임신 랫트의 페놀 노출에 따른 태자의 발육 지연효과

정문구,Chung, Moon-koo 대한수의학회 1994 大韓獸醫學會誌 Vol.34 No.3

This study was carried out to investigate the potential of phenol to induce embryotoxicity in the Sprague-Dawley rat. Seventy mated rats were distributed among three treated troups, a vehicle control group and a negative control group. Phenol was at dose levels of 20, 60 and 180mg/kg/day adminsistered by gavage to pregnant rats three times per day from days 7 to 12 of gestation. All dams were subjected to the caesarean section on day 20 of gestation. At 120mg/kg, dams exhibited decreased locomotivity. In addition, both weight reduction and retarded ossification of fetuses were observed. There were no signs of maternal toxicity or embryotoxicity at 20 and 60mg/kg. The results show that phenol induces fetal growth retardation at maternally subtoxic dose in rats.

Embryotoxic effects of DA-125, a new anthracycline anticancer agent, in rats

정문구,김종춘,Chung, Moon-koo,Kim, Jong-choon The Korean Society of Veterinary Science 1994 大韓獸醫學會誌 Vol.34 No.1

DA-125는 새로운 안트라사이클린계 항암성 항생제로서 아드리아마이신의 유도체이다. Sprague-Dawley 랫트를 이용하여 DA-125의 배아 및 태자독성발현능력을 조사하였다. 교미확인(정충확인일=0일)된 120마리의 랫트를 4개군으로 나눈후 0, 0.1, 0.3 및 1.0mg/kg의 용량으로 임신 7일 부터 임신 17일까지 1일 1회 연속 정맥투여 하였으며 임신 20일째에 제왕절개를 하여 태자를 적출하였다. 1mg/kg 투여군에서는 모동물의 사료섭취량의 감소, 체중감소 및 비장중량의 감소와 배아 흡수율의 증가 및 태자체중의 감소가 관찰되었다. 또한 여러가지 종류의 외표, 내부장기 및 골격기형들이 각각 11.9, 41.8 및 14.5%의 빈도로 출현했다. 그중 특이 기형소견으로는 뇌탈출증, 복벽파열, 외측 및 제3뇌실의 확장, 늑골유착 등을 들 수 있다. 0.1 및 0.3mg/kg 투여군에서는 어떠한 배아 및 태자 독성증상도 나타나지 않았다. 이상의 결과에서 DA-125는 랫트에 있어서 경미한 모독성 용량에서 배아 및 태자독성효과를 나타냄을 알 수 있었다. DA-125 is a new anthracycline antitumor antibiotic, which is derived from adriamycin. The potential of DA-125 to induce embryotoxicity was evaluated in the Sprague-Dawley rats. One hundred twenty naturally mated SD rats(sperm in vaginal lavage=day 0) were distributed among three treated groups and a control group. DA-125 was administered intravenously at dose levels of 0. 0.1, 0.3 and 1.0mg/ kg/day. Dams were treated from day 7 to 17 of gestation and were subjected to the caesarean section on day 20. At 1 mg/kg, reduced food intake, reduced body weight and decreased weight of spleen were observed in dams. An increase in the resorption rate and a reduction in the fetal weight were also found. In addition, various types of external, visceral and skeletal malformations occurred at an incidence of 11.9, 41.8 and 14.5%, respectively. Characteristic malformations include exencephalia, gastroschisis, cleft lip, dilatation of lateral and 3rd ventricle, fused ribs, among others. There were no signs of maternal toxicity or embryotoxicity at 0.1 and 0.3mg/kg. The results show that the test agent DA-125 is embryotoxic at maternally subtoxic dose in rats.

