• Geomechanics and Engineering
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• v.15 no.6
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• pp.1193-1205
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• 2018

A footing located on slopes possess relatively lower bearing capacity as compared to the footing located on the level ground. The bearing capacity further reduces under seismic loading. The adverse effect of slope inclination and seismic loading on bearing capacity can be minimized by proving sufficient setback distance. Though few earlier studies considered setback distance in their analysis, the range of considered setback distance was very narrow. No study has explored the critical setback distance. An attempt has been made in the present study to comprehensively investigate the effect of setback distance on footing under seismic loading conditions. The pseudo-static method has been incorporated to study the influence of seismic loading. The rate of decrease in seismic bearing capacity with slope inclination become more evident with the increase in embedment depth of footing and angle of shearing resistance of soil. The increase in bearing capacity with setback distance relative to level ground reduces with slope inclination, soil density, embedment depth of footing and seismic acceleration. The critical value of setback distance is found to increase with slope inclination, embedment depth of footing and density of soil. The critical setback distance in seismic case is found to be more than those observed in the static case. The failure mechanisms of footing under seismic loading is presented in detail. The statistical analysis was also performed to develop three equations to predict the critical setback distance, seismic bearing capacity factor ($N_{{\gamma}qs}$) and change in seismic bearing capacity (BCR) with slope geometry, footing depth and seismic loading.

• Toxicological Research
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• v.17
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• pp.41-45
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• 2001

The methods used for risk assessment from exposure to chemicals are well established. in most cases where toxicity other than carcinogenesis is being considered, the standard method relies on establishing the No Observed Adverse Effect Level (NOAEL) in the most sensitive animal toxicity study and using an appropriate safety factor (SF) to determine the exposure which would be associated with an acceptable risk. For carcinogens a different approach is used because it has been argued there is no threshold of effect. Thus mathematical equations are used to extrapolate from the high doses used in ani-mal experiments. These methods have been strongly criticised in recent years on several grounds. The most cogent criticisms are a) the equations are not based on a thorough understanding of the mechanisms of carcinogenesis and b) the outcome of a risk assessment based on such models varies more as a consequence of changes to the assumptions and equation used than it does from the data derived from carcinogenicity experiments. Other criticisms include the absence of any measure of the variance on the risk assessment and the selection of default values that are very conservative. Recent advances in the application of risk assessment emphasise that measures of both the exposure and the hazard should be considered as a distribution of values. The outcome of such a risk assessment provides an estimate of the distribution of the risks.

• Journal of Environmental Impact Assessment
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• v.17 no.2
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• pp.143-151
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• 2008

As the NOAFL of copper based on liver toxicity in the human body is set and the TDI of copper is lower, it is necessary to strengthen the drinking water standard of copper according to toxic effects and the TDI of copper in humans. It is difficult to calculate the accurate drinking water standard because of the part of uncertainty for chronic effects of acute human with Wilson's disease and baby in the current studies. In order to improve the drinking water standard of copper considering of liver toxicity, it is desired to set the drinking water standard with concerning of the revising tendency in the foreign countries such as US, EC and WHO.

• 월간산업보건
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• s.276
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• pp.27-31
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• 2011

Perfluorobutyl ethylene(PFBE)은 유기용제 혼합물에 주로 사용되는 산업화학물질로 동물에게 경구, 피부, 눈 그리고 흡입 노출되는 경우 급성 독성이 매우 낮다. Perfluorobutyl ethylene을 흰쥐에게 하루 6시간, 일주일에 5일씩 2주간을 0, 500 ppm, 5,000 ppm, 50,000 ppm을 흡입 노출시킨 연구에서 최대무작용량(no-observed-adverse effect level, NOAEL)으로 500 ppm이 결정되었으며 5,000 pm에서는 단핵 백혈구가 약간 증가하였다. 50,000 ppm에서도 병리학적 변화는 없었다. 그 후의 흡입연구는 하루 6시간, 28일간 연속적으로 흰쥐 암수에게 400 ppm, 2,000 pm, 10,000 ppm의 농도로 perfluorobutyl ethylene 증기를 노출시켰다. 최종 노출 후 흰쥐를 희생시켜 관찰한 결과, 체내 기관 무게변화를 포함한 어떠한 변화도 관찰되지 않았다. 그러나 10,000 ppm에 노출된 수컷 흰쥐 5마리 중 4마리는 작은 다중간세포질 액포가 발견되었다. Perfluorobutyl ethylene 증기 10,000 ppm에 노출된 수컷 흰쥐는 부분적으로 평균 혈액응고 촉진 시간이 감소하였다. 이 연구에서는 최대무작용량을 2,000 ppm으로 결정하였다. Perfluorobutyl ethylene의 TLV-TWA 100 ppm은 노출 후 악영향을 최소화하는데 충분한 농도이며 "피부흡수(Skin)", "감작제(SEN)" 그리고 발암성에 대한 경고주석을 설정하기에는 유용한 연구가 충분하지 않다.

