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28-day Repeated-dose Toxicity Study of Flutamide, an Anti- androgenic Agent, in Rats: Establishment of Screening Methods for Endocrine Disruptors (내분비계 장애물질 검색법의 확립을 위한 항안드로젠성 물질 flutamide의 랫드 28일 반복투여 독성실험)

  • 정문구;김종춘;임광현;하창수
    • Toxicological Research
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    • v.16 no.2
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    • pp.163-172
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    • 2000
  • Recently, there is a worldwide concern that a great number of man-made chemicals have a hormone-like action both in humans and in animals. DECD is developing screening programs using validated test systems to determine whether certain substances may have an effect in humans. In the present study. the establishment oj repeated-dose toxicity test method was tried. Flutamide. an anti-androgenic agent. was administered by gavage to Sprague-Dawley rats for 28 days at dose levels of 0. 0.5. 3 and 18 mg/kg body weight (10-15 rats/sex/group) to examine the effects on general findings. especially reproductive and endocrine parameters. Clinical signs. body weights, food consumption, and sexual cycle were checked and measured. For the gross and microscopic examinations. 10 rats/sex/group were sacrificed at the end of dosing period and the remaining animals of control and high dose groups (5 each) were sacrificed after 14 days recovery. Examinations for hematology and clinical chemistry were carried out at necropsy. There were no treatment-related changes in clinical signs. body weights, food consumption. gross necropsy. hematology and clinical chemistry at all doses of both sexes. The period and regularity of sexual cycle were not adversely affected at all doses by the test agent. At 18 mg/kg. both decreased weights of prostate, seminal vesicle and epididymis in males and increased weights of spleen and thymus in females were observed. In addition, decreased number of spermatids and sperms. increased serum testosterone concentration and increased incidence (100%) of interstitial cell hyperplasia were seen in males. At 18 mg/kg of the recovery group. decreased prostate weight. reduced sperm count and increased incidence (20%) of interstitial cell hyperplasia in males and increased thymus weight in females were observed. At 3 mg/kg. reduced sperm count was found. There were no adverse effects on parameters examined at 0.5 mg/kg of both sexes. The results suggested that the potential target organs of flutamide may be accessory sexual glands including testes for males and spleen and thymus for females. Taken together. this test method was found to be a useful screening test system for endocrine disrupting chemicals.

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Single-dose oral toxicity study of genetically modified silkworm expressing EGFP protein in ICR mouse

  • Jang, Kyung-Min;Kim, Sung-Gun;Park, Ji-Young;Choi, Won-Ho;Lee, Jae-Woo;Jegal, Hyeon-Young;Kweon, Soon-Jong;Choi, Kwang-Ho;Park, Jung-Ho
    • Korean Journal of Agricultural Science
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    • v.43 no.1
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    • pp.109-115
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    • 2016
  • Silk has had a reputation as a luxurious and sensuous fabric but it is not popular due to the expensive price and poor durability. To develop the silk materials that apply the various industries, the artificially synthesized gene can be introduced into the silkworm and expressed in the silk gland. Transgenic silkworms for the mass production of green fluorescent silks are generated using a fibroin H-chain expression system. For commercial use, safety assessment of the transgenic silkworms is essential. The purpose of this study was to examine the potential acute oral toxicity of EGFP protein expressed in genetically modified (GM) fluorescence silkworm and to obtain the approximative lethal dose in the male and female at 6-weeks ICR mice. EGFP protein was fed at a dose of 2,000 mg/kg body weight in five male or five female mice. Mortalities, clinical findings and body weight changes were monitored for 1, 3, 7, 14 days after dosing. At the end of 14 day observation period, all mice were sacrificed, and the postmortem necropsy were performed. The test group was not observed death case. Also the effect was not admitted by test substance administration in common symptoms, the body weight and postmortem. The results of single-dose oral toxicity test showed that approximative lethal dose of EGFP protein expressed in fluorescence silkworm was considered to exceed the 2,000 mg/kg body weight in both sexes.

