• Title/Summary/Keyword: Acute toxicity test

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Health Damages and Lessons of the Use of Humidifier Disinfectants in Korea (가습기살균제 피해사건과 교훈)

  • Choi, Ye-Yong;Lim, Heung-Kyu;Lim, Sin-Ye;Paek, Do-Myung
    • Journal of Environmental Health Sciences
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    • v.38 no.2
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    • pp.166-174
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    • 2012
  • Introduction: After 17 years since the first production of humidifier disinfectants in Korea, Korea Centers for Disease Control and Prevention (KCDC) announced that the odds ratio of lung injury related with humidifier disinfectant usage was 47.3 (95% confidence interval 6.0-369.7) according to a case-control study with 18 adult cases, including 8 pregnant women at a university hospital in Seoul. Results: From September 2011 to April 2012, one-hundred and seventy four victim cases have been reported to an environmental non-governmental group (NGO). We summarized timetable of humidifier disinfectants accidents, analyzed health outcomes (death, lung or lung and heart transplantation, pulmonary disease) of reported victims, and classified some information for humidifier disinfectants with health outcomes, and government action for this accident. Among the victims, number of death cases are 52 (30.0%), including 26 babies less than 3 years old. Sixty-nine victims come from twenty-seven family with 2 to 4 members per family. About twenty types of humidifier disinfectant products and about 600,000 product items a year have been sold. Fifty-two death cases used 7 different types of disinfectant products, including imported goods and some private brands of well-known supermarkets. KCDC confirmed inhalation toxicity of 6 products through an animal experimental test, and based on this observation recalled disinfectants containing PHMG (polyhexamethylene guanidine) and PGH (Oligo(2-(2-ethoxy)ethoxyethyl guanidinium chloride). Discussions: The use of these biocides involved highly fatal consequences among biologically vulnerable victims, such as pregnant women, several family member victims after semi-acute exposure. This is the first biocide disaster in Korea with non-specific targets, and unknown scale of victims, warranting concerns on use of biocides in the living environment. Conclusions: Special administrative agency for chemical safety and compensation act for environmental health victims are needed to prevent similar problems.

Pharmacodynamic Modeling of Vincristine in Lymphoma Patients (림프종 환자에서 회귀모형을 이용한 vincristine의 약물 용량 예측 인자 및 부작용 모델 연구)

  • Seo, Jeong-Won;Kim, Dong-Hyun;Yun, Jin-Sang;Kim, Seon-Hwa;Choi, Bo-Yoon;Oh, Jung-Mi;Kwon, Kwang-Il
    • Korean Journal of Clinical Pharmacy
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    • v.21 no.2
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    • pp.145-155
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    • 2011
  • The objective of this study was to determine whether any pretreatment parameters were associated with pharmacological effect or toxicity parameters after vincristine administration and to describe a mathematical model, which explains the interpatient pharmacodynamic variability. The relationship between patient characteristics and vincristine dose and hematological toxicity were evaluated. 68 pediatric and adolescence patients and 107 adults with acute lymphoblastic leukemia were treated with vincristine $1.5mg/m^2/day$ IV and other anticancer drugs as scheduled. Complete blood counts and other blood test results were obtained. The input variables were age, gender, weight, lean body weight (LBW), height, body surface area, vincristine dose and total vincristine dose. The outcome measures were nadir values (white blood cells, absolute neutrophil counts, hemoglobin, and platelets); the absolute decrease, relative decrease, and survival fraction of blood cells. Polynomial regression analysis was carried out to determine the other significant covariates. The variability of $WBC_{nadir}$ was modeled with good precision and accuracy with a two-covariate model. This model should be validated and improved on with further clinical data. We believe that such pharmacodynamic modeling should be explored further to determine its performance and clinical relevance compared with modeling using pharmacokinetic parameter.

Ecotoxicological effects of Alum and Ferric chloride on the population of Eisenia fetida (Annelida : Oligochaeta) (Alum과 Ferric chloride가 줄지렁이 개체군에 미치는 생태독성학적 영향)

  • Park, Kwang-Il;Bae, Yoon-Hwan
    • Journal of the Korea Organic Resources Recycling Association
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    • v.20 no.1
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    • pp.50-60
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    • 2012
  • This study was carried out to evaluate the ecotoxicological effects of Alum and Ferric chloride on the population of Eisenia fetida in vermicomposting of sewage sludge. Using contact filter toxicity test, it was shown that LC50 of Alum and Ferric chloride on adult Eisenia fetida were 457.4 mg $kg^{-1}$ and 1,665.2 mg $kg^{-1}$, respectively,which meant Ferric chloride had much higher acute toxicity on earthworm than Alum. Alum didn't affect on cocoon production, hatchability and number of hatched larvae of Eisenia fetida. Ferric chloride didn't have any efects on number of hatched larvae per cocoon, but reduced cocoon production and hatchability. Larval density of next generation was reduced by the food containing Alum and Ferric chloride. Above results indicated that the Alum and Ferric chloride could be one of the hazardous materials that made extinction of earthworm population when the sewage sludge treated with Alum and Ferric chloride was supplied to the earthworms.

