• Reproductive and Developmental Biology
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• 제38권3호
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• pp.107-114
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• 2014

Oral exposure of humans by excess amounts of arsenic may cause disturbances of the reproductive system. In the present study, such exposure was modelled in rats, with the support of sperm principal parameters and histopathological observations. Male Sprague-Dawley rats were randomly divided into three groups where the group I was served as a normal control, group II was received sodium meta-arsenite as arsenic (10 mg/kg b.w/day) and a combination of sodium meta-arsenite and sodium selenite (3 mg/kg b.w/day) in group III. After 6 weeks, there was no significant change in testis weight and in total motility of all the three experimental groups, whereas, rapid moving spermatozoa, moderately moving spermatozoa and slow moving spermatozoa were significantly decreased in arsenic treated rats as compared to control rats. The other sperm principal parameters like progressiveness, average path velocity, straightness linear velocity (VSL), curvilinear velocity (VCL), straightness, linearity sperm head elongation ratio, area, linearity amplitude of lateral head department (ALH) and beat cross frequency (BCF) were found to be reduced in arsenic intoxicated rats. These results are not correlated with the histological studies. On oral administration of selenium ameliorated the adverse effects of arsenic as compared to arsenic alone treated rats. Our findings clearly demonstrate that administration of selenium could prevent some of the deleterious effects of arsenic in the testis.

• 한국산업보건학회지
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• 제30권3호
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• pp.270-279
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• 2020

Objective: The aim of this study was to propose revision of the occupational exposure limit(OEL) for 1-Bromopropane(1-BP) following a review of the appropriateness of the standard in light of increasing epidemiological data and handling risk. Materials and Methods: The results of toxicity and epidemiologic investigations for 1-BP and agencies' OELs were compared and reviewed through a literature review. In order to investigate the status of 1-BP handling in South Korea, data from work environment actual condition survey results and work environment measurement results were used. Results: The toxicity of 1-BP, such as central nervous system(CNS) damage, peripheral neuropathy, hematological adverse effects, and developmental and reproductive toxicity(male and female) has been reported. ACGIH recommends 0.1 ppm as a TLV-TWA value, but the OEL of South Korea stands at 25 ppm, which is 250 times higher than the TLV-TWA. Although 1-BP is a specially managed substance under the Industrial Safety and Health Law, the currently applied OEL cannot be said to be a safe level based on the results of epidemiological studies to date. In a work environment measurement in 2017, the total number of samples was 626, which were derived from 78 industries, and the average concentration was 1.173 ppm(standard deviation 2.88). Conclusions: To protect the health of workers handling 1-BP, estimated to be 780 in South Korea, it is necessary to strengthen the OEL(TWA) to a level of 0.3 ppm(lower than the 0.34 ppm with known toxic effects), which is believed to be safe as a result of epidemiological investigation. "Skin" notation should be recommended.

• Toxicological Research
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• 제21권1호
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• pp.23-29
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• 2005

A developmental study of CONP01, a new antiarthritic agent, was conducted in Sprague-Dawley rats. Dosage of CONP01 0, 111, 333, and 1000 mg/kg/day were administered to dams orally from day 6 to day 16 of gestation. Two-third of dams per group were subjected to caesarean section on day day 20 of pregnancy for examination of their fetuses, and the remaining one-third of dams per group were allowed to deliver naturally for postnatal examination of their offspring. There was no change in the dams body weights, food consumptions, specific clinical sings and gross findings. There was significant decrease only in the absolute and relative weights of right ovary in 111 mg/kg treatment group, when compared with the vehicle control, whereas other organ weights were not changed. Moreover, no increase in the frequencies of external, visceral and skeletal malformation of fetuses were observed in the treated groups. These results suggest that the oral NOAEL (no observed adverse effect level) of CONP01 may be over 1,000 mg/kg in dams and fetuses of rats.

• Toxicological Research
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• 제33권2호
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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.

• Reproductive and Developmental Biology
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• 제34권3호
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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.