Coagulation Control of High Turbid Water Samples Using a Streaming Current Control System (유동흐름 전류계를 이용한 정수장 고탁도 유입수 응집 제어 방법에 대한 연구)

  • Nam, Seung-Woo;Jo, Byung-Il;Kim, Won-Kyong;Zoh, Kyung-Duk
    • Journal of Environmental Health Sciences
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    • v.38 no.2
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    • pp.128-135
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    • 2012
  • Objectives: This study was aimed at determining the optimum coagulation dosage in a high turbid kaolin water sample using streaming current detection (SCD) as an alternative to the jar test. Methods: SCD is able to optimize coagulant dosing by titration of negatively charged particles. Kaolin particles were used to mimic highly turbid water ranging from 50 to 600 NTU, and polyaluminum chloride (PAC, 17%) was applied as a titrant and coagulant. The coagulation consisted of rapid stirring (5 min at 140 rpm), reduced stirring (20 min at 70 rpm), and settling (60 min). To confirm the coagulation effect, a jar test was also compared with the SCD titration results. Results: SCD titration of kaolin water samples showed that the dose of PAC increased as the pH rose. However, supernatant turbidity less than 1 NTU after coagulation was not achieved for high turbid water by SCD titration. Instead, a conversion factor was used to calculate the optimum PAC dosage for high turbid water by correlating a jar test result with that from an SCD titration. Using this approach, we were able to successfully achieve less than 1 NTU in treated water. Conclusions: For high turbid water influent in a water treatment plant, particularly during summer, the application of SCD control by applying a conversion factor can be more useful than a jar test due to the rapid calculation of coagulation dosage. Also, the interpolation of converted PAC dose could successfully achieve turbidity in the treated water of less than 1 NTU. This result indicates that an SCD system can be effectively used in a water treatment plant even for high turbid water during the rainy season.

Digital Microflow Controllers Using Fluidic Digital-to-Analog Converters with Binary-Weighted Flow Resistor Network (이진가중형 유체 디지털-아날로그 변환기를 이용한 고정도 미소유량 조절기)

  • Yoon, Sang-Hee;Cho, Young-Ho
    • Transactions of the Korean Society of Mechanical Engineers A
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    • v.28 no.12
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    • pp.1923-1930
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    • 2004
  • This paper presents digital microflow controllers(DMFC), where a fluidic digital-to-analog converter(DAC) is used to achieve high-linearity, fine-level flow control for applications to precision biomedical dosing systems. The fluidic DAC, composed of binary-weighted flow resistance, controls the flow-rate based on the ratio of the flow resistance to achieve high-precision flow-rate control. The binary-weighted flow resistance has been specified by a serial or a parallel connection of an identical flow resistor to improve the linearity of the flow-rate control, thereby making the flow-resistance ratio insensitive to the size uncertainty in flow resistors due to micromachining errors. We have designed and fabricated three different types of 4-digit DMFC: Prototype S and P are composed of the serial and the parallel combinations of an identical flow resistor, while Prototype V is based on the width-varied flow resistors. In the experimental study, we perform a static test for DMFC at the forward and backward flow conditions as well as a dynamic tests at pulsating flow conditions. The fabricated DMFC shows the nonlinearity of 5.0% and the flow-rate levels of 16(2$^{N}$) for the digital control of 4(N) valves. Among the 4-digit DMFC fabricated with micromachining errors, Prototypes S and P show 27.2% and 27.6% of the flow-rate deviation measured from Prototype V, respectively; thus verifying that Prototypes S and P are less sensitive to the micromachining error than Prototype V.V.

Effects of Rumen Protozoa of Brahman Heifers and Nitrate on Fermentation and In vitro Methane Production

  • Nguyen, S.H.;Li, L.;Hegarty, R.S.
    • Asian-Australasian Journal of Animal Sciences
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    • v.29 no.6
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    • pp.807-813
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    • 2016
  • Two experiments were conducted assessing the effects of presence or absence of rumen protozoa and dietary nitrate addition on rumen fermentation characteristics and in vitro methane production in Brahman heifers. The first experiment assessed changes in rumen fermentation pattern and in vitro methane production post-refaunation and the second experiment investigated whether addition of nitrate to the incubation would give rise to methane mitigation additional to that contributed by defaunation. Ten Brahman heifers were progressively adapted to a diet containing 4.5% coconut oil distillate for 18 d and then all heifers were defaunated using sodium 1-(2-sulfonatooxyethoxy) dodecane (Empicol). After 15 d, the heifers were given a second dose of Empicol. Fifteen days after the second dosing, all heifers were allocated to defaunated or refaunated groups by stratified randomisation, and the experiment commenced (d 0). On d 0, an oral dose of rumen fluid collected from unrelated faunated cattle was used to inoculate 5 heifers and form a refaunated group so that the effects of re-establishment of protozoa on fermentation characteristics could be investigated. Samples of rumen fluid collected from each animal using oesophageal intubation before feeding on d 0, 7, 14, and 21 were incubated for in vitro methane production. On d 35, 2% nitrate (as $NaNO_3$) was included in in vitro incubations to test for additivity of nitrate and absence of protozoa effects on fermentation and methane production. It was concluded that increasing protozoal numbers were associated with increased methane production in refaunated heifers 7, 14, and 21 d after refaunation. Methane production rate was significantly higher from refaunated heifers than from defaunated heifers 35 d after refaunation. Concentration and proportions of major volatile fatty acids, however, were not affected by protozoal treatments. There is scope for further reducing methane output through combining defaunation and dietary nitrate as the addition of nitrate in the defaunated heifers resulted in 86% reduction in methane production in vitro.

