Acute and chronic toxicity studies with monochlorobenzene in rainbow trout

The toxicity of monochlorobenzene (CB) was investigated in rainbow trout following acute intraperitoneal (i.p.) administration and chronic exposure via the water in a continuously flowing system for 15 or 30 days.In the acute study overt toxicity and hepatotoxicity were monitored over a 96-h time period. Variables measured to assess toxicity included weight changes, liver weight to body weight ratios, behavioral changes, alanine aminotransferase activity (GPT), sulfobromophthalein (BSP) retention, total plasma protein concentration and liver histopathology. In the chronic study the same measures of toxicity were followed as well as food consumption and alkaline phosphatase (AP) activity.Upon acute i.p. exposure the toxicant (9.8 mmol/kg) caused behavioral changes in the fish which were consistent with the known anesthetic properties of CB in mammals. Elevations in BSP retention and GPT activity, and histopathology indicated that CB was hepatotoxic in fish.The LC₅₀ of CB in trout exposed via the water for 96 h was 4.7 mg/l. Chronic exposure of trout to 2 or 3 mg/l CB resulted in similar behavioral changes as seen in the acute study. Liver toxicity was evident from elevations in GPT activity. BSP retention and AP activity appeared to be affected by the nutritional status of the trout as much as by the CB treatment. After 30 days of exposure to 3 mg/l CB, trout appeared to have developed some tolerance to the toxic effects.     

Comparative studies of the effects of quinuronium sulfate and diminazene diaceturate in sheep

Biochemical parameters in 20 sheep were investigated following administration of quinuronium sulfate or diminazene diaceturate. The usual signs of salivation, micturition, anorexia, depression, muscular tremors and ataxia were observed within 20 min in sheep receiving therapeutic and double doses of quinuronium sulfate. There was an increased dose dependent plasma LDH activity above baseline values following administration of quinuronium sulfate and a non-dose dependent increased trend in diminazene diaceturate treatment. Plasma CK activity had an increased trend (p less than 0.05) above baseline values following administration of the two babesicides. Plasma BUN levels increased significantly (p less than 0.05) following administration of the two drugs. This study indicated that quinuronium sulfate is more organotoxic and hypotensive than diminazene diaceturate at therapeutic and/or above therapeutic dosages.     

补骨脂素和异补骨脂素的急性毒性和相互作用

目的 探究补骨脂素、异补骨脂素的急性毒性及两者（1∶1）混合使用后的相互作用。方法 补骨脂素（1 125、843、633、475 mg/kg）、异补骨脂素（475、404、343、292 mg/kg）以及两者1∶1的混合物（633、538、457、389、330 mg/kg）1次性ig给予小鼠,连续观察并记录14 d小鼠的毒性反应和死亡情况,用SPSS计算补骨脂素、异补骨脂素以及两者混合使用后的半数致死量（LD₅₀）,用等效线图解法判断两者的相互作用。结果 给药组小鼠均出现僵直、腹部贴地、活动力减弱,甚至抽搐、口眼周有分泌物,心率减慢直至死亡的现象,与助溶剂组比较,体质量呈降低趋势;补骨脂素LD₅₀为638.69 mg/kg,95%可信限为526.91～785.78mg/kg;异补骨脂素LD₅₀为351.72 mg/kg,95%可信限为248.17～394.57 mg/kg;两者1∶1混合给药的LD₅₀为454.66 mg/kg,95%可信限为422.58～489.59;两者合用的LD₅₀在补骨脂素和异补骨脂素相加等效线上。结论 补骨脂素和异补骨脂素大剂量给予小鼠时,引起药物急性毒性反应,1∶1混合给药具有相加作用。     

薏苡仁多糖急性毒性及遗传毒性试验研究

目的了解薏苡仁多糖的毒理学安全性。方法小鼠急性毒性试验和遗传毒性试验（Ames试验、小鼠骨髓嗜多染红细胞微核试验、小鼠精子畸形试验）。结果薏苡仁多糖的小鼠经口LD50〉20g·kg^-1;在Ames试验、小鼠骨髓嗜多染红细胞微核试验、小鼠精子畸形试验中均呈阴性反应,未显示有遗传毒性作用。结论薏苡仁多糖基本无毒性。     

Aquatic toxicology of cypermethrin. I. Acute toxicity to some freshwater fish and invertebrates in laboratory tests

