• Title/Summary/Keyword: Toxicity of NO

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Teratogenicity Study of tert-Butyl Acetate in Rats (랫드에서 초산 제3부틸의 최기형성 시험)

  • Ahn, Tai-Hwan;Yang, Young-Su;Lee, Jong-Chan;Kang, Seong-Soo;Bae, Chun-Sik;Kim, Sung-Ho;Kim, Jong-Choon;Kim, Hyeon-Yeong;Chung, Yong-Hyun
    • Toxicological Research
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    • v.23 no.2
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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.

Reproductive and Developmental Toxicity of Amitraz in Sprague-Dawley Rats

  • Lim, Jeong-Hyeon;Kim, Sung-Hwan;Kim, Kang-Hyeon;Park, Na-Hyeong;Shin, In-Sik;Moon, Chang-Jong;Park, Soo-Hyun;Kim, Sung-Ho;Kim, Jong-Choon
    • Toxicological Research
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    • v.26 no.1
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    • pp.67-74
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    • 2010
  • The present study was conducted to obtain information on the effects of amitraz on reproductive and developmental parameters in rats. The test chemical was administered via the drinking water containing 0, 40, 120, and 360 ppm to male rats from 2 weeks before mating to the end of 14-day mating period and to females from 2 weeks before mating, throughout mating, gestation and up to lactational day 4. During the study period, clinical signs, body weights, food intake, organ weights, reproductive and littering findings, necropsy findings, sperm parameters, and histopathology were examined. At 360 ppm, decreases in the body weight gain, food consumption, and the number of live pups and an increase in the post-implantation loss were observed. In addition, decreases in the seminal vesicle weight and sperm motility were found in males. At 120 ppm, a decrease in the food consumption was found transiently in both males and females, but no reproductive and developmental toxicity was observed in both sexes. There were no signs of either general or reproductive and developmental toxicity in the 40 ppm group. Based on these results, it was concluded that the repeated oral administration of amitraz to rats resulted in a decrease in the food consumption at 120 ppm and decreases in the seminal vesicle weight, sperm motility, and the number of live pups and an increase in the post-implantation loss at 360 ppm in rats. Under these experimental conditions, the no-observed-adverse-effect level (NOAEL) of amitraz for general and reproduction/developmental toxicity was believed to be 120 ppm, and the no-observed-effect level (NOEL) of amitraz was believed to be 40 ppm in rats.

A Study on the Degradation of Parathion and Reduction of Acute Toxicity in Solar $TiO_2$ Photocatalysis (태양광 $TiO_2$ 광촉매를 이용한 Parathion의 분해와 독성저감에 관한 연구)

  • Kim, Tak-Soo;Kim, Jung-Kon;Choi, Kyung-Ho;Zoh, Kyung-Duk
    • Journal of Korean Society of Environmental Engineers
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    • v.27 no.8
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    • pp.822-828
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    • 2005
  • The photocatalytic degradation of methyl parathion was carried out using a circulating $TiO_2$/solar system. Under the photocatalytic condition, parathion was more effectively degraded than by the photolysis or $TiO_2$ only condition. The parathion degradation followed pseudo first-order kinetics. With photocatalysis, 10 mg/L parathion was completely degraded within 90 min with a TOC decrease exceeding 63% after 150 min. The nitrogen from parathion was recovered mainly as ${NO_2}^-$, ${NO_3}^-$, and ${NH_4}^+$, 80% of sulfur as ${SO_4}^{2-}$, and less than 5% of phosphorus as ${PO_4}^{3-}$ during photocatalysis. The organic intermediates 4-nitrophenol and paraoxon were also identified, and these were further degraded. Two different bioassays using V. fischeri and D. magna were employed to measure the toxicity reduction in the solutions treated by both photocatalysis and photolysis. Relative toxicity was reduced almost completely after 150 min in both organisms under the photocatalysis, whereas in photolysis, 76 and 57% reduction was achieved for V. fischeri and D. magna, respectively. The acute toxicity reduction pattern corresponded with the decrease in parathion and TOC concentrations.

