• Toxicological Research
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• 제17권3호
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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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• 제17권2호
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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.

• Toxicological Research
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• 제19권3호
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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.

• Environmental Analysis Health and Toxicology
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• 제26권
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• pp.6.1-6.8
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• 2011

Objectives: The present study investigated the potential adverse effects of multi-wall carbon nanotubes (MWCNTs) on pregnant dams and embryonic development following maternal exposure in rats. Methods: MWCNTs were orally administered to pregnant rats from gestational day (GD) 6 through 19 at dose levels of 0, 8, 40, 200, and 1000 mg/kg/day. During the test period, clinical signs, mortality, body weights, food consumption, serum biochemistry, oxidant-antioxidant status, gross findings, organ weights, and Caesarean section findings were examined. Results: All animals survived to the end of the study. A decrease in thymus weight was observed in the highest dose group. However, maternal body weight, food consumption, serum biochemical parameters, and oxidant-antioxidant balance in the kidneys were not affected by treatment with MWCNTs. No treatment-related differences in gestational index, embryo-fetal mortality, or fetal and placental weights were observed between treated and control groups. Conclusions: The results show that 14-day repeated oral dosing of MWCNTs during pregnancy induces minimal maternal toxicity at 1000 mg/kg/day in rats. Under these experimental conditions, the no-observed-adverse-effect level of MWCNTs is considered to be 200 mg/kg/day for dams and 1000 mg/kg/day for embryonic development.

• Environmental Analysis Health and Toxicology
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• 제25권4호
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• pp.279-286
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• 2010

Objectives : Platinum nanoparticles (PNPs) are potentially useful for sensing, catalysis, and other applications in the biological and medical sciences. However, little is known about PNP toxicity. In this study, adverse effects of PNPs on the postnatal development of mouse pubs were investigated. Methods : PNPs (size: 20 nm) were prepared and orally administered to mice during premating, gestation, and lactation periods (0.25 mg/kg, 0.5 mg/kg, and 1 mg/kg). Maternal and pup toxicity were evaluated. Results : PNPs did not affect blood biochemical parameters or mortality in dams during the experimental period. Histopathological signs were not observed and pup number was not different between the control and treated groups. Deformity and stillbirth were not observed in the pups. However, PNPs increased pup mortality and decreased the infant growth rate during the lactation period. Conclusion : PNPs may have adverse effects to the postnatal development of mouse pups.

• 한국산업보건학회지
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• 제23권3호
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• pp.273-286
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• 2013

Objectives: The present study was conducted in order to investigate the reproductive toxicity in rats exposed to 1,4-dichlorobutane. Methods: The test chemical was administered orally at 0, 8.3, 50 and 300 mg/kg/day. Males were administered daily for 10 weeks prior to the mating period. Females were administered from between two weeks before mating to the 21stday of lactation. Results: In both sexes, a decrease in body weight and an increase in the weights of the liver and kidneys were observed. In males, discoloration of the liver, hepatocyte hypertrophy and mineralization in the kidneys were observed. In females, animal deaths, dystocia and pup deaths due to maternal dysfunction were observed. In F1 animals of both sexes, a decrease in body weight was observed at 300 mg/kg/day. An increase in the weights of the liver in both sexes, mineralization in the kidneys of males, animal deaths, hepatocyte hypertrophy and pup deaths due to maternal dysfunction were observed at 50 mg/kg/day. Mineralization in the kidneys of males was observed at 8.3 mg/kg/day. Therefore, the no-observed-adverse-effect levels (NOAELs) of 1,4- dichlorobutane were considered to be under 8.3 mg/kg/day for males, 8.3 mg/kg/day for females, more than 300 mg/kg/day for fertility in both sexes, 8.3 mg/kg/day for maternal functions and 50 mg/kg/day for F1 offspring. The absolute toxic dose was believed to be 8.3 mg/kg/day for males, 50 mg/kg/day for females, 50 mg/kg/day for maternal functions and 300 mg/kg/day for F1 offspring. However NOAEL for fertility could not be determined since there were no treatment-related changes. Conclusions: Under the present experimental conditions, 1,4-dichlorobutane is a Category 1B Reproductive Toxicant (presumed human reproductive or developmental toxicant).

• Toxicological Research
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• 제23권2호
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• pp.151-158
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• 2007