• 한국환경보건학회지
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• 제30권2호
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• pp.71-78
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• 2004

This study was performed to evaluate developmental and estrogenic activity of bisphenol A (BPA) and butyl benzyl phthalate (BBP) to the second generation of Sprague-Dawley rats ingested during gestational or lactational periods. Rats were given BPA 20$\mu\textrm{g}$/kg BBP 100mg/kg of pregnancy or lactation periods. Maternal body weight and neonatal body weight were recorded. The rats were sacrificed on day 21 after birth. Reproductive organs of dam and neonate were utilized for receptor binding assay. The plasma concentrations of BPA and MBep, one of the major metabolites of BBP were analyzed with HPLC. The co-administration of BPA and BBP induced slow weight gain compared with single administration in dams. Also, such mixture induced low neonatal body weights in next generation. The dams treated with BPA and BBP during lactational periods showed significant organ weight changes in liver and spleen. The dams exposed during lactational periods showed significant organ weight changes not only in liver and spleen but also in kidney, uterus and ovary. The F1 female rats exposed during lactation periods showed significant organ weight changes in liver, spleen, ovary. The F1 male rats showed significant organ weight changes in liver, kidney, epididymis, vesicular glands, prostate. However, no clear synergistic effects of BPA and BBP were noted. There was no significantly different ER$\alpha$ expression pattern between control and treated groups. However, ER$\alpha$ expression were increased in F1 male testis and female uterus. PI male showed distinct ER$\alpha$ expression, especially in the group of lactational combined exposure. Synergistic ER$\alpha$ expression was found by combined treatment of BPA and BBP. We could not find any evidences of synergistic effects on BPA and/or BBP combined administration on dams and their fetuses, except in ER$\alpha$ expression of F1 male.

• Toxicological Research
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• 제12권2호
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• pp.203-211
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• 1996

Methanol has been widely used as an industrial solvent and environmental exposure to methanol would be expected to be increasing. In humans, methanol causes metabolic acidosis and damage to ocular system, and can lead to death in severe and untreated case. Clinical symptoms are attributed to accumulation of forrnic acid which is a metabolic product of methanol. In humans and primates, formic acid is accumulated after methanol intake but not in rodents due to the rapid metabolism of methanol. Neverthless, the developmental and reproductive toxicity were reported in rodents. Previous reports showed that perinatal exposure to ethanol produces a variety of damage in human central nervous system by direct neurotoxicity. This suggests that the mechanism of toxic symptoms by methanol in rodents might mimic that of ethanol in human. In the present study I hypothesized that methanol can also induce toxicity in neuronal cells. For the study, primary culture of rat hippocampal neurons and glias were empolyed. Hippocampal cells were prepared from the embryonic day-17 fetuses and maintained up to 7 days. Effect of methanol (10, 100, 500 and 1000 mM) on neurite outgrowth and cell viability was investigated at 0, 18 and 24 hours following methanol treatment. To study the changes in proliferation of glial cells, protein content was measured at 7 days. Neuronal cell viability in culture was not altered during 0-24 hours after methanol treatment. 10 and 100 mM methanol treatment significantly enhanced neurite outgrowth between 18-24 hours. 7-day exposure to 10 or 100 mM methanol significantly increased protein contents but that to 1000 mM methanol decreased in culture. In conclusion, methanol may have a variety of effects on growing and differentiation of neurons and glial cells in hippocampus. Treatment with low concentration of methanol caused that neurite outgrowth was enhanced during 18-24 hours and the numbers of glial cell were increased for 7 days. High concentration of methanol brought about decreased protein contents. At present, the mechanism responsible for the methanol- induced enhancement of neurite outgrowth is not clear. Further studies are required to delineate the mechanism possibly by employing molecular biological techniques.

• Toxicological Research
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• 제35권2호
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• pp.137-154
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• 2019

Triclosan (TCS) is an antimicrobial compound used in consumer products. The purpose of current study was to examine toxicology and risk assessment of TCS based on available data. Acute toxicities of oral, transdermal and inhalation routes were low, and phototoxicity and neurotoxicity were not observed. Topical treatment of TCS to animal caused mild irritation. TCS did not induce reproductive and developmental toxicity in rodents. In addition, genotoxicity was not considered based on in vitro and in vivo tests of TCS. It is not classified as a carcinogen in international authorities such as International Agency for Research on Cancer (IARC). No-observed-adverse-effect level (NOAEL) was determined 12 mg/kg bw/day for TCS, based on haematoxicity and reduction of absolute and relative spleen weights in a 104-week oral toxicity study in rats. Percutaneous absorption rate was set as 14%, which was human skin absorption study reported by National Industrial Chemicals Notification and Assessment Scheme (NICNAS) (2009). The systemic exposure dosage (SED) of TCS has been derived by two scenarios depending on the cosmetics usage of Koreans. The first scenario is the combined use of representative cosmetics and oral care products. The second scenario is the combined use of rinse-off products of cleansing, deodorants, coloring products, and oral care products. SEDs have been calculated as 0.14337 mg/kg bw/day for the first scenario and 0.04733 mg/kg bw/day for the second scenario. As a result, margin of safety (MOS) for the first and second scenarios was estimated to 84 and 253.5, respectively. Based on these results, exposure of TCS contained in rinse-off products, deodorants, and coloring products would not pose a significant health risk when it is used up to 0.3%.

