• Journal of Marine Bioscience and Biotechnology
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• v.11 no.2
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• pp.52-61
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• 2019

Over the past few decades, microalgae-based biotechnology conjugated with innovative CRISPR/Cas9-mediated genetic engineering has been attracted much attention for the cost-effective and eco-friendly value-added compounds production. However, the discharge of reproducible living modified organism (LMO) into environmental condition potentially causes serious problem in aquatic environment, and thus it is essential to assess potential environmental risk for human health. Accordingly, in this study, we monitored discharged genetically modified microalgae (GMM) near the research complex which is located in Daejeon, South Korea. After testing samples obtained from 6 points of near streams, several green-colored microalgal colonies were detected under hygromicin-containing agar plate. By identification of selection marker genes, the GMM was not detected from all the samples. For the lab-scale environmental risk assessment of GMM, acute toxicity test using rotifer Brachionus calcyflorus was performed by feeding GMM. After feeding, there was no significant difference in mortality between WT and transformant Chlamydomonas reinhardtii. According to further analysis of horizontal transfer of green fluorescence protein (GFP)-coding gene after 24 h of incubation in synthetic freshwater, we concluded that the GFP-expressed gene not transferred into predator. However, further risk assessments and construction of standard methods including prolonged toxicity test are required for the accurate ecological risk assessment.

• Korean Journal of Environmental Agriculture
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• v.6 no.2
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• pp.66-72
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• 1987

Sensitivity of the three freshwater fish, Cyprinus carpio, Oryzias latipes (wildtype indigenous to Korea), and O. latipes (Japanese killifish) to 30 pesticide formulations were studied in terms of 48 hr $LC_{50}$ determined with the static method. The correlation between C. carpio and O. latipes (Japanese killifish) was higher than that between C. carpio and O. latipes with correlation coefficients of 0.89 and 0.80, respectively. The sensitivity of O. latipes and O. latipes (Japanese killifish) to pesticides showed very high correlation with a coefficient of 0.93. Therefore, it is suggested that the acute toxicity data concerning O. latipes (Japanese killifish) could represent those C. carpio or O. latipes which are indigenous species in Korea. Also, it is found that the present protocol for the toxicity test with carp in Korea has difficulties in maintaining the proper concentration of dissolved oxygen in the test chamber because of the abrupt decrease of dissolved oxygen to 2mg/l, which is not acceptable according to general guidelines of foreign countries.

• Journal of Pharmacopuncture
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• v.8 no.1
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• pp.21-30
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• 2005

Objectives : To observe physiological anti-body effects of anti-BV, acute toxic response, measurement of $LD_{50}$, and the effects of anti-body were evaluated. Methods : $LD_{50}$ of Anti-Bee Venom were measured, and to analyze acute toxic responses, weight, and the anti-body effects various concentrations of Anti-BV were diluted and the survival rate was measured. Cell blood count (CBC), liver, spleen, and kidney pathologies were observed from the histological aspects. Results : Experiment was conducted to observe Anti-BV as the anti-body to the bee venom and the following results were obtained : 1.anti-BV was injected intraperitoneally and no toxic responses were witnessed. All of the experiment subjects stayed alive during the experiment, making $LD_{50}$ analysis impossible. 2.Anti-BV was injected intraperitoneally in mice and no significant weight changes were measured between the control group and the experiment groups. 3. Measuring the concentration dependent survival rate, the highest survival rate was at the concentration of $1.25{\times}10^2mg/kg$(1/2.000) for Anti-BV. 4. No particular results were shown in the CBC test. 5. Observation of changes in the organ tissues, Anti-BV was found to suppress blood stasis in the liver and inhibit necrosis of the cells. Conclusion : Above results suggest that Anti-BV doesn't cause any toxic responses in the body and works as an anti-body to the bee venom. Further studies must be followed to secure the findings.

• Journal of The Korean Society of Clinical Toxicology
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• v.9 no.2
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• pp.49-55
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• 2011

