The subchronic toxicity of acridine in the rat

Abstract

The subchronic toxicity of acridine was investigated in rats following dietary exposure at 0, 1, 10, 100 and 500 ppm for 13 weeks. The growth rate and food consumption were not affected by treatment and no clinical signs of toxicity were observed. There was a slight but significant decrease in spleen weight, both in absolute terms and as a percent of body weight, in the 500 ppm males and a slight increase in absolute thymus weight in the females of the same dose group. Both hepatic ethoxyresorufin O‐deethylase (EROD) and pentoxyresorufin O‐dealkylase (PROD) activities were slightly, but significantly, elevated in females in the 500 ppm dose group. No haematological or other biochemical changes were observed. Females also displayed dose‐related increases in inorganic phosphate and uric acid levels. Treatment‐related histopathological changes were seen in the thyroid, liver and kidney and included hepatic anisokaryosis and vesiculation of nuclei and glomerular adhesions, reticulin sclerosis and nuclear pyknosis in the kidney. Residue data showed a dose‐dependent accumulation of acridine in liver, kidney and adipose with the highest concentration being found in the fat of the 500 ppm dose group. Based on these data, the no observable adverse effect level of acridine was judged to be 100 ppm or 12 mg/kg bw/day.     

PFOS青春期暴露对成年期雄性大鼠的生殖毒性

为探究青春期的PFOS暴露对成年后的SD大鼠的生殖毒性,对出生后第21天(PND21)的SD大鼠经口灌胃不同剂量的PFOS(5、10和20mg·kg~(-1)),连续染毒7d,在出生后第56天(PND56)时,对各染毒组SD大鼠的体质量、精子数量、血清中的睾酮浓度,以及睾丸间质细胞睾酮合成的相关基因mRNA水平进行了检测。结果显示,10mg·kg~(-1)剂量组大鼠体质量较对照组明显下降(P<0.01);精子数量在10mg·kg~(-1)和20mg·kg~(-1)剂量组明显降低(P<0.05);血清中睾酮浓度随着PFOS剂量的加大有明显下降的趋势,20mg·kg~(-1)剂量组显著低于对照组(P<0.05);类/胆固醇相关基因star和cyp11α1的mRNA表达水平明显下调。研究表明,青春期的PFOS暴露会导致睾酮合成途径中相关因子的功能缺失,破坏成熟睾丸间质细胞的功能,致使睾酮水平降低,并抑制精子生成,从而破坏生殖系统的功能。     

Inductive potency of TCDD, TBDD and three 2,3,7,8-mixed-halogenated dioxins in liver microsomes of male rats. Enzyme kinetic considerations

The enzyme inducing potency of single doses of three 2,3,7,8-substituted mixed halogenated dibenzo-p-dioxins was investigated and compared with 2,3,7,8-TCDD and 2,3,7,8-TBDD. All substances showed a quite similar potency for EROD induction. The use of a substrate concentration of 0.5 μM ethoxyresorufin is strongly recommended.     

经皮肤暴露四溴双酚A对Wistar雄性大鼠的毒性效应

尘/土以及含阻燃剂产品的皮肤接触是四溴双酚A(TBBPA)重要的人体暴露途径。为研究TBBPA经皮肤亚慢性暴露毒性效应,选择无特定病原菌级别(SPF级)Wistar雄性大鼠作为受试生物,分别设空白对照组(K)、溶剂对照组(Z),以及20mg·kg~(-1)(A)、60 mg·kg~(-1)(B)、200 mg·kg~(-1)(C)、600 mg·kg~(-1)(D)共4个不同剂量的TBBPA暴露组,采用皮肤接触的方式连续暴露90 d。暴露期间观察大鼠状态并称重,于第91天解剖大鼠,分离主要脏器称重计算脏器系数,并对暴露皮肤进行组织病理学检查。研究发现,经皮肤暴露TBBPA后,90 d暴露期间不同实验组Wistar大鼠在表观形态、行动、进食方面无差异,TBBPA暴露导致大鼠体重略微降低,但各处理组间大鼠体重无显著差异;90 d暴露后不同剂量组间大鼠的器官脏器系数没有显著的剂量-效应关系,不同剂量组大鼠皮肤暴露区域均有一定程度的炎症细胞浸润及部分组织胶原间隙增宽。研究结果表明,TBBP A 90 d亚慢性皮肤暴露对Wistar大鼠无明显毒性效应。     

