Toxicokinetics,metabolism, and microsomal studies of chlorpropham in rats

A study on the toxicokinetic behavior, metabolism of chlorpropham, and its effect on cytochrome P₄₅₀ from liver microsomes was carried out in albino rats after a single and consecutive oral administration at 500?mg?kg^?1 body weight for 10 and 20 days. Chlorpropham was detected in the blood at 0.08?h (11.43?±?1.72?µg?mL^?1) reaching a maximum concentration at 2?h (30.90?±?2.55?µg?mL^?1) and a minimum at 48?h (1.95?±?0.20?µg?mL^?1) after a single oral administration of 500?mg?kg^?1. The absorption rate constant (K _a) was 0.66?±?0.48?h^?1. The Vd _area (18.01?±?2.78?L?kg^?1) and t _1/2 β (12.23?±?1.96?h) values suggested a wide distribution and long persistence of the compound in the body, respectively. The higher Cl_R (0.82?±?0.00?L?kg^?1?h^?1) compared to Cl_H (0.18?±?0.02?L?kg^?1?h^?1) value indicated that a major portion of chlorpropham was excreted through the urine (30%) compared to the faeces (2.81%). Chlorpropham residue was detected in all tissues of rat at 0.25?h while its metabolite, meta-chloroaniline was detected in liver, kidney, heart, lung, and spleen tissue at 0.25?h. Meta-chloroaniline was not detected in skeletal muscle, brain, fat, and stomach tissue at any time of the observation period. Maximum concentrations of chlorpropham and meta-chloroaniline were detected at 2?h (except in the spleen), and minimum concentrations of chlorpropham at 24 (heart, lung, spleen, skeletal muscle, and stomach) and 48?h (liver, kidney, brain, and fat tissue) respectively; and meta-chloroaniline at 24?h (except heart and spleen). The tissue half-life of chlorpropham in rat varied from 3.80 to 11.60?h. Repeated oral administration of chlorpropham at 500?mg?kg^?1 for 10 and 20 days caused an induction of the liver microsomal pellet of rat.     

Accumulation and phytoavailability of benzo[a]pyrene in an acid sandy soil

Effects of benzo[a]pyrene (B[a]P) on ryegrass (Lolium perenne L.) growth, plant accumulation and dissipiation of B[a]P in a red sandy soil (Hapli-Udic Argosol) were studied in a pot experiment. The plants were grown for 61 days in soil spiked with B[a]P at 0, 12.5, 25 and 50 mg kg⁻¹. Control pots without plants were also set up. Soil extractable B[a]P, plant shoot and root biomass, and concentrations of B[a]P in plant shoots and roots were determined. Ryegrass biomass was increased by addition of B[a]P and root B[a]P concentrations were significantly correlated with B[a]P application rate, but no such correlation was found for shoot B[a]P concentrations. This indicates that B[a]P enhanced the growth of the ryegrass. The extractable B[a]P concentration in the planted soil was significantly lower than that in the unplanted control soil at the rate of 50 mg B[a]P kg⁻¹. This indicates that ryegrass may help to dissipate B[a]P in soil at concentrations over 50 mg kg⁻¹ soil although the mechanism for this is not understood.     

Benzo [a] pyrene concentrations in topsoils of North Bahrain

A comprehensive field study was conducted to determine the background concentrations of benzo [a] pyrene (B[a]P) in soil samples collected at different points on a grid covering most of the northern and middle parts of the Kingdom of Bahrain. The average B[a]P concentration was 108.4?ng?g^?1 in winter and 73.0?ng?g^?1 in summer. The capital city, Manama, and the industrial areas of the country showed the highest levels of B[a]P.     

