• 한국환경보건학회:학술대회논문집
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• 한국환경보건학회 2004년도 International Conference Global Environmental Problems and their Health Consequences
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• pp.185-187
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• 2004

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 showed significant organ weight changes in liver, spleen exposed during lactational periods. But the dams exposed during lactational periods showed significant organ weight changes not only in liver, 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 could be found. Estrogen receptor ${\alpha}$ expression by BPA and BBP in the uterus(dam, F1 female) and testis(F1 male) were studied. There was no significant different $ER{\alpha}$ expression pattern between control and treated groups. But $ER{\alpha}$ expression were increased in F1 male testis and female uterus. F1 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.

• 한국식품영양과학회지
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• 제16권2호
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• pp.63-68
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• 1987

The effects of various levels of copper(Cu) intake on the concentrations of copper, iron (Fe) and 3inc(Zn) in rat tissues were studied in growing rats. For different groups the drinking water was supplemented with 0(control), 25, 50, 100 and 200ppm Cu(as copper sulphate) for 1 day respectively. All animal groups were fed with the control diet (Cu contents, 12.8%mg/kg diet) during the experiment. At the end of the 4 week experiment, body weight gain was slightly lower in the Cu supply groups than in control group. Liver and serum Cu were significantly higher in 50, 100 and 200ppm Cu of male and in 200ppm Cu of female than in control groups. Spleen Cu was significantly increased by the supplementation of Cu. Liver and heart Fe of male and heart Fe of female were increased by incresing supplementary Cu levels. In 50ppm Cu group, liver, spleen and kidney Fe of female increased but the others did not. Fe of tissues was different in male and female rats according to Cu levels supplied. Serum Zn of male and female was significantly lower in 50, 100 and 200ppm Cu groups than in control and 25ppm Cu groups. When supplemented with Cu levels there were no significant differences among groups for liver, kidney, spleen and heart Zn as well as heart and kidney Cu.

• Toxicological Research
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• 제31권4호
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• pp.371-392
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• 2015

TS-DP2 is a recombinant human granulocyte colony stimulating factor (rhG-CSF) manufactured by TS Corporation. We conducted a four-week study of TS-DP2 (test article) in repeated intravenous doses in male and female Sprague-Dawley (SD) rats. Lenograstim was used as a reference article and was administered intravenously at a dose of $1000{\mu}g/kg/day$. Rats received TS-DP2 intravenously at doses of 250, 500, and $1000{\mu}g/kg/day$ once daily for 4 weeks, and evaluated following a 2-week recovery period. Edema in the hind limbs and loss of mean body weight and body weight gain were observed in both the highest dose group of TS-DP2 and the lenograstim group in male rats. Fibro-osseous lesions were observed in the lenograstim group in both sexes, and at all groups of TS-DP2 in males, and at doses of TS-DP2 $500{\mu}g/kg/day$ and higher in females. The lesion was considered a toxicological change. Therefore, bone is the primary toxicological target of TS-DP2. The lowest observed adverse effect level (LOAEL) in males was $250{\mu}g/kg/day$, and no observed adverse effect level (NOAEL) in females was $250{\mu}g/kg/day$ in this study. In the toxicokinetic study, the serum concentrations of G-CSF were maintained until 8 hr after administration. The systemic exposures ($AUC_{0-24h}$ and $C_0$) were not markedly different between male and female rats, between the administration periods, or between TS-DP2 and lenograstim. In conclusion, TS-DP2 shows toxicological similarity to lenograstim over 4-weeks of repeated doses in rats.

• 농약과학회지
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• 제12권3호
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• pp.207-214
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• 2008

