• Title/Summary/Keyword: No observed adverse effect level

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Single-dose and 4-week repeated dose Toxicity of Aconitum Sinomontanum Nakai Pharmacopuncture: An Experimental Study

  • Woo, Sang Ha;Lee, Jung Hee;Lee, Cho-in;Lee, Yun Kyu;Lee, Hyun-Jong;Kim, Jae Soo
    • Journal of Acupuncture Research
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    • v.38 no.1
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    • pp.47-59
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    • 2021
  • Background: This study aimed to assess the toxicity of Aconitum sinomontanum Nakai (ASN) pharmacopuncture. Methods: To investigate the toxicity of ASN pharmacopuncture, single and 4-week repeated dose toxicity experiments were conducted on BALB/c mice. In the single-dose toxicity experiment, mice were assigned 1 of 4 groups (5 males, 5 females per group). Then, 31.25, 62.5, and 125 mg/kg of ASN pharmacopuncture were administered to the mice in the experimental groups at acupoint ST36, while 0.2 mL of normal saline was administered to the control group at ST36. After a 4-week repeated dose regimen, the mice were assigned into 4 groups (5 males, 5 females per group). Then, 15.625, 31.25, and 62.5 mg/kg of ASN pharmacopuncture at ST36 were administered to the mice in the experimental groups, while 0.2 mL of normal saline was administered to the control group at ST36. Mortality, morbidity, general body and organ weight changes (after 4 weeks repeated dose), serum hematological and biochemical values, and histopathological changes in the liver and kidney were observed. Results: In both single and 4-week repeated dose toxicity experiments, no deaths or symptoms occurred in any of the groups. There were no significant differences between groups in terms of body and organ weights, serum hematological and biochemical values, and specific organ histopathological changes. Conclusion: ASN pharmacopuncture injection did not demonstrate significant toxicity in BALB/c mice compared with the control group, with a no-observed-adverse-effect level for a single dose of >125 mg/kg, and for 4 weeks repeated dose it was more than 62.5 mg/kg/day.

Effects of Enzyme Addition to Broiler Diets Containing Varying Levels of Double Zero Rapeseed Meal

  • Ramesh, K.R.;Devegowda, G.;Khosravinia, H.
    • Asian-Australasian Journal of Animal Sciences
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    • v.19 no.9
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    • pp.1354-1360
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    • 2006
  • Maize-soybean meal diets with 0, 100, 200 and 300 g/kg double zero rapeseed meal ('00' RSM) with and without an enzyme mixture (xylanase, pectinase, cellulase) at a level of 1.6 g/kg were evaluated with 624 day-old broiler chicks for 5 weeks. The birds were randomly allocated to eight dietary treatments with three replicates of 26 birds each. Average daily gain (ADG) and feed intake (FI) were recorded weekly and ileal viscosity, organ weights, serum enzyme activity, hormonal profile and hematological parameters were measured at the end of week 5. Average daily gain during the weekly periods was significantly influenced by the dietary level of '00'RSM (p<0.01). Inclusion of '00' RSM improved the ADG up to day 28 with the increased level; beyond that time no improvement was recorded when compared to control groups. However, ADG from 1-35 days was significantly different between 300 g/kg inclusion level of '00' RSM and the control diet. Inconsistent decline in feed intake and feed conversion ratio was observed up to day 21 and the trend was reversed thereafter. The proportion of '00' RSM in the diet had a significant ($p{\leq}0.05$) influence on thyroid weight but had no effect on the relative weights of liver and heart, serum enzyme activities (${\gamma}$-glutamyl transferase, alanine amino transferase and aspartate amino transferase), thyroid hormones ($T_3$ and $T_4$), hemoglobin level and hematocrit. Significant improvement in ADG was recorded during the 2nd week of age with the addition of enzyme, whereas for all other periods, including the whole period of the trial, higher but non-significant ADG was observed. FI and FCR were not affected by the addition of enzyme but there was a numerical reduction in FCR during the whole period. The addition of enzyme reduced the ileal viscosity at all levels of '00' RSM inclusion. The results suggest that '00' RSM can be included up to 300 g/kg in broiler diets without any adverse effects on health and performance. The addition of commercial enzyme mixture containing xylanase, pectinase, cellulase to broiler diets containing '00'RSM has some effect on growth rate and feed conversion efficiency.

