• Toxicological Research
• /
• 제22권2호
• /
• pp.109-116
• /
• 2006

Safety pharmacology studies are conducted to investigated the potential undesirable pharmacodynamic effects of a substance on physiological functions in relation to exposure in the therapeutic range and above. In the International Conference on Harmonisation (ICH), the guideline 'S7A: Safety Pharmacology Studies for Human Pharmaceuticals' has been developed and reached Step 5 of the ICH process in 2001. Now the Korea Food and Drug Administration (KFDA) are going to transfer 'The Guideline for General Pharmacology' into 'The Guideline for Safety Pharmacology'. Safety pharmacology studies should be performed in compliance with Good Laboratory Practice (GLP). Thus, the present paper reviews the Japanese GLP guidelines for pharmaceuticals to help the conduct and inspection of safety pharmacology studies in compliance with GLP. We also reviewed the ICH guidelines 'S7B revised : The Nonclinical Evaluation of the Potential for Delayed Ventricular Repolarization (QT Interval Prolongation) by Human Pharmaceuticals' and 'E14 : The Clinical Evaluation of QT/QTc Interval Prolongation and Proarrhythmic Potential for Non-antiarrhythmic Drugs' to apply our drug approval systems.

• Toxicological Research
• /
• 제16권3호
• /
• pp.229-238
• /
• 2000

The purpose of reproductive toxicity studies is to evaluate all effects resulting from paternal or maternal exposure that interfere with conception, development, birth, and maturation of offspring. In 1966, the US Food and Drug Administration (US FDA) published guidelines for a three-segment study for drug testing to examine adverse effects on fertility and pregnancy. Three segments were proposed: Segment I, Study of Fertility and General Reproductive Performance, to provide information on breeding, fertility, nidation, parturition, neonatal effects and lactation: Segment II, Teratological study, to provide information on embryo toxicity and teratogenicity: and Segment III. perinatal and Postnatal Study, to provide information on late fetal development, labour and delivery, neonatal viability, and growth and lactation. The classic guideline is still used to this day with only monor modification throughout the world. In the present review, the principles and methods of reproductive toxicity studies are discussed with special attention given to scientific issues.

• Biomolecules & Therapeutics
• /
• 제27권4호
• /
• pp.357-362
• /
• 2019

Limonene is a cyclic terpene found in citrus essential oils and inhibits methamphetamine- induced locomotor activity. Drug dependence is a severe neuropsychiatric condition that depends in part on changes in neurotransmission and neuroadaptation, induced by exposure to recreational drugs such as morphine and methamphetamine. In this study, we investigated the effects of limonene on the psychological dependence induced by drug abuse. The development of sensitization, dopamine receptor supersensitivity, and conditioned place preferences in rats was measured following administration of limonene (10 or 20 mg/kg) and methamphetamine (1 mg/kg) for 4 days. Limonene inhibits methamphetamine- induced sensitization to locomotor activity. Expression of dopamine receptor supersensitivity induced by apomorphine, a dopamine receptor agonist, was significantly reduced in limonenepretreated rats. However, there was no significant difference in methamphetamine-induced conditioned place preferences between the limonene and control groups. These results suggest that limonene may ameliorate drug addiction-related behaviors by regulating postsynaptic dopamine receptor supersensitivity.

• 한국임상약학회지
• /
• 제22권2호
• /
• pp.103-112
• /
• 2012

Performance of coronary angiography for exact diagnosis and treatments of cardiovascular disease have been increased recently and it also brings increase of the contrast-induced nephropathy (CIN) referred from increasing use of radiological contrast agents. The variation of estimated glomerular filtration rate (eGFR) is an indicator of CIN, which is known to increase when renal function is decreased. Therefore, this study was to evaluate the affecting factors including concomitant drug on variation of eGFR of patients who underwent coronary angiography according to the conditions of renal function. Medical records of 66 patients were evaluated retrospectively and the patients underwent coronary angiography or angioplasty with nonionic and isotonic contrast media (iodixanol) at Chungnam national university hospital from 1 Jan 2008 to 30 Jul 2010. Patients group was divided into 2 groups; the patients in stages 3-4 chronic kidney disease (CKD) and the patients in stage 2 CKD. Each group was researched about the effect of concomitant drug and clinical characteristics on eGFR variation. The change of eGFR was compared among baseline and 2 or 3 day after coronary angiography. In results, the eGFR variation in group over age 75 was significantly decreased after radiological contrast agents exposure (p $$\leq_-$$ 0.05). The eGFR variation in anemia was significantly decreased after radiological contrast agents exposure in stage 2 CKD (p > 0.05). The eGFR variation in group under $HbA_{1c}$ 6.5% was significantly decreased after radiological contrast agents exposure in stages 3-4 CKD (p $$\leq_-$$ 0.05). The eGFR variation by taking statins, angiotensin converting enzyme inhibitors, calcium channel blockers and nitroglycerin was increased after radiological contrast agents exposure in stage 2 CKD (p $$\leq_-$$ 0.05). The eGFR variation by using of diuretics was significantly decreased after radiological contrast agents exposure in stages 3-4 CKD (p $$\leq_-$$ 0.05). The eGFR variation by taking statins, nitroglylcerin was increased after radiological contrast agents exposure in stages 3-4 CKD(p > 0.05). The eGFR variation in group over contrast dosage 150 ml was significantly decreased after radiological contrast agents exposure in stages 3-4 CKD (p $$\leq_-$$ 0.05). Therefore, when undergoing coronary angiography, contrast dosage should be minimized less than 150 ml, and diuretics should be restricted as possible in stages 3-4 CKD. Patients over age 75 require special attention to prevent CIN, and if patients undergo coronary angiography in stages 3-4 CKD, $HbA_{1c}$ is also requried to maintain below 6.5% to prevent CIN.

