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Background: This study aimed to assess the toxicity of capsaicin (CP) pharmacopunture in an animal model.Methods: The toxicity of a single-muscular dose of CP (45.45 mg/mL) was evaluated in 6-week-old male and female Sprague-Dawley rats. A total of 20 rats were assigned to 2 groups which were sex and weight matched. All rats acclimatized for 1 week before receiving 1.0 mL of CP (45.45 mg/mL) or normal saline solution(control) intramuscularly. The general condition and mortality of the animals were observed. The rats were sacrificed 2 weeks after CP was administered and histopathology was performed.Results: No abnormal symptoms or deaths were observed, and there was no difference in body weights between the CP and control groups throughout the study. No significant differences in histopathology were observed between the groups.Conclusion: No toxicological changes related to the administration of CP were observed. This study indicated that the safe dose of CP in Sprague-Dawley rats was 1.0 mL of CP (45.45 mg/mL) or less. Further studies are needed to confirm the safety of CP in the human body.

Objectives: TA is a polyherbal extract comprising seven herbs, typically used for the pharmacopuncture treatment of patients with traffic accident- related injuries and musculoskeletal diseases. This animal study was conducted to evaluate the safety of the TA extract, using a single-dose toxicity test. Methods: The dose range and sampling time were first established. Six- week-old Sprague–Dawley rats were administered 1.0 mL of TA or normal saline (control), intramuscularly, for the single-dose toxicity test. The general condition, mortality, and histology of all rats were observed for 2 weeks. Results: No abnormal symptoms or deaths were ob served in any group. The body weights of the rats in the TA and control groups were similar. No significant differences in histopathology were observed between the groups. Conclusion : Our study indicates that 1.0 mL of TA extract may be safely administered for pharmacopuncture for treatment of patients in traditional medicine clinics.

Genus Ficus is important plant for health benefits. Hairy fig (F. hispida) trees grow abundantly in tropical regions and fruiting throughout the year. In West Asian countries, the fruit is commonly used as food and medicinal materials. However, in Indonesia, the fruit has not been utilized. First step in exploring the potential of natural resources for consumption is toxicity test to provide information about safety and adverse effects. This research was aimed to study acute oral toxicity of young and ripe hairy fig fruits using Wistar rats as model. Procedure followed OECD Guideline Test No.420 with modification. Pure filtrate (100 %) of young or ripe fruits were administered orally at volume 1 mL/individual on day-0 in fasting animals. Control received distilled water in the same way. Parameters observed including mortality, sublethal effects, behavior/activities, body weight, complete blood count, as well as evaluation of liver, heart, and renal functions. Results showed that values for all variables fluctuated during the experiment but eventually back into normal range. However, the number of lymphocytes elevated until the end of experiment (day-14) thus increased the total leukocytes count. Accordingly, we are preparing to conduct further toxicity tests to investigate this finding. Key words : acute oral toxicity, Ficus hispida, fruit filtrate, hairy fig, single dose toxicity

Background. ML171 is a potent nicotinamide adenine dinucleotide phosphate oxidase (NOX) inhibitor with isoform selectivity only for NOX1. This study is aimed at investigating the safety of ML171 after a single intraperitoneal (IP) injection in mice. Methods. The toxicity of a single dose of ML171 was evaluated in 6-week-old Institute of Cancer Research (ICR) mice in a good laboratory practice (GLP) laboratory. Twenty-five mice of each sex were assigned to five groups: negative control, vehicle control, and 125, 250, and 500 mg/kg of ML171. All mice were acclimatized for one week before beginning the study. Mice received an IP injection of ML171 or vehicle. The general condition and mortality of the animals were observed. The mice were sacrificed to evaluate histopathology 14 days after the administration of ML171 or vehicle. Results. Bodyweights were not significantly different in any group. Three males and one female died due to ML171 administration in the 500 mg/kg dose group. Autopsies of the surviving mice did not reveal any significant abnormalities after the injection of 125 mg/kg of ML171. However, the anterior lobe edge of the liver was thickened and adhesions between the liver and adjacent organs were observed in mice treated with 250 or 500 mg/kg of ML171. In addition, hypertrophy of centrilobular hepatocytes and inflammatory cell infiltration were observed after injection of 250 and 500 mg/kg of ML171. Conclusion. Our results indicate that the lethal IP injection dose of ML171 is 500 mg/kg for both males and females. Mortality were not observed for lower doses of ML171. The safe dose of single IP ML171 in ICR mice was 250 mg/kg or less. Further studies are needed to confirm the safety of ML171 in the human body.