복합항생제 SM-101 ( 설박탐 , 메탐피실린 ) 의 생식독성연구 랫트 수태능력시험

정문구(Moon Koo Chung),송시환(Si Whan Song),노정구(Jung Koo Roh) 한국응용약물학회 1996 Biomolecules & Therapeutics(구 응용약물학회지) Vol.4 No.1

A new composite antibiotic, SM-101(sulbactam·metampicillin), was at dose levels of 0, 250, 500 and 1000 ㎎/㎏/day administered intravenously to Sprague-Dawley male rats from premating to mating period and to females from premating to early gestation period. Effects of test agent on general findings and reproductive performance of parent animals and embryonic development were examined. In male parents, two deaths occurred at 1000 ㎎/㎏. The increase in kidney weight of the 1000 ㎎/㎏ group were also observed. The decrease in body weight and food consumption were found at 500 and 1000 ㎎/㎏. The decrease in spleen weight were seen at 250, 500 and 1000 ㎎/㎏. In female parents, three deaths were found at 1000 ㎎/㎏. Mating performance and fertility of parent animals were not adversely affected by all doses tested. F1 fetuses showed no changes related to treatment of SM-101. The results show that the no effect dose level(NOEL) for general toxicity of parent animals is under 250 ㎎/㎏/day and NOELs for reproductive capability and fetal development are over 1000 ㎎/㎏/day.

복합항생제 SM-101 ( 설박탐 , 메탐피실린 ) 의 생식독성연구 랫트 최기형시험

정문구(Moon Koo Chung),김종춘(Jong Choon Kim),한상섭(Sang Seop Han) 한국응용약물학회 1996 Biomolecules & Therapeutics(구 응용약물학회지) Vol.4 No.1

A new composite antibiotic, SM-101(sulbactam ·metampicillin), was at dose levels of 0, 375, 750 and 1500 ㎎/㎏/day administered intravenously to pregnant Sprague-Dawley rats during the organogenetic period. Two-third of dams per group were subjected to caesarean section on day 20 of pregnancy and the remaining 10 dams per group were allowed to deliver. Effects of test substance on dams, embryonal development of F1 fetuses, as well as growth, behaviour and mating performance of F1 offspring were examined. In dams, two deaths occurred at 375 and 1500 ㎎/㎏, respectively. The decrease in the weight of adrenal glands of the 1500 ㎎/㎏ group was observed. The prolongation of pregnancy period was found at 1500 ㎎/㎏. F1 fetuses showed no changes related to the treatment of SM-101. In F1 offspring, the increase in spleen weight was seen at all doses treated. No treatment-related abnormalities were observed in each treated group in terms of development, behaviour and reproductive performance. In F2 fetuses, no drug-induced abnormalities occurred at all doses. The results show that the no-effect dose levels (NOELs) for dams and F1 offspring are under 375 ㎎/㎏/day and NOELs for F1/F2 fetuses are over 1500 ㎎/㎏/day.

새로운 인체 재조합 적혈구 조혈인자 LB00014 의 생식독성 랫드 최기형성시험

정문구(Moon Koo Chung),양병철(Byung Chul Yang),김종춘(Jong Choon Kim),송시환(Si Whan Song),이상구(Sang Koo Lee) 한국응용약물학회 1998 Biomolecules & Therapeutics(구 응용약물학회지) Vol.6 No.1

LB00014, a new recombinant human erythropoietin, was at dose levels of 0, 120, 600, and 3,000 IU/kg/day administered intravenously to pregnant Sprague-Dawley rats during the organogenetic period. All dams were subjected to caesarean section on day 20 of pregnancy. Effects of test substance on dams and embryonic development of F1 fetuses were examined. No treatment-related changes in clinical signs, body weight, and food consumption were observed at all doses tested. At necropsy spleen enlargement was found at 3,000 IU/kg. There was an increase in the spleen weight at 600 and 3,000 IU/kg. Developmental toxicity was evident as increased resorprions at 3,000 IU/kg. At 600 and 3,000 IU/kg, retarded ossification of fetuses occurred at an incidence of 31.3% and 64.7%, respectively. In addition, there was a delay in ossification of sternebrae and sacrocaudal vertebrae at 600 and 3,000 IU/kg. A decrease in the number of metacarpi and metatarsi was also seen at 3,000 IU/kg. The results show that the no observed adverse effect dose level (NOAEL) for maternal toxicity was over 3,000 IU/kg/day and the NOAEL for developmental toxicity was 120 IU/kg/day.