Inhalation toxicity assesment of C.I.No. Reactive Red 195 in Rats (아조계 반응성염료 C.I.No. Reactive Red 195의 흡입독성평가)

  • Chung, Yong Hyun;Han, Jeong Hee;Song, Kyung Seuk;Kim, Hyeon Yeong;Lee, Sung Bae;Yu, Il Je
    • Journal of Korean Society of Occupational and Environmental Hygiene
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    • v.11 no.3
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    • pp.198-205
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    • 2001
  • Many reactive dyes have been used in occupational settings without knowing their toxicity and health hazard information. To investigate the toxicity of reactive dye, C.I.No. Reactive Red 195 was exposed to male and female Sprague Dawley rats by inhalation for 28 days. The rats were exposed C.I.No. Reactive Red 195 for 6 hrs per day and 5days per week. The concentrations for the inhalation exposure were 0, 10, 40 and $160mg/m^3$. After 4 weeks of exposure, rats were examined for exposure related changes through pathology, blood biochemistry and hematology. There were no dose related changes including clinical signs, body weight and relative organ weight changes, hematological and biochemical and histopathological findings. The results indicate that no observed adverse effect level (NOAEL) of 28 days inhalatrion toxicity test for C.I.No. Reactive Red 195 was $160mg/m^3$.

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Repeated Intramuscular-dose Toxicity Test of Water-soluble Carthami Flos (WCF) Pharmacopuncture in Sprague-Dawley Rats

  • Choi, Yoo-Min;Jung, Da-Jung;Kim, Seok-Hee;Kim, Jong-Uk;Yook, Tae-Han
    • Journal of Pharmacopuncture
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    • v.18 no.1
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    • pp.36-43
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    • 2015
  • Objectives: Water-soluble carthami flos (WCF) is a new mixture of Carthami flos (CF) pharmacopuncture. We conducted a 4-week toxicity test of repeated intramuscular injections of WCF in Sprague-Dawley rats. Methods: Forty male and 40 female rats were divided into 4 groups of 10 male and 10 female SD rats: The control group received 0.5 mL/animal/day of normal saline whereas the three experimental groups received WCF at doses of 0.125, 0.25, and 0.5 mL/animal/day, respectively. For 4 weeks, the solutions were injected into the femoral muscle of the rats alternating from side to side. Clinical signs, body weights, and food consumption were observed; opthalmological examinations and urinalyses were performed. On day 29, blood samples were taken for hematological and clinical chemistry analyses. Then, necropsy was conducted in all animals to observe weights and external and histopathological changes in the bodily organs. All data were tested using a statistical analysis system (SAS). Results: No deaths were observed. Temporary irregular respiration was observed in male rats of the experimental group for the first 10 days. Body weights, food consumptions, opthalmological examinations, urinalyses, clinical chemistry analyses, organ weights and necropsy produced no findings with toxicological meaning. In the hematological analysis, delay of prothrombin time (PT) was observed in male rats of the 0.25- and the 0.5-mL/animal/day groups. In the histopathological test, a dose-dependent inflammatory cell infiltration into the fascia and panniculitis in perimuscular tissues was observed in all animals of the experimental groups. However, those symptoms were limited to local injection points. No toxicological meanings, except localized changes, were noted. Conclusion: WCF solution has no significant toxicological meaning, but does produce localized symptoms. No observed adverse effect level (NOAEL) of WCF in male and female rats is expected for doses over 0.5 mL/animal/day.

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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Toxicity of Methylcyclohexane and Its Effect on the Reproductive System in SD Rats

