• Title/Summary/Keyword: Dose toxicity study

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Vaginal Dose, Toxicity and Sexual Outcomes in Patients of Cervical Cancer Undergoing Image Based Brachytherapy

  • Rai, Bhavana;Dhanireddy, Bhaswanth;Patel, Firuza Darius;Kumari, Reena;Oinam, Arun Singh;Simha, Vijai;Sharma, Suresh
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.8
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    • pp.3619-3623
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    • 2014
  • Background: The aim of the study was to evaluate the vaginal dose and toxicity in patients of cervical cancer treated with image guided brachytherapy at our institute. Materials and Methods: Thirty-five patients treated with image based brachytherapy for cervical cancer were included. Vaginal contouring was done on MRI at brachytherapy and with CT scans of subsequent brachytherapy fractions. Dose volume parameters (DVH) were reported in accordance with the GEC-ESTRO guidelines. These were correlated with vaginal toxicity (assessed by CTCAE version 3) and quality of sexual life assessed at one year of completion of treatment. Results: Vaginal shortness was observed in 22 out of 30 (62.8%) patients, Nine (25.7%) had vaginal dryness and in 10 (28.5%) patients, there was contact bleeding. No association could be demonstrated between the dose volume parameters and vaginal toxicity in the present study. Conclusions: The lack of association between dose volume parameters of vagina with vaginal morbidity may be due to uncertainties involved in the delineation of vaginal wall and dosimetry. Future research is required to accurately define vaginal dose distribution to study its correlation with vaginal morbidity. Vaginal morbidity needs to be documented in order to improve the sexual outcome in these patients.

Single Oral Dose Toxicity Test and Four Weeks Repeated Oral Dose Determination Test of Oplopanax elatus (Nakai) Nakai Hydrothermal Extract Powder in Sprague-Dawley Rats (Sprague-Dawley 랫드를 이용한 땃두릅나무 열수추출물 분말의 단회 경구투여 독성시험 및 4주 반복 경구투여 용량 결정 시험)

  • Yoo, Nam Ho;Kwon, Yongsoo;Chun, Hyeon Soo;An, Kyu Sup;Kim, Hye Jin;Ryu, Hyeon Yeol;Lee, So Min;Song, Kyung Seuk;Park, Byung Jun;Kim, Myong Jo
    • Korean Journal of Pharmacognosy
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    • v.50 no.3
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    • pp.205-218
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    • 2019
  • This study was conducted to investigate the toxicity symptoms and approximate lethal dose (ALD) of Oplopanax elatus (Nakai) Nakai hydrothermal extract powder by single oral dose toxicity and 4 weeks of repeated oral dose determination. The Sprague-Dawley (SD) male and female rats were treated with 1,250 (low- dosage group), 2,500 (medium- dosage group) and 5,000 (high- dosage group) mg/kg. In the single oral dose toxicity test, no dead animals and toxic symptoms were observed during the experiment. And there were no related with anomalies in normal weight changes and autopsy results. In the four-week repeated oral dose determination test, no death animals and toxicity symptoms were observed during the experiment, and there were no abnormal results in weight changes, feed and negative intake measurements. Results of eye examination, urinalysis, hematological values and serum biochemical values, gross findings and absolute organ were not of singularity. These result demonstrated that no toxic symptoms were observed by the test substance Oplopanax elatus (Nakai) Nakai hydrothermal extract powder under this test condition, and the non-toxic content is determined to be 5,000 mg/kg/day.