OECD High Production Volume Chemicals Program: Ecological Risk Assessment of Copper Cyanide (대량생산화학물질 초기위해성평가: 시안화구리의 초기 생태위해성평가)

  • Baek, Yong-Wook;Kim, Eun-Ju;Yoo, Sun-Kyoung;Ro, Hee-Young;Kim, Hyun-Mi;Eom, Ig-Chun;Kim, Pil-Je
    • Korean Journal of Ecology and Environment
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    • v.44 no.3
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    • pp.272-279
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    • 2011
  • Copper cyanide is a chemical produced in large quantities with 2,500 tonnes being produced in 2006. It is mainly used for electroplating copper, particularly alkali-Cu plate and brass plating. The purpose of this study is to reassess the physicochemical properties and environmental fate of copper cyanide based on reliable data and and to conduct an ecotoxicity test according to the OECD test guidelines as an initial environmental risk assessment (need to state where this was done). Metal containing inorganic substances are not subject to degradation, biodegradation or hydrolysis. Aquatic toxicity tests of copper cyanide were conducted according to OECD test guideline 201, 202 and 203 for green algae, daphnia, and fish, respectively. The following acute toxicity test results were obtained for aquatic species: 0.089 mg $L^{-1}$ (Algae, 72 Hr-$EC_{50}$); 0.21 mg $L^{-1}$ (flea, 48 Hr-$LC_{50}$); 0.62 mg $L^{-1}$ (Fish, 96 Hr-$ErC_{50}$). The chemical possesses properties indicating a hazard for the aquatic environment (acute toxicity in fish, daphnia and algae below 1.0 mg $L^{-1}$). As a result of this study, copper cyanide has become a candidate for detailed risk assessment. Countries that produce this chemical in significant quantities are recommended to perform specific assessments.

Isolation of Polysaccharides Modulating Intestinal Immune System and Single Oral Dose Toxicity Test in Astragalus membranaceus Abovegroud Parts (황기 지상부로부터 장관면역 활성 다당체의 분리 및 단회 경구 투여 독성시험)

  • Choi, Ri Na;Park, Yeong Chul;Lee, Ji Sun;Kim, Jung Woo;Kim, Jong Bong;Cheoi, Yu Soon;Kim, Kwang Ki;Lee, Jae Geun;Yu, Chang Yeon;Kim, Seung Hyn;Chung, Ill Min;Kim, Jae Kwang;Lim, Jung Dae
    • Korean Journal of Medicinal Crop Science
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    • v.22 no.4
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    • pp.276-288
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    • 2014
  • The six polysaccharide fractions were prepared by chromatographic procedure from the hot water extracts of the aboveground parts of Astragalus membranaceus. These six polysaccharides from aboveground parts of Astragalus membranaceus Bunge were tested for gut-mucosal immune activity and acute toxicity. In a view of molecular weight, the six fractions were estimated to be 75000, 88000, 129000 and 345000 Da, respectively. Component sugar analysis indicated that these fractions were mainly consisted of galactose (46.3 ~ 11.8%) and arabinose (35.4 ~ 9.9%) in addition to glucose, rhamnose, fucose, arabinose, xylose, mannose, glucuronic acid and galacturonic acid. Among the six major purified polysaccharides, AMA-1-b-PS2 showed highest bone merrow cell proliferation and lymphocyte of Peyer's patch stimulating activity. It may be concluded that intestinal immune system modulating activity of aboveground parts from Astragalus membranaceus Bunge is caused by polysaccharides having a polygalacturonan moiety with neutral sugars such as arabinose and galactose. In single oral dose toxicity study, no differences were observed between control and treated groups in clinical signs. The results indicated that lethal dose 50 ($LD_{50}$) of water extracts from Astragalus membranaceus-aboveground parts was found to be higher than 5000 mg/kg/day in this experiment. From the above results, we may suggest that Astragalus membranaceus-aboveground parts might have useful as a safe material for functional food and pharmaceutics.