• 농약과학회지
• /
• 제15권4호
• /
• pp.357-365
• /
• 2011

농약을 살포하는 농작업자의 농약 노출 측정은 농약의 건강 위해성 평가에서 중요한 부분을 차지하기 때문에 정량적이고 신뢰성 있는 노출량의 측정을 위해서 노출 측정에 사용되는 재료와 기기/기구 및 방법은 포장 노출 시험 전에 미리 검증해야 한다. 본 연구는 유기인계 농약 중에서 살충제 fenthion을 대상으로 농작업자의 노출량 측정을 위한 분석/시험방법의 검증을 수행하였다. LOD는 0.01 ng, LOQ는 0.05 ng로 설정하였고, 표준 검량선의 직선성($R^2$ > 0.999)과 분석재현성(C.V. < 3%)은 매우 우수하였다. 또한 3수준(LOQ, 10LOQ, 100LOQ)으로 수행한 노출 시료(장갑, 양말, 마스크, 패치, 고체흡착제, 유리섬유필터) 중 fenthion의 회수율은 76~113%(C.V. < 3%)이었고, 호흡 노출 실험의 검증 중에서 포집효율은 95~105%이었다. 파과실험 결과 fenthion은 1차 고체흡착제 부분에만 존재하였다. 이와 같은 분석/실험법의 검증을 통하여 실제 포장 실험에서 유래한 노출 시료들을 신뢰성 있게 분석할 수 있는 방법을 확인/검증/확립하였다. 이러한 분석/시험법 검증은 실험실 수준에서 수행할 수 있고, 농약의 종류에 따라서도 크게 다르지 않기 때문에 신체 부위별 평균 체표면적이나, 평균 호흡량과의 조합을 통해서 농약 노출 연구에 적극적으로 활용될 것으로 판단한다.

• 한국산업보건학회지
• /
• 제16권2호
• /
• pp.110-122
• /
• 2006

Objective : This study was conducted to quantify chronic lead exposure from various media(ie. working environment, food, ambient air), and to certify the usefulness of exposure assessment using Monte-Carlo simulation in the fields of occupational health. Methods : Data were obtained from Korean Industrial Health Association, Korea Food and Drug Administration, and the Ministry of Environment. Then lead worker's exposure was estimated indirectly from various media and parameters (ie. volume inhaled, body weight, dietary intake, etc.). Uncertainty was analyzed by Monte Carlo simulation with Crystal Ball software. Exposure doses and hazard indices were simulated with various hypothetical scenarios including weekly working hours and respiratory protective equipment. Results : Without respiratory protective equipment, the total exposure dose per kilogram of body weight of lead workers was estimated as $5.45{\times}10^{-3}mg/kg/day$, and hazard index was estimated as 2.26, and exposure contributions were calculated as follows : working environment(82.42 %); foods(17.57 %); and ambient air(0.01 %). But, if working condition has changed - reduction of working hours and using respiratory protective equipment, the total exposure dose per kilogram of body weight was estimated between $1.34{\times}10^{-3}-1.49{\times}10^{-3}mg/kg/day$, and hazard index was estimated between 0.56 - 0.62. Conclusions : This study suggested that occurrence of hazardous impact(ie. increased blood pressure) through lifetime lead exposure would be expected, and that the Monte-Carlo simulation was useful for the fields of occupational health.

