OBJECTIVE: To observe the acute toxic reaction of the Li-Dan-He-Ji granules, and to evaluate its safety. METHODS: Sixty C57BL6/J mice were randomly divided into normal control group, vehicle group and drug treatment group, with 10 females and 10 males in each group. According to the Technical guidelines for the study of toxicity of single drug administration, the maximum administration dosage (MAD) was used to intragastric administration of Li-Dan-He-Ji granules 0.04 mL/g (42.8 g/kg), three times within 24 hours, with an interval of 6 hours. The vehicle group was fed with the same pure water. The normal control group received no treatment. The mice were observed continuously for 14 days, and the appearance characteristics, behavioral activities, body weight changes and the number of deaths in each group were recorded. At the 14 days, blood samples were collected from the eyeballs, and routine blood tests such as white blood cell count (WBC), lymphocyte count (LYM), neutrophil count (NEU), lymphocyte percentage (LYM%), neutrophil percentage (NEU%), red blood cell count (RBC), hemoglobin (Hb), and platelet count (PLT) were performed. And alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN), creatinine (Cr) and other biochemical indicators. The mice were then sacrificed, and the histopathological changes of liver and kidney were observed by hematoxylin-eosin (HE) staining. The organ indexes of heart, liver, spleen, lung, kidney and thymus were calculated. RESULTS: The median lethal dose (LD₅₀) of Li-Dan-He-Ji granules were not obtained. During the MAD experiment, the animals in each group did not die, their behavioral activities were normal, and there was no significant change in liver and kidney histopathological examination. There were no significant differences in body weight, blood routine, biochemical indexes and organ index among all groups (all P > 0.05). The body weight (g) of normal control female and male group, vehicle female and male group and drug female and male group before administration were 18.96±1.14, 19.65±1.45, 19.33±1.30, 19.53±1.22, 19.28±1.69 and 19.48±1.28; 14 days after administration were 27.69±0.81, 28.19±2.22, 27.77±1.00, 27.88±1.85, 27.92±1.33 and 28.07±1.93, respectively. CONCLUSIONS The Li-Dan-He-Ji granules have low oral toxicity, combined with clinical observation, can be safely used in infants.
Animals ; Female ; Humans ; Male ; Mice ; Body Weight ; Kidney ; Leukocyte Count ; Liver ; Toxicity Tests, Acute

Objective: To verify the health advisory for short-term exposure to phenol. Methods: The method of this validation experiment was the same as the US Environmental Protection Agency (EPA) methodology for toxicology experiments used to determine phenol drinking water equivalent level (DWEL). Pregnant female Sprague-Dawley rats were administered phenol in distilled water by gavage at daily doses of 15, 30, 60, 120, and 240 mg/kg body weight (b.w.) from implantation (the 6th day post-mating) to the day prior to the scheduled caesarean section (the 20th day of pregnancy). The following information was recorded: general behavior; body weight; number of corpus luteum, live birth, fetus, stillbirth, and implantation; fetal gender; body weight; body length; tail length; and abnormalities and pathomorphological changes in the dams. Results: In the 60 mg/kg b.w. dose group, the mortality of pregnant rats increased with increasing doses, suggesting maternal toxicity. Fetal and placental weights decreased as phenol dose increased from 30 mg/kg b.w., and were significantly different compared those in the vehicle control group, which suggested developmental toxicity in the fetuses. However, the phenol-exposed groups showed no significant change in other parameters compared with the vehicle control group ( > 0.05). Conclusion Despite using the same method as the US EPA, a different NOEAL of 15 mg/(kg·d) was obtained in this study.
Animals ; Dose-Response Relationship, Drug ; Environmental Pollutants ; toxicity ; Female ; Fetal Development ; drug effects ; Phenol ; toxicity ; Pregnancy ; Rats ; Rats, Sprague-Dawley ; Toxicity Tests, Acute

Based on metabolomics,the metabolites of larvae zebrafish with overdose of Panax notoginseng saponins( PNS) were compared with those in normal group of larvae zebrafish to investigate the possible toxicity mechanism of overdose PNS in larvae zebrafish. An experimental animal model of long-term toxicity induced by PNS overdose was established by administering 1-6 dpf at low,medium and high doses of PNS,respectively. The ultra-performance liquid chromatography-quadrupole-time of flight mass spectrometry( UPLC-Q-TOF-MS) technique was combined with principal component analysis( PCA) and orthogonal partial least squares discriminant analysis( OPLS-DA) to screen and identify biomarkers associated with toxicity,and then the MetaboAnalyst database was used to analyze metabolism-related pathways. The results showed that the metabolites of each group could be distinguished distinctly,and they deviated more from the normal group in a time and dose dependent manner. Twenty-nine potential biomarkers related to toxicity( VIP>1,P<0. 05) were identified preliminarily,mainly involving six metabolic pathways. From the metabonomics point of view,the toxicity mechanism of overdose PNS may be related to the disorders of lipid metabolism,amino acid metabolism and energy metabolism.
Amino Acids ; metabolism ; Animals ; Chromatography, High Pressure Liquid ; Energy Metabolism ; Larva ; drug effects ; Lipid Metabolism ; Mass Spectrometry ; Metabolomics ; Panax notoginseng ; toxicity ; Saponins ; toxicity ; Toxicity Tests, Acute ; Zebrafish

