• Biomolecules & Therapeutics
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• v.9 no.4
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• pp.311-317
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• 2001

YHB6211, a newly developed recombinant human granulocyte colonystimulating factor, was administered at dose levels of 0, 3, 15, and 75 $\mu$g/kg/day intravenously to the pregnant New Zealand White rabbits (20 rabbits per group) during the organogenetic period, days 6 to 18 of gestation. All dams were subjected to Caesarian section on day 28 of gestation and their fetuses were examined for external, visceral, and skeletal abnormalities. No abnormalities in clinical signs, body weight changes, gross findings, mortality, and external appearance were found in all dams and fetuses exposed to 0, 3, and 15 $\mu$g/kg/day of YHB6211. However, in the group treated with 75 $\mu\textrm{g}$/kg/day of YHB6211, maternal body and uterine weights, fetal body weights and length, and the number of live fetuses were significantly decreased and further fetal mortality was remarkably increased. It is suggested that YHB6211 may have no side effect up to the dose level of 15 $\mu$g/kg/day, and there would be no teratogenicity for fetuses of rabbits up to 75 $\mu\textrm{g}$/kg/day even if it may have some toxic effects over 75$\mu\textrm{g}$/kg/day for dams and fetuses of rabbits.

• Development and Reproduction
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• v.26 no.4
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• pp.155-163
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• 2022

Human pluripotent stem cells (hPSCs) can give rise to a vast array of differentiated derivatives, which have gained great attention in the field of in vitro toxicity evaluation. We have previously demonstrated that hPSC-derived alveolar epithelial cells (AECs) are phenotypically and functionally similar to primary AECs and could be more biologically relevant alternatives for assessing the potential toxic materials including in fine dust and cigarette smoking. Therefore, in this study, we employed hPSC-AECs to evaluate their responses to exposure of various concentrations of diesel particulate matter (dPM), cigarette smoke extract (CSE) and nicotine for 48 hrs in terms of cell death, inflammation, and oxidative stress. We found that all of these toxic materials significantly upregulated the transcription of pro-inflammatory cytokines such as IL-1α, IL-β, IL-6, and TNF-α. Furthermore, the exposure of dPM (100 ㎍/mL) strongly induced upregulation of genes related with cell death, inflammation, and oxidative stress compared with other concentrations of CSE and nicotine. These results suggest that hPSC-AECs could be a robust in vitro platform to evaluate pulmotoxicity of various air pollutants and harmful chemicals.

• Proceedings of the Korea Society of Environmental Biology Conference
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• 2005.12a
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• pp.38-45
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• 2005

The egg bags of Korean salamander(Hynobius leechii) were collected from farmlands in Gyeongsangnam-do area. The assumed breeding time, numerical variation of embryos in each egg bag, mortality and the rates of abnormalities were investigated. The toxicity of benomyl, the metabolite carbendazim and BIC which were frequently spread in agricultural area and caused spontaneous embryonic malformation was investigated. The assumed breeding time between the end of February and the end of March has the difference about a month because of a habitat and it takes about 2 or 3 weeks from laying eggs to hatching. The length of each egg bag and the number of embryos were very varied in each area. It is due to geographical variation. Among egg bags in total study area, only 406 of egg bags(17.70% of total egg bags) developed all of embryos to normal larvae, and 78.49% of total embryos were normally developed. The patterns of spontaneous embryonic malformation were 26 species from A to Z and the abnormal patterns in individual were 8 species and above. the geographical differences about the abnormal pattern were identified and 11 habitats categorized 4 groups. The most frequent abnormality in Gyeongsangnam-do area is the dysplasia of external gill. The caudal dysplasia, abdominal blister and dysplasia of fin were also frequently observed. Individuals showing severe external defect were histologically studied and they showed retinal hypo-pigmentation, thyroid carcinoma, somatic muscular dysplasia, degeneration of cephalic neuron and various organ dysplasia. Benomyl and carbendazim were treated by 10pM$^{\sim}$10uM and BIC was treated by 1$^{\sim}$40ppm to know the effect of toxicity about toxic substance of salamander. After benomyl was treated, a survival rate was sharply dropped from 2 to 8 days. $LC_{100}$ identified in $1{\mu}M$, $LC_{50}$ identified between 100nM and $1{\mu}M$. $EC_{50}$ was assumed between 10nM and 100nM. The prevalent external malformation was abdomen swelled abnormally and histo-pathological effects were abdomen, neural tube and lens hernia. This suggests that benomyl is the toxicitic substance which inhibits the development of digestive system and nervous system. The result of treated carbendazim was similar to that of the treated benomyl. The survival rate is sharply dropped between 2 and 6 days. $LC_{100}$ was identified $1{\mu}M$ and $LC_{50}$ was identified between 10nM and 100nM. This shows that cabendazim has stronger lethal toxicity than benomyl. Ventral blister, eye dysplasia and cephalic dysplasia in the individual of external malformation mean that cabendazim affected nervous system much more than benomyl. Because the toxicity of BIC affected less in the beginning but affected more in the near hatching period, the period causing toxicity is somewhat different. $LC_{100}$ identified near 40ppm and $LC_{50}$ identified near 25ppm. The external defect shows mainly ventral blister and histo-pathological results show intestinal deformities. This result suggests the BIC inhibited strongly the development of digestive system. These abnormal developments may be caused by antimitotic action, inhibition of tubulin complex, destruction of microtubule, inhibitions of neurulation and closing of neural fold, and by the inhibition of movement of neural crest cells of benomyl. These abnormal developments may be caused by the rupture of epithelium, the loss of microtubule, the reduction of spindle size, the inhibition of spindle assembly formation, the destruction of spindle poles of carbendazim. These abnormal developments may be caused cytotoxicity by inhibition of the synthesis of a number of macromolecules and similar reaction the inhibition of benomyl.

