• Proceedings of the Korean Society of Toxicology Conference
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• 2002.05a
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• pp.71-72
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• 2002

Thimerosal is a mercury-containing compound used in trace amounts to prevent bacteria and other organisms from contaminating vaccines, especially in opened multi-dose vials. The toxicity of mercury is well known and those most at risk are occurred in unborn and newborn babies.(omitted)

• Proceedings of the Korea Environmental Mutagen Society Conference
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• 2002.05a
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• pp.71-72
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• 2002

• Toxicological Research
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• v.35 no.4
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• pp.343-351
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• 2019

Many in vitro developmental toxicity assays have been proposed over several decades. Since the late 1980s, we have made intermittent attempts to introduce in vitro assays as screening tests for developmental toxicity of inhouse candidate products. Two cell-based assays which were developed two decades apart were intensively studied. One was an assay of inhibitory effects on mouse ascites tumor cell attachment to a concanavalin A-coated plastic sheet surface (MOT assay), which we studied in the early days of assay development. The other was an assay of inhibitory effects on the differentiation of mouse embryonic stem cell to beating heart cells (EST assay), which we assessed more recently. We evaluated the suitability of the assays for screening in-house candidates. The concordance rates with in vivo developmental toxicity were at the 60% level. The EST assay classified chemicals that inhibited cell proliferation as embryo-toxic. Both assays had a significant false positive rate. The assays were generally considered unsuitable for screening the developmental toxicity of our candidate compounds. Recent test systems adopt advanced technologies. Despite such evolution of materials and methods, the concordance rates of the EST and MOT systems were similar. This may suggest that the fundamental predictivity of in vitro developmental toxicity assays has remained basically unchanged for decades. To improve their predictivity, in vitro developmental toxicity assays should be strictly based on elucidated pathogenetic mechanisms of developmental toxicity.

• Toxicological Research
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• v.17 no.3
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• pp.225-234
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• 2001

The present study was conducted to investigate the effects of Korean red ginseng water extract (KRGWE) on developmental toxicity caused by the environmental estrogen bisphenol A (BPA) in Sprague-Dawley rats. fifty males successfully mated were randomly assigned to five experimental groups, 1.e., group I (vehicle control), group II (BPA 1000mg/kg), group III (KRGWE 400mg/kg), group IV (BPA 1000mg/kg & KRGWE 200mg/kg), and group V (BPA 1000mg/kg & KRGWE 400mg/kg). The test articles were administered by gavage to mated females from gestational days (GD) 1 through 20 (sperm vaginal lavage=day O). All females were subjected to caesarean section on GD 21 and their fetuses were examined for external, visceral, and skeletal abnormalities. In the group II, significant maternal toxic effects including suppressed body weight, decreased body weight gain during pregnancy, and reduced food consumption were observed in pregnant rats. The minimal developmental toxicity including fetal ossification delay was also found in fetuses. In addition, a tendency for increased pregnancy failure, increased pre-and postimplantation loss, and decreased fetal body weight was observed. However, no fetal morpho-logical abnormalities were seen in surviving fetuses at a dose level of 1000mg BPA/kg. On the other hand, the maternal toxicity and developmental toxicity found in the groups IV and V were comparable to those of the group II. There were no adverse signs of either maternal toxicity or developmental toxicity in the group III. These results showed that administration of BPA at a dose level of 1000mg/kg to pregnant rats resulted in significant maternal toxicity and minimal developmental toxicity, and that no protective effects on BPA-induced maternal toxicity and developmental toxicity were found by concomitant gavage dosing of KRGWE.

• Toxicological Research
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• v.29 no.4
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• pp.221-227
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• 2013

Embryonic stem (ES) cells have potential for use in evaluation of developmental toxicity because they are generated in large numbers and differentiate into three germ layers following formation of embryoid bodies (EBs). In earlier study, embryonic stem cell test (EST) was established for assessment of the embryotoxic potential of compounds. Using EBs indicating the onset of differentiation of mouse ES cells, many toxicologists have refined the developmental toxicity of a variety of compounds. However, due to some limitation of the EST method resulting from species-specific differences between humans and mouse, it is an incomplete approach. In this regard, we examined the effects of several developmental toxic chemicals on formation of EBs using human ES cells. Although human ES cells are fastidious in culture and differentiation, we concluded that the relevancy of our experimental method is more accurate than that of EST using mouse ES cells. These types of studies could extend our understanding of how human ES cells could be used for monitoring developmental toxicity and its relevance in relation to its differentiation progress. In addition, this concept will be used as a model system for screening for developmental toxicity of various chemicals. This article might update new information about the usage of embryonic stem cells in the context of their possible ability in the toxicological fields.