Bartogenic acid (BA), an active pentacyclic triterpenoid, has been reported for anti-diabetic, anti-inflammatory, anti-arthritic, anti-cancer, and anti-tumor activity. However, toxicity profiling of BA has not been reported till date. Hence, this study is designed to evaluate the single dose (12.5, 25, 50 and 100 mg/kg) and repeated dose (1.5, 6, and 24 mg/kg) intravenous toxicity of BA in BALB/c mice. Control group received vehicle. In single dose toxicity study, two mortalities were observed at 100 mg/kg of BA whereas lower doses were well tolerated. In repeated dose toxicity study, no mortality was observed. 1.5 mg/kg of BA was well tolerated in mice of both sexes. At 6 mg/kg of BA, female mice showed significant reduction in the body weight as compared to the control group however no significant change was observed in male mice. 24 mg/kg of BA showed significant reduction in the body weight in mice of both sexes. Further, these mice showed significant change in the relative organ weight. However, no toxicologically relevant changes were observed in hematology, biochemistry, and histopathology. Based on the findings, No-Observed-Adverse-Effect-Level (NOAEL) for BA were found to be less than 24 mg/kg for male mice and less than 6 mg/kg for female mice.

Nanomedicine is widely explored nowadays for treatment of life threatening diseases, yet comes with various challenges and questions. The present study encapsulates the acute toxicological aspects of the Euphorbia thymifolia coupled silver nanoparticles (ET-Ag NP). For acute toxicity studies according to OCED (Organization for Economic Cooperation Development) guidelines Swiss Albino mice (6-8 weeks) were used and were given single intraperitoneal dose of 2000 and 5000 mg/kg body weight and were observed for mortality and other side effects for 14 days. The individual components of the formulation, viz. silver oxide in surface modified nano form and at low dose, and Euphorbia thymifolia are both biocompatible materials. No changes were found for general appearance, behavior and body weight, thus concluding that the nanocomposite formulation does not have single dose toxicity.

Objectives Bufonis venonum (BV) is toad venom and is the dried, white secretions of the auricular and the skin glands of toads. This study was performed to evaluate the toxicity of intravenous injection of Bufonis venonum pharmacopuncture (BVP) through a single- dose test with sprague-dawley (SD) rats. Methods Twenty male and 20 female 6-week-old SD rats were injected intravenously in the caudal vein with BVP or normal saline. The animals were divided into four groups with five female and five male rats per group: the control group injected with normal saline, the low-dosage group injected with 0.1 mL/animal of BVP, the medium-dosage group injected with 0.5 mL/ animal of BVP and the high-dosage group injected with 1.0 mL/animal of BVP. We performed clinical observations every day and body weight measurements on days 3, 7 and 14 after the injection. We also conducted hematology, serum biochemistry, and histological observations immediately after the observation period. Results No mortalities were observed in any experimental group. Paleness occurred in the medium- and the high-dosage groups, and congestion on tails was observed in females in the medium- and the high-dosage groups. No significant changes in weight, hematology, serum biochemistry, and histological observations that could be attributed to the intravenous injection of BVP were observed in any experimental group. Conclusion The lethal dose of intravenously-administered BVP in SD rats is over 1.0 mL/animal.

Objectives :This study was conducted to analyze the single dose toxicity of Mecasin (Gami-Jakyak Gamcho buja Decoction) herbal acupuncture administered in the vein of Sprague-Dawley rats. Methods :All experiments were performed at the Medvill, an institution licensed to conduct nonclinical studies, under the Good Laboratory Practice (GLP) regulations. Sprague-Dawley rats were chosen in this pilot study. In the experiment, Sprague-Dawley rats were divided into four groups of five male and five female animals per group. Doses of Mecasin herbal acupuncture, at 0, 500, 1,000, and 2,000 mg/kg, were given to the experimental groups, and a dose of normal saline solution, at 2 ml/kg, was administered to the control group. Mecasin herb acupuncture and normal saline were injected into the vein at once, and we observed mortality, clinical signs, weights, and gross findings for 14 days after injection. This study was conducted under the approval of the Institutional Animal Ethics Committee. Results : There is no death or abnormality in any of the four groups. All groups put on weights favorably. There are no significant gross findings in necropsy examinations. Conclusions :The above results showed that intravenous injection of 500-2,000 mg/kg of Mecasin herb acupuncture did not cause any changes in weight or, in the results of necropsy examinations, in mortalities. Therefore, the toxicity of Mecasin herb acupuncture was not confirmed, and the presumptive lethal dose of Mecasin herb acupuncture was higher than 2,000 mg/kg. The outcomes suggest that treatment with Mecasin herbal acupuncture is relatively safe. Further evaluations on this subject are needed to yield more concrete evidence.