  • Kim, Hyeon-Yeong;Kang, Min-Gu;Kim, Tae-Gyun;Kang, Chung-Won
    • Safety and Health at Work
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    • v.2 no.3
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    • pp.290-300
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    • 2011
  • Objectives: There is limited data regarding the toxicity of methylcyclohexane, despite its wide use in rubber adhesives, paint diluents, and cleansing agents. This study aimed to verify the toxicity and influence on the reproductive system of methylcyclohexane after its repeated injection in Sprague Dawley (SD) rats. Methods: Methylcyclohexane was injected subcutaneously into male and female SD rats once a day, five times a week, for 13 weeks at different doses (0, 10, 100, and 1,000 mg/kg/day) for each group. The toxicity of testing material was verified by observing the change in body and organ weight, hematological change, pathological findings, and effect on the reproductive system at each different concentration. Results: In the 1,000 mg/kg/day group, there were cases of animal deaths. In animals that survived, hematological changes, including a decrease in the red blood cell count, were observed. A considerable weight gain or loss and pathological abnormalities in the liver, kidney, and other organs were found. However, the 10 and 100 mg/kg/day groups did not cause deaths or other specific abnormalities. In terms of reproductive toxicity, there were changes in hormone levels, including a significant decrease in hormones such as estradiol and progesterone (p < 0.001) in male animals. Menstrual cycle change for female animals did not show concentration dependency. Conclusion: When injected repeatedly for 13 weeks, methylcyclohexane proved to be toxic for the liver, heart, and kidney at a high dose. The absolute toxic dose was 1,000 mg/kg/day, while the no observed adverse effect level was less than 100 mg/kg/day. The substance exerted little influence on the reproductive system.

Potential Human Health and Fish Risks Associated with Hypothetical Contaminated Sediments Using a Risk Assessment Model ($TrophicTrace^{(R)}$) (위험평가모형($TrophicTrace^{(R)}$)을 이용한 가상 해양오염퇴적물의 쥐노래미와 인체 영향 예비평가)

  • Yang, Dong-Beom;Hong, Gi-Hoon;Kim, Kyung-Ryon
    • Journal of Korean Society of Environmental Engineers
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    • v.33 no.1
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    • pp.60-70
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    • 2011
  • The sediment removal index derived from the chemical contaminants, $CI_{HC}$, is currently in use to identify and define the spatial extent of the contaminated sediments in the sea. In order to analyze the sensitivity of the ecological and human risk associated with contaminated sediment, we evaluated five hypothetical contaminated sediments, whose $CI_{HC}$ values are identical but consisted of different contaminant contents, using $TrophicTrace^{(R)}$ model dedicated to evaluate sediment risk, against the resident greenling (Hexagrammos otakii) and humans by calculating No-Observed-Adverse-Effect-Level based Toxicity Quotient (NOAEL TQ) and Lowest-Observed-Adverse-Effect-Level based Toxicity Quotient (LOAEL TQ), and cancer risks and hazard indices (HI), respectively, based on the site conceptual model and exposure assumptions of fish ingestion to human receptor populations. NOAEL and LOAEL TQ values varied as much as a factor of 2 among 5 hypothetical sediments. Chemical element specific contribution to the carcinogenic risk and HI varied also greatly in these sediments. The reason for this significant dissimilarity in ecological and human risk stems from the different risk of each contaminant to the resident fish and human receptor. When the conceptual food web model is constructed for the target biological species for a given site, the ecological and human risk analysis considering trophic transfer of contaminants will add a ecosystem based tool for the management of contaminated sediments.

Effect of Dietary Thyroid Hormone on Growth Performance, Body Composition, Serum Thyroid Hormone Concentration and Energy Metabolism of Broiler Chicks (갑상선 호르몬의 경구투여가 육계의 사양성적, 체조성, 혈청 호르몬 농도 및 에너지 대사에 미치는 영향)

  • 가천흥;김창혁;채병조;이영철
    • Korean Journal of Poultry Science
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    • v.26 no.4
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    • pp.237-245
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    • 1999
  • This study was conducted to investigate the effect of dietary thyroid hormone (T$_3$and T$_4$) on growth, feed conversion ratio and serum T$_3$or T$_4$concentration of broiler chicks. Zero to six week-old broiler chicks were randomly allocated into seven treatment groups for feeding trials with three replication : control, T$_3$(0.1), T$_3$(1.0), T$_3$(5.0), T$_4$(0.1), T$_4$(1.0), T$_4$(5.0) ppm group. Concentrations of T$_3$and T$_4$in serum were analyzed. The weight gain of T$_3$(1.0), T$_3$(5.0) and T$_4$(5.0) groups were significantly lower than that of control. No statistically significant adverse effect was observed in other groups (p〉0.05). Feed intake was significantly lower in T$_3$(0.1, 1.0 and 5.0) and T$_4$(5.0) than in control group (p〈0.05), and the feed conversion ratio had a similar trend to the feed intake change. The contents of liquid and abdominal fat pad in carcass were significantly decreased in all T$_3$and T$_4$groups (p〈0.05). T$_3$and T$_4$concentration in serum was significantly increased at over 1.0ppm of the hormone supplementation level. As T$_3$addition level increased, T$_4$concentration in serum reduced ; however, T$_3$in serum was directly proportional during fasted were slightly increased when T$_3$or T$_4$was added to broiler diets.

