• Title/Summary/Keyword: No-observed-adverse-concentration level

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Subacute(13-week) Inhalation Toxicity Study of Methyl Acrylate in Rats (랫드를 이용한 Methyl Acrylate의 아급성(13주) 흡입독성 연구)

  • Han, Jeong Hee;Park, Sang Yong;Kang, Min Gu;Chung, Yong Hyun;Yang, Jung Sun
    • Journal of Korean Society of Occupational and Environmental Hygiene
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    • v.22 no.4
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    • pp.316-328
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    • 2012
  • Objectives: This study was designed to provide the information regarding chemicals classification and health hazard by evaluating the toxicological effect through repeated inhalation exposure of methyl acrylate(MA) in Sprague-Dawley(SD) rat for 13 weeks. Methods: According to the notification with Ministry of Labor(No. 2009-68) and OECD Test Guideline 413, the rats were exposed to MA at concentration of 0, 56, 168, 280 ppm via whole body inhalation for 6 hours per day, 5 days per week, for 13 weeks. All animals were observed for mortality, morbidity and the change of body weight and food consumption were determined during the exposure period. Necropsy finding, organ weight, hematology, clinical biochemistry and histopathological examination following exposure were also performed. Results: There were no death and abnormal clinical signs relate to exposure MA. However, At 160 ppm and 280 ppm exposure groups, body weight and food consumption showed statistically significant decrease and histopathological changes in lung, trachea, nasal cavity, larynx were observed. Conclusions: MA was mainly affected respiratory tract. It is consequently provided to be classified as category 2(0.2 mg/L/6h < category 2 ${\leq}$ 1.0 mg/L/6h) for specific target organ toxicity following repeated exposure according to Standard for Classification and Labeling of Chemical Substance and Material Safety Data Sheet. The NOAEL(no observable adverse effect level) of MA was also determined to be lower than 56 ppm.

Subchronic Inhalation Toxicity of iso-Butylalcohol in Rats

  • Jang, Beom-Su;Lim, Jong-Hwan;Yun, Hyo-In;Park, Jong-Il;Ha, Chang-Su;Kim, Jong-Choon;Kim, Hyeon-Yeong;Chung, Yong-Hyun;Jeong, Jae-Hwang
    • Toxicological Research
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    • v.16 no.4
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    • pp.302-309
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    • 2000
  • The purpose of this study is to investigate toxic effects of iso-butylalcohol (iBA) in Sprague-Dawley (SD) rats under the exposure of 6 hours a day, 5 days a week for 13 weeks by inhalation, and to evaluate the occupational safety of iBA in comparison with the permissible exposure level (PEL) stipulated by the Occupational Safety and Health Administration (OSHA). iBA did not induce any abnormal changes from the aspects of clinical signs, feed consumption, ophthalmic test, urinalysis, hematology and blood chemistry during and at the terminal of the inhalation toxicity tests. We did not find any abnormal findings in the gross and microscopic observations due to the inhalation of iBA. There was no alteration in relative organ weights by the inhalation of iBA. No observed adverse effect level (NOAEL) of iBA was considered to be more than 3,000 ppm in rats under the inhalation of 6 hours a day, 5 days a week for 13 weeks. Fifty ppm of iBA, the PEL regulated by OSHA, is too conservative for working places. As iBA showed no abnormal observations in all the experimental parameters at any concentration under this experimental condition, we suggest that 150 ppm is safe enough for the PEL of iBA in the working areas, even taking into onsideration that OSHA lowered the PEL to 50 ppm for fear of the probable risk of its skin irritation.

