• Title/Summary/Keyword: mixing temperature

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Risk Assessment of Operator Exposure During Treatment of Fungicide Dithianon on Apple Orchard (사과 과수원에서 농약살포시 살균제 Dithianon의 농작업자 위해성 평가)

  • Cho, ll Kyu;Kim, Su Jin;Kim, Ji Myung;Oh, Young Goun;Seol, Jae Ung;Lee, Ji Ho;Kim, Jeong Han
    • Korean Journal of Environmental Agriculture
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    • v.37 no.4
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    • pp.302-311
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    • 2018
  • BACKGROUND: Dithianon (75%) formulation were mixed and sprayed as closely as possible by normal practice on the ten farms located in the Mungeong of South Korea. Patches, cotton gloves, socks, masks, and XAD-2 resin were used for measurement of the potential exposure of dithianon on the applicators wearing standardized whole-body outer and inner dosimeter (WBD). This study has been carried out to determine the dermal and inhalation exposure to dithianon during preparation of spray suspension and application with a power sprayer on a apple orchard. METHODS AND RESULTS: A personal air monitor equipped with an air pump, IOM sampler and cassette, and glass fiber filter was used for inhalation exposure. The field studies were carried out in a apple orchard. The temperature and relative humidity were monitored with a thermometer and a hygrometer. Wind speed was measured using a pocket weather meter. All mean field fortification recoveries were between 85.1% and 99.1% in the level of 100 LOQ (limit of quantification), while the LOQ for dithianon was $0.05{\mu}g/mL$ using HPLC-DAD. The exposure to dithianon on arms of the mixer/loader (0.0794 mg) was higher than other body parts (head, hands, upper body, or legs). The exposure to dithianon on the applicator's legs (3.78 mg) was highest in the body parts. The dermal exposures for mixer/loader and applicator were 10 and 8.10 mg, respectively, from a grape orchard. The inhalation exposure during application was estimated as 0.151 mg, and the ratio of inhalation exposure was 11.2% of the dermal exposure (inner clothes). CONCLUSION: The dermal and inhalation exposure on the applicator appeared to be 4.203 mg - 25.064 mg and $0.529{\mu}g-116.241{\mu}g$, respectively. The total exposures on the agricultural applicators were at the level of 2.596 mg - 25.069 mg to dithianon during treatment for apple orchard. The TER showed 3.421 (>1) when AOEL of dithianon was used as a reference dose for the purpose of risk assessment of the mixing/loading and application.

Evaluation and Physicochemical Property for Building Materials from the Japanese Ministry of General Affairs in Joseon Dynasty (일제강점기 조선통감부 건축재료의 물리화학적 특성과 평가)

  • Park, Seok Tae;Lee, Jeongeun;Lee, Chan Hee
    • Economic and Environmental Geology
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    • v.55 no.4
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    • pp.317-338
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    • 2022
  • Physicochemical characteristics and evaluation were studied by subdividing the concretes, bricks and earth pipes on the site of the Japanese Ministry of General Affairs in Joseon Dynasty, known as modern architecture, into three periods. Concretes showed similar specific gravity and absorption ratio, and large amounts of aggregates, quartz, feldspar, calcite and portlandite were detected. Porosity of the 1907 bricks were higher than those of 1910 and 1950 bricks. All earthen pipe is similar, but the earlier one was found to be more dense. Bricks and earthen pipes are dark red to brown in color within many cracks and pores, but the matrix of the earthen pipe is relatively homogeneous. Quartz, feldspar and hematite are detected in bricks, and mullite is confirmed with quartz and feldspar in earthen pipes, so it is interpreted that the materials have a firing temperature about 1,000 to 1,100℃. Concretes showed similar CaO content, but brick and earthen pipe had low SiO2 and high Al2O3 in the 1907 specimen. However, the materials have high genetic homogeneity based on similar geochemical behaviors. Ultrasonic velocity and rebound hardness of the concrete foundation differed due to the residual state, but indicated relatively weak physical properties. Converting the unconfined compressive strength, the 1st extended area had the highest mean values of 45.30 and 46.33 kgf/cm2, and the 2nd extended area showed the lowest mean values (20.05 and 24.76 kgf/cm2). In particular, the low CaO content and absorption ratio, the higher ultrasonic velocity and rebound hardness. It seems that the concrete used in the constructions of the Japanese Ministry of General Affairs in Joseon Dynasty had similar mixing characteristics and relatively constant specifications for each year. It is interpreted that the bricks and earthen pipes were through a similar manufacturing process using almost the same raw materials.