Effects of liposomal-curcumin on five opportunistic bacterial strains found in the equine hindgut - preliminary study

  • Bland, S.D.;Venable, E.B.;McPherson, J.L.;Atkinson, R.L.
    • Journal of Animal Science and Technology
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    • v.59 no.6
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    • pp.15.1-15.5
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    • 2017
  • Background: The horse intestinal tract is sensitive and contains a highly complex microbial population. A shift in the microbial population can lead to various issues such as inflammation and colic. The use of nutraceuticals in the equine industry is on the rise and curcumin is thought to possess antimicrobial properties that may help to minimize the proliferation of opportunistic bacteria. Methods: Four cecally-cannulated horses were utilized to determine the optimal dose of liposomal-curcumin (LIPC) on reducing Streptococcus bovis/equinus complex (SBEC), Escherichia coli K-12, Escherichia coli general, Clostridium difficile, and Clostridium perfringens in the equine hindgut without adversely affecting cecal characteristics. In the first study cecal fluid was collected from each horse and composited for an in vitro, 24 h batch culture to examine LIPC at four different dosages (15, 20, 25, and 30 g) in a completely randomized design. A subsequent in vivo $4{\times}4$ Latin square design study was conducted to evaluate no LIPC (control, CON) or LIPC dosed at 15, 25, and 35 g per day (dosages determined from in vitro results) for 9 days on the efficacy of LIPC on selected bacterial strains, pH, and volatile fatty acids. Each period was 14 days with 9 d for acclimation and 5 d withdrawal period. Results: In the in vitro study dosage had no effect ($P{\geq}0.42$) on Clostridium strains, but as the dose increased SBEC concentrations increased (P = 0.001). Concentrations of the E. coli strain varied with dose. In vivo, LIPC's antimicrobial properties, at 15 g, significantly decreased (P = 0.02) SBEC when compared to 25 and 35 g dosages. C. perfringens decreased linearly (P = 0.03) as LIPC dose increased. Butyrate decreased linearly (P = 0.01) as LIPC dose increased. Conclusion: Further studies should be conducted with a longer dosing period to examine the antimicrobial properties of curcumin without adversely affecting cecal characteristics.

Effects of Copper Reduction on Angiogenesis-Related Factors in Recurrent Glioblastoma Cases

  • Jazayeri, Shima;Feli, Alireza;Bitaraf, Mohammad Ali;Dodaran, Masoud Solaymani;Alikhani, Mazdak;Hosseinzadeh-Attar, Mohammad Javad
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.10
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    • pp.4609-4614
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    • 2016
  • Purpose: To evaluate the therapeutic effects of copper reduction on angiogenesis-related factors in patients with glioblastoma multiforme treated by gamma knife radiosurgery. Materials and Methods: In the present block randomized, placebo-controlled trial, fifty eligible patients with a diagnosis of glioblastoma multiforme who were candidates for gamma knife radiosurgery were randomly assigned into two groups to receive daily either 1gr penicillamine and a low copper diet or placebo for three months. The intervention started on the same day as gamma knife radiosurgery. Serum interleukin-6 (IL-6), tumor necrosis $factor-{\alpha}$ ($TNF-{\alpha}$), vascular endothelial growth factor (VEGF) and copper levels were measured at baseline and after the intervention. The serum copper level was used as the final index of compliance with the diet. In order to control probable side effects of intervention, laboratory tests were conducted at the beginning, middle and end of the study. Results: The patients had a mean age and Karnofsky Performance Scale of 43.7 years and 75 respectively. Mean serum copper levels were significantly reduced in intervention group. Mean survival time was 18.5 months in intervention group vs. 14.9 in placebo group. VEGF and IL-6 levels in the intervention group were also significantly reduced compared to the placebo group and $TNF-{\alpha}$ increased less. Conclusions: It seems that reducing the level of copper in the diet and dosing with penicillamine leads to decline of angiogenesis-related factors such as VEGF, IL-6 and $TNF-{\alpha}$. Approaches targeting angiogenesis may improve survival and can be used as a future therapeutic strategy.

