• Proceedings of the Korea Environmental Mutagen Society Conference
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• 2004.05a
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• pp.102-103
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• 2004

• Toxicological Research
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• v.20 no.1
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• pp.1-11
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• 2004

Evaluation of toxicological pathology is to some extend subjective judgments by pathologist and the accuracy of pathologist's works is based on the individual training and experiences. It has been required to establish a peer review system for toxicologic pathology and these review system has been employed by various practice of toxicological pathology. It would be pointed out that the possible causes of drifts in pathology are due to 1) lack of knowledge or experience of individual pathologists, 2) poorly maintained consistence of grading among animals in study, 3) different interpretation of findings between pathologists, or 4) pathology data processing. Example cases of diagnostic errors and current practice of peer review including tissue selection criteria, documentation and problem resolution for short-term and carcinogenicity studies were introduced. For sound regulatory system and high integrity of practice in toxicological pathology, current approaches of peer review system were reviewed.

• Korean Journal of Veterinary Pathology
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• v.1 no.2
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• pp.91-96
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• 1997

General steps in the discovery and development of novel drugs in the United States are presented. The first step is the discovery of novel drugs. Brief histories and mechanisms of a few novel drugs in the American market are outlined. In this presentation preclinical animal toxicologic studies (drug safety evaluateion) are emphasized in regard to drug development. When preclinical animal studies have defined the toxicity and the doses at which it occurs an Investigational new Drug Application (IND) is submitted to the Food and Drug Administration (FDA) An IND notifies the FDA the intention to begin testing a novel drug in human subjects.

• Toxicological Research
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• v.26 no.3
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• pp.217-222
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• 2010

Many studies have reported that bleomycin, anti-cancer drug, induces pulmonary fibrosis as a side effect. However, few investigations have focused on the dose-response effects of bleomycin on pulmonary fibrosis. Therefore, in the present study, we investigated the effects of different doses of bleomycin in male mice. ICR mice were given 3 consecutive doses of bleomycin: 1, 2, or 4 mg/kg in bleomycin-treated (BT) groups and saline only in vehicle control (VC) groups. The animals were sacrificed at 7 and 24 days postinstillation. The severity of pulmonary fibrosis was evaluated according to inflammatory cell count and lactate dehydrogenase (LDH) activity in the broncho alveolar lavage fluid (BALF), and lung tissues were histologically evaluated after hematoxylin and eosin (H&E), and Masson's trichrome staining. BT groups exhibited changed cellular profiles in BAL fluid compared to the VC group, which had an increased number of total cells, neutrophils, and lymphocytes and a modest increase in the number of macrophages at 7 days post-bleomycin instillation. Moreover, BT groups showed a dose-dependent increase in LDH levels and inflammatory cell counts. However, at 24 days after treatment, collagen deposition, interstitial thickening, and granulomatous lesions were observed in the alveolar spaces in addition to a decrease in inflammatory cells. These results indicate that pulmonary fibrosis induced by 4 mg/kg bleomycin was more severe than that induced by 1 or 2 mg/kg. These data will be utilized in experimental animal models and as basic data to evaluate therapeutic candidates through non-invasive monitoring using the pulmonary fibrosis mouse model established in this study.

• Korean Journal of Veterinary Pathology
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• v.1 no.1
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• pp.66-71
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• 1997

Eighteen NZW rabbits used for local skin irritation study were examined grossly and microscopically for natural infection with Encephalitozoon cuniculi. For microscopic tissue evaluation histochemical techniques such as PAS Gram iron hematoxylin and HE stain were used. Although rabbits in the study had no abnormal clinical signs 7/18(38.9%) animals were microscopically infected with E. cuniculi. The affected rabbits had gray-whitish and depressed approximately 0.1∼0.6 cm diameter lesions in the kidneys. All other organs examined were grossly unremarkable. Histopathologically however in addition to segmental interstitial nephritis focal lymphocytic myocarditis and granulomatous inflammatory reaction in portal areas of the liver multifocal granulomatous foci with vasculitis were present in the brain kidney and lungs. Aggregates of minute oval organisms were observed in brain and kidney sections frequently within the granulomatous foci and sometimes without any inflammatory reaction particularly in the renal tubules. in histochemical stains the organisms were gram positive stained with iron hematoxylin and had PAS positive granule at one pole. They measured approximately 1.5×2.5μm consistent with E. cuniculi. Histochemical characterization is important to differentiate E. cuniculi from other common protozoal infection such as Toxoplasma gondii. This study demonstrate the importance of subclinical. E. cunuculi infection and the associated histological alterations may interfere with tissue evaluation in toxicologic studies.