羰基镍急性中毒对大鼠骨髓细胞的DNA损伤

通过动物实验观察不同剂量羰基镍对大鼠骨髓细胞DNA损伤程度。采用SD大鼠,以135 mg·m~(-3)和250 mg·m~(-3)羰基镍为染毒组,250 mg·m~(-3)氯气为阳性对照组,静态方式染毒30 min。未染毒组为正常对照组,大鼠染毒后1、2、3和7 d分别采集样本。采用单细胞凝胶电泳检测每组大鼠骨髓细胞DNA的损伤程度。彗星尾长和Olive尾矩2个指标的分析结果表明,大鼠骨髓细胞DNA损伤程度随着羰基镍染毒剂量的增加而增加,在4个时间点各剂量组间均有显著差异(P0.05)且随时间的变化有一定的规律,损伤程度在3 d时达到最大,而后缓慢下降。羰基镍急性中毒对大鼠骨髓细胞DNA有一定的损伤,且存在剂量-效应关系,各剂量组损伤程度有一定的时间效应规律。     

Low level inhalation experiments with four different cadmium compounds in rats†

This long‐term inhalation study was designed to describe the toxicity and the carcinogenic risk from Cd compounds because it had been shown from former long‐term inhalation studies that cadmium choloride induced primary lung tumors in Wistar rats. It was therefore logical to examine whether other cadmium compounds to which human beings are more frequently exposed have also carcinogenic potency. In a long‐term inhalation study cadmium aerosols consisting of cadmium chloride (CdCl₂), cadmium oxide (CdO) as dusts and fumes, cadmium sulfate (CdSO₄), cadmium sulfide (CdS) and a combination of cadmium oxide/zinc oxide were used. Wistar rats were continuously exposed in inhalation chambers for 18 months 22 hrs a day or for 40 hrs a week. The studies will be terminated at the mean survival life time of the species. The aerosols were generated by several different systems. The particles of the cadmium aerosols have the average mass medium diameters in the range from 0.2 to 0.5 μm.     

Detection of metallothionein in the intestinal mucosa and brain with 109cadmium∗

Metallothionein (MT) has a great capacity of binding metal ions showing an interesting connection with metal toxicology, as a biochemical marker for environmental metal pollution.

To normal male Wistar rats (200±10 g) and other groups with ferropenic anemia, are administered 1 mg Cd/Kg/day, during 6 days, and MT labelled with the administration 2 h before sacrifice of 3 μCi ¹⁰⁹CdCl₂, also through intragastric catheter. The MT concentration in the intestinal mucosa is expressed in μg MT/g fresh tissue, being for control rats 1.4 ± 0.5; for rats administered with 6 doses of Cd 2.5 ± 0.6 (P<0.05); with ferropenic anemia 4.3±0.7 (P<0.001), and for anemic rats treated with 6 doses Cd 12 + 0,3 (P<0.001) μg MT/g fresh tissue respectively. PAGE 15% T, 2% C_Bis show for intestinal mucosa 2 MT peaks and for brain 3 MT peaks. Anemia induce MT accumulation and increases cadmium incorporation, being anemic subjects eligibles to be submitted first to control and detoxication than the rest of the population, and also MT should be studied as biochemical marker of the pollution.     

Histopathological effects of artemether on selected organs in rat

Dose and treatment-duration neurotoxic effects are reported for artemisinin drugs of mostly the liposoluble derivatives; and yet artemether, the only parenteral formulation of the artemisinin series available in Nigeria is fat-soluble and also has a treatment-duration of 5–7 days (in an attempt to delay recrudescence). Since parenteral drugs are usually resorted to in severe/complicated or multidrug-resistant malaria against the oral artemisinin co-formulated therapies (ACT), this study is aimed to investigate the pathological changes on selected tissues (if any), in rats, of the normal 7-days artemether-injections when used both in the normal and higher doses. Artemether was administered i.p., at three dose levels, equivalent to therapeutic dose (1.5 mg kg^?1) as well as 5 and 10 times higher (7.5 and 15 mg kg^?1). A three percentage v/v Tween 80 vehicle was used for the control experiment. The pathological changes in the kidney, heart, liver, and lungs evaluated using percentage mean organ:body-weight ratio showed no changes in the organs. No histopathological effect was observed in the organs of rats treated with 1.5 mg kg^?1. However, rats treated with 7.5 and 15 mg kg^?1 revealed necrositic lesions with mononuclear cellular-infiltration in the liver and brain. The liver had focal area necrosis, while the brain had liquefactive necrosis, neuronal degeneration, congested blood vessels, hemorrhage, and vacuolations. The interstitial spaces of the glomerulus and renal tubules of one kidney from rats that received 15 mg kg^?1 had focal area fibrositic-necrosis.