• 한국환경독성학회:학술대회논문집
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• 한국환경독성학회 2002년도 추계국제학술대회
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• pp.170-170
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• 2002

College of Pharmacy, Ewha womans University, Seoul, 120-750, Korea 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is the most potent halogenated aromatic hydrocarbon congener that induces expression of several genes including CYP1A1. Exposure to TCDD results in many toxic actions such as carcinogenesis, hepatotoxicity, immune suppression, and reproductive and developmental toxicity. Dramatic differences in dioxin toxicity have been observed between the sexes of some animal species, suggesting hormonal modulation of dioxin action. Many studies have been reported and propose several mechanisms of anti-estrogenic effects of TCDD. In contrast, the effect of estrogen on the regulation of CYP1A1 are not clear at present. There are several reports showing conflicting results. It seems that induction/inhibition of CYP1A1 may be dependent on cell-type and concentration. The purpose of this study was to investigate the regulation of TCDD-induced CYP1A1 gene expression by estradiol and its metabolites. We examined whether estradiol and its metabolites altered TCDD-mediated induction of CYP1A1 enzyme activity. 17 ${\beta}$ estradiol and 16 ${\alpha}$ estriol at non cytotoxic concentrations caused a significant concentration dependent decline of TCDD-induced EROD activity To determine whether reduced EROD activity reflected altered CYP1A1 mRNA expression, we measured CYP1A1 mRNA level by RT-PCR. And to examine whether estradiol and its metabolites have effects on TCDD-induced CYP1A1 gene expression at the transcription level, we also peformed transient transfection with an AhR responsive reporter plasmid containing the 5' flanking region of the human CYP1A1 gene to examine whether estradiol and its metabolites have effects on TCDD-induced CYP1A1 gene expression at the transcription level.

• 대한예방한의학회지
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• 제14권2호
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• pp.91-104
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• 2010

The experiments were undertaken to evaluate the effects of herbal medicine, Bojungiggitang and Gwibitang in pregnant rats and their fetuses. Female Sprague-Dawley rats were orally administered with the Bojungiggitang and Gwibitang at dose of 5ml/kg/day for 20 days. Pregnant rats were sacrificed at 20th day of gestation, and the internal and reproductive organs. Approximately live fetuses in the 20th day of gestation were randomly selected and fixed in 95% ethanol. To observe skeletal malformations, fetuses were stained with alcian blue and alizarin red S. Maternal body weights of Bojungiggitang and Gwibitang treated group has a tendency to increase compared to that of control group. There were no significant differences in internal and reproductive organs. There were no significant changes between two groups in blood chemistry and hematological values. There were no significant changes in number of corpus luteum, implantation and live fetuses. But Bojungiggitang and Gwibitang administered group showed higher implantation rate than the control group. Also, Bojungiggitang and Gwibitang administered groups showed lower early resorption rate than the control group. And Gwibitang had the higher value in all the other groups in all items. From the sex ratio, the number of females were larger than the number of males in the control group, and more males than females in Gwibitang administered group. Neonatal body weight and the number of fetus of Bojungiggitang and Gwibitang group were higher than that of control group. The fetuses of dams treated with Bojungiggitang and Gwibitang did not show external malformation. Vertebral and sternal variations were observed in Bojungiggitang and Gwibitang administered group compared to the control group. Those variations were insignificant. There were no significant changes in number of ribs, cervical, thoracic, lumbar, sacral and caudal vertebras. From these results, it can be concluded that Bojungiggitang and Gwibitang showed no toxic effects on maternal body weight and the number of live fetuses. There were no significant changes in organ weight, hematological data, and reproductive organs. Although skeletal variations were shown in vertebra and sternum, Bojungiggitang, Gwibitang were shown insignificant changes in bone malformation.