• Title/Summary/Keyword: Toxicity study

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GSTT1 null and MPO -463G>A Polymorphisms and Carboplatin Toxicity in an Indian Population

  • Bag, Arundhati;Pant, Nirdosh Kumar;Jeena, Lalit Mohan;Bag, Niladri;Jyala, Narayan Singh
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.8
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    • pp.4739-4742
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    • 2013
  • Carboplatin, a second generation platinum drug, is widely used to treat different types of cancers. However, myelosuppression remains a major consideration in its use. Genetic polymorphisms of enzymes involved in drug disposition can influence therapeutic outcome. The homozygous null deletion of phase II metabolic gene GSTT1 that abolishes its xenobiotic- detoxifying ability may be associated with carboplatin toxicity. Further, since carboplatin generates oxidative stress, polymorphisms of oxidative stress genes that regulate the cellular level of free radicals may have important roles in generating drug- related adverse effects. We here investigated the null polymorphism of GSTT1, and the -463G>A promoter polymorphism of oxidative stress gene myeloperoxidase (MPO) for carboplatin toxicity in a population of northern India. Cancer patients who were treated with carboplatin, and developed toxicity was considered. The study group comprised of 10 patients who developed therapy- related adverse effects. Peripheral blood was taken from patients for DNA isolation. GSTT1 null genotype was determined by conducting duplex PCR and MPO-463 G>A was determined by PCR followed by RFLP. Hematologic toxicity was experienced by 5 patients, 2 of them had grade 3 and 4 toxicity and 3 others had grade 2 toxicity. They also had gastrointestinal (GI) toxicity. Remaining 5 individuals developed GI toxicity but no hematological toxicity. While GG homozygous of MPO was present in majority of patients having hematologic toxicity (in 4 out of 5 individuals), one A allele (AG genotype) was present in 4 patients who did not have any hematological toxicity. Thus variant A allele of MPO -463G>A may be related to lower hematological toxicity. These preliminary data, however, are required to be confirmed in larger studies along with other relevant polymorphisms.

Single Oral Dose Toxicity Test of Bojungikgi-tang (Buzhongyiqi-tang) and Fermented Bojungikgi-tang (Buzhongyiqi-tang) Extracts in Mice (보중익기탕 및 발효보중익기탕의 단회투여 독성에 대한 연구)

  • Lee, Ji-Hye;Hwang, Yoon-Hwan;Kwak, Dong-Hoon;Kim, Tae-Soo;Ma, Jin-Yeul
    • The Journal of Internal Korean Medicine
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    • v.32 no.4
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    • pp.599-609
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    • 2011
  • Objectives : The aim of this study was to evaluate the single oral dose toxicity and safety of Bojungikgi-tang (Buzhongyiqi-tang) and fermented Bojungikgi-tang (Buzhongyiqi-tang) extracts in male and female ICR mice. Methods : In the single oral dose toxicity study, non-fermented and fermented Bojungikgi-tang (Buzhongyiqi-tang) were administered to male and female ICR mice as an oral dose of 1250, 2500 and 5000 mg/kg. Changes of body weights, general behaviors, adverse effects and mortality were determined throughout the experimental period. Hematological parameters, serum chemistry, organ weights and necropsy findings were evaluated at the end of the experiment. Results : There was no mortality or sign of toxicity in the single oral dose toxicity study. There were also no significant differences in body weights, organ weights, and hematological parameters, serum chemistry values between treatment and control groups. Conclusions : The results obtained in this study suggest that the 50% lethal dose of fermented Bojungikgi-tang (Buzhongyiqi -tang) in both female and male mice can be considered as well over 5,000 mg/kg, so these medicines can be safe in clinics.

Acute and Subacute Oral Toxicity Evaluation of Crude Antifungal Compounds Produced by Lactobacillus plantarum HD1 in Rats

  • Son, Hee-Kyoung;Chang, Hae-Choon;Lee, Jae-Joon
    • Preventive Nutrition and Food Science
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    • v.20 no.3
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    • pp.190-197
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    • 2015
  • The aim of this study was to investigate the acute and subacute oral toxicity of crude antifungal compounds produced by Lactobacillus plantarum HD1 in Sprague-Dawley rats. In the acute toxicity study, the crude antifungal compounds (0.625, 1.25, 2.5, and 5.0 g/kg) did not produce mortality, significant changes in general behavior, or changes in the gross appearance of the organs. In the subacute toxicity study, the crude antifungal compounds were administered orally to rats at doses of 0, 0.5, 1.0, and 2.0 g/kg daily for 28 days. There were no test article-related deaths, abnormal clinical signs, or body weight changes. The study also showed no significant differences between the control and treated groups in hematological and serum biochemical parameters, histopathological examination, or any other findings. These results suggest that acute or subacute oral administration of crude antifungal compounds from L. plantarum HD1 is not toxic in rats.