Study of Single-dose Toxicity of Guseonwangdo-go Glucose Intramuscular Injection in Sprague-Dawley Rats

  • Jo, Su-Jeong;Kim, Sung-Chul;Kim, Yu-Jong;Kim, Eun-Jung;Kim, Kap-Sung;Lee, Seung-Deok
    • Journal of Pharmacopuncture
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    • v.17 no.1
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    • pp.51-58
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    • 2014
  • Objectives: This study was performed to analyze single-dose intramuscular toxicity of Guseonwangdo-go glucose pharmacopuncture. Methods: Eighty six-week-old Sprague-Dawley rats were divided into two large groups of forty rats; Guseonwangdo-go glucose 5% and Guseonwangdo-go glucose 20% groups. Each group was sub-divided into four smaller groups of five males and five females, with the following dosages of pharmacopuncture being administered by intramuscular (IM) injection in each group: group 1 (G1, control group): 1.0 mL of normal saline solution, group 2 (G2, low-dose group): 0.1 mL, group 3 (G3, mid-dose group): 0.5 mL, and group 4 (G4, high-dose group): 1.0 mL. Results: No mortalities or clinical signs were observed in any group. Also, no significant changes in body weights or in hematological/biochemical analyses were observed between the control and the experimental groups during necropsy or histopathology. Conclusion: The above findings suggest that the lethal dose of Guseonwangdo-go glucose 5% and 20% pharmacopuncture administered via IM injection is more than 1.0 mL per animal in both male and female rats. Further studies on the repeated-dose toxicity of Guseonwangdo-go glucose should be conducted to yield more concrete data.

Single and 28-day repeated dose toxicity studies of botulinum toxin type A in mice and rats (마우스 및 랫드에서 botulinum toxin type A의 단회 및 28일 반복투여 독성시험)

  • Jeon, Tae-Won;Kim, Ji-Young;Hyun, Sun-Hee;Kim, Nam-Hee;Lee, Sang-Kyu;Kim, Chun-Hwa;Woo, Hee-Dong;Yang, Gi-Hyeok;Jung, Hyun-Ho;Jeong, Tae-Cheon
    • Korean Journal of Veterinary Research
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    • v.43 no.1
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    • pp.57-66
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    • 2003
  • Single and 28-day repeated dose toxicity studies of botulimnn toxin type A were carried out in ICR mice and Sprague-Dawley rats, respectively. In the single dose toxicity study, botulinwn toxin was injected intraperitoneally to male and female mice at a single dose of 40, 59, 89 133 and 200 ng/10 ml saline/kg. All animals died from 59 ng/kg group. Some clinical signs, such as decrease in locomotor activity, dyspnea, prone position and ptosis, were observed in most of both sexes from 59 ng/kg group, but no signs were seen in all animals at 40 ng/kg group. The results showed that the median lethal dose of botulinum toxin might be in the range of 40-59 ng/kg in both sexes. In the repeated dose toxicity study, the test material was administered intradermally for 28 days at doses of 0 (vehicle-treated control), 1.25, 2.5, 5.0 and $10.0ng/head/50{\mu}{\ell}$ saline in male and female rats. No test material-related changes were noted in survivals, clinical signs, food and water consumptions and gross finding in any group. Botulinum toxin treatment significantly decreased the body weight gain rate in male of 5.0 ng/head group and over and in female of 10.0 ng/head group compared to vehicle-treated control. One or more relative organ weights (i.e., spleen, thymus, liver and kidney) were increased significantly from 5.0 ng/head group compared to vehicle-treated control in both sexes. Serum biochemistry revealed increases in aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatine phosphokinase, total protein and albumin in male, and increases in AST and ALT and decreases in $K^+$ and $Cl^-$ in female without dose-pendent manners. In the histopathological study, physical stimulation by needle caused slight inflammations of dennis. In addition, botulinum toxin treatment induced denervation of nerve cell and disuse of muscle, resulting in atrophy of skeletal muscle in both sexes from 2.5 ng/head group. When the antibodies to toxin were determined in all animals, a significant increase in serum antibodies was observed from 5.0 ng/head group. The results showed that the NOAEL of botulinum toxin might be 1.25 ng/head for 28-day repeated dose toxicity in rats.