새로운 안트라사이클린계 항암제 DA-125 의 생식독성연구 토끼 최기형시험

정문구(Moon Koo Chung),김종춘(Jong Choon Kim),한상섭(Sang Seop Han),노정구(Jung Koo Roh) 한국응용약물학회 1995 Biomolecules & Therapeutics(구 응용약물학회지) Vol.3 No.1

DA-125, a new anthracycline antitumor antibiotic, was administered at dose levels of 0, 0.2, 0.6 and 1.8 mg/kg/day intravenously to pregnant New Zealand White rabbits from day 6 through 18 of gestation. The does were subjected to the caesarean section on day 28 of gestation. Effects of test agent on general toxicity of does and embryonic development of F1 fetuses were examined. At 1.8 mg/kg, the organ weight for ovary of does was significantly decreased. The decrease in the number of corpus lutea, implantations and litter size, and the increase in the rate of resorptions were also observed. In addition, various types of external, visceral and skeletal malformations occurred in fetuses at an incidence of 7.7, 7.7 and 20.6 %, respectively. The results show that the no effect dose levels (NOELs) of DA-125 are 0.6 mg/kg/day for does and F1 fetuses.

새로운 안트라사이클린계 항암제 DA-125 의 생식독성연구 랫트 주산기 및 수유기시험

정문구(Moon Koo Chung),이순복(Soon Bok Lee),한상섭(Sang Seop Han),노정구(Jung Koo Roh) 한국응용약물학회 1995 Biomolecules & Therapeutics(구 응용약물학회지) Vol.3 No.1

DA-125, a new anthracycline antitumor antibiotic, was administered at dose levels of 0, 0.04, 0.2 and 1.0 mg/kg/day intravenously to pregnant and subsequently delivered Sprague-Dawley rats from day 17 of gestation to day 21 of lactation. Effects of test agent on general toxicity of dams and growth, behaviour and mating performance of F1 offspring were examined. At 1 mg/kg, one out of the twenfytwo dams showed difficult delivery, characterised by a stillbirth. Reduction in body weight, loss in food intake, and decrease in spleen weight were also observed in dams. In addition, the lower rates of successful performances in memory test (28.6%) and necrosis of tail end (9.5%) were seen in F1 offspring. At 0.04 and 0.2 mg/kg, no toxic effect on dams and F1 offspring was observed. There were no malformed F1 and F2 fetuses in all groups. The results indicate that the no effect dose levels(NOELs) of DA-125 are 0.2 mg/kg/day for dams and F1 offspring, and over 1 mg/kg/day for F2 fetuses.

복합항생제 SM-101 ( 설박탐 - 메탐피실린 ) 의 생식독성연구 랫트 주산기 및 수유기시험

정문구(Moon Koo Chung),김종춘(Jong Choon Kim) 한국응용약물학회 1996 Biomolecules & Therapeutics(구 응용약물학회지) Vol.4 No.4

A new composite antibiotic, SM-101 (sulbactam ·metampicillin), was at dose levels of 0, 250, 500 and 1000 ㎎/㎏/day administered intravenously to pregnant and subsequently delivered Sprague-Dawley rats from day 17 of gestation to day 21 of lactation. Effects of test agent on dams and growth, behaviour and mating performance of F1 offspring were examined. In dams, one death occurred at 1000 ㎎/㎏. The increase in kidney weight of the 250, 500 and 1000 ㎎/㎏ group was found. In F1 offspring, both delayed incisors eruption and decreased body weight were observed in females of the 1000 ㎎/㎏ group. The increase in the weights of liver and kidney was found in males of the 1000 ㎎/㎏ group. No treatment-related abnormalities were observed in each treated group in terms of behaviour and reproductive performance. In F1/F2 fetuses, no drug-induced abnormalities occurred at all doses tested. The results show that the no effect dose level (NOEL) of SM-101 is under 250 ㎎/㎏/day for dams and 500 ㎎/㎏/day for F1 offspring, and over 1000 ㎎/㎏/day for F1/F2 fetuses.