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Enhanced Germination & Initial Seedling Development by Liquid Phase Ozonation of Plant Seeds (식물종자의 액상오존처리에 의한 종자 발아 및 초기 성장 증진)

  • Yang, Heekyung;Jeong, Yuna;Choi, Wonchul;Bae, Bumhan
    • Journal of Soil and Groundwater Environment
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    • v.24 no.5
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    • pp.1-10
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    • 2019
  • The effects of liquid phase ozonation on seed dormant alleviation and subsequent seedling growth were studied using two plant seeds of Indian jointvetch (Aeschynomene indica L.) and Indian mallow (Abutilon avicennae Gaertn.). At a constant ozone concentration ($80g/m^3$), contact time varied from 10 to 60 min with 10 min interval. Germination rate, root length, and specific root length were compared after 3-day incubation on gel-medium. The germination rate increased significantly (p<0.05) in the 50 min treatment of Indian mallow by 30% compared to the control. Enhanced root elongation was observed in the seeds of 30 min treatment of Indian jointvetch and 30~50 min treatment of Indian mallow. Specific root length, an indicator of environmental change, did not show significant changes, suggesting the level of ozone treatment has no adverse effect on seedling development. The results indicate that liquid phase seed ozonation can be an effective on-site germination alleviation method in the application of phytoremediation.

Significance of varying concentrations of T-2 toxin on growth performance, serum biochemical and hematological parameters in broiler chickens

  • Singh, Ram;Park, Sungkwon;Koo, Jin Su;Kim, In Ho;Balasubramanian, Balamuralikrishnan
    • Journal of Animal Science and Technology
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    • v.62 no.4
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    • pp.468-474
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    • 2020
  • The study was to determine the effects of diverse concentrations of T-2 toxin in broiler diet. Three hundred 1-day-old chicks with initial body weight of 46 ± 0.52 g were chosen and randomly assigned into five dietary treatments with 5 replicate cages and 12 broilers per cage for 42 d feeding trial. Dietary treatments were prepared with basal diets containing 0 (T1), 50 (T2), 100 (T3), 150 (T4), 200 (T5) ppb T2-toxin. Significant results were observed in the decreased intake of feed, feed conversion ratio (FCR), body weight gain (BWG), level of serum protein, cholesterol and hemoglobulin of broilers in increased concentration of the T-2 toxin in diet (150 and 200 ppb) groups than control. Also, observed that the uric acid, serum glutamic pyruvic transferase (SGPT), serum glutamic oxaloacetic transferase (SGOT) and Heterophil/Lymphocyte (H/L) ratio value were significantly higher (p < 0.05) in groups T4 and T5 than control. However, the BWG, feed intake and FCR, as well blood biochemical profiles of serum protein, cholesterol, hemoglobulin, uric acid, SGPT, SGOT and H/L ratio in groups T2 and T3 were statistically similar to control diet of broilers. It was concluded that the results showed that no adverse effects on growth performance and blood biochemical parameters in broilers feed with T-2 toxin (50 and 100 ppb) during the entire trial.

Supplementation of enzyme cocktail in chickens diet is an effective approach to increase the utilization of nutrient in wheat-based diets

  • Ko, Hanseo;Kang, Hwan Ku;Moturi, Joseph;Ingale, Santosh Laxman;Kim, Jinsoo
    • Journal of Animal Science and Technology
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    • v.63 no.1
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    • pp.69-76
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    • 2021
  • This experiment was conducted to evaluate the effect of supplementing enzyme cocktail on growth performance, digestibility of nutrients, and monosaccharide concentration in ileum and ceca of broiler chickens fed wheat-based diets. A total of 600 male broilers (42.26 ± 1.76 g, 0 day old) were used for 35 days of feeding trial consisting of 2 phases (starter phase from d 0 to 21 and finisher phase from d 21 to 35). Four dietary treatments were prepared based on wheat diets containing four levels of enzyme cocktail supplementation at 0, 0.2, 0.3, and 20 g/kg. Overall, dietary enzyme cocktail supplementation decreased feed conversion ratio (linear p = 0.007; quadratic p = 0.013) and improved (linear p < 0.05) the apparent ileal digestibility of dry matter (DM), crude protein, and soluble and insoluble non-starch polysaccharides. The apparent total tract digestibility of DM and gross energy were increased (linear p < 0.01) with increasing supplementation levels of the dietary enzyme cocktail. The concentrations of arabinose, xylose, mannose, and glucose in ileal digesta were linearly increased (p < 0.01) with increasing enzyme cocktail supplementation levels. In addition, the quadratic effect was observed (quadratic p = 0.046) in mannose concentration of ileal digesta. The concentration of arabinose, xylose, mannose, and galactose in cecal digesta was increased (linear p < 0.05) with increasing dietary enzyme cocktail supplementation levels. The supplementation of enzyme cocktail efficiently increased the utilization of nutrients in broiler and there was no adverse effects of high dosage supplementation level.

