• Title/Summary/Keyword: Inhalation toxicity study

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Subacute Inhalation Toxicity Study of Dimethyl Disulfide in F344 Rats (F344 랫드를 이용한 이황화메틸의 아급성 흡입독성연구)

  • Kim Hyeon-Yeong;Lee Sung-Bae;Han Jung-Hee;Chung Yong-Hyun;Kim Hyoung-Chin;Shin Jin-Young;Shin Dong-Ho;Kim Jong-Choon;Lee Young-Mook
    • Journal of Life Science
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    • v.15 no.1 s.68
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    • pp.1-8
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    • 2005
  • The purpose of this study was to investigate the potential subacute toxicity of dimethyl disulfide by 3 weeks inhalation in F344 rats. The test article, dimethyl disulfide was exposed by inhalation to male and female rats at dose levels of 0, 5, 25, or 125 ppm/6 hrs/ day for 3 weeks. Five rats/ sex/ group were sacrificed on day 4 after the initiation of treatment, while 5 rats/ sex/ group were sacrificed at the end of treatment period. During the test period, clinical signs, mortality, body weights, food consumption, hematology, serum biochemistry, and gross findings were examined. Slight decreases in body weight gain were noted in both sexes of the highest dose group in a dose dependent manner but were only statistically different from the control animals in males of the group. A slight non-significant reduction in food consumption were also noted in the both sexes of the highest dose group. There were no adverse effects on mortality, clinical signs, hematology, serum biochemistry, and necropsy findings at any dose tested. Based on these results, it was concluded that the 3 weeks repeated dose of dimethyl disulfide by inhalation resulted in suppressed body weight gain and decreased food consumption at 125 ppm of both sexes. In the present experimental conditions, the target organ was not determined in rats. The no­observed-adverse-effect level (NOAEL) was considered to be 25 ppm/6 hrs/day for both sexes.

Risk Assessment of Drometrizole, a Cosmetic Ingredient used as an Ultraviolet Light Absorber

  • Lee, Jae Kwon;Kim, Kyu-Bong;Lee, Jung Dae;Shin, Chan Young;Kwack, Seung Jun;Lee, Byung-Mu;Lee, Joo Young
    • Toxicological Research
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    • v.35 no.2
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    • pp.119-129
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    • 2019
  • As the use of cosmetics has greatly increased in a daily life, safety issues with cosmetic ingredients have drawn an attention. Drometrizole [2-(2'-hydroxy-5'-methylphenyl)benzotriazole] is categorized as a sunscreen ingredient and is used in cosmetics and non-cosmetics as a UV light absorber. No significant toxicity has been observed in acute oral, inhalation, or dermal toxicity studies. In a 13-week oral toxicity study in beagle dogs, No observed adverse effect level (NOAEL) was determined as 31.75 mg/kg bw/day in males and 34.6 mg/kg bw/day in females, based on increased serum alanine aminotransferase activity. Although drometrizole was negative for skin sensitization in two Magnusson-Kligman maximization tests in guinea pigs, there were two case reports of consumers presenting with allergic contact dermatitis. Drometrizole showed no teratogenicity in reproductive and developmental toxicity studies in which rats and mice were treated for 6 to 15 days of the gestation period. Ames tests showed that drometrizole was not mutagenic. A long-term carcinogenicity study using mice and rats showed no significant carcinogenic effect. A nail product containing 0.03% drometrizole was nonirritating, non-sensitizing and non-photosensitizing in a test with 147 human subjects. For risk assessment, the NOAEL chosen was 31.75 mg/kg bw/day in a 13-week oral toxicity study. Systemic exposure dosages were 0.27228 mg/kg bw/day and 1.90598 mg/kg bw/day for 1% and 7% drometrizole in cosmetics, respectively. Risk characterization studies demonstrated that when cosmetic products contain 1.0% of drometrizole, the margin of safety was greater than 100. Based on the risk assessment data, the MFDS revised the regulatory concentration of drometrizole from 7% to 1% in 2015. Under current regulation, drometrizole is considered to be safe for use in cosmetics. If new toxicological data are obtained in the future, the risk assessment should be carried out to update the appropriate guidelines.