Cypermethrin is a synthetic pyrethroid. Its acute toxicity to ten freshwater invertebrates (Daphnia magna, Asellus aquaticus, Gammarus pulex, Cloeon dipterum, Gyrinus natator, Chironomus thummi, Aedes aegypti Cheoborus crystallinus, Corixa punctata, and Piona carnea) was determined in the laboratory using 24-h static water tests. The 24-h EC₅₀ values (based on reduced motility) ranged from 0.02 μg·l^?1for A. aquaticus and P. carnea to 2 μg·l^?1 for D. magna, and for seven of the species the EC₅₀ values were < 0.1 fig μg·l^?1 The 24-h LC₅₀values for G. natator, C. thummi, and C. punctata were > 5 μg·l^?1 For the seven more susceptible species the 24-h LC₅₀values ranged from 2 μg·l^?1 to 0.05 μg·l^?1The acute toxicity of cypermethrin to some species of fish (Cyprinus carpio. Scardinius erythrophthalmus, Salmo gairdneri, Salmo trutta and Tilapia nilotica) was determined using 96-h continuous-flow tests. The 96-h LC₅₀ values obtained were within the range 0.4–2.2 μg·l^?1.The solubility of cypermethrin within the range of test temperatures (15–25°C was estimated to be in the range 5–10 μg·l^?1.     

替莫唑胺的小鼠急性毒性试验

目的观察替莫唑胺对小鼠的急性毒性。方法采用灌胃给药和腹腔注射给药两种途径进行试验,采用Bliss法计算半数致死量(LD50)。结果一次给药替莫唑胺可以对小鼠产生急性毒性,使小鼠陆续死亡,观察至给药后14d及以上仍有动物死亡。结论本品小鼠灌胃给药LD50为173.90mg/kg(95%的可信限为154.49～199.75mg/kg),腹腔注射给药LD50为164.53mg/kg(95%的可信限为144.36～187.49mg/kg)。     

Acute and subacute (28-Day) toxicity studies of ionic liquid,didecyldimethyl ammonium acesulfamate,in rats

The aim of this study was to investigate acute and subacute oral toxicity of an ionic liquid, didecyldimethylammonium acesulfamate [DDA][Ace], in rats. The compound tested was classified to the fourth toxicity class with a fixed LD₅₀ cut-off value of 500?mg/kg. Organ pathology induced by [DDA][Ace] in acute experiments included exfoliation of the surface layer of the digestive tract and alveolar septa in lung parenchyma. In a subacute experiment, rats were administered 10, 50, and 100?mg/kg/day [DDA][Ace] for 28 days. Reduced body weight gain and reduced food consumption was observed in mid- and high-dose rats. Statistically significant hematology changes were found mostly in high-dose groups of both sexes: increases in hematocrit, mean corpuscular volume, and mean platelet volume. Statistically significant changes in clinical chemistry parameters included increases in the GGT, SDH, and LDH activity and bilirubin concentration, and decreases in triglycerides, glucose, and inorganic phosphorus concentration. No treatment-related microscopic changes were observed. Under the conditions of this study, the lowest-observed-adverse-effect level of [DDA][Ace] was considered to be 10?mg/kg/day.     

Acute and sub-chronic toxicity studies of honokiol microemulsion

The purpose of this study was to investigate the acute and sub-chronic toxicity of honokiol microemulsion. In the acute toxicity tests, the mice were intravenously injected graded doses of honokiol microemulsion and were observed for toxic symptoms and mortality daily for 14 days. In the sub-chronic toxicity study, rats were injected honokiol microemulsion at doses of 100, 500, 2500 μg/kg body weight (BW) for 30 days. After 30 days treatment and 14 days recovery, the rats were sacrificed for hematological, biochemical and histological examination. In the acute toxicity tests, the estimated median lethal dosage (LD₅₀) was 50.5 mg/kg body weight in mice. In the sub-chronic toxicity tests, the non-toxic reaction dose was 500 μg/kg body weight. In each treatment group, degeneration or/and necrosis in vascular endothelial cells and structure change of vessel wall can be observed in the injection site (cauda vein) of a few animals while there were no changes in the vessels of other organs. The overall findings of this study indicate that the honokiol microemulsion is non-toxic up to 500 μg/kg body weight, and it has irritation to the vascular of the injection site which should be paid attention to in clinical medication.     

