Microelectronic cell sensor assay for detection of cytotoxicity and prediction of acute toxicity.

This study reports in-house assessment of a real-time cell electronic sensing (RT-CES) system used as a test platform for both cytotoxicity assay and predicting acute toxicity. For cytotoxicity determination, the RT-CES assay displayed equal sensitivity and coefficients of variation values with good correlation to NRU assay. The IC50 values and the LD50 values for the cytotoxicity reference materials were compared in the context of the proposed prediction model for acute rodent toxicity. The results obtained from RT-CES assay fitted within the acceptance limits of the prediction model and showed that the RT-CES cytotoxicity assay met the qualification guidelines in NIH Publication #01-4500 to accurately predict acute toxicity. In addition to cell viability, the RT-CES assay provided dynamic information that can be used to identify maximum toxicity and reversibility of the toxic effects which are difficult to achieve by the endpoint assays and, therefore, the RT-CES assay is more accurate for assessment of cytotoxicity. The features of the RT-CES assay, such as labeling free, automatic detection, and easy operation, give this assay potential to replace BALB/c 3T3 NRU assay and be used as routine setting for drug monitoring in the toxicological laboratory.     

701跌打镇痛膏安全性实验研究

的 研究701 跌打镇痛膏经皮给药急性毒性、皮肤刺激性和过敏性,为其临床应用和推广提供实验依据。 方法 选用新西兰兔和 Hartley 豚鼠为研究对象,分别采用最大耐受量法和同体左右侧对照给药的方法考察701 跌打镇痛膏经皮给药的急性毒性、皮肤刺激性和过敏性。 结果 701 跌打镇痛膏经皮给药后对新西兰兔未见明显毒性反应;对新西兰兔破损皮肤会产生刺激性反应,但此刺激性可于停药后14 d 完全恢复;对新西兰兔完整皮肤也会产生轻度刺激性,但此刺激性是一过性反应;对 Hartley 豚鼠未产生明显过敏反应。 结论 701 跌打镇痛膏具有良好的安全性,经皮单次和多次给药后除轻微的皮肤刺激性外未见其他明显毒性反应,且所产生的皮肤刺激性均为可逆性反应,值得进一步推广应用。 但在临床应用中701 跌打镇痛膏应尽量在损伤局部皮肤无明显破损时使用,尽量避免在破损皮肤上使用,以减少药物对皮肤的刺激性。     

提取方式对北豆根“质量-毒性”综合评价模式的影响

目的 对不同提取方式制备的北豆根中生物碱的含量和急性毒性大小进行比较研究,探讨不同提取方式对北豆根“质量-毒性”综合评价模式的影响.方法 以0.5％硫酸为溶剂,用热回流法、超声法、渗漉法、温浸法4种方法提取北豆根总生物碱,用酸碱滴定法测定了总生物碱的含量,用高效液相色谱法测定提取物中蝙蝠葛碱的含量,用经典急性毒性实验法进行急性毒性比较研究.结果 不同提取样品中总生物碱含量大小依次为:超声法＞渗漉法,热回流法和温浸法所得提取样品总生物碱含量无法测出.蝙蝠葛碱的含量是热回流法大于温浸法,但超声法和渗漉法未测出蝙蝠葛碱含量.不同提取方式对小鼠急性毒性最大给药量( MLD)大小为:渗漉法＞超声法＞热回流法＞温浸法,以温浸法所得提取样品的急性毒性最大.结论 提取方式不同,北豆根主要化学成分含量和毒性大小不同,而且其毒性大小与总生物碱和蝙蝠葛碱含量有一定的关系,但不完全一致.说明提取方式对北豆根“质量-毒性”综合评价模式有一定的影响,通过此综合评价模式确定有毒中药的提取方式,更全面客观合理.     