• Asian-Australasian Journal of Animal Sciences
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• v.15 no.4
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• pp.485-493
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• 2002

Different factors may affect the sensitivity of porcine oocytes during cryopreservation. The effect of two methods (cooling and vitrification), four cryoprotectants [glycerol (GLY), 1, 2-propanediol (PROH), dimethyl sulfoxide (DMSO) or ethylene glycol (EG)] and two vitrification media (1 M sucrose (SUC)+8 M EG; 8 M EG) on the developmental capacity of porcine oocytes at the germinal vesicle (GV) stage or after IVM at the metaphase II (M II) stage were examined. Survival was assessed by FDA staining, maturation and cleavage following IVF and IVC. A toxicity test for different cryoprotectants (GLY, PROH, DMSO, EG) was conducted at room temperature before cooling. GV and M II-oocytes were equilibrated stepwise in 1.5 M cryoprotectant and diluted out in sucrose. The survival rate of GV-oocytes in the GLY group was significantly lower (82%, p<0.01) than that of the other group (92 to 95%). The EG group achieved a significantly higher maturation rate (84%, p<0.05) but a lower cleavage rate (34%, p<0.01) than the DMSO group and the controls. For M II-oocytes, the survival rates for all groups were 95 to 99% and the cleavage rate of the GLY group was lower than the PROH-group (21 vs 43%, p<0.01). After cooling to $10^{\circ}C$, the survival rates of GV-oocytes in the cryoprotectant groups were 34 to 51%, however, the maturation rates of these oocytes were low (1%) and none developed after IVF. For M II-oocytes, the EG group showed a significantly higher survival rate than those of the other cryoprotectant groups (40% vs 23-26%, p<0.05) and the cleavage rates of PROH, DMSO and EG group reached only 1 to 2%. For a toxicity test of different vitrification media, GV and M II-oocytes were equilibrated stepwise in 100% 8 M EG (group 1) and 1 M SUC + 8 M EG (group 2) or equilibrated in sucrose and then in 8 M EG (SUC+8 M EG, group 3). For GV-oocytes, the survival, maturation and cleavage rates of Group 1 were significantly lower than those in group 2, 3 and control group (p<0.05). For M II-oocytes, there were no differences in survival, maturation and cleavage rates between groups. After vitrification, the survival rates of GV and M II-oocytes in group 2 and 3 were similarly low (4-9%) and none of them matured nor cleaved after in vitro maturation, fertilization and culture. In conclusion, porcine GV and M II-oocytes do not seem to be damaged by a variety of cryoprotectants tested, but will succumb to a temperature decrease to $10^{\circ}C$ or to the process of vitrification, regardless of the cryoprotectant used.

