically administered to mice in a positive control group, and the mice in the negative control group were administered with the same volume of distilled water. In the treated groups, the ERWE or EREE was intragastrically administered at the doses of 1.25, 250 and 5.00 g x kg(-1), respectively, via the same route with the positive control group. The administration was carried out once daily for 5 consecutive days. The sperm suspension was prepared from caudal epididymis of male mice at 35th day after treatment with different doses of the extract. The suspension was stained with Eosin-Y and air-dried smears were prepared. One thousand sperms per animal were analysed for abnormal shapes and the rates of sperm aberration was calculated. In the mouse bone marrow micronucleus assay, 50 healthy adult male and female Kunming mice, weighing 25 to 30 g, were randomly assigned to five groups (1 positive control, 1 negative control and 3 treated groups) which each had 10 mice, five males and five females. The mice were intragastrically administered twice at intervals of 24 h with the ERWE or EREE at doses of 1.25, 2.50 and 5.00 g x kg(-1) in the positive control group. A single dose of 60 g x kg(-1) of cyclophosphamide in a positive control group and the same volume of distilled water in a negative control groups were intragastrically administered, respectively. Mouse bone marrow was obtained from 10 animals for each group at 6 h after the last dose administration. Smears were stained with Giemsa and analysed for the presence of mouse bone marrow micronucleus from 1 000 cells.

RESULTThe oral acute toxicity study in mice revealed that the LD50 of the both ERWE and EREE was more than 10.0 g x kg(-1). The mice with both the poisoned sign or died had not been observed after intragastrical administration of ERWE or EREE at the doses of 1.00, 2.15, 4.64 and 10.00 g x kg(-1). The results of genotoxicity tests were all negative, including Ames, mouse marrow cell micronucleus and mouse sperm aberration test. In the all assay in vivo, the mice showed a normally progressive increase in body weight from the start to the end of the experiment.

CONCLUSIONThe oral LD50 of the ERWE and EREE in mice was more than 10.0 g x kg(-1) belonging to non-toxicity on the acute toxicity rating criteria. The both ERWE and EREE showed no genotoxicity in the experimental condition.

Animals ; Body Weight ; drug effects ; Bone Marrow Cells ; drug effects ; Drugs, Chinese Herbal ; administration & dosage ; adverse effects ; toxicity ; Ethanol ; chemistry ; Evodia ; adverse effects ; chemistry ; growth & development ; toxicity ; Female ; Fruit ; adverse effects ; chemistry ; growth & development ; toxicity ; Lethal Dose 50 ; Male ; Mice ; Mutagenesis ; drug effects ; Mutagenicity Tests ; Spermatozoa ; drug effects ; Toxicity Tests, Acute ; Water ; chemistry

OBJECTIVETo study the acute toxicity of the water extracts (ERWE) and 60% ethanol extracts (EREE) from different processed products of Radix Polygalae (crude Radix Polygalae, licorice, and honey processed Radix Polygalae), thus providing scientific evidence for toxicity study of Radix Polygalae and its safe clinical application.

METHODSThe ERWE and EREE were prepared from different processed products of Radix Polygalae. Their contents of saponins were respectively determined. The poisoning condition and death of the mice administered with ERWE and EREE by gastrogavage were observed within fourteen days. The modified Karber's method was used to calculate LD50 and 95% confidence interval (CI).

RESULTSThe EREE of licorice processed Radix Polygalae had the maximum toxicity with highest content of saponins, while the ERWE of honey processed Radix Polygalae had the minimum toxicity with lowest content of saponins.

CONCLUSIONSDifferent processing methods have effects on the contents of saponins in Radix Polygalae. The experiment showed that the toxicity of Radix Polygalae is in direct proportion to the content of saponins. The higher the saponins contents, the higher the toxicity.

Animals ; Female ; Lethal Dose 50 ; Male ; Mice ; Mice, Inbred Strains ; Plant Extracts ; toxicity ; Polygala ; Saponins ; toxicity ; Toxicity Tests, Acute

OBJECTIVETo investigate the acute toxicity and assess the median lethal dose (LD50) of matrine in Kunming mice.

METHODSMatrine at different doses were administered in Kunming mice via intraperitoneal injection, and the toxic reactions and LD50 of matrine was observed and determined.

RESULTSThe acute toxicity test of matrine indicated that the tolerable dose of matrine was above 80 mg/kg in Kunming mice, and the LD50 was 157.13 mg/kg (95%CI, 88.08-280.31 mg/kg). Morphological observation revealed degenerative changes of the nerve cells in the brain tissue of the mice.

CONCLUSIONThe nervous system is the main target organ by the toxicity of matrine.

Alkaloids ; toxicity ; Animals ; Brain ; drug effects ; pathology ; Female ; Lethal Dose 50 ; Male ; Mice ; Quinolizines ; toxicity ; Toxicity Tests, Acute

OBJECTIVETo 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.

METHODS( 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.

RESULTS( 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.

CONCLUSIONAcute toxicity grade DNTF low toxicity level compounds, target organ toxicity of liver, kidney and lung.

