• Title/Summary/Keyword: reproductive and developmental toxicity

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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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Study on the Reproductive and Developmental Toxicity of 3-MCPD (3-MCPD의 생식ㆍ발생독성에 관한 연구)

  • 곽승준;김순준;최요우;이규식;손경희;이이다;채수영;정용현;유일재
    • Toxicological Research
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    • v.20 no.2
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    • pp.131-136
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    • 2004
  • 3-Monochloro-1,2-propanediol(3-MCPD) is a toxic compound, often present in different foods containing acid hydrolyzed(AH) protein, like seasonings and savory food products. The purpose of the present study was to investigate the effects of 3-MCPD on male fertility, sperm and testosterone secretion. In vivo male fertility test was performed for observing the adverse effects of 3-MCPD on the function of male reproductive system and pregnancy outcome. 0.01, 0.05, 0.25, 1 and 5 mg/kg b.w. of 3-MCPD was given daily by gavage to groups of 15 adult male SD rats for 4 weeks. At the end of pre-treatment period, males were mated overnight with normal females. Following morning, males demonstrating successful induction of pregnancy were sacrificed on that day to assess sperm parameters and histopathology of reproductive organs. The resulting pregnant females were sacrificed on day 20 of gestation to evaluate pregnancy outcome. As a result, four-week paternal administration with 3-MCPD resulted in adverse effects on male fertility and pregnancy outcome without remarkable histopathological changes in testes and epididymides; sperm motility, copulation index and fertility index were markedly decreased in the treated group and numbers of live fetuses showed steep dose-response curves. Also, spermatogenesis was investigated in this experiment. However, no effect was observed on production of sperm in testes treated with 3-MCPD for 4 weeks. Hormone assay was performed for observing the effects of 3-MCPD on testosterone and luteinizing hormone (LH) in blood and testes of male SD rats and cultured primary Leydig cell. In result, significant changes of related hormones did not observed by treatment of 3-MCPD. These results indicated that paternal treatment with 3-MCPD induced spermatotoxic effect, which caused an antifertility on male.

Reproductive Toxicity Study of LBO0014, A New Recombinant Human Erythropoietin: Teratogenicity Study in Rats (새로운 인체 재조합 적혈구 조혈인자 LB00014의 생식독성연구: 랫드 최기형성시험)

  • 정문기;양병철;김종춘;송시환;이상구
    • Biomolecules & Therapeutics
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    • v.6 no.1
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    • pp.82-88
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    • 1998
  • LBO0014, 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 Fl 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 lU/kg. There was an ulcrease in the spleen weight at 600 and 3,0007/kg. Developmental toxicity was evident as increased resorptions at 3,000 lU/kg. At 600 and 3,000 RJ/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 lU/kg. A decrease in the number of metacarpi and metatarsi was also seen at 3,000 nJ/kg. The results show that the no observed adverse effect dose level (NOAEL) for material toxicity was over 3,000 IU/kg/day and the NOAEL for developmental toxicity was 120 IU/kg/day.

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Combined Repeated Dose and Reproductive/Developmental Toxicities of Benzoyl Peroxide (Benzoyl Peroxide의 반복투여 독성과 생식 및 발생독성)

  • 송상환;김수현;배희경;김미경;구현주;박광식;이상균;박중훈;최은실
    • Toxicological Research
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    • v.19 no.2
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    • pp.123-131
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    • 2003
  • This study was carried out to assess the combined repeated dose, reproduction and developmental toxicities of benzoyl peroxide for OECD SIDS (Screening Information Data Set) program. Male and female Sprague-Dawley rats were exposed to benzoyl peroxide at dose levels of 0, 250, 500 and 1,000 mg/kg/day for 29 days for males and for 41-51 days for females. No deaths were found in all animals including control group during exposure period. No hematological effects attributable to benzoyl peroxide were observed in all treated groups. Significant decrease in the weight of testes and epididymis were observed in males at 1,000 mg/kg/day. In females at 1,000 mg/kg/day, slight histopathological effects in uterus such as epithelial vacuolation or hyperplasia were observed. No treatment-related changes in precoital time and rate of copulation, fertility and gestation period were noted in all treated groups. There was no evidence of teratogenic effect of benzoyl peroxide, but body weight of pups at 1,000 mg/kg/day was significantly decreased. NOAEL for combined repeated dose and reproduction/developmental toxicity was 500 mg/kg/day.

Reproductive Toxicity Study of Aspalatone, A New Antithrombetic Agent: Teratogenicity Study in Rats (항혈전제 아스파라톤의 생식독성연구:랫드 최기헝성시험)

  • 정문구;이상준;김종춘;송시환
    • Biomolecules & Therapeutics
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    • v.6 no.2
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    • pp.151-158
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    • 1998
  • 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. Develo-pmental 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.

