• Journal of Food Hygiene and Safety
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• v.27 no.1
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• pp.96-102
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• 2012

This study was designed to evaluate a repeated oral dose toxicity and immunomodulating activity of $Pulsatilla$ $koreana$ and $Artemisiae$ $annuae$ in Sprague-Dawley rats. The female rats were treated with $Pulsatilla$ $koreana$ and $Artemisiae$ $annuae$ of control group, low group (0.5 ml/kg), medium group (1 ml/kg), high group (2 ml/kg) for distilled water, intragastrically for 4 weeks, respectively. To ensure the safety of $Pulsatilla$ $koreana $ and $Artemisiae$ $annuae$ such as the following were observed and tested. We examined the body weight, the feed intake, the clinical signs, the ophthalmological test, the hematological and the serum biochemical analysis. We also observed the histopathological changes of liver and kidney in rats. Hematological results were the increase of neutrophils, lymphocytes and monocytes in the high dose group of $Pulsatilla$ $koreana$. The increase immune cells in the high dose group of $Pulsatilla$ $koreana$ might immunomodulating activity. No significant differences in body weight, feed intake, serum biochemical analysis and histopathological between control and fed group were found. In conclusion, $Pulsatilla$ $koreana$ and $Artemisiae$ $annuae$ is physiologically safe and improve immunomodulating activity.

• Journal of Dairy Science and Biotechnology
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• v.34 no.2
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• pp.117-135
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• 2016

The present study was performed to develop a functional raw food material from hydrolyzed whey protein powder (23%-GNANA) medication containing sialic acid as a marker compound that is naturally occurring at 7% concentration in GMP (glycomacropeptide). GMP is used worldwide in foodstuffs for babies and infants and is obtained from the milk protein as safe food. While the purpose of our detailed evaluation was aimed to assess preliminary NOAEL values for and above 2,000 mg/kg/day, a clinical dose allowance for 23%-GNANA (as per characteristic of a functional health product, a highly refined test substance of 23% (v/v) sialic acid combined in GMP), at the same time we also wanted to assess the safety of GMP hydrolyzate lacking sialic acid but with identical properties as GMP. Animal safety evaluation was conducted using 23%-GNANA as the test substance, produced from hydrolyzed whey protein powder (product name: HELICOBACTROL-23; provided by Medinutrol Inc. [Korea]; composed of 23% sialic acid and GMP protein) after isolating the sialic acid using enzymes approved as food additives, with GMP as a raw material, and subsequently increasing the content of xx up to 23% through 80% (v/v) ethanol soaking and concentrating, in accordance with GLP Guideline. The animal safety evaluation mentioned above was made on the basis of toxicity in SPF Sprague-Dawley female and male rats dosed with 10 mL of the test substance diluted to 0, 1,250, 2,500, and 5,000 mg/kg directly into their stomachs for 90 d. This was determined in terms of the general symptoms and animal viability, weight and amount of feed intake, eye examination, uracrasia tests, hematological and blood biochemical disorder tests, blood coagulation test, abnormal intestine weight, abnormalities during postmortem and histopathological examinations. Statistical significance was set at P<0.05. Based on the toxicity determination, a certain minor effect associated with the test substance was observed in male rats with no major effects of the tested substance, in comparison with the control group dosed with sterilized water. Nevertheless, the NOAEL value, evaluated as per toxicity criteria, was verified as 5,000 mg/kg/day (P<0.05). Similarly, for female rats, a certain minor effect associated with the test substance was observed in 5,000 mg/kg/day dosed group, with no major effect, yet the NOAEL value (as assessed as per toxicity criteria) was determined to be 5,000 mg/kg/day (P<0.05), which was the same as for male rats. Accordingly, the NOAEL values of the test substances for all female and male rats were finally verified as 5,000 mg/kg/day (P<0.05). In conclusion, it was determined that the 23%-GNANA test substance exceeds 2,000 mg/kg/day, the clinical allowance characteristic for functional health food, and was finally evaluated to cause no safety concerns when used as a raw material in functional health food production, which was the ultimate goal of the present study.

• Biomolecules & Therapeutics
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• v.25 no.5
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• pp.545-552
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• 2017

Increasing concern is being given to the association between risk of cancer and exposure to low-dose bisphenol A (BPA), especially in young-aged population. In this study, we investigated the effects of repeated oral treatment of low to high dose BPA in juvenile Sprague-Dawley rats. Exposing juvenile rats to BPA (0, 0.5, 5, 50, and 250 mg/kg oral gavage) from post-natal day 9 for 90 days resulted in higher food intakes and increased body weights in biphasic dose-effect relationship. Male mammary glands were atrophied at high dose, which coincided with sexual pre-maturation of females. Notably, proliferative changes with altered cell foci and focal inflammation were observed around bile ducts in the liver of all BPA-dosed groups in males, which achieved statistical significance from 0.5 mg/kg (ANOVA, Dunnett's test, p<0.05). Toxicokinetic analysis revealed that systemic exposure to BPA was greater at early age (e.g., 210-fold in $C_{max}$, and 26-fold in AUC at 50 mg/kg in male on day 1 over day 90) and in females (e.g., 4-fold in $C_{max}$ and 1.6-fold in AUC at 50 mg/kg vs. male on day 1), which might have stemmed from either age- or gender-dependent differences in metabolic capacity. These results may serve as evidence for the association between risk of cancer and exposure to low-dose BPA, especially in young children, as well as for varying toxicity of xenobiotics in different age and gender groups.

• Toxicological Research
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• v.18 no.1
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• pp.23-29
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• 2002

Disodium disulphite, the HPV chemical, was assigned to Korea in order to implement OECD SIDS program in 1999. It was produced about 3,200 ton/year in 1998. This report evaluates the toxic potency of disodium disulphite based on the environmental and mammalian effects as well as human exposure. Oral $LD_{50}$ in rats is 1,540 mg/kg b.w. and effects was observed to the stomach, liver and the GI track that was filled with blood. For repeated dose toxicity, the predominant effect was the induction of stomach lesion due to local irritation. The no observed adverse