• Journal of The Korean Society of Clinical Toxicology
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• v.14 no.2
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• pp.136-143
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• 2016

Purpose: In patients with altered mentality caused by drugs or unknown causes, ammonia is checked to facilitate differential diagnosis or diagnose hepatic coma. This helps early prevention and treatment of brain damage due to hyperammonemia. This study was conducted to evaluate clinical characteristics of intoxicated adult patients with hyperammonemia. Methods: We evaluated 95 patients with hyperammonemia among intoxicated patients above the age of 15 who visited our ED from January 2013 to December 2015. We analyzed the demographic characteristics and type of poisoning substance, reason for ingestion, toxicological characteristics such as elapsed time from ingestion to hospital visit, lab, clinical progression and complications. Data were evaluated using the student's t test or Mann-Whitney U test for continuous variables, and Chi-square test and Fisher's exact test for frequency analysis of categorical variables. Results: When compared to healthy individuals, patients with hyperammonemia showed statistical significance on their SOFA score (p=0.016) and poison severity score (p<0.001). Additionally, patients with hyperammonemia showed significantly different initial serum AST level (p=0.012) and maximum serum AST level during the hospital stay (p=0.026) when compared to healthy individuals. Moreover, individuals with sustained hyperammonemia compared to transient hyperammonemia showed clinically significant SOFA scores (p<0.001), poison severity scores (p=0.007), mortality rates in the ICU (p=0.021), as well as different duration of hospital stay (p=0.037), serum creatinine level (p=0.002), erythrocyte sedimentation rate (p=0.025), and serum myoglobin (p=0.015). Conclusion: Most poisoning-induced hyperammonemia cases were transient and recovered without special treatment. Therefore, hyperammonemia is almost non-specific among poisoning patients.

• Korean Journal of Environmental Agriculture
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• v.35 no.3
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• pp.216-222
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• 2016

BACKGROUND: Polychlorinated biphenyls (PCBs) are one of the most common environmental contaminants. Because of their recalcitrant properties and long-term toxicity, numerous studies have been performed. The toxicological concerns are focused on endocrinological effects of animal. Several different metabolites have been reported, including hydroxy PCBs, PCB quinones, and methylsulfonyl PCBs from animal tissues. However, details in plants have never been studied. It is well-known that plants can produce phytoalexin in response to chemical, physical, or pathological stress.METHODS AND RESULTS: In this study, the several PCBs and hydroxy derivatives were prepared by chemical syntheses. Their effects on secondary metabolite biosynthesis were determined in carrot roots. The levels of 6-methoxymellein were determined in several different treatments, using gas chromatography-mass spectrometry. In general, the concentration of 6-methoxymellein reached a maximum at 2 days and gradually decreased to trace level at 5 days in control experiments. However, the effects of PCBs or hydroxy derivatives were highly dependent on compounds. For example, the maximum concentrations of 6-methoxymellein were observed at 3 days for 2-hydroxy/4-hydroxybiphenyl, while 3,3',4,4',5-pentachlorobiphenyl and 3,5-dichloro-2-hydroxybiphenyl showed a rapid accumulation within 1 day, followed by rapid dissipation to undetectable levels.CONCLUSION: Biphenyl derivatives were effective elicitor of 6-methoxymellein accumulation. In general, hydroxybiphenyls (phenols) more efficiently induced phytoalexin biosynthesis than those without hydroxy groups. It can be concluded that PCBs or their possible metabolites could change the plant secondary metabolism.

• Journal of Pharmacopuncture
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• v.19 no.4
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• pp.319-328
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• 2016

Objectives: Advancements in nanotechnology have led to nanoparticle (NP) use in various fields of medicine. Although the potential of NPs is promising, the lack of documented evidence on the toxicological effects of NPs is concerning. A few studies have documented that homeopathy uses NPs. Unfortunately, very few sound scientific studies have explored the toxic effects of homeopathic drugs. Citing this lack of high-quality scientific evidence, regulatory agencies have been reluctant to endorse homeopathic treatment as an alternative or adjunct treatment. This study aimed to enhance our insight into the impact of commercially-available homeopathic drugs, to study the presence of NPs in those drugs and any deleterious effects they might have, and to determine the distribution pattern of NPs in zebrafish embryos (Danio rerio). Methods: Homeopathic dilutions were studied using high-resolution transmission electron microscopy with selected area electron diffraction (SAED). For the toxicity assessment on Zebrafish, embryos were exposed to a test solution from 4 - 6 hours post-fertilization, and embryos/larvae were assessed up to 5 days post-fertilization (dpf ) for viability and morphology. Toxicity was recorded in terms of mortality, hatching delay, phenotypic defects and metal accumulation. Around 5 dpf was found to be the optimum developmental stage for evaluation. Results: The present study aimed to conclusively prove the presence of NPs in all high dilutions of homeopathic drugs. Embryonic zebrafish were exposed to three homeopathic drugs with two potencies (30CH, 200CH) during early embryogenesis. The resulting morphological and cellular responses were observed. Exposure to these potencies produced no visibly significant malformations, pericardial edema, and mortality and no necrotic and apoptotic cellular death. Conclusion: Our findings clearly demonstrate that no toxic effects were observed for these three homeopathic drugs at the potencies and exposure times used in this study. The embryonic zebrafish model is recommended as a well-established method for rapidly assessing the toxicity of homeopathic drugs.

• Toxicological Research
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• v.28 no.2
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• pp.73-79
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• 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.

• Toxicological Research
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• v.29 no.2
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• pp.121-127
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• 2013

Nanotoxicological research has shown toxicity of nanomaterials to be inversely related to particle size. However, the contribution of agglomeration to the toxicity of nanomaterials has not been sufficiently studied, although it is known that agglomeration is associated with increased nanomaterial size. In this study, we prepared aerosols of nano-sized carbon black by 2 different ways to verify the effects of agglomeration on the toxicity and deposition of nano-sized carbon black. The 2 methods of preparation included the carbon black dispersion method that facilitated clustering without sonication and the carbon black dispersion method involving sonication to achieve scattering and deagglomeration. Male Sprague-Dawley rats were exposed to carbon black aerosols 6 hr a day for 3 days or for 2 weeks. The median mass aerodynamic diameter of carbon black aerosols averaged $2.08{\mu}m$ (for aerosol prepared without sonication; group N) and $1.79{\mu}m$ (for aerosol prepared without sonication; group S). The average concentration of carbon black during the exposure period for group N and group S was $13.08{\pm}3.18mg/m^3$ and $13.67{\pm}3.54mg/m^3$, respectively, in the 3-day experiment. The average concentration during the 2-week experiment was $9.83{\pm}3.42mg/m^3$ and $9.08{\pm}4.49mg/m^3$ for group N and group S, respectively. The amount of carbon black deposition in the lungs was significantly higher in group S than in group N in both 3-day and 2-week experiments. The number of total cells, macrophages and polymorphonuclear leukocytes in the bronchoalveolar lavage (BAL) fluid, and the number of total white blood cells and neutrophils in the blood in the 2-week experiment were significantly higher in group S than in normal control. However, differences were not found in the inflammatory cytokine levels (IL-$1{\beta}$, TNF-${\alpha}$, IL-6, etc.) and protein indicators of cell damage (albumin and lactate dehydrogenase) in the BAL fluid of both group N and group S as compared to the normal control. In conclusion, carbon black aerosol generated by sonication possesses smaller nanoparticles that are deposited to a greater extent in the lungs than is aerosol formulated without sonication. Additionally, rats were narrowly more affected when exposed to carbon black aerosol generated by sonication as compared to that produced without sonication.

• Toxicological Research
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• v.31 no.3
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• pp.255-264
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• 2015

Heterocyclic amines (HCAs) and acrylamide are unintended hazardous substances generated by heating or processing of foods and are known as carcinogenic and mutagenic agents by the animal experiments. A simple method was established for a rapid and accurate determination of 12 types of HCAs (IQ, MeIQ, Glu-P-1, Glu-P-2, MeIQx, Trp-P-1, Trp-P-2, PhIP, $A{\alpha}C$, $MeA{\alpha}C$, Harman and Norharman) and acrylamide in three food matrices (non-fat liquid, non-fat solid and fat solid) by isotope dilution liquid chromatography-tandem mass spectrometry (LC-MS/MS). In every sample, a mixture of internal standards including $IQ-d_3$, $MeIQx-d_3$, $PhIP-d_3$, $Trp-P-2-^{13}C_2-^{15}N$ and $MeA{\alpha}C-d_3$ was spiked for quantification of HCAs and $^{13}C_3$-acrylamide was also spiked for the analysis of acrylamide. HCAs and acrylamide in sample were extracted with acetonitrile and water, respectively, and then two solid-phase extraction cartridges, ChemElut: HLB for HCAs and Accucat: HLB for acrylamide, were used for efficiently removing interferences such as pigment, lipid, polar, nonpolar and ionic compounds. Established method was validated in terms of recovery, accuracy, precision, limit of detection, limit of quantitation, and linearity. This method showed good precision (RSD < 20%), accuracy (71.8~119.1%) and recovery (66.0~118.9%). The detection limits were < 3.1 ng/g for all analytes. The correlation coefficients for all the HCAs and acrylamide were > 0.995, showing excellent linearity. These methods for the detection of HCAs and acrylamide by LC-MS/MS were applied to real samples and were successfully used for quantitative monitoring in the total diet study and this can be applied to risk assessment in various food matrices.

• The Korean Journal of Pesticide Science
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• v.13 no.3
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• pp.197-202
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• 2009

Based on the insecticidal efficacy by insecticide treatment methods, neurophysiological responses were compared with the larvae of diamondback moth (DBM) and beet armyworm (BAW) using pyrethroids working on nervous system. By body spray method, all pyrethroids were showed lower insecticidal activity below 50% on the larvae of DBM and BAW. By leaf dipping method, DBM larvae were showed the insecticidal activity as 100% at 50 ppm deltamethrin, 80.0% at fenvalervate and 63.3% at permethrin. However, BAW larvae were showed lower insecticidal activity as similar as control in all concentration. In order to examine electrophysiological response on nervous system on DBM and BAW larvae when treated three insecticides, we investigated the voltage and reaction degree. The voltage of DBM were responded as high as $10^{-7}M$ in deltamethrin, $10^{-5}M$ in fenvalerate and $10^{-3}M$ in permethrin. However, those of BAW were showed dull responses with small variation of voltage to all three insecticides.

• Journal of Environmental Health Sciences
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• v.40 no.2
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• pp.114-126
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• 2014

Objectives: We aimed to develop a measurement method of five metabolites of trichloroethylene (TCE) in a concurrent biological sample, e.g., trichloroacetic acid (TCA), dichloroacetic acid (DCA), S-(1,2-dichlorovinyl) glutathione (DCVG), S-(1,2-dichlorovinyl)-L-cysteine (DCVC), and N-Acetyl-S-(1,2-dichlorovinyl)-L-cysteine (NAcDCVC) and to validate the method before application to pharmacokinetic study. Methods: TCE metabolites were simultaneously analyzed using high performance liquid chromatography coupled with electrospray ionization mass spectrometry (HPLC-ESI-MS/MS) with as little as 50 ${\mu}L$ of serum and urine. DCA, TCA and NAcDCVC were extracted with diethyl ether, while DCVC and DCVG were extracted by solid phase extraction. This method was validated according to the guidelines for bioanalytical method validation of the Korean National Institute of Toxicological Research. Then, we determined the five metabolites in five strains of mice at 24 hr after exposure to 1 g TCE /kg body weight. Results: The limits of detection for the five metabolites in biological samples ranged from 0.001 to 0.076 nmol/mL, which is comparable to or better than those previously reported. Most calibration curves showed good linearity ($R^2=0.99$), and between-batch variation was less than 20% expressing acceptable robustness and reproducibility. Using this method, we found TCA and DCA were detected in all test mice at 24 hr after the oral administration while NAcDCVC and DCVC were detected in some strains, which showed strain-dependent metabolism of TCE. Conclusions: The present method could provide robust and accurate measurements of major key metabolites of TCE in biological media, which allowed concurrent analysis of TCE metabolism for limited amounts of biospecimens.

• Safety and Health at Work
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• v.2 no.3
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• pp.282-289
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• 2011

Objectives: We sought to establish a novel method to generate nano-sized carbon black particles (nano-CBPs) with an average size smaller than 100 nm for examining the inhalation exposure risks of experimental rats. We also tested the effect of nano-CBPs on the pulmonary and circulatory systems. Methods: We used chemical vapor deposition (CVD) without the addition of any additives to generate nano-CBPs with a particle size (electrical mobility diameter) of less than 100nm to examine the effects of inhalation exposure. Nano-CBPs were applied to a nose-only inhalation chamber system for studying the inhalation toxicity in rats. The effect on the lungs and circulatory system was determined according to the degree of inflammation as quantified by bronchoalveolar lavage fluid (BALF). The functional alteration of the hemostatic and vasomotor activities was measured by plasma coagulation, platelet activity, contraction and relaxation of blood vessels. Results: Nano-CBPs were generated in the range of 83.3-87.9 nm. Rats were exposed for 4 hour/day, 5 days/week for 4 weeks to $4.2{\times}10^6$, $6.2{\times}10^5$, and $1.3{\times}10^5$ particles/$cm^3$. Exposure of nano-CBPs by inhalation resulted in minimal pulmonary inflammation and did not appear to damage the lung tissue. In addition, there was no significant effect on blood functions, such as plasma coagulation and platelet aggregation, or on vasomotor function. Conclusion: We successfully generated nano-CBPs in the range of 83.3-87.9 nm at a maximum concentration of $4.2{\times}10^6$ particles/$cm^3$ in a nose-only inhalation chamber system. This reliable method can be useful to investigate the biological and toxicological effects of inhalation exposure to nano-CBPs on experimental rats.

• Journal of Oriental Neuropsychiatry
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• v.20 no.2
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• pp.111-120
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• 2009

Objectives : This study was performed to investigate the effects of Needle Electrode Electrical Stimulation (NEES) on ischemia-induced cerebrovascular accidents. After obstruction and reperfusion of ${\ast}{\ast}$ arteries in white mice, the amounts of necrosis and inflammation related substances IL-6, Caspase-3, and PARP, C-fos were measured in neurons of the hippocampus. The following results were obtained. Methods : This study used 21 male specific pathogen free (SPF) SD (Sprague Dawley) rats, 8 weeks of age and approximately 300 g in weight, that were given at least 1 week to adapt to the lab environment Each exposed artery was completely occluded with non-absorbent suture thread and kept in that state for 5 minutes. The sutures were then removed to allow reperfusion of blood. Test group is control group for comparison with the common carotid artery occlusion models, a GI group that underwent common carotid artery occlusion, and a needle electrode electrical stimulation (NEES) group that underwent NEES after artery occlusion. The GI and NEES groups were given 12, 24, or 48 hours of reperfusion before NEES. NEES device (PG6, ITO, Japan, 9V, current, 2Hz) was used to stimulate the right and left acupoint ST36 of the SD rats for 30 minutes while they were sedated with 3% isoflurane. An immunohistochemistry test was done on the forebrains of the GI induced rats. All the data collected from this study was symbolized and analyzed using a statistics processing program (SPSS 12.0K/PC). The level of significance was set at ${\alpha}$=0.05 and a T-TEST analysis was used to find out the effects of treatment on each of the groups: the normal group, the CVA induced group, and the treatment after CVA induction group. Results : Both PARP and C-fos immuno-reactive cells, related to apoptosis, were greater in the GI groups than the NEES group. Caspase and IL-6 immuno-reactive cells, related to inflammation, were greater in the GI and NEES groups than the control group. Conclusions : This research was conducted to study the effects of NEES on CVA due to ischemia. Occlusion and reperfusion was performed on the common carotid arteries of white rats, after which amounts of substances related to neuron necrosis and inflammation - PARP, IL-6, Caspase-3, and C-fos - were measured in the Hippocampus