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.

Effects of bifenthrin on Daphnia magna during chronic toxicity test and the recovery test

The acute and chronic toxic effects of bifenthrin on Daphnia magna were studied. The results showed that 24 h-EC 50 , 48 h-LC 50 and 96 h-LC 50 of bifenthrin on D. magna were 3.24, 12.40 and 1.40 μg/L respectively. And the LOEC and NOEC of bifenthrin were 0.02 and 0.004 μg/L respectively. The recovery test of bifenthrin on Daphnia magna was presented. Daphnia magna(F 0 generation) were exposed during 21 d to different bifenthrin concentrations. Offspring(animals from the first and third brood: F 1(1st) and F 1(3rd), respectively) were transferred to a free pesticide medium during a 21 d recovery period. In this recovery study, survival, growth, reproduction(mean total young per female, onset of reproduction and number broods per female) and the intrinsic rate of natural increase (r) were assessed as parameters. Reproduction such as number of young per female as well as length was still reduced in F 1(1st) generation daphnids from parentals(F 0) exposed to the bifenthrin. However F 1(3rd) individuals from parentals exposed to pesticide concentrations were able to restore reproduction when a recovery period of 21 d was allowed, but the length of F 1(3rd) from parentals exposed to the 0.5 and 0.75 μg/L bifenthrin concentration was still significantly effected(P<0.05).

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%.

A novel respirometer for biological toxicity tests

A respirometer has been developed for microbial toxicity tests. The respirometer is based on luminescence quenching by molecular oxygen. The oxygen sensing film consists of luminescent ruthenium complex adsorbed on amorphous fumed silica and immobilized inside silicone rubber. The luminescence intensity depends on the oxygen concentration of sample in contact with sensing film. The inhibition effect of heavy metals on the respiration rate of microorganisms can be evaluated by monitoring the luminescence intensity of the sensing film. The toxicity of Cu^(2+), Zn^(2+), Ni^(2+), Cr^(3+), Pb^(2+)and Hg^( 2+) on activated sludge was tested using the respirometer. The results indicated that the proposed method was sensitive to the heavy metals tested in this experiment. It was feasible to use the respirometer for microbial toxicity tests.

Prospects for the continued development of environmentally-realistic toxicity test susing microorganisms

The focus of environmental regulations has changed significantly since the introduction of the bioassay as a standard means of assessing environmental impact. Prominent in this change is an increasing emphasis on protecting the integrity of natural ecosystems, which incorporate community- and system-level properties as well as organismal and population processes. Consequently, support for the use of multispecies testing has widened to include not only ecologists in academia but environmental scientists in the regulatory and industrial sector as well. The reason for this trend is clear: the additional environmental realism gained from tests utilizing communities of organisms allows for greater insight into the potential hazard of chemicals and other forms of human activity to natural ecosystems that cannot be obtained from single species tests alone. Many of the problems cited for multispecies testing early in their evolution as a hazard assessment tool have been refuted or overcome. In particular, the use of natural microbial communities minimizes several shortcomings typically associated with multispecies toxicity testing. This discussion includes the utility of microcosm and mesocosm tests using aquatic microbial communities as hazard assessment tools in conjunction with accumulating information on their performance in toxicity testing protocols. An increasing body of experimental evidence supports an expansion in the use of these tests for a variety of regulatory and research purposes. A shift in research focus is needed, however, to answer remaining questions and further refine standard protocols for these valuable ecotoxicological tools.

Toxicity Tests of Soil Contaminated by Recycling of Scrap Plastics

The present investigation studied the toxicity of soil contaminated by untreated discharge from a factory that recycles used plastics. The nearby agricultural areas and freshwater fish ponds were polluted with high concentrations of Cu, Ni, and Mn. Water extracts from the contaminated soil retarded root growth of Brassica chinensis (Chinese white cabbage) and Cynodon dactylon (Bermuda grass) where their seeds were obtained commercially. The contaminated populations of C. dactylon, Panicum repen (panic grass), and Imperata cylindrica (wooly grass) were able to withstand higher concentrations of Cu. Ni, and Mn, especially C. dactylon, when compared with their uncontaminated counterparts. 1990 Academic Press, Inc.

