• Toxicological Research
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• 제13권3호
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• pp.237-245
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• 1997

As the development of a pharmaceutical product is a dynamic process which involves continuousfeed-back between non-clinical and clinical studies, the integration of pharmacokinetics into toxicity testing became increasingly important in recent years. Toxicokinetic measurements in the toxicity studies is considered to be an important scientific approach in the interpretation of the toxicology findings and the promotion of rational study design development. Primarily this research project was conducted to determine the systemic exposure achieved in acute toxicity test and its relationship to dose level and the time course of the toxicity study. Acute hepatotoxicity study and its relevant toxicokinetic study in mice were performed using acetarninophen (AA) as a model compound. The correlation between acute hepatotoxicity indices and toxicokinetic parameters following intraperitoneally administration of various dosages of AA in mice was evaluated and discussed minutely in the text. Based on these studies, single-dose toxicity testing of AA including kinetic studies was evaluated in ICR mice for 7 days and interpreted in the text. Our results from the integration of toxicokinetic monitoring into single-dose toxicity study enable to elucidate the relation of the exposure achieved in toxicity study to toxicological findings and assist in the selection of appropriate dose levels for use in repeated-dose toxicity or later studies.

• IMMUNE NETWORK
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• 제20권1호
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• pp.9.1-9.21
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• 2020

Immune checkpoint inhibitors (ICIs) have been changing the paradigm of cancer treatment. However, immune-related adverse effects (irAEs) have also increased with the exponential increase in the use of ICIs. ICIs can break up the immunologic homeostasis and reduce T-cell tolerance. Therefore, inhibition of immune checkpoint can lead to the activation of autoreactive T-cells, resulting in various irAEs similar to autoimmune diseases. Gastrointestinal toxicity, endocrine toxicity, and dermatologic toxicity are common side effects. Neurotoxicity, cardiotoxicity, and pulmonary toxicity are relatively rare but can be fatal. ICI-related gastrointestinal toxicity, dermatologic toxicity, and hypophysitis are more common with anti- CTLA-4 agents. ICI-related pulmonary toxicity, thyroid dysfunction, and myasthenia gravis are more common with PD-1/PD-L1 inhibitors. Treatment with systemic steroids is the principal strategy against irAEs. The use of immune-modulatory agents should be considered in case of no response to the steroid therapy. Treatment under the supervision of multidisciplinary specialists is also essential, because the symptoms and treatments of irAEs could involve many organs. Thus, this review focuses on the mechanism, clinical presentation, incidence, and treatment of various irAEs.

• Journal of Medicine and Life Science
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• 제18권2호
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• pp.35-39
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• 2021

Exaggerated acute and late toxicities following radiotherapy have been reported in patients with pre-existing connective tissue diseases, such as systemic lupus and scleroderma. Behcet's disease (BD) is a relapsing multisystem connective tissue disease characterized by vasculitis in the mucocutaneous, ocular, gastrointestinal, respiratory, neurologic, urogenital, articular, and cardiovascular systems. Data concerning the relationship between radiotherapy toxicity and BD are limited in the literature. Here, we report a case of lung cancer treated with radiotherapy (60 Gy) in a patient with BD. No severe radiation-induced toxicity was observed. Radiation-induced toxicity in patients with BD has also been discussed.

• Environmental Analysis Health and Toxicology
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• 제31권
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• pp.4.1-4.2
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• 2016

Once released into the air, humidifier disinfectants became tiny nano-size particles, and resulted in chemical bronchoalveolitis. Families had lost their most beloved members, and even some of them became broken. Based on an estimate of two million potential victims who had experienced adverse effects from the use of humidifier disinfectants, we can say that what we have observed was only the tip of the iceberg. Problems of entire airways, as well as other systemic effects, should be examined, as we know these nano-size particles can irritate cell membranes and migrate into systemic circulation. The story of humidifier disinfectant is not finished yet.

• Asian Pacific Journal of Cancer Prevention
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• 제15권24호
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• pp.10769-10772
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• 2015

Purpose: This analysis was conducted to evaluate cardiovascular toxicity of commonly used anti-VEGF therapeutic agent, bevacizumab, in treating patients with cancer. Methods: Clinical studies evaluating the efficacy and safety of bevacizumab-based regimens on response and safety for patients with cancer were identified using a predefined search strategy, allowing cardiovascular toxicity and other side effects of treatment to be estimated. Results: In bevacizumab based regimens, 4 clinical studies including 282 patients with advanced cancer (including gliomas, cervical, breast and ovarian cancer) were considered eligible for inclusion. These bevacizumab-based regimens included docetaxel, irinitecan and carboplatin. Systematic analysis suggested that, of 282 patients treated by bevacizumab based regimens, hypertension and thrombo-embolism occurred in 2.5% (7/282), while only 3 patients reported cardiovascular events (1.1%). No treatment related death occurred in bevacizumab based treatment. Conclusion: This systemic analysis suggests that bevacizumab based regimens are associated with reasonable and accepted cardiovascular toxicity when treating patients with gliomas, cervical, breast and ovarian cancer.