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Mitochondrial oxidative damage by co-exposure to bisphenol A and acetaminophen in rat testes and its amelioration by melatonin

  • Hina Rashid;Mohammad Suhail Akhter;Saeed Alshahrani;Marwa Qadri;Yousra Nomier;Maryam Sageer;Andleeb Khan;Mohammad F. Alam;Tarique Anwer;Razan Ayoub;Rana J. H. Bahkali
    • Clinical and Experimental Reproductive Medicine
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    • v.50 no.1
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    • pp.26-33
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    • 2023
  • Objective: Human exposure to multiple xenobiotics, over various developmental windows, results in adverse health effects arising from these concomitant exposures. Humans are widely exposed to bisphenol A, and acetaminophen is the most commonly used over-the-counter drug worldwide. Bisphenol A is a well-recognized male reproductive toxicant, and increasing evidence suggests that acetaminophen is also detrimental to the male reproductive system. The recent recognition of male reproductive system dysfunction in conditions of suboptimal reproductive outcomes makes it crucial to investigate the contributions of toxicant exposures to infertility and sub-fertility. We aimed to identify toxicity in the male reproductive system at the mitochondrial level in response to co-exposure to bisphenol A and acetaminophen, and we investigated whether melatonin ameliorated this toxicity. Methods: Male Wistar rats were divided into six groups (n=10 each): a control group and groups that received melatonin, bisphenol A, acetaminophen, bisphenol A and acetaminophen, and bisphenol A and acetaminophen with melatonin treatment. Results: Significantly higher lipid peroxidation was observed in the testicular mitochondria and sperm in the treatment groups than in the control group. Levels of glutathione and the activities of catalase, glutathione peroxidase, glutathione reductase, and manganese superoxide dismutase decreased significantly in response to the toxicant treatments. Likewise, the toxicant treatments significantly decreased the sperm count and motility, while significantly increasing sperm mortality. Melatonin mitigated the adverse effects of bisphenol A and acetaminophen. Conclusion: Co-exposure to bisphenol A and acetaminophen elevated oxidative stress in the testicular mitochondria, and this effect was alleviated by melatonin.

The effects of estradiol and its metabolites on the regulation of CYP 1A1 expression.

  • Joung, Ki-Eun;Sheen, Yhun-Yhong
    • Proceedings of the PSK Conference
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    • 2002.10a
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    • pp.294.1-294.1
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    • 2002
  • The effects of estradiol and its metabolites on the regulation of CYP1A1 expression. K.E. Joung and Y.Y. Sheen College of Pharmacy, Ewha womans University, Seoul. 120-750, Korea 2, 3.7.8-Tetrachlorodibenzo-p-dioxin (TCDD) is the most potent halogenated aromatic hydrocarbon congener that induces expression of several genes including CYP1A1. Exposure to TCDD results in many toxic actions such as carcinogenesis, hepatotoxicity. immune suppression. and reproductive and developmental toxicity. (omitted)

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Working Environment and Risk Assessment of Gasoline in Workplace (Gasoline 취급 사업장의 작업환경 측정 및 위해성 평가)

  • Kim, Hyeon-Yeong
    • Journal of the Korean Institute of Gas
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    • v.18 no.4
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    • pp.1-7
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    • 2014
  • To protect the workers' health, we evaluated the hazards of gasoline which the large amounts of use and lack of information, and perform the risk assessment through the measurement of working environment. It is estimated the reproductive toxicity, and has germ cell mutagenicity class 1B, also IARC 2B, ACGIH A3 with carcinogenicity. With working environment, it is measured as below the TLV-TWA $900mg/m^3$. It is also calculated $0.3mg/m^3$ as carcinogenicity RfC (worker), $2.7mg/m^3$ as chronic inhalation toxicity RfC (worker), $2.7mg/m^3$ as developmental toxicity RfC (worker). From all of these results, it is calculated that the risks are 459, 51 and 51 as carcinogenicity, chronic inhalation toxicity and developmental toxicity, respectively. It is concluded that the risk of gasoline is evaluated over 1.

Toxicological Characterization of Phthalic Acid

  • Bang, Du-Yeon;Lee, In-Kyung;Lee, Byung-Mu
    • Toxicological Research
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    • v.27 no.4
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    • pp.191-203
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    • 2011
  • There has been growing concern about the toxicity of phthalate esters. Phthalate esters are being used widely for the production of perfume, nail varnish, hairsprays and other personal/cosmetic uses. Recently, exposure to phthalates has been assessed by analyzing urine for their metabolites. The parent phthalate is rapidly metabolized to its monoester (the active metabolite) and also glucuronidated, then excreted. The objective of this study is to evaluate the toxicity of phthalic acid (PA), which is the final common metabolic form of phthalic acid esters (PAEs). The individual PA isomers are extensively employed in the synthesis of synthetic agents, for example isophthalic acid (IPA), and terephthalic acid (TPA), which have very broad applications in the preparation of phthalate ester plasticizers and components of polyester fiber, film and fabricated items. There is a broad potential for exposure by industrial workers during the manufacturing process and by the general public (via vehicle exhausts, consumer products, etc). This review suggests that PA shows in vitro and in vivo toxicity (mutagenicity, developmental toxicity, reproductive toxicity, etc.). In addition, PA seems to be a useful biomarker for multiple exposure to PAEs in humans.

The Toxicological Effects of Ahnjon-Yichun-Tang in Pregnant Rats and Fetuses (안존이천탕 추출물이 흰쥐의 모체 및 태자에 미치는 영향)

  • Kim, Bum Hoi
    • 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.