桑黄发酵多糖胶囊急性毒性和遗传毒性研究

本文通过急性毒性试验、小鼠精子畸形试验和骨髓微核试验,研究桑黄发酵多糖胶囊的急性毒性和遗传毒性的影响。试验结果表明,小鼠对桑黄发酵多糖胶囊的最大耐受量大于20g/kg,与空白组相比,胶囊组小鼠的精子畸形率和骨髓细胞微核率无显著性差异。结果表明,桑黄发酵多糖胶囊属实际无毒物质,无遗传毒性。     

Validity of in vitro testing

In summary, the extent of toxicity studies which can be carried out with bound residues of nitroimidazole drugs will be dictated by the availability and the amount of residues that can be produced. For evaluating their toxicity the use of the Salmonella assay, which has been proven to be sensitive for the parent drugs, is proposed. Furthermore, it is suggested that the toxicity of bound residues for in vivo effects should be investigated in cells of target tissues, such as the epithelial cells of the gastrointestinal tract. Nuclear aberration and sister chromatid exchange assays in this tissue would be good candidates for evaluation. It should be pointed out also that an examination of the literature for genotoxic effects of nitroimidazole drugs reveals an apparent contradiction, especially in the context of genotoxicity testing strategy discussed above. It appears first that these drugs are potent mutagens in vitro in microbial systems (Salmonella and yeast). However, they are not active in mammalian cells in vitro, in both mutation and chromosomal aberration assays, as well as in vivo, in assays such as the dominant lethal test and the micronucleus assay. Thus, it may be of interest to speculate that, although these drugs are in vitro mutagens, they may not be in vivo mutagens in mammals. Their tumorigenic effects, which have been detected at high doses in rodents, may, therefore, be due to other than genotoxic activity. To resolve this conflict, reassessment of genotoxicity of these drugs in vivo would be a worthwhile pursuit. In addition, such seeming discrepancies would also argue strongly for toxicity screening to be conducted in a battery of complementary short-term in vitro and in vivo tests. This would help insure the likelihood of detection of at least some meaningful biological activity, which would serve to flag chemicals warranting further testing.     

Toxicological studies on a new macrolide antibiotic, midecamycin acetate (miocamycin). Part IV-6. Toxicity of metabolites of miocamycin: subacute toxicity of Mb2 in rats

Miocamycin (MOM) is a derivative of midecamycin, a macrolide antibiotic and is metabolized into 4 main metabolites of Mb1, Mb2, Mb6 and Mb12. At previous study, the acute and subacute toxicity of Mb1 and acute toxicity of Mb2 were performed that those metabolites did not exhibit any lethal toxicity even at the maximum physically applicable dose. The object of this study was to examine subacute toxicity in male and female rats after repeated p.o. administration of Mb2 for 5 weeks at a daily dosage of 125, 250, 500 and 1,000 mg/kg. It is, therefore, concluded that Mb2 exerted no toxic effects in this subacute toxicity.     

The toxicity and mutagenicity of S-3-iodo-N-(1-ethyl-2-pyrrolidinyl)methyl-2-hydroxy-6-methoxybenzamide (IBZM), a new CNS D-2 dopamine receptor imaging agent

IBZM is one of several benzamide derivatives showing a high affinity for the CNS D-2 dopamine receptor. Carrier-free [123I]IBZM is potentially useful as a nuclear medicine imaging agent for investigating CNS D-2 dopamine receptor in humans. This study describes the acute toxicity of IBZM in the rat and rabbit, its subchronic toxicity in the rabbit and its mutagenicity measured by the Ames test. IBZM had a 24 hour LD50 of 400 mg/kg in the rat and 50 mg/kg in the rabbit when administered i.v. Deaths occurred within minutes of dosing. Some necrosis was evident at the injection site in IBZM treated animals which was not found in the controls. No gross or histological differences between experimental animals and controls were evident in surviving animals when necropsied 14 days after dosing. Repeated exposure of rabbits to IBZM at a total cumulative dose of 100,000 times the expected clinical dose revealed no consistent changes in hematology, blood chemistry, blood enzymes or tissue pathology. IBZM was not mutagenic in the modified Ames assay with or without metabolic activation in the TA98 and TA100 tester strains. It is therefore unlikely that acute adverse effects will be associated with the diagnostic use of this drug in man.     