• Toxicological Research
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• 제18권1호
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• pp.87-98
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• 2002

This study was conducted to evaluate the safety of a recombinant human Factor VIII(GC-$\gamma$ AHF) manufactured by Korea Green Cross Company with different technology according to the Regulation of Korean Food and Drug Administration (l 998. 12. 3). In acute toxicity test, both genders of Sprague-Dawley rats and Beagle dogs were administered intravenously with GC-$\gamma$ AHF of three doses (3,125, 625 and 125 IU/kg), and single dose of 3,125 IU/kg, respectively. No dead animal and abnormal autopsy findings were found in Control and GC-$\gamma$ AHF treated group. Therefore, the 50% lethal dose ($LD_{50}$) of GC-$\gamma$ AHF was conidered to be higher than 3,125 IU/kg in rats and dogs. In the four weeks repeated intravenous toxicity study, GC-$\gamma$ AHF was administrated intravenosly to both genders of rats and dogs with 3 doses (500, 150, 50 IU/kg). There were neither dead animals nor significant changes of body weights during the experimental Period. In addition, no significant GC-$\gamma$ AHF related changes were found in clinical sign, urinalysis and other finding. Statistically changes were observed in hematological, biochemical and organ weight parameters of treated groups: however these changes were not dose dependent. No histopathological lesion were observed in both control and treated animals. Above data suggest that no observed adverse effect level of test materials in rats and dogs might be over 500 IU/kg/day in this study. In ocular irritation test, any injury on iris, conjunctiva and cornea in rabbits were not observed. The acute ocular irritation index (A.O.I.), mean ocular irritation index (M.O.I.) and Day-7 individual ocular irritation Index (I.O.I.) of GC-$\gamma$ AHF were 0. In the primary skin Irritation test, the primary irritation index (P.I.I.) oj GC-$\gamma$ AHF were 0. Therefore, the GC-$\gamma$ AHF is considered not to have the primary skin and eye toxicity in rabbits. In active systemic anaphylaxis (ASA) test, GC-$\gamma$ AHF and GC-$\gamma$ AHF emulsified with Freund's complete adjuvant (FCA) did not induce any symptom of anaphylactic shock in guinea pigs. In passive cutaneous anaphylxis (PCA) test, after sensitization with antisera of GC-$\gamma$ AHF sensitized mice, blue spots were observed on the hypodermis of back of rats, but diameter of each spot was smaller than 5 mm in each test groups except the positive control group. Based on the results of this study, GC-$\gamma$ AHF is not conidered to have any antigenic potential. In conclusion, at levels of up to 500 IU/kg, GC-$\gamma$ AHF did not produce treatment-related toxicity under the conditions of these acute-, four week repeated-toxicity, primary skin and eye toxicity, and antigenicity test.

• Asian Pacific Journal of Cancer Prevention
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• 제16권5호
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• pp.1993-1995
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• 2015

Purpose: This analysis was conducted to evaluate the efficacy and safety of irinotecan based regimens as second-line chemotherapy in treating patients with small cell lung cancer. Methods: Clinical studies evaluating the efficacy and safety of irinotecan based regimens as second-line chemotherapy for patients with small cell lung cancer were identified using a predefined search strategy. Pooled response rates (RRs) of treatment were calculated. Results: In irinotecan based regimens as second-line chemotherapy, 4 clinical studies which including 155 patients with small cell lung cancer were considered eligible for inclusion. In all chemotherapy consisted of irinotecan with or without nedaplatin. Pooled analysis suggested that, in all patients, the pooled RR was 27.1% (42/155) in irinotecan based regimens. Nausea, vomiting, diarrhea and myelosuppression were the main side effects. No grade III or IV renal or liver toxicity was observed. No treatment related death occurred with the irinotecan based treatments. Conclusion: This systemic analysis suggests that irinotecan based regimens as second-line chemotherapy are associated with mild response rate and acceptable toxicity for patients with small cell lung cancer.