Embryotoxicity and Toxicokinetics of the Antimalarial Artesunate in Rats

  • Chung, Moon-Koo;Yu, Wook-Joon;Lee, Jin-Soo;Lee, Jong-Hwa
    • Toxicological Research
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    • v.29 no.1
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    • pp.27-34
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    • 2013
  • This study was conducted to investigate the potential embryo-fetal toxicity and toxicokinetics of the antimalarial agent artesunate (ARTS) in Sprague-Dawley rats. Pregnant rats were administered ARTS daily from gestational day 6~15 via oral gavage, at test doses of 0, 2, 4, or 8 mg/kg (22 females per group). The fetuses were examined for external, visceral, and skeletal abnormalities on gestational day 20. With regard to the dams, there were no deaths, treatment-related clinical signs, changes in body weight, or food intake in any of the treatment groups. There were no treatment-related gross findings at necropsy in any treatment group. In the 8 mg/kg group, there was a decrease in gravid uterine weight and in the weight of female fetuses. There was also an increase in fetal deaths (primarily late resorptions) and an increase in post-implantation losses (37%) at 8 mg/kg. An increase in the incidence of visceral and skeletal variations at 4 and 8 mg/kg was observed. These defects included minor changes in the appearance of the kidney and thymus, as well as absent ribs or thoracic vertebrae. Toxicokinetics were assessed in a parallel study, using 4 mated females per group. Using liquid chromatography-mass spectrometry (LC-MS) analysis, the concentration of ARTS and its metabolite dihydroartemisinin (DHA) were quantified in plasma from rats on gestational days 5, 6, 10, and 15. Amniotic fluid was assayed for ARTS and DHA on gestational day 15. There was evidence of rapid conversion of ARTS to the metabolite DHA in maternal plasma, since ARTS could not be consistently detected in plasma at the three doses tested. ARTS and DHA were not detected in amniotic fluid at gestational day 15, indicating limited placental transfer of the two agents. The embryo-fetal no-observable-adverse-effect level (NOAEL) of the test item was considered to be 8 mg/kg/day for dams, and 2 mg/kg/day for embryo-fetal development.

Development and Research on a Functional Hydrolyzed Whey Protein Powder Product with Sialic Acid as a Marker Compound - II. Repeated 90-day Oral Administration Toxicity Test using Rats Administered Whey Protein Powder containing Highly Concentrated Sialic Acid (23%) produced by Enzyme Separation and Solvent Enrichment Method - (Sialic Acid를 지표성분으로 하는 유청가수분해단백분말의 기능성식품 개발연구 - II. 효소분리 용매정제로 고농도 Sialic Acid가 함유된 유청가수분해단백분말(23%)의 랫드를 이용한 90일 반복경구투여 독성시험 평가 연구 -)