Purpose: Acetanilide has been in widespread use as an amide herbicide compound. However, available data regarding acute human poisoning is scarce. The aim of this study was to analyze the clinical characteristics of acetanilide poisoning in order to identify the risk factors associated with severity. Methods: We conducted a retrospective observational study encompassing the period January 2005 to December 2010, including adult ED patients suffering from acetanilide intoxication. Toxicological history, symptoms observed, clinical signs of toxicity, and laboratory test results were collected for each patient. The patients were classified into two groups for analysis, according their poisoning severity score (PSS). Resulting clinical data and prognostic variables were compared between mild-to-moderate poisoning (PSS 1/2 grades), and severe poisonings and fatalities (PSS 3/4 grades). Results: There were a total of 37 patients, including 26 alachlor, 6 s-metolachlor, 4 mefenacet, and 1 butachlor cases. The majority of patients (81.1%) were assigned PSS 1/2 grades. Changes in mental status and observation of adverse neurologic symptoms were more common in the PSS 3/4 group. The median ingested volume of amide herbicide compound was 250 ml (IQR 200-300 ml) in the PSS 3/4 group, and 80 ml (IQR 50-138 ml) in the PSS 1/2 group. Also, the median GCS observed in the PSS 3/4 group was 13 (IQR 10-14), which was markedly low as compared to a median GCS of 15 in the PSS 1/2 group. Overall mortality rate was 5.4%, and profound cardiogenic shock was observed prior to death in all fatalities. Conclusion: When compared to previous reports, acute acetanilide poisoning resulted in relatively moderate severity. The presence of neurologic manifestations, hypotension, lower GCS score, and larger ingested volumes was associated with more serious effects and mortalities.

• Toxicological Research
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• v.18 no.1
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• pp.23-29
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• 2002

Disodium disulphite, the HPV chemical, was assigned to Korea in order to implement OECD SIDS program in 1999. It was produced about 3,200 ton/year in 1998. This report evaluates the toxic potency of disodium disulphite based on the environmental and mammalian effects as well as human exposure. Oral $LD_{50}$ in rats is 1,540 mg/kg b.w. and effects was observed to the stomach, liver and the GI track that was filled with blood. For repeated dose toxicity, the predominant effect was the induction of stomach lesion due to local irritation. The no observed adverse effect lever for local (stomach irritation) was about 217 mg/kg bw/day. There is no evidence that disodium disulphite is genotoxic in vivo. No reproductive or developmental toxicty of disodium disulphite was observed for the period up to 2 yr and over three generation. In humans, urticaria and asthma with itching, edema, rhinitis, and nasal congestion were reported. Disodium disulphite is unlikely to induce respiratory sensitization but may enhance symptom of asthma in sensitive individuals. This chemical would be mainly transported to water compartment when released to environmental compartments since it is highly water soluble (470 g/l at 20). Low K oc (2.447) indicates disodium disulphite is so mobile in soil that it may not stay in the terrestrial compartment. The chemical has been tested in a limited number of aquatic species. hem acute toxicity test to fish, 96 hr-$LC_{50}$ was > 100 mg/1. For algae, 72 hr-$XC_{50}$ was 48.1 mg/1. For daphnid, the acute toxicity value of 48 hr-$EC_{50}$ was 88.76 mg/1, and chronic value of 21day-NOEC was > 10 mg/1. Therefore, PNEC of 0.1 mg/l for the aquatic organism was obtained from the chronic value of daphnid using the assessment factor of 100. Based on these data the disodium disulphite was recommended as low priority for further post-SIDS work in OECD.

• Korean Journal of Veterinary Research
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• v.44 no.1
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• pp.49-55
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• 2004

The present study was carried out to investigate the potential acute toxicity of CKD-602 by a single intravenous dose in Beagle dogs. The test chemical was administered intravenously to male and female Beagle dogs at dose levels of 0.3, 0.5, or 2.5 mg/kg. Mortalities, clinical findings, and body weight changes were monitored for the 14-day period following the administration. At the end of 14-day observation period, all animals were sacrificed and complete gross postmortem examinations were performed. All males and females of the 2.5 mg/kg dose group were found dead between the fourth and seventh day after the injection. Treatment related clinical signs, including vomiting, anorexia, mucous stool, diarrhea, and no stool were observed. Decrease or suppression of body weight was observed in a dose-dependent manner. In autopsy, dark red discoloration of the gastrointestinal tract, atrophy of the thymus, paleness of the spleen, sporadic dark red spots of the lung and petechia of the heart were observed in dead animals of the 2.5 mg/kg dose group. There were no specific adverse effects on males and females of the 0.3 and 0.5 mg/kg dose groups, except for the transient clinical signs such as anorexia, vomiting, and mucus/no stool. On the basis of the results, it was concluded that a single intravenous injection of CKD-602 to Beagle dogs resulted in increased incidence of abnormal clinical signs and death, decreased body weight, and increased incidence of abnormal gross findings. The absolute toxic dose of this chemical was 2.5 mg/kg for both genders. The $LD_{50}$ value was 1.1 mg/kg (95% confidence limit not specified) for both genders. The no-observed-effect level (NOEL) was considered to be below 0.3 mg/kg for both genders.