Changes in the Expression of Ras-family Genes in Rats Exposed to Formaldehyde by Inhalation

  • Li, Guang-Yong;Lee, Hye-Young;Choi, You-Jin;Lee, Mi-Ock;Shin, Ho-Sang;Kim, Hyeon-Young;Lee, Sung-Bae;Lee, Byung-Hoon
    • Toxicological Research
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    • v.24 no.3
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    • pp.201-206
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    • 2008
  • Exposure to formaldehyde(FA) is closely associated with adverse health effects such as irritation, inflammation, and squamous cell carcinomas of the nasal cavities. Owing to its rapid metabolism and elimination, exposure to FA does not always result in an increased concentration in blood or urine of animals and humans. Therefore, the development of biomarkers for FA exposure is necessary for risk assessment. In the present study, the effects of FA were investigated on the expression of genes involved in the MAPK pathway in vitro and results confirmed in rats exposed to FA by inhalation. Treatment of Hs 680.Tr human tracheal epithelial cells with FA induced gene expression for PDGFA, TNFSF11, SHC1, and HRAS. HRAS expression was also increased in tracheas of rats exposed to FA. In addition, FA exposure induced the expression of RASSF4, a member of the Rasassociation domain family of Ras effectors, in rat tracheas. In conclusion, data showed FA-inducible expression of genes involved in the MAPK pathway occurred and increased expression of HRAS and RASSF4 was noted in rat tracheas subchronically exposed to FA by inhalation. These genes may serve as molecular targets of FA toxicity facilitating the understanding of the toxic mechanism.

A Study on the Combustion Characteristics of Organic Insulation Materials According to the Gas Toxicity Evaluation Method (가스유해성 평가방법에 따른 유기단열재의 연소특성에 관한 연구)

  • Shim, Ji-Hun;Lee, Jae-Geol;Han, Kyoung-Ho;Kim, Ju-Wan;Song, Seok-Hun;Jo, Hyung-Won;Yoon, Do-Young
    • Korean Chemical Engineering Research
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    • v.60 no.4
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    • pp.519-524
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    • 2022
  • Domestic building finishing materials are being evaluated according to KS F 2271 standards according to the notification of the Ministry of Land, Infrastructure and Transport, and this test is evaluated using laboratory animals. In this study, experiments were conducted on highly combustible organic insulation materials such as EPS, urethane, and phenolic foam. The purpose of this study was to analyze the cause of the behavioral suspension of the experimental mice by measuring the average behavioral suspension time of the mice caused by the harmful gas generated when these three types of insulation materials were burned. FTIR analysis and smoke density experiment were performed as a cause analysis method for the behavioral suspension of mice, and the experimental results were analyzed by dividing the causes of behavioral suspension into suffocation by particulate matter and toxic inhalation by gaseous substances. As a result of the test, urethane was evaluated as the most harmful insulation material, and as a result of FTIR analysis and smoke density test as a cause analysis for the gas toxicity test results, it is judged that the behavioral stop of the rats by suffocation is higher than the effect of toxic inhalation. This study is a basic study on the cause analysis of harmful gases, and it will be necessary to prepare the toxicity basis and analyze various materials and gases.

`oxicological study of carbaryl in rats

  • Lee, Wan-Koo;Hong, Sa-Uk
    • Archives of Pharmacal Research
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    • v.8 no.3
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    • pp.119-132
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    • 1985
  • The apparent effectiveness of 1-naphthyl-N-methyl carbamate (carbaryl) against a wide variety of insects motivated the study of its mammalian toxicity. In this toxicological study of carbaryl, mature male rats inhaled carbaryl at a mean concentration of 112mg, 168mg and 224 mg/$m^{3}$ for one hour. After inhalation, pentobarbital sleeping time, Nadph-cytochrome c reductase activity, cytochrome p-450 and protein content in liver microsomes, various tissue residues, cholinesterase inhibition in plasma and histopathological findings at autopsy were observed. The pentobarbital sleeping time was prolonged in rats inhaled with carbaryl for one day while the sleeping time was shortened in the 3 days inhaled group. The changes of cytochrome p-450 content and NADPH-cytochrome c reductase activity exhibited biphasic response showing the decrease in the one day inhaled group and the increase in the 3 days inhaled group. The marked depression of plasma ChE activity was observed in rats inhaled with carbaryl at 112 mg/$m^{3}$, however no more progressive effect was observed at the higher concentration of the compound. The main observations in histopathological finding were ciliary detachment, epithelial swelling and subepithelial inflammatory cellular infiltration in trachea due to the irritation.