Pharmacogenetic aspects of the use of tacrolimus in renal transplantation: recent developments and ethnic considerations

Introduction: Tacrolimus (Tac) is effective in preventing acute rejection but has considerable toxicity and inter-individual variability in pharmacokinetics and pharmacodynamics. Part of this is explained by polymorphisms in genes encoding Tac-metabolizing enzymes and transporters. A better understanding of Tac pharmacokinetics and pharmacodynamics may help to minimize different outcomes amongst transplant recipients by personalizing immunosuppression.

Areas covered: The pharmacogenetic contribution of Tac metabolism will be examined, with a focus on recent discoveries, new developments and ethnic considerations.

Expert opinion: The strongest and most consistent association in pharmacogenetics is between the CYP3A5 genotype and Tac dose requirement, with CYP3A5 expressers having a ~ 40–50% higher dose requirement compared to non-expressers. Two recent randomized-controlled clinical trials using CYP3A5 genotype, however, did not show a decrease in acute rejections nor reduced toxicity. CYP3A4*22, CYP3A4*26, and POR*28 are also associated with Tac dose requirements and may be included to provide the expected improvement of Tac therapy. Studies focusing on the intracellular drug concentrations and on calcineurin inhibitor-induced nephrotoxicity also seem promising. For all studies, however, the ethnic prevalence of genotypes should be taken into account, as this may significantly impact the effect of pre-emptive genotyping.     

Toxicity ranking of heavy metals with screening method using adult Caenorhabditis elegans and propidium iodide replicates toxicity ranking in rat

The utility of any model system for toxicity screening depends on the level of correlation between test responses and toxic reactions in humans. Assays in Caenorhabditis elegans can be fast and inexpensive, however few studies have been done comparing toxic responses in this easily cultured nematode with data on mammalian toxicity. Here we report that a screening assay for acute toxicity, using adult C. elegans grown in axenic liquid culture, replicated LD50 toxicity ranking in rat for five metals. This assay utilized the COPAS Biosort and propidium iodide (PI) as a fluorescent indicator of morbidity and mortality after 30-h exposures. We found that chronic toxicity assays of 2-week treatment duration, followed by analysis of PI induced red fluorescence levels, produced less consistent results than the acute assays. However, other chronic toxicity endpoints were compound and concentration specific, including changes in vulval and gonadal morphology, intestinal thickness and integrity, and the presence of retained internal eggs in post-reproductive animals. Some of these endpoints reflect similar findings in mammals, indicating that measurements of morbidity and mortality in conjunction with morphology analyses in C. elegans may have the potential to predict mammalian toxic responses.     

Development of a base set of toxicity tests using ultrafine TiO2 particles as a component of nanoparticle risk management

The development of a risk management system for nanoscale or ultrafine particle-types requires a base set of hazard data. Assessing risk is a function of hazard and exposure data. Previously, we have suggested "parallel tracks" as a strategy for conducting nanoparticle research. On the one hand, mechanistic studies on "representative" nanoparticles could be supported by governmental agencies. Alternatively, with regard to commercial nanoparticles, the environmental, health and safety (EHS) framework would include a minimum base set of toxicity studies which should be supported by the companies that are developing nano-based products. The minimum base set could include the following criteria: substantial particle characterization, pulmonary toxicity studies, acute dermal toxicity and sensitization studies, acute oral and ocular toxicity studies, along with screening type genotoxicity, and aquatic toxicity studies. We report here the toxicity results of a base set of hazard tests on a set of newly developed, well-characterized, ultrafine TiO(2) (uf-TiO(2)) particle-types. In vivo pulmonary toxicity studies in rats demonstrated low inflammatory potential and lung tissue toxicity. Acute dermal irritation studies in rabbits and local lymph node assay results in mice indicated that uf-TiO(2) was not a skin irritant or dermal sensitizer. Acute oral toxicity studies demonstrated very low toxicity and uf-TiO(2) produced short-term and reversible ocular conjunctival redness in rabbits. Genotoxicity tests demonstrated that uf-TiO(2) was negative in both the bacterial reverse mutation test and in an in vitro mammalian chromosome aberration test with Chinese hamster ovary cells. The results of aquatic toxicity screening studies demonstrated that uf-TiO(2) exhibited low concern for aquatic hazard in unaerated, 48h, static acute tests using the water flea, Daphnia magna; exhibited low concern for aquatic hazard in unaerated, 96h, static acute tests using the rainbow trout, Oncorhynchus mykiss; and exhibited medium concern in a 72h acute test using the green algae Pseudokirchneriella subcapitata. To summarize the findings, the results of most of the studies demonstrated low hazard potential in mammals or aquatic species following acute exposures to the ultrafine TiO(2) particle-types tested in this program.     