Morphological Features of Agaricus bisporus and Indoor Toxicity Test of Chemicals

Through separating and purifying diseased mushrooms infected by Mycogone perniciosa in Gaochun Area, Nanjing City, morphological features of the bacteria were identified, and toxicity of the bacterial strains was tested. The results showed that five bactericides in the experiment had obvious inhibitory effect on the growth of M. perniciosa, especially 50% Prochloraz manganese chloride complex WP 5 g/L had the best efficiency.

Reply to 'Statistical testing and distribution for lead chloride toxicity'

We are very grateful for the letter written by Dr Lange,and indeed apologize for the mistakes noted in the word-ing of our text regarding statistical analysis.This wasdue to changes carried out while revising the manuscriptat the request of reviewers,whom we thank for,point-ing out several issues that were actually similar to thosenoted by Dr.Lange.Unfortunately,we were unable todescribe and discuss our findings properly in the context

Acute Toxicity Test of Miantan Fuzheng Powder

[Objectives] An acute toxicity test of Miantan Fuzheng Powder was conducted on rabbits,which were given Miantan Fuzheng Powder at its maximum administration dosage and observed for 14 d,so as to provide reference for medicine development and clinical test.[Methods] New zealand rabbits were divided into four groups randomly,each of which included 4 rabbits,half male and half female.The Miantan Fuzheng Powder-intact skin and Miantan Fuzheng Powderdamaged skin groups were applied with Miantan Fuzheng Powder once at a dose of 5 g/kg body weight,and the blank control group-intact skin and blank controldamaged skin groups were given the auxiliary material( vaseline) once.The rabbits were observed continuously for 14 d after the administration,and variation in body weight was recorded during the observation and then statistically analyzed with SPSS.After the 14 d of observation,the animals were killed through pentobarbital anesthesia and anatomized to observe main visceral organs including heart,liver,spleen lung and kidney.If toxic effect or organ abnormality exists,pathological sections would be prepared and observed.[Results] Rabbits in the blank control and Miantan Fuzheng Powder groups all showed normal appearance,behavior,breath state,position and posture,response to stimulation and growth of body weight,and no irritative erythema and edema on the skin,and the damaged skin recovered naturally within 14 d.No obvious abnormality was observed on visceral organs in autopsy.The Miantan Fuzheng Powder-intact skin and Miantan Fuzheng Powder-damaged skin groups had no significant differences in body weight from the blank control group-intact skin and blank control-damaged skin groups before administration,and on the 7^(th) and 14^(th) day after administration.[Conclusions] In this acute toxicity test,the Miantan Fuzheng Powder-intact skin and Miantan Fuzheng Powder-damaged skin groups were given the drug at the maximum administration dosage of 5 g/kg body weight,which was about 119 times of the clinical dose for human,and no obvious toxic effect was observed.

Long-term Toxicity of Maxing Erchen Zhike Granules

[Objectives]To study the long-term toxicity of Maxing Erchen Zhike granules to rats after intragastric administration,so as to provide reference for its preclinical safety evaluation.[Methods]Total 80 rats were randomly and evenly divided into high-dose group(1.2 mL/100 g,120 g/kg),middle-dose group(96.0 g/kg),low-dose group(72.0 g/kg)and blank control group.The rats in the treatment groups were administered with corresponding doses of Maxing Erchen Zhike granules,and those in the blank control group were given with equal-amount normal saline.The administration lasted for 30 consecutive days.During the experiment,the rats'feed intake,activity,feces and other conditions and toxicity reactions were observed every day.After 24 h of the last administration,12 rats(half male and half female)were randomly selected from each group.Each of the rats was anesthetized with 10%chloral hydrate solution(0.3 mL/100 g)through intraperitoneal injection and subjected to abdominal aorta blood collection(two tubes)for hematological examination and blood biochemical examination(serum).Then,the main organs of the rats were weighed,and pathological examinations were performed.After that,the main organs were weighed and pathological examination was performed.The remaining rats in each group were discontinued and observed for 14 d.On the 15th d,they were subjected to the same treatment,and the body weight,organ coefficients,hematological indices,blood biochemical indices and pathological indices were examined.[Results]After 30 d of administration,there was no abnormality in the appearance and behavior of the animals.There was no significant difference in the daily consumption of feed among the groups,and there was no special case of weight gain.Among the blood biochemical indices,the ALB and ALT levels of each administration group were significantly different from those of the blank control group(P<0.05).The results of histopathological examination show that there was one case of interstitial pneumonia in each of the high-dose group,middle-dose group and blank control group.After 14 d that the administration was stopped,one case of focal myocarditis appeared in the high-dose group,and one case of interstitial pneumonia appeared in the middle-dose group.[Conclusions]Maxing Erchen Zhike granules are safe to be administered to rats at 100 times the clinical dose.and there should be no safety hazards clinically when used at conventional doses.