• Reproductive and Developmental Biology
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• v.39 no.3
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• pp.77-81
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• 2015

This study was carried out to evaluate the effects of embryonic stage and toxicities of cryoprotectant on the rates of survival and development of the cryopreserved mouse early embryo and finally to establish the cryopreservation method of surplus embryos obtained during assisted reproductive technology. Toxicities of two cryoprotectants, dimethyl sulfoxide (DMSO) and ethylene glycol (EG) were investigated using a murine embryo model. Female F-1 mice were stimulated with gonadotropin, induced ovulation with hCG and mated. Two cell embryos were collected and cultured after exposure to either DMSO or EG. Embryo development was evaluated up to the blastocyst stage. The total cell count of blastocysts that were treated with DMSO ($68.1{\pm}24.1$) at the 2-cell stage was significantly lower than that were treated with EG ($81.2{\pm}27.0$) or the control ($99.0{\pm}18.3$) (p<0.001). On comparison of two cryoprotectant treated groups, the DMSO treated group showed a decreased cell count compared with the EG treated group (p<0.05). Both DMSO ($15.4{\pm}1.5$) and EG ($10.2{\pm}1.4$) treated groups showed higher apoptosis rates of cells in the blastocyst compared with the control ($6.1{\pm}0.9$, p<0.0001). In addition, the DMSO treated group showed more apoptotic cells than the EG treated group (p<0.001). The potential toxicity of cryoprotectants was uncovered by prolonged exposure of murine embryos to either DMSO or EG at room temperature. When comparing two cryoprotective agents, EG appeared to be less toxic than DMSO at least in a murine embryo model.

• Reproductive and Developmental Biology
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• v.32 no.3
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• pp.141-146
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• 2008

To search a new porcine pheromonal odorant, the models of four type (2D-QSAR, HQSAR, CoMFA & CoMSlA) were derived from quantitative structure-activity relationship (QSAR) between tetrahydrofuran-2-yl family compounds and their observed binding affinity constants (Obs.p$[Od]_{50}$). The optimized CoMFA model (predictability; $r^{2}_{cv.}(q^2)$=0.886 & correlation coefficient: $r^{2}_{ncv.}$=0.984) from ligand based approaches was confirmed as the best model among them. The $N^{1}$-allyl-$N^{2}$-(tetrahydrofuran-2-yl)methyl)oxalamide (P1), 2-(4-trimethylammoniummethylcyclohexyloxy)tetrahydrofurane (P5) and 2-(3-trimethylammoniummethylcyclohexyloxy)tetrahydrofurane (P6) molecules predicted as porcine pheromonal odorant by the CoMFA model were showed relatively high binding affinity constant values (Pred.p$[Od]_{50}=8{\sim}10$) and very lower toxicity values against some sorts of toxicity.

• Biomolecules & Therapeutics
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• v.26 no.5
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• pp.512-519
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• 2018

Phthalates widely used in the manufacture of plastics have deeply penetrated into our everyday lives. Recently, a concern over the toxicity of phthalates on thyroid, has been raised but in most of cases, the doses employed were unrealistically high. To investigate the effects of phthalates on thyroid, we investigated the effects of the repeated oral exposure to low to high doses (0.3, 3, 30 and 150 mg/kg) di-2-ethylhexylphthalate (DEHP) from weaning to maturity for 90 days in juvenile rats on the thyroid. The histological examination revealed that DEHP significantly induced hyperplasia in the thyroid from the doses of 30 mg/kg, which was confirmed with Ki67 staining. In line with this finding, increased mRNA expression of thyrotropin releasing hormone (Trh) was observed in the thyroid of female at 0.3 mg/kg and 150 mg/kg as determined by RNAseq analysis. Moreover, significantly increased expression of parathyroid hormone (Pth) in the female at 0.3 mg/kg, and thyroglobulin (Tg) and thyroid hormone responsive (Thrsp) in the male at 0.3 mg/kg were noted in the blood, of which changes were substantially attenuated at 150 m/kg, alluding the meaningful effects of low dose DEHP on the thyroid hormone regulation. Urinary excretion of mono-2-ethylhexyl-phthalate (MEHP), a major metabolite of DEHP was determined to be 4.10 and 12.26 ppb in male, 6.65 and 324 ppb in female at 0.3 and 30 mg/kg DEHP, respectively, which fell within reported human urine levels. Collectively, these results suggest a potential adverse effects of low dose phthalates on the thyroid.

• Development and Reproduction
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• v.3 no.1
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• pp.45-51
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• 1999