Objectives: Bufonis venonum (BV) is the dried white secretions of the auricular and skin glands of the toads Bufo bufo gargarizans or Bufo melanosticus Schneider. This study was performed to evaluate the toxicity of intramuscularly- administered Bufonis venonum pharmacopuncture (BVP) and to calculate its approximate lethality through a single-dose test with Sprague-Dawley (SD) rats. Methods: Twenty male and 20 female 6-week-old SD rats were injected intramuscularly with BVP or normal saline. The animals were divided into four groups with five female and five male rats per group: the control group injected with normal saline at 0.5 mL/animal, the low-dosage group injected with 0.125 mL/animal of BVP, the medium-dosage group injected with 0.25 mL/animal of BVP and the high-dosage group injected with 0.5 mL/animal of BVP. All injections were in the left thighs of the rats. After administration, we conducted clinical observations everyday and body weight measurements on days 3, 7 and 14 after the injection. We also carried out hematology, serum biochemistry, and histological observations on day 15 after treatment. Results: No mortalities were observed in any experimental group. No significant changes in weight, hematology, serum biochemistry, and histological observations that could be attributed to the intramuscular injection of BVP were observed in any experimental group. Conclusion: Lethal dose of BVP administered via intramuscular injection in SD rats is over 0.5 mL/animal.

Objectives: This study was carried out to analyze the single dose toxicity of Mecasin(Gami-Jakyak Gamcho buja Decoction) pharmacopuncture in muscle of Sprague-Dawley rats. Methods: All experiments were performed at the Medvill, an institution acknowledged to conduct non-clinical studies, under the Good Laboratory Practice (GLP) regulations. Sprague-Dawley rats were chosen in this pilot study. The reason Sprague-Dawley rats were chosen is that they have been widely used in safety test in the field of medicine, so the results can be easily compared with many other databases. Doses of Mecasin pharmacopuncture, 0, 500, 1,000, and 2,000mg/kg, were registered to the experimental groups, and a dose of normal saline solution, 10 ml/kg, was registered to the control group. Mecasin pharmacopuncture and normal saline were injected into the thigh of the rats by disposable syringes at intervals of six hours twice a day. This study was performed under the approval of the Institutional Animal Ethic Committee. Results: There is no death or abnormality in any of the four groups. No significant changes in weight, hematological parameters or clinical chemistry between the control group and the experimental groups were observed. To inspect abnormalities in organs and tissues, we used microscopy to examine representative histological sections of each specified organ; the results showed no significant differences in any of the organs or tissues. Conclusion: The above outcomes suggest that treatment with Mecasin pharmacopuncture is relatively safe. Further evaluations and studies on this subject are needed to prove more concrete evidence.