• Journal of Life Science
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• v.14 no.4
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• pp.547-552
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• 2004

The present study was carried out to investigate the potential acute toxicity of amitraz by a single subcutaneous dose in beagle dogs. The test chemical was administered subcutaneously to male beagle dogs at dose levels of 0, 2, 10, or 50 mg/kg. Mortalities, clinical findings, and body weight changes were monitored for the 14-day period following the administration. At the end of 14-day observation period, hematology, serum biochemistry, and gross postmortem examinations were examined. A single dog in the 50 mg/kg group was found dead on day 3 after treatment and the other two dogs in the group were sacrificed because of the severe clinical signs on day 7 after treatment. Treatment related clinical signs, including anorexia, edema, mass and abscess formation in the injection sites, depression, vomiting, lacrimation, decreased locomotor activity, ataxia, recumbency, paresis in the limbs, and/or moribundity were observed in all treatment groups in a dose-dependent manner. Decreased or suppressed body weight gain was also observed dose-dependently in all treated groups. In autopsy, dead animals in the 50 mg/kg group showed muscular hemorrhage and inflammation in the injection sites and congestion in the liver and kidney. The terminal sacrificed animals in the 10 mg/kg group also exhibited muscular hemorrhage and inflammation in the injection sites. Whereas, no treatment related effects on hematology and serum biochemistry were observed on day 14 after treatment at any dose tested. On the basis of the results, it was concluded that a single subcutaneous injection of amitraz to beagle dogs resulted in increased incidence of abnormal clinical signs and death, decreased body weight, and increased incidence of abnormal gross findings. In the experimental conditions, the $LD_{50}$value of amitraz was 22.3 mg/kg (95% confidence limit not specified) and the no-observed-adverse-effect level (NOAEL) was considered to be below 2 mg/kg for male dogs.

• The Korean Journal of Physiology and Pharmacology
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• v.19 no.4
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• pp.365-372
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• 2015

Aripiprazole (ARI) is a commonly prescribed medication used to treat schizophrenia and bipolar disorder. To date, there have been no studies regarding the molecular pathological and immunotoxicological profiling of aripiprazole. Thus, in the present study, we prepared two different formulas of aripiprazole [Free base crystal of aripiprazole (ARPGCB) and cocrystal of aripiprazole (GCB3004)], and explored their effects on the patterns of survival and apoptosis-regulatory proteins under acute toxicity and cytotoxicity test conditions. Furthermore, we also evaluated the modulatory activity of the different formulations on the immunological responses in macrophages primed by various stimulators such as lipopolysaccharide (LPS), pam3CSK, and poly(I:C) via toll-like receptor 4 (TLR4), TLR2, and TLR3 pathways, respectively. In liver, both ARPGCB and GCB3004 produced similar toxicity profiles. In particular, these two formulas exhibited similar phospho-protein profiling of p65/nuclear factor $(NF)-{\kappa}B$, c-Jun/activator protein (AP)-1, ERK, JNK, p38, caspase 3, and bcl-2 in brain. In contrast, the patterns of these phospho-proteins were variable in other tissues. Moreover, these two formulas did not exhibit any cytotoxicity in C6 glioma cells. Finally, the two formulations at available in vivo concentrations did not block nitric oxide (NO) production from activated macrophage-like RAW264.7 cells stimulated with LPS, pam3CSK, or poly(I:C), nor did they alter the morphological changes of the activated macrophages. Taken together, our present work, as a comparative study of two different formulas of aripiprazole, suggests that these two formulas can be used to achieve similar functional activation of brain proteins related to cell survival and apoptosis and immunotoxicological activities of macrophages.

• Radiation Oncology Journal
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• v.24 no.1
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• pp.11-20
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• 2006