Toxicity and Field Efficacy Test of Several Insecticides against Carsidara marginalis Walker

[Objective]The paper was to study the prevention and control effect of different chemical insecticides on Carsidara marginalis Walker.[Method]The indoor toxicity and field efficacy of six insecticides against C.marginalis were determined by residual film method and field efficacy test.The toxicity and field efficacy were comparatively analyzed.[Result]The LC50 of 5%abamectin EC,24%spirotetramat EC,10%lambdacyhalothrin EC,10%nitenpyram SL,25%pymetrozine WP and 20%imidacloprid EC against C.marginalis were 3.585,12.083,15.012,18.754,23.373 and 61.161 mg/L,respectively.The field efficacies against C.marginalis at 1 d post administration were 78.04%,80.05%,69.92%,82.27%,71.72%and 76.72%,respectively.The field efficacies against C.marginalis at 10 d post administration were 92.49%,82.41%,83.80%,88.24%,94.10%and 97.01%,respectively.[Conclusion]The agents with strong quick effect and insecticides with strong systematic conductivity should be mixed together,in order to achieve quick and continuous insecticidal effects.

Sensitivity of Different Cytotoxic Responses of Vero Cells Exposed to Organic Chemical Pollutants and their Reliability in the Bio-toxicity Test of Trace Chemical Pollutants

Objective To find a sensitive cytotoxic response to reflect the bio-toxicity of trace organic pollutants, the sensitivity and reliability of morphological change and proliferation inhibition of Vero cells exposed to 2, 4, 6-trichlorophenol （TCP） and the leachate from products related to drinking water （PRDW） were compared, and the mechanism of the morphological change in Vero cells exposed to chemical pollutants was studied. Methods Vero cells were treated by different concentration of TCP and the leachate from PRDW. Methylthiazol-2-yl-2, 5-diphenyl tetrazolium bromide （MTT） assay was carried out for proliferation inhibition. Bioluminescence method was carried out as another method to test the toxicity of TCP. Flow Cytometry assay was used to test cell Apoptosis and damage of cell-membrane. Results 0.25 mg/L TCP had an effect on cell morphology, and the proportion of morphologically changed cells increased with increasing TCP concentration. At low TCP concentrations, inhibition of cell proliferation did not seem to correlate to TCP concentration, and was negative when TCP concentration was 〈1.0 mg/L. After exposure to leachate from PRDW extracted at different temperatures, the percentage of morphologically changed cells increased with extracting temperature, but the inhibition of cell proliferation failed to reflect the correlation between extracting temperature and proliferation inhibition of Vero cells. Although the Sensitivity of bioluminescence method seems to be similar to morphological change in Veto cells, the bacterial in this method is not homologous enough with human body cells to reflect the toxicity to human body. These imply cell morphological change is a more sensitive and reliable method to reflect bio-toxicity of organic pollutants than proliferation inhibition. Flow cytometry analysis and cell rejuvenation experiments indicated cell membrane damage, which results in cell morphological change, was an early and sensitive cytotoxic response comparing with necrosis. Conelusion These results indicated that the cell membrane toxicity represented by morphological changes is a more sensitive and reliable method to indicate the composite bio-toxicity of trace chemicals than proliferation inhibition, inhibition on bioluminescence and necrosis. Nevertheless, the quantification of morphological change should be studied further.

