[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 acc...[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.展开更多
Vanadium compounds are promising anti-diabetic agents. However, the concern in the toxicity, especially the long-term renal side effect along with diabetic status, is restricting the further development of this metal ...Vanadium compounds are promising anti-diabetic agents. However, the concern in the toxicity, especially the long-term renal side effect along with diabetic status, is restricting the further development of this metal drug. Recently, we have prepared a bis（（5-hydroxy-4-oxo-4H-pyran-2-yl） methyl 2-hydroxy-benzoatato） oxovanadium（BSOV）, which exhibited excellent hypoglycemic effect with low acute toxicity. In order to facilitate the development of anti-diabetic vanadium complexes, especially BSOV, we studied the long-term toxicity and hypoglycemic effect of BSOV in comparison with bis（maltolato） oxovanadium（BMOV） on both non-diabetic and type II diabetic mice. The experiments confirmed a stable hypoglycemic effect for both the vanadium complexes over the testing period（6–7 months）. However, the chronic administration of vanadium compounds slightly increased oxidative stress in ICR mice and the induced renal interstitial edema（RIE） in a part of the diabetic animals associated with low levels of serum albumin. The use of an antioxidant dietary supplement（a combination of vitamin C and Zinc gluconate） could prevent vanadium-induced oxidative stress but have marginal effect on RIE. However, BSOV caused much lower incidence of RIE than BMOV did, suggesting that BSOV is an important step towards the successful development of anti-diabetic vanadium drugs.展开更多
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...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%.展开更多
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 r...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).展开更多
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 o...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.展开更多
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 prote...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.展开更多
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 co...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.展开更多
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 test...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.展开更多
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 manu...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展开更多
[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 ...[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.展开更多
To address the controversial issue of the toxicity of dental alloys and silver nanoparticles in medical ap- plications, an in vivo-like LO2 3-D model was constructed within polyvinylidene fluoride hollow fiber materia...To address the controversial issue of the toxicity of dental alloys and silver nanoparticles in medical ap- plications, an in vivo-like LO2 3-D model was constructed within polyvinylidene fluoride hollow fiber materials to mimic the microenvironment of liver tissue. The use of microscopy methods and the measurement of liver-specific functions optimized the model for best cell performances and also proved the superiority of the 3-D LO2 model when compared with the traditional monolayer model. Toxicity tests were conducted using the newly constructed model, finding that four dental castings coated with silver nanoparticles were toxic to human hepatocytes after cell viability assays. In general, the toxicity of both the castings and the coated silver nanoparticles aggravated as time increased, yet the nanoparticles attenuated the general toxicity by preventing metal ion release, especially at high concentrations.展开更多
[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 random...[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.展开更多
[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.margin...[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.展开更多
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...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.展开更多
[Objective] The paper was to screen the pesticides with good control effects against pests in mulberry and small impact on silkworm. [Method] The combined method of indoor toxicity test, field efficacy test, fast test...[Objective] The paper was to screen the pesticides with good control effects against pests in mulberry and small impact on silkworm. [Method] The combined method of indoor toxicity test, field efficacy test, fast testing of pesticide residues and residual toxicity determination were adopted to carry out test. [ Re- suit] Indoor toxicity results showed that LC50 of mulberry No. 1 against Hyalopterus amygdale was （316.1±57.3） mg/kg, and the control effect of mulberry No. 1 at 14 d reached 62.58% ; fast testing of pesticide residues at 7 d showed that the mulberry leaves were safe to silkworms, which reached the standard of leaves for silkworm. [ Conclusion] Mulberry No. 1 was recommended to be the Special pesticide to apply in mulberry field.展开更多
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 hemorr...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.展开更多
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 acceptab...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）.展开更多