A Study on GHS Classification of 3-Methylpentane by Subacute Inhalation Toxicity (아급성흡입독성시험을 이용한 3-Methylpentane의 GHS 분류·표시)

  • Chung, Yong Hyun;Han, Jeong Hee;Shin, Seo Ho
    • Journal of the Korean Institute of Gas
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    • v.21 no.1
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    • pp.6-17
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    • 2017
  • Objectives : The purpose of this study was to obtain information regarding Globally Harmonized System(GHS) classification and health hazards that may result from a 4 weeks inhalation exposure of 3-Methylpentane in Sprague-Dawley rats. Methods : The testing method was conducted in accordance with OECD guidelines for the testing of chemicals No. 412(Subacute Inhalation Toxicity). The Rats were divided into 4 groups(5 male and 5 female rats in each group) and exposed to 0 ppm, 284 ppm, 1,135 ppm, 4,540 ppm 3-Methylpentane in each exposure chamber for 6 h/day, 5 days/week, for 4 weeks. After two weeks, the test animals were autopsied and carried out blood test and biochemical tests and histopathological examination. We used PRISTIMA (Toxicology data management system) to confirm the system and to have confidence of the raw data. Results : No death and particular clinical presentation including weight change and change of feed rate was observed. Relationship between dose, gender and response was also not significantly changed in hematologic examination, biochemical examination of blood and blood coagulation time. The histopathologic lesions caused by the test substance did not appear. Conclusions : NOAEL(No Observable Adverse Effect Level) of 3-Methylpentane is more than 4,540 ppm in male group and female group and the Ministry of Employment and Labor Guidance Announcement No. 2013-37(criteria for the classification marks and Safety of Chemicals) Specific target organ toxicity(repeated exposure) was determined with a substance that is not the separator material.

Four-Week Dose-Range Finding and 13-Week Repeated Dose Intravenous Toxicity Studies in Rats with DA-125, a New Anthracycline Antitumor Antibiotic (새로운 Anthracycline계 항암성 항생물질 DA-125의 랫드에 대한 4주 용량설정시험(DRF)과 13주 아급성 독성시험)

  • ;;;;;;Eric J. F. Spicer;Susan Novitsky;Lee Bernal
    • Biomolecules & Therapeutics
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    • v.2 no.2
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    • pp.190-205
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    • 1994
  • This study was conducted to investigate the repeated dose toxicity of DA-125, a new anthracycline antitumor antibiotic, in rats. Before the 13-week main study, a 4-week dose-range finding (DRF) study was carried out. The administration of DA-125 intravenously at dosage levels of 0, 0.125, 0.5, 2.0, and 8.0 mg/kg/day to rats for 4 weeks resulted in premature deaths of all animals in the 8.0 mg/kg/day group and in the deaths of 4 males and 4 females at 2.0 mg/kg/day. Body weights were markedly reduced in the 8.0 mg/kg/day group and showed dose-related decreases in all treatment groups when compared with the control group. Reductions in weight gain were slight and not significantly different at 0.125 mg/kg/day but animals receiving 0.5 mg/kg/day showed more marked decreases in gain in a clear dose-related manner Based On the results of the above DRF study, a 13-week repeated dose intravenous toxicity study in rats with DA-125 was performed at a dose level of 0, 0.012, 0.08 and 0.3 mg/kg/day. No treatment related effects were noted in behavior or body weight in all treatment groups. One male at the highest dose level died on study day 26, but the death could not be related to test article toxicity. Swelling and scabbing of the ears was present in all of the groups, including the control group. There were no treatment related changes in the hematological, biochemical or urinalysis values in all treatment groups. Thymus weights were significantly reduced ill males receiving 0.3 mg/kg/day and they were sligltly, and not significantly, reduced in females of the same group. While there were no associated histological changes. Treatment related necrosis was found in the tail vein (injection site) at 0.08 and 0.3 mg/kg/day. On the basis of these results, the no observed effect level (NOEL) was 0.012 mg/kg/day and the maximum tolerated dose (MTD) was estimated to be more than 0.3 mg/kg/day under the conditions tested.