내분비장애 추정물질의 분류를 위해 많은 시험법이 연구되고 있는데 추후 내분비장애 추정물질로 분류된 기등록 농약에 대한 자료요구 또는 신규 등록농약에 대한 등록기준의 추가 등을 고려하여 OECD와 EPA에서 권장하는 시험법을 확립하고자 본 연구를 수행하였다. 시험약제를 30일간 경구 투여하여 조사한 결과, alachlor 투여 수컷에서 25 mg/kg/day, 50 mg/kg/day에서 고환과 갑성선의 중량이 증가하였다. Alachlor 투여 암컷에서는 질의 중량이 25, 50 mg/kg/day에서 감소하였고 25 mg/kg/day에서 갑상선의 중량이 감소하였다. Alachlor 투여 암컷 25, 50 mg/kg/day에서 주요 갑상선 호르몬인 T4와 성호르몬 testosterone이 감소하였다. 따라서 pubertal assay 결과 alachlor는 갑상선 호르몬성 영향이 의심되었다. 시험세포를 이용한 시험 결과, 시험약제를 1 nM에서 1000 nM까지 처리하였을 때 음성대조군과 비교하여 alachlor는 100-134%의 갑상선 호르몬성 영향을 나타내었다. 따라서 세포를 이용한 시험에서는 alachlor에 의한 갑상선 호르몬성 영향이 나타나는 것으로 판단되었다. 항갑상선 호르몬성 영향 시험에서는 시험약제 100 nM과 T4의 혼합 처리시 alachlor는 항갑상선 호르몬성 영향은 나타나지 않았다.

• 대한약침학회지
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• 제18권4호
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• pp.45-50
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• 2015

Objectives: In this study, we investigated the 4-week repeated-dose oral toxicity of gami-jakyak gamcho buja decoction (Mecasin) to develop safe treatments. Methods: In order to investigate the 4-week oral toxicity of Mecasin, we administered Mecasin orally to rats. Sprague-Dawley (SD) rats were divided into four groups of five male and five female animals per group: group 1 being the control group and groups 2, 3, and 4 being the experimental groups. Doses of Mecasin of 500, 1,000, and 2,000 mg/kg of body weight were administered to the experimental groups, and a dose of normal saline solution of 10 mL/kg was administered to the control group. We examined the survival rate, weight, clinical signs, and gross findings for four weeks. This study was conducted under the approval of the Institutional Animal Ethics Committee. Results: No deaths occurred in any of the four groups. No significant changes in weights or food consumption between the control group and the experimental groups were observed. Serum biochemistry revealed that some groups showed significant decrease in inorganic phosphorus (IP) (P < 0.05). During necropsy on the rats, one abnormal macroscopic feature, a slight loss of fur, was observed in the mid dosage (1,000 mg/kg) male group. No abnormalities were observed in any other rats. In histopathological findings, the tubular basophilia and cast of the kidney and extramedullary hematopoiesis of the spleen were found. However, those changes were minimal and had occurred naturally or sporadically. No other organ abnormalities were observed. Conclusion: During this 4-week, repeated, oral toxicity test of Mecasin in SD rats, no toxicity changes due to Mecasin were observed in any of the male or the female rats in the high dosage group. Thus, we suggest that the doses in a 13-week, repeated test should be 0, 500, 1,000, and 2,000 mg/kg respectively.

• 한국식품영양과학회지
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• 제42권4호
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• pp.600-607
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• 2013

본 연구는 김치 유래 유산균인 Leuc. citreum GR1의 안정성을 평가하고자 Leuc. citreum GR1을 SD 계통의 흰쥐에게 4주간 반복 경구투여를 통하여 장기투여에 의한 안전성을 확인하고자 식품의약품안전청의 의약품 등의 독성시험기준에 따라 실시하였다. SD 계열의 암수 흰쥐에 시험물질을 0, 500, 1,000 및 2,000 mg/kg/day의 용량으로 4주간 반복 경구투여 한 후 사망률, 일반증상, 체중변화, 사료섭취량, 수분섭취량, 부검소견, 장기무게의 변화, 혈액학적, 혈액생화학적 및 병리조직학적 검사를 실시하였다. 모든 시험군에서 시험기간 시험물질로 인한 일반증상 및 사망동물이 관찰되지 않았다. 전 시험기간 동안 Leuc. citreum GR1의 4주간의 경구투여 결과 체중이 지속적으로 증가되었지만 대조군과 유의성 있는 변화가 관찰되지 않았다. 또한 장기의 육안적 관찰, 장기 중량변화, 혈액학적, 혈액생화학적 및 병리조직학적 검사에서도 모든 시험물질 투여군이 대조군과 유의성이 있는 차이를 보이지 않았으며, 모두 정상 범위를 벗어나지 않아 시험물질에 기인하는 이상 소견을 발견할 수 없었다. 이상의 결과로 보아 4주 반복투여 독성시험 결과 김치 유산균인 Leuc. citreum GR1은 저독성의 안전한 물질로 판정되며, 본 시험물질의 무독성량은 암수 모두 2,000 mg/kg/day 이상을 상회하는 것으로 판단되었다.