Subchronic Oral Toxicity Evaluation of Lanthanum： A 90-day, Repeated Dose Study in Rats

Objective The present study was undertaken to evaluate the subchronic toxicity of lanthanum and to determine the no observed adverse effect level（NOAEL）,which is a critical factor in the establishment of an acceptable dietary intake（ADI）.Methods In accordance with the Organization for Economic Co-operation and Development（OECD） testing guidelines,lanthanum nitrate was administered once daily by gavage to Sprague-Dawley（SD） rats at dose levels of 0,1.5,6.0,24.0,and 144.0 mg/kg body weight（BW） per day for 90 days,followed by a recovery period of 4 weeks in the 144.0 mg/kg BW per day and normal control groups.Outcome parameters were mortality,clinical symptoms,body and organ weights,serum chemistry,and food consumption,as well as ophthalmic,urinary,hematologic,and histopathologic indicators.The benchmark dose（BMD） approach was applied to estimate a point of departure for the hazard risk assessment of lanthanum.Results Significant decreases were found in the 144.0 mg/kg BW group in the growth index,including body weight,organ weights,and food consumption.This study suggests that the NOAEL of lanthanum nitrate is 24.0 mg/kg BW per day.Importantly,the 95% lower confidence value of the benchmark dose（BMDL） was estimated as 9.4 mg/kg BW per day in females and 19.3 mg/kg BW per day in males.Conclusion The present subchronic oral exposure toxicity study may provide scientific data for the risk assessment of lanthanum and other rare earth elements（REEs）.

Preparation and toxicity evaluation of a novel nattokinase-tauroursodeoxycholate complex

Nattokinase(NK), which has been identified as a potent fibrinolytic protease, has remarkable potential in treatment of thrombolysis, and even has the ability to ameliorate chronic vein thrombosis. To reduce the hemorrhagic risk from an intravenous injection of NK,nattokinase-tauroursodeoxycholate(NK-TUDCA) complex was prepared at different pH values and with different ratios of NK and TUDCA. When assessing survival time, survival state,tail injury, and the body weight of mice, it was found that the NK-TUDCA complex(NK: 10 k IU/ml; TUDCA: 10 mg/ml; pH 5.0) had a lower toxicity when administered at an NK dosage of 130 kIU/kg in the acute toxicity test and 13 kIU/kg in the repeated low-dose challenge. From the results of the in vitro thrombolytic test and characterization of NKTUDCA, we speculated that the delayed release of NK-TUDCA might be the main cause of toxicity reduction by the complex. This study described the preparation of an NK complex with low toxicity following intravenous administration, which could be utilized for further clinical study of NK.

Human Embryo Neuronal Culture <i>in Vitro</i>: A Model to Study Cellular Physiology, Receptors, Power and Toxicity of Cytostatic Drugs for Human Use

Neural cells cultures from human embryo brain of 9° - 11°W gestational age have been used to study ERα (Estrogens Receptor α) and to perform toxicity test for Mitomycin C and Methotrexate. Histochemical confirmation of cellular neuronal phenotype was based on histochemical evidence of NSE (Neuron Specific Enolase).The detection of ERα in neuronal cells was performed with a rabbit Monoclonal Antibody. ERα was absent both on neurons grown in vitro and on tissue brain specimens. This finding is apparently in contrast with the positive immunoreactivity of ERα and ERβ reported by other Authors on foetal and adult CNS (Central Nervous System). The absence of nuclear ERα on neurons in culture and in brain tissue specimens in our experiment is not in contrast with the relevant physiologic role of estrogens on nervous central system, but it could be correlated to the embryonic period of life and could represent a protection of male brain from an undue estrogens imprinting. The mitomycin C, alkylation agent, has shown in our experiment a major neurotoxic and cytostatic power in comparison with methotrexate. Our conclusion is that human embryo neuronal culture in vitro is a powerful instrument for physiology and human therapy for cancer and neurodegenerative diseases.