It is crucial to remove trophectoderm (TE) cells of blastocysts for an efficient isolation of pluripotent embryonic stem (ES)-like cells from bovine blastocysts. We evaluated the effectiveness of chemosurgery using calcium ionophore A23l87 (CIPA) by investigating the viability and pluripotency of ES-like cell lines isolated from in vitro-produced bovine blastocysts after CIPA treatment. The blastocysts treated with 50 $\mu$M CIPA for 25 min colonized most efficiently (51% of blastocysts) and developed to ES-like cell lines through 10 passages (4.8% of blastocysts) among CIPA-treated groups with different concentration and duration. In comparison with CIPA-untreated blastocysts, the colonization rate and overall viability of the CIPA-treated blastocysts were five times higher, suggesting that CIPA treatment condition defined in this study was highly efficient for establishing ES-like cell lines without apparent toxicity of CIPA. We evaluated in vitro pluripotency of the established three ES-like cell lines by examining alkaline phosphatase (AP) activity, capability of embryoid body formation, and chromosomal euploidity of the cells. Our cells showed a heterogeneous AP activity similarly to other reports. The cells were able to form simple embryoid bodies during suspension culture and majority of them showed a normal chromosome number of 60, the euploid chromosomal complement of bovine Therefore, our data suggest that CIPA treatment can be safely used for an efficient isolation of ES-like cell lines from bovine blastocysts.

• Journal of Food Hygiene and Safety
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• v.22 no.1
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• pp.1-14
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• 2007

The term, "food safety", has traditionally been viewed as a practical science aimed at assuring the prevention acute illnesses caused by biological microorganisms, and only to a minor extent, chronic diseases cause by chronic low level exposures to natural and synthetic chemicals or pollutants. "food safety" meant to prevent microbiological agents/toxins in/on foods, due to contamination any where from "farm to Fork", from causing acute health effects, especially to the young, immune-compromised, genetically-predisposed and elderly. However, today a broader view must also include the fact that diet, perse (nutrients, vitamins/minerals, calories), as well as low level toxins and pollutant or supplemented synthetic chemicals, can alter gene expressions of stem/progenitor/terminally-differentiated cells, leading to chronic inflammation and other mal-functions that could lead to diseases such as cancer, diabetes, atherogenesis and possibly reproductive and neurological disorders. Understanding of the mechanisms by which natural or synthetic chemical toxins/toxicants, in/on food, interact with the pathogenesis of acute and chronic diseases, should lead to a "systems" approach to "food safety". Clearly, the interactions of diet/food with the genetic background, gender, and developmental state of the individual, together with (a) interactions of other endogenous/exogenous chemicals/drugs; (b) the specific biology of the cells being affected; (c) the mechanisms by which the presence or absence of toxins/toxicants and nutrients work to cause toxicities; and (d) how those mechanisms affect the pathogenesis of acute and/or chronic diseases, must be integrated into a "system" approach. Mechanisms of how toxins/toxicants cause cellular toxicities, such as mutagenesis; cytotoxicity and altered gene expression, must take into account (a) irreversible or reversal changes caused by these toxins or toxicants; (b)concepts of thresholds or no-thresholds of action; and (c) concepts of differential effects on stem cells, progenitor cells and terminally differentiated cells in different organs. This brief Commentary tries to illustrate this complex interaction between what is on/in foods with one disease, namely cancer. Since the understanding of cancer, while still incomplete, can shed light on the multiple ways that toxins/toxicants, as well as dietary modulation of nutrients/vitamins/metals/ calories, can either enhance or reduce the risk to cancer. In particular, diets that alter the embryo-fetal micro-environment might dramatically alter disease formation later in life. In effect "food safety" can not be assessed without understanding how food could be 'toxic', or how that mechanism of toxicity interacts with the pathogenesis of any disease.

• Korean Journal of Fisheries and Aquatic Sciences
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• v.30 no.3
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• pp.488-495
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• 1997

The effects of ammonia on survival and growth of the flounder larva, Paralichthys olivaceus, were examined by a static renewal bioassay method. The $96\;hr-LC_{50}$ with the developmental stages during the period from 1day to 23 day-old larvae ranged 0.273 to 1.023 mg $NH_3/\ell$. Tolerance of the larvae to ammonia toxicity was much sensitive at the early larval stage, and increased with the growth of the larvae. Threshold $96hr-LC_{50}$ in 1, 3 and S day-old larvae after hatching were 0.293, 0.248 and 0.379 mg $NH_3/\ell$, respectively. Survival rate and growth in body weight and body weight of the larva were reduced with increase of ammonia concentration in the range of 0.055 and 0.341 mg $NH_3/\ell$. The no-observable-effect concentration (NOEC) and lowest-observable- effect concentration (LOEC) of the flounder larve were 0.102 and 0.174 mg $NH_3/\ell$ for body length, and 0.151 and 0.198 mg $NH_3/\ell$ for body weight, respectively. Chronic value (ChV), which is the geometric mean of the NOEC and $NH_3/\ell$ to body length of the larvae were 0.124 mg $NH_3/\ell$. The coefficient of variation (CV) for body length was higher at high concentration than at low concentration.