tert-Butyl acetate is an organic solvent used for coatings, industrial cleaning, and surface treatment applications. This study investigated the potential adverse effects of tert-butyl acetate on pregnant dams and embryo-fetal development after maternal exposure on gestational days 6 through 19 in rats. The test chemical was administered to pregnant rats by gavage at dose levels of 0, 500, 1,000, 1,500, and 2,000 mg/kg/day. All dams were subjected to a caesarean section on day 20 of gestation and their fetuses were examined for any external, visceral, and skeletal abnormalities. At 2,000 mg/kg, treatment-related clinical signs, including piloerection, abnormal gait, decreased locomotor activity, loss of fur, reddish tear, anorexia, nasal discharge, vocalization and coma, were observed in a dose-dependent manner. All dams died between the 2nd day and 5th day of treatment due to a severe systemic toxicity. At 1,500 mg/kg, minimal maternal toxicity including an increase in the incidence of decreased locomotor activity and loss of fur, and an increase in the weights of adrenal glands and liver was observed. On the contrary, no significant adverse effect on the embryo-fetal development was detected. There were no adverse effects on either pregnant dams or embryo-fetal development at <1,000 mg/kg. These results show that a 14-day repeated oral dose of tert-butyl acetate in rats caused a minimal maternal toxicity including increases in the incidence of clinical signs and the weights of adrenal glands and liver, but no embryotoxicity and teratogenicity at 1,500 mg/kg/day. Under these experimental conditions, the no-observed-adverse-effect level (NOAEL) of tert-butyl acetate is estimated to be 1,000 mg/kg per day for dams and 1,500 mg/kg per day for embryo-fetal development.

• Toxicological Research
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• 제16권2호
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• pp.117-124
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• 2000

The objective of this experiment is to investigate neurobehavioral and developmental effects of fumonisin B1 (FB1) after prenatal FB1 administration in rats. FB1 (0.8 or 1.6 mg/kg) was orally exposed to pregnant rats during gestational days 13 to 20, whereas the vehicle alone was administered to control group. Maternal and offspring body weights, physical landmarks of incisor eruption, eye opening, testes descending and vaginal opening, open field activity, running wheel activity, and complex maze performance were included as endpoints for developmental and neurobehavioral measurement. Maternal body weights were not signfficantly altered after FB1 exposure. Percentage of maternal weight gain difference between control and 1.6 mg/kg FBI groups was about 4%. Pre- and post-weanling weight of offsprings after prenatal exposure to FB1 was not signfficantly changed, suggesting that FB1 at 0.8 or 1.6 kg/kg doses may not cross the placenta. Significant gender difference in running wheel activity on postnatal days 57 to 63 and complex maze performance on postnatal days 75 to 78 was observed.

• Toxicological Research
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• 제22권2호
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• pp.127-133
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• 2006

Recently, we have reported that the environmental pollutant 2-bromopropane (2-BP) induces a significant embryo-fetal developmental toxicity in rats. However, the cause of developmental toxicity and the relationship between maternal and developmental toxicities could not be elucidated because the developmental toxicity of 2-BP was observed only in the presence of maternal toxicity The in vitro teratogenicity study using whole embryo culture was carried out to understand the teratogenic properties and the possible mechanism of teratogenicity induced by 2-BP in rats. Rat embryos aged 9.5 days were cultured in vitro for 48 hrs at medium concentrations of 0, 1, 3, or 10 mg/ml of 2-BP. Embryos were evaluated for growth, differentiation, and morphological alterations at the end of the culture period. At 10 mg/ml, 2-BP caused a delay in the growth and differentiation of embryos and an increase in the incidence of morphological alterations, including altered yolk sac circulation, abnormal axial rotation, craniofacial hypoplasia, open neuropore, absent optic vesicle and kinked somites. At 3 mg/ml, only a delay in the growth and differentiation of embryos was observed. There were no adverse effects on embryonic growth and development at the concentration of 1 mg/ml. The results showed that the exposure of 2-BP to rat embryos results in a developmental delay and morphological alterations at dose levels of 3 mg/ml culture media or higher and that 2-BP can induce a direct developmental toxicity in rat embryos.

• 생명과학회지
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• 제11권5호
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• pp.447-456
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• 2001

임신랫드에서 fluoroquinolone 항균제 DW-116에 의해 유발된 발생독성이 모동물의 사료섭취량 감소에 의한 영양 결핍이 주요 원인인지 아니면 DW-116이 배.태자에 직접적으로 작용하여 유발된것인지를 조사하고자 시험물질을 랫드에 임신 6일에서 16일까지 0 및 500 mg/kg 용량으로 반복 경구투여하였다. 사료제한군은 시험물질 투여군의 모동물의 섭취한 동일한 양의 사료를 제한급여하였다. 모든모동물을 임신 20일째에 제왕절개하였고, 모독성 및 발생독성을 평가하였다. 시험물질 투여군에서는 독성증상과 체중의 감소, 투여 및 투여후 기간의 체중증가 억제, 사료섭취량의 감소를 포함하는 모독성이 부형제대조군및 사료제한군에 비해 현저하게 증가하였다. 또한, 태자사망의 증가, 생존태자의 감소, 태자체중과 태반중량의 감소, 태자기형의 증가 및 골환지연을 포함하는 발생독성도 현저하게 증가하였다. 반면, 사료제한군에서는 모체 및 태자에서 경미한 독성고견만 인정되었고, 태자사망이나 태자기형 등의 심각한 발생독성은 관찰되지 않았다. 결론적으로 시험물질투여군에서 관찰된 발생독성은 사료섭취량의 감소에 의한 모체의 영양결핍에 기인된 것이 아니라 DW-116의 투여에 기인된 직접효과인 것으로 판단된다.