离子液体[C_8 mim]Cl对泥鳅胚胎和仔鱼的毒性

以泥鳅的胚胎及仔鱼为试验材料,选择胚胎发育的4个不同时期(囊胚期、原肠胚中期、神经胚期、尾芽期)及仔鱼期为处理开始的时间点,探讨了离子液体[C8mim]Cl的毒性作用。结果表明,随着[C8mim]Cl浓度增加,泥鳅胚胎的孵化率下降,畸形率上升,具有明显的剂量-效应关系,67~150 mg·L-1的[C8mim]Cl对泥鳅胚胎均表现出明显的致畸毒性效应;随着[C8mim]Cl浓度增加,泥鳅仔鱼死亡率上升,而100~225 mg·L-1的[C8mim]Cl对泥鳅仔鱼具有明显的致畸、致死作用。其中,[C8mim]Cl对孵出期泥鳅仔鱼的24 h、48 h的半致死浓度分别为97.95和86.77 mg·L-1;而[C8mim]Cl对孵出后3 d泥鳅仔鱼的24 h、48 h的半致死浓度分别为73.77和40.98 mg·L-1。由上可知,在一定的剂量内,[C8mim]Cl对泥鳅胚胎及仔鱼的发育有明显的致畸、致死作用,这为离子液体[C8mim]Cl的合理使用提供了理论依据。     

Degradation of Benzo[a]Pyrene in Soil with Arbuscular Mycorrhizal Alfalfa

Mycorrhizal and non-mycorrhizal alfalfa (Medicago sativa) was grown in pots containing soil artificially contaminated with various levels of benzo[a]pyrene (B[a]P)(0, 1, 10 and 100 mg kg^–1). Soil and plants were sampled after 30, 40, 50, 60 and 90 days and compared with unlanted pots. The percentage of mycorrhizal root length colonized by Glomus caledoniun was not significantly affected by the addition of B[a]P up to 10 mg kg^–1 but was significantly lower at 100 mg kg^–1B[a]P compared with low concentrations (p < 0.05). There was no difference in soil polyphenol oxidase and dehydrogenase activity among the controls and applications of 1 and 10 mg kg^–1 of B[a]P. However, enzyme activities were significantly higher at 100 mg kg^–1B[a]P compared with the other three treatments, and there was no mycorrhizal effect. Over a period of 90 days the concentration of B[a]P in soil in which alfalfa was grown was significantly lower than in unplanted soil (p < 0.05). Degradation rates of B[a]P added at 1, 10 and 100 mg kg^–1 without G. caledonium were 76, 78 and 53%, and with mycorrhizal inoculation were 86, 87 and 57%. The degradation rate in unplanted soil was significantly lower than in planted soil, and was significantly higher in medium- and low-B[a]P treatments than in the high B[a]P concentration tested. There is a possibility of enhancement phytoremediation of PAHs in rhizosphere soil with arbuscular mycorrhizal fungi.     

Autoradiographic study to detect metabolically active phytoplankton and bacteria in the Rhode river estuary

The rate of utilization of inorganic carbon (C) and phosphate (P) by phytoplankton and bacteria in the Rhode River estuary has been estimated using liquid-emulsion autoradiography during four times of the year. Metabolic activity of phytoplankton was estimated by calculating silver grains above individual species. From these counts, the relative C and P uptake rates of individual species per unit of biomass and per volume of water were estimated. Examination of the autoradiograms showed that the metabolically most active, algae were smaller than 10 m. Both C and P were paken up by these smaller species at a higher rate than their proportion of the total biomass per volume of water would indicate. Uptake of C and P per unit of cell volume varied within a species and among the various phytoplankton at the different seasons of the year. Metabolic activity of planktonic bacteria in safranin-stained autoradiograms was also estimated by counting bacteria with associated grains and cells without grains. The ratio of 33p-labeled to unlabeled bacteria was highest in November. This high metabolic activity of bacteria in November corresponded with high P uptake rates of the phytoplankton at that time. Throughout this study, only 28 to 42% of the total phytoplankton biomass was metabolically active and, 63 to 85% of the bacteria.     

Pharmacokinetics of [14C]-atrazine in rhesus monkeys,single-dose intravenous and oral administration

