• Herbal Formula Science
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• v.16 no.1
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• pp.65-78
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• 2008

Objectives : this study was to access the effect of Hyeonggaeyeongyotang water extracts, a polyherbal formula has been used as folk medicine, on the fertility and early embryonic development of male and female Wistar rats when administered by oral gavage. Methods : In male rats, Hyeonggaeyeongyotang extract were dosed 4 weeks before pairing and 2 weeks after mating including the mating periods up to termination after necropsy of the majority of the females. In female rats, they were dosed 2 weeks before pairing, and from Day 0 to Day 7 of gestation. This study was conducted in accordance with the recommendations of the KFDA Guideline [2005-60] for Detection of Toxicity to Reproduction for Medicinal Products. Results: 1. No Hyeonggaeyeongyotang extract treatment-related changes on the clinical signs and mortalities, the Food consumptions, the Body weights and gains were demonstrated in all dosed levels tested in this study except for 500ml/kg-dosing male group in which a significant(p<0.05) increase of body gains was detected during day 0-7 after dosing. 2. No Hyeonggaeyeongyotang extract treatment-related changes on the pre-coital intervals, the estrus cycles, the mating index, conception rate and fertility index were demonstrated in all dosed levels tested in this study. 3. No Hyeonggaeyeongyotang extract treatment-related gross findings on reproductive organs, the weights of reproductive organs, histopathological findings on reproductive organs, the corpora lutea number, implantation site number, live fetus number, number of resorpted embryo and pre-and post-implatation loss were demonstrated in all dosed levels tested in this study. Conclusions : Base on the results, it is considered that the NOAEL (No-Observed-Adverse-Effect Level) for fertility and early embryonic development toxicity of Hyeonggaeyeongyotang extract was under 2000ml/kg/day in Wistar male and female rats because there no treatment-related changes on the fertility and early embryonic developmental index were demonstrated in all dosed levels tested.

• Toxicological Research
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• v.18 no.1
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• pp.23-29
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• 2002

Disodium disulphite, the HPV chemical, was assigned to Korea in order to implement OECD SIDS program in 1999. It was produced about 3,200 ton/year in 1998. This report evaluates the toxic potency of disodium disulphite based on the environmental and mammalian effects as well as human exposure. Oral $LD_{50}$ in rats is 1,540 mg/kg b.w. and effects was observed to the stomach, liver and the GI track that was filled with blood. For repeated dose toxicity, the predominant effect was the induction of stomach lesion due to local irritation. The no observed adverse effect lever for local (stomach irritation) was about 217 mg/kg bw/day. There is no evidence that disodium disulphite is genotoxic in vivo. No reproductive or developmental toxicty of disodium disulphite was observed for the period up to 2 yr and over three generation. In humans, urticaria and asthma with itching, edema, rhinitis, and nasal congestion were reported. Disodium disulphite is unlikely to induce respiratory sensitization but may enhance symptom of asthma in sensitive individuals. This chemical would be mainly transported to water compartment when released to environmental compartments since it is highly water soluble (470 g/l at 20). Low K oc (2.447) indicates disodium disulphite is so mobile in soil that it may not stay in the terrestrial compartment. The chemical has been tested in a limited number of aquatic species. hem acute toxicity test to fish, 96 hr-$LC_{50}$ was > 100 mg/1. For algae, 72 hr-$XC_{50}$ was 48.1 mg/1. For daphnid, the acute toxicity value of 48 hr-$EC_{50}$ was 88.76 mg/1, and chronic value of 21day-NOEC was > 10 mg/1. Therefore, PNEC of 0.1 mg/l for the aquatic organism was obtained from the chronic value of daphnid using the assessment factor of 100. Based on these data the disodium disulphite was recommended as low priority for further post-SIDS work in OECD.

• Environmental Analysis Health and Toxicology
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• v.15 no.1_2
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• pp.31-37
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• 2000

Acetanilide may be released into the environment through air and wastewater from its production and use sites and exposed to human. Acetanilide is known to produce an analgesic effect and may pose adverse effects on human health by overly exposure. According to the EUSES system, acetanilide showed a high MOS (Margin of safety) value exceeding 6$\times$10$^4$ on a regional exposure, which is safe enough for public health. Whereas the lowest MOS value in dermal exposure was estimated as 3$\times$10$^{-4}$ on a local basis (workplace), the risk could be partly counteracted by taking preventive measures such as using mask and globes and good ventilation in the work places. Acetanilide may pose a potential risk for workers by dust inhalation. For the sake of health protection in the work places, additional data should be accumulated with respect to repeated dose toxicity, reproduction toxicity and developmental toxicity, etc. It is, therefore, recommended that acetanilide should be a candidate for further work to supplement the lacking data until it is proved to be safe in the occupational health aspects.

