• 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.

• Proceedings of the Korea Environmental Mutagen Society Conference
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• 2004.05a
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• pp.115-115
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• 2004

• Journal of Society of Preventive Korean Medicine
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• v.17 no.2
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• pp.157-168
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• 2013

The objective of this study was to characterize the adverse effects of Ahnjon-Yichun-Tang during early pregnancy. Following successful mating, female Sprague-Dawley rats were given Ahnjon-Yichun-Tang(AYT) extract by oral administration daily with dose of 150mg (n=10), 300mg(n=10), 450mg(n=10) for 20 days of pregnancy. The rats in Control group(n=10) were orally administrated with Saline. All pregnant rats of Ahnjon-Yichun-Tang-treated and Control groups were sacrificed on day 20 of pregnancy. The pregnancy outcome was determined and the internal and reproductive organs of pregnant rat were observed. The fetuses were examined for the presence of various developmental toxic endpoints and stained with alcian blue and alizarin red S, and observed skeletal malformations. The results obtained in this study represent that there is no significant changes between Control and Ahnjon-Yichun-Tang-treated groups in body weight, organ weight, blood chemistry values, hematological values and pregnancy indexes of pregnant rat. The skeletal malformation of fetus was not observed as well. These results suggest that oral administration of Ahnjon-Yichun-Tang does not produce either maternal or developmental toxicity.

• The Korea Journal of Herbology
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• v.26 no.1
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• pp.47-52
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• 2011

Objectives : The present study has been undertaken to investigate the effects of Leonuri Sibirici Herba and Pruni Persicae Semen on pregnant rats. Method : In this experiment, the pregnant rats were administered by water extracts of Leonuri Sibirici Herba and Pruni Persicae Semen. The levels of weights, ALT, AST, ALP, BUN, creatinine, progesterone, Na and K in serum and reproductive indices of the rats were measured after treatment. Results : 1. The levels of body weight gains were not significantly changed in comparison with Control group in Leonuri Sibirici Herba group and Pruni Persicae Semen group. 2. In the levels of reproductive indices of the rats, the number of corpora lutea, implantation, viable fetuses, pre-implantation loss, post-implantation loss, fetal weight and placental wight were not significantly changed in comparison with Control group in Leonuri Sibirici Herba group and Pruni Persicae Semen group. 3. The levels of BUN, creatine, ALT, AST and ALP were not significantly changed in comparison with Control group in Leonuri Sibirici Herba group and Pruni Persicae Semen group. 4. The level of progesterone was not significantly changed in comparison with Control group in Leonuri Sibirici Herba group and Pruni Persicae Semen group. 5. The levels of Na and K were not significantly changed in comparison with Control group in Leonuri Sibirici Herba group and Pruni Persicae Semen group. Conclusion : Reviewing these experimetal results, it appeared that Leonuri Sibirici Herba and Pruni Persicae Semen had not toxicity on pregnant rats.

• The Korea Journal of Herbology
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• v.28 no.3
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• pp.33-38
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• 2013

Objectives : The present study has been undertaken to investigate the effects of Carthami Semen and Jogyeongjongok-Tang on pregnant rats. Method : In this experiment, the pregnant rats were administered by water extracts of Carthami Semen and Jogyeongjongok-Tang. The levels of weights, ALT, AST, ALP, BUN, creatinine, progesterone, Na and K in serum and reproductive indices of the rats were measured after treatment. Results : The levels of body weight gains were not significantly changed in comparison with Control group in Carthami Semen group and Jogyeongjongok-Tang group. In the levels of reproductive indices of the rats, the number of corpora lutea, implantation and viable fetuses, post-implantation loss, fetal weight and placental wight were not significantly changed in comparison with Control group in Carthami Semen group and Jogyeongjongok-Tang group. But pre-implantation loss was significantly increased in comparison with Control group in Carthami Semen group. The levels of BUN, creatine, ALT, AST and ALP were not significantly changed in comparison with Control group in Carthami Semen group and Jogyeongjongok-Tang group. The level of progesterone was not significantly changed in comparison with Control group in Carthami Semen group and Jogyeongjongok-Tang group. The levels of Na and K were not significantly changed in comparison with Control group in Carthami Semen group and Jogyeongjongok-Tang group. Conclusion : Reviewing these experimetal results, it appeared that Carthami Semen and Jogyeongjongok-Tang had not toxicity on pregnant rats.

• Toxicological Research
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• v.19 no.3
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• pp.227-234
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• 2003

2-Bromopropane (2-BP), a halogenated propane analogue, is a substitute for chlorofluorocarbones (CFCs) which have a great potential to destroy the ozone layer and to warm the earth's environment. The present study was undertaken to evaluate the potential adverse effects of 2-BP on pregnant dams and embryo-fetal development after maternal exposure during the gestational days (GD) 6 through 17 in ICR mice. The test chemical was administered subcutaneously to pregnant mice at dose levels of 0, 313, 625 or 1,250 mg/kg/day. All dams were subjected to caesarean section on GD 18 and their fetuses were examined for external, visceral and skeletal abnormalities. In the 1,250 mg/kg group, maternal toxicity included an increase in the incidence of abnormal clinical signs and a decrease in the maternal body weight, body weight gain, and corrected body weight. Developmental toxicity included a decrease in the fetal body weight, a reduction in the placental weight, an increase in the fetal skeletal variation and ossification delay. There were no adverse effects on either pregnant dams or embryo-fetal development in the 313 and 625 mg/kg groups. These results suggest that a 12-day subcutaneous dose of 2-BP is embryotoxic at a maternally toxic dose (i.e., 1,250 mg/kg/day) in ICR mice. In the present experimental condition, the no-observed-adverse-effect level of 2-BP is considered to be 625 mg/kg/day for dams and embryo-fetuses, respectively.