• Biomolecules & Therapeutics
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• v.6 no.2
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• pp.151-158
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• 1998

Aspalatone, a new antithrombotic agent, was administered orally to pregnant Sprague-Dawley rats during the organogenetic period at dose levels of 0, 20, 100 and 500 mg/kg/day. All dams were subjected to caesarean section on day 20 of pregnancy. Effects of test substance on dams and embryonic development of F1 fetuses were examined There were treatment-related decreases in body weight and food consumption in the 500 mg/kg group. There was a increase in the spleen weight in the 100 and 500 mg/kg groups. Develo-pmental toxicity was evident as decreased fetal body weights and increased fetal malformations in the 500 mg/ kg group. External and skeletal malformations of fetuses occurred at an incidence of 1 and 8.2%, respectively. In addition, there was a delay in ossification of sternebrae and sacrocaudal vertebrae in the 500 mg/kg group. The results show that the no observed adverse effect dose level (NOAEL) for maternal toxicity was 20 mg/kg/ day and for developmental toxicity was 100 mg/kg/day.

• Journal of Applied Biological Chemistry
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• v.65 no.1
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• pp.43-48
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• 2022

Medicinal herb demonstrated in many pharmacological effects and recognized to be safe has been used for a long time. However, side effects including safety of medicinal herb have not been identified yet. The aim of the study was to estimate safety evaluation of Magnoliae Flos used for the treatment of pain, rhinitis, and pneumonia in Korea, China and Japan through four-week dose range finding toxicity test in male and female Sprague-Dawley rats. Magnoliae Flos was orally administered to male and female SD rats once a day for 28 days at 1,500 and 3,000 mg/kg. The safety evaluation was determined to examine clinical signs, mortality, body weight, food intake, hematology, serum biochemistry and relative organ weights and there were no significant changes related toxicity. Consequently, these findings indicates that Magnoliae Flos did not show any side effects including toxicity in dose range finding toxicity test and the no observed adverse effect level for Magnoliae Flos was estimated as more than 3,000 mg/kg.

• Toxicological Research
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• v.35 no.2
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• pp.119-129
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• 2019

As the use of cosmetics has greatly increased in a daily life, safety issues with cosmetic ingredients have drawn an attention. Drometrizole [2-(2'-hydroxy-5'-methylphenyl)benzotriazole] is categorized as a sunscreen ingredient and is used in cosmetics and non-cosmetics as a UV light absorber. No significant toxicity has been observed in acute oral, inhalation, or dermal toxicity studies. In a 13-week oral toxicity study in beagle dogs, No observed adverse effect level (NOAEL) was determined as 31.75 mg/kg bw/day in males and 34.6 mg/kg bw/day in females, based on increased serum alanine aminotransferase activity. Although drometrizole was negative for skin sensitization in two Magnusson-Kligman maximization tests in guinea pigs, there were two case reports of consumers presenting with allergic contact dermatitis. Drometrizole showed no teratogenicity in reproductive and developmental toxicity studies in which rats and mice were treated for 6 to 15 days of the gestation period. Ames tests showed that drometrizole was not mutagenic. A long-term carcinogenicity study using mice and rats showed no significant carcinogenic effect. A nail product containing 0.03% drometrizole was nonirritating, non-sensitizing and non-photosensitizing in a test with 147 human subjects. For risk assessment, the NOAEL chosen was 31.75 mg/kg bw/day in a 13-week oral toxicity study. Systemic exposure dosages were 0.27228 mg/kg bw/day and 1.90598 mg/kg bw/day for 1% and 7% drometrizole in cosmetics, respectively. Risk characterization studies demonstrated that when cosmetic products contain 1.0% of drometrizole, the margin of safety was greater than 100. Based on the risk assessment data, the MFDS revised the regulatory concentration of drometrizole from 7% to 1% in 2015. Under current regulation, drometrizole is considered to be safe for use in cosmetics. If new toxicological data are obtained in the future, the risk assessment should be carried out to update the appropriate guidelines.

• Toxicological Research
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• v.18 no.1
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• pp.31-41
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• 2002

The present study was conducted to investigate the potential subacute toxicity of plant sterol esters by a 4-week repeated oral dose in Sprague-Dawley rats. The test article was administered once daily by gavage to rats at dose levels of 0, 1000, 3000, and 9000 mg/kg/day for 4 weeks. During the test period, clinical sign, mortality, body weights, food and water consumption, ophthalmoscopy, urinalysis, hematology, serum biochemistry, gross finding, organ weight, and histopathology were evaluated. A reduction in the body weight was observed in females of the 9000 mg/kg group on day 27 after the initiation of treatment, but not in males of the group. There were no treatment-related effects on mortality, clinical sign, food and water consumption, ophthalmoscopy, urinarlysis, hematology, serum biochemistry, necropsy findings, organ weights, and histopathology in any treatment group. Based on these results, it was concluded that the 4-week repeated oral dose of plant sterol esters resulted in suppressed body weight in female rats at a dose level of 9000 mg/kg/day. In the condition of this study, target organ was not observed and the no-observed-adverse-effect level (NOAEL) was considered to be 9000 mg/kg/day for males and 5000 mg/kg/day for females.

• Toxicological Research
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• v.20 no.2
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• pp.143-151
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• 2004

This study was to investigate single and repeated-dose toxicities of CJ-11555, an anticirrhotic agent, in Sprague-Dawley (SO) rats. In single-dose oral toxicity study, the test article were administered once by gavage to males and females at dose levels of 0 and 2,000 mg/kg. No dead animals and abnormal necropsy findings were found in control and CJ-11555 treated group. Therefore, the approximate lethal dose of CJ-11555 was considered to be higher than 2,000 mg/kg in rats. In the 4-week repeated oral toxicity study, the test article was administered once daily by gavage to male and female rats at dose levels of 0, 10, 50 and 200 mg/kg/day for 4-weeks. In clinical signs, yellow-colored urine and yellow hair coat were observed in the 50 and 200 mg/kg male and female groups. In hematology, erythrocyte count and hemoglobin were significantly decreased in the 200mg/kg male and female groups. In serum biochemistry, total cholesterol was significantly increased and aspartate aminotransferase (AST) was significantly decreased in the 50 or 200 mg/kg male and female groups. In histopathological examinations, centrilobular hepatocellular hypertrophy in the liver, congestion and pigmentation in the spleen, hyaline droplets in the kidney were observed in the 50 and 200 mg/kg male and female groups. In toxicokinetic study, CJ-11555 was dose-dependent in systemic exposure and showed better absorption in female with minimum accumulation after multidosing. Based on these results, it was concluded that the 4-week repeated oral dose of CJ-11555 resulted in the suppression of AST activity and centrilobular hepatocellular hypertrophy in both sexes at a dose level of 50 or 200 mg/kg/day. The target organ was estimated to be liver, spleen and male's kidney. The no-observed-adverse-effect level (NOAEL) for CJ-11555 in rats following gavage for at least 4-week is 10 mg/kg/day.

• Biomolecules & Therapeutics
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• v.6 no.2
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• pp.182-190
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• 1998

DA-3585 is a recombinant human erythropoietin produced by Dong-A pharmaceutical Co. Ltd. using recombinant DNA technique. Recently, recombinant human erythropoietin (rHu-EPO) has been used to treat various types of anemia. In this study, we examined acute and subacute toxicity of DA-3585 in rats. DA-3585 was intravenously administered to rats at dose levels of 0, 6,250, 12,500 and 25,000 lU/kg for single dose toxicity study and at dose levels of 0,100,500 and 2,500IU/kg daily for 4 week-repeated dose toxicity study. In the single dose toxicity study, there were no death, clinical signs and changes in body weight gain related to the treatment. Necropsy revealed no evidence of toxicity related to DA-3585, In the repeated dose toxicity study, all the rats survived throughout the study. There were no treatment-related changes in clinical signs, food and water intake, and body weight. Hematological examination showed increases in the number of erythrocytes, hemoglobin concentration, hematocrit value and mean corpuscular volume, and decrease in the number of platelet in 500 and 2,500 lU/kg dosed groups. Extramedullary hematopoiesis in the spleen and erythroid hyperplasia in the bone marrow were noted as treatment-related histological changes. Toxicologically significant changes were not observed in blood biochemistry, urinalysis, organ weights and in any other examinations. The treatment-related changes observed in this study were hematological or histological changes associated with pharmacological effects of DA-3585. On the basis of the results of this study, LD5n value of DA-3585 was above 25,000 lU/kg and the no-observed-adverse-effect-level was estimated to be 100 lU/kg.