Toxicity of novel anti-hepatitis drug bicyclol: A preclinical study

AIM: To study the toxicity of bicyclol to animals.METHODS: Acute toxicity test was performed in Kunming strain mice that were orally given bicyclol at the doses of 3 and 5 g/kg body weight, respectively. Wistar rats were orally administered bicyclol at a dose of 5 g/kg body weight. Death and clinical symptoms of animals were recorded within 7 d. Sub-acute toxicity test was carried out in rats that were treated with various doses of bicyclol (150, 300, 600 mg/kg) once daily for 14 d.Animal behaviors, blood biochemical markers, blood and urine pictures were examined. Chronic toxicity test was conducted in 80 Wistar rats of both sexes. The animals were orally administered with various doses of bicyclol[150, 300, 600 mg/kg, 100-400 folds corresponding to for patients] once daily for 6 mo except for Sunday. The control group was given the same volume of 0.2%sodium carboxyl methylcellulose (Na-CMC). Twenty-one beagle dogs received bicyclol (25, 75, 225 mg/kg, 16.6,50, 150 folds corresponding to the proposed therapeutic dose of bicyclol for patients) once a day for 6 mo except for Sunday. The body weight, food intake, urine and feces, blood picture, blood biochemical markers, and pathological examination of main organs were determined. Mutagenicity and teratogenicity were determined. Mutagenicity assay included Ames's test, chromosome aberration test in CHL cells and micronucleus test in mice. For the teratogenicity assay, pregnant Wistar rats weighing 200-250 g were treated with 0.2, 1.0 g/kg bicyclol once daily from the 7th d of gestation for 10 d.RESULTS: The oral LD50 of bicyclol was over 5 g/kg in mice and rats. No noticeable alterations in subacute and chronic toxicity of rats and dogs were demonstrated. No mutagenicity and teratogenicity of bicyclol were found.CONCLUSION: Bicyclol has no detectable chronic toxicity as well as mutagenicity and teratogenicity in animals.

Subchronic Oral Toxicity Evaluation of Sodium Dehydroacetate: A 90-day Repeated Dose Study in Rats

Objective The present study was undertaken to evaluate the subchronic oral toxicity of sodium dehydroacetate(DHA-Na)and to determine the point of departure(POD),which is a critical factor in the establishment of an acceptable dietary intake.Methods DHA-Na was administered once daily by gavage to Sprague–Dawley rats at dose levels of 0.0,31.0,62.0,and 124.0 mg/kg BW per day for 90 days,followed by a recovery period of 4 weeks in the control and 124.0 mg/kg BW per day groups.The outcome parameters were mortality,clinical observations,body weights,food consumption,hematology and clinical biochemistry,endocrine hormone levels,and ophthalmic,urinary,and histopathologic indicators.The benchmark dose(BMD)approach was applied to estimate the POD.Results Significant decreases were found in the 62.0 and 124.0 mg/kg BW groups in terms of the body weight and food utilization rate,whereas a significant increase was found in the thyroid stimulating hormone levels of the 124.0 mg/kg BW group.Importantly,the 95%lower confidence limit on the BMD of 51.7 mg/kg BW was modeled for a reduction in body weight.Conclusion The repeated-dose study indicated the slight systemic toxicity of DHA-Na at certain levels(62.0 and 124.0 mg/kg BW)after a 90-day oral exposure.

Evaluation of Acute Chromium (III) Toxicity in Relation to Daphnia Similis

Acute chromium (III) toxicity in relation to Daphnia similis, most appropriate for Brazilian environment has been evaluated. The preliminary toxicity test showed that the median effective concentration was 10 mg/l. After having performed the final test, the immobility percentage was calculated for each concentration in relation to the total number of the used organisms within the chosen pH range. It was shown that the proposed methodology rendered realistic results and the 48-h CE50 value under the test conditions is 3.24 mg/l. The minimum concentration that did not show any toxicity to Daphnia similis was 2.5 mg of chromium (III) per liter. The obtained level is superior to the maximum limit recommended by the Brazilian norms, 0.5 mg/l.

Indoor Toxicity and Field Efficacy of Five Insecticides against Cerataphis lataniae Biosduval

[ Objective ] The paper aimed to screen out efficient and safe insecticides against Gerataphis lataniae Biosduval. [ Method ] Control effects of five insecticides against C. lataniae were studied through indoor bioassay and field trial. [ Result] Bioassay results showed that the indoor toxieities of 10% ct-cyper- methrin, 22% sulfoxaflor and 10% imidecloprid were higher, with LC50 of 15.28, 30.00 and 30.23 rag/L, respectively. In field trials, the control effects of 10% α-cypermethrin, 22% sulfoxaflor and 10% imidacloprid against C. lataniae were over 90% for all the concentrations at 10 d post adminstration. The control effect of 22% sulfoxaflor reached 100% for all the concentrations at 5 d post administration. [ Conclusion] 10% α-cypermethrin was a superior pesticide against C. /a- taniae, but 22% sulfoxaflor and 10% imidaclopfid were more efficient in emergency.