This is the first study regarding the pharmacokinetics of [¹⁴C]-atrazine conducted with rhesus monkeys. The animals received one dose (0.25 mg) intravenously (IV) or three doses (1, 10, or 100 mg) orally. Plasma, urine, and feces were collected at defined times up to 7 days post-dosing. Sample radioactivity was measured to determine the mass equivalent. IV administered [¹⁴C]-atrazine disappeared rapidly from blood, with an elimination half-life of about 5.5 ± 1.1 h. The pharmacokinetic profiles of [¹⁴C]-atrazine following oral administration at the three dose levels show that kinetic parameters such as AUC and C _max are linearly correlated with the dose. Seven days after dosing, urinary and fecal excretion of [¹⁴C]-atrazine reached 99% of total administered dose in the IV group and 91–95% in the three oral dose groups. In the IV-administered monkeys, approximately 85% of the dose was excreted in urine and 12% in feces. In three oral dose groups, urinary and fecal radioactivity recoveries approximated 57% and 21%, 58% and 25%, and 53% and 35%, respectively. More than 50% of the total urinary excreted radioactivity was found within the first 24 h after dosing. In conclusion, the principal elimination of [¹⁴C]-atrazine, IV and orally administered, is via urine. The oral bioavailability was 60% or higher. There was a significant linear correlation between administered oral dose and plasma concentration. Overall oral dose accountability ranged from 91% to 95%. Data generated may be useful in the risk assessment of human exposure to environmental atrazine contamination.     

Effect of the chemical composition of organic extracts from environmental and industrial atmospheric samples on the genotoxicity of polycyclic aromatic hydrocarbons mixtures

Particulate organic matter (PM) present in the atmosphere is a complex mixture of chemicals like polycyclic aromatic hydrocarbons (PAH) that may exert adverse health effects including respiratory and cardiovascular disturbances and cancer. In this study, airborne samples from environmental or industrial areas exhibiting different physicochemical composition were compared for their capacities to induce DNA damage in human hepatocytes HepG2. DNA strand breaks and DNA adducts formed by benzo[a]pyrene-7,8-dihydrodiol-9,10-epoxide (BPDE), the most reactive metabolite of the carcinogenic benzo[a]pyrene (B[a]P), were measured with the comet assay and by high-performance liquid chromatography (HPLC)/mass spectrometry, respectively. Cells were exposed to organic matter extracted from PM. Experiments were performed either at a constant concentration of B[a]P or at concentrations corresponding to fixed air volumes. Results show that industrial extracts tend to produce more benzo[a]pyrene diol epoxide-N ²-2′-deoxyguanosine (BPDE-N ²-dGuo) DNA adducts than strand breaks, whereas the opposite was observed with environmental extracts. The chemical composition of the extracts significantly impacts the nature and levels of DNA damage. The amount of B[a]P and interaction with other contaminants in the extracts need to be considered to explain the formation of DNA damage. These results emphasize the use of in vitro tests as promising and complementary tools to widely used toxic equivalent factor (TEF) approach in order to assess health hazards related to chemical exposure of the general population.     

Parameters of light-dependent photosynthesis for phytoplankton size fractions in temperate estuarine and coastal environments

Photosynthetic parameters for netplankton (>22 m) and nanoplankton (<22 m) varied over similar ranges but exhibited different seasonal and geographic patterns of variation. Nanoplankton a was relatively constant (0.06 mg C [mg Chl · h]^-1 [E m^-2 s^-1]^-1), but P _m ^B (mg C [mg Chl · d]^-1) was an exponential function of temperature independent of nutrient concentration and vertical stability in the euphotic zone. The temperature function gives a P _m ^B of 24 at 25°C for nanoplankton growing in an estuarine environment characterized by high nutrient concentrations and a shallow, stratified euphotic zone. Variations in netplankton a and P _m ^B were less predictable and were not correlated with temperature, nutrients or vertical stability. Chain forming diatoms with small cells were able to achieve high (0.10 to 0.15) and P _m ^B (20 to 24) that were 3 to 5 times higher than large-celled diatoms and dinoflagellates were able to achieve.     

3种农药及其复配剂对日本鹌鹑的急性毒性比较

采用"经口灌胃法"测定了3种农药及其复配剂对鹌鹑的24 h、48 h、72 h和168 h急性毒性,根据我国《化学农药环境安全评价实验准则》中对鸟类的急性经口毒性划分的规定,3种农药及其复配剂对鹌鹑的毒性等级如下:35%精甲霜灵悬浮种衣剂对鸟类的24 h、48 h、72 h和168 h-LD_(50)均大于500 a.i.mg·kg~(-1)bw(以单位体重计),属"低毒"级,25 g·L~(-1)咯菌腈悬浮种衣剂对鸟类的24 h、48 h、72 h和168 h-LD_(50)也均大于500 a.i.mg·kg~(-1)bw,属"低毒"级,25%噻虫嗪水分散粒剂对鸟类的24 h、48 h、72 h和168 h-LD_(50)分别是695 mg·kg~(-1)bw、587 mg·kg~(-1)bw、502 mg·kg~(-1)bw、502 mg·kg~(-1)bw,属于"低毒"级;25%噻虫嗪·咯菌腈·精甲霜灵悬浮种衣剂对鸟类的24 h、48 h、72 h和168 h-LD_(50)分别是754 mg·kg~(-1)bw、504 mg·kg~(-1)bw、504 mg·kg~(-1)bw、504mg·kg~(-1)bw,也属于"低毒"级。     

