The present study was carried out to investigate the potential adverse effects of 1,3-dichloro-2-propanol on pregnant dams after maternal exposure during the gestational days (GD) 6 through 19 in Sprague-Dawley rats. The tested chemical was administered orally to pregnant rats at dose levels of 0, 10, 30, or 90 mg/kg/day. During the test period, clinical signs, mortality, body weights, food consumption, serum biochemistry, gross findings, organ weights, and Caesarean section findings were examined. In the 90 mg/kg group, decreases in the body weight gain and food consumption, and increases in the weights of liver and adrenal glands were observed. Serum biochemical investigations revealed increases in aspartate aminotransferase (AST), alanine aminotransferase (ALT), cholesterol (CHO), triglyceride (TG), alkaline phosphatase (ALP), and bilirubin (BIL) and decreases in glucose (GLU), albumin (ALB) and total protein (TP). In the 30 mg/kg group, a decrease in the food consumption and an increase in the liver weight were observed. Serum biochemical investigation also showed increases in CHO and TG and a decrease in glucose. Since there were no signs of maternal toxicity in the 10 mg/kg group, it is considered to be the no-observed-adverse-effect level (NOAEL) of 1,3-dichloro-2-propanol. It is concluded that successive oral administration of 1,3-dichloro- 2-propanol to pregnant rats for 14 days may cause significant toxicities in body weight and liver at a dose rate ${\geq}$ 30 mg/kg/day.
This study was carried out to evaluate the residual characteristics of azoxystrobin in fresh ginseng and calculate its processing factors in processed products, such as dried ginseng, red ginseng and their extracts. Azoxystrobin was sprayed annually onto four-year-old ginseng according to its pre-harvest interval (PHI) for two years. Harvested ginsengs were processed according to the commercially well-qualified conventional methods provided by the Korea Ginseng Corporation. Limits of detection (LODs) of azoxystrobin in fresh ginseng and its processed products were 0.001 and 0.002 mg/kg, respectively. Also limits of quantitation (LOQs) in fresh ginseng and its processed products were 0.003 and 0.007 mg/kg, respectively. Recoveries of the analytical methods in fresh ginseng and its processed products ranged from 69.3 to 114.8%. Highest residue amounts in fresh ginseng and its processed products were 0.025 and 0.118 mg/kg, respectively. Processing factors of the processed products ranged from 1.85 to 3.17 in four-year-old ginseng and from 2.48 to 5.84 five-year-old ginseng.
Kim, Byung-Soo;Edler, Lutz;Park, Jin-Joo;Fournier, Dietrich Von;Haase, Wulf;Sautter-Bihl, Mare-Luise;Hagmuller, Egbert;Gotzes, Florian;Thielmann, Heinz Walter
Toxicological Research
/
v.20
no.2
/
pp.89-100
/
2004
The comet assay (also called the single-cell gel electrophoresis assay) has been widely used for detecting DNA damage and repair in individual cells. Since the conventional methods of evaluating comet assay data using frequency statistics are unsatisfactory we developed a new quantitative measure of DNA damage/repair that is based on all information residing in the dose/time-response curves of a comet experiment. Blood samples were taken from 25 breast cancer patients before undergoing radiotherapy. The comet assay was performed under alkaline conditions using isolated lymphocytes. Tail DNA, tail length, tail moment and tail inertia of the comet were measured for each patient at four doses of $\gamma$-rays (0, 2, 4 and 8 Gy) and at four time points after irradiation (0, 10, 20 and 30 min) using 100 cells each. The resulting three-dimensional dose-time response surface was modeled by multiple regression, and the second derivative, termed 2D, on dose and time was determined. A software module was programmed in SAS/AF to compute 2D values. We applied the new method successfully to data obtained from cancer patients to be assessed for their radiation sensitivity. We computed the 2D values for the four damage measures, i.e., tail moment, tail length, tail DNA and tail inertia, and examined the pairwise correlation coefficients of 2D both on the log scale and the unlogged scale. 2D values based on tail moment and tail DNA showed a high correlation and, therefore, these two damage measures can be used interchangeably as far as DNA repair is concerned. 2D values based on tail inertia have a correlation profile different from the other 2D values which may reflect different facets of DNA damage/repair. Using the dose-time response surface, other statistical models, e.g., the proportional hazards model, become applicable for data analysis. The 2D approach can be applied to all DNA repair measures, Le., tail moment, tail length, tail DNA and tail inertia, and appears to be superior to conventional evaluation methods as it integrates all data of the dose/time-response curves of a comet assay.