• Preventive Nutrition and Food Science
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• 제7권3호
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• pp.278-281
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• 2002

The objective of the current study was to determine the influences of dietary proteins and methionine on plasma lipid concentrations. Thirty growing male Sprague-Dawley rats were fed diets similar in all respects except that dietary protein was from either casein, soy protein isolate, or soy protein isolate supplemented with L-methionine (0.24 %). The animals were fed experimental diets ad libitum for nine weeks. Plasma total-cholesterol concentrations were unaffected by the protein source or methionine supplementation. Plasma triglyceride concentrations were lower in rats of methionine supplemented soy protein diets (76 mg/dL) than in the rats fed casein or soy diet (120 mg/dL, 109 mg/dL, respectively). These results indicate that soy protein reduces plasma triglycerides relative to casein in rats fed cholesterol free diets, and that methionine-supplemented soy diets decrease plasma triglyceride concentrations more than soy protein alone.

• 대한가정학회지
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• 제24권2호
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• pp.51-62
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• 1986

This study was designed to observe the effects of nutritional supplementation of general Korean diet on protein metabolism in growing rats. Seventy weanling Sprague-Dawely male rats weighing 76.8$\pm$1.45g were blocked into ten groups and fed ten different experimental diets for eight weeks. The rats in cereal-vegetable group were fed ad libitum for all the experimental period and those in other experimental groups were pairfed following the feed intake of rats in C-V gp. Control group was given 72% cornstarch-29% casein diet : C-V gp was fed cerealvegetable diet composed of rice, barley, soybean and Chinese cabbage : the other eight groups were fed C-V diets supplemented with casein, vitamin B\sub 2\ calcium, vitamin A, vitamin B\sub 2\ and vitamin A, vitamin A and calcium, vitamin B\sub 2\ and calcium, vitamin A and vitamin B\sub 2\ and calcium, respectively, on the basis of each nutrients content of standard diet.

• 약학회지
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• 제38권1호
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• pp.46-56
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• 1994

Daily oral administration to Sprague Dawly rats for 4 weeks of DWP-301, at doses of 0, 500, 1000, 2000 mg/kg presented following results; 1) No animals died and there were no significant differences in general signs, body weight, food consumption, urinalysis haematological, biochemical, gross pathological and histopathological examination between control and treated rats. 2) Water consumption, pH-, protein- urobilinogen-, ketone-values in urine were significantly increased in the treated male and female rats. It is supposed that these differences in animals are a consistent feature of repeated overdosage with test suspensions. The results indicate that the non toxic dose of test compounds in rats is over 2000 mg/kg in this test system.

• 한국가축번식학회지
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• 제19권2호
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• pp.141-145
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• 1995

The effect of splenectomy on the concentration of progesterone in pregnant wistar rats showing 4-day regular estrous cycles more than two cycles were investigated. The day after mating with the same male animal was designated day 0 of pregnancy. Splenectomy was conducted on day 0 (early-S), 6 (middle-S) and 13 (late-S) of pregnant rat, respectively. Blood sample were collected at day 1, 7, 14 and 21 of pregnancy. Concentraton of serum progesterone was determined by emzyme-linked immunosorbent assay (ELISA) using specific antibodies and emzyme conjugate(progesterone peroxidase labeled). In normal pregnant rats, serum progesterone concentrations were increased significantly (P<0.05) on day 7 and 14 of pregnancy compared with on day 1 of pregnancy and then dramatically decreased on day 21. However in early and middle splenectomized rats, progesterone concentrations were significantly (P<0.05) decreased on day 7 and 14 of pregnancy compared with same day of normal rats. These observations indicate that luteotropic action and steroidogenesis by corpus luteum of ovary may be regulated by splenocytes in rat.