The plants Myracrodruon urundeuva (aroeira), Poincianella pyramidalis (catingueira) and Anadenanthera colubrina (angico), are commonly used in the popular medicine of Cariri Paraibano, for the treatment of various intestinal, gynecological, healing and respiratory diseases. The objective of this study was to evaluate the acute non - clinical toxicological profile of infusions and nebulized dry extracts of the plant drugs of M. urundeuva, P. pyramidalis and A. colubrina. The powder infusions of the plant drugs of the studied plants were evaluated in the sizes of particles of coarse powder (710-355 µm), semifinished powder (355-180 µm) and fine powder (150-75 µm) in the swiss Single dose, evaluated for 14 days, regarding behavioral changes, water consumption, feed and body mass. The spray dried extracts M. urundeuva, P. pyramidalis and A. colubrina were evaluated at concentrations of 500, 1000 and 2000 mg / kg per animal in a single oral dose in male / female mice for 14 days, Observing the behavioral changes, water consumption, ration and body mass. We also determined the mass of the heart, liver, kidney, lung and spleen organs, with morphological evaluation of these organs. The repeated doses studies using the ESN of the studied plant drugs at a concentration of 2000 mg / kg / day / animal in mouse and male / female rabbits, evaluated during 30 days, regarding behavioral changes, water consumption, feed and body mass, As well as mass of the heart, liver, kidney, lung and spleen organs, as well as the analysis of the hematological and biochemical, morphological and histopathological parameters of the organs studied. Control groups were used by administering distilled water in mice and rabbits. The data obtained with infusions showed no signs of systemic toxicity for all particle sizes of the studied plant drugs. Singledose toxicity studies with NSAs at three concentrations also showed no behavioral change in water and feed intake, body mass, body mass, liver, kidney, lung and spleen organs. At repeated doses at the concentration of 2000 mg / kg per animal of each ESN of the plant drugs M. urundeuva, P. pyramidalis and A. colubrina, there was no evidence of systemic and behavioral toxicological changes or death in mice and rabbits treated with their respective control groups. Acute non-clinical toxicological studies have shown that the infusions and dry extracts of the species studied can be used in topical formulations at concentrations evaluated with proven safety. Nenhuma As plantas Myracrodruon urundeuva (aroeira), Poincianella pyramidalis (catingueira) e Anadenanthera colubrina (angico), são comumente utilizadas na medicina popular do Cariri paraibano, para o tratamento de diversas afecções intestinais, ginecológicas, de cicatrização e respiratórias. O trabalho teve como objetivo avaliar o perfil toxicológico não clínico agudo, dos infusos e dos extratos secos nebulizados das drogas vegetais das folhas de M. urundeuva, P. pyramidalis e A. colubrina. Foram avaliados os infusos dos pós das drogas vegetais das plantas estudadas, nos tamanhos de partículas de pó grosso (710-355 µm), pó semifino (355-180 µm) e o pó finíssimo (150-75 µm), nos camundongos swiss em dose única, avaliados durante 14 dias, quanto às alterações comportamentais, consumo de água, ração e massa corporal. Os extratos secos nebulizados (ESN) das drogas vegetais M. urundeuva, P. pyramidalis e A. colubrina foram avaliados nas dose de 500, 1000 e 2000 mg/kg por animal em dose única via oral em camundongos machos/fêmeas durante 14 dias, observando-se às alterações comportamentais, consumo de água, ração e massa corporal. Foram determinados, também, a massa dos órgãos coração, fígado, rins, pulmão e baço, com avaliação morfológica desses órgãos. Os estudos em doses repetidas utilizando o ESN das drogas vegetais estudadas, na dose de 2000 mg/kg/dia /animal em camundongo e coelhos machos/fêmeas, avaliados durante 30 dias, quanto às alterações comportamentais, consumo de água, ração e massa corporal, bem como massa dos órgãos coração, fígado, rins, pulmão e baço, além da análise dos parâmetros hematológicos e bioquímicos, morfológicos e histopatológicos dos órgãos estudados. Foram utilizados grupos controle administrando-se solução salina (NaCl 0,9%) em camundongos e coelhos. Os dados obtidos com os infusos evidenciaram a não existência de sinais de toxicidade sistêmica para todos os tamanhos de partículas das drogas vegetais estudadas. Os estudos toxicológicos de dose única com os ESN nas três dose também evidenciaram nenhuma alteração comportamental, no consumo de água e ração, na massa corporal, massa dos órgãos coração, fígado, rins, pulmão e baço. Em doses repetidas de 2000 mg/kg por animal de cada ESN das drogas vegetais M. urundeuva, P. pyramidalis e A. colubrina ficaram demonstradas a não existência de alterações toxicológicas sistêmicas e comportamentais ou morte nos camundongos e coelhos tratados em relação aos seus respectivos grupos controle. Os estudos toxicológicos não-clínicos agudos mostraram que os infusos e extratos secos das espécies estudadas podem ser utilizados em formulações tópicas nas dose avaliadas com segurança comprovada.

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.

Objective: This study was performed to analyze the single-dose toxicity of D-amino acid oxidase (DAAO) extracts. Methods: All experiments were conducted at the Korea Testing & Research Institute (KTR), an institution authorized to perform non-clinical studies, under the regulations of Good Laboratory Practice (GLP). Sprague-Dawley rats were chosen for the pilot study. Doses of DAAO extracts, 0.1 to 0.3 cc, were administered to the experimental group, and the same doses of normal saline solution were administered to the control group. This study was conducted under the approval of the Institutional Animal Ethics Committee. Results: In all 4 groups, no deaths occurred, and the LD50 of DAAO extracts administered by IV was over 0.3 ml/kg. No significant changes in the weight between the control group and the experimental group were observed. To check for abnormalities in organs and tissues, we used microscopy to examine representative histological sections of each specified organ, the results showed no significant differences in any organs or tissues. Conclusion: The above findings suggest that treatment with D-amino acid oxidase extracts is relatively safe. Further studies on this subject should be conducted to yield more concrete evidence.

Zerumbone (ZER), a bioactive compound isolated from Zingiber zerumbet Smith, was examined for single and repeated-dose toxicity at dosages with antitumor effects on imprinting control regions (ICR) mice and mice of either sex for repeated dose, respectively. For the single dose toxicity study, ZER was administrated to ICR mice at a dose of 500 mg/kg via intraperitoneal injection, while for the repeated dose toxicity study, mice of either sex were studied at dosages of 5, 25 and 50 mg/kg for a period of 28 days. The effects on body and organ weight, food and water consumption, hematology, serum biochemistry as well as histology, were evaluated. No mortality or significant changes in the clinical signs were produced at the single dose toxicity. There were no significant differences in the general condition, growth, organ weights, hematology, serum biochemistry, or histopathological analysis in the repeated dose toxicity as well. These results suggest that ZER is safe in a toxicity study for the cancer treatment in mice regardless of whether male or female mice. Key words: Zerumbone, toxicity, antitumor effect, single and repeated dose, safety.

