• Title/Summary/Keyword: Reproductive Toxicity

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Reproductive Toxicity Study of SM-101(sulbactam.metampicillin): Fertility Study in Rats (복합항생제 SM-101(설박탐.메탐피실린)의 생식독성연구: 랫트 수태능력시험)

  • 정문구;송시환;노정구
    • Biomolecules & Therapeutics
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    • v.4 no.1
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    • pp.51-58
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    • 1996
  • A new composite antibiotic, SM-101(sulbactam.metampicillin), was at dose levels of 0, 250, 500 and 1000 mg/kg/day administered intravenously to Sprague-Dawley male rats from predating 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 mg/kg. The increase in kidney weight of the 1000 mg/kg group were also observed. The decrease in body weight and food consumption were found at 500 and 1000 mg/kg. The decrease in spleen weight were seen at 250, 500 and 1000 mg/kg. In female parents, three deaths were found at 1000 mg/kg. 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 mg/kg/day and NOELS for reproductive capability and fatal development are over 1000 mg/kg/day.

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Estrogenic and Androgenic Potential of Phthalates and Their Alternatives (프탈레이트류와 그 대체물질의 내분비계 교란독성: 에스트로겐성과 안드로겐성을 중심으로)

  • Kwon, Bareum;Ji, Kyunghee
    • Journal of Environmental Health Sciences
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    • v.42 no.3
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    • pp.169-188
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    • 2016
  • Objectives: Although information on the toxicity of phthalate diesters is readily available, little is known about phthalate alternatives. The present article provides a summary of available information on the toxicity of phthalate diesters and their alternatives, with a special focus on estrogenicity and androgenicity. Methods: We collected a battery of in vitro and in vivo assay data from the literature to assess the estrogenicity/anti-estrogenicity and androgenicity/anti-androgenicity of 15 phthalate diesters and 21 phthalate alternatives. Results: A number of in vitro studies show that certain phthalate diesters can bind to estrogen receptors and have a weak estrogenic potential. However, this potential was not seen in in vivo studies. Phthalate diesters produced anti-androgenic effects in animals by reducing testosterone production. Among them, di-(2-ethyl-hexyl) phthalate (DEHP) was the most potent. While almost all phthalate alternatives have a lower toxic potential than does DEHP, evidence of reproductive toxicity and estrogenic potential were found in several substances. Conclusion: Significant data gaps exist for phthalate alternatives regarding reproductive endocrine disruption, requiring further investigation.

Protective Effects of Water Extract from Cuscutae Semen on Ketoconazole-Induced Oxidative Stress in Testicular Damage Male Rats (토사자 추출물의 ketoconazole로 유도된 고환 독성 흰쥐의 산화적 스트레스 저해효과)

  • Kim, Sung-Hoon;Choi, Jong -Won
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.25 no.3
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    • pp.417-424
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    • 2011
  • Ketoconazole (KET) is an antifungal drug with a broad spectrum of activity that also induces reproductive toxicity in humans and animals. KET inhibits C17-20 lyase which blocks the conversion of 17 ${\alpha}$-hydroxyprogesterone to androstenedione. The effect of Cuscutae semen(CS) extract against KET-induced testicular damage was evaluated in male rats. CS extract was administered orally (100 and 200 mg/kg) for 26 days. Three weeks after CS extract administration, KET was CS-administered intraperitoneally at a dose of 100 mg/kg once a day for 5 days. KET-induced reproductive toxicity was associated with clear reductions of the weights of testes and epididymides, sperm indices and serum testosterone levels. In addition, marked oxidative damage to testicular lipids and alterations of natural antioxidant enzymes were reported in association with KET toxicity. Most of the KET-induced effects were greatly decreased with the concomitant application of CS extract. This study suggests a protective role of Cuscutae semen extract that could be attributed to its antioxidant properties.

A Study on the Priority for the Hazard and Risk Evaluation of Chemicals (HREC) According to the Industrial Safety and Health Act (ISHA) (산업안전보건법 상 관리수준 검토를 위한 화학물질 유해성.위험성 평가대상 후보물질 선정에 관한 연구)

  • Yang, Jeong Sun;Lim, Cheol Hong;Park, Sang Young
    • Journal of Korean Society of Occupational and Environmental Hygiene
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    • v.22 no.1
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    • pp.73-81
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    • 2012
  • Object: The aim of this study is to suggest a list of priority chemicals for the Hazard & Risk Evaluation of Chemicals (HREC) controlled by the Industrial Safety and Health Act (ISHA). Method: Screening assessment was done for 642 chemicals whose exposure threshold limit values were set by the Ministry of Employment and Labor (MOEL). Hazard data were collected from Korea Occupational Safety & Health Agency (KOSHA) and/or other toxicity database. Exposure data were obtained from KOSHA internal database. The hazard and exposure scores of chemicals were listed by order of priority in accordance with GHS classification and exposure index data. Result: From the result of screening risk assessment for 642 chemicals, we extracted a list of 13 priority chemicals for HREC performed by the ISHA. A priority list of 27 chemicals which have carcinogen, mutagen and/or reproductive toxicity but not controlled by the ISHA was suggested for additional evaluation as "chemicals for special management".