랫드를 이용한 Acetanilide의 반복투여 및 생식/발생독성 병행시험

정문구(Moon-Koo Chung),백성수(Sung-Soo Baek),이상희(Sang-Hee Lee),김현미(Hyun-Mi Kim),최경희(Kyung-Hee Choi),한상섭(Sang-Seop Han) 한국독성학회 2007 Toxicological Research Vol.23 No.2

The study was conducted to assess the repeated dose and reproduction and developmental toxicities of acetanilide, an intermediate for drug production, as a part of OECD Screening Information Data Set (SIDS) program. The test agent was administered by gavage at dose levels of 0, 22, 67, 200 and 600 ㎎/㎏ to Sprague-Dawley rats (12/group/sex) during pre-mating and mating period for males(up to 30 days) and females and pregnancy and early lactation period for females (up to 39~50 days). At 22 ㎎/㎏, decreases in HGB, HCT (males) and MCHC (females), hyperplasia of spleen red pulp, hyperplasia of femur bone marrow (both sexes) were observed. At 67 ㎎/㎏, salivation (males), reduced food consumption (both sexes), decreases in RBC, HGB, HCT and MCHC (males), increases in MCV (males) and spleen weight (males), hyperplasia of spleen red pulp and femur bone marrow (both sexes) were observed. At 200 ㎎/㎏, decreases in locomotor activity and salivation (both sexes), reduced food consumption (both sexes), decreases in RBC, HGB, HCT and increases in MCV, MCH, BUN, T-BIL (males), enlargement of spleen (both sexes), increased weight of spleen (males), hyperplasia of spleen red pulp and femur bone marrow and extramedullary hematopoiesis of liver (both sexes), atrophy of thymus and corpus luteum hyperplasia of ovary (females) were observed. At 600 ㎎/㎏, decreases in locomotor activity, cyanosis (both sexes), reddish tear, and salivation (males), mortality (4 out of 12 females), decreased body weight (females), reduced food consumption (both sexes), decreases in RBC, HGB, HCT and MCHC and increases in WBC, MCV, MCH, reticulocyte, neutrophil, lymphocyte, monocyte, AST, ALT, BUN, T-BIL, ALB, Ca and A/G ratio (males), enlargement of spleen, increased weights of spleen (both sexes), liver (males), kidney and ovary, decreased weights of thymus (females), hyperplasia of spleen red pulp, hyperplasia of femur bone marrow and extramedullary hematopoiesis of liver (both sexes), and atrophy of thymus and corpus luteum hyperplasia of ovary (females) were observed. Regarding the reproduction and development toxicities, there were no treatment- related changes in precoital time, mating index, fertility index and pregnancy index at all doses tested. At 22 and 67 ㎎/㎏, there were no adverse effects on all the parameters observed. At 200 ㎎/㎏, decreased body weight of pups (day 4 p.p.) were observed. At 600 ㎎/㎏, decreased body weight of pups (day 0 and 4 p.p.) and viability index (day 4 p.p.), increased incidence of newborns dead or with abnormal clinical signs were observed. The results suggest that the NOAELs for general toxicity are < 22 ㎎/㎏, LOAELs are 22 ㎎/㎏ and the NOAELs for reproductive toxicity are 67 ㎎/㎏.

항혈전제 아스파라톤의 생식독성연구 랫드 최기형성시험

정문구(Moon Koo Chung),이상준(Sang Joon Lee),김종춘(Jong Choon Kim),송시환(Si Whan Song) 한국응용약물학회 1998 Biomolecules & Therapeutics(구 응용약물학회지) Vol.6 No.2

Aspalatone, a new antithrombotic agent, was administered orally to pregnant Sprague-Dawley rats during the organogenetic period at dose levels of 0, 20, 100 and 500 mg/kg/day. All dams were subjected to caesarean section on day 20 of pregnancy. Effects of test substance on dams and embryonic development of F1 fetuses were examined There were treatment-related decreases in body weight and food consumption in the 500 mg/kg group. There was a increase in the spleen weight in the 100 and 500 mg/kg groups. Developmental toxicity was evident as decreased fetal body weights and increased fetal malformations in the 500 mg/kg group. External and skeletal malformations of fetuses occurred at an incidence of 1 and 8.2%, respectively. In addition, there was a delay in ossification of sternebrae and sacrocaudal vertebrae in the 500 mg/kg group. The results show that the no observed adverse effect dose level (NOAEL) for maternal toxicity was 20 mg/kg/day and for developmental toxicity was 100 mg/kg/day.