• Toxicological Research
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• v.21 no.2
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• pp.179-186
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• 2005

Dimethylamine (DMA) is a widely used commodity chemical with few toxicity data. Groups of 10 male and female F-344 rats were exposed by inhalation to 0, 5, 10, 20, 40 and 80 ppm of DMA for 6 hrs/day, 5 days/week for 90 days. The changes of body weight, organ weight, hematology, clinical chemistry, and histopathological changes were evaluated after the exposure. As the results, the body weight was significantly decreased at 80 ppm in male and female rats (p<0.05). The absolute lung weight showed no statistically significant changes in any group. In contrast, the relative lung weight significantly increased at 80 ppm in male and female rats (p<0.05). Erythrocytes, mean cell hemoglobin, leukocytes, neutrophil, and platelet numbers were significantly increased in male and female at 40 or 80 ppm of DMA (p<0.05, p<0.01). In addition, the serum values of total protein, urea nitrogen were increased in male and creatine kinase, total protein were increased in female rats at 40 or 80 ppm (p<0.05, p<0.01). Histopathological examinations of the male and female lung samples showed slight hyperplasia and congestion at 80 ppm. Taken together, our study revealed that maximum tolerated dose of DMA would be over 40 ppm.

• Journal of Korean Ophthalmic Optics Society
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• v.10 no.4
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• pp.293-304
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• 2005

As the eye irritant test of lens washing agent, ReNu$^{TM}$ was analysed using Draize methods (1959) according to KFDA Guidelines. In addition, to test the potential toxicity of test articles the ratio of inflammatory cells and non-inflammatory epitheloid cells were also observed using smear cytology methods against ocular discharge. At test, the histopathological changes on the cornea, iris, retina and sclera were also observed in all animals. Slight irritancy of the cornea and conjunctiva were observed at 1, 2 and 3 days after dropping in non-washing group. The Mean Index of Ocular Irritation(MIOI) of these points are detected as 4.17, 3.00 and 1.33, respectively. In washing group, slight irritancy of the cornea and conjunctiva were observed at 1 and 2 days after dropping with MIOI as 0.67 and 1.33, respectively. Therefore, ReNu$^{TM}$ was considered as non-irritating materials because the MIOI is detected below 5.00 throughout the whole experimental periods in both washing and non-washing groups. The Index of Acute Ocular Irritation(IAOI) is also detected as 4.17(1 day after dropping). Except of the somewhat increase trend of the inflammatory cell ratios in ocular discharge at 1 day after dropping of non-washing group, but significances are not detected, on the other hand, no meaningful changes on smear cytology of ocular discharges are observed in this study. In addition, no abnormal histopathological changes on the cornea, iris, retina and sclera were also not detected in ReNu$^{TM}$ dropping group compared to that of non-treated control eyes.

• Toxicological Research
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• v.24 no.1
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• pp.51-58
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• 2008

The present study was designed to explore the immunotoxic effects of orally administered aluminum (AI) on pregnant rats (n = 60) and their growing fetuses and consequently on the animal wealth. The animals were randomly allocated into three equal groups of 20 rats each. The first group has no treatment and kept as a control (G1). The second and third groups of pregnant rats were treated orally with aluminum chloride at 345 mg/Kg b.wt. The second group (G2) received the tested compound from the $6^{th}$ day of gestation to the end of weaning, whereas the third group (G3) received the tested compound from the $15^{th}$h day of gestation to the end of weaning. Control and treated animals (dams and offspring) were immunized ip with (0.5 ml) 20% sheep red blood cell (SRBC) suspension seven days before the end of experiments. At the end of exposure, ten dams and ten offspring from each group were used for assessment of cell-mediated immunity and a similar number of animals were sacrificed for evaluating the humoral immune response and serum protein profile. Aluminum chloride exposure of dams ($G_2&G_3$) caused significant suppression of both cell mediated and humoral immune responses in the obtained offsprings compared to the control group ($G_1$) without any significant effect on the immune responses of these dams. Moreover, the serum total globulins, albumin/ globulin (A/G) ratio and gamma globulin fraction were significantly decreased in the treated dam's offsprings compared to the corresponding controls while the serum total protein and all serum protein fractions showed non significant difference between the control and treated dams and between the two treated dam groups themselves. There were no histopathological changes observed in thymus, spleen and liver of the control and treated dams. Thymus of treated dam's offsprings (G2) showed lymphoid depletion in both cortex and medulla. Their spleens showed lymphoid depletion in the white pulps and congestion with hemosiderosis in the red pulps. Liver of treated dam's offsprings showed dilation and congestion of its central vein with degenerative changes in the hepatocytes. These histopathological changes were more severe in G2 than in G3 offsprings. It can be concluded that gestational and/ or lactation exposure of pregnant dams to AI chloride caused suppression of both cellular and humoral immune responses of their offsprings.