The production of water-soluble pigments by fungal strains indigenous to South Korea was investigated to find those that are highly productive in submerged culture. Among 113 candidates, 34 strains that colored the inoculated potato dextrose agar medium were selected. They were cultured in potato dextrose broth and extracted with ethanol. The productivity, functionality (radical-scavenging activities), and color information (CIELAB values) of the pigment extracts were measured. Five species produced intense yellowish pigments, and two produced intense reddish pigments that ranked the highest in terms of absorbance units produced per day. The pigment extracts of Penicillium miczynskii, Sanghuangporus baumii, Trichoderma sp. 1, and Trichoderma afroharzianum exhibited high radical-scavenging activity. However, the S. baumii extract showed moderate toxicity in the acute toxicity test, which limits the industrial application of this pigment. In conclusion, P. miczynskii KUC1721, Trichoderma sp. 1 KUC1716, and T. afroharzianum KUC21213 were the best fungal candidates to be industrial producers of safe, functional water-soluble pigments.
Agar ; Colorimetry ; Efficiency ; Ethanol ; Fungi* ; Glucose ; Korea ; Penicillium ; Solanum tuberosum ; Toxicity Tests, Acute ; Trichoderma

OBJECTIVEThis study investigated the acute and subacute toxicity of whole-plant aqueous extract of Vernonia mespilifolia Less. (AEVM) in rats for evaluating its safety profile.

METHODSAEVM for the acute (2000 and 5000 mg/kg) and subacute (200, 400 and 600 mg/kg) toxicity studies was administered orally to rats according the guidelines 425 and 407 of Organization for Economic Cooperation and Development, respectively. Food and water intake as well as body and organ weight of animals were recorded. Signs of toxicity were assessed, and hematological, biochemical and histopathological analyses were performed.

RESULTSIn the acute toxicity study, a single dose of the aqueous extract at 2000 or 5000 mg/kg caused no mortality in the animals, suggesting that the median lethal dose is greater than 5000 mg/kg. In the subacute toxicity study, administration of the extract for 28 d, at all doses, caused no significant changes in the body weights or organ weights of rats in the treated groups when compared with the control group. In addition, hematological and biochemical parameters also revealed no toxic effects of the extract on rats. Histological sections of the heart, liver and kidney from test animals showed no signs of degeneration.

CONCLUSIONThese results showed that AEVM at dosage levels up to 600 mg/kg is nontoxic and could also offer protection on some body tissues. AEVM could, therefore, be considered safe.

Animals ; Female ; Heart ; drug effects ; Kidney ; drug effects ; Lethal Dose 50 ; Liver ; drug effects ; Male ; Plant Extracts ; toxicity ; Plant Leaves ; Rats, Wistar ; Toxicity Tests, Acute ; Toxicity Tests, Subacute ; Vernonia ; toxicity

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%.
Animals ; Bone and Bones ; chemistry ; metabolism ; Rats ; Rats, Sprague-Dawley ; T-2 Toxin ; analogs & derivatives ; pharmacokinetics ; toxicity ; Tissue Distribution ; Toxicity Tests, Acute

OBJECTIVETo evaluate the acute and sub-chronic toxicity of intravenously administered tetrandrine (TET) in female BALB/c mice.

METHODSThe median lethal dose (LD) of intravenously administered TET was calculated in mice using Dixon's up-and-down method. In the acute toxicity study, mice were intravenously administered with TET at a single dose of 20, 100, 180, 260 and 340 mg/kg, respectively and were evaluated at 14 days after administration. In the sub-acute toxicity study, mice were intravenously administered various doses of TET (30, 90 and 150 mg/kg) each day for 14 consecutive days. Clinical symptoms, mortality, body weight, serum biochemistry, organ weight and histopathology were examined at the end of the experiment, as well as after a 1-week recovery period.