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Inhalation toxicity study of H menthol (Nicotine free-tob acco free)herbal cigarettes

  • Jung, Ji-Won;Cho, Sung-Dae;Cho, Jong-Ho;Kim, Kyung-Bae;Lee, Ji-Hae;Ahn, Nam-Shik;Yang, Se-Ran;Park, Joon-Suk;Lee, Yong-Soon;Kang, Kyung-Sun
    • Proceedings of the Korean Society of Food Hygiene and Safety Conference
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    • 2002.05a
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    • pp.216-216
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    • 2002
  • Generally, tobacco smoking has noxious effects such as DNA damage, lung cancer induction, coronary artery disease. Nowadays, as concerns on health and longevity increases, a huge variety of products that aim to assist to quit smoking or reduce addictive symptoms such as nicotine patches are developed and manufactured with safely evaluation, but the safety of the most recent products of interest which do not contain tobacco and nicotine, and shape cigarettes is not evaluated and guaranteed relatively. In this study, we used H-menthol(nicotine free-tobacco fine) which are widely consumed through the world to evaluate the single and repeated dose inhalation toxicity and genotoxicity of H menthol (Nicotine free-tobacco free) herbal cigarettes provided by Cigastop Ltd. in ICR mice.

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Changes of [A-a] gas Gradient in Rabbits with Oxygen Toxicity (산소중독시 가토의 [A-a] gas Gradient 의 변화)

  • 이두연
    • Journal of Chest Surgery
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    • v.20 no.1
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    • pp.1-12
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    • 1987
  • Respiratory care with oxygen inhalation is often a necessity to maintain life, and it is one of the important therapeutic adjuncts in respiratory disease and in intensive care after surgery. However, it has been reported that oxygen toxicity occurs after prolonged exposure to 100% 0, [Smith, 1899; Kistler et al. 1967; Schaffner et al. 1967; Rowland and Newman, 1969. Subjective symptoms of oxygen toxicity include tracheal irritation, frequent cough, some burning sensation in the trachea, tachypnea, severe dyspnea, etc. [Welch, 1963; Fisher et al, 1968; Milier et al, 1970; Clark and Lambertsen, 1971; Sackner, 1975]. Pathologic findings are atelectasis, injuries to the pulmonary capillaries and hemorrhage in the alveoli in gross specimens. There can be inflammation, proliferation of fibrin, thickening of alveolar membranes, degeneration of collagen fibers and interstitial edema in the microscopic findings. [Penrod, 1956; Cedergren, 1959; Bean, 1965; Schaffner, 1967]. Dubois and colleagues [1961] found that the amount of pulmonary surfactant was decreased in oxygen toxicity and atelectasis followed by the decreased pulmonary surfactant. Many authors reported that vital capacity, inspiratory force, pulmonary compliance, pulmonary capillary blood flow and pulmonary elasticity were deceased and arteriovenous shunting increased. [Comroe et al, 1945; Fuson et al, 1965; Kistler et al, 1966; Knowles and Blenner-hassett, 1967; Barber et al, 1978]. Many human volunteers were examined after prolonged exposure in a high oxygenated chamber and there were a few reports on animals with oxygen toxicity, subjects including rabbits. Gas partial pressures of alveoli and arteries were measured in rabbits exposed to 100% $O_2$ and the alveolar-arterial gas gradients were analyzed, which is the basis for the study of oxygen toxicity. These rabbits were divided into two groups; rabbits under natural respiration, and second group under artificial respiration with a respirator. The alveolar $PO_2$ [$P]AO_2$] and $PCO_2$ [$PACO_2$], and the arterial $PO_2$ [$PaO_2$] were measured under varying $O_2$ pressures; 15% $O_2$, 21% $O_2$ and 100% $O_2$.

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Health Damages and Lessons of the Use of Humidifier Disinfectants in Korea (가습기살균제 피해사건과 교훈)

  • Choi, Ye-Yong;Lim, Heung-Kyu;Lim, Sin-Ye;Paek, Do-Myung
    • Journal of Environmental Health Sciences
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    • v.38 no.2
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    • pp.166-174
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    • 2012
  • Introduction: After 17 years since the first production of humidifier disinfectants in Korea, Korea Centers for Disease Control and Prevention (KCDC) announced that the odds ratio of lung injury related with humidifier disinfectant usage was 47.3 (95% confidence interval 6.0-369.7) according to a case-control study with 18 adult cases, including 8 pregnant women at a university hospital in Seoul. Results: From September 2011 to April 2012, one-hundred and seventy four victim cases have been reported to an environmental non-governmental group (NGO). We summarized timetable of humidifier disinfectants accidents, analyzed health outcomes (death, lung or lung and heart transplantation, pulmonary disease) of reported victims, and classified some information for humidifier disinfectants with health outcomes, and government action for this accident. Among the victims, number of death cases are 52 (30.0%), including 26 babies less than 3 years old. Sixty-nine victims come from twenty-seven family with 2 to 4 members per family. About twenty types of humidifier disinfectant products and about 600,000 product items a year have been sold. Fifty-two death cases used 7 different types of disinfectant products, including imported goods and some private brands of well-known supermarkets. KCDC confirmed inhalation toxicity of 6 products through an animal experimental test, and based on this observation recalled disinfectants containing PHMG (polyhexamethylene guanidine) and PGH (Oligo(2-(2-ethoxy)ethoxyethyl guanidinium chloride). Discussions: The use of these biocides involved highly fatal consequences among biologically vulnerable victims, such as pregnant women, several family member victims after semi-acute exposure. This is the first biocide disaster in Korea with non-specific targets, and unknown scale of victims, warranting concerns on use of biocides in the living environment. Conclusions: Special administrative agency for chemical safety and compensation act for environmental health victims are needed to prevent similar problems.