OBJECTIVE: To observe toxicity-reduced effects of Leigongteng(Radix et Rhizoma Tripterygii)(LGT) via compatibility with Jinqiancao(Herba Lysimachiae)(JQC) in H22-bearing mice and investigate the possible underlying me...OBJECTIVE: To observe toxicity-reduced effects of Leigongteng(Radix et Rhizoma Tripterygii)(LGT) via compatibility with Jinqiancao(Herba Lysimachiae)(JQC) in H22-bearing mice and investigate the possible underlying mechanism, and further explore whether JQC can enhance LGT-evoked anti-tumor effect.METHODS: H22-bearing mice were orally administered with LGT alone and its compatibility with JQC, and tumors, serum, livers and kidneys were collected to evaluate the toxicity-reduced efficacy and the possible mechanism.RESULTS: LGT evoked significantly elevated biochemical indicators including serum alanine/aspartate transaminase(ALT/AST), creatinine(Cr) and urea nitrogen(BUN) as well as pathological damage in mice, which were all obviously reversed by JQC via compatibility at the ratios from 4/1 to 1/4.Further analysis indicated that pro-inflammatory cytokine tumor necrosis factor-alpha(TNF-α), and malondialdehyde(MDA) levels significantly decreased, while anti-inflammatory cytokine interleukin(IL)-10, and glutathione(GSH), GSH-s transferase(GST), GSH peroxidase(GSH-Px), superoxide dismutase(SOD) and catalase(CAT) levels all increased in livers and kidneys of mice. Besides, after compatibility with JQC at the ratios of 4/1, 2/1, 1/1,1/2 and 1/4, LGT-decreased tumor weight was further decreased by 48.4%, 57.3%, 54.0%, 49.3% and52.9%, respectively(all P < 0.01).CONCLUSION: JQC could reduce LGT-induced hepatotoxicity and nephrotoxicity, and enhance the antitumor efficacy via compatibility with JQC, and the toxicity-reduced mechanism could involve inhibiting hepatic and kidney oxidative stress and inflammation.展开更多
[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 g...[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）.展开更多
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 ...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 the proposed therapeutic dose (1.5 mg/(kg·d)) of bicyclol 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.展开更多
基金Supported by Modern Pharmaceutical Program of Guiyang Scientific and Technological Planning Project in 2013(ZKHT[2013204]4-6)Special Fund for Research and Development of Traditional Chinese Medicine(TCM)Modernization Technology Industry(QKHZYZ[2011]5012)~~
文摘[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.
基金National Natural Science Foundation of China(Grant No.21271012)
文摘Vanadium compounds are promising anti-diabetic agents. However, the concern in the toxicity, especially the long-term renal side effect along with diabetic status, is restricting the further development of this metal drug. Recently, we have prepared a bis（（5-hydroxy-4-oxo-4H-pyran-2-yl） methyl 2-hydroxy-benzoatato） oxovanadium（BSOV）, which exhibited excellent hypoglycemic effect with low acute toxicity. In order to facilitate the development of anti-diabetic vanadium complexes, especially BSOV, we studied the long-term toxicity and hypoglycemic effect of BSOV in comparison with bis（maltolato） oxovanadium（BMOV） on both non-diabetic and type II diabetic mice. The experiments confirmed a stable hypoglycemic effect for both the vanadium complexes over the testing period（6–7 months）. However, the chronic administration of vanadium compounds slightly increased oxidative stress in ICR mice and the induced renal interstitial edema（RIE） in a part of the diabetic animals associated with low levels of serum albumin. The use of an antioxidant dietary supplement（a combination of vitamin C and Zinc gluconate） could prevent vanadium-induced oxidative stress but have marginal effect on RIE. However, BSOV caused much lower incidence of RIE than BMOV did, suggesting that BSOV is an important step towards the successful development of anti-diabetic vanadium drugs.
基金partially supported by National Natural Scientific Foundation of China[81620108026,81302393]
文摘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%.
文摘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).
文摘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.
基金This manuscript and specific ex periments discussed within were sponsored,in part,by grants from The Procter&Gamble Company and the du Pont Educational Foundation,altbough the authors take full responsibility for the views ex-pressed herein.
文摘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.
文摘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.
基金Sponsored by Qing Lan Project&Research Program of Jiangsu Polytechnic College of Agriculture and Forestry(2011KJ14)
文摘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.
文摘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
基金Supported by Guizhou Scientific and Technological Cooperation Program[QKHLHZ(2015)7254]
文摘[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.
基金Project supported by the Zhejiang Provincial Natural Science Foundation of China(No.LZ14C200001)the Public Welfare Project of Science Technology Department of Zhejiang Province(No.2013c33139),China
文摘To address the controversial issue of the toxicity of dental alloys and silver nanoparticles in medical ap- plications, an in vivo-like LO2 3-D model was constructed within polyvinylidene fluoride hollow fiber materials to mimic the microenvironment of liver tissue. The use of microscopy methods and the measurement of liver-specific functions optimized the model for best cell performances and also proved the superiority of the 3-D LO2 model when compared with the traditional monolayer model. Toxicity tests were conducted using the newly constructed model, finding that four dental castings coated with silver nanoparticles were toxic to human hepatocytes after cell viability assays. In general, the toxicity of both the castings and the coated silver nanoparticles aggravated as time increased, yet the nanoparticles attenuated the general toxicity by preventing metal ion release, especially at high concentrations.