Study on a 4-Week Recovery Test of Sweet Bee Venom after a 13-Week, Repeated, Intramuscular Dose Toxicity Test in Sprague-Dawley Rats

  • Kang, Hyunmin;Lim, Chungsan;Lee, Seungbae;Kim, Byoungwoo;Kwon, Kirok;Lee, Kwangho
    • Journal of Pharmacopuncture
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    • v.17 no.2
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    • pp.18-26
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    • 2014
  • Objectives: This study was performed to check for reversibility in the changes induced by a 13-week, repeated, dose toxicity test of Sweet Bee Venom (SBV) in Sprague-Dawley (SD) rats. Methods: Fifteen male and 15 female SD rats were treated with 0.28 mg/kg of SBV (high-dosage group) and the same numbers of male and female SD rats were treated with 0.2 mL/kg of normal saline (control group) for 13 weeks. We selected five male and five female SD rats from the high-dosage group and the same numbers of male and female SD rats from the control group, and we observed these rats for four weeks. We conducted body-weight measurements, ophthalmic examinations, urinalyses and hematology, biochemistry, histology tests. Results: (1) Hyperemia and movement disorder were observed in the 13-week, repeated, dose toxicity test, but these symptoms were not observed during the recovery period. (2) The rats in the high-dose group showed no significant changes in weight compared to the control group. (3) No significant differences in the ophthalmic parameters, urine analyses, complete blood cell counts (CBCs), and biochemistry were observed among the recovery groups. (4) No changes in organ weights were observed during the recovery period. (5) Histological examination of the thigh muscle indicated cell infiltration, inflammation, degeneration, necrosis of muscle fiber, and fibrosis during the treatment period, but these changes were not observed during the recovery period. The fatty liver change that was observed during the toxicity test was not observed during the recovery period. No other organ abnormalities were observed. Conclusion: The changes that occurred during the 13-week, repeated, dose toxicity test are reversible, and SBV can be safely used as a treatment modality.

Single Dose Oral Toxicity Test of Peucedani Radix in ICR Mice (ICR 마우스를 이용한 전호의 단회경구투여 독성 실험)

  • Kwon, Da-hye;Kim, Min-young;Hwangbo, Hyun;Ji, Seon-yeong;Park, Cheol;Choi, Yung-hyun;Hong, Su-hyun
    • The Journal of Internal Korean Medicine
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    • v.39 no.4
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    • pp.676-685
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    • 2018
  • Objectives: The aim of this study was to estimate the single oral toxicity of Peucedani Radix (PR) ethanol extracts. PR is one of the important herbs for removal of phlegm, the viscous turbid pathological product that can accumulate in the body and cause a variety of diseases. However, research on the pharmacologic toxicity of PR is lacking. Methods: In this study, PR was orally administered to 5-week-old male ICR mice at an oral dose of 2,000, 3,000, or 5,000 mg/kg. After a single-dose administration, the mortality and behavioral changes were observed daily and body weights were measured every two days. After 14 days, the organ weight, organ index, macroscopy, hematological analysis, and serum biochemistry analysis were determined. Results: No mortality, body weight changes, abnormal behavioral changes, or anatomical signs of toxicity were found. The organ weight, organ index, hematological analysis, and serum biochemistry analysis were also within the normal ranges. Conclusions: These results suggest that the 50% lethal dose of PR is more than 5,000 mg/kg. This could indicate that PR is a safe drug without acute toxicity and side effects.

Metabolic profiling study of ketoprofen-induced toxicity using 1H NMR spectroscopy coupled with multivariate analysis