Characteristics on spatial distributions of phytoplankton communities in relation to water masses in the western South Sea, Korea in early autumn 2021 (2021년 이른 가을 남해 서부 해역의 수괴 분포 및 식물플랑크톤 군집의 공간분포 특성)

  • Yang Ho Yoon
    • Korean Journal of Environmental Biology
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    • v.39 no.4
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    • pp.559-572
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    • 2021
  • A survey was conducted to analyze water masses and spatial distributions of phytoplankton communities at 15 stations on the surface and chlorophyll a maximum layers (CML) in the western South Sea of Korea from September 8 to 9, 2021. As a result, water masses were classified into Coastal Waters (CW) with relatively low salinity, the Tsushima Warm Current (TWC) with high water temperature and high salinity, and mixed waters (MW) showing a mixture of these two water masses. Turbidity showed high concentration in both the surface and CML. The chlorophyll a concentration was as low as 0.90±0.43 ㎍ L-1 in the surface, more than 1.1 ㎍ L-1 in CW, around 1.0 ㎍ L-1 in MW, and less than 0.5 ㎍ L-1 in the TWC. CML was 1.64±0.54 ㎍ L-1. Regarding species composition of phytoplankton communities, there were 57 species in 31 genera(diatoms, 57.8%; dinoflagellates, 35.1%; and other phytoflagellates, 7.1%). The phytoplankton standing crop had 4.6±7.6 cells mL-1 in the surface, more than 30 cells mL-1 in the CW, 2-5 cells mL-1 in the MW, and less than 2 cells mL-1 in the TWC. CML was slightly higher than the surface with a variation of 5.7±8.4 cells mL-1. Dominant species were found to be Rhizosolenia flagilissima f. flagilissima, Skeletonema costatum-ls, and Nitzschia sp./ small size in the surface. For the CML Rh. flagilisima f. flagilissima showed a dominance of 12.0%. For the surface, the diversity variation was 2.36±0.40, which was high for TWC but low for MW. For CML, the diversity variation was 2.29±0.52, which was slightly lower than that of the surface. The dominance in the surface was 0.50±0.15, with a fluctuation range of more than 0.5 in MW and less than 0.5 in the TWC, which was different from the diversity. According to correlation analysis and principal component analysis (PCA), the presence of phytoplankton standing crops was high in CW but low in MW and TWC. That is, phytoplankton communities in early autumn were strongly affected by the expansion and mixing of water masses in western South Sea.

A Study on change in thermal properties and chemical structure of Zr-Ni delay system by aging (노화에 따른 Zr-Ni계 지연관의 열 특성 및 화학적 구조 변화에 관한 연구)

  • Park, Byung Chan;Chang, Il Ho;Kim, Sun Tae;Hwang, Taek Sung;Lee, Seungho
    • Analytical Science and Technology
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    • v.22 no.4
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    • pp.285-292
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    • 2009
  • It has been observed that, after long term storage, some ammunitions are misfired by tamping (combustionstopping) due to aging of the chemicals loaded in the ammunitions. Used in ammunitions are percussion powder which provides the initial energy, igniter which ignites the percussion powder, and a delay system that delays the combustion for a period of time. The percussion powder is loaded first, followed by the igniter and then the delay system, and the ammunitions explode by the energy being transferred in the same order. Tamping occurs by combustion-stopping of the igniter or insufficient energy transfer from the igniter to the delay system or the combustion-stopping of the delay system, which are suspected to be caused by low purity of the components, inappropriate mixing ratio, size distribution of particulate components, type of the binder, blending method, hydrolysis by the humidity penetrated during the long term storage, and chemical changes of the components by high temperature. Goal of this study is to find the causes of the combustion-stopping of the igniter and the delay system of the ammunitions after long term storage. In this study, a method was developed for testing of the combustion-stopping, and the size distributions of the particulate components were analyzed with field-flow fractionation (FFF), and then the mechanism of chemical change during long term storage was investigated by thermal analysis (differential scanning calorimetry), XRD (X-ray diffractometry), and XPS (X-ray photoelectron spectroscopy). For the ignition system, M (metal)-O (oxygen) and M-OH peaks were observed at the oxygen's 1s position in the XPS spectrum. It was also found by XRD that $Fe_3O_4$ was produced. Thus it can be concluded that the combustion-stopping is caused by reduction in energy due to oxidation of the igniter.