Rat Single Oral Dose Toxicity Test of Armeniacae Semen (Including Endocarp) (행인(杏仁)의 랫트 단회 경구 투여 독성시험)

  • Kim, Se-Ran;Lee, Jin-Won;Lim, So-Yeon;Jung, Yu-Sun;Choi, Hae-Yun;Kim, Jong-Dae
    • The Journal of Internal Korean Medicine
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    • v.33 no.2
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    • pp.145-159
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    • 2012
  • Objectives : The object of this study was to obtain acute toxicity information (single oral dose toxicity) of Armeniacae Semen (AS), a medicinal herb used for treating constipation and various respiratory diseases, in rats. Methods : In order to observe the $LD_{50}$ (50% lethal dose), approximate lethal dosage (ALD) and target organs, AS aqueous extracts were orally administered once to female and male Sprague Dawley rats at dose levels of 2,000, 1,000, 500 and 0 (control) mg/kg (body weight). The mortality, changes in the body weight, clinical signs and gross observation were monitored for 14 days after single oral treatment of AS extracts, and the organ weights and histopathological findings of principle organs were observed after sacrifice. Results : After single oral treatment of AS 2,000 and 1,000 mg/kg, all (5/5; 100%) female and male rats died within 30 minutes after treatment, while no mortalities were observed in the female and male rats treated with 500 mg/kg of AS extract. Therefore, $LD_{50}$ in female and male rats was calculated as 741.95 mg/kg. Seizure, loss of locomotion, salivation, increases of respiration and heart-beat were observed after AS extract treatment, which were observed in all rats including the lowest dosage group, 500 mg/kg in the present study. In addition, lung congestion was visible in all mortal rats with AS 2,000 and 1,000 mg/kg, respectively. Conclusions : The results obtained in this study suggest that AS extract ranges in Class III, because the $LD_{50}$ and ALD in both female and male rats were calculated as 741.95 mg/kg and 500~1,000 mg/kg, respectively. However, AS extract should be carefully treated at clinical applications, because salivation, increase of respiration and heart-beat were also observed in the lowest dosage group, 500 mg/kg in the present study.

Stability and Safety of Bee Venom with and without Additives (첨가물에 의한 봉독의 안정화 및 안전성)

  • Bae, Young Hyeon;Lee, Chong Hwan;Kim, Hae Sol;Kim, Ho Sun;Suh, Chang Yong;Kim, No Hyeon;Lee, Jin Ho;Ha, In Hyuk;Kim, Me Riong;Chung, Hwa Jin;Lee, In Hee;Kim, Min Jeong;Kim, Eun Jee;Lee, Jae Woong
    • Journal of Acupuncture Research
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    • v.32 no.3
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    • pp.127-133
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    • 2015
  • Objectives : Previous studies have shown that the amount of melittin, the main active ingredient in bee venom pharmacopuncture, tends to decrease substantially with time during pharmacopuncture manufacture. This study aimed to assess whether the stability of bee venom pharmacopuncture improved with pharmacopuncture additives. Methods : Components were measured using high performance liquid chromatography. Acute toxicity and antigenicity tests by subcutaneous and venous routes were conducted at Korea Pharmaceutical Test & Research Institute and mortality, adverse reactions, and body weight changes were assessed. Results : Stability tests using additives revealed that bee venom without additives was most stable. Bee venom pharmacopuncture without additives was further tested for toxicity in subcutaneous and venous administration in mice and no changes pertaining to toxicity were found over the testing period. Conclusions : Bee venom pharmacopuncture without additives was found to be most stable, and further, it did not show toxicity or antigenicity in subcutaneous and venous administration in mice.

Single Oral Dose Toxicity Study of Aqueous Extracts of Binso-san in ICR Mice

  • Park, Kyung;Kim, Dae-Jun;Byun, Joon-Seok
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.24 no.1
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    • pp.134-142
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    • 2010
  • Although BinSo-San(BSS), a mixed herbal formula consisted of 11 types of medicinal herbs and have been used as anti-inflammatory agent, In the present study, the acute toxicity (single oral dose toxicity) of lyophilized BSS aqueous extracts was monitored in male and female mice after oral administration according to Korea Food and Drug Administration (KFDA) Guidelines (2005-60, 2005). In order to observe the 50% lethal dose ($LD_{50}$), approximate lethal dosage (ALD), maximum tolerance dosage (MTD) and target organs, test articles were once orally administered to female and male ICR mice at dose levels of 2000, 1000, 500, 250 and 0 (control) mg/kg (body wt.) according to the recommendation of KFDA Guidelines (2005-60, 2005). The mortality and changes on body weight, clinical signs and gross observation were monitored during 14 days after dosing according to KFDA Guidelines (2005-60, 2005) with organ weight and histopathology of 12 types of principle organs. We could not find any mortality, clinical signs and changes in the body weights except for dose-independent increases of body weight and gains restricted in 1000 mg/kg of BSS extracts-dosing female group. Hypertrophic changes of lymphoid organs.thymus, spleen and popliteal lymph nodes were detectedat postmortem observation with BSS extracts dose-dependent increases of lymphoid organ weights, and hyperplasia of lymphoid cells in these all three lymphoid organs at histopathological observations. These changes are considered as results of pharmacological effects of BSS extracts or their components, immunomodulating effects, not toxicological signs. In addition, some sporadic accidental findings such as congestion spots, cyst formation in kidney, atrophy of thymus and spleen with depletion of lymphoid cells, and edematous changes of uterus with desquamation of uterus mucosa as estrus cycles were detected throughout the whole experimental groups including both male and female vehicle controls. The significant (p<0.01) increases of absolute weights of kidney and pancreas detected in BSS extracts 1000 mg/kg-treated female group are considered as secondary changes from increases of body weights. The results obtained in this study suggest that the BSS extract is non-toxic in mice and is therefore likely to be safe for clinical use. The LD50 and ALD of BSS aqueous extracts in both female and male mice were considered as over 2000 mg/kg because no mortalities were detected upto 2000 mg/kg that was the highest dose recommended by KFDA and OECD. In addition, the MTD of BSS extracts was also considered as over 2000 mg/kg because no BSS extracts-treatment related toxicological signs were detected at histopathological observation except for BSS or their component-related pharmacological effects, the immunomodulating effects detected in the present study.

