• Toxicological Research
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• v.33 no.1
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• pp.43-48
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• 2017

With ultraviolet and visible light exposure, some pharmaceutical substances applied systemically or topically may cause phototoxic skin irritation. The major factor in phototoxicity is the generation of reactive oxygen species (ROS) such as singlet oxygen and superoxide anion that cause oxidative damage to DNA, lipids and proteins. Thus, measuring the generation of ROS can predict the phototoxic potential of a given substance indirectly. For this reason, a standard ROS assay (ROS assay) was developed and validated and provides an alternative method for phototoxicity evaluation. However, negative substances are over-predicted by the assay. Except for ultraviolet A (UVA), other UV ranges are not a major factor in causing phototoxicity and may lead to incorrect labeling of some non-phototoxic substances as being phototoxic in the ROS assay when using a solar simulator. A UVA stimulator is also widely used to evaluate phototoxicity in various test substances. Consequently, we identified the applicability of a UVA simulator to the ROS assay for photoreactivity. In this study, we tested 60 pharmaceutical substances including 50 phototoxins and 10 non-phototoxins to predict their phototoxic potential via the ROS assay with a UVA simulator. Following the ROS protocol, all test substances were dissolved in dimethyl sulfoxide or sodium phosphate buffer. The final concentration of the test solutions in the reaction mixture was 20 to $200{\mu}M$. The exposure was with $2.0{\sim}2.2mW/cm^2$ irradiance and optimization for a relevant dose of UVA was performed. The generation of ROS was compared before and after UVA exposure and was measured by a microplate spectrophotometer. Sensitivity and specificity values were 85.7% and 100.0% respectively, and the accuracy was 88.1%. From this analysis, the ROS assay with a UVA simulator is suitable for testing the photoreactivity and estimating the phototoxic potential of various test pharmaceutical substances.

• 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.

• Journal of Food Hygiene and Safety
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• v.33 no.4
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• pp.240-247
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• 2018

This study was carried out to determine the levels of lead and cadmium as found in nine agricultural products (n = 578) sold in Korea, and to estimate the risk to human health that is summarily associated with their intake. The concentrations of Pb and Cd were measured using an ICP-MS after microwave digestion in this study. The average contents of Pb and Cd were measured as 0.014 and 0.017 mg/kg for barley, 0.006 and 0.005 mg/kg for mung bean, 0.008 and 0.007 mg/kg for kidney bean, 0.010 and 0.004 mg/kg for green bean, 0.008 and 0.001 mg/kg for pineapple, 0.016 and 0.002 mg/kg for apricot, 0.015 and 0.002 mg/kg for Japanese apricot, 0.021 and 0.002 mg/kg for plum and 0.019 and 0.003 mg/kg for jujube, respectively. The levels of Pb and Cd in the study samples were less than the maximum residual levels established by the European Union (EU), CODEX, and the Korea Food Code. As we have seen, the daily dietary exposures of Pb and Cd from these agricultural products for the general population were noted as 0.067% of PTWI ($25{\mu}g/kg$ b.w./week) and 0.28% of PTMI ($25{\mu}g/kg$ b.w./month), respectively. In line with the study conclusions, these results suggest that the current dietary intakes of Pb and Cd from these agricultural products in Korea have no appreciable risk effects on health for humans as noted in this experiment.

• Journal of Microbiology and Biotechnology
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• v.33 no.10
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• pp.1281-1291
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• 2023

Infectious diseases caused by drug-resistant Escherichia coli (E. coli) pose a critical concern for medical institutions as they can lead to high morbidity and mortality rates. In this study, amygdalin exhibited anti-inflammatory and antioxidant activities, as well as other potentials. However, whether it could influence the drug-resistant E. coli-infected cells remained unanswered. Amygdalin was therefore tested in a cellular model in which human macrophages were exposed to resistant E. coli. Apoptosis was measured by flow cytometry and the lactate dehydrogenase (LDH) assay. Western immunoblotting and quantitative reverse-transcription polymerase chain reaction (qRT-PCR) were used to quantify interleukin-18 (IL-18), interleukin-1β (IL-1β), and interleukin-6 (IL-6). The production of reactive oxygen species (ROS) in macrophages was detected by ROS kit. The expression of pan-apoptotic proteins in macrophages was measured by qRT-PCR and Western immunoblotting. Drug-Resistant E. coli inhibited cell viability and enhanced apoptosis in the cellular model. In cells treated with amygdalin, this compound can inhibit cell apoptosis and reduce the expression of pro - inflammatory cytokines such as IL-1β, IL-18 and IL-6. Additionally, it decreases the production of PANoptosis proteins, Furthermore, amygdalin lowered the levels of reactive oxygen species induced by drug-resistant E. coli, in cells, demonstrating its antioxidant effects. Amygdalin, a drug with a protective role, alleviated cell damage caused by drug-resistant E. coli in human macrophages by inhibiting the PANoptosis signaling pathway.