Hydrochemistry and Noble Gas Origin of Various Hot Spring Waters from the Eastern area in South Korea (동해안지역 온천유형별 수리화학적 특성 및 영족기체 기원)

  • Jeong, Chan-Ho;Nagao, Keisuke;Kim, Kyu-Han;Choi, Hun-Kong;Sumino, Hirochika;Park, Ji-Sun;Park, Chung-Hwa;Lee, Jong-Ig;Hur, Soon-Do
    • Journal of Soil and Groundwater Environment
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    • v.13 no.1
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    • pp.1-12
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    • 2008
  • The purpose of this study is to characterize the hydrogeochemical characteristics of hot spring waters and to interpret the source of noble gases and the geochemical environment of the hot spring waters distributed along the eastern area of the Korean peninsula. For this purpose, We carried out the chemical, stable isotopic and noble gas isotopic analyses for eleven hot spring water and fourteen hot spring gas samples collected from six hot spring sites. The hot spring waters except the Osaek hot spring water show the pH range of 7.0 to 9.1. However, the Osaek $CO_2$-rich hot spring water shows a weak acid of pH 5.7. The temperature of hot spring waters in the study area ranges from $25.7^{\circ}C$ to $68.3^{\circ}C$. Electrical conductivity of hot spring waters varies widely from 202 to $7,130{\mu}S/cm$. High electrical conductivity (av., $3,890{\mu}S/sm$) by high Na and Cl contents of the Haeundae and the Dongrae hot spring waters indicates that the hot spring waters were mixed with seawater in the subsurface thermal system. The type of hot springs in the viewpoint of dissolved components can be grouped into three types: (1) alkaline Na-$HCO_3$ type including sulfur gas of the Osaek, Baekam, Dukgu and Chuksan hot springs, and (2) saline Na-Cl type of the Haeundae and Dongrae hot springs, and (3) weak acid $CO_2$-rich Na-$HCO_3$ type of Osaek hot spring. Tritium ratios of the Haeundae and the Dongrae hot springs indicate different residence time in their aquifers of older water of $0.0{\sim}0.3$ TU and younger water of $5.9{\sim}8.8$ TU. The ${\delta}^{18}O$ and ${\delta}D$ values of hot spring waters indicate that they originate from the meteoric water, and that the values also reflect a latitude effect according to their locations. $^3He/^4He$ ratios of the hot spring waters except Osaek $CO_2$-rich hot spring water range from $0.1{\times}10^{-6}$ to $1.1{\times}10^{-6}$ which are plotted above the mixing line between air and crustal components. It means that the He gas in hot spring waters was originated mainly from atmosphere and crust sources, and partly from mantle sources. The Osaek $CO_2$-rich hot spring water shows $3.3{\times}10^{-6}$ in $^3He/^4He$ ratio that is 2.4 times higher than those of atmosphere. It provides clearly a helium source from the deep mantle. $^{40}Ar/^{36}Ar$ ratios of hot spring water are in the range of an atmosphere source.

Effect of xylazine hydrochloride on histamine release (Xylazine이 histamine 유리에 미치는 영향)