Acute and subchronic toxicity of xylo-oligosaccharide in mice and rats

Xylo-oligosaccharide (XOS) is sugar oligomers composed of a β-1,4-linked xylopyranosyl backbone that are obtained by either chemical or, more commonly, enzymatic hydrolysis of xylan polysaccharides extracted from plant cell wall. In this study, acute and subchronic toxicity of XOS in mice and rats have been evaluated, respectively. In the acute study, no obvious clinical signs of toxicity or mortality were observed in mice at the dosage of 32?g/kg BW XOS, excepting transient unformed stools were observed. In the subchronic study, XOS was evaluated in rats with dietary administration at concentrations of 0 (control), 0.9, 2.9, 8.8 and 10% for 13 weeks. Measurements included clinical observations, body weight, food consumption, food conversion efficiency, hematology, blood chemistry, gross necropsy, organ weight and histopathology. Under the conditions, no treatment-related changes were noted in behavior or appearance of the rats and no mortalities occurred. No toxicological findings were found in food consumption, food conversion efficiency, hematology, clinical biochemistry or organ weights in either sex. It is concluded, therefore, that the high dose level, at which the female and male rats consumed about 11.51 and 14.95?g XOS/kg bw/d, respectively, is the no observed adverse effect level (NOAEL) of this 13-week toxicity study.     

Acute toxicity of 50 metals to Daphnia magna

Metals are essential for human life and physiological functions but may sometimes cause disorders. Therefore, we conducted acute toxicity testing of 50 metals in Daphnia magna: EC50s of seven elements (Be, Cu, Ag, Cd, Os, Au and Hg) were < 100 µg l^?1; EC50s of 13 elements (Al, Sc, Cr, Co, Ni, Zn, Se, Rb, Y, Rh, Pt, Tl and Pb) were between 100 and 1000 µg l^?1; EC50s of 14 elements (Li, V, Mn, Fe, Ge, As, In, Sn, Sb, Te, Cs, Ba, W and Ir) were between 1,001 and 100,000 µg l^?1; EC50s of six elements (Na, Mg, K, Ca, Sr and Mo) were > 100,000 µg l^?1; and. 7 elements (Ti, Zr, Bi, Nb, Hf, Re and Ta) did not show EC50 at the upper limit of respective aqueous solubility, and EC50s were not obtained. Ga, Ru and Pd adhered to the body of D. magna and physically retarded the movement of D. magna. These metals formed hydroxides after adjusting the pH. Therefore, here, we distinguished this physical effect from the physiological toxic effect. The acute toxicity results of 40 elements obtained in this study were not correlated with electronegativity. Similarly, the acute toxicity results of metals including the rare metals were also not correlated with first ionization energy, atomic weight, atomic number, covalent radius, atomic radius or ionic radius. Copyright © 2014 John Wiley & Sons, Ltd.     

Acute toxicity of monochlorophenols, dichlorophenols and pentachlorophenol in the mouse

Acute oral LD50 values were determined for 2-, 3-, and 4-chlorophenol, 2,3-, 2,4-, 2,5-, 2,6-, 3,4-, and 3,5 dichlorophenol and pentachlorophenol in male and female mice. LD50 values (mg/kg) ranged from 117 (females) and 177 (males) for pentachlorophenol to 2389 (females) and 2643 (males) for 3,5-dichlorophenol. It was found that 2-chlorophenol and 3-chlorophenol were considerably more toxic than the dichlorophenol series. Values for males and females were generally similar, the major differences being with pentachlorophenol and 2,5-dichlorophenol, where in both cases the female LD50 was lower.     

Reproductive, acute and subacute toxicity studies with nefopam in laboratory animals.

Nefopam hydrochloride, a compound with non-narcotic analgesic activity, was evaluated for its acute and subacute toxicity in mice, rats, and dogs. Potential teratogenic effects in mice and rabbits and its effect on general reproduction and postnatal development in rats were also studied. The LD50 by various routes of administration showed that in all three species oral LD50 values (80–178 mg/kg) were greater than im LD50 values (30–57 mg/kg) which were higher than iv LD50 values (20–45 mg/kg). A comparative oral acute toxicity study did indicate a strain difference in rats. Repeated daily administration of nefopam hydrochloride to rats and dogs at doses up to 10 mg/kg/day parenterally and 80 mg/kg/day orally revealed no toxic effects except for mild tissue irritation at injection sites and slight weight loss in some dogs receiving the high dose. Reproduction studies did not reveal any effects on fertility, lactation, or pup development and viability.     