硫磺熏制白芍的安全性评价初步研究

建立硫磺熏制白芍中芍药苷及其衍生物芍药苷亚硫酸酯、芍药内酯苷的高效液相色谱含量测定方法,并通过对芍药苷亚硫酸酯的细胞毒性以及白芍药材的小鼠急性毒性评价,对硫磺熏制前后的白芍进行安全性评价研究。含量测定采用Shiseido Capcell PAK C18(250 mm×4.6 mm ID,5μm)色谱柱,流动相乙腈—0.02%磷酸水溶液(15∶85),检测波长230 nm,流速1.0 mL.min-1,柱温30℃;采用MTT法考察芍药苷亚硫酸酯对小鼠原代肝细胞和人原代肝细胞的毒性;采用小鼠灌胃最大给药量法考察芍药苷亚硫酸酯和白芍的急性毒性。芍药苷亚硫酸酯、芍药苷和芍药内酯苷分别在0.041 8～1.045 0 mg.mL-1、0.023 5～0.587 5 mg.mL-1和0.039 8～0.995 0 mg.mL-1内呈良好线性,r>0.999 8,平均回收率99.11%～101.71%,RSD<2%;芍药苷亚硫酸酯的浓度≤300μmol.L-1,各检测浓度均无明显细胞毒性;芍药苷亚硫酸酯水溶液和白芍水提物分别进行小鼠灌胃给药,最大耐受量分别为5 g.kg—1和80 g.kg-1。建立的白芍中3个成分含量测定方法简单快速、准确可靠、重复性好;硫磺熏制后白芍中芍药苷的含量显著降低,且芍药苷亚硫酸酯的含量与芍药苷的含量呈负相关;体外肝细胞和体内小鼠急性毒性实验未发现芍药苷亚硫酸酯的毒性,硫磺熏制白芍及白芍水提物比较无显著的毒性。     

Cardiovascular toxicity associated with small molecule tyrosine kinase inhibitors currently in clinical use

INTRODUCTION: Tyrosine kinase inhibitors (TKIs) have changed the concepts of systemic therapy for a variety of advanced solid and hematologic malignancies. However, their toxicity can be significant, and includes both cardiac and non-cardiac effects. AREAS COVERED: The authors evaluate comprehensively the adverse cardiovascular portfolio of small molecule TKIs, postulate their underlying mechanisms and offer recommendations regarding prevention and therapy of these toxicities. EXPERT OPINION: For most pan-selective TKIs, there might not be a clear-cut relationship between specific patterns of TK inhibition and cardiovascular toxicity. Cardiovascular side effects are likely due to dysregulation of multiple kinase regulated pathways. The cardiovascular effects of small molecule TKIs include peripheral edema and congestive heart failure, systemic and pulmonary hypertension, acute coronary syndromes and cardiac arrest due to QTc prolongation. Caution should be sought in patients with pre-existing cardiac dysfunction before initiating any of these agents. It is hoped that newer TKI generations will display minimal if any cardiovascular toxicity, while maintaining their anticancer efficacy. As of today, the high likelihood of morbidity without treatment mandates that cardiovascular toxicity of TKIs be carefully assessed and balanced with the known benefits of administering these agents.     