  • 김영환;박준형
    • Korean Journal of Veterinary Service
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    • v.25 no.1
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    • pp.53-73
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    • 2002
  • It has been reported that degranulation of mast cells in rats, rabbits and dog was observed after dosing xylazine hydrochloride(Xh) which has been widely used as sedative, analgesic and muscular relaxant. Therefore, this experiment was conducted to examine the relations between Xh and histamine release and to identify the action of ${\alpha}$-adrenoceptors which exists on the suface of mast cells. 1. The content of histamine within serum was measured with HPLC by performing the O-phthalaldehyde(OPA) fluorescent derivation. The pretreatment method had a little modification from the conventional method. The pretreament was carried out in the following method. 0.2$m\ell$ of serum and 1$m\ell$ of butanol were added to mixed together and then the liquid was centrifugally separated at 4$^{\circ}C$ and 2,000 rpm for 3 minutes. 0.4$m\ell$ of 0.1N HCl and 1.6$m\ell$ of heptane were added to 0.8$m\ell$ of supernatant taken from the liquid, and they were mixed together. This mixture was also centrifugally separated at 4$^{\circ}C$ and 2,000 rpm for 5 minutes. The supernatant was thrown away and the OPA fluorescent derivation was carried out with 0.2$m\ell$ of the lower liquid then, 5 minutes after mixing 400${\mu}\ell$ of 0.1N HCl, 120${\mu}\ell$ of 1N NaOH and 40${\mu}\ell$ of 0.1% OPA in the 0.2$m\ell$ of the lower liquid,120${\mu}\ell$ of 3.57N H$_3$PO$_4$ was added to the mixed liquid, and the liquid, was mixed again and syringe-filtered. Then, the measurement was done with HPLC in the 30 : 70(ν/ν) ratio of 0.004M KH$_2$PO$_4$: CH$_3$CN, flow rate of 1.0$m\ell$/min., and a wavelength of λex= 350nm and λem=444nm at the column temperature of 27$^{\circ}C$, using the fluorescence detector. 2. The content of histamine in each laboratory animal appeared to be higher in such an order as rabbit, rat, guinea pig, dog, Korean indigenous goat, swine, Korean indigenous cattle, Holstein, and mouse, of which the individual mean values${\pm}$standard deviation were 2.0668 ${\pm}$ 0.6049. 0.4999 ${\pm}$ 0.2278, 0.4241 ${\pm}$ 0.1974, 0.1054 ${\pm}$ 0.0556, 0.1028 ${\pm}$ 0.0276, 0.0972 ${\pm}$ 0.0513, 0.0872 ${\pm}$ 0.0373, 0.0717 ${\pm}$ 0.0379, and 0.0706 ${\pm}$ 0.0366, respectively. 3. The content of histamine was measured at the moments of 15-, 30-, 60-, 120-minutes after inoamuscular injection of 20mg/100kg Xh into two to 4 years old Holstein weighing 600∼700kg. The result showed that there was a significant increase at the times of 30- and 90-minutes after injection(p<0.05). 4. Intramuscular injection of 3mg/10kg Xh was given to crossbred pug dogs weighing 2.5∼4.3kg. The content of histamine was measured at the times of 30-, 60-, 90- and 120-minutes after injection. The result revealed that there was a significant increase at the times of 60-and 90-minutes after injection(p<0.05). 5. Intramuscular injection of 10mg/$m\ell$∼25mg/$m\ell$ Xh in concentration of 0.1$m\ell$ was applied to Korean indigenous goat over 5 months old. Then, the content of histamine was measured at the times of 15-, 30-, 60- and 90-minutes after injection. A significant increase was shown at the times of 30- and 60-minutes after injection(p<0.05). 6. The content of histamine was measured at the moments of 30- and 60-minutes after intramuscular injection of 0.1-0.2$m\ell$ Xh (20mg/$m\ell$) into male rabbits weighting 2.5-4kg. A significant increase was found at the moment of 60 minutes after injection(p<0.001). 7. After administering Xh to the mast cell taken from the abdominal cavity of mouse, the content of histamine was measured. The result showed that the higher the concentration, the more significantly the content of histamine was increased(p<0.05). 8. Compound 48/80 was administered in concentration of 5$\mu\textrm{g}$/$m\ell$ and 10$\mu\textrm{g}$/$m\ell$ to the mast cell picked from the abdominal cavity of mouse. The result showed that there was a significant increase in the content of histamine in case of the concentration of 10$\mu\textrm{g}$/$m\ell$(p<0.05). It was found to be about 10,000 to 500,000 times stronger than the Xh. 9. After premedication of 1mg/kg of yohimbine hydrochloride as ${\alpha}$$_2$-adrenergic antagonist to rabbits, the Xh was administered to them. The result was that the value of histamine within serum was decreased significantly(p<0.001). 10. After premeditation of 1mg/kg of prazosin hydrochloride as ${\alpha}$$_1$-adrenergic antagonist to rabbits, the Xh was administered to them. It was found that the value of histamine within serum was decreased significantly(p<0.005). 11, Prazosin hydrochloride and yohimbine hydrochloride as ${\alpha}$$_1$-adrenergic antagonist, respectively, and ${\alpha}$$_2$-adrenergic antagonist were administerd. In this case, the value of histamine within serum was decreased significantly(p<0.0001). As the results, when the Xh is administered to various kinds of animals, the amount of histamine release within serum is increased. In view of the results so far achieved, it is concluded that Xh acted on both a$_1$-adrenoreceptor and ${\alpha}$$_2$-adrenoreceptor induces the degranulation of mast cell.