  • Noh, Hye-Ji;Cho, Hyang-Hyun;Kim, Hee-Kyong;Koh, Hong-Bum
    • Journal of Dairy Science and Biotechnology
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    • v.34 no.2
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    • pp.117-135
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    • 2016
  • The present study was performed to develop a functional raw food material from hydrolyzed whey protein powder (23%-GNANA) medication containing sialic acid as a marker compound that is naturally occurring at 7% concentration in GMP (glycomacropeptide). GMP is used worldwide in foodstuffs for babies and infants and is obtained from the milk protein as safe food. While the purpose of our detailed evaluation was aimed to assess preliminary NOAEL values for and above 2,000 mg/kg/day, a clinical dose allowance for 23%-GNANA (as per characteristic of a functional health product, a highly refined test substance of 23% (v/v) sialic acid combined in GMP), at the same time we also wanted to assess the safety of GMP hydrolyzate lacking sialic acid but with identical properties as GMP. Animal safety evaluation was conducted using 23%-GNANA as the test substance, produced from hydrolyzed whey protein powder (product name: HELICOBACTROL-23; provided by Medinutrol Inc. [Korea]; composed of 23% sialic acid and GMP protein) after isolating the sialic acid using enzymes approved as food additives, with GMP as a raw material, and subsequently increasing the content of xx up to 23% through 80% (v/v) ethanol soaking and concentrating, in accordance with GLP Guideline. The animal safety evaluation mentioned above was made on the basis of toxicity in SPF Sprague-Dawley female and male rats dosed with 10 mL of the test substance diluted to 0, 1,250, 2,500, and 5,000 mg/kg directly into their stomachs for 90 d. This was determined in terms of the general symptoms and animal viability, weight and amount of feed intake, eye examination, uracrasia tests, hematological and blood biochemical disorder tests, blood coagulation test, abnormal intestine weight, abnormalities during postmortem and histopathological examinations. Statistical significance was set at P<0.05. Based on the toxicity determination, a certain minor effect associated with the test substance was observed in male rats with no major effects of the tested substance, in comparison with the control group dosed with sterilized water. Nevertheless, the NOAEL value, evaluated as per toxicity criteria, was verified as 5,000 mg/kg/day (P<0.05). Similarly, for female rats, a certain minor effect associated with the test substance was observed in 5,000 mg/kg/day dosed group, with no major effect, yet the NOAEL value (as assessed as per toxicity criteria) was determined to be 5,000 mg/kg/day (P<0.05), which was the same as for male rats. Accordingly, the NOAEL values of the test substances for all female and male rats were finally verified as 5,000 mg/kg/day (P<0.05). In conclusion, it was determined that the 23%-GNANA test substance exceeds 2,000 mg/kg/day, the clinical allowance characteristic for functional health food, and was finally evaluated to cause no safety concerns when used as a raw material in functional health food production, which was the ultimate goal of the present study.

Recommendation of an Occupational Exposure Limit and Legal Control Following an Acute Hepatotoxicity Incident from HCFC-123 (HCFC-123의 급성 독성간질환 발생 사례에 따른 노출기준 및 법 관리 필요성 권고)

  • Lee, Kwon Seob;Jo, Ji hoon;Choi, Bo Kyung;Lee, Hye Lim;Byeon, Sang Hoon
    • Journal of Korean Society of Occupational and Environmental Hygiene
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    • v.28 no.1
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    • pp.80-90
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    • 2018
  • Objectives: This study was performed to propose a domestic occupational exposure limit(OEL) following a health hazard assessment, calculation of a non-carcinogenicity reference concentration worker($RfC_{worker}$) value, and examination of international agencies' exposure limits. It also recommends legal management within the Occupational Safety and Health Act for HCFC-123, which caused an acute hepatotoxicity incident. Methods: An acute hepatotoxicity incident due to the fire extinguishing agent HCFC-123 was investigated. Toxicological hazard and health hazard classifications were examined and a non-carcinogenicity $RfC_{worker}$ value was calculated for HCFC-123. An OEL and the necessity of legal management were recommended as well. Results and Conclusions: An OEL for HCFC-123 of 10 ppm($62.5mg/m^3$), which considered the $RfC_{worker}$ value, 5.56 ppm, produced in dose-response assessment and the exposure level of 19.1-20.9 ppm measured as an eight-hour TWA(time-weighted average) in the incident place, is recommended. HCFC-123 is urged to be included as a chemical requiring legal management in the Occupational Safety and Health Regulations. In addition, it is recommended that a peak exposure of ACGIH be adopted in the Notice of the Ministry of Employment and Labor.