• Korean Journal of Veterinary Research
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• v.43 no.4
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• pp.657-666
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• 2003

The present study was undertaken to evaluate the potential adverse effects of 2-BP on pregnant dams and embryo-fetal development after maternal exposure during the gestational days (GD) 6 through 19 in Sprague-Dawley rats. The test chemical was administered subcutaneously to pregnant rats at dose levels of 0, 375, 750 and 1250 mg/kg/day. During the test period, clinical signs, mortality, body weights and food consumption were examined. All dams were subjected to caesarean section on GD 20 and their fetuses were examined for external, visceral and skeletal abnormalities. At above 750 mg/kg, toxic effects including signs of toxicity, suppressed body weight, decreased gravid uterine weight and reduced food intake were observed in pregnant dams. An increase in the fetal deaths, a decrease in the litter size, a reduction in the fetal body weight and an increase in the incidence of fetal morphological alterations were also found. There were no adverse effects on either pregnant dams or embryo-fetal development at a dose level of 375 mg/kg. These results suggest that a 14-day subcutaneous dose of 2-BP is embryolethal and teratogenic at above 750 mg/kg/day in pregnant rats. In the present experimental condition, the no-observed-adverse-effect level of 2-BP is considered to be 375 mg/kg/day for dams and embryo-fetuses, respectively.

• 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.

• Journal of Environmental Health Sciences
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• v.47 no.5
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• pp.446-453
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• 2021

Background: Plastic particles less than 5 mm in diameter (microplastics) are well-known for causing various toxicities such as lung inflammation, oxidative stress, genotoxicity, and reproductive toxicity. As microplastics become smaller, they can move across cell membranes, the placenta, and the blood-brain barrier. Objectives: We evaluated the toxicities of polyethylene microplastics (PE-PMs) in dams and neonates through intragastric intubation of pregnant ICR mice. Methods: Low concentrations (0.01 mg/mouse/day) and high concentrations (0.1 mg/mouse/day) of polyethylene microplastics were administered from the ninth day of pregnancy to postnatal day seven. The control group was administered with distilled water. On the day of sacrifice, the weight of dams and neonates and the organ weight of neonates was measured. Further, acetylcholinesterase levels and glutathione peroxidase levels were evaluated by using a blood sample obtained on the sacrifice day. Results: No significant difference in the number of neonates was found, but the body weight gain of dams was seen to be lower in the low-dose group. On the other hand, we observed a consecutively declining trend in the weight gain and organ weight of neonates among the high-, control, and low-dose groups. Meanwhile, the serum acetylcholinesterase and glutathione peroxidase level were higher in the low-dose group compared to the control group. Further, the dose-dependent accumulation of microplastics in the organs of neonates revealed the transport of plastic particles from dams to their offspring. Conclusions: Although the exact mechanism of toxicity caused by microplastics could not be confirmed, it was validated that exposure to microplastics during pregnancy and lactation causes its migration between generations and accumulation throughout the body. Hence, it is necessary to evaluate the systemic toxicity of microplastics and assessment of co-morbidities such as second-generation toxicity, neurotoxicity, and depression following long-term exposure.

• Journal of Environmental Health Sciences
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• v.48 no.2
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• pp.106-115
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• 2022

Background: Current research suggests that humans are exposed to microplastics through consumption of foods and beverages, the airway route, and a variety of other means. Objectives: We evaluated oxidative stress and inflammation from polyethylene microplastics (PE-MPs) in the neonatal liver through intragastric administration or intratracheal instillation in pregnant mice. Methods: PE-MPs were administered from gestational day 9 to postnatal day 7. The intragastric administration group (0.01 mg/mouse/day or 0.1 mg/mouse/day) and intratracheal instillation group (6 ㎍/mouse/day or 60 ㎍/mouse/day) of PE-MPs were administered. After sacrifice, the oxidative stress and inflammation of the neonatal livers were measured. Results: As a result of the oxidative stress caused by PE-MPs in the neonatal livers, glutathione peroxidase decreased in a concentration-dependent manner in the intragastric administration group compared to the control group and intratracheal instillation decreased in high concentration PE-MPs. The catalase level increased at high concentrations of intragastric administration and intratracheal instillation. To confirm the level of inflammation caused by PE-MPs, monocyte chemoattractant protein-1 and tumor necrosis factoralpha were increased compared to the control group except for intratracheal intilation-high concentration PEMPs. The C-reactive protein level was decreased by intragastric administration compared to the control group and intratracheal instillation was increased compared to the control group. Conclusions: Despite the difficulty in comparing the toxic intensity between intragastric administration and intratracheal instillation of PE-MPs, our study revealed that oxidative stress and inflammation were induced in the neonatal liver. However, it is necessary to evaluate the toxic effects of microplastics on various organs as well. Overall, the present study indicates that the evaluation of toxic effects of long-term microplastic exposure, potential of microplastic toxicity on next-generation offspring and toxicity mechanism in human should be considered for further investigations.