  • Jung, Jee-Youn;Hwang, Geum-Sook
    • Journal of the Korean Magnetic Resonance Society
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    • v.15 no.1
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    • pp.54-68
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    • 2011
  • $^1H$ nuclear magnetic resonance (NMR) spectroscopy of biological samples has been proven to be an effective and nondestructive approach to probe drug toxicity within an organism. In this study, ketoprofen toxicity was investigated using $^1H$-NMR spectroscopy coupled with multivariate statistical analysis. Histopathologic test of ketoprofen-induced acute gastrointestinal damage in rats demonstrated a significant dose-dependent effect. Furthermore, principal component analysis (PCA) derived from $^1H$-NMR spectra of urinary samples showed clear separation between the vehicle-treated control and ketoprofen-treated groups. Moreover, PCA derived from endogenous metabolite concentrations through targeted profiling revealed a dose-dependent metabolic shift between the vehicle-treated control, low-dose ketoprofen-treated (10 mg/kg body weight), and high-dose ketoprofen-treated (50 mg/kg) groups coinciding with their gastric damage scores after ketoprofen administration. The resultant metabolic profiles demonstrated that the ketoprofen-induced gastric damage exhibited energy metabolism perturbations that increased urinary levels of citrate, cis-aconitate, succinate, and phosphocreatine. In addition, ketoprofen administration induced an enhancement of xenobiotic activity in fatty oxidation, which caused increase levels of N-isovalerylglycine, adipate, phenylacetylglycine, dimethylamine, betaine, hippurate, 3-indoxylsulfate, N,N-dimethylglycine, trimethyl-N-oxide, and glycine. These findings demonstrate that $^1H$-NMR-based urinary metabolic profiling can be used for noninvasive and rapid way to diagnose adverse drug effects and is suitable for explaining the possible biological pathways perturbed by nonsteroidal anti-inflammatory drug toxicity.

Single-Dose Toxicity and Four Week Repeated-Dose Toxicity Study on Tensolin-F® (3,9-diferuloyl-6-oxopterocarpen) (Tensolin-F® (3,9-diferuloyl-6-oxopterocarpen)의 단회 독성시험 및 4주 반복투여 독성시험)

  • Kim, Keun-Su;Park, Sung-Min;Lee, Nam-Jin;Pyo, Hyeong-Bae;Chai, Hee-Yul;Jung, Yu-Ri;Lin, Chun-Mai;Kim, Sun-Hee;Lee, Hye-Young;Kang, Jong-Koo
    • Toxicological Research
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    • v.23 no.4
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    • pp.405-413
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    • 2007
  • This study was to investigate single and repeated-dose toxicities of Tensolin-$F^{(R)}$, an anti-wrinkle agent, in Sprague-Dawley (SD) rats or ICR mice. In single-dose oral toxicity study, the test materials were administered once by gavage to male and female SD rats at dose levels of 0 and 2,000 mg/kg. No dead animals and abnormal necropsy findings were found in control and Tensolin-$F^{(R)}$ treated group. Therefore, the approximate lethal dose of Tensolin-$F^{(R)}$ was considered to be higher than 2,000 mg/kg in rats. In the 4-week repeated oral toxicity study, the test material was administered once daily by gavage to male and female ICR mice at dose levels of 0, 25, 50 and 100 mg/kg/day for 4-weeks. In the results, no abnormality was observed in mortality, clinical findings, body weight changes, food and water consumptions, opthalmoscopic findings, necropsy findings, histopathological findings. In hematological analysis, there was a trend of increase in reticulocyte at male 25 mg/kg, although such changes were in normal ranges. On the other hand, there was a trend of decrease in hemoglobin at female 50, 100 mg/kg, such changes were in normal ranges. In addition, serum biochemical parameters including sodium, BUN and chloride increased at 25, 50 and 100 mg/kg. Relative organ weights of right testis, brain, lung and left epididymis were increased in 100 mg/kg groups of male rats in contrast to not change in female groups. However, these changes of relative organ weights, hematological and serum biochemical parameters were not accompanied with related signs such as histopathological changes or clinical findings. In conclusion, 4-week repeated oral dose of Tensolin-$F^{(R)}$ to ICR mice did not cause apparent toxicological change at the dose of 25, 50, 100 mg/kg body weight. Consequently the no-observed-adverse-effect level (NOAEL) for Tensolin-$F^{(R)}$ in ICR mice following gavage for at least 4-week is higher than 100 mg/kg/day.