克班宁急性毒性与抗心律失常活性的初步研究

目的 研究克班宁（crebanine,Cre）的急性毒性与抗心律失常作用。方法 以改良寇氏法考察小鼠静注LD50,以BaCl2致大鼠心律失常模型观察Cre的治疗与预防作用。结果 LD50为9．382mg／kg,95％可信限为8.314-10.600mg／kg;治疗组与预防组iv Cre2．5mg／kg可使大鼠恢复窦律,与对照（生理盐水）组相比,差异有显著性意义。结论 Cre有一定的毒性,对大鼠实验性心律失常具有治疗与预防作用。     

Acute and sub-chronic toxicity studies of the extract of Thunberg Fritillary Bulb

The aim of this study was to investigate the acute and sub-chronic toxicity of extract of Thunberg Fritillary Bulb. For the acute toxicity tests, graded doses of the extract were administered orally to mice. The animals were observed for toxic symptoms and mortality daily for 14 days. In the sub-chronic toxicity study, rats were orally administered the extract at doses of 1 and 3 mg/kg body weight (BW) for 26 weeks. After 26 weeks, the rats were sacrificed for hematological, biochemical and histological examination. In the acute toxicity tests, the estimated median lethal dosage (LD₅₀) was 52.2 mg/kg body weight in the mice. In the sub-chronic toxicity tests, a dose of 1 mg/kg body weight presented no toxicity. Above the 1 mg/kg dose, the main adverse signs observed in male rats were body or head tremor and spontaneous motor activity reduction. There were no other significant changes observed in hematology, blood biochemistry, organ weight and organ histology. The overall findings of this study indicate that the extract of Thunberg Fritillary Bulb is non-toxic up to 1 mg/kg body weight, which can be considered a safe application dose.     

欧前胡素急性毒性和安全药理学研究

目的观察欧前胡素对大、小鼠的急性毒性,以及对小鼠神经系统和犬心血管系统、呼吸系统的影响。方法通过腹腔内注射给药（ip）和灌胃给药（培）研究欧前胡素对小鼠的急性毒性,以及培对大鼠的急性毒性实验。安全药理学实验中以50、100、200mg／kg分别单次培给予小鼠欧前胡素,观察对小鼠神经系统的影响（包括小鼠自发活动、爬杆能力、小鼠阈下剂量戊巴比妥钠催眠协同实验）;以25、50、100mg／kg分别单次口服给药（po）欧前胡素,观察对犬心血管系统和呼吸系统的影响（包括心电图、血压、心率,以及呼吸频率、幅度、节律等指标）。结果欧前胡素培对小鼠的LD50为988．5mg/kg;ip对小鼠的LD50为603．3mg／kg;ig对大鼠的LD50为3188．7mg／kg。欧前胡素单次ig对小鼠神经系统无明显影响;单次po对犬心血管系统指标和呼吸系统指标无明显影响。结论欧前胡素安全范围较大,毒性较容易控制,且对正常动物（包括小鼠、大鼠和犬）的降压作用不显著,因此具有较大的临床应用可能性。     

Safety assessment of aditoprim acute,subchronic toxicity and mutagenicity studies

Aditoprim (ADP), a new developed dihydrofolate reductase (DHFR) inhibitor, has great potential in clinical veterinary medicine because of its greater pharmacokinetic properties than structural analogs. Preclinical toxicology studies were performed to assess the safety of ADP including an acute oral toxicity test, a subchronic toxicity test and five mutagenicity tests. In the acute oral toxicity test, ADP was administered singly by oral gavage to Wistar rats and Kunming mice. The LD₅₀ calculated was 1400 mg kg^–1 body weight (BW) day^–1 in rats and 1130 mg kg^–1 BW day^–1 in mice. In a subchronic study, Wistar rats were administered ADP at dose levels of 0, 20, 100 and 1000 mg kg^–1 diet for 90 days. Significant decreases were observed on body weight and food efficiency in the high‐dose group. Treatment‐related changes in clinical serum biochemistry were found in the medium‐ and high‐dose groups. Significant increases in the relative weights of livers and kidneys in females and testis in males in the 1000 mg kg^–1 diet, and significant decrease in relative weights of livers in males in the 100 mg kg^–1 diet were noted. Histopathological observations revealed that the 1000 mg kg^–1 ADP diet could induce lymphocytic infiltration and hepatocytic necrosis near the hepatic portal area. The genotoxicity of ADP was negative in tests, such as the bacterial reverse mutation assay, mice bone marrow erythrocyte micronucleus assay, in vitro chromosomal aberration test, in vitro cho/hgprt mammalian cell mutagenesis assay and mice testicle cells chromosome aberration. Based on the subchronic study, the no‐observed‐adverse‐effect level for ADP was a 20 mg kg^–1 diet, which is about 1.44‐1.53 mg kg^–1 BW day^–1 in rats. Copyright © 2015 John Wiley & Sons, Ltd.     