Digoxin-Specific Antibody Fragments

Digitalis glycoside poisoning is an important clinical problem and the development of digoxin-specific antibody fragments (Fab) 30 years ago has changed clinical practice. Nevertheless, doubts still exist as to the appropriate dose indications for therapy. This paper reviews relevant literature, describes the difficulties associated with current treatment protocols and proposes an approach to therapy, which is based on theoretical principles and evidence gleaned from currently available clinical data sets. In patients with ‘acute’ poisoning, serum digoxin concentrations do not equate to the total body burden, as tissue distribution will not have occurred, and the calculations for present protocols, which use serum concentrations, are therefore likely to result in too much antibody being administered. Since a therapeutic quantity of digoxin will have little effect in a normal individual, complete neutralisation of all digoxin is also unnecessary. The pharmacokinetic and dynamic logic of using a smaller initial loading dose than predicted from total body calculations is rational. It is recommended that half the calculated loading dose, either based on serum concentration or history, should be administered and the impact on clinical features observed. If a clinical response is not seen within 1–2 hours, a further similar dose should be given. In the event of a full response, patients should be monitored for 6–12 hours; a second dose should only be given in the event of recurrence of toxicity. In patients with ‘chronic’ digoxin poisoning, the serum digoxin concentration will reflect the total body load. However, since such patients are invariably receiving digoxin for therapeutic purposes, full neutralisation is again not indicated. In addition, tissue redistribution of digoxin from deeper stores will occur following the binding of biologically active digoxin in the circulation. This process will occur over a number of hours and if the total calculated dose of antibody is administered in a single bolus, significant quantities will be excreted prior to redistribution of digoxin. Pharmacokinetic logic, therefore, suggests that half the calculated loading dose, based on serum concentration, should be administered and the impact on clinical features observed; a second dose should be given in the event of recurrence of toxicity.     

Evaluation of toxicity test procedure for screening treatability potential of waste in soil

A toxicity procedure has been developed and proposed for use in establishing acceptable initial loading rates and detoxification potentials for hazardous industrial waste when combined with soil. The procedure involves conducting toxicity screening and toxicity reduction experiments using selected waste-soil combinations. These experiments employ a bacterial bioluminescence assay (Microtox^TM) to determine acute toxicity of organic contaminants contained in the water soluble fraction (WSF) of waste-soil mixtures. Toxicity screening test results are used to establish a range of loading rates acceptable for use in subsequent waste-soil treatability studies. Toxicity reduction experimental results are used to determine soil detoxification potentials over time for soluble toxic organics contained in the waste-soil loading combination selected. A major factor in determining acceptability of any test procedure is whether or not different investigators can achieve reproducible and comparable results. This paper describes the proposed procedure and reports results from toxicity experiments conducted concurrently by two laboratories using aliquots from the same soil and waste samples. Comparability of results was reported to be a function of the similarity of waste sample aliquots used in the toxicity experiments. Toxicity screening results for uniform technical grade creosote aliquots were highly comparable between the two laboratories, while results for highly variable creosote wood preserving waste (WPC) aliquots were much less comparable. Toxicity reduction experimental results for the WPC waste also indicated significant variation between laboratories for initial (Day 0) samples; however, the same patterns of detoxification over time were observed by each laboratory with toxicity results at the end of the experimental period (Day 42) being similar. Although the research described in this article has been funded wholly or in part by the U.S. Environmental Protection Agency, it has not been subjected to the agency's peer and administrative review and therefore may not necessarily reflect the views of the agency and no official endorsement should be inferred.     

