• Toxicological Research
• /
• v.27 no.4
• /
• pp.261-267
• /
• 2011

Artemisia iwayomogi, a member of the Compositae, is a perennial herb easily found in Korea and used as a traditional medicine to treat liver disease. AIP1, a water-soluble carbohydrate fraction from Artemisia iwayomogi, showed anti-tumor and immuno-modulating activities in animal studies. A subacute toxicological evaluation of AIP1 was performed for 4 weeks in ICR mice. After administration of AIP1 (0, 20, 100, 500 mg/kg/day), the clinical signs, mortalities, body weight changes, hematology, blood clinical biochemistry, urinalysis, organ histopathology, organ weights and gross finding were examined. The results showed that there were no significant differences in body weight changes, food intakes, water consumptions, or organ weights among different dose groups. Also we observed no death and abnormal clinical signs during the experimental period. Between the groups orally treated with AIP1 and the control group, there was no statistical significance in hematological test or serum biochemical values. Histopathological examination showed no abnormal changes in AIP1 groups. These results suggest that no observed adverse effect level (NOAEL) of the oral administration of AIP1 for 4 weeks was considered to be more than 500 mg/kg/day in mice under the condition investigated in current study.

• Toxicological Research
• /
• v.26 no.2
• /
• pp.117-121
• /
• 2010

The crude ethanol extract of B. repanda showed the cytotoxic activity against Polio virus (25% activity at $150{\mu}g$/disk) and the minor cytotoxic activity against BSC cells (African green monkey kidney). However, the crude ethanol extract of B. repanda was non-toxic to murine leukaemia cells CCL 46 P388D1 ($IC_{50}$, > 62,500 ng/ml). Cytotoxic and antifungal activities were strongly shown by Fr. 64-3 which was eluted with 90% $CH_3CN/H_2O$, 100% $CH_3CN$, and 50% $CH_3CN/H_2O$(SM 2 at $150{\mu}g$/disk). The fraction 64-3 also showed the most cytotoxic activity against murine leukaemia cells (128 mg, $IC_{50}$ 10,051 ng/ml at $75{\mu}g$/disk). These results suggest that this fraction has a potent antifungal activity against the dermatophytic fungus Trichophyton mentagrophytes ATCC 28185.

• Toxicological Research
• /
• v.35 no.4
• /
• pp.311-317
• /
• 2019

The transport systems for metals play crucial roles in both the physiological functions of essential metals and the toxic effects of hazardous metals in mammals and plants. In mammalian cells, Zn transporters such as ZIP8 and ZIP14 have been found to function as the transporters for Mn(II) and Cd(II), contributing to the maintenance of Mn homeostasis and metallothionein-independent transports of Cd, respectively. In rice, the Mn transporter OsNramp5 expressed in the root is used for the uptake of Cd from the soil. Japan began to cultivate OsNramp5 mutant rice, which was found to accumulate little Cd, to prevent Cd accumulation. Inorganic trivalent arsenic (As(III)) is absorbed into mammalian cells via aquaglyceroporin, a water and glycerol channel. The ortholog of aquaporin in rice, OsLsi1, was found to be an Si transporter expressed in rice root, and is responsible for the absorption of soil As(III) into the root. Since rice is a hyperaccumulator of Si, higher amounts of As(III) are incorporated into rice compared to other plants. Thus, the transporters of essential metals are also utilized to incorporate toxic metals in both mammals and plants, and understanding the mechanisms of metal transports is important for the development of mitigation strategies against food contamination.

• Toxicological Research
• /
• v.22 no.4
• /
• pp.307-313
• /
• 2006

The development of in vitro assays has been recommended to screening and testing the potential endocrine disruptors (EDs). These assay systems focus only on identifying the estrogenic or antiestrogenic activity of EDs, whereas a few studies have been carried out to screen the thyroid hormone (TH) disruptors. The aim of this study was to evaluate a test system to detect TH disruptors using rat pituitary tumor $GH_3$ cells. The test system is based on the TH-dependent increase in growth rate. As expected, L-3,5,3-triiodothyronine ($(T_3)$ markedly induced a morphological change in $GH_3$ cells from flattened fibroblastic types to rounded or spindle-shaped types. $T_3$ stimulated $GH_3$ cell growth in a dose-dependent manner with the maximum growth-stimulating effect being observed at a concentration $1{\times}10^9M$. In addition, $T_3$ increased the release of growth hormone and prolactin into the medium of the $GH_3$ cells culture. Using this assay system, the TH-disrupting activities of bisphenol A (BPA) and its related compounds were examined. BPA, dimethy/bisphenol A (DMBPA), and TCI-EP significantly enhanced the growth of $GH_3$ cells in the range of $1{\times}10^{-5}M\;to\;1{\times}10^{-6}M$ concentrations. In conclusion, this in vitro assay system might be useful for identifying potential TH disruptors. However, this method will require further evaluation and standardization before it can be used as a broad-based screening tool.