Developmental toxicity of diesel exhaust: A review of studies in experimental animals

Diesel exhaust (DE) is a complex mixture of combustion products of diesel fuel, including gases and diesel exhaust particles (DEPs), commonly known as soot, that contains many toxic air contaminants. Studies of pre- and postnatal exposure to DE or DEPs have revealed changes in growth, sexual development, hormone levels, spermatogenesis, weights of the reproductive and accessory organs, behavior, monoaminergic system, expression of immune-related genes, histopathology of the testes and brain, susceptibility to allergies, and inflammatory and genotoxic endpoints in rodent offspring. Changes in gene expression for gonadal development were also observed after exposure to DE. As for the causative agent for the developmental toxicity of DE, DEPs and the gaseous phase, conflicting findings were reported. Although this paper provides initial information on the potential developmental toxicity of DE including the gaseous phase and DEPs, further studies using relevant concentrations closely reflecting expected levels of human exposure are needed.     

A review of toxicity studies on graphene-based nanomaterials in laboratory animals

We summarized the findings of toxicity studies on graphene-based nanomaterials (GNMs) in laboratory mammals. The inhalation of graphene (GP) and graphene oxide (GO) induced only minimal pulmonary toxicity. Bolus airway exposure to GP and GO caused acute and subacute pulmonary inflammation. Large-sized GO (L-GO) was more toxic than small-sized GO (S-GO). Intratracheally administered GP passed through the air-blood barrier into the blood and intravenous GO distributed mainly in the lungs, liver, and spleen. S-GO and L-GO mainly accumulated in the liver and lungs, respectively. Limited information showed the potential behavioral, reproductive, and developmental toxicity and genotoxicity of GNMs. There are indications that oxidative stress and inflammation may be involved in the toxicity of GNMs. The surface reactivity, size, and dispersion status of GNMs play an important role in the induction of toxicity and biodistribution of GNMs. Although this review paper provides initial information on the potential toxicity of GNMs, data are still very limited, especially when taking into account the many different types of GNMs and their potential modifications. To fill the data gap, further studies should be performed using laboratory mammals exposed using the route and dose anticipated for human exposure scenarios.     

青蒿酯钠静脉注射对犬的急性毒性

按Deichmenn,Le Blauc法,给犬单次iv青蒿酯钠,给药后观察14d。结果表明:无毒副反应的最大剂量(MTD)为70mg/kg,近似致死量(ALD)为240mg/kg。毒副作用的主要表现为胃肠道和神经系统症状,致死剂量还引起肉眼血尿。化验检查以网织红细胞减少和血浆ALP升高发生最早,变化明显。病理损伤按出现所需剂量由小到大为红系造血抑制,内脏淤血,胆汁淤滞,胃肠粘膜坏死,肠道出血及肝,肾实质细胞退行性变,量效关系显著。33mg/kg未见任何毒副作用,可视为安全界量。     

Acute and 30-day oral toxicity studies of administered carnosic acid

Purpose

Increasing interest in carnosic acid (CA) is due to its pharmacological properties. The aim of this study was to evaluate the acute and 30-day oral toxicity of CA.

Methods

The acute oral toxicity study in Kuming mice design followed the OECD-guidelines 423, and a 30-day chronic oral toxicity study in Wistar rats based on the enhanced OECD test guideline 407 were performed.

Results

The oral lethal dose (LD50) for mice was 7100 mg/kg of body weight in the acute toxicity study. The histopathological changes were observed in the heart, liver and kidney for the survival mice treated with a single dose CA. For the sub chronic toxicity study, CA administered for 30 days produced slightly reductions in the weight gain pattern, which did not reach the significant level when compared with the control values. With respect to serum biochemistry test, decreased total serum protein levels, but conversely increased aspartate aminotransferase (AST) levels were detected in the high-dose and moderate-dose groups. Histopathologically, light pathological changes were observed in the heart, liver, and kidney of rats treated with the high-dose CA.

Conclusion

The present work suggests that a short-term oral administration of CA has a relatively low toxicity profile.