Objective This study was performed to analyze the singledose toxicity of Aconitum kusnezoffii Reichb. pharmacopuncture (AKRP). Methods All experiments were conducted at the Korea Testing & Research Institute (KTRI), an institute authorized to perform non-clinical studies, under the regulations of Good Laboratory Practice (GLP). Twenty (20) Sprague-Dawley rats were chosen for the pilot study. The animals were divided into four groups of five animals per group: group 1 (G1) being the control group with each animal receiving an injection of 0.3 ml of saline and groups 2, 3, and 4 (G2, G3, and G4) being the experimental groups with each animal receiving an injection of 0.1, 0.2 or 0.3 ml of AKRP, respectively. This study was conducted with the approval of the Institutional Animal Ethics Committee. Results No deaths occurred in any of the 4 groups, and the LD50 of AKRP administered via IV was higher than 1.77 ml/kg. Some changes in the weights of the male rates were observed between the control group and the experimental groups, but no significant differences were noted in the weights of the female rats. To check for abnormalities in organs and tissues, we stained representative sections of each specified organ with Hematoxylin & Eosin for light microscopic examination. The results showed no significant differences in any of the organs or tissues. Conclusions The above findings suggest that Aconitum kusnezoffii Reichb. pharmacopuncture is a relatively safe treatment. Further studies on the subject should be conducted to yield more concrete evidence.

The present study was carried out to investigate the oral single and repeat toxicity of cross-linked β-cyclodextrin (β-CD) made with adipic acid. Ten each of female and male rats were orally administered a 5000 mg/kg single dose. At this dose, mortality or macroscopic changes of internal organs were not observed. Dose levels 500, 1000, or 2000 mg/kg of β-CD were given daily to 5 each of female and male rats by oral gavage for 14 days. Body and organ weights were not significantly different during the study ( P < .05). Hematology and clinical chemistry did not show any toxicity from the cross-linked β-CD. Macroscopic or microscopic changes were not observed between the controls and the treated rats. Based on these results, the cross-linked β-CD did not produce any signs of toxicity or other adverse effects at dose levels up to 2000 mg/kg per d for 14 days.

Objectives : This study was performed to analyse single dose toxicity of Sweet Bee Venom(Sweet BV) extracted from the bee venom in Beagle dogs. Methods : All experiments were conducted under the regulations of Good Laboratory Practice (GLP) at Biotoxtech Company, a non-clinical study authorized institution. Male and female Beagle dogs of 5-6 months old were chosen for the pilot study of single dose toxicity of Sweet BV which was administered at the level of 9.0 mg/kg body weight which is 1300 times higher than the clinical application dosage as the high dosage, followed by 3.0 and 1.0 mg/kg as midium and low dosage, respectively. Equal amount of excipient(normal saline) to the Sweet BV experiment groups was administered as the control group. Results : 1. No mortality was witnessed in all of the experiment groups. 2. Hyperemia and movement disorder were observed around the area of administration in all the experiment groups, and higher occurrence in the higher dosage treatment. 3. For weight measurement, Neither male nor female groups showed significant changes. 4. To verify abnormalities of organs and tissues, thigh muscle which treated with Sweet BV, brain, liver, lung, kidney, and spinal cords were removed and histologocal observation using H-E staining was conducted. In the histologocal observation of thigh muscle, cell infiltration, inflammation, degeneration, necrosis of muscle fiber, and fibrosis were found in both thigh tissue. And the changes depend on the dose of Sweet BV. But the other organs did not showed in any abnormality. 5. The maximum dose of Sweet BV in Beagle dogs were over 9 mg/kg in this study. Conclusions : The above findings of this study suggest that Sweet BV is a relatively safe treatment medium. Further studies on the toxicity of Sweet BV should be conducted to yield more concrete evidences.

Objectives: This study was performed to analyse single dose toxicity of pure melittin(Sweet Bee Venom-Sweet BV) extracted from the bee venom by utilizing protein isolation method of gel filtration. Methods: All experiments were conducted at Biotoxtech, a non-clinical studies authorized institution, under the regulations of Good Laboratory Practice (GLP). Six weeks old female Sprague-Dawley rats were chosen for the pilot study and determined 30㎎/㎏ which is 4285 times higher than the clinical application dosage as the high dosage, followed by 15 and 7.5㎎/㎏ as mid and lose dosage, respectively. Equal amount of excipient to the Sweet BV experiment groups was administered as the control group. Results: 1. No mortality was witnessed in all of the experiment groups. 2. Hyperemia and movement disorder were observed around the area of administration in all groups, and higher occurrence in the higher dosage groups. Hyperemia and movement disorder diminished with elapsed time. 3. For the weight measurement, male groups showed larger reduction in weight in accordance with higher dosage. Female groups didn`t s how significant changes. 4. To verify abnormalities of organs and tissues, cerebellum, cerebrum, liver, lung, kidney, and spinal nerves were removed and conducted histological observation with H-E staining. No abnormalities were detected in any of organs and tissues. 5. One female rat in the 30㎎/㎏ group had amputated toe near the administered area and histopathological finding was hemorrhage with inflammation. This is presumed as a secondary infection after the administration of Sweet BV. Conclusion: Above findings suggest Sweet BV is relatively s safe treatment medium. Further studies on the subject should be conducted to yield more concrete evidences.