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Toxicities Demonstrated in Dams and Neonates following Intragastric Intubation of Polyethylene Microplastics to Pregnant Mice (폴리에틸렌 미세플라스틱의 임신 마우스 위내투여에 따른 모체 및 신생자 독성평가)

  • Song, YoungMin;Kim, ChangYul
    • Journal of Environmental Health Sciences
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    • v.47 no.5
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    • pp.446-453
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    • 2021
  • Background: Plastic particles less than 5 mm in diameter (microplastics) are well-known for causing various toxicities such as lung inflammation, oxidative stress, genotoxicity, and reproductive toxicity. As microplastics become smaller, they can move across cell membranes, the placenta, and the blood-brain barrier. Objectives: We evaluated the toxicities of polyethylene microplastics (PE-PMs) in dams and neonates through intragastric intubation of pregnant ICR mice. Methods: Low concentrations (0.01 mg/mouse/day) and high concentrations (0.1 mg/mouse/day) of polyethylene microplastics were administered from the ninth day of pregnancy to postnatal day seven. The control group was administered with distilled water. On the day of sacrifice, the weight of dams and neonates and the organ weight of neonates was measured. Further, acetylcholinesterase levels and glutathione peroxidase levels were evaluated by using a blood sample obtained on the sacrifice day. Results: No significant difference in the number of neonates was found, but the body weight gain of dams was seen to be lower in the low-dose group. On the other hand, we observed a consecutively declining trend in the weight gain and organ weight of neonates among the high-, control, and low-dose groups. Meanwhile, the serum acetylcholinesterase and glutathione peroxidase level were higher in the low-dose group compared to the control group. Further, the dose-dependent accumulation of microplastics in the organs of neonates revealed the transport of plastic particles from dams to their offspring. Conclusions: Although the exact mechanism of toxicity caused by microplastics could not be confirmed, it was validated that exposure to microplastics during pregnancy and lactation causes its migration between generations and accumulation throughout the body. Hence, it is necessary to evaluate the systemic toxicity of microplastics and assessment of co-morbidities such as second-generation toxicity, neurotoxicity, and depression following long-term exposure.

Application of a Microbial Toxicity Assay for Monitoring Treatment Efficiency of Pentachlorophenol in Water using UV Photolysis and $TiO_2$ Photocatalysis

  • Kim, Jung-Kon;Cho, Il-Hyung;Zoh, Kyung-Duk;Choi, Kyung-Ho
    • Proceedings of the Korean Environmental Health Society Conference
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    • 2004.06a
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    • pp.146-150
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    • 2004
  • Degradation efficiency of pentachlorophenol (PCP) by using direct UV photolysis and $TiO_2$ photocatalysis was evaluated with both chemical analyses and acute toxicity assessment employing luminescent bacteria Vibrio fischeri. PCP was chosen as a target compound in this study because of its wide application as fungicide, bactericide, insecticide and wood preservative in agriculture and many industries, in addition to its well-known environmental consequences. The acute toxicity to the microbe was reduced by >60% when applying UV alone, and was completely removed when treated with $UV-TiO_2$ combinations. Toxicity reduction pattern determined with the Microtox Assay generally corresponds with the chemistry data: However, it should be noted that toxicity was greater than expected by the chemistry data. Formation of TCBQ, a toxic byprodut, could not explain observed microbial toxicity. These observations are probably due to the presence of unidentified toxic PCP byproducts, which may include polychlorinated dibenzodioxins and polychlorinated dibenzofurans. When Microtox results were compared between different exposure time, i.e.,5 min and 15 min, an interesting pattern was noted with $UVA-\;TiO_2$ treatment. While no microbial toxicity was observed with 5 min exposure, an EC50 value of 45.4% was estimated with 15 min exposure, which was not observed in $UVB-\;TiO_2$ exposure. This result may suggest the presence of unidentified toxic degradation products generated in the later stage of treatment. Based on this study, $TiO_2$ photocatalyst, together with UVB photolysis could improve the removal of both PCP and its toxic derivatives in more efficient way. The Microtox Assay is promising and economical method for monitoring efficiency of wastewater treatment processes.