• Toxicological Research
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• v.31 no.4
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• pp.403-414
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• 2015

Lithospermum erythrorhizon has long been used as a traditional oriental medicine. In this study, the acute and 28-day subacute oral dose toxicity studies of hexane extracts of the roots of L. erythrorhizon (LEH) were performed in Sprague-Dawley rats. In the acute toxicity study, LEH was administered once orally to 5 male and 5 female rats at dose levels of 500, 1,000, and 2,000 mg/kg. Mortality, clinical signs, and body weight changes were monitored for 14 days. Salivation, soft stool, soiled perineal region, compound-colored stool, chromaturia and a decrease in body weight were observed in the extract-treated groups, and no deaths occurred during the study. Therefore, the approximate lethal dose (ALD) of LEH in male and female rats was higher than 2,000 mg/kg. In the subacute toxicity study, LEH was administered orally to male and female rats for 28 days at dose levels of 25, 100, and 400 mg/kg/day. There was no LEH-related toxic effect in the body weight, food consumption, ophthalmology, hematology, clinical chemistry and organ weights. Compound-colored (black) stool, chromaturia and increased protein, ketone bodies, bilirubin and occult blood in urine were observed in the male and female rats treated with the test substance. In addition, the necropsy revealed dark red discoloration of the kidneys, and the histopathological examination showed presence of red brown pigment or increased hyaline droplets in the renal tubules of the renal cortex. However, there were no test substance-related toxic effects in the hematology and clinical chemistry, and no morphological changes were observed in the histopathological examination of the kidneys. Therefore, it was determined that there was no significant toxicity because the changes observed were caused by the intrinsic color of the test substance. These results suggest that the no-observed-adverse-effect Level (NOAEL) of LEH is greater than 400 mg/kg/day in both sexes.

• Journal of Korean Ophthalmic Optics Society
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• v.12 no.2
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• pp.67-78
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• 2007

The eye irritant test of lens washing agent, CLIWELL$^{TM}$ was conducted using Draize methods according to KFDA Guidelines. In addition, to test the potential toxicity of test articles, the ratio of inflammatory cells and non-inflammatory epitheloid cells was also observed using smear cytology methods against ocular discharge. At sacrifice, the histopathological changes on Cornea, Iris, Retina and Sclera were also observed in all animals. Slight irritancy of cornea and conjunctiva was observed at 1, 2 and 3 days after dropping in non-washing group. The MIOI of these points are detected as 4.50, 1.67 and 0.67, respectively. In washing group, slight irritancy of cornea and conjunctiva were observed at 1 and 2 days after dropping with MIOI as 0.67, respectively. Therefore, CLIWELL$^{TM}$ was considered as non-irritating materials because the MIOI is detected below 5.00 throughout the whole experimental periods in both washing and non-washing groups and the IAOI was also detected as 4.50. Except for significant increase of the inflammatory cell ratios in ocular discharge at 1 day after dropping of non-washing group compared to that non-treated intact eyes, no meaningful changes on smear cytology of ocular discharges are observed in this study. In addition, no abnormal histopathological changes on the cornea, iris, retina and sclera were also detected in CLIWELL$^{TM}$ dropping group compared to that of non-treated intact eyes.

• Journal of Korean Ophthalmic Optics Society
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• v.11 no.4
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• pp.299-310
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• 2006

The eye irritant test of lens washing agent, $SOLOCARE^{TM}$ was conducted using Draize methods according to KFDA Guidelines 1999-61. In addition, to test the potential toxicity of test articles the ratio of inflammatory cells and non-inflammatory epitheloid cells were also observed using smear cytology methods against ocular discharge. At sacrifice, the histopathological changes on Cornea, Iris, Retina and Sclera were also observed in all animals. Slight (1~2 degrees) irritancy of cornea and conjunctiva were observed at 1, 2 and 3 days after dropping in non-washing group. The MIOI of these points are detected as 4.33, 3.33 and 2.00, respectively. In washing group, slight irritancy of cornea and conjunctiva were restricted to 1 and 2 days after dropping with MIOI as 3.00 and 1.33, respectively. Therefore, $SOLOCARE^{TM}$ was also considered as non-irritating materials because the MIOI is detected below 5.00 throughout the whole experimental periods in both washing and non-washing groups and the IAOI is also detected as 4.33 (1 day after dropping). No meaningful changes on smear cytology of ocular discharges are observed in this study compared to that of non-treated intact eyes. In addition, no abnormal histopathological changes on the cornea, iris, retina and sclera were also detected in $SOLOCARE^{TM}$ dropping group compared to that of non-treated intact eyes.