Final report on the safety assessment of Triethylene Glycol and PEG-4

Triethylene Glycol and PEG-4 (polyethylene glycol) are polymers of ethylene oxide alcohol. Triethylene Glycol is a specific three-unit chain, whereas PEG-4 is a polymer with an average of four units, but may contain polymers ranging from two to eight ethylene oxide units. In the same manner, other PEG compounds, e.g., PEG-6, are mixtures and likely contain some Triethylene Glycol and PEG-4. Triethylene Glycol is a fragrance ingredient and viscosity decreasing agent in cosmetic formulations, with a maximum concentration of use of 0.08% in skin-cleansing products. Following oral doses, Triethylene Glycol and its metabolites are excreted primarily in urine, with small amounts released in feces and expired air. With oral LD50 values in rodents from 15 to 22 g/kg, this compound has little acute toxicity. Rats given short term oral doses of 3% in water showed no signs of toxicity, whereas all rats given 10% died by the 12th day of exposure. At levels up to 1 g/m3, rats exposed to aerosolized Triethylene Glycol for 6 h per day for 9 days showed no signs of toxicity. Rats fed a diet containing 4% Triethylene Glycol for 2 years showed no signs of toxicity. There were no treatment-related effects on rats exposed to supersaturated Triethylene Glycol vapor for 13 months nor in rats that consumed 0.533 cc Triethylene Glycol per day in drinking water for 13 months. Triethylene Glycol was not irritating to the skin of rabbits and produced only minimal injury to the eye. In reproductive and developmental toxicity studies in rats and mice, Triethylene Glycol did not produce biologically significant embryotoxicity or teratogenicity. However, some maternal toxicity was seen in dams given 10 ml/kg/day during gestation. Triethylene Glycol was not mutagenic or genotoxic in Ames-type assays, the Chinese hamster ovary mutation assay, and the sister chromatid exchange assays. PEG-4 is a humectant and solvent in cosmetic products, with a maximum concentration of use of 20% in the "other manicuring preparations" product category. This ingredient, with an oral LD50 in rats of 32.77 g/kg, has low acute toxicity. Rats given up to 50,000 ppm PEG-4 in drinking water for 5 days showed no permanent signs of toxicity. Rats given daily oral doses up to 2 g/kg/day of PEG-4 for 33 days showed no signs of toxicity. Undiluted PEG-4 produced only minimal injury to the rabbit eye. PEG-4 was not mutagenic in Ames-type assays, did not induce chromosome aberration in an in vivo bone marrow assay, and was negative for genotoxicity in a dominant lethal assay using rats. Other PEG compounds, which have previously been reviewed by the Cosmetic Ingredient Review (CIR) Expert Panel, e.g., PEG-6, are mixtures that likely include Triethylene Glycol and PEG-4, so these data were also considered. PEG-6 and PEG-8 were not dermal irritants in several rabbit studies. PEG-2 Stearate had a potential for slight irritation in rabbits but was not a sensitizer in guinea pigs. PEG-2 Cocamine was a moderate irritant in rabbits, producing severe erythema. In one dermal study, PEG-2 Cocamine was determined to be corrosive to rabbit skin, causing eschar and necrosis. PEG-6 and PEG-8 caused little to no ocular irritation. PEG-8 was not mutagenic or genotoxic in a Chinese hamster ovary assay, a sister-chromatid exchange assay, and in an unscheduled DNA synthesis assay. In clinical studies on normal skin, PEG-6 and PEG-8 caused mild cases of immediate hypersensitivity; PEG-8 was not a sensitizer; PEG-2 Stearate was not an irritant, a sensitizer, or a photosensitizer; and PEG-6 Stearate was not an irritant or sensitizer. In damaged skin, cases of systemic toxicity and contact dermatitis in burn patients were attributed to a PEG-based topical ointment. The CIR Expert Panel acknowledged the lack of dermal sensitization data for Triethylene Glycol and dermal irritation and sensitization data for PEG-4. That PEG-6, PEG-8, and PEG-2 Stearate were not irritants or sensitizers suggested that Triethylene Glycol and PEG-4 also would not be irritants or sensitizers, and the absence of any reported reactions in the case literature and the professional experience of the Expert Panel further supported the absence of any significant sensitization potential. The need for additional data to demonstrate the safety of PEGs Cocamine was related to the Cocamine moiety and is not relevant here. The Panel reminded formulators of cosmetic products that, as with other PEG compounds, Triethylene Glycol and PEG-4 should not be used on damaged skin because of cases of systemic toxicity and contact dermatitis in burn patients have been attributed to a PEG-based topical ointment. Based on its consideration of the available information, the CIR Expert Panel concluded that Triethylene Glycol and PEG-4 are safe as cosmetic ingredients in the present practices and concentrations of use as described in this safety assessment.     