Single and 13-week Repeated Dose Toxicity Study of DA-3002, An Authentic Recombinant Human Growth Hormone (천연형 인성장호르몬 DA-3002의 단회 및 13주 반복투여독성연구)

  • 김옥진;강경구;안병옥;백남기;이순복;김원배;양중익
    • Biomolecules & Therapeutics
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    • v.2 no.2
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    • pp.161-172
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    • 1994
  • This study was conducted to examine DA-3002, a biosynthetic human growth hormone, for its acute and subacute toxicities in mice and rats. The drug was administered subcutaneously and orally at a dose level of 1.0, 3.0, 8.9, 26.7 or 80.0 lU/kg once for single dose toxicity and given subcutaneously at a dose level of 0.34, 1.7 or 8.4 lU/kg daily for 13 weeks to investigate repeated dose toxicity. In the acute toxicity study, doses up to 80 lU/kg had no adverse effect on the behavior or body weight gain. Pathological examinations revealed no abnormal changes which could be attributed to toxic effect of DA-3002. In the subacute toxicity study, the growth hormone was tolerated well in broth mice and rats. No drug related deaths occurred and all animals appeared to be normal throughout the dosing period. Increases in body weight gain, food utilisation and absolute organ weights were observed in the rats in the high dose group. Mild changes in the blood chemical parameters were also seen in the treated groups. Histopathologically, however, no abnormal changes were observed in any organ. The changes noted during the treatment periods presumably represent exaggerated pharmacological effects of the growth hormone, and no observed adverse effect level (NOAEL) was considered to be more than 8.4 lu/kg/day.

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ACUTE TOXICITY STUDY OF HEPACCINE-B(HEPATITIS B VACCINE)

  • Lee, Yong-Soon;Cho, Jung-Silk;Kim, Sun-Chul
    • Toxicological Research
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    • v.2 no.1
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    • pp.23-30
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    • 1986
  • Acute toxicity study was conducted on a Hepatitis B vaccine (Hepaccine-B-inj.) with mice, guinea pigs, and rabbits, in accordance with the norms suggested by the F.D.A. in U.S.A. Dose ranges were 2 doses/mouse, 5 doses/guinea pig, 10 doses/rabbit. They received the vaccine subcutaneously and intraperitoneally. Thereafter, all animals injected were observed of general signsdaily, and of body weight for two weeks. At the end of the observation period (or at the time of death), all animals received the highest dose group were autopsied and gross observation was made on various organs and tissues. No significant toxicity was noted.

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Single Dose Toxicity Study of Socheongryong-tang in Sprague-Dawley Rats (Sprague-Dawley 랫드를 이용한 소청룡탕의 단회투여독성시험)

  • Lee, Chul-Won;An, Won-Gun
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.25 no.2
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    • pp.242-245
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    • 2011
  • Socheongryong-tang has been used for the treatment of inflammatory allergic diseases such as allergic rhinitis and bronchial asthma in Asian countries. This study was conducted to investigate the safety of Socheongryong-tang in rats. The safety of this tang on acute toxicity was evaluated by single dose toxicity study. Rats were orally administrated in a single dose of 0 and 2000 mg/kg (limited dose) Socheongryong-tang. There were 7 rats in each groups. All animals were sacrificed after 14 days of treatment. After single administration, mortality, clinlcal signs, body weight changes and gross pathological findings were observed for 14 days. Three parameters were tested: organ weight measurement, clinical chemistry, and hematology. In this study with rats, Socheongryong-tang treatment did not show any acute toxicity. No mortality was noted for 14 days of treatment. There were no adverse effects on clinical signs, body weight, organ eight and gross pathological findings at all treatment groups. The clinical chemistry parameters attesting to liver and kidney functions as well as the hematological parameters were within the normal ranges. From single dose toxicity study with rats, it is considered that $LD_{50}$ of Socheongryong-tang is over 2000 mg/kg in oral administration. This finding of the safety on single dose toxicity study of Socheongryong-tang are expected to strengthen the position of Socheongryong-tang as nontoxic medicine.

A Study of Ecotoxicity Test for Byproducts of Ozone in the Ballast Water Treatment System with Ozonation

  • Park, Sung-Jin;Ha, Shin-Young;Kim, In-Soo
    • Journal of Navigation and Port Research
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    • v.35 no.9
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    • pp.741-747
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    • 2011
  • Ecological toxicity testing of the whole-effluent from the ozone ballast water treatment system was conducted as specified in the quality assurance project plans (QAPP). The growth inhibition test with microalgae, acute aquatic toxicity test with the Rotifer reproduction, toxicity test (or population growth) with the Rotifer, survival and growth toxicity test with larval fish and sediment toxicity test with amphipod were carried out to evaluate ecological toxicity on the movile test barge.