Alteration and Mineralization in the Xiaoxinancha Porphyry Copper Deposit, Yianbin, China: Fluid Inclusion and Sulfur Isotope Study (중국 연변 쇼시난차 반암동 광상의 광화작용 및 변질작용: 유체포유물 및 황동위원소 연구)

  • Seong-Taek Yun;Chil-Sup So;Bai-Lu Jin;Chul-Ho Heo;Seung-Jun Youm
    • Economic and Environmental Geology
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    • v.35 no.3
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    • pp.211-220
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    • 2002
  • The Xiaoxinancha Cu-Au deposit in the Jilin province, located in NNE 800 km of Beijing, is hosted by diorite. The ore mineralization of Xiaoxinancha Cu-Au deposit show a stockwork occurrence that is concentrated on the potassic and phyllic alteration zones. The Xiaoxinancha Cu-Au deposit in the south is being mined with its reserves grading 0.8% Cu, 3.64 g/t Au and 16.8 g/t Ag and in the north, grading 0.63% Cu, 3.80 g/t Au and 6.8 glt Ag. The alteration assemblage occurs as a supergene blanket over deposit. Hydrothermal alteration at the Xiaoxinancha Cu-Au deposit is centered about the stock and was extensively related to the emplacement of the stock. Early hydrothermal alteration was dominantly potassic and followed by propylitic alteration. Chalcocite, often associated with hematite, account for the ore-grade copper, while chalcopyrite, bornite, quartz, epidote, chlorite and calcite constitute the typical gangue assemblage. Other minor opaque phases include pyrite, marcasite, native gold, electrum, hessite, hedleyite, volynskite, galenobismutite, covellite and goethite. Fluid inclusion data indicate that the formation of this porphyry copper deposit is thought to be a result of cooling followed by mixing with dilute and cooler meteoric water with time. In stage II vein, early boiling occurred at 497$^{\circ}$C was succeeded by the occurrence of halite-bearing type III fluid inclusion with homogenization temperature as much as 100$^{\circ}$C lower. The salinities of type 1II fluid inclusion in stage II vein are 54.3 to 66.9 wt.% NaCI + KCI equiv. at 383$^{\circ}$ to 495$^{\circ}$C, indicating the formation depth less than 1 km. Type I cupriferous fluids in stage III vein have the homogenization temperatures and salinity of 168$^{\circ}$ to 365$^{\circ}$C and 1.1 to 9.0 wt.% NaCI equiv. These fluid inclusions in stage III veins were trapped in quartz veins containing highly fractured breccia, indicating the predominance of boiling evidence. This corresponds to hydrostatic pressure of 50 to 80 bars. The $\delta$$^{34}S$ value of sulfide minerals increase slightly with paragenetic time and yield calculated $\delta$$^{34}S_{H2S}$ values of 0.8 to 3.7$\textperthousand$. There is no mineralogical evidence that fugacity of oxygen decreased, and it is thought that the oxygen fugacity of the mineralizing fluids have been buffered through reaction with magnetite. We interpreted the range of the calculated $\delta$$^{34}S_{H2S}$ values for sulfides to represent the incorporation of sulfur from two sources into the Xiaoxinancha Cu-Au hydrothermal fluids: (1) an isotopically light source with a $\delta$$^{34}S$ value of I to 2$\textperthousand$, probably a Mesozoic granitoid related to the ore mineralization. We can infer from the fact that diorite as the host rock in the Xiaoxinancha Cu-Au deposit area intruded plagiogranite; (2) an isotopically heavier source with a $\delta$$^{34}S$ value of > 4.0$\textperthousand$, probably the local porphyry.