Single-dose toxicity test of germanium-fortified lettuce was investigated in mice. Both sexes of C57BL/6 mice were orally administered once at a dose of 2,000 mg/kg. No death, clinical signs and pathological findings related to the treatment were observed. In addition, no significant changes in feed consumption and body weight gain were obtained during the treatment period, in spite of day-to-day fluctuation of water consumption. There were no considerable changes in hematology and serum biochemistry, except a significant decrease in GPT, GOT and LDH. Several alterations were observed in organ weight and blood biochemistry, including thymus, ovaries, heart, kidney and platelet in male or female mice. The ability of spleen cells proliferation was almost same level as shown in control group. However the population of B cells, helper T cells and cytotoxic T cells was not comparably changed in all groups. Taken together, it is suggested that single oral dose of germanium-fortified lettuce to C57BU6 mice did not cause apparent toxicological change at the dose of 2,000 mg/kg body weight.

This study was to investigate single and repeated-dose toxicities of Tensolin-, 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- treated group. Therefore, the approximate lethal dose of Tensolin- 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- 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- in ICR mice following gavage for at least 4-week is higher than 100 mg/kg/day.

Recombinant human granulocyte-macrophage colony stimulating factor (hGM-CSF) regulates proliferation and differentiation of hematopoietic progenitor cells and modulates function of the mature hematopoietic cells. In the previous study, we reported that hGM-CSF could be produced in transgenic rice cell suspension culture, termed rhGM-CSF. In the present study we examined the single and repeated dose toxicity of rice cells-derived hGM-CSF in SD rats. During single dose toxicity study for 7 days, there were no any toxic effects at any dose of from 10 to 1000 ㎍/㎏. The lethal dose (LD??) was not found in this range. Moreover, repeated dose toxicity study of 14-days period and at the doses of 50 and 200 ㎍/㎏ (i.v.) of rhGM-CSF did not show any changes in food and water intake. There were also no significant changes in both body and organ weights between the control and the test groups. The hematological and blood biochemical parameters were statistically not different in all the groups. These results suggest that rhGM-CSF has no toxicity in SD rats.

Objectives: The purpose of this study was to examine the single-dose intravenous toxicity of Guseonwangdo-go glucose 5% pharmacopuncture (GWG5). Methods: Forty Sprague-Dawley rats were divided into four groups of five males and five females per group: an intravenous (IV) injection of 1.0 mL of normal saline solution per animal was administered to the control group; IV injections of 0.1, 0.5, and 1.0 mL of GWG5 per animal were administered to the experimental groups (G: 0.1, G: 0.5, and G: 1.0). Observation of clinical signs and body weight measurements were carried out for 14 days following the injections. At the end of the observation period, hematological, biochemical, and histopathological tests, as well as necropsy examinations, were performed on the injected parts. Results: No mortalities or adverse clinical signs were observed in any of the groups. The body weights of all groups continuously increased. In the hematological and the biochemical tests, females in G-0.1 had minimal changes, but those changes were not dose dependent. On necropsy examination, no abnormalities were observed. In the histopathological test, focal inflammatory cell infiltrations were observed in two female rats, one in the control group and one in G-1.0. Also, one female rat in the control group had an epidermis crust. These changes were concluded to have been caused by the insertion of the needle into a vein. Conclusion: The above findings suggest that the lethal dose of GWG5 administered via IV injection is more than 1.0 mL per animal in both male and female rats. Further studies are needed to establish more detailed evidence of its toxicity.