• 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.

• Korean Journal of Oriental Medicine
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• v.16 no.2
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• pp.143-157
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• 2010

Objectives : The objective of this study was to access the effect of Artemisiae capillaris herba Extracts on the organogenetic reproductive toxicity of New Zealand White rabbits when administered by oral gavage. Methods : Gestational New Zealand White rabbits were dosed from 6 days of gestation to 18 days of gestation. It was conducted in accordance with the recommendations of the KFDA Guideline for Detection of Toxicity to Reproduction for Medicinal Products. In addition, serum AST, ALT, LDH and ALP levels were detected with their necropsy and histopathological observation Results: No significant changes of body weights, gains and food consumption were demonstrated in all dosed groups compared to those of vehicle control group except for 2,000mg/kg-dosing group, which showed significantly increase of body weight compared to that of vehicle control group. Normal gross findings were demonstrated in all tested groups. No significant changes of number of corpora lutea, implantation, implantation rate, number of fetal death, loss rate of post-implantation, number of live youngs at C-section, survival rate of post-implantation, number of male live youngs at C-section, number of female live youngs, sex ratio of live young, external anomalies of live youngs and body weight of live youngs were demonstrated in all dosed groups compared to those of vehicle control group. Although some visceral variations such as thymic reminant in the neck, dilation of renal pelvis, dilated ureter and malpositioned left common carotid artery, no significant changes were demonstrated in all dosed groups compared to that of vehicle control group. Some malformations and variation were demonstrated with retardations. However, no significant changes were demonstrated in all dosed groups compared to that of vehicle control group. In addition, similar ossification numbers were detected in sternebrae, metacarpals, metatarsals, phalanges, cervical vertebrae, and sacral and caudal vertebrae. No Artemisiae capillaris herba Extracts treatment-related changes of serum AST, ALT, LDH and ALP levels were demonstrated in all dosed levels in this study. Conclusions : We could conclude that oral administration of Artemisiae capillaris herba Extracts hasn't an influence on the organogenetic reproductive toxicity.

• Journal of Pharmacopuncture
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• v.19 no.4
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• pp.336-343
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• 2016

Objectives: This study was conducted to analyze the single-dose toxicity and the safety of Mahwangcheonoh pharmacopuncture extracts. Methods: Six-week-old Sprague-Dawley rats were used for this study. Doses of Mahwangcheonoh pharmacopuncture extracts were set at 0.25 mL (low-dose), 0.5 mL (medium-dose) and 1.0 mL (high-dose) for the test groups. A dose of 1.0 mL of normal saline solution was set for the control group. During 14 days, general symptoms, mortalities, and changes in hematology, blood biochemistry and histopathology of all rats were observed. Results: No death was observed in all test groups. Any abnormal symptom was not observed in all of the groups. No significant changes in weight between the control group and the test groups were observed. In addition, no significant differences in the hematology signs, the blood biochemistry levels and the histopathological signs related to the Mahwangcheonoh pharmacopuncture extracts injection were observed. Conclusion: The findings of this study indicate that Mahwangcheonoh pharmacopuncture at doses of 1.0 mL or less may be consider safe and non-toxic. So, it can be used for therapy of obesity sufficiently. But further studies on this subject must be performed to confirm and verify this conclusion.

• The Journal of Internal Korean Medicine
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• v.39 no.4
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• pp.451-462
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• 2018

Hubakmawhang-tang (HMT), listed in Geumgweyoryak, is an oriental medicine used for the symptoms of asthma, such as cough and dyspnea. In this study, we investigated the HMT effects on ovalbumin-induced asthmatic in mice. We examined weight changes, airway hyperresponsiveness, histopathological abnormalities, immune cell infiltrations, immunoglobulin and inflammatory cytokine levels, and spleen body weight ratios in asthmatic mice. HMT inhibited airway hyperresponsiveness, immune cell infiltration, and airway remodeling and caused a significant lowering of serum IgE and IgG1 levels. The asthmatic mice had elevated IL-4 levels in lung tissue and this elevation was effectively prevented by HMT. HMT did not cause changes in body weight or in the spleen body weight ratio. Therefore, HMT might have an anti-asthmatic effect in the ovalbumin-induced mouse model.