"In vivo" effects of lithium sulphate on the turnover of rat tissue nucleotides

The effects of lithium sulphate following acute administration to Wistar rats - in therapeutic and toxic doses - were investigated, using as markers the levels and turnover of brain, kidney and liver nucleotides. Adenine- and guanine-dependent nucleotides were assayed concomitantly, using a high- performance liquid chromatographic method. Following acute administration, lithium's effects on 3',5'- cAMP levels were more significant at hepatic and cerebral level, in a dose-dependant manner. The effect on 3',5'-cGMP had tissue specificity and was not dose-dependant. It might be possible that 3',5'-cGMP is a better indicator of lithium toxicity than 3',5'-cAMP.     

Safety evaluation and biochemical behavior of monotertiarybutylhydroquinone

The safety of monotertiarybutylhydroquinone as an oil-soluble food grade antioxidant was evaluated in acute studies with rats and dogs, in subacute feedings in rats, in rat reproductive efficiency and placental transfer studies, and in subacute feedings with monotertiarybutylhydroquinone heated in vegetable oil. In lifetime feedings in rats and 2 year feedings in dogs, wt gain, feed consumption, behavior, mortality, hemograms, clinical chemistries, gross, microscopic, and electron microscopy were evaluated. There were no toxic or untoward effects. Monotertiarybutylhydroquinone was handled similarly by rats, dogs, and humans. Rats eliminated single oral 0.1–0.4 g/kg doses mostly in the urine in 3–4 days as the 4-0-sulfate (57–80%) and the 4-0-glucuronide (4%) and with 4–12% unchanged. 2,3,5,6-¹⁴C-Monotertiarybutylhydroquinone was eliminated similarly with <0.1% as¹⁴CO₂ and <0.2% remaining in the animal after 4 days. Oral 0.1 g/kg doses to dogs gave a somewhat higher glucuronide contribution. The elimination pattern was little altered in long term feedings. Humans eliminated 0.002 g/kg single doses (high fat vehicle) almost completely in the urine in 2–3 days, with <0.1% unchanged, 73–88% as the 4-0-sulfate, and 15–22% as the 0-glucuronide. Monotertiarybutylhydroquinone residues in most tissues of long term animals were below lower detection limits or negligible. Monotertiarybutylhydroquinone did not induce liver microsomal mixed function oxidases in short and long term rat and dog feedings. The feeding studies and comparative biochemical studies showed monotertiarybutylhydroquinone to be safe for its intended use.     

0.5%溴敌隆微乳剂的研制

报道了０．５％溴敌隆微乳剂的组成和制备方法,研究了温度、水质和贮存时间对制剂稳定性的影响,老查了制剂的杀鼠毒力和对鼠的适口性。     

Das Verhalten von Glas beim maschinellen Geschirrspülen

The Behaviour of Glass in Mechanical Dish-Washing Under the conditions involved in mechanical dish-washing there is only a slight difference in the behaviour of glasses of different compositions. The higher temperatures attained thereby are mostly responsible for the damages to the glass. Alkaline, especially strongly alkaline solutions, attack more than the acidic ones. The percentage of the complaints lodged for the glass damages is still relatively small. However, the rapidly increasing number of household dish-washing machines makes it necessary that everybody concerned should discuss the problem of cloudiness of glass.     

三氟羧草醚的毒性研究

三氟羧草醚对雄,雌小白鼠性经口ＬＤ５０分别为１４７０ｍｇ／ｋｇ和２３３０ｍｇ／ｋｇ;对雄、雌大白鼠急性经口ＬＤ５０分别为１２６０ｍｇ／ｋｇ和１７１０ｍｇ／ｋｇ,急性经皮ＬＤ５０〉４６４０ｍｇ／ｋｇ;微核和精子畸形试验结果为阴性。     

