• Toxicological Research
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• v.32 no.1
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• pp.9-14
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• 2016

The National Toxicology Program Interagency Center for the Evaluation of Alternative Toxicological Methods (NICEATM) provides validation support for US Federal agencies and the US Tox21 interagency consortium, an interagency collaboration that is using high throughput screening (HTS) and other advanced approaches to better understand and predict chemical hazards to humans and the environment. The use of HTS data from assays relevant to the estrogen receptor signaling data pathway is used as an example of how HTS data can be combined with computational modeling to meet the needs of US agencies. As brief summary of US efforts in the areas of biologics testing, acute toxicity, and skin sensitization will also be provided.

• Korean Journal of Pharmacognosy
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• v.40 no.3
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• pp.184-189
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• 2009

A simple and reliable reverse phase HPLC method of Coptidis Rhizoma and Salviae Miltiorrhizae Radix were developed to determine pharmacologically active marker compounds. The water-extract of two natural medicines were evaluated by the HPLC methods. The stability test for two extract were examined for five months. However, no significant change in the content of the marker compounds of each extract observed during the time of investigation.

• Korean Journal of Environmental Agriculture
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• v.8 no.2
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• pp.148-171
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• 1989

• Archives of Pharmacal Research
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• v.22 no.2
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• pp.143-150
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• 1999

melatonin (MLT), N-acetyl-5-methoxytryptamine, is mainly secreted by the pineal gland. The ultraviolet (UV), infrared (IR) and 1H-NMR spectra of irradiated and non-irradiated MLT were measured, and phototoxicity tests of MLT, anthracence (positive control) and sodium lauryl sulfate (SLS, negative control) were performed. The methods employed include both in vitro test such as MTS assay using the human fibroblast cell and yeast growth inhibition assay using Candida albicans and in vivo method using the skin of guinea pig. UV absorption spectra and 1H-NMR spectra of MLT were changed by UVA (365 nm, 15 J/$\textrm{cm}^2$), but IR spectra of MLT were not changed. The fifty percent inhibitory concentration (IC50) ratio (UV-/UV+) of MLT was 10. The inhibition zone of irradiated-paper disks treated with MLT was not observed. According to the results of histophathological examination, no pathologic lesion was observed in the non-irradiated group, but slight degeneration of keratinocytes in the epidermis, homorrhage and vasodilation in dermis were observed in the irradiated group. These results indicated that the molecular structure of MLT is altered by UVA to unidentified photoproducts and a moderate phototoxicity of MLT is predicted.

• Korean Journal of Pharmacognosy
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• v.39 no.3
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• pp.241-245
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• 2008

Quantitative methods for the marker compounds of Cimicifugae Rhizoma, Achyranthis Radix, Artemisiae Capillaris Herba, Moutan Cortex Radicis and Arecae Semen, respectively, were developed using HPLC-DAD. Using the established methods, each extract of the natural medicines were evaluated. In addition, long term and accelerated stability test in the extracts were examined for six months. No significant change in content of the marker compounds of each extract observed during the time of investigation.

• Toxicological Research
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• v.33 no.2
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• pp.107-118
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• 2017

Although alternative test methods based on the 3Rs (Replacement, Reduction, Refinement) are being developed to replace animal testing in reproductive and developmental toxicology, they are still in an early stage. Consequently, we aimed to develop alternative test methods in male animals using mouse spermatogonial stem cells (mSSCs). Here, we modified the OECD TG 489 and optimized the in vitro comet assay in our previous study. This study aimed to verify the validity of in vitro tests involving mSSCs by comparing their results with those of in vivo tests using C57BL/6 mice by gavage. We selected hydroxyurea (HU), which is known to chemically induce male reproductive toxicity. The 50% inhibitory concentration ($IC_{50}$) value of HU was 0.9 mM, as determined by the MTT assay. In the in vitro comet assay, % tail DNA and Olive tail moment (OTM) after HU administration increased significantly, compared to the control. Annexin V, PI staining and TUNEL assays showed that HU caused apoptosis in mSSCs. In order to compare in vitro tests with in vivo tests, the same substances were administered to male C57BL/6 mice. Reproductive toxicity was observed at 25, 50, 100, and 200 mg/kg/day as measured by clinical measures of reduction in sperm motility and testicular weight. The comet assay, DCFH-DA assay, H&E staining, and TUNEL assay were also performed. The results of the test with C57BL/6 mice were similar to those with mSSCs for HU treatment. Finally, linear regression analysis showed a strong positive correlation between results of in vitro tests and those of in vivo. In conclusion, the present study is the first to demonstrate the effect of HU-induced DNA damage, ROS formation, and apoptosis in mSSCs. Further, the results of the current study suggest that mSSCs could be a useful model to predict male reproductive toxicity.