RESULTLDwas found to be 444.67±35.76 mg/kg. In the acute toxicity study, no statistically signifificant differences in body weight, blood biochemistry, or organ histology were observed between the administration and control groups when mice were intravenously administered with single dose at 20, 100, 180, 260 and 340 mg/kg of TET (P >0.05). In the sub-acute toxicity study, no signifificant changes in body weight, biochemistry and organ histology were observed with up to 90 mg/kg of TET compared with the control group (P >0.05), however, in the 150 mg/kg administered group, TET induced transient toxicity to liver, lungs and kidneys, but withdrawal of TET can lead to reversal of the pathological conditions.

CONCLUSIONSThe overall fifindings of this study indicate that TET is relatively non-toxic from a single dose of 20, 100, 180, 260 or 340 mg/kg, and that up to 90 mg/kg daily for 14 consecutive days can be considered a safe application dose.

Administration, Intravenous ; Animals ; Benzylisoquinolines ; administration & dosage ; toxicity ; Body Weight ; drug effects ; Female ; Mice, Inbred BALB C ; Organ Specificity ; drug effects ; Toxicity Tests, Acute ; Toxicity Tests, Chronic

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

No data were available on the acute oral toxicity, short-term oral toxicity of vegetable carbon in animals. This study was designed to evaluate the safety of two commercially available dietary bamboo charcoal powders (BCP1 and BCP2). The size distribution of the two powders was determined by a Mastersizer 2000 laser particle size analyzer prior to the in vivo safety studies. For the acute toxicity study, a single dose of 11.24 g/kg body weight of BCP1 and BCP2 was given once orally to healthy Sprague-Dawley (SD) rats. Mortality and clinical symptoms were observed and recorded for the first 30 min after treatment, at 4 h post-administration, and then at least once daily for 14 days after administration. In the repeated dose 28-day oral toxicity study, BCP1 and BCP2 were administered orally at doses of 2.81, 5.62, and 11.24 g/kg body weight for 28 days to SD rats. Animals were sacrificed and organs and blood samples were analyzed. Results showed that both BCP1 and BCP2 were micro-sized and various in size. In the acute toxicity and the repeated dose 28-day oral toxicity studies, BCP caused neither mortality nor visible signs of toxicity in rats. No significant differences were found in the relative organ weights or in biochemical parameters in BCP treated groups compared to a control group. No treatment-related histological changes were observed in the organs of these animals. Based on these data, it is concluded that the median lethal dose (LD50) of BCP for both male and female rats is more than 11.24 g/kg body weight and the no-observed-adverse-effect level (NOAEL) is >11.24 g/kg body weight for 28 days.
Animals ; Bambusa ; chemistry ; Diet ; Female ; Male ; Powders ; Rats ; Rats, Sprague-Dawley ; Toxicity Tests, Acute

OBJECTIVETo explore the effects of exposure to aluminum (Al) on long-term potentiation (LTP) and AMPA receptor subunits in rats in vivo.

METHODSDifferent dosages of aluminum-maltolate complex [Al(mal)3] were given to rats via acute intracerebroventricular (i.c.v.) injection and subchronic intraperitoneal (i.p.) injection. Following Al exposure, the hippocampal LTP were recorded by field potentiation technique in vivo and the expression of AMPAR subunit proteins (GluR1 and GluR2) in both total and membrane-enriched extracts from the CA1 area of rat hippocampus were detected by Western blot assay.

RESULTSAcute Al treatment produced dose-dependent suppression of LTP in the rat hippocampus and dose-dependent decreases of GluR1 and GluR2 in membrane extracts; however, no similar changes were found in the total cell extracts, which suggests decreased trafficking of AMPA receptor subunits from intracellular pools to synaptic sites in the hippocampus. The dose-dependent suppressive effects on LTP and the expression of AMPA receptor subunits both in the membrane and in total extracts were found after subchronic Al treatment, indicating a decrease in AMPA receptor subunit trafficking from intracellular pools to synaptic sites and an additional reduction in the expression of the subunits.

CONCLUSIONAl(mal)3 obviously and dose-dependently suppressed LTP in the rat hippocampal CA1 region in vivo, and this suppression may be related to both trafficking and decreases in the expression of AMPA receptor subunit proteins. However, the mechanisms underlying these observations need further investigation.

Aluminum ; toxicity ; Animals ; Down-Regulation ; drug effects ; genetics ; physiology ; Hippocampus ; drug effects ; physiology ; Long-Term Potentiation ; drug effects ; genetics ; physiology ; Male ; Protein Transport ; drug effects ; genetics ; physiology ; Random Allocation ; Rats ; Receptors, AMPA ; antagonists & inhibitors ; genetics ; metabolism ; Toxicity Tests, Acute ; Toxicity Tests, Subchronic