Pharmacological Studies of Cefoperazone(T-1551) (Cefoperazone(T-1551)의 약리학적 연구)

  • Lim J.K.;Hong S.A.;Park C.W.;Kim M.S.;Suh Y.H.;Shin S.G.;Kim Y.S.;Kim H.W.;Lee J.S.;Chang K.C.;Lee S.K.;Chang K.C.;Kim I.S.
    • The Korean Journal of Pharmacology
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    • v.16 no.2 s.27
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    • pp.55-70
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    • 1980
  • The pharmacological and microbiological studies of Cefoperazone (T-1551, Toyama Chemical Co., Japan) were conducted in vitro and in vivo. The studies included stability and physicochemical characteristics, antimicrobial activity, animal and human pharmacokinetics, animal pharmacodynamics and safety evaluation of Cefoperazone sodium for injection. 1) Stability and physicochemical characteristics. Sodium salt of cefoperazone for injection had a general appearance of white crystalline powder which contained 0.5% water, and of which melting point was $187.2^{\circ}C$. The pH's of 10% and 25% aqueous solutions were 5.03 ana 5.16 at $25^{\circ}C$. The preparations of cefoperazone did not contain any pyrogenic substances and did not liberate histamine in cats. The drug was highly compatible with common infusion solutions including 5% Dextrose solution and no significant potency decrease was observed in 5 hours after mixing. Powdered cefoperazone sodium contained in hermetically sealed and ligt-shielded container was highly stable at $4^circ}C{\sim}37^{\circ}C$ for 12 weeks. When stored at $4^{\circ}C$ the potency was retained almost completely for up to one year. 2) Antimicrobial activity against clinical isolates. Among the 230 clinical isolates included, Salmonella typhi was the most susceptible to cefoperazone, with 100% inhibition at MIC of ${\leq}0.5{\mu}g/ml$. Cefoperazone was also highly active against Streptococcus pyogenes(group A), Kletsiella pneumoniae, Staphylococcus aureus and Shigella flexneri, with 100% inhibition at $16{\mu}g/ml$ or less. More than 80% of Escherichia coli, Enterobacter aerogenes and Salmonella paratyphi was inhibited at ${\leq}16{\mu}/ml$, while Enterobacter cloaceae, Serratia marcescens and Pseudomonas aerogenosa were somewhat less sensitive to cefoperagone, with inhibitions of 60%, 55% and 35% respectively at the same MIC. 3) Animal pharmacokinetics Serum concentration, organ distritution and excretion of cefoperazone in rats were observed after single intramuscular injections at doses of 20 mg/kg and 50 mg/kg. The extent of protein binding to human plasma protein was also measured in vitro br equilibrium dialysis method. The mean Peak serum concentrations of $7.4{\mu}g/ml$ and $16.4{\mu}/ml$ were obtained at 30 min. after administration of cefoperazone at doses of 20 mg/kg and 50 mg/kg respectively. The tissue concentrations of cefoperazone measured at 30 and 60 min. were highest in kidney. And the concentrations of the drug in kidney, liver and small intestine were much higher than in blood. Urinary and fecal excretion over 24 hours after injetcion ranged form 12.5% to 15.0% in urine and from 19.6% to 25.0% in feces, indicating that the gastrointestinal system is more important than renal system for the excretion of cefoperazone. The extent of binding to human plasma protein measured by equilibrium dialysis was $76.3%{\sim}76.9%$, which was somewhat lower than the others utilizing centrifugal ultrafiltration method. 4) Animal pharmacodynamics Central nervous system : Effects of cefoperazone on the spontaneous movement and general behavioral patterns of rats, the pentobarbital sleeping time in mice and the body temperature in rabbits were observed. Single intraperitoneal injections at doses of $500{\sim}2,000mg/kg$ in rats did not affect the spontaneous movement ana the general behavioral patterns of the animal. Doses of $125{\sim}500mg/kg$ of cefoperazone injected intraperitonealy in mice neither increased nor decreased the pentobarbital-induced sleeping time. In rabbits the normal body temperature was maintained following the single intravenous injections of $125{\sim}2,000mg/kg$ dose. Respiratory and circulatory system: Respiration rate, blood pressure, heart rate and ECG