Multiple-time contamination of benzo(a)pyrene in soils inhibits soil enzymatic activities

Benzo[a]pyrene (B[a]P) is accumulating in soils in a low-dose cumulative manner. The objectives of this study were to investigate the effects of B[a]P on the extractable and available fractions of B[a]P and on soil enzymatic activity using multiple-time superimposed and one-time contamination approaches. Results showed that the contents of B[a]P rapidly decreased in the first 14?d and later decreased slowly from 14 to 56?d in both one-time and multiple-time contamination tests. The contents of B[a]P in the multiple-time contamination test were lower than those in the one-time test. Soil urease, sucrase and dehydrogenase activities were rapidly inhibited in the early stage (14?d) and stimulated during the rest of the incubation, and soil dehydrogenase activity was more sensitive to B[a]P contamination than the other enzymes. High concentrations of B[a]P in soil led to greater inhibition of enzymatic activity than that at low concentrations in the early period of culture. Soil enzyme activities were weakly inhibited in multiple-time compared with in one-time contamination tests and were lower in the subsurface layer than in the surface layer. Our results revealed that the multiple-time superimposed approach might be better than one-time contamination for evaluating B[a]P risk in soil.     

载带苯并[a]芘的纳米碳／二氧化硅颗粒引起大鼠氧化应激作用的研究

通过人工制备载带B[a]P的纳米碳(C)和纳米二氧化硅(SiO2)颗粒,采用气管滴注染毒方式,以7.5mg·kg-1(以体重计)的染毒剂量急性染毒大鼠,观察染毒24小时后载带B[a]P的纳米C/SiO2颗粒对机体产生氧化应激损伤的联合毒性效应.结果表明,在急性染毒后大鼠外周血中反映机体脂质过氧化损伤程度指标的丙二醛(MDA)含量表现为染毒组较对照组显著增加(p<0.05),表明纳米颗粒诱发机体发生了氧化应激反应.在急性染毒后各组大鼠肺泡灌洗液中谷胱苷肽过氧化物酶(GSH-PX)和超氧化物岐化酶(T-SOD)活力与对照组相比显著增加(p<0.05)(载带B[a]P的纳米SiO2组除外);载带B[a]P的纳米SiO2组肺泡灌洗液中GSH-PX活力与对照组相比无显著差异,而与单纯纳米SiO2组和B[a]P组比较显著降低,推测与抗氧化酶的一过性增高有关;载带B[a]P的纳米C组肺泡灌洗液T-SOD活力与其单纯纳米C组和单纯B[a]P组比较显著增加(p<0.05),由此表明载带B[a]P的复合纳米C/SiO2颗粒在致机体氧化损伤效应方面二者存在一定的协同作用.     

口服纳米银对大鼠的生物有效性及其体内分布的研究

由于独特的抗菌特性,纳米银(AgNP)在诸多领域得到广泛应用,但是其生物有效性、动物组织分布及排出尚不清楚。将聚乙烯吡咯烷酮包被的AgNP溶液按照10 mg kg^-1给雌性SD大鼠灌胃,采用ICP-MS检测SD大鼠组织、粪便及尿液中总银浓度。实验结果表明,AgNP通过小肠吸收后,可以通过血液循环快速分布在肝、肾、脾、肺、脑等靶器官。灌胃后1 h,大鼠各组织中总银浓度达到最大值(肝、肾、脾、肺、脑中银浓度分别为0.29 ± 0.13 mg kg^-1、0.23 ± 0.04 mg kg^-1、0.17 ± 0.05 mg kg^-1、0.11 ± 0.01 mg kg^-1、0.06 ±0.02 mg kg^-1),之后银浓度随时间降低直至和对照组无显著性差异。在灌胃途径下,AgNP对SD大鼠的有效性为8.5%,且73%的AgNP是通过粪便的途径排出体外。     