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The Toxicity and Anti-cancer Activity of the Hexane Layer of Melia azedarach L. var. japonica Makino's Bark Extract

  • Kim, Hyun-Woo;Kang, Se-Chan
    • Toxicological Research
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    • v.28 no.1
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    • pp.57-65
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    • 2012
  • In this study, the 4-week oral toxicity and anti-cancer activity of the hexane layer of Melia azedarach L. var. japonica Makino's bark extract were investigated. We carried out a hollow fiber (HF) assay and 28-day repeated toxicity study to confirm the anti-cancer effect and safety of the hexane layer. The HF assay was carried out using an A549 human adenocarcinoma cell via intraperitoneal (IP) site with or without cisplatin. In the result, the 200 mg/kg b.w of hexane layer with 4 mg/kg b.w of cisplatin treated group, showed the highest cytotoxicity aginst A549 carcinoma cells. For the 28-day repeated toxicity study, 6 groups of 10 male and female mice were given by gavage 200, 100, or 50 mg/kg b.w hexane layer with or without 4 mg/kg b.w of cisplatin against body weight, and were then sacrificed for blood and tissue sampling. The subacute oral toxicity study in mice with doses of 200, 100, and 50 mg/kg b.w hexane layer showed no significant changes in body weight gain and general behavior. The cisplatin-treated group significantly decreased in body weight compared to the control group but regained weight with 100 and 200 mg/kg b.w of hexane layer. The biochemical analysis showed significant increase in several parameters (ALT, total billirubin, AST, creatinine, and BUN) in cisplatin-treated groups. However, in the group given a co-treatment of hexane layer (200 mg/kg b.w), levels of these parameters decreased. In hematological analysis, cisplatin induced the reduction of WBCs and neutrophils but co-treatment with hexane layer (100 and 200 mg/kg b.w) improved these toxicities caused by cisplatin. The histological profile of the livers showed eosinophilic cell foci in central vein and portal triad in cisplatin treated mice. These results show that hexane layer might have an anti-cancer activity and could improve the toxicity of cisplatin.

Toxicity of the Puffer fish, Takifugu pardalis (Jolbok) and Takifugu niphobles (Bokseom) from Coastal Area of Korea (한국 연안산 졸복(Takifugu pardalis)과 복섬(Takifugu niphobles)의 독성)

  • Kim, Ji-Hoe;Son, Kwang-Tae;Mok, Jong-Soo;Oh, Eun-Gyoung;Hwang, Hye-Jin;Yu, Hong-Sik;Lee, Hee-Jung
    • Korean Journal of Fisheries and Aquatic Sciences
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    • v.40 no.5
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    • pp.269-275
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    • 2007
  • The toxicity of two species of puffer fish, Takifugu pardalis and T. niphobles, collected from the coastal regions of Korea was determined using a mouse bioassay. In T. pardalis collected at Tongyeong, the proportion of toxic specimens containing ${\geq}10MU/g$ exceeded 90% for the skin, fins, liver, intestine, ovary, and gallbladder, 11.1% for the testis, and 6.9% for the muscle. In each of the organs, the highest toxin levels were several tens (14-39) of mouse units (MU) per gram in the muscle, testis, and eyeball, but thousands (1,444-5,755) of MU per gram in the skin, liver, intestine, ovary, and gallbladder. The organs of T. pardalis exhibited remarkable variation in toxicity. In T. niphobles, the proportion of toxic specimens exceeded 90% for the ovary and skin, 60-80% for the fins, liver, intestine, and gallbladder, and 4.5% for the muscle; no toxicity was detected in the testis or eyeball using the mouse bioassay. The highest toxin levels were thousands (2,291-7,777) of MU per gram in the liver, intestine, ovary, and gallbladder, hundreds(146-328) of MU per gram in the skin and fins, and 18 MU/g in the muscle. Takifugu niphobles toxicity also exhibited remarkable regional variation. The toxicity in the edible muscle of T. pardalis and T. niphobles was at acceptable levels for human consumption, while the toxicity of the skin of both species of puffer fish was very high, so that care must be taken when used for human consumption.