• Development and Reproduction
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• v.13 no.4
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• pp.321-327
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• 2009

This study aimed to examine the testis toxicities of metal compound, manganese (Mn), which may be generated as mist or fume in the industrial sites. As well as serum prolactin (PRL) concentration was analyzed because Mn accumulation in basal ganglia up-regulates serum PRL and hyperprolactinemia consecutively induces the testis toxicity. Male F344 rats were divided into the 4 groups (2 controls and 2 Mn treated groups, n=10) on the basis of the test condition (inhalation, Mn $1.5mg/m^3$ or not) and treatment period (for 4-weeks and 13-weeks). The treatment time was 6 hr. a day, 5 days a week for the whole body. Basic tests including changes in body weight, feed rate were observed. Blood and testis Mn concentration, and testis toxicity test such as the number and deformity test of sperm were also observed. Serum PRL level was analyzed by ELISA to certify the relationship between the Mn induced increase of the serum PRL level and sperm production. Blood and testis Mn concentrations were significantly and dose-dependently increased. Sperm count was decreased in Mn-treatment groups than control in a treatment time dependent manner. Morphological analysis of cauda epidydimal sperm showed that the frequencies of morphologically abnormal sperms such as bent tail and small head were increased in the both Mn-treatment groups than control. A significant increase in serum PRL levels was found in response to Mn treatment but it was not hyperprolactinemia range. These results suggest that treatment of Mn up-regulates the serum PRL concentration and induces the testis toxicity. The No Aversed Effect Level (NOAEL) of inhaled Mn on the male rat testis may be under the $1.5mg/m^3$.

• Journal of Life Science
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• v.25 no.7
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• pp.765-772
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• 2015

The aim of this study was to determine the effect of decursin (D) and decursinol angelate (DA) against bisphenol A (BPA) toxicity in a rat two-generation study. Adult rats were divided into the following three groups: (1) control, (2) BPA, and (3) BPA+D/DA. The D and DA treatment of F0 parents increased the terminal body weight and relative adult organ weights (testes, kidneys, spleen, and liver) when compared with the BPA group. A significant decrease in sperm count was found in the BPA+D/DA (7.69%) and BPA (64.70%, p<0.01) groups, when compared with the sperm count in the control group. No offspring were obtained in the F1 generation of the BPA (50 mg/kg/day) group, but the addition of D/DA in the BPA+D/DA group significantly restored fertility (55.78%) and gestation indices (98.87%) in the F1 generation. No significant differences were found in the fertility index between the control (75.02%) and the BPA+D/DA (78.11%) groups in the two-generation study, when compared with the one-generation study. The viability ratio during lactation in the D/DA group was also similar to that of the control group. These data indicate that D/DA (50 mg/kg/day) administered over two generations causes significant positive changes in reproductive or developmental parameters.

• Biomolecules & Therapeutics
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• v.25 no.5
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• pp.545-552
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• 2017

Increasing concern is being given to the association between risk of cancer and exposure to low-dose bisphenol A (BPA), especially in young-aged population. In this study, we investigated the effects of repeated oral treatment of low to high dose BPA in juvenile Sprague-Dawley rats. Exposing juvenile rats to BPA (0, 0.5, 5, 50, and 250 mg/kg oral gavage) from post-natal day 9 for 90 days resulted in higher food intakes and increased body weights in biphasic dose-effect relationship. Male mammary glands were atrophied at high dose, which coincided with sexual pre-maturation of females. Notably, proliferative changes with altered cell foci and focal inflammation were observed around bile ducts in the liver of all BPA-dosed groups in males, which achieved statistical significance from 0.5 mg/kg (ANOVA, Dunnett's test, p<0.05). Toxicokinetic analysis revealed that systemic exposure to BPA was greater at early age (e.g., 210-fold in $C_{max}$, and 26-fold in AUC at 50 mg/kg in male on day 1 over day 90) and in females (e.g., 4-fold in $C_{max}$ and 1.6-fold in AUC at 50 mg/kg vs. male on day 1), which might have stemmed from either age- or gender-dependent differences in metabolic capacity. These results may serve as evidence for the association between risk of cancer and exposure to low-dose BPA, especially in young children, as well as for varying toxicity of xenobiotics in different age and gender groups.