Extra- and intracellular acid-base balance and ionic regulation in cod (Gadus morhua ) during combined and isolated exposures to hypercapnia and copper

Cod (Gadus morhua) were exposed to hypercapnia (water Pco₂ = 7.5 mmHg), elevated copper level (0.4 ppm) or a combination of both in order to study extra- and intracellular acid-base regulation and the influence hereupon of copper. During pure hypercapnia, the extracellular respiratory acidosis was completely compensated within 12 to 24 h via a chloride-mediated increase in extracellular [HCO₃ ⁻]. Exposure to copper in normocapnic seawater caused a large and progressive increase in plasma [Na⁺] and [Cl⁻] and a metabolic acidosis. Exposure to copper in hypercapnic seawater was associated with smaller elevations of plasma [Na⁺] and [Cl⁻] than in normocapnic seawater, showing that hypercapnia had a protective effect on the copper-induced osmoregulatory disturbances. The compensation of the hypercapnic acidosis was, however, slow and incomplete in fish exposed to both copper and hypercapnia. Extracellular pH remained depressed by 0.3 pH units after 72 h. The data reveal that acid-base regulation was immediately and persistently inhibited by copper. The limited acid-base regulation during combined copper and hypercapnia exposure was chloride-mediated as during hypercapnia alone. Intracellular pH recovery was complete and very rapid in ventricular and skeletal muscle tissues during environmental hypercapnia, whereas acid-base compensation in liver tissue was slower, the kinetics being similar to that in the extracellular compartment. Intracellular pH compensation was significantly slowed down by copper. Copper concentration increased drastically in gill tissue already at 3 h, while copper concentrations in liver, muscle and plasma were significantly elevated only after 48 h, with liver showing the largest elevation. Received: 15 November 1996 / Accepted: 2 December 1996     

Hematoxicity and hepatoxicity attributed to zinc and cadmium in the Norwegian rat

This study was carried out to determine changes in the blood and liver of rats given oral doses of cadmium (Cd) and zinc (Zn). Thirty 3 month old rats were kept six to a compartment in a well-demarcated five compartment cage labeled A, B, C, D, and E. After 2 weeks of acclimatization, and with ad libitum administration of water and feed, group A and B rats were, respectively, exposed to 100 mg CdSO₄ and 2200 mg ZnSO₄, respectively, mixed with their feed. Group C rats were fed with a combination of 100 mg CdSO₄ and 2200 mg ZnSO₄ mixed with their feed, while group D rats were exposed to 100 mg CdSO₄ mixed with their feed for 48 h, and after they were given 2200 mg ZnSO₄ for 96 h. Group E rats served as control and were fed a normal diet. Analysis of blood samples after 5 days showed that in rats of groups A, B, C, and D, WBC count increased from 6800 to 12,400 mm^?3 and platelets from 26,000 to 88,000 mm^?3. Reduction in blood counts were found for RBC from 13.8 to 4.7 × 10⁶ mm^?3, hemoglobin from 15.6 to 11.4 dL^?1, and PCV from 47 to 34%. ESR was the same 1.0 mm h^?1 in all groups. Severe damage to the liver was also shown by severe degeneration of hepatocytes and increase in Kuppfer cells. The above observations were mildest in the liver of group C rats. A reduction of body weight was observed in all treatment groups. Cd and Zn were found to be hematoxic and hepatotoxic in the Norwegian rat with Cd exhibiting greater toxicity than Zn. Toxicity of Cd was suppressed by Zn only when both metals were admistered at the same time, but a delay in intake of Zn (after 48 h) had little effect on Cd toxicity.     

Oxidative and genotoxic effects of bisphenol A on primary gill cell culture of Lake Van Fish (Alburnus tarichi Güldenstädt, 1814)

Lake Van is the largest lake in Turkey. The lake limits lifespan due to its high pH and brackish water. For this reason, only a single species of fish (Van Fish) is living in the lake that has been adapted to these conditions. In the present study, we investigated the total oxidant status (TOS), total antioxidant status (TAS), malondialdehyde (MDA) level and DNA damage effect of bisphenol A (BPA) (10^?7, 10^?6 and 10^?5?M) on primary gill cell culture of Van Fish for 24 and 48?h of incubation periods. TAS levels were not changed when compared to those of the control group, but TOS levels were decreased in both 24 and 48?h. The MDA level increased only at the highest concentration (10^?5) at the end of 12 and 24?h (p?.05). DNA damage increased only at the 10^?5?M concentration after 48?h. At the end of the experiment, BPA exposure caused lipid peroxidation and genotoxic effect. These results indicate that high levels of BPA exposure induced oxidative stress and DNA damage by time- and concentration-dependent fashion in the gill cell culture of Van Fish. Gill cell culture is a useful model for the rapid identification of the harmful effects of chemicals in the aquatic environment.     