• Korean Journal of Food Science and Technology
• /
• v.28 no.6
• /
• pp.1059-1064
• /
• 1996

The inhibitory effects of chitosan on mutagenicity induced by 3-amino-1-methyl-5H-pyrido [4,3-b] indole (Trp-P-2), sodium azide (SA), 2-nitrofluorene (2-NF), and 4-nitroquinoline oxide (4-NQO) were investigated using Salmonella typhimurium reversion assay and SOS Chromotest. In Salmonella typhimurium reversion assay. Chitosan showed 24-65% of inhibitory effect against the mutagenicity of an indirect-acting mutagen, Trp-P-2. On the other hand, no inhibitory effect was observed against the mutagenicity of direct-acting mutagens (2-NF, SA). In SOS chromotest. chitosan showed 46-49% effects on SOS function induced by 4-NQO. Chitosan inhibited the mutagenicity induced by Trp-P-2 with 9-39% of inhibition rate. It was also evaluated whether inhibitory effect of chitosan is due to its bio-antimutagenic or desmutagenic action. Chitosan at high concentrations showed a bio-antimutagenicity with dose-dependent manner, but it showed a desmutagenicity at low concentrations against the mutation induced by Trp-P-2.

• Journal of the East Asian Society of Dietary Life
• /
• v.18 no.5
• /
• pp.746-752
• /
• 2008

In this study, the antioxidative activity and antimutagenic effect of ethanol extracts from Schizandra Chinensis Baillon were assessed with regard to natural antioxidants. The antioxidative activity and antimutagenicity of ethanol extracts from Schizandra chinensis Baillon were evaluated by measuring the radical-scavenging effect on 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals, and by performing the Ames test using 4-nitroquinoline-1-oxide (4-NQO) and sodium azaid as a mutagen with Salmonella typhimurium TA100, respectively. The total polyphenolic compound and flavonoid compound contents of Schisandra chinensis Baillon were also assessed. The DPPH radical-scavenging activity of ethanol extracts from Schisandra chinensis Baillon was 57.2% on the $500\;{\mu}g$/assay. The $IC_{50}$ on DPPH radical-scavenging effect of ethanol extract was $435\;{\mu}g$/assay. In addition, the inhibition rates of ethanol extract from Schisandra chinensis Baillon toward mutagenicity induced by 4-NQO and sodium azide were 82.45% and 45.3%, respectively. Furthermore, the total polyphenol and total flavonoid contents of the extract were 9.53 mg/g and 3.97 mg/g, respectively. These results indicate that the ethanol extract from Schisandra chinensis Baillon evidences a fairly good antioxidative and antimutagenic effect.

• Toxicological Research
• /
• v.18 no.1
• /
• pp.31-41
• /
• 2002

The present study was conducted to investigate the potential subacute toxicity of plant sterol esters by a 4-week repeated oral dose in Sprague-Dawley rats. The test article was administered once daily by gavage to rats at dose levels of 0, 1000, 3000, and 9000 mg/kg/day for 4 weeks. During the test period, clinical sign, mortality, body weights, food and water consumption, ophthalmoscopy, urinalysis, hematology, serum biochemistry, gross finding, organ weight, and histopathology were evaluated. A reduction in the body weight was observed in females of the 9000 mg/kg group on day 27 after the initiation of treatment, but not in males of the group. There were no treatment-related effects on mortality, clinical sign, food and water consumption, ophthalmoscopy, urinarlysis, hematology, serum biochemistry, necropsy findings, organ weights, and histopathology in any treatment group. Based on these results, it was concluded that the 4-week repeated oral dose of plant sterol esters resulted in suppressed body weight in female rats at a dose level of 9000 mg/kg/day. In the condition of this study, target organ was not observed and the no-observed-adverse-effect level (NOAEL) was considered to be 9000 mg/kg/day for males and 5000 mg/kg/day for females.