注射用重组人B淋巴细胞刺激因子受体-抗体融合蛋白对大鼠生育力及早期胚胎发育的毒性作用

目的观察注射用重组人B淋巴细胞刺激因子受体-抗体融合蛋白(RCT-18)对大鼠生育力及早期胚胎发育的毒性作用。方法将SD大鼠随机分为4组,分别经皮下注射RCT-18 129、37、11 mg/(kg.d)和0.9%NaCl注射液,每2 d给药1次。雄鼠连续给药5周、雌鼠连续给药2周后,按雌雄1∶1的比例合笼交配,合笼期为2周,计算交配率。雄鼠继续给药至交配成功,雌鼠继续给药至妊娠第6天。实验过程中观察动物的一般反应、体重及摄食量变化。确定雌鼠受精后处死雄鼠,解剖检查睾丸和附睾等生殖器官。于妊娠第15天解剖孕鼠,综合评价妊娠及胚胎形成和早期发育等情况。结果 RCT-18高、中、低剂量组雌性和雄性大鼠均未出现明显的母体毒性反应。各组大鼠各脏器均未见肉眼可见的异常。各剂量RCT-18对大鼠的交配率、妊娠率、生殖系统脏器重量和系数以及早期胚胎发育均无明显影响。结论RCT-18对SD大鼠的生育力及早期胚胎发育无明显毒性作用。     

Acute Oral Toxicity Evaluations of Some Zinc(II) Complexes Derived from 1-(2-Salicylaldiminoethyl)piperazine Schiff Bases in Rats

The current study described the synthesis and the in vivo acute oral toxicity evaluations in Sprague Dawley rats. The compounds were characterized by elemental analyses, LC-MS, FTIR, (1)H NMR, (13)C NMR and UV-visible spectroscopy. In the acute toxicity study, a single administration of the compounds was performed orally to the rats at the single doses of 2000 mg/kg and they were then monitored for possible side effects, mortality or behavioral changes up to 14 days. The serum level of aspartate (AST), alanine aminotransferases (ALT), alkaline phosphate (ALP), triglyceride, high density lipoprotein (HDL), immunoglobulins (GAM) and the C-reactive proteins did not significantly change. The hematological indices white blood cells (WBC), haematocrit (HCT), red blood cells (RBC), mean corpuscular volume (MCV), mean corpuscular haemoglobin concentration (MCHC), and mean corpuscular hemoglobin (MCH) were within the normal range. The renal function indices examined were also within the reference range. Generally, the compounds exhibited low toxic effects as required for further in vivo therapeutic studies.     

重组人干扰素α2b脂质体乳膏的抗病毒作用及毒理学研究

目的观察重组人干扰素α2b(rhIFNα2b)脂质体乳膏的抗病毒及毒性作用。方法采用体外和体内抗病毒试验以及大鼠急性和长期毒性试验,检测rhIFNα2b脂体乳膏的抗病毒及毒性作用。结果rhIFNα2b脂质体乳膏对单纯疱疹病毒和水痘疱疹病毒均有明显的抑制作用。在大鼠试验中,10000倍临床剂量用药后1周以及4000倍临床剂量用药后4周,均未出现毒性反应。结论rhIFNα2b脂质体乳膏用于治疗病毒性疱疹病是安全有效的。     

Pulmonary toxicity screening studies in male rats with TiO2 particulates substantially encapsulated with pyrogenically deposited, amorphous silica

The aim of this study was to evaluate the acute lung toxicity in rats of intratracheally instilled TiO₂ particles that have been substantially encapsulated with pyrogenically deposited, amorphous silica. Groups of rats were intratracheally instilled either with doses of 1 or 5 mg/kg of hydrophilic Pigment A TiO₂ particles or doses of 1 or 5 mg/kg of the following control or particle-types: 1) R-100 TiO₂ particles (hydrophilic in nature); 2) quartz particles, 3) carbonyl iron particles. Phosphate-buffered saline (PBS) instilled rats served as additional controls. Following exposures, the lungs of PBS and particle-exposed rats were evaluated for bronchoalveolar lavage (BAL) fluid inflammatory markers, cell proliferation, and by histopathology at post-instillation time points of 24 hrs, 1 week, 1 month and 3 months.     