Toxic Effect of Zinc Undecylenate on the Embryogenesis of Sea Urchins Hemicentrotus pulcherrimus and Mesocentrotus nudus (Zinc Undecylenate가 말똥성게(Hemicentrotus pulcherrimus)와 둥근성게(Mesocentrotus nudus)의 배아발생에 미치는 독성 영향)

  • Choi, Hoon;Park, Yun-Ho;Lee, Ju-Wook;Lee, Seung-Min;Choi, Youn-Seok;Hwang, Un-Ki
    • Journal of Marine Life Science
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    • v.5 no.2
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    • pp.43-50
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    • 2020
  • The aim of this study is toxicity assessment using two types of sea urchins (H. pulcherrimus, M. nudus) that can representative primary consumers in potential coastal environments pollutants, Zinc undecylenate (ZU), which is used for various purposes, such as pharmaceutical agents and anti-bacterial and anti-fungi. The Fertilization rate and normal embryogenesis rate of H. pulcherrimus and M. nudus were concentration-dependent decreased. Besides, EC50 of fertilization rate with H. pulcherrimus and M. nudus were 11.27 mgl-1 and 1.48 mgl-1, and EC50 of normal embryogenesis were 0.94 mgl-1 and 3.78 mgl-1. NOEC of normal embryogenesis were 0.20 and 0.78 mgl-1, respectively. In addition, to find the safety criteria of the ZU on the marine environment. PNEC value was 0.0094 mgl-1, calculated using the toxicity values of two species of sea urchin derived from this study and the acute toxicity results of the coastal area through literature research. The above results will be used as basic data for establishing environmental protection strategies for marine environmental pollutants.

Marine Ecotoxicological Evaluation on HNS Spill Accident : Nitric Acid Spill Case Study (HNS 유출사고가 해양생물에 미치는 생물독성 영향평가 : HNO3 유출사고 대상)

  • Kim, Tae-Won;Kim, Young Ryun;Jo, So Eun;Son, Min Ho;Lee, Moonjin;Oh, Sangwoo
    • Journal of the Korean Society of Marine Environment & Safety
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    • v.21 no.6
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    • pp.655-661
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    • 2015
  • This study intends to evaluate the effect of nitric acid($HNO_3$) spill accidents on the marine ecosystem, while $HNO_3$ is known as one of the typical HNS. For this purpose, we performed (1) the growth inhibition test by using phytoplankton(Skeletonema costatum), (2) acute and chronic toxicity test by using invertebrate(Brachionus plicatilis and Monocorphium acherusicum), (3) fish(Cyprinodon variegatus) and (4) bacteria(Vibrio fischeri). In these tests, we observed the (1) pH changes induced by the nitric acid spill and (2) changes in nitrate($NO_3$) concentration disassociated from nitric acid after the accident, respectively. The toxicity test result on pH changes induced by $HNO_3$ shows that the no observed effect concentration(NOEC), lowest observed effect concentration(LOEC) and 50 % effect concentration($72h-EC_{50}$) values of M. acherusicum are pH 7 (0.3 mM), pH 5(1.1 mM) and pH 5.2(1.4 mM), respectively, indicating that M. acherusicum is the most sensitive species. The chronic toxicity test (population growth rate test) on $NO_3{^-}$ of B. plicatilis show that the NOEC, LOEC and $96h-EC_{50}$ are 5.9 mM, 11.8 mM and 32.6 mM, respectively, indicating that B. plicatilis is the most sensitive species. In conclusion, toxic effecst on the marine organism caused by the nitric acid spill accident is determined to be so slightly except for the most adjacent area of the ship in pH scale and such concentration of nitrate, to the extent of directly influencing the survival and reproduction of the marine organism, is determined practically not to be applicable in the typical accidents in the sea.