Objectives: This study was performed to analyze the toxicity and to find the lethal dose of the test substance Hominis placenta pharmacopuncture when used as a single-dose in 6 week old, male and female Sprague-Dawley (SD) rats. Methods: All experiments were conducted at Biotoxtech (Chungwon, Korea), an institution authorized to perform non clinical studies, under the regulations of Good Laboratory Practice (GLP). SD rats were chosen for the pilot study. Doses of Hominis placenta pharmacopuncture extracts, 0.125, 0.25 and 0.5 mL, were administered to the experimental group, and 0.5 mL doses of normal saline solution were administered to the control group. This study was conducted under the approv al of the Institutional Animal Ethics Committee. Results: No deaths or abnormalities occurred in any of the groups. Also, no significant changes in body weights were observed among the groups, and no significant differences in hematology/biochemistry, necropsy, and histopathology results were noted. Hematologically, some changes in the male rats in two experimental groups were observed, but those changes had no clinical or toxicological meaning because they were not dose dependent. Histopathological tests on the injected parts showed cell infiltration in the male rats in one of the experimental groups; however, that result was due to spontaneous generation and had no toxicological meaning. Therefore, this study showed that Hom inis placenta pharmacopuncture had no effect on the injected parts in terms of clinical signs, body weight, hematology, clinical chemistry, and necropsy. Conclusion: As a result of single-dose tests of the test substance Hominis placenta pharmacopuncture in 4 groups of rats, the lethal dose for both males and females exceeded 0.5 mL/animal. Therefore, the above findings suggest that treatment with Hominis placenta pharmacopuncture is relatively safe. Further studies on this subject are needed.

The fluorescent tracer agent 3,6-diamino-2,5-bis{N-[(1R)-1-carboxy-2-hydroxyethyl]carbamoyl}pyrazine, designated MB-102, has been developed with properties and attributes for use as a direct measure of glomerular filtration rate (GFR). In comparison to known standard exogenous GFR agents in animal models, MB-102 has demonstrated an excellent correlation. A battery of toxicity tests has been completed on this new fluorescent tracer agent, including single dose toxicity studies in rats and dogs to determine overall toxicity and toxicokinetics of the compound. Blood compatibility, mutation assay, chromosomal aberration assay, and several other assays were also completed. Toxicity assessments were based on mortality, clinical signs, body weight, food consumption and anatomical pathology. Doses of up to 200-300 times the estimated human dose were administered. No test-article related effects were noted on body weight, food consumption, ophthalmic observations and no abnormal pathology was seen in either macroscopic or microscopic evaluations of any organs or tissues. All animals survived to scheduled sacrifice. Transient discoloration of skin and urine was noted at the higher dose levels in both species as expected from a highly fluorescent compound and was not considered pathological. Thus initial toxicology studies of this new fluorescent tracer agent MB-102 have resulted in negligible demonstrable pathological test article concerns.

Objectives: Mountain ginseng pharmacopuncture (MGP) is an extract distilled from either mountain cultivated ginseng or mountain wild ginseng. This is the first intravenous injection of pharmacopuncture in Korea. The word intravenous does not discriminate between arteries, veins, and capillaries in Oriental Medicine, but only the vein is used for MGP. The aim of this study is to evaluate the intravenous injection toxicity of MGP through a single-dose test in Sprague-Dawley (SD) rats. Methods: Male and female 6-week-old SD rats were injected intravenously with MGP (high dosage of 20 mL/kg or low dosage of 10 mL/kg). Normal saline was injected into the rats in the control group by using the same method. After the rats has treated, we conducted clinical observations, body-weight measurements and histological observations. Results: In this study, no mortalities were observed in any of the experimental groups. Also, no significant changes by the intravenous injection of MGP were observed in the body weights, or the histological observations in any of the experimental groups compared to the control group. The lethal dose for intravenous in jection of MGP was found to be over 20 mL/kg in SD rats. Conclusion: Considering that the dosage of MGP generally used each time in clinical practice is about 0.3 mL/kg, we concluded with confidence that MGP is safe pharmacopuncture.

Pesticide toxicology study design has evolved from concern for oral exposure via food residues. The emphasis on the oral route does not generally apply to workers that are exposed primarily via the dermal route either handling pesticides or re-entering treated fields. As a result numerous assumptions about how oral toxicology results relate to dermal exposure must be made when conducting worker risk assessments. These assumptions introduce a high degree of uncertainty. Alternative toxicology study designs are suggested to reduce uncertainty when assessing risk. Because the dermal route is so important to characterizing occupational risk, methods to improve the accuracy of dermal absorption estimates are suggested, including the use of human subjects to study dermal absorption. Additional suggestions include tailoring dermal, oral and inhalation kinetic study designs to reflect worker exposure dosages. Suggestions are made to routinely conduct a single dose toxicity study patterned after the neurotoxicity study design to distinguish single dose effects and NOAELs from those resulting from multiple doses. Finally, interspecies pharmacokinetics studies are proposed to determine which toxicology study regimen of dosing best reflects intermittent worker exposure.  2001 Published by Elsevier Science Ltd on behalf of British Occupational Hygiene Society