of anesthetized rabbits were monitored for 3 hours following single intravenous injections of cefoperazone at doses of $125{\sim}2,000mg/kg$. The respiration rate decreased by $3{\sim}l7%$ at all the doses of cefoperazone administered. Blood pressure did not show any changes but slight decrease from 130/113 to 125/107 by the highest dose(2,000 mg/kg) injected in this experiment. The dosages of 1,000 and 2,000 mg/kg seemed to slightly decrease the heart rate, but it was not significantly different from the normal control. All the doses of cefoperazone injected were not associated with any abnormal changes in ECG findings throughout the monitering period. Autonomic nervous system and smooth muscle: Effects of cefoperazone on the automatic movement of rabbit isolated small intestine, large intestine, stomach and uterus were observed in vitro. The autonomic movement and tonus of intestinal smooth muscle increased at dose of $40{\mu}g/ml$ in small intestine and at 0.4 mg/ml in large intestine. However, in stomach and uterine smooth muscle the autonomic movement was slightly increased by the much higher doses of 5-10 mg/ml. Blood: In vitro osmotic fragility of rabbit RBC suspension was not affected by cefoperazone of $1{\sim}10mg/ml$. Doses of 7.5 and 10 mg/ml were associated with 11.8% and 15.3% prolongation of whole blood coagulation time. Liver and kidney function: When measured at 3 hours after single intravenous injections of cefoperaonze in rabbits, the values of serum GOT, GPT, Bilirubin, TTT, BUN and creatine were not significantly different from the normal control. 5) Safety evaluation Acute toxicity: The acute toxicity of cefoperazone was studied following intraperitoneal and intravenous injections to mice(A strain, 4 week old) and rats(Sprague-Dawler, 6 week old). The LD_(50)'s of intraperitonealy injected cefoperazone were 9.7g/kg in male mice, 9.6g/kg in female mice and over 15g/kg in both male and female rats. And when administered intravenously in rats, LD_(50)'s were 5.1g/kg in male and 5.0g/kg in female. Administrations of the high doses of the drug were associated with slight inhibition of spontaneous movement and convulsion. Atdominal transudate and intestinal hyperemia were observed in animals administered intraperitonealy. In rats receiving high doses of the drug intravenously rhinorrhea and pulmonary congestion and edema were also observed. Renal proximal tubular epithelial degeneration was found in animals dosing in high concentrations of cefoperazone. Subacute toxicity: Rats(Sprague-Dawley, 6 week old) dosing 0.5, 1.0 and 2.0 g/kg/day of cefoperazone intraperitonealy were observed for one month and sacrificed at 24 hours after the last dose. In animals with a high dose, slight inhibition of spontaneous movement was observed during the experimental period. Soft stool or diarrhea appeared at first or second week of the administration in rats receiving 2.0g/kg. Daily food consumption and weekly weight gain were similar to control during the administration. Urinalysis, blood chemistry and hematology after one month administration were not different from control either. Cecal enlargement, which is an expected effect of broad spectrum antibiotic altering the normal intestinal microbial flora, was observed. Intestinal or peritoneal congestion and peritonitis were found. These findings seemed to be attributed to the local irritation following prolonged intraperitoneal injections of hypertonic and acidic cefoperazone solution. Among the histopathologic findings renal proximal tubular epithelial degeneration was characteristic in rats receiving 1 and 2g/kg/day, which were 10 and 20 times higher than the maximal clinical dose (100 mg/kg) of the drug. 6) Human pharmacokinetics Serum concentrations and urinary excretion were determined following a single intravenous injection of 1g cefoperazone in eight healthy, male volunteers. Mean serum concentrations of 89.3, 61.3, 26.6, 12.3, 2.3, and $1.8{\mu}g/ml$ occured at 1,2,4,6,8 and 12 hours after injection respectively, and the biological half-life was 108 minutes. Urinary excretion over 24 hours after injection was up to 43.5% of administered dose.

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