Subchronic Oral Toxicity Study of Acanthopanax divaricatus var. albeofructus in Rats

  • Kim, Myoung Jun;Lee, Mi Ju;Lee, Yong-Hoon;Park, Sun Hee;Kim, Duyeol;Park, Cheol Beom;Kang, Jin Seok;Kang, Jong-Koo
    • Toxicological Research
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    • v.33 no.1
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    • pp.15-23
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    • 2017
  • Acanthopanax divaricatus (Siebold & Zucc.) Seem. var. albeofructus (ADA), a traditional medical herb, has been used to treat arthritis and muscular injury, to strengthen muscle and bone, and to get vital energy. However, information regarding its toxicity is limited. ADA was administered by oral gavage to groups of rats at doses of 0 (control), 1,000, 1,500, 2,000, 2,500, and 3,000 mg/kg five times per week for 13 weeks. Mortality, clinical signs, body weights, food consumption, hematology, serum chemistry, urinalysis, organ weights, necropsy, histopathological finding, vaginal cytology, and sperm morphology were compared between control and ADA-treated groups. Salivation was intermittently observed in both sexes receiving 2,500 and 3,000 mg/kg directly after dosing. Absolute liver weights increased in females receiving 2,000, 2,500, and 3,000 mg/kg ADA (P < 0.05, P < 0.01, and P < 0.01, respectively) and so did the relative liver weights (P < 0.001). Salivation and increased liver weight were ADA-related changes but not considered to be adverse effects. Salivation was intermittent and transient, and the liver weight increase was minor and not accompanied by other changes such as hepatic morphological or functional alterations. The no-observed-adverse-effect-level was determined to be at least 3,000 mg/kg in both sexes of rats.

A Study on the Coagulation of Wastewater Containing Fine Silica Particles with the Waste Slurry from Soda Ash Manufacturing Industries (소오다회 제조 공장의 폐슬러리를 이용한 미세 실리카 함유 폐수의 응집에 관한 연구)

  • Jun, Se Jin;Yim, Sung Sam
    • Applied Chemistry for Engineering
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    • v.10 no.7
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    • pp.1073-1078
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    • 1999
  • The objectives of this study are to examine the applicability of waste slurry from soda ash manufacturing industries as a coagulant for the treatment of wastewater containing fine silica particles, and to reduce the cost of wastewater treatment containing silica. Acceptable water quality can be obtained with a little dosing of waste slurry by gelation before the coagulation process so it could be concluded that the waste slurry from soda ash can be used as a coagulant. Based on the results of experiments, the optimum pH of gelation for silica in wastewater was around five and the treatment process with the gelation of silica could reduce the chemical dosage and waste sludge after coagulation. Dewatering and settling characteristics of the floc after coagulation with the waste slurry are better than those of the floc after coagulation with the lime milk only.

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A study on Genotoxicity Test of Hyeong-gae-yeon-gyo-tang extract (형개연교탕(荊芥連翹湯) 추출물의 유전독성(遺傳毒性) 평가)

  • Jee, Seon-Young;Hwang, Sun-Yi;Lee, Jong-Rok;Kim, Sang-Chan
    • The Korea Journal of Herbology
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    • v.22 no.4
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    • pp.287-300
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    • 2007
  • Objectives : The genotoxicity of extract of "Hyeonggaeyeongyotang", a polyherbal formula has been used as a tonic agents in oriental medicine was tested. Methods : Extract of "Hyeonggaeyeongyotang" was tested by In Vitro Chromosome Aberration Test, Bacterial Reverse Mutation Assay and Micronucleus test according to OECD Guidelines and KFDA Guidelines [2005-60]. Results : The obtained results were as follows: 1. Chromosome Aberration Test: No significant changes in the number of aberrant metaphases having structural and number of aberrations were detected in all concentrations of "Hyeonggaeyeongyotang" extracts treated in this study. 2. Bacterial Reverse Mutation Assay: No significant increases in the number of revertant colonies compared to its negative control were detected in all concentrations of "Hyeonggaeyeongyotang" extracts treated in this study against all 5 strains except for $50{\mu}g/ml$ treated group where significantly decreases in colony numbers were detected agains all five strains used in this study as pharmacological effects not genotoxicity. 3. Micronucleus test: No significant changes in the number of micronucleated polychromatic erythrocytes among 2000 polychromatic erythrocytes compared to negative control were detected in all "Hyeonggaeyeongyotang" extracts-dosing groups tested. Conclusions : From above-mentioned results, it is concluded that "Hyeonggaeyeongyotang" extracts have not any genotoxicity against In Vitro Chromosome Aberration Test, Bacterial Reverse Mutation Assay and Micronucleus test.

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