The effects of dietary gossypol on animals

The pathological effects of gossypol in animals and the effects of protein quality and quantity on its toxicity are described. The method used for the isolation of gossypol from the liver of gossypol-intoxicated pigs and its identification are presented. Wide distribution of gossypol in swine is shown by determining the free and bound gossypol in the various organs. The levels of iron necessary to overcome toxicity and to lower its accumulation in pigs were investigated. Effects of copper, zinc, manganese and iron, alone and in combination, on the gains and the accumulation of gossypol in the liver of rats were studied. Iron was definitely the most effective detoxifying agent. Paper No. 3173 of the Journal Series of the N.C. State Univ. Agr. Exp. Station.     

An investigation of 2'-deoxyribonucleoside cyanoboranes in mice for therapeutic safety

A standard acute toxicity study was undertaken to assess 2'-deoxyribonucleoside cyanoboranes for therapeutic safety. 2'-Deoxyribonucleoside cyanoboranes and related derivatives were nontoxic at doses required for anti-neoplastic and hypolipidemic activities. At higher doses (50 and 100 mg/kg/day IP for 7 days), all treated animals survived with slight reductions in total body weight and small decrements in daily food consumption. No clinical chemistry value was elevated to a magnitude suggesting onset of organ specific toxicity. However, agents appeared to modulate subpopulations of white blood cells, i.e., more lymphocytes than PMNs were present in blood from treated animals as determined by differential cell counts. This modulation is correlated with increases in granulomatous foci in the spleen and mesentery of treated animals after 7 days. The kidney was damaged only by Compound 5 at 50 and 100 mg/kg/day; Compound 5 had the most potent anti-neoplastic activity. The compounds demonstrated no in vitro toxicity against human HCT-8 ileum cells. LD(50) values were greater than 1000 mg/kg, IP, for all compounds.     

Toxicity of fatty ozonides and peroxides

Studies on the acute toxicity of the ozonides and hydroperoxides of methyl linoleate are reported. High purity preparations of these compounds were injected intravenously or administered orally to adult male rats. The lethal dose by iv injection of these compounds was virtually the same −0.07 mmol/100 g body wt. No deaths were caused in a 24 hr period by single oral dosages of these compounds of ca. 10-fold that causing death by the iv route. The major effect of these compounds was on the lungs. The lungs became enlarged from edema and accumulation of fluid, and the animals died of lung congestion and injury similar to the effects of ozone toxicity. There was no destruction of vitamin E in the tissues of animals given lethal dosages of ozonides or peroxides intravenously, but significant changes occurred in fatty acid composition of the lipids of the serum and lung. Arachidonic acid increased at the expense of linoleic and oleic acids in these tissues. Only small amounts of peroxidic and TBA positive substances were detected in lung and serum, indicating that the injected ozonides and hydroperoxides were destroyed in the tissues.     

Synthesis and Biological Evaluation of 10-Substituted Camptothecin Derivatives with Improved Water Solubility and Activity

Despite remarkable clinical achievements, camptothecin (CPT) still suffers from poor solubility and severe toxicity. Therefore, it is necessary to redevelop CPT derivatives as supplementary antitumor agents with good water solubility and small side effects. In this work, 27 camptothecin derivatives were synthesized and screened for their cytotoxicity against A549 (lung) and HCT-116 (colon) cancer cell lines. Among them, compound B7 , 7-ethyl-10-(2-oxo-2-(4-methylpiperidin-1-yl)ethoxy)camptothecin,was demonstrated in vitro to be a more potent antitumor agent than SN-38 by comparison of their inhibitory activities against cell proliferation and colony formation and interference effect on process of cell cycle and cell apoptosis. Additionally, a molecular docking model revealed that B7 can interact with the topoisomerase I–DNA complex, and that the solubility of B7 reached 5.73 μg/mL in water. Moreover, B7 significantly inhibited tumor growth in an A549 xenograft model at dosages of 0.4 and 2.0 mg/kg, and exhibited minimum lethal doses comparable to those of irinotecan. These results indicated that B7 , with improved solubility, enhanced activity and acceptable acute toxicity, can be used as a lead compound for the development of novel anticancer agents.     