Acute and Repeated 28-Day Oral Dose Toxicity Studies of Thymus vulgaris L. Essential Oil in Rats

  • Rojas-Armas, Juan;Arroyo-Acevedo, Jorge;Ortiz-Sanchez, Manuel;Palomino-Pacheco, Miriam;Castro-Luna, Americo;Ramos-Cevallos, Norma;Justil-Guerrero, Hugo;Hilario-Vargas, Julio;Herrera-Calderon, Oscar
    • Toxicological Research
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    • v.35 no.3
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    • pp.225-232
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    • 2019
  • Thymus vulgaris L. is widely used as an ingredient in cooking and in herbal medicine. However, there is little information about its toxicity. The present study was performed to evaluate the acute and repeated 28-day oral dose toxicity of thyme essential oil in rats. For the acute toxicity test, two groups of three rats were used. The rats received a single dose of essential oil: 300 or 2,000 mg/kg of body weight (bw). The rats were observed individually during the first four hours, and then daily until day 14. For the toxicity test with repeated doses, four groups of 10 rats were used. Doses of 100, 250, and 500 mg/kg/day were tested for 28 days. At the end of the experiment, blood was collected and the animals were sacrificed. Histopathological examination showed that in the lungs of rats given the 2,000 mg/kg bw dose, polymorph nuclear infiltrates, hemosiderin macrophages, and interstitial space thickening were present. In the repeated dose study, all rats survived the 28-day treatment period and apparently showed no signs of toxicity. The hematological and biochemical parameters were not altered. The histopathological study of the organs showed severe changes in the lung, with the dose of 500 mg/kg/day; in the other organs, no alterations were observed or the changes were slight. The body weight was only altered in male rats given the 500 mg/kg dose. The relative weight of the organs did not show any significant changes. Our studies revealed that the essential oil of Thymus vulgaris has moderate oral toxicity according to the results of the acute test, whereas the results of the 28-day oral toxicity test suggest that the no-observed-adverse effect level (NOAEL) is greater than 250 mg/kg/day.

Subacute Oral Toxicity Assesment of Ethanol Extract of Mariposa christia vespertilionis Leaves in Male Sprague Dawley Rats

  • Nurul, Syahirah Ahmad Sayuti;Hazilawati, Hamzah;Mohd, Rosly Shaari;Mohd, Farhan Hanif Reduan;Noordin, Mohamed Mustapha;Norhaizan, Md Esa
    • Toxicological Research
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    • v.34 no.2
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    • pp.85-95
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    • 2018
  • The term Butterfly tea refers to decoction of Mariposa christia vespertilionis leaves which is widely consumed by cancer patients throughout Malaysia and has gained a huge popularity among Malaysians, not only cancer patients but also researchers to discover the real potential of this plant. Herein, the study is aimed at evaluating the possible toxicity in 28-day subacute oral toxicity of ethanolic extract M. christia vespertilionis in male Sprague Dawley rats. The 28-day subacute toxicity study was conducted to detect the no-observed adverse effect level (NOAEL). In this study, a total of 30 rats were divided into the control, 5% DMSO (vehicle), low dose (75 mg/kg), medium dose (125 mg/kg) and high dose (250 mg/kg) groups. The extract was administered daily from day 1 until day 28. At the end of the study, the animals were humanely sacrificed and assessed for the effect extract of Mariposa christia vespertilionis leaves on body weight and relative organ weights and haematological, biochemical and histopathological parameters. The haematological and serum biochemical parameters for the assessment of kidney and liver injuries were carried out. Results of haematological and serum biochemistry results showed no changes in the control and treated groups. In the histopathology, evaluation of kidney tissues in all treated groups showed no significant (p > 0.05) lesions. In contrast to kidney, liver tissues showed significant differences (p < 0.05) in lesions observed in low dose (430 mg), medium dose (700 mg) and high dose (1480 mg) groups with very mild, mild and mild to moderate lesion of hepatic necrosis, in the respective groups, and very mild hepatic degeneration and hepatitis were scored in all three groups.