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Evaluation of Maternal Toxicity in Rats Exposed to 1,3-Dichloro-2-propanol during Pregnancy

  • Lee, Jong-Chan;Shin, In-Sik;Kim, Gang-Hyeon;Park, Na-Hyeong;Moon, Chang-Jong;Bae, Chun-Sik;Kang, Sung-Soo;Kim, Sung-Ho;Shin, Dong-Ho;Kim, Jong-Choon
    • Toxicological Research
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    • v.24 no.4
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    • pp.307-314
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    • 2008
  • The present study was carried out to investigate the potential adverse effects of 1,3-dichloro-2-propanol on pregnant dams after maternal exposure during the gestational days (GD) 6 through 19 in Sprague-Dawley rats. The tested chemical was administered orally to pregnant rats at dose levels of 0, 10, 30, or 90 mg/kg/day. During the test period, clinical signs, mortality, body weights, food consumption, serum biochemistry, gross findings, organ weights, and Caesarean section findings were examined. In the 90 mg/kg group, decreases in the body weight gain and food consumption, and increases in the weights of liver and adrenal glands were observed. Serum biochemical investigations revealed increases in aspartate aminotransferase (AST), alanine aminotransferase (ALT), cholesterol (CHO), triglyceride (TG), alkaline phosphatase (ALP), and bilirubin (BIL) and decreases in glucose (GLU), albumin (ALB) and total protein (TP). In the 30 mg/kg group, a decrease in the food consumption and an increase in the liver weight were observed. Serum biochemical investigation also showed increases in CHO and TG and a decrease in glucose. Since there were no signs of maternal toxicity in the 10 mg/kg group, it is considered to be the no-observed-adverse-effect level (NOAEL) of 1,3-dichloro-2-propanol. It is concluded that successive oral administration of 1,3-dichloro- 2-propanol to pregnant rats for 14 days may cause significant toxicities in body weight and liver at a dose rate ${\geq}$ 30 mg/kg/day.

Two -week Oral Toxicity Study of 1- (4-methylpiperazinyl) -3- phenylisoquinoline (CWJ-a-5) in sprague-Dawley (SD) Rats (1-(4-methylpiperazinyl)-3-phenylisoquinoline (CWJ- a-5)의 Sprague-Dawley(SD) 랫드를 이용한 2주간 반복 경구투여 독성시험)

  • 강부현;조원제;김대덕;김용범;차신우;장순재
    • Toxicological Research
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    • v.18 no.1
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    • pp.47-57
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    • 2002
  • The subacute oral toxicity of 1-(4-methylpiperazinyl)-3-phenylisoquinoline (CWJ- a-5) was investigated in Sprague-Dawley (SD) rats. Five groups of 5 males and 5 females were orally administered at doses of 0, 37.5, 75, 150 and 200 mg/kg with CWJ-a-5 for 2 weeks. In clinical signs, Salivation was observed in the 75, 150 and 500 mg/kg male and female groups. Loss of fur was observed in the 500 mg/kg male and female group. Body weight were significantly decreased in the 150 and 500 mg/kg male groups and in the 500 mg/kg female group. Food consumption was significantly decreased in the 300 mg/kg male group. In serum biochemistry, total cholesterol and phospholipid were significantly increased in 500 mg/kg male and female group. Aspartate aminotransferase was significantly increased in the 500 mg/kg female group. In histopathological examination, vacuolar degeneration of renal tubules in the kidney, vacuolar degeneration of hepatocytes in the liver vacuolar degeneration of myocytes in the heart, vacuolar degeneration of histiocytes in the spleen and thymus, atrophy of seminiferous tubule and degeneration of germinal epithelium in the testis, vacuolar degeneration of corpus luteum, granulosa cell and theca cell in the ovary were observed in the 150 and 500 mg/kg male and female groups. Based on these results, the no observed adverse effect level (NOAEL) with CWJ-a-5 was considered to be 75 mg/kg and the absolute toxic dose was considered to be 150 mg/kg in this study