A Study on the Recommendation of the Candidate Substances and Methods for an Additional Designation of Special Management Materials in Occupational Safety and Health Act(OSHA) (산업안전보건법 특별관리물질의 추가 지정방법 및 후보물질 권고에 관한 연구)

  • Lee, Kwon Seob;Hong, Mun Ki;Lee, Hye Jin;Byeon, Sang-Hoon;Park, Jung Sun
    • Journal of Korean Society of Occupational and Environmental Hygiene
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    • v.24 no.1
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    • pp.91-102
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    • 2014
  • Objectives: This study was performed in order to devise a procedure for supplementing the Special Management Materials in the Occupational Safety and Health Act and recommend candidate materials. The results are expected to be used as fundamental data for classification and criteria necessary to manage Special Management Materials in workplaces. Also, they are expected to be used as a basis for selecting target materials to nominate as additional Special Management Material. Methods: We investigated the selection standards for candidates and review ranges of data sources to nominate Special Management Materials. The substances classified as GHS(Globally Harmonized System of classification and labeling of chemicals) category 1A(known to have carcinogenic potential and reproductive toxicity for humans) or 1B(presumed to have carcinogenic potential and reproductive toxicity for humans) carcinogens and reproductive toxicants among the Controlled Hazardous Substances of the Regulation on Occupational Safety and Health Standards and substances with OELs(Occupational Exposure Limits) were inspected as the candidates for Special Management Materials. Conclusions: A seven-step procedure for selecting candidates to designate as Special Management Materials was suggested, including the setting of target chemicals for evaluation, classification of CMR(Carcinogens, Mutagens or Reproductive toxicants) by GHS classification and criteria, suggestion and selection of the candidates, and more. This study recommends 58 chemicals as qualified candidates to supplement the Special Management Materials.

Effects of Shingi-whan on the Male Reproductive and Sexual Function : Enhancing Spermatogenesis, Reducing Testicular Toxicity, and Relaxing Smooth Muscle of Corpus Cavernosum (신기환(腎氣丸)의 남성 생식기능 및 성기능 개선효과 : 정자생성 촉진, 고환독성 완화 및 음경해면체 평활근의 이완)

  • Seo, Il-Bok;Park, Sun-Young
    • The Korea Journal of Herbology
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    • v.30 no.3
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    • pp.55-61
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    • 2015
  • Objectives : This study aimed to investigate the effects of Shingi-whan(SG) on the male reproductive and sexual function, so we measured the spermatogenesis and the testicular toxicity in mice and the vasorelaxation in isolated rabbit corpus cavernosum smooth muscle. Methods : To evaluate effect on the spermatogenesis in mice, we prepared two groups, control group and SG group that was orally administered SG(1,000mg/kg) for 20 days, and compared. To analyze testicular toxicity in mice, we also prepared two groups, doxo group that was injected with doxorubicin (3mg/kg) on three times and doxo + SG group that was injected with doxorubicin and SG for 20 days, and compared. To investigate sexual function of SG in mice, we prepared three groups, normal group and aging elicited group consisting of 18-month-old mice, SG treated aging group that was orally administered SG for 60 days, and compared using histochemical staining on mice corpus cavernous tissues. In order to define the relaxation effects of SG, rabbit corpus cavernous tissues were prepared in $2{\times}2{\times}6mm$ sized strip. Then the dose-dependent relaxation responses of SG at 0.01-3.0 mg/ml in contracted strips induced by phenylephrine were measured. Results : The sperm density in dutus epididymis and the diameter of seminiferous tubules of SG group was significantly increased when compared to control group. The testicular weight and the diameter and height of epithelial layer of seminiferous tubules of doxo + SG group was significantly increased when compared to doxo group. The cavernous strips were significantly relaxed by SG extract In SG treated aging group, ratio of smooth muscles to collagen fibers and red blood cell count in venous sinus was increased as compared to aging elicited group. Conclusions : Our findings have shown that SG extract have effect on spermatogenesis and mitigating effect on doxo-induced testicular toxicity. Further, it also have the vasorelaxant effect on rabbit corpus cavernosum.