Risk Assessment of Ethylhexyl Dimethyl PABA in Cosmetics

  • Sung, Chi Rim;Kim, Kyu-Bong;Lee, Joo Young;Lee, Byung-Mu;Kwack, Seung Jun
    • Toxicological Research
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    • v.35 no.2
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    • pp.131-136
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    • 2019
  • Ethylhexyl dimethyl para-aminobenzoic acid (PABA) is an oily yellow liquid derivative of water-soluble PABA commonly used in sunscreen. Ethylhexyl dimethyl PABA is widely used as an ingredient in many cosmetics at an average concentration of 1.25% (0.5-2.0%) in Korea. Previous studies, including those involving animals, have demonstrated that ethylhexyl dimethyl PABA is toxic to the following four organs: testis, epididymis, spleen, and liver. In addition, experiments using human keratinocytes found that ethylhexyl dimethyl PABA inhibits cell growth and DNA synthesis at low concentrations, and halted the cell cycle of MM96L cells (human melanoma cell line) at the G1 phase. Despite limited clinical data in humans, many studies have confirmed increased mutagenicity of ethylhexyl dimethyl PABA following exposure to sunlight, which suggests that this molecule is likely to contribute to onset of sun-induced cancer despite protecting the skin through absorption of UVB. For risk assessment, the no observed adverse effect level (NOAEL) chosen was 100 mg/kg bw/day in a 4 weeks oral toxicity study. Systemic exposure dosage (SED) was 0.588 mg/kg bw/day for maximum use of ethylhexyl dimethyl PABA in cosmetics. Based on the risk assessment and exposure scenarios conducted in this study, the margin of safety (MOS) was calculated to be 180.18 for a sunscreen containing 8% ethylhexyl dimethyl PABA, which is the maximum level allowed by the relevant domestic authorities.

Recommendation of Occupational Exposure Limit through occupational hazard assessment of PHMG-Phosphate (PHMG-Phosphate의 직업적 유해성평가를 통한 노출기준 제안 연구)

  • Lee, Hye Lim;Byeon, Sang Hoon;Lee, Kwon Seob
    • Journal of Korean Society of Occupational and Environmental Hygiene
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    • v.29 no.1
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    • pp.13-20
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    • 2019
  • Objective: This study was performed to propose a domestic occupational exposure limit(OEL) following a health hazard assessment, calculation of a non-carcinogenicity reference concentration worker($RfC_{worker}$) value, and examination of international agencies' exposure limits. It also recommends legal management within the Occupational Safety and Health Act for PHMG-Phosphate(CAS No. 89697-78-9), It is a humidifier disinfectant that generated many lung injuries. Methods: We have investigated the recommendation or guidelines of foreign OEL for PHMG-Phosphate and the actual state of legal management in Korea. To examine the procedures and methods for recommendation OEL. Toxicological hazard and health hazard classifications were examined and a non-carcinogenicity $RfC_{worker}$ value was calculated for PHMG-Phosphate. An OEL and the necessity of legal management were recommended as well. Results and Conclusions: The OEL for PHMG-Phosphate is recommended to be $0.01mg/m^3$. The recommended OEL is close to 10 times the RfCworker value of $0.000833mg/m^3$ calculated from the chemical dose-response hazard assessment, which is a 2017 study. The CMIT/MIT(3:1) mixture, which was a social issue as a humidifier disinfectant substance, was also exposed to the same ratio in March 2018, establish the OEL. It is recommended to establish OEL for PHMG-Phosphate to prevent worker health hazards and for chemical safety management.