复方龙脷胶囊急性毒性实验研究

目的：观察复方龙脷胶囊的急性毒性反应,为临床安全用药提供实验依据.方法：采用小鼠灌胃给药测定复方龙脷胶囊的半数致死量（LD50）和最大给药量,观察其急性毒性作用.结果：LD50未测出,小鼠最大给药量为164.76g· kg-1 ·d-1,相当于成人临床日剂量的1 176.86倍,小鼠无死亡,未见异常急性毒性反应.结论：复方龙脷胶囊经小鼠灌胃给药无明显急性毒性反应.     

Treatment of acute isoniazid toxicity.

The clinical symptoms and treatment of acute isoniazid toxicity are presented. The use of supportive measures and chemotherapy are discussed in detail. The pharmacology and biochemistry underlying the symptons of isoniazid poisoning are aslo presented. It is concluded that diazepam in combination with pyridoxine is the treatment of choice for the management of convulsions associated with isoniazid toxicity. Pyridoxine should be administered intravenously in amounts equal to the estimated quantity of isoniazid ingested, even if seizures have not occurred.     

Predicting the outcome of chemotherapy for colorectal cancer

Colorectal cancer is the second leading cause of cancer-related deaths in the Western world. Recently, improvements have been made in treating patients with advanced colorectal cancer; however, response rates still remain low at only 40-50% following combination therapy. The major limitation in treating these patients is the development of drug resistance. Therefore, there is a need to identify which patients will respond to a given chemotherapy regime so that they will be spared the unnecessary time and toxicity of being placed on a regime from which they will derive no benefit. It is also widely accepted that exposure to these chemotherapies themselves can induced acute resistance. Recent developments have been made in predicting response to chemotherapy using global approaches, with the ultimate aim of individualising patient treatment and improving overall survival rates.     

The acute toxicity of surfactants on fish cells, Daphnia magna and fish-a comparative study.

There is a need to replace acute toxicity tests on fish (LC(50)) with more cost effective assays. The main objective of this study was to explore whether gill epithelial cells, hepatocytes and Daphnia magna could be used to predict acute toxicity of surfactants on fish. The acute toxicity of 10 synthetic surfactants (anionic, cationic, nonionic and zwitterionic) and two resin acids were determined on hepatocytes and gill epithelial cells from rainbow trout (Oncorhynchus mykiss), on Daphnia magna and on fish. Cell viability was measured with the fluorescent viability probe calcein-AM, immobilization was determined for Daphnia and 24-hr LC(50) for rainbow trout. The EC(50) values for the cellular tests were clearly higher than the corresponding values for Daphnia and fish, indicating that the cellular tests with the endpoint used are less sensitive than whole organisms. A combination of the EC(50) values for Daphnia and freshly isolated gill epithelial cells in suspension showed, however, a good correlation with acute toxicity on fish (r(2)=0.91 and slope=1.09). The combination seems to be a promising in vitro alternative to acute toxicity tests on fish (LC(50)), but a more exhaustive comparison, including a broad spectrum of chemicals should be made before the predictive value of the combined in vitro test can be evaluated.     

“网脱Ⅰ号”口服液对小鼠的急性毒性实验

目的:观察"网脱Ⅰ号"口服液的急性毒性反应,为临床安全使用提供实验数据。方法:采用经典的急性毒性实验方法测定"网脱Ⅰ号"口服液的半数致死量(LD₅₀)和最大给药量,观察其急性毒性症状,记录累积死亡数及小鼠体质量变化。结果:LD₅₀未测出,小鼠最大给药量为150g·kg^-1·d^-1,相当于成人日剂量的140倍。结论:"网脱Ⅰ号"口服液无明显毒性反应,是安全可靠的。