• Toxicological Research
• /
• v.19 no.3
• /
• pp.211-215
• /
• 2003

This study was carried out to investigate the acute oral toxicity of a crude extract derived from fruiting body of Phellinus gilvus (PGE) using male and female SD rats. Groups consisted of five male and female rats were treated with a single dose of the test substance intragastrically at 0, 500, 1,000, 2,000, and 5,000 mg/kgaj, respectively. Clinical signs, body weight change, and food and water consumption change were observed for 14 days after administration. No mortality or abnormal clinical signs in animals were shown during the observation period at the dose used in this study. Also there was no difference in net body weight gain, water and food consumption or gross pathological findings at terminal sacrifice among the groups of rat treated with different doses of the test substance. The results suggested that acute oral toxicity of PGE in rats is very low at the conditions employed in this study and $LD_{50}$ of PGE was estimated to be over 5,000 mg/$\textrm{m}{\ell}$ in both sexes of rats.

• Toxicological Research
• /
• v.13 no.1_2
• /
• pp.175-182
• /
• 1997

LBD-001, a recombinant human interferon $\gamma$ produced by genetically engineered yeast as a host system, was intravenously administered to pregnant female rats (Sprague-Dawley) from day 17 of gestation to day 21 of lactation at dose levels.of $0.35 \times 10^6$, $0.69 \times 10^6$, and $1.38 \times 10^6$ I.U./kg/day. In vasopressin-treated group, vasopressin (5 I.U./kg/day) was intravenously injected only for 5 days of perinatal period. (1) No signicant changes by the treatment of LBD-001 were observed in the body weights, food and water consumption, feeding and nurshing behaviors, and the weights of main organs of mother rats. In vasopressin-treated group, no significant changes were observed except the decrease in the food consumption on day 18 of gestation and one case of abnormal offspring with bleeding spots on the skin. (2) No significant changes in the body weights, survival rates, locomotor activity, emotional development. and the motor coordination of offsprings (F1) by the treatment of LBD-001 were observed except the fact that increase of ambulation in the female offsprings of LBD-001 ($0.69 \times 10^6$ or $1.38 \times 10^6$ I.U./kg/day)-treated groups and the increase of rearing in the males of LBD-($1.38 \times 10^6$ I.U./kg/day)-treated group, and the increase of the weight of liver and ovaries in the female offsprings in the LBD-001 ($1.38 \times 10^6$ I.U./kg/day)-treated group were observed. Altogether, the results show that LBD-001 at the dose of $1.38 \times 10^6$ I.U./kg/day or less does not significantly affect the mother rats and their offsprings (F1) except the minor influences when treated during the perinatal and postnatal period.

• Toxicological Research
• /
• v.16 no.2
• /
• pp.163-172
• /
• 2000

Recently, there is a worldwide concern that a great number of man-made chemicals have a hormone-like action both in humans and in animals. DECD is developing screening programs using validated test systems to determine whether certain substances may have an effect in humans. In the present study. the establishment oj repeated-dose toxicity test method was tried. Flutamide. an anti-androgenic agent. was administered by gavage to Sprague-Dawley rats for 28 days at dose levels of 0. 0.5. 3 and 18 mg/kg body weight (10-15 rats/sex/group) to examine the effects on general findings. especially reproductive and endocrine parameters. Clinical signs. body weights, food consumption, and sexual cycle were checked and measured. For the gross and microscopic examinations. 10 rats/sex/group were sacrificed at the end of dosing period and the remaining animals of control and high dose groups (5 each) were sacrificed after 14 days recovery. Examinations for hematology and clinical chemistry were carried out at necropsy. There were no treatment-related changes in clinical signs. body weights, food consumption. gross necropsy. hematology and clinical chemistry at all doses of both sexes. The period and regularity of sexual cycle were not adversely affected at all doses by the test agent. At 18 mg/kg. both decreased weights of prostate, seminal vesicle and epididymis in males and increased weights of spleen and thymus in females were observed. In addition, decreased number of spermatids and sperms. increased serum testosterone concentration and increased incidence (100%) of interstitial cell hyperplasia were seen in males. At 18 mg/kg of the recovery group. decreased prostate weight. reduced sperm count and increased incidence (20%) of interstitial cell hyperplasia in males and increased thymus weight in females were observed. At 3 mg/kg. reduced sperm count was found. There were no adverse effects on parameters examined at 0.5 mg/kg of both sexes. The results suggested that the potential target organs of flutamide may be accessory sexual glands including testes for males and spleen and thymus for females. Taken together. this test method was found to be a useful screening test system for endocrine disrupting chemicals.