Objectives: This study was performed to analyze the single dose toxicity of Chukyu (spine-healing) pharmacopuncture. Methods: All experiments were conducted at the Biotoxtech, an institution authorized to perform non-clinical studies under the regulations of Good Laboratory Practice (GLP) regulations. Sprague-Dawley rats were chosen for the pilot study. Doses of Chukyu (spine-healing) pharmacopuncture, 0.1, 0.5 and 1.0 mL, were administered to the experimental groups, and a dose of normal saline solution, 1.0 mL, was administered to the control group. This study was conducted under the approval of the Institutional Animal Ethic Committee. Results: No deaths or abnormalities occurred in any of the four groups. No significant changes in weight, he matological parameters or clinical chemistry between the control group and the experimental groups were observed. To check for abnormalities in organs and tissues, we used microscopy to examine representative histological sections of each specified organ; the results showed no significant differences in any of the organs or tissues except in one case, where interstitial infiltrating macrophages were found in one female rat in the 0.5-mL/animal experimental group. Conclusion: The above findings suggest that treat ment with Chukyu (spine-healing) pharmacopuncture is relatively safe. Further studies on this subject are needed to yield more concrete evidence.

The single-dose intravenous toxicities of iodixanol, a new nonionic iso-osmolar contrast medium, were investigated in mice, rats and monkeys. The LD50 values were estimated to be 17.9 gI/kg for male mice and 16.2 gI/kg for female mice, 18.8 gI/kg for male rats and 22.0 gI/kg for female rats, and more than 10.0 gI/kg for monkeys. There was no marked sex difference in mice or rats, nor any significant difference observed between these two rodent species. Decrease in spontaneous locomotor activity, ptosis, respiratory depression and abdominal posture were observed in many mice and rats. These signs disappeared mostly by 8 days after dosing in surviving animals. Death occurred between immediately and 4 days after dosing in mice, and between immediately and 14 days after dosing in rats. Transient depression of body weight gain was observed in the surviving mice and rats by 7 days after dosing. Histological examinations revealed congestion or hemorrhage in the renal medulla, vacuolation or necrosis of the renal proximal tubular epithelium in mice and rats that died and vacuolation of the renal proximal tubular epithelium in surviving rats. There were no significant treatment-related changes in the laboratory and pathological examinations in monkeys.

Montirelin hydrate (NS-3) is a new drug for the treatment of disturbance of consciousness. The single dose toxicity studies of its degradation product and impurity (CNK-603) and its metabolite (CNK-6004) were conducted in Slc: ddY mice. The Compounds Were administered intravenously to male and female mice. Deaths occurred in both sexes of mice receiving more than 125 mg/kg of CNK-603. There were no treatment-related effects on survival in both sexes of mice receiving doses up to 2, 000 mg/kg of CNK-6004. Approximate lethal dose of CNK-603 was 125 mg/kg and lethal dose of CNK-6004 was more than 2, 000 mg/kg. Decrease in locomotor activity was observed in mice receiving the two compounds. Tremor, prone position and dyspnea were seen in mice receiving CNK-603. The body weight showed no changes attributable to the dosing of the two compounds in mice. In autopsies, congestion and hemorrhage in the lung were observed in dead mice given CNK-603. There were no remarkable changes in mice given CNK-6004. These results show that the lethal dose of CNK-603 is over 4 times lower than that of montirelin hydrate, and that CNK-6004 is less toxic than montirelin hydrate.

The leaves and stems of the plant Rubus coreanus Miquel (RCMLS) are rich in vitamins, minerals and phytochemicals which have antioxidant, anti-hemolytic, anti-inflammatory, anti-fatigue and anti-cancer effects. However, RCMLS is not included in the Korean Food Standards Codex due to the lack of safety assurance concerning RCMLS. We evaluated single and repeated oral dose toxicity of RCMLS in Sprague-Dawley rats. RCMLS did not induce any significant toxicological changes in both male and female rats at a single doses of 2500 mg/kg/day. Repeated oral dose toxicity studies showed no adverse effects in clinical signs, body weight, food consumption, ophthalmic examination, urinalysis, hematology, serum biochemistry, necropsy findings, organ weight, and histopathology at doses of 625, 1250, and 2500 mg/kg/day. The LD50 and LOAEL of RCMLS might be over 2500 mg/kg body weight/day and no target organs were identified. Therefore, this study revealed that single and repeated oral doses of RCMLS are safe.

Male beagle dogs were orally given lactitol, a hepatic encephalopathy drug, in a single dose of 7.5, 15.0 or 30.0 g/kg. Vomiting was seen within 30 minutes after dosing in all treated groups. Diarrhea was observed 3 or 5 hours after dosing in the 15.0 and 30.0 g/kg dose groups. There were no drug related effects on survival, food and water consumption, body weight gain or tissues and organs.