Puroose: In order to find out whether stereotactic radiation therapy (RT) using CyberKnife (CK) could improve survival rate and lower acute toxicity compared to conventional RT. Materials and Methods: From April 2003 through April 2004, 19 patients with Eastern Cooperative Oncology Group (ECOG) performance status ${\leq}3$ and locally advanced pancreas cancer without distant metastasis, evaluated by CT or PET/CT, were included. We administered stereotactic RT consisting of either 33 Gy, 36 Gy or 39 Gy in 3 fractions to 6, 4 and 9 patients, respectively, in an effort to increase the radiation dose step by step, and analyzed the survival rate and gastrointestinal toxicities by the acute radiation morbidity criteria of Radiation Therapeutic Oncology Group (RTOG). Prognostic factors of age, sex, ECOG performance score, chemotherapy, bypass surgery, radiation dose, CA 19-9, planning target volume (PTV), and adjacent organ and vessel invasion on CT scan were evaluated by Log Rank test. Results: The median survival time was 11 months with 1-year survival rate of 36.8%. During follow-up period (range $3{\sim}20$ months, median 10 months), no significant gastrointestinal acute toxicity (RTOG grade 3) was observed. In univariate analysis, age, sex, ECOG performance score, chemotherapy, bypass surgery, radiation dose, CA 19-9 level, and adjacent organ and vessel invasion did not show any significant changes of survival rate, however, patients with PTV (80 cc showed more favorable survival rate than those with PTV>80 cc (p-value<0.05). In multivariate analysis, age younger than 65 years and PTV>80 cc showed better survival rate. Conclusion: In terms of survival, the efficacy of stereotactic radiation therapy using CK was found to be superior or similar to other recent studies achieved with conventional RT with intensive chemotherapy, high dose conformal RT, intraoperative RT (IORT), or intensity modulated RT (IMRT). Furthermore, severe toxicity was not observed. Short treatment time in relation to the short life expectancy gave patients more convenience and, finally, quality of life would be increased. Consequently, this could be regarded as an effective novel treatment modality for locally advanced, unresectable pancreas cancer. PTV would be a helpful prognostic factor for CK.

• Radiation Oncology Journal
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• v.17 no.2
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• pp.113-119
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• 1999

Purpose : To evaluate possible acute toxicity and early response of concurrent radiation therapy and low dose daily cisplatin as a radiosensitizer in patients with locally advanced uterine cervical carcinomas. Materials and Method : From December 1996 to January 1999, 38 previously untreated Patients with locally advanced squamous cell carcinoma of the uterine cervix (from stage IIB to stage IIIB) were treated at Inha University Hospital. All patients underwent standard pretreatment staging Procedures after the initial evaluation by gynecologists and radiation oncologists. Sixteen Patients with huge cervical mass (>4 cm) were submitted to the group treated with concurrent radiation therapy and low dose daily cisplatin while the remainder was treated with radiation therapy alone. Radiation therapy consisted of 4500 cGy external beam irradiation to whole pelvis (midline block after 3000 cGy), 900$\~$1000 cGy boost to involved parametrium, and high dose-rate intracavitary brachytherapy (a total dose of 3000$\~$3500 cGy/500 cGy per fraction to point A, twice per week). In the group treated with low dose cisplatin concurrently, 10 mg of daily intravenous cisplatin was given from the 1st day of radiation therapy to the 20th day of radiation therapy. Acute toxicity was measured according to expanded common toxicity criteria of the NCI (C) Clinical Trials. Early response data were analyzed at minimum 4 weeks' follow-up after completion of the treatment protocol. Results: Hematolgic toxici쇼 was more prominent in patients treated with radiation therapy and cisplatin. Six of 16 patients (37.5$\~$) treated with radiation therapy and cisplatin and one of 22 patients (4.5$\~$) treated with radiation therapy alone experienced grade 3 leukopenia. In Fisher's exact test, there was statistically significant difference between two groups regarding leukopenia (P=0.030). There was no apparent difference in the frequency of gastrointestinal and genitourinary toxicity between two groups (P=0.066). Three of 16 patients (18.7$\~$) treated with radiation therapy and cisplatin and two of 22 patients (9.1$\~$) treated with radiation therapy alone experienced more than 5 kg weight loss during the treatment. There was no statistically significant difference on weight loss between two groups (P=0.63). Two patients on each group were not evaluable for the early response because of incomplete treatment. The complete response rate at four weeks' follow-up was 80$\~$(16/20) for the radiation therapy alone group and 78$\~$ (11/14) for the radiation therapy and cisplatin group. There was no statistically significant difference in early response between two treatment groups (P=0.126). Conclusion : This study led to the conclusion that the hematologic toxicity from the treatment with concurrent radiation therapy and low dose daily cisplatin seems to be more prominent than that from the treatment of radiation therapy alone. There was no grade 4 hematologic toxicity or mortality in both groups. The hematologic toxicity in both treatment groups seems to be well managable modically. Since the risk factors were not balanced between two treatment groups, the direct comparison of early response of both groups was not possible. However, preliminary results regarding early response for patients with bulky cervical tumor mass treated with radiation therapy and low dose daily cisplatin was encouraging. Longer follow-up is necessary to evaluate the survival data. A phase III study is needed to evaluate the efficacy of concurrent daily low dose cisplatin with radiation therapy in bulky cervical cancer.