• Toxicological Research
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• v.35 no.1
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• pp.65-74
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• 2019

Tetrahydrocurcumin (THC) is a major metabolite of curcumin, which is obtained from Curcuma longa. THC has various benefits and overcomes the bioavailability issue of curcumin. To establish it as a pharmacologically active molecule, its safety profile has to be determined. Thus, the present study aimed to determine the preclinical safety profile of THC in a 90-day subchronic and reproductive/developmental toxicity study in Wistar rats. THC at oral doses of 100, 200, and 400 mg/kg was administered daily for 90 days. Rats in the recovery group were kept for 14 days after treatment termination. The animals were observed for treatment-related morbidity, mortality, and changes in clinical signs, clinical pathology, and histopathology. In the reproductive/developmental toxicity study, THC at 100, 200, and 400 mg/kg was administered orally to rats and the reproductive/developmental parameters in adult male and female rats and pups were observed. THC at up to 400 mg/kg/day of did not have any significant effect on all parameters in male and female rats in both toxicity studies. Thus, 400 mg/kg/day can be considered as the no-observed-adverse-effect-level of THC in rats.

• Toxicological Research
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• v.17 no.2
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• pp.83-90
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• 2001

The background control data were compiled from rat developmental toxicity studies con-ducted at Toxicology Research Center, KRICT during the 1993-1999 period. These data were assembled in order to provide background in formation for the maternal and fetal data collected in 13 developmental toxicity studies using Sprague-Dawley rats. A total of 325 mated females were used in these studies during the seven-year period and overall pregnancy rate of these females was 93.8%. The present background control data included body weights, food consumption, hematological values, and organ weights of pregnant females, caesarean section data, and fetal examination data. These data can be used not only as a historical database for the meaningful interpretation of data from reproductive and developmental toxicity studies, but also as a contribution to biological characterization oj Sprague-Dawley rats.

• Communications for Statistical Applications and Methods
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• v.29 no.2
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• pp.239-250
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• 2022

In many applications, we frequently encounter correlated multiple outcomes measured on the same subject. Joint modeling of such multiple outcomes can improve efficiency of inference compared to independent modeling. For instance, in developmental toxicity studies, fetal weight and number of malformed pups are measured on the pregnant dams exposed to different levels of a toxic substance, in which the association between such outcomes should be taken into account in the model. The number of malformations may possibly have many zeros, which should be analyzed via zero-inflated count models. Motivated by applications in developmental toxicity studies, we propose a Bayesian joint modeling framework for continuous and count outcomes with excess zeros. In our model, zero-inflated Poisson (ZIP) regression model would be used to describe count data, and a subject-specific random effects would account for the correlation across the two outcomes. We implement a Bayesian approach using MCMC procedure with data augmentation method and adaptive rejection sampling. We apply our proposed model to dose-response analysis in a developmental toxicity study to estimate the benchmark dose in a risk assessment.

• Proceedings of the Korean Society of Toxicology Conference
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• 2005.05a
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• pp.130-130
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• 2005

• Journal of Environmental Health Sciences
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• v.44 no.5
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• pp.468-479
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• 2018

Objectives: Recently, a report was published that the humidifier disinfectant CMIT/MIT did not cause developmental toxicity and was not detected in systemic circulation as a result of an inhalation toxicity test. Therefore, this study was carried out to investigate any associations between CMIT/MIT exposure and developmental toxicity using the in vivo apical toxicity test method. Methods: Groups of pregnant ICR mice were instilled in the trachea with chloromethylisothiazolinone/methylisothiazolinone (CMIT/MIT) using a visual instillobot over a period of seven days from days 11 to 17 days post-coitum. For the in vivo apical toxicity test method, an $LD_{50}$-based dose-range finding model was applied to decide the dose range for inducing developmental toxicity. Results: Among the groups of 0, 0.1, 0.5, 1.0, and 1.5 mg ai/kg/day CMIT/MIT, the exposure groups of 0.5 mg and 1.0 ai/kg/day CMIT/MIT were estimated to reflect the thresholds for the stillbirth and death of pregnant mice, respectively. The groups of 0.5, 1.0, and 1.5 mg ai/kg/day CMIT/MIT induced stillbirth rates of 2.57, 10, and 53.8%, respectively. Another exposure group of 0.75 mg ai/kg/day CMIT/MIT did not induce any deaths of pregnant mice and resulted in a stillbirth rate of 8% in only one of six pregnant mice. Conclusions: CMIT/MIT can induce stillbirth in pregnant mice. It was also concluded that CMIT/MIT moves through the pulmonary circulation system and then continues on through systemic circulation and the placenta. There is a possibility of stillbirth and other health causalities in humans beyond the lungs caused by CMIT/MIT exposure.