• Proceedings of the Korean Society of Veterinary Pathology Conference
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• 2002.11a
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• pp.12-20
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• 2002

1. 질병명 : Interstitial pneumonia 2. 본질명의 개요 역사 및 역학 Michael R Elwell, Joel F Mahler, G N Rao: “ Have You Seen This\ulcorner" ; Inflammatory Lesions in the Lungs of Rats. Toxicologic Pathology, 25: 529-531, 1997. Male and female F344 rats, approximately 19 weeks old, from prechronic toxicity studies performed for NTP/NIEHS over a period of several years at different laboraories located throughout the US. The rats were supplied by 2 different production colonies located in the eastern and western areas of the US. Gross findings ㆍ In some rats the lesions were noted as pale or tan foci in the lungs Microscopic findings ㆍ A prominent increase in perivascular lymphocytes ㆍ A variable increase in the amount of peribronchiolar lymphoid tissues ㆍ Frequently an inflammatory cell exudate within the alveolar spaces ㆍ Focal hyperplasia of alveolar type 2 cells Similar lung lesions were not observed in B6C3F1 mice concurrently on study with affected rats. Similar lung lesions were not observed in F344 rats at the end of 2-year NTP studies. Virus, mycoplasma, bacterial serology, bacterial culture, protozoal identification: negative EM: ㆍ No virus particles were identified. ㆍ Rod shaped bacteria were observed in the alveolar spaces. ㆍ Bacteria were not observed in the bronchi/ bronchioles of rats with alveolar organism. (omitted)

• Environmental Analysis Health and Toxicology
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• v.25 no.3
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• pp.215-222
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• 2010

The market size of engineered nanoparticles is rapidly increasing due to the fast application of nanotechnologies into different industries and consumer products. The development of new technology and materials has improved human's quality of life, but it also entails the possibility of exposure to new materials. In this study, we compared the distribution in the body by the inflow of silver nanoparticles having another diameter and shape at 1 h or 24 h after injection via the tail vein. And, we compared the cell composition and cytokine concentration in BAL fluid, and histopathological changes. As results, discharge of silver nanoparticles having small diameter and sphere shape was more rapid than that of big diameter or plate shape. It is estimated that the toxicity in liver and lung was proportional to accumulation level. The persistence of inflammation was also longer in mice treated with plate shape. Consequently, we suggest that the first choice of silver nanoparticles having small diameter and sphere shape in applying is desirable.

• Toxicological Research
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• v.26 no.4
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• pp.293-300
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• 2010

tert-Butyl acetate (TBAc) is an organic solvent, which is commonly used in architectural coatings and industrial solvents. It has recently been exempted from the definition of a volatile organic compound (VOC) by the Air Resources Board (ARB). Since the use of TBAc as a substitute for other VOCs has increased, thus its potential risk in humans has also increased. However, its inhalation toxicity data in the literature are very limited. Hence, inhalation exposure to TBAc was carried out to investigate its toxic effects in this study. Adult male rats were exposed to TBAc for 4 h for 1 day by using a nose-only inhalation exposure chamber (low dose, $2370\;mg/m^3$ (500 ppm); high dose, $9482\;mg/m^3$ (2000 ppm)). Shamtreated control rats were exposed to clean air in the inhalation chamber for the same period. The animals were killed at 2, 7, and 15 days after exposure. At each time point, body weight measurement, bronchoalveolar lavage fluid (BALF) analysis, histopathological examination, and biochemical assay were performed. No treatment-related abnormal effects were observed in any group according to time course. Based on those findings, the median lethal concentration ($LC_{50}$) of TBAc was over $9482\;mg/m^3$ in this study. According to the MSDS, the 4 h $LC_{50}$ for TBAc for rats is over $2230\;mg/m^3$. We suggested that this value is changed and these findings may be applied in the risk assessment of TBAc which could be beneficial in a sub-acute study.