• Toxicological Research
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• v.32 no.3
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• pp.259-267
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• 2016

Animal testing was used traditionally in the cosmetics industry to confirm product safety, but has begun to be banned; alternative methods to replace animal experiments are either in development, or are being validated, worldwide. Research data related to test substances are critical for developing novel alternative tests. Moreover, safety information on cosmetic materials has neither been collected in a database nor shared among researchers. Therefore, it is imperative to build and share a database of safety information on toxicological mechanisms and pathways collected through in vivo, in vitro, and in silico methods. We developed the CAMSEC database (named after the research team; the Consortium of Alternative Methods for Safety Evaluation of Cosmetics) to fulfill this purpose. On the same website, our aim is to provide updates on current alternative research methods in Korea. The database will not be used directly to conduct safety evaluations, but researchers or regulatory individuals can use it to facilitate their work in formulating safety evaluations for cosmetic materials. We hope this database will help establish new alternative research methods to conduct efficient safety evaluations of cosmetic materials.

• Toxicological Research
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• v.30 no.3
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• pp.185-191
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• 2014

Statistical methods are frequently used in toxicology, yet it is not clear whether the methods employed by the studies are used consistently and conducted based on sound statistical grounds. The purpose of this paper is to describe statistical methods used in top toxicology journals. More specifically, we sampled 30 papers published in 2014 from Toxicology and Applied Pharmacology, Archives of Toxicology, and Toxicological Science and described methodologies used to provide descriptive and inferential statistics. One hundred thirteen endpoints were observed in those 30 papers, and most studies had sample size less than 10, with the median and the mode being 6 and 3 & 6, respectively. Mean (105/113, 93%) was dominantly used to measure central tendency, and standard error of the mean (64/113, 57%) and standard deviation (39/113, 34%) were used to measure dispersion, while few studies provide justifications regarding why the methods being selected. Inferential statistics were frequently conducted (93/113, 82%), with one-way ANOVA being most popular (52/93, 56%), yet few studies conducted either normality or equal variance test. These results suggest that more consistent and appropriate use of statistical method is necessary which may enhance the role of toxicology in public health.

• Safety and Health at Work
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• v.2 no.1
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• pp.34-38
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• 2011

Objectives: The antimicrobial activity of silver nanoparticles has resulted in their widespread use in many consumer products. Yet, despite their many advantages, it is also important to determine whether silver nanoparticles may represent a hazard to the environment and human health. Methods: Thus, to evaluate the genotoxic potential of silver nanoparticles, in vivo genotoxicity testing (OECD 474, in vivo micronuclei test) was conducted after exposing male and female Sprague-Dawley rats to silver nanoparticles by inhalation for 90 days according to OECD test guideline 413 (Subchronic Inhalation Toxicity: 90 Day Study) with a good laboratory practice system. The rats were exposed to silver nanoparticles (18 nm diameter) at concentrations of $0.7\;{\times}\;10^6$ particles/$cm^3$ (low dose), $1.4\;{\times}\;10^6$ particles/$cm^3$ (middle dose), and $2.9\;{\times}\;10^6$ particles/$cm^3$ (high dose) for 6 hr/day in an inhalation chamber for 90 days. The rats were killed 24 hr after the last administration, then the femurs were removed and the bone marrow collected and evaluated for micronucleus induction. Results: There were no statistically significant differences in the micronucleated polychromatic erythrocytes or in the ratio of polychromatic erythrocytes among the total erythrocytes after silver nanoparticle exposure when compared with the control. Conclusion: The present results suggest that exposure to silver nanoparticles by inhalation for 90 days does not induce genetic toxicity in male and female rat bone marrow in vivo.

• Korean journal of applied entomology
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• v.31 no.1
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• pp.1-6
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• 1992

These studies were carried out to compare toxicological test methods of two spotted spider mite, Tetranychus urticae Koch,; and to investigate relationship between in vivo resistant level of highly acaricide-selected population, and in vitro insensitivity of the AChE in the same population to carbophenothion and ethion. The slide dip method (CV = 8.7%) was of more accuracy and suitability than that of the leaf dip method(CV=12.2%) and leaf disc method (CV= 13.6 %) in determination of the resistant levels of twospotted spider mite to acaricides. The slide dip method also had the advantages of simple treatment with different populations on a slide at the same time, standardization of post-treatement conditions and living plants exclud¬ed from the test. Even though the topical application method(CV =8.1 %) showed high accuracy, it had the demerits of the much time consuming, need of expensive equipment and difficulty of test manipulation. For a limited time, the 22nd successive carbophenothion-selected population of two-spotted spider mite showed 156- and 128-fold resistant levels to carbophenothion and ethion(both alPs), respectively. However, the 24th successive ethion-selected population revealed 64.1- and 65-fold resistant levels to ethion and carbophenothion, respectively. In the inhibition of AChE activity, the carbophenothion-selected population showed 3.3- and 2.7-fold insensitivity in AChE activity to carbophenothion and ethion, respectively. Likewise, the ethion -selected population exhibited 3- and 2.6-fold insensitivity in AChE activity to carbophenothion and ethion, respectively, as compared with that of susceptible population. As a result, a good relation was recognized between in vivo resistance to organophosphorous acaricides and in vitro insensitivity of the AChE to corresponding inhibitors.