The silkworm extract powder contain 1-deoxynojirimycin (DNJ), a potent ${\alpha}$-glycosidase inhibitor, has therapeutic potency against diabetes mellitus. Therefore, natural products containing DNJ from mulberry leaves and silkworm are consumed as health functional food. The present study was performed to evaluate the safety of the silkworm extract powder, a health food which containing the DNJ. The repeated toxicity studies and gentic toxicity studies of the silkworm extract powder were performed to obtain the data for new functional food approval in MFDS. The safety was evaluated by a single-dose oral toxicity study and a 90 day repeated-dose oral toxicity study in Sprague-Dawley rats. The silkworm extract powder was also evaluated for its mutagenic potential in a battery of genetic toxicity test: in vitro bacterial reverse mutation assay, in vitro chromosomal aberration test, and in vivo mouse bone marrow micronucleus assay. The results of the genetic toxicology assays were negative in all of the assays. The approximate lethal dose in single oral dose toxicity study was considered to be higher than 5000 mg/kg in rats. In the 90 day study, the dose levels were wet at 0, 500, 1000, 2000 mg/kg/day, and 10 animals/sex/dose were treated with oral gavage. The parameters that were monitored were clinical signs, body weights, food and water consumptions, ophthalmic examination, urinalysis, hematology, serum biochemistry, necropsy findings, organ weights, and histopathological examination. No adverse effects were observed after the 90 day administration of the silkworm extract powder. The No-Observed-Adverse-Effect-Level (NOAEL) of silkworm extract powder in the 90 day study was 2000 mg/kg/day in both sexes, and no target organ was identified.
Chemotherapy is associated with male infertility. Cisplatin (cis-diamminedichloro-platinum (II) (CDDP) as a chemotherapy medication used to treat a number of cancers has been reported to most likely induce testicular toxicity. Administration of antioxidants, such as pentoxifylline (PTX) may reduce some Adverse Drug Reactions (ADRs) of CDDP. Therefore, this study investigated the potentially protective effects of PTX on CDDP-induced testicular toxicity in adult male rats. For this purpose, 42 male rats were randomly divided into 7 groups. The rats were orally pretreated with PTX at the 3 doses of 75, 150, and 300 mg/kg once a day for 14 successive days. On the $14^{th}$ day of the study, they were intraperitoneally (IP) administered with a single dose of CDDP (7 mg/kg). Finally, the sperm/testis parameters, serum levels of reproductive hormones, including testosterone, Luteinizing Hormone (LH), and Follicle Stimulating Hormone (FSH) as the pivotal endocrine factors controlling testicular functions, and histopathological changes of testis tissue were examined. Pretreatment with the two doses of 75 and 150 mg/kg PTX indicated significant increases in the sperm count and motility induced by CDDP administration. The right and significantly left testis weights were decreased following the treatment with 300 mg/kg of PTX plus CDDP. However, 75 mg/kg of PTX plus CDDP showed the best near-to-normal histopathological features. The results demonstrated that PTX alone enhanced some parameters, such as the sperm count, while reducing other parameters, including sperm fast motility and germ layer thickness. Furthermore, despite testosterone or LH levels, the mean serum FSH level was significantly augmented by the doses of 75 and 150 mg/kg. It was concluded that PTX administration cannot reduce CDDP-induced testicular toxicity even at high doses (e.g., 300 mg/kg), while it seemed to partially intensify CDDP toxicity effects at a dose of 75 mg/kg. Thus, further research is required in this regard.
Kang, Changgeun;Lee, Hyungkyoung;Yoo, Yong-San;Hah, Do-Yun;Kim, Chung Hui;Kim, Euikyung;Kim, Jong Shu
Toxicological Research
/
v.29
no.1
/
pp.43-52
/
2013
Zearalenone (ZEN) is a non-steroidal estrogenic mycotoxin produced by several species of Fusarium that are found in cereals and agricultural products. ZEN has been implicated in mycotoxicosis in farm animals and in humans. The toxic effects of ZEN are well known, but the ability of an alkaline Comet assay to assess ZEN-induced oxidative DNA damage in Chang liver cells has not been established. The first aim of this study was to evaluate the Comet assay for the determination of cytotoxicity and extent of DNA damage induced by ZEN toxin, and the second aim was to investigate the ability of N-acetylcysteine amide (NACA) to protect cells from ZEN-induced toxicity. In the Comet assay, DNA damage was assessed by quantifying the tail extent moment (TEM; arbitrary unit) and tail length (TL; arbitrary unit), which are used as indicators of DNA strand breaks in SCGE. The cytotoxic effects of ZEN in Chang liver cells were mediated by inhibition of cell proliferation and induction of oxidative DNA damage. Increasing the concentration of ZEN increased the extent of DNA damage. The extent of DNA migration, and percentage of cells with tails were significantly increased in a concentration-dependent manner following treatment with ZEN toxin (p < 0.05). Treatment with a low concentration of ZEN toxin (25 ${\mu}M$) induced a relatively low level of DNA damage, compared to treatment of cells with a high concentration of ZEN toxin (250 ${\mu}M$). Oxidative DNA damage appeared to be a key determinant of ZEN-induced toxicity in Chang liver cells. Significant reductions in cytolethality and oxidative DNA damage were observed when cells were pretreated with NACA prior to exposure to any concentration of ZEN. Our data suggest that ZEN induces DNA damage in Chang liver cells, and that the antioxidant activity of NACA may contribute to the reduction of ZEN-induced DNA damage and cytotoxicity via elimination of oxidative stress.