In vivo toxicological evaluation of barium-doped bioactive glass in rats

Bioactive glasses (BGs) are inorganic biomaterials with several FDA-approved marketed products, mainly for orthopedic and dental applications. However, in the last few decades, the soft tissue regenerative potential of BGs has also been established preclinically, and its clinical translation requires elaborate in vivo toxicity studies for future biomedical applications. Thus, in the present study, we evaluated the comparative acute and sub-acute toxicity of orally administered barium-doped BG (BaBG) with 45S5 in rats. The lethal dose (LD₅₀) of BaBG and 45S5 was more than 2000 mg/kg body weight (b.w.), with no mortality at the highest dose tested. The oral acute toxicity study was performed at doses of 300 and 2000 mg/kg b.w. according to OECD 423. The organ coefficients of vital organs and histological analysis affirmed the safety profile of BaBG. Moreover, various biochemical indices like alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), creatinine, and CK-MB confirmed that BaBG did not cause organ toxicity at all doses tested. Similarly, the repeated dose 28-days sub-acute toxicity study was performed according to OECD 407 at doses 50, 500, and 1000 mg/kg b.w. There was no alteration in the hematological parameters, which ascertains that BaBG had no toxic effects on the hematopoietic centers like 45S5. Furthermore, there was no observed neuro-behavioral toxicity of 45S5 and BaBG. Thus, these findings confirm that BaBG is non-toxic and can be used for therapeutic applications in different disease models.     

重组碱性成纤维细胞生长因子凝胶剂的制备

目的制备重组碱性成纤维细胞生长因子(bFGF)凝胶剂。方法以卡波姆940、甘油、1,2丙二醇为基质,加入复方保护剂(肝素钠、人血白蛋白、甘露醇和HP-β-CD),制成bFGF凝胶剂,观察25和4℃保存的稳定性,并进行家兔局部刺激试验、急性毒性试验、促烧伤创面愈合试验。结果bFGF凝胶剂在25℃保存18个月、4℃保存24个月,效价维持在原效价的80%以上;局部用药未见皮肤刺激反应和急性毒性反应;促家兔烧伤创面愈合的效果明显优于水溶液剂。结论制备的bFGF凝胶剂安全有效,具有缓释作用,稳定性良好,具有广阔的临床应用前景。     

Effect of fractionation and treatment on the acute oral toxicity and on the gossypol and gossypurpurin content of cottonseed pigment glands

Summary Twenty-one preparations from cottonseed pigment glands were tested for their acute oral toxicity in 1,208 fasted rats and for their content of extractable gossypol and gossypurpurin. LD₅₀ studies on six samples of pure gossypol were performed on 167 fasted rats. There was no correlation between the toxicity of the various samples of cottonseed pigment glands and their extractable gossypol or gossypurpurin content. Samples containing very large amounts of extractable gossypol were less toxic than many samples with considerably lower extractable gossypol content. Various fractionation procedures carried out on the same lot of cottonseed pigment glands caused wide alterations in their toxicity, from the extreme of very marked toxicity for the water-soluble, acetone-soluble fraction (LD₅₀ ca. 700 mg./kg.) to no detectable toxicity for the acetone-insoluble residue (LD₅₀<6,000 mg./kg.). There was a decreased toxicity of subsequently prepared pigment glands with increased time of storage of the cottonseed in a silo. Storage of the pigment glands themselves at 7°C. however had little effect on their toxicity even after 26 and 32 months. The procedures causing greatest detoxification of cottonseed pigment glands, given in the order of increasing effectiveness, were: heating in the presence of water < extraction with ethanol < extraction with acetone. In the fasted rat the acute oral toxicity of pure gossypol was less than that of 17 preparations from cottonseed pigment glands having extractable gossypol contents ranging from as little as 24 to as much as 90%. Report of a study in which certain phase were carried on under the Research and Marketing Act of 1946. Presented at fall meeting, American Oil Chemists' Society, Chicago, Oct. 31, Nov. 1–2, 1949. This work was conducted with Swift and Company under a memorandum of understanding with the Bureau of Agricultural and Industrial Chemistry. The preparation of the samples of gossypol and cottonseed pigment glands and the analyses for gossypol and gossypurpurin content were carried out in the Southern Regional Research Laboratory; all of the animal experiments were performed in the Research Laboratories of Swift and Company. One of the laboratories of the Bureau of Agricultural and Industrial Chemistry, Agricultural Research Administration, U. S. Department of Agriculture.     