• Asian Pacific Journal of Cancer Prevention
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• 제15권17호
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• pp.7277-7280
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• 2014

This analysis was conducted to evaluate the efficacy and safety of carboplatin based chemotherapy in treating pediatric patients with Wilms tumors. Methods: Clinical studies evaluating the efficacy and safety of carboplatin based regimens on response and safety for pediatric patients with Wilms tumors were identified using a predefined search strategy. Pooled response rates (RRs) of treatment were calculated. Results: In carboplatin based regimens, 4 clinical studies which including 127 patients with advanced Wilms tumors were considered eligible for inclusion. With this carboplatin based chemotherapy, 2 clinical studies included carboplatin, ifosfamide and etoposide. Systemic analysis suggested that, in all patients, the pooled PR was 64.5% (82/127) in carboplatin based regimens. Thrombocytopenia and leukocytopenia were the main side effects. No grade III or IV renal or liver toxicity was observed. No treatment related death occurred with carboplatin based treatment. Conclusion: This systemic analysis suggests that carboplatine based regimens are associated with a reasonable response rate and accepted toxicities for treating pediatric patients with Wilms tumors.

• 농약과학회지
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• 제17권3호
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• pp.178-184
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• 2013

꿀벌에 대한 급성독성이 강한 침투이행성 농약을 대상으로 토양처리 후 흡수이행에 의해 나타나는 꿀벌(Apis mellifera)에 대한 영향을 조사하고자 꿀벌 엽상잔류독성시험을 수행하였다. 본 연구에서는 침투이행성 농약인 dinotefuran 입제와 imidacloprid 입제 그리고 clothianidin 입제를 토마토 정식시 3가지 처리량으로 토양에 파구처리를 하였다. 처리 후 경과시간에 따라 잎을 채취하여 잎에서의 잔류농도를 분석하였고 꿀벌에 노출시켜 꿀벌치사율을 조사하였다. Dinotefuran 입제 처리구의 꿀벌 독성은 7일 이후 꿀벌치사율이 100%로 나타났고 17일 이후 감소하였다. Imidacloprid 입제의 경우 꿀벌 최대치사율이 44~72%로 낮았으나 그 영향은 18일까지 지속된 후 감소하였고 clothianidin 입제는 처리 후 7일에 꿀벌치사율이 100%이었으며 14일 이후 점차 감소하였다. 시험농약 처리 후 경과시간에 따른 잎의 잔류 경향성과 각 시험농약에서 꿀벌의 치사율은 유사한 경향성을 보였으며, 토마토의 생장이 활발한 14일 이후에는 토마토 잎에서의 잔류량이 점차 감소하였고, 실제 사용량 처리시 21일 이후에는 엽상잔류에 의한 꿀벌의 영향도 확연하게 감소하였다.

• 한국가스학회지
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• 제19권3호
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• pp.1-8
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• 2015

본 연구는 신발, 타이어, 접착제 제조에 많이 사용되는 클로로프렌(chloroprene)에 대해 취급근로자의 건강장해 예방을 위해 유해성을 조사하고, 취급사업장에 대해 작업환경을 측정 노출농도 및 용량반응을 통해 위험성을 평가하였다. 클로로프렌은 국제암연구소(IARC)로부터 발암추정물질(2B), 표적장기 전신독성 및 생식독성물질로 국내 취급 사업장은 27개소, 연간 약 1,300톤이 사용되었으며, 노출 위험성은 노출환경에 따라 Monte-carlo simulation을 이용하여 산출하였다. 그 결과 국소배기장치가 없으며 1일 4시간 초과 작업시 발암을 일으킬 수 있는 위험성의 평균값은 26,404로, 국소배기장치가 있으며 15분 미만의 단시간 작업 경우 2,199에 비교해 매우 높은 위험성을 보였다. 그리고 표적장기 전신독성의 경우도 169.06으로 단시간 작업 경우 4.10에 비교해 표적장기 전신독성 발생 위험이 높은 것으로 평가되어 물질의 노출시간 및 환기방식에 깊은 상관관계가 있는 것으로 나타났다. 따라서 클로로프렌 노출에 의한 근로자의 건강장해 예방하기 위해 국소배기장치의 가동과 방독마스크의 착용 등 노출저감을 위한 작업환경 관리의 필요성이 있었다. 특히 클로로프렌은 발암성, 생식독성 물질로 미국 산업안전보건청(OSHA)에서는 TWA를 5 ppm($18mg/m^3$) 이하로 관리하고 있으며, 본 유해성조사 결과에서도 현행 노출기준 10 ppm이하에서 표적장기독성, 생식기 장해 등 생체에 미치는 영향이 있는 것으로 나타나 있어, 위험성이 강하게 예측되므로 현재 사용하고 있는 우리나라 작업환경 노출기준(TWA 10 ppm)도 5 ppm 수준으로 강화하여 근로자 건강장해 예방에 기여할 필요성이 있는 것으로 판단되었다.