基金Scientific Research Project of the First Affiliated Hospital of Guangxi University of Chinese Medicine(2017ZJ006)Key Research and Development Project of Department of Science and Technology of Guangxi Zhuang Autonomous Region(AB19110003).
文摘[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.
基金Supported by Guangxi Special Fund for Innovation-driven Development(GK AA17204045-4)National Natural Science Foundation of China(31860533)。
文摘[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.
基金supported by the National Natural Science Foundation in China(No.20677043 and 40871217).
文摘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.
基金Supported by Education Science Foundation of Guangxi Education Department(GJKY[2007]No.34)~~
文摘[Objective] The paper was to screen the pesticides with good control effects against pests in mulberry and small impact on silkworm. [Method] The combined method of indoor toxicity test, field efficacy test, fast testing of pesticide residues and residual toxicity determination were adopted to carry out test. [ Re- suit] Indoor toxicity results showed that LC50 of mulberry No. 1 against Hyalopterus amygdale was （316.1±57.3） mg/kg, and the control effect of mulberry No. 1 at 14 d reached 62.58% ; fast testing of pesticide residues at 7 d showed that the mulberry leaves were safe to silkworms, which reached the standard of leaves for silkworm. [ Conclusion] Mulberry No. 1 was recommended to be the Special pesticide to apply in mulberry field.
文摘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.
基金supported by China Food Safety Talent Competency Development Initiative:CFSA 523 Programthe National Natural Science Foundation of China[No.81402683]
文摘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）.
基金Supported by the National Natural Science Foundation of China(No.81503269)the Science and Technology Innovation Talent Fund of Henan Chinese Medicine(No.2015XCXRC01)the Provincial Fundamental Research Fund in Henan University of Chinese Medicine(No.2014KYYWF-QN01)
文摘OBJECTIVE: To observe toxicity-reduced effects of Leigongteng(Radix et Rhizoma Tripterygii)(LGT) via compatibility with Jinqiancao(Herba Lysimachiae)(JQC) in H22-bearing mice and investigate the possible underlying mechanism, and further explore whether JQC can enhance LGT-evoked anti-tumor effect.METHODS: H22-bearing mice were orally administered with LGT alone and its compatibility with JQC, and tumors, serum, livers and kidneys were collected to evaluate the toxicity-reduced efficacy and the possible mechanism.RESULTS: LGT evoked significantly elevated biochemical indicators including serum alanine/aspartate transaminase(ALT/AST), creatinine(Cr) and urea nitrogen(BUN) as well as pathological damage in mice, which were all obviously reversed by JQC via compatibility at the ratios from 4/1 to 1/4.Further analysis indicated that pro-inflammatory cytokine tumor necrosis factor-alpha(TNF-α), and malondialdehyde(MDA) levels significantly decreased, while anti-inflammatory cytokine interleukin(IL)-10, and glutathione(GSH), GSH-s transferase(GST), GSH peroxidase(GSH-Px), superoxide dismutase(SOD) and catalase(CAT) levels all increased in livers and kidneys of mice. Besides, after compatibility with JQC at the ratios of 4/1, 2/1, 1/1,1/2 and 1/4, LGT-decreased tumor weight was further decreased by 48.4%, 57.3%, 54.0%, 49.3% and52.9%, respectively(all P < 0.01).CONCLUSION: JQC could reduce LGT-induced hepatotoxicity and nephrotoxicity, and enhance the antitumor efficacy via compatibility with JQC, and the toxicity-reduced mechanism could involve inhibiting hepatic and kidney oxidative stress and inflammation.
基金Supported by Traditional Chinese Medicine and Ethnic Minority Medicine Technique Research Subject of Guizhou Administrative Bureau of TCM(QZYY-2015-134,QZYY-2014-026)~~
文摘[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）.
基金Supported by the Grant From Ministry of Sciences and Technology of China, No.96-901-01 -45
文摘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 the proposed therapeutic dose (1.5 mg/(kg·d)) of bicyclol 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.