Fütterungsversuche mit dimeren Triglyceriden aus Sojaölraffinat

Feeding Experiments with Dimeric Triglycerides Isolated from Refined Soya Bean Oil At pilot plant scale a fraction containing 20% of dimeric triglycerides was isolated from refined soya bean oil by chromatography on silica gel. Additional fractionation by preparative gel permeation chromatography yielded a product containing 92% of dimeric triglycerides. By this for the first time genuine dimeric triglycerides have been available for animal feeding experiments at a very high concentration which otherwise occur in refined soya bean oils only in very low amounts. The acute toxicity test with mice, in which the 92% concentrate was fed, did not show any symptoms of toxicity with all doses applied. The acute LD₅₀ (24 hours and 7 days) was higher than 20 ml/kg. To test the chronical toxicity and metabolism the product with 20% dimeric triglycerides was added at 15% (w/w) to the diet and fed to mice over 12 months. A control group of test animals received a diet with 15% (w/w) refined soya bean oil. During the experiment a. o. clinical symptoms, behavioural disorders, gain in weight, uptake of feed and water, feed efficiency and mortality have been evaluated. Histological investigations as well as a reproduction study were performed. In all these investigations no differences between the animals of the control and test groups could be found. Fat analytical investigations revealed that the dimeric triglycerides are saponified in the gastro-intestinal tract and that a high percentage of dimeric fatty acids is excreted with the faeces. Liquids isolated from the adipose tissue, the kidneys and brain did not show any difference between the animals of the control and test group.     

阿维菌素原药急性吸人毒性试验的研究

目的：通过短时间吸入染毒可初步了解阿维茵素原药经呼吸道进入机体而引起动物的中毒症状及死亡率,求出吸入染毒的LC50,为急性吸入毒性分级、标签管理和其它有关的毒理学研究提供科学的参考资料,也能够为制定生产和应用过程中的防护措施提供依据。方法：GB15670-1995《农药登记毒理学试验方法》中吸入染毒方法。结果：阿维菌素原药急性吸入LC如（2h）：雌性-584（430-794）mg／m……3,雄性-681（---）mg／m^3,根据我国农药的急性毒性分级标准,阿维菌素原药对雌雄大鼠急性吸入毒性均属中毒。     

Acute toxicity oftrans-5-hydroxy-2-nonenal in fisher 344 rats

The potential toxicity oftrans-4-hydroxy-2-nonenal (HNE), a product formedin vivo during lipid peroxidation, which is also present in foods, was investigated in Fisher 344 rats. Five groups of five male rats each were given by gavage 1000, 300, 100, 30 or 10 mg/kg body weight HNE dissolved in 0.5 mL corn oil. The sixth group, the control, received corn oil alone. Two rats died 6 and 8 hr after being treated with 1000 mg/kg HNE. These two rats showed extensive acute tubular necrosis of the kidney, but had very little liver damage. Diffuse liver cell necrosis was observed in a dose dependent manner in all the rats killed 14 days after treatment, whereas renal change was mild. Interestingly, body weight of the lowest dosage group was significantly higher than that of the control group at termination of the experiment. The results of this study show that HNE has almost the same toxicity as other enals, such astrans-2-heptenal, and that kidney and liver are the main organs affected by toxicity of HNE. Although animals may have efficient defense systems, such as glutathione, to detoxify low to moderate dosages of HNE, at high doses of HNE this defense system is overwhelmed, resulting in serious renal and hepatic damage.