• Journal of the korean academy of Pediatric Dentistry
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• v.35 no.1
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• pp.144-150
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• 2008

Multimodal cancer therapy including surgery, chemotherapy, and radiotherapy could not only improve the prognosis of malignancy but also reduce the dosage and toxicity of cancer drug for treatment of malignant tumor. The effects of radiotherapy are generally localized, additive, and accumulative, and depend on dosage, site and cell sensitivity. However, in growing individuals, the dental and skeletal sequelae to radiotherapy result in dental or facial abnormalities that are irreversible : arrested root development, disturbances in enamel formation, microdontia, anodontia, altered tooth eruption and mandibular or maxillary hypoplasia. Especially, the teeth which are developing is affected according to the stage. We report three cases of developmental disturbance of permanent teeth after radiotherapy. These children had received radiotherapy for malignant tumor at the age of 3 to 4 years, in which root hypoplasia, short tapered root and early apex closure were observed. For the management of radiation caries and radiotherapy-related teeth, periodic recall check and oral hygiene instruction are required.

• Korean Journal of Environmental Biology
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• v.22 no.2
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• pp.300-307
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• 2004

The chloroacetanilide herbicide alachlor (2-chloro-2', 6'-diethyl-N-(methoxymethyl)-acetanilide) and organochlorine insecticide endosulfan (6, 7, 8, 9, 10, 10-hexachloro-l, 5, 5a, 6, 9, 9a-hexahydro-6, 9-methano-2, 3, 4-benzodioxathiepin-3-oxide)are the highly toxic agricultural chemicals. Bombina orientalis is one of the most common amphibians in the world and comprises a large proportion of their total number. B. orientalis spawns in the farming regions at Spring when the massive application of agricultural chemicals occurs. These chemicals in farmland may threaten the reproduction of this frog. Therefore, we examined the embryotoxic and survival effects of alachlor and endosulfan at various concentrations in B. orientalis embryos. The survival rates of embryos at 312h post fertilization treated with alachlor and endosulfan were decreased with concentration dependent manner. Also, developmental malformations appeared by alachlor and endosulfan in B. orientalis embryos. The malformations showed in order of frequency with bent trunk, tail dysplasia, bent tail, thick-set body and ventral blister in alachlor treated embryos. The exposure of endosulfan produced 7 types of severe external malformations with tail dysplasia, pectoral blister, bent trunk, bent tail, cephalic dysplasia, ventral blister, and thick-set body. Following exposure to alachlor and endosulfan the types of malformations were diverse, suggesting these chemicals target multiple events in embryonic and larval development in this species. These results suggested that alachlor and endosulfan were detrimental for survival and development of B. orientalis embryos.

• Reproductive and Developmental Biology
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• v.34 no.3
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• pp.153-159
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• 2010

The 34 potently pig pheromonal odorants (1-32, 5755 & 7113) through structure-based virtual screening and ligand-based virtual screening method were selected and their ADMET and pharmacokinetics characters were evaluated and discussed quantitatively. The pheromonal odorants were projected on the following pre-calculated models, Caco-2 cell permeability, blood-brain barrier permeation, hERG inhibition and volume-distribution. From the results of in silico study, it is found that an optimal compound (31) either penetrating or have a little ($P_{caco2}$=-8.143) for Caco-2 cell permeability, moderate penetrating ability ($P_{BBB}$=0.082) for blood-brain barrier permeation, the low QT prolongation ($P_{hERG}$=1.137) for the hERG $K^+$ channel inhibition, and low distribution into tissues ($P_{VD}$=-5.468) for volume-distribution. Therefore, it is predicted that the compound (31) a topical application may be preferable from these based foundings.

• Journal of Embryo Transfer
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• v.28 no.2
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• pp.95-111
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• 2013

Worldwide there is concern about the continuing release of a broad range of environmental endocrine disrupting chemicals, including polychlorinated biphenyls, dioxins, phthalates, polybrominated diphenyl ethers (PBDEs), and other halogenated organochlorines persistent organic pollutants (POPs) into the environment. They are condemned for health adverse effects such as cancer, reproductive defects, neurobehavioral abnormalities, endocrine and immunological toxicity. These effects can be elicited via a number of mechanisms among others include disruption of endocrine system, oxidation stress and epigenetic. However, most of the mechanisms are not clear, thus several number of studies are ongoing trying to elucidate them in order to protect the public by reducing these adverse effects. In this review, we briefly limited review the process, the impacts, and the potential mechanisms of dioxin/dioxin like compound, particularly, their possible roles in adverse developmental and reproductive processes, diseases, and gene expression and associated molecular pathways in cells.