Animals ; Female ; Lethal Dose 50 ; Male ; Mice ; Nitrofurazone ; analogs & derivatives ; toxicity ; Oxadiazoles ; toxicity ; Rats ; Rats, Sprague-Dawley ; Toxicity Tests

OBJECTIVES: A hazard assessment of di(2-ethylhexyl) phthalate (DEHP), a commonly used workplace chemical, was conducted in order to protect the occupational health of workers. A literature review, consisting of both domestic and international references, examined the chemical management system, working environment, level of exposure, and possible associated risks. This information may be utilized in the future to determine appropriate exposure levels in working environments. METHODS: Hazard assessment was performed using chemical hazard information obtained from international agencies, such as Organization for Economic Cooperation and Development-generated Screening Information Data Set and International Program on Chemical Safety. Information was obtained from surveys conducted by the Minister of Employment and Labor (“Survey on the work environment”) and by the Ministry of Environment (“Survey on the circulation amount of chemicals”). Risk was determined according to exposure in workplaces and chemical hazard. RESULTS: In 229 workplaces over the country, 831 tons of DEHP have been used as plasticizers, insecticides, and ink solvent. Calculated 50% lethal dose values ranged from 14.2 to 50 g/kg, as determined via acute toxicity testing in rodents. Chronic carcinogenicity tests revealed cases of lung and liver degeneration, shrinkage of the testes, and liver cancer. The no-observed-adverse-effect level and the lowest-observed-adverse-effect level were determined to be 28.9 g/kg and 146.6 g/kg, respectively. The working environment assessment revealed the maximum exposure level to be 0.990 mg/m³, as compared to the threshold exposure level of 5 mg/m³. The relative risk of chronic toxicity and reproductive toxicity were 0.264 and 0.330, respectively, while the risk of carcinogenicity was 1.3, which is higher than the accepted safety value of one. CONCLUSIONS: DEHP was identified as a carcinogen, and may be dangerous even at concentrations lower than the occupational exposure limit. Therefore, we suggest management of working environments, with exposure levels below 5 mg/m³ and all workers utilizing local exhaust ventilation and respiratory protection when handling DEHP.
Carcinogenicity Tests ; Chemical Safety ; Clergy ; Dataset ; Diethylhexyl Phthalate ; Employment ; Humans ; Ink ; Insecticides ; International Agencies ; Liver ; Liver Neoplasms ; Lung ; Mass Screening ; No-Observed-Adverse-Effect Level ; Occupational Exposure ; Occupational Health ; Plasticizers ; Plastics ; Risk Assessment* ; Rodentia ; Testis ; Toxicity Tests, Acute ; Ventilation

Preclinical evaluation of medical devices (prototype products) offers the opportunity to investigate and study the intended use of device materials. Preclinical evaluation programs are designed to determine the efficacy, safety, and biocompatibility of biomaterials, prostheses, and medical devices. The purpose of safety testing is to determine if a material presents potential harm to the human; it evaluates the interaction of the material with the in vivo environment and determines the effect of the host on the implant. Preclinical evaluation is the determination of the ability of the prototype product to perform with appropriate host response in a specific application, considered from the perspective of human clinical use. Therefore, preclinical data should include materials science and engineering, biology, biochemistry, medicine, host reactions and their evaluation, the testing of biomaterials, and the degradation of materials in a biological environment.
Animal ; Carcinogenicity Tests ; Equipment and Supplies*/adverse effects ; Hemolysis ; Human ; Pyrogens/toxicity ; Sterilization

OBJECTIVETo evaluate three alternative methods for LD50 test-Fixed Dose Procedure (FDP), the Acute Toxic Class Method (ATC) and Up and Down Procedure (UDP).

METHODSFemale SD rats (8-12 weeks of age, 160-200 g) were used. Three alternative methods from OECD were applied to assess 22 chemicals (10 cosmetic raw materials and 12 raw materials of personal and home care products). The toxicity ranking for tested chemicals was established according to Globally Harmonized System (GSH). The results LD50 test were compared for the consistency and correlation between alternative methods and traditional test.

RESULTSFor cosmetic raw materials, the concordance rate of the three alternative methods was 80% (8/10); for raw material of personal and home care products, the concordance rates of FDP, ATC and UDP was 91.7% (11/12), 75.0% (9/12) and 83.0% (10/12), respectively. The number of animals required in three alternative methods was significantly lower than that in traditional test (P < 0.05), but the time required in three alternative methods was significantly higher than that in traditional test (P < 0.05).

CONCLUSIONSHigh consistency and correlation were found between each alternative method and LD50 test. FDP may be more potential when applied to assess acute oral toxicity of cosmetic raw materials.

Administration, Oral ; Animals ; Cosmetics ; toxicity ; Dose-Response Relationship, Drug ; Female ; Hazardous Substances ; toxicity ; Lethal Dose 50 ; Rats ; Rats, Sprague-Dawley ; Toxicity Tests, Acute ; methods