• Korean Journal of Food Science and Technology
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• v.44 no.6
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• pp.666-672
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• 2012

The present study was carried out in order to assess the dietary exposure as well as the risk for lead (Pb) and cadmium (Cd) exposure through mushrooms among the Korean population. Various samples (n=536) covering 17 kinds of mushrooms were collected from retail outlets and markets in Korea. The contents of Pb were 0.005 (King oyster)-0.026 (Matsutake) mg/kg in raw mushrooms and 0.014 (Oyster)-16.411 (Manna lichen) mg/kg in dry mushrooms, respectively. The contents of Cd were 0.002 (Enoki)-0.205 (Hericium erinaciium) mg/kg in raw mushrooms and 0.021 (Vegetable worms)-2.650 (Agaricus blazei Muill) mg/kg in dry mushrooms, respectively. The mean dietary exposure of Pb for the general population was $0.053{\mu}g/day$, taking 0.03% of provisional tolerable weekly intake (PTWI). The mean dietary exposure of Cd for the general population was $0.168{\mu}g/day$, corresponding to 0.37% of provisional tolerable monthly intake (PTMI). Therefore, the level of the overall dietary exposure to heavy metals through mushroom for the Korean population was far below the recommended JECFA levels, indicating little possibility of concern.

• Journal of Food Hygiene and Safety
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• v.25 no.4
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• pp.395-401
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• 2010

This research was carried out as a survey on the contents of Lead (Pb) and Cadmium (Cd) in 5 type agricultural products unestablished safety guideline in Korea. The average levels of Pb: onion 0.010 mg/kg, cucumber 0.018 mg/kg, garlic 0.012 mg/kg, green pepper 0.027 mg/kg, sesame 0.029 mg/kg. The average levels of Cd: onion 0.006 mg/kg, cucumber 0.002 mg/kg, garlic 0.008 mg/kg, green pepper 0.011 mg/kg, sesame 0.024 mg/kg. The present result of this study showed that Pb and Cd contents in the whole samples were less than the maximum residual levels of the codex standard. The levels of exposure assessment for Pb and Cd by intake from vegetables and sesame were merely at $1.3{\times}10^{-4}$(mean) ~ $5.1{\times}10^{-4}$($95^{th}$ percentiles) ${\mu}$g/kg bw/day for Pb, $7.5{\times}10^{-5}$(mean) ~ $3.6{\times}10^{-4}$($95^{th}$ percentiles) ${\mu$}g/kg bw/day for Cd. The data from this research will be valuable source for database construction for science-based safety control and management for the trace metal contamination in food including agricultural products.

• Nutrition Research and Practice
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• v.6 no.5
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• pp.436-443
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• 2012

Previous Korean total diet studies (KTDSs) have estimated dietary exposure to toxic chemicals based on 110-120 representative foods selected from over 500 foods appeared in the Korea National Health & Nutrition Examination Surveys (KNHANES), which would result in a possible underestimation. In order to find measures for a closer-to-real estimate of dietary exposure to heavy metals, this study examined the feasibility of mapping foods to the representative foods in the KTDS by comparing estimates. In mapping, those foods not analyzed in the 2009 KTDS (443 out of 559 foods appeared in the 2007 KNHANES) were mapped to the 114 representative foods used in the 2009 KTDS based on the closeness in regards to biological systematics and morphological similarity. Dietary exposures to total mercury and lead were re-estimated using the content of total mercury and lead in 114 foods analyzed in the 2009 KTDS, food intake, and individual's own body weight for respondents in the 2007 KNHANES instead of mean body weight of Koreans used in the 2009 KTDS. The re-estimates of exposure with mapping were approximately 50% higher than the original estimates reported in the 2009 KTDS. In addition, mapping enabled the comparison of percentile distribution of the exposure among populations of different age groups. In conclusion, estimates via mapping resulted in a more comprehensive estimation of dietary exposure to heavy metals present in foods that Koreans consume.