A Study on thinner's Physicochemical property and its effect on genital organ of rat (시너(thinner)의 물리화학적 특성과 랫트의 생식기에 미치는 영향 연구)

  • Kim, Hyeon-Yeong;Lee, Sung-Bae;Han, Jeong-Hee;Kim, Tae-Gyun;Lee, Jung-Suk;Kang, Min-Gu;Lee, Chae-Kwan
    • Journal of Korean Society of Occupational and Environmental Hygiene
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    • v.18 no.3
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    • pp.224-238
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    • 2008
  • The aim of this study is to confirm the physicochemical property and hazard of thinner (012), which is a diluent of enamel paint used for floor coating for waterproofing and oil painting for the outer wall. The literatures of physicochemical property and hazard of thinner were surveyed and its physicochemical property were evaluated. And then, the inhalation toxicity of thinner affecting the central nervous system and reproductive organs in rats were examined by subchronic (6 h./day. 5 days/ week for 13 weeks) inhalation test. 1) According to the 13-week subchronic inhalation test, there were no significant changes in clinical test and body weight. However, a significant evidence of toxicity was observed in the hematological test and organ weight such as heart, kidney, liver and brain (p<0.01) in the 200 ppm and 1,000 ppm exposure groups in a dose response manner. In the histopathology analysis, there were no significant evidence of toxicity. Therefore, thinner was not classified as an organ targeted toxic agent. In case of Harmfulness, it could be classified as a chronic toxic agent 3($500 ppm/4hr, rat). 2) The reproductive toxicity such as extension of the period of estrous cycle, reduction of serum estradiol concentration and increase of frequency of the abnormal sperm was observed in the 1,000 ppm exposed animals. 3) The result of the physicochemical property of the test material showed that the specific gravity was 0.793, boiling point $155.8^{\circ}C$, steam pressure 2.1 kPa, ignition point $34.5^{\circ}C$, and spontaneous ignition point $280^{\circ}C$. The endothermic and exothermic values were 371.4 J/g and 159.1 J/g. respectively. The explosion limit was 214 mg/l. These data showed that thinner could be classified as an explosion agent level 1.2 and ignitive liquid agent 3 ($23-60^{\circ}C$) according to the notification No. 2008-1 of the Labor Ministry, "Classifying Standard of Chemical Materials."

Studies on the Reproductive and Developmental Toxicity of Herbal Medicine Containing Aristolochic Acids

  • Sohn, K-H;Rhee, G-S;Kim, S-S;Kim, S-H;Kwack, S-J;Chae, S-Y;Park, C-H;Kim, B-H;Kil, K-S;Choi, K-S;Park, K-L
    • Proceedings of the Korean Society of Embryo Transfer Conference
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    • 2002.11a
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    • pp.110-110
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    • 2002
  • Rapidly progressive interstitial renal fibrosis has recently been reported in young women who have been on a slimming regimen including chinese herbs. Aristolochic acid, suspected as the causal factor of this renal disease, is a well known carcinogen. It has been known that Madouling (Aristolochiae fructus) contains aristolochic acid. The objective of this study was to investigate the effects of Madouling, Madouling-tang, which are the extract mixture from 10 different chinese herbs including Madouling, and aristolochic acid on reproductive and developmental toxicity. Female rats were administered orally with the extracts of Madouling, madouling-tang, and aristolochic acid from 14 days before mating to day 17 of gestation. Madouling (8mg/kg) decreased fertility in the 8mg/kg group, but Madouling-tang and aristolochic acids did not. Significant decrease of mean fetal body weights were observed in the 16mg/kg group of aristolochic acids. External, visceral and skeletal malformation of fetuses were not observed with treatment. Histopathological examination showed the discrete damage of kidney in the 8mg/kg group of Madouling and 16mg/kg groups of aristolochic acid. In whole embryo culture, Madouling and Madouling-tang caused the retardation of growth and development of embryo in the dose of 1 $\mu$g/ml and 0.02 $\mu\textrm{g}$/kg, respectively while aristolochic acids showed the similar effect in the dose of 300 $\mu\textrm{g}$/kg. These results indicate that Madouling, up to 0.05mg/kg (prescription dose to human) has no adverse effects on the fertility, reproduction and development of Sprague-Dawley rats.

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THE REGULATION OF CYP1A1 GENE EXPRESSION BY ESTRADIOL AND ITS METABOLITES

  • Joung, Ki-Eun;Sheen, Yhun-Yhong
    • Proceedings of the Korean Society of Toxicology Conference
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    • 2002.11b
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    • pp.149-150
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    • 2002
  • 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is the most potent halogenated aromatic hydrocarbon congener that induces expression of several genes including CYP1A. Exposure to TCDD results in many toxic actions such as carcinogenesis, hepatotoxicity, immune suppression, reproductive toxicity and developmental toxicity.(omitted)

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