Lee Na-Young;Jo Cheorun;Kang Ho-Jin;Hong Sang-Pill;Kim Young-Ho;Lee Kyong-Haeng;Byun Myung-Woo
Food Science of Animal Resources
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v.25
no.1
/
pp.13-19
/
2005
The radio-sensitivity of pathogens and the effect of irradiation on microbiologican safety and mutagenicity of meat products such as seasoned and cooked beef and ham were investigated. Samples were radiation-sterilized and inoculated at 10/sup 7/ cfu/g with each of the four pathogens including Salmonella typhimurium, Escherichia coli, Staphylcoccus aureus, and Listeria ivanovii. No viable cells of pathogens were observed in the sample irradiated with 3 kGy. The D/sub 10/ value of inoculated pathogens in seasoned and cooked beef and ham were 0.24∼0.48 and 0.39∼0.45, respectively. Results of Ames test performed with non-irradiated and irradiated seasoned and cooked beef and ham were both negative at the level of 625, 1,250, 2,500, 50,000, and! 10,000 ㎍ sample/plate, respectively. Results indicate that low dose (2∼3 kGy) irradiation is effective to ensure safety for seasoned and cooked beef and ham with toxicological wholesomeness.
Novel food sources have enormous potential as nutritional supplements. For instance, edible insects are considered as an alternative food source due to their higher protein content; moreover, they are economically efficient reproducers and have high in nutritional value. In this study, we investigated the toxicity of the freeze-dried powder of Locusta migratoria (fdLM), known to contain rich proteins as well as fatty acids. The objective of the present study was to evaluate the subacute toxicity of fdLM in male and female Sprague-Dawley (SD) rats. The SD rats were divided into four groups based on the dosage of fdLM administered: dosage of 0 (vehicle control), 750, 1,500, and 3,000 mg/kg/day were administered for 28 days. Toxicological assessments including observations on food consumption, body and organ weights, clinical signs, mortality, ophthalmologic tests, urinalyses, hematologic tests, clinical chemistry tests, gross findings, and histopathology tests were performed. Clinical signs, urinalyses, hematology, serum biochemistry tests, and organ weight examinations revealed no fdLM-related toxicity. The no-observed-adverse-effect level for fdLM was higher than 3,000 mg/kg/day in rats of both sexes; therefore, fdLM, in conclusion, can be considered safe as an edible alternative human and animal food source material.
Journal of the Korean Society for Marine Environment & Energy
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v.7
no.2
/
pp.75-81
/
2004
A large amount 2.1×106 ㎥ of the polluted sediment was dredged from the Masan Bay and deposited in Gapo confined area, Masan. The dissolved metal concentrations of seawater in the dumping site (Gapo area) were observed during one tidal cycle and compared with those of seawater obtained from Jinhae Bay. The sediment was evaluated as from Non polluted to Moderately polluted by USEPA standards. It was judged that toxicological effects of sediment analyzed ranged from ERL to ERM with copper and zinc, and ERL with cadmium, chrome, lead, and nickel by the Adverse Biological Effects. The pollutant concentration was low in surface sediment compared to deeper sediment since the sediments with relatively low concentrations of pollutant were dumped to the surface. The pollutant concentration was low in surface sediment compared to deeper sediment since the sediments with relatively low concentrations of pollutant were dumped to the surface. The benthic organisms in Gapo area had higher concentrations of trace metals (Oyster: Zn 238.96, Cu 5.29 ㎍/g wet wt., Clam: Zn 17.71, Cu 1.00 ㎍/g wet wt., Mussel. Zn 187.98, Pb 0.28, Cr 0.15, Mn 4.23, Sr 1.45 and Fe 100.33 ㎍/g wet wt.) compared to outside of dumping site. However, the trace metal level in the bivalves was less than the NFPQIS (National Fisheries Products Quality Inspection Service) standard.
Gamma irradiation at 5 kGy was applied to beefs for evaluation of their possible genotoxicity and acute oral toxicity. The genotoxicity of 5 kGy irradiated beef was evaluated by Salmonella typhimurium reversion assay and in vivo micronucleus assay using mouse bone marrow cells. The results were negative in the bacterial reversion assay with S. typhimurium TA98, TA100, TA1535, TA1537. Clastogenic effects were not shown in vivo mouse micronucleus assay at 5 kGy dose tested. In an acute toxicity test, 5 kGy-irradiated beef was administrated orally at a dose level of 313 to 5,000 mg/kg, and then number of deaths, clinical signs, body weights, and pathological examinations were examined daily for 14 days post-administration. The results indicate that 5 kGy irradiated beef did not show any toxic effect on mice and oral $LD_{50}$ value was over 5,000 mg/kg on ICR mice.
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