Review on Safety and Health Information on Humidifier Disinfectant (가습기 살균제 제품에 표기된 안전보건정보 고찰)

  • Park, Dong-Uk;Lee, Seunghee;Lim, Heung-Kyu;Bae, Seo-Youn;Ryu, Seung-Hun;Ahn, Jong-Ju
    • Journal of Environmental Health Sciences
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    • v.43 no.5
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    • pp.349-359
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    • 2017
  • The objective of this study is to review the safety and health information displayed on containers of humidifier disinfectants (HD). We summarized not only general characteristics related to the marketing and manufacturing of HD, such as the duration sold and the name of the company, but also the safety and health information, such as identification of disinfectants, recommended use volume, and precautions. All of this information was reviewed by HD brand. We collected safety and health information from 31 HD brands. We found that companies that sold and manufactured HD brands differ. Two companies were found to sell their HD without permission after 2011 when the health effects caused by HD were widely known. The name of the disinfectants were not identified on the container of HD. The recommended volumes were found not to be based on toxicological evidence and set without consideration of the level of susceptibility of users. Most companies displayed phrases such "this HD is safe for humans, even children" on the front of the container. No inhalation and skin toxicity precautions were provided. In conclusion, most HD did not properly display information related to safety and health to protect the health of HD users. There has been no official investigation to evaluate the risks posed by HD, such as the sales volume by HD, identification of chemical disinfectants, or their concentration, nor have there been actions to control the chemical quality of HD. In addition, government actions to punish the malicious practices of companies that manufactured and sold HD were found to inappropriate.

Effect of Mn and Fe Compound on the Absorption in the Body and Genital Organs, Activity with F344 Rats (F344 rats를 이용 망간 및 철 화합물의 체내 흡수와 생식기 및 운동성에 미치는 영향)

  • Kim, Hyeon-Yeong;Lee, Sung-Bae;Han, Jeong-Hee;Choi, Sung-Bong;Kang, Min-Gu;Lee, Chae-Kwan
    • Journal of Korean Society of Occupational and Environmental Hygiene
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    • v.17 no.3
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    • pp.224-234
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    • 2007
  • This study aimed to examine the harmful effects of Mn and Fe, which may be generated as dust or fume in the industrial sites, on the body and genital organs by their inhalation. It is intended to find the characteristics and differences of the hazardousness by inhaling a single and the mixed materials of Mn and Fe. Male F344 rats were divided into the control group and 3 exposed groups on the basis of the test material compound (Mn $1.5mg/m^3$, Mn 1.5 and Fe $3.0mg/m^3$, Fe $3.0mg/m^3$). The 4 groups were divided into 4 subgroups again on the basis of the exposure period (4 and 13 weeks) and the recovery period (4 and 13 weeks). The exposure condition was 6 hours a day, 5 days a week for the whole body. Clinical tests including changes in weight and feed rate, blood biochemical test, motility change, changes in the number and the amount of spermatozoon (sperm count), daily sperm production (DSP), deformity test of spermatozoon and changes in the accumulation of Mn and Fe in blood and internal organs were performed. Motility was reduced by Mn exposure. Especially, the effect of Mn was exposure period responsible. By mixing with Fe, no significant change in motility Mn and Fe accumulation in organs was observed. Sperm count and daily sperm production (DSP) were decreased by Mn. Additional effect like the reduction of sperm count and DSP, and delayed restoration of sperm count and DSP during the recovery period were observed in the mixed exposure group. These results indicate that Mn and Fe may affect the motility reduced and has male reproductive toxicity. Mixed exposure of Mn and Fe lead to synergic effects on the male reproductive toxicity.