Comparative studies of liver and brain glycogen content of male and female Clarias batrachus (L.) after exposure of different doses of arsenic

Different doses of arsenic (As) were used to investigate comparative toxicity on the liver and brain glycogen content on male and female Indian catfish Clarias batrachus (L.). As-induced effects were associated with gender, dose (5, 10, or 15?mg?L^?1), and varying time periods (48, 96, or 144?h). It was noted that As produced dose- and time-dependent liver glycogenolysis and late brain glycogenolysis. Liver glycogenolysis was significantly increased after 48?h at all three As doses. At the highest dose 15?mg?L^?1, liver glycogen were markedly diminished at in both male and female fish, but in females more reduction was observed than in males. However, with brain glycogen, the significant decrease was noted at 144?h with all three dose levels in both genders, with male being more susceptible. Thus, this study indicates that As produces glycogenolysis. The reduction in the liver glycogen content was more pronounced in female than in the male fish, whereas brain glycogen content decrease was more prominent in males.     

甲基异噻唑啉酮对斑马鱼胚胎的急性毒性和机制研究

甲基异噻唑啉酮(methylisothiazolinone,MIT)作为防腐剂,广泛用于个人护理品、日用品和涂料中。MIT随着污水进入地表水循环,普遍存在于水体中,但目前关于MIT对水生生物毒性的研究还比较少。本文以模式生物斑马鱼的胚胎作为受试对象,评价MIT对斑马鱼胚胎的毒性。将受精后3 h的健康斑马鱼胚胎暴露于梯度浓度的MIT下,观察其对胚胎生长发育的影响,用吖啶橙(AO)染色检测细胞凋亡情况。结果发现,48 h暴露浓度大于1.0 mg·L-1的胚胎孵化被显著抑制,72 h浓度大于1.52 mg·L-1的幼鱼心率显著降低,统计96 h幼鱼死亡和畸形数,并重复验证和计算得到96 h半致死浓度(96 h 50%lethal concentration,96 h-LC50)为6.15 mg·L-1,96 h半致畸浓度(96 h 50%teratogenesis concentration,96 h-TC50)为3.89 mg·L-1,测量96 h胚胎体长,分析最小生长抑制浓度(minimum concentration to inhibit growth,MCIG)为2.31 mg·L-1,AO染色显示72 h胚胎的凋亡细胞主要集中在脑部和尾部。不同时期下镜检观察到,胚胎出现的畸形主要包括尾部发育不良,脊柱弯曲,卵黄囊水肿和心包水肿。此外,高浓度处理组24 h胚胎自主抽动次数增加,72 h和96 h活动能力减弱,触碰反应迟钝。因此,推断MIT对斑马鱼胚胎的发育有较大影响,同时有一定的神经毒性。根据《危险化学品鱼类急性毒性分级试验方法》,判定MIT对斑马鱼胚胎为高毒,该毒性实验结果可为MIT在工业生产和环境中的风险管理提供依据。     

Transfer of radioactive carbon within the copepod Temora longicornis

Standard autoradiographic techniques have been used to describe the temporal pattern in the transfer of radioactive carbon from the chlorophyte Tetraselmis suesica (Kylin) to females of the neritic copepod Temora longicornis (Müller, 1792). After 4 and 6 h exposure to labelled phytoplankton, silver grains were deposited only in the cells of the gut-wall. After 24 h exposure, grains were deposited in most tissues, with highest concentrations in cells of the gut-wall and in oocytes within the ovary. Experiments with Centropages typicus (Krøyer), Centropages hamatus (Lilljeborg), and Labidocera aestiva Wheeler demonstrated that much of the assimilated label was not turning over rapidly and that the amount of label assimilated was correlated with known food preferences of these species.