The Study on Acute Subacute Toxicity and Anti-cancer Effect of K-herbal-acupuncture (K-약침(藥鍼)의 급성(急性) 아급성(亞急性) 독성실험(毒性實驗) 및 항암효과(항암효과)에 관(關)한 실험적(實驗的) 연구(硏究))

  • Kim, Kwang-Ho;Kwon, Ki-Rok
    • Journal of Pharmacopuncture
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    • v.6 no.1
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    • pp.76-94
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    • 2003
  • Objectives : The purpose of this study was to investigate Acute$\cdot$Subacute Toxicity and Anti-cancer Effect of K-Herbal-acupuncture in mice and rats. Methods : Balb/c mice were injected intraperitoneally with K-herbal-acupuncture for $LD_{50}$ and acute toxicity test. Sprague-Dawley rats were injected intraperitoneally with K-herbal-acupuncture for subacute toxicity test. K-Herbal-acupuncture was injected on abdomen of mice with S-180 cancer cell line. Result : 1. $LD_{50}$ of K-Herbal-acupuncture was limited $4{\times}10^{-3}$ml/kg~$2{\times}10^{-3}$ml/kg by the test. 2. In acute toxicity test, all of mice were down to the moving reflex, but the weight of mice was increased in treatment group, compared with the normal group. (P<0.05) 3. In acute toxicity test of serum biochemical values of mice, glucose was increased in treatment II group, total cholesterol was increased both treatments.(P<0.05) 4. In subacute toxicity test, the clinical signs of toxication was down to the moving reflex, but it is not severe like acute toxicity test, and observed weight loss at the treatments. 5. In subacute toxicity test, liver weight was decreased compared with the normal group. (P<0.05) 6. In subacute toxicity test of complete blood count test (CBC) of rat, HCT was decreased in treatments, compared with the normal group.(P<0.05) 7. In subacute toxicity test of serum biochemical values of rat, uric acid and triglyceride were decreased, and glucose was increased in treatment groups compared with the control group. (P<0.05) 8. Median survival time was increased about $45\%$ in treatment groups compared with the control group.(P<0.05) 9. Natural killer cell activity was increased in B16F10 lung cancer model, but it was not in sarcoma-180 abdomen cancer. 10. In interleukin-2 productivity test, treatment groups didn't show significant change in lung cancer and abdomen cancer, compared with the normal group.(P<0.005) 11. In making an examination of metastatic cancer with the naked eye, melanoma metastasized in the Lung of C57BL/6 mice. The treated group showed more Melanoma than the control in the numbers and volume. Conclusion : According to the result, K-herbal-acupuncture need further study to know the function and effect in cancer.

Toxicity of Novel Solubilizer of Paclitaxel, Aceporol 330, in Beagle Dogs

  • Kim, Yeo-Woon;Chung, Kyu-Nung;Kang, Hoon-Suk;Sheen, Yhun-Yhong
    • Biomolecules & Therapeutics
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    • v.16 no.1
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    • pp.61-68
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    • 2008
  • In order to develop an improved paclitaxel formulation vehicle, a micelle forming solubilizer, Aceporol 330 was synthesized. It was previously reported that Aceporol 330 provided the linearity of paclitaxel plasma pharmacokinetics. In this study, the single dose toxicity test and 2-week repeated dose toxicity test of Aceporol 330 was performed in beagle dogs after intravenous administration. Single dose and 2-week repeated dose toxicity test of Aceporol 330 showed fever/generalized erythema, severe vomiting, and diarrhea in beagle dogs. However, those toxicities were less severe than those of Cremophor EL. Blood chemistry analysis of 2-week repeatedly treated beagle dogs with Aceporol 330 showed significant elevation of total cholesterol (TCHO) and triglyceride (TG) compared to that of control group. Cremophor EL also significantly increased total cholesterol (TCHO) and triglyceride (TG) as much as Aceporol 330. Results from this study indicated that Aceporol 330 was less toxic than Cremophor EL. Based on the pharmacokinetic advantages and the low toxicity of Aceporol 330 in single dose and 2-week repeated dose toxicity test, Aceporol 330 has a potential for use as a safer solubilizer for paclitaxel than Cremophor EL.

A Research for Assessment Fire Toxic Gas of Construction Material Using FT-IR and FED (FT-IR과 FED를 이용한 건축 재료의 연소독성평가에 관한 연구)

  • Kim, Sung-Soo;Cho, Nam-Wook;Rie, Dong-Ho
    • Fire Science and Engineering
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    • v.25 no.6
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    • pp.27-31
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    • 2011
  • In this study, combustion toxicity evaluation for building interior materials and study for toxicity as using FT-IR analysis. this experiment for the calculation of toxicity index, it using a cone calorimeter model in KS F ISO/TR 9122-4 as a fire model. It is following ISO 19702 procedure for assessing fire toxic gas using FT-IR. This experiment used calculation method for toxicity index (FED) among the international standards. $LC_{50}$ is a concentration that it can cause death to 50 % of experimental animal in 30 minutes - exposure gas test. comparison with the three kinds of toxicity fire gas of construction materials using toxicity index.