• Toxicological Research
• /
• 제28권2호
• /
• pp.73-79
• /
• 2012

While the ability to develop nanomaterials and incorporate them into products is advancing rapidly worldwide, understanding of the potential health safety effects of nanomaterials has proceeded at a much slower pace. Since 2008, Korea Food and Drug Administration (KFDA) started an investigation to prepare "Strategic Action Plan" to evaluate safety and nano risk management associated with foods, drugs, medical devices and cosmetics using nano-scale materials. Although there are some studies related to potential risk of nanomaterials, physical-chemical characterization of nanomaterials is not clear yet and these do not offer enough information due to their limitations. Their uncertainties make it impossible to determine whether nanomaterials are actually hazardous to human. According to the above mention, we have some problems to conduct the human exposure risk assessment currently. On the other hand, uncertainty about safety may lead to polarized public debate and to businesses unwillingness for further nanotechnology investigation. Therefore, the criteria and methods to assess possible adverse effects of nanomaterials have been vigorously taken into consideration by many international organizations: the World Health Organization, the Organization for Economic and Commercial Development and the European Commission. The object of this study was to develop risk assessment principles for safety management of future nanoproducts and also to identify areas of research to strengthen risk assessment for nanomaterials. The research roadmaps which were proposed in this study will be helpful to fill up the current gaps in knowledge relevant nano risk assessment.

• 생물정신의학
• /
• 제8권1호
• /
• pp.37-46
• /
• 2001

Whenever a clinician manages the patients with depression, he may meet various problems that make it difficult to treat them. Even though he has good skills and knowledge about depression, some barriers will be appear during his practice. In general, the difficulties in treating depression are treatment-resistance, adverse effects of antidepressants, pregnancy in female patients, comorbid medical conditions, poor compliance, drug-drug interactions, and so on, which are related with pharmacological treatments. Here, only the two of them, the treatment-resistant depression and difficult problems concerned with pregnancy, were discussed. Some level of treatment resistance is the norm rather than the exception. As the treatment failure stems from inadequate treatment, it is important that the clinician should prescribe medications with sufficient doseage and adequate duration. And to overcome the treatment resistant depression the polypharmacy is necessary, in that case, the side effects and toxicities should be explored and managed immediately. So the clinician have to learn more about the pharmacokinetic and pharmacodynamic mechanisms of each drugs used in treatment of depression. When the risk of the fetus by the exposure is higher than the risk of untreated maternal psychiatric disorder, psychotropic medications should be used during pregnancy. Women who are maintained on psychotropics and become pregnant, as well as women with the new onset of psychiatric symptoms during pregnancy, should be carefully reassessed. However, data concerning the potential risk of long-term behavioral changes following prenatal exposure to psychotropics is rare, so further longitudinal follow-up studies are needed.

• 대한수의학회지
• /
• 제37권1호
• /
• pp.203-212
• /
• 1997

Antibacterial efficacy and safety of copper sulfate pentahydrate (5% solution) was evaluated in laboratory and field studies for disinfection of some fish bacterial pathogens in cultured fish, flounder(Paralichthys olivaceus), mirror carp(Cyprinus carpio), gold fish(Carrassius auratus) and eel(Anguilla japonica). Dipping of fishes for acute toxicity was performed for a period of 48h, and the TLm value(median tolerance limit) were 4.0ppm in mirror carp and flounder, 4.4ppm in rainbow trout, and 10.0ppm in gold fish. After exposure below than TLm value for 1 month, no side effects and histopathological changes were observed. The test drug were shown high antibacterial activities against most bacterial pathogens by exposure in the laboratory and field trials. However, Aeromonas salmonicida showed a resistance to the dosage. We can prevent outbreaks of bacterial diseases of fish by the dosage of 1ppm for 6hr and the test drug is thought to be used effectively and widely as a disinfectant against most bacterial fish pathogens.

• 농약과학회지
• /
• 제19권1호
• /
• pp.32-40
• /
• 2015

본 연구는 유통 농산물의 잔류 실태를 조사하여 잔류농약에 대한 안전성을 평가하기 위해 수행되었다. 전국 9개 지역에서 수거된 농산물 15개 품목 232건을 식품공전 다종농약다성분 분석법으로 분석하였으며, GC/MSMS로 분석 가능한 농약 196종을 대상으로 하였다. 그 결과 53건의 시료에서 64종의 농약이 검출되었고 이 중 chlorpyrifos와 procymidone이 가장 빈번히 검출되었다. 검출된 64종 중 깻잎에서 검출된 chlorpyrifos와 복숭아에서 검출된 picoxystrobin은 잔류허용기준을 초과하였으며, 나머지는 각각의 잔류허용기준을 초과하지 않았다. 잔류허용기준을 초과한 chlorpyrifos와 picoxystrobin을 포함한 검출 농약에 대해 위해평가를 수행한 결과, 1일 섭취허용량(acceptable daily intake, ADI) 대비 1일 추정섭취량(estimated daily intake, EDI)이 0.001~0.902%로 조사되어 매우 낮은 수준임을 확인할 수 있었다. 이번 연구 결과 유통 농산물에서 잔류농약은 안전하게 관리되고 있음을 확인 할 수 있었고, 향후 식품안전 정책 수립의 기초 자료로 활용할 수 있을 것을 생각된다.