• Journal of Pharmaceutical Investigation
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• v.30 no.3
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• pp.191-199
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• 2000

Genomics is providing targets faster than we can validate them and combinatorial chemistry is providing new chemical entities faster than we can screen them. Historically, the drug discovery cascade has been established as a sequential process initiated with a potency screening against a selected biological target. In this sequential process, pharmacokinetics was often regarded as a low-throughput activity. Typically, limited pharmacokinetics studies would be conducted prior to acceptance of a compound for safety evaluation and, as a result, compounds often failed to reach a clinical testing due to unfavorable pharmacokinetic characteristics. A new paradigm in drug discovery has emerged in which the entire sample collection is rapidly screened using robotized high-throughput assays at the outset of the program. Higher-throughput pharmacokinetics (HTPK) is being achieved through introduction of new techniques, including automation for sample preparation and new experimental approaches. A number of in vitro and in vivo methods are being developed for the HTPK. In vitro studies, in which many cell lines are used to screen absorption and metabolism, are generally faster than in vivo screening, and, in this sense, in vitro screening is often considered as a real HTPK. Despite the elegance of the in vitro models, however, in vivo screenings are always essential for the final confirmation. Among these in vivo methods, cassette dosing technique, is believed the methods that is applicable in the screening of pharmacokinetics of many compounds at a time. The widespread use of liquid chromatography (LC) interfaced to mass spectrometry (MS) or tandem mass spectrometry (MS/MS) allowed the feasibility of the cassette dosing technique. Another approach to increase the throughput of in vivo screening of pharmacokinetics is to reduce the number of sample analysis. Two common approaches are used for this purpose. First, samples from identical study designs but that contain different drug candidate can be pooled to produce single set of samples, thus, reducing sample to be analyzed. Second, for a single test compound, serial plasma samples can be pooled to produce a single composite sample for analysis. In this review, we validated the issue whether the second method can be applied to practical screening of in vivo pharmacokinetics using data from seven of our previous bioequivalence studies. For a given drug, equally spaced serial plasma samples were pooled to achieve a 'Pooled Concentration' for the drug. An area under the plasma drug concentration-time curve (AUC) was then calculated theoretically using the pooled concentration and the predicted AUC value was statistically compared with the traditionally calculated AUC value. The comparison revealed that the sample pooling method generated reasonably accurate AUC values when compared with those obtained by the traditional approach. It is especially noteworthy that the accuracy was obtained by the analysis of only one sample instead of analyses of a number of samples that necessitates a significant man-power and time. Thus, we propose the sample pooling method as an alternative to in vivo pharmacokinetic approach in the selection potential lead(s) from combinatorial libraries.

• Journal of Food Hygiene and Safety
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• v.27 no.4
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• pp.456-460
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• 2012

This study was carried out as a survey on the level of lead (Pb), cadmium (Cd), arsenic (As) and mercury (Hg) in 5 items of agricultural products (lettuce, pumpkin, head lettuce, cabbage and crown daisy) for which safety guidelines are not yet established in Korea. The 407 samples were collected from local markets in 9 regional places and the levels of metals were measured by ICP-MS and mercury analyzer. The average levels of Pb, Cd, As and Hg were 0.026, 0.018, 0.008 and 0.003 mg/kg for lettuce, 0.002, 0.001, 0.001 and 0.0006 mg/kg for pumpkin, 0.002, 0.005, 0.001 and 0.0005 mg/kg for head lettuce, 0.001, 0.002, 0.0002 and 0.0006 mg/kg for cabbage and 0.022, 0.014, 0.006 and 0.004 mg/kg for crown daisy. For risk assessment, the daily dietary exposures of Pb, Cd and Hg by intake of these agricultural products were calculated and compared with PTWI (provisional tolerable weekly intake) established by JECFA. The daily dietary exposure of heavy metals by intake of these agricultural products were 0.13, 0.56 and 0.09% of PTWI, respectively. These monitoring results will be utilized as fundamental data for the establishment of Korean standards of Pb, Cd, As and Hg in 5 items of agricultural products and valuable source for DB construction for science-based safety control of heavy metals in foods including agricultural products.

• Korean Journal of Food Science and Technology
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• v.34 no.6
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• pp.992-997
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• 2002

Contents of heavy metals in sugar products were estimated to provide a scientific basis for standardization of Korea Food Code of heavy metals. The contents of mercury (Hg), lead (Pb), cadmium (Cd), arsenic (As) and copper (Cu) were determined in 285 sugar product samples using a mercury analyzer, atomic absorption spectrophotometer, and inductively coupled plasma spectrometer. The values of heavy metals in sugar products $[minimum{\sim}maximum\;(mean),\;mg/kg]$ were as follows: $Hg,\;N.D.{\sim}0.006 (0.001);$ $Pb,\;N.D.{\sim}0.47 (0.03);$ $Cd,\;N.D.{\sim}0.06(0.005);\;As,\;N.D.{\sim}0.10(0.004);\;Cu,\;N.D.{\sim}1.89(0.15)$. These results show that metal contents of domestic sugar products are similar to those reported in other countries. Weekly average intakes of lead, cadmium, and mercury from sugar products were $0.004{\sim}0.1%$ of Provisional Tolerable Weekly Intake set by FAO/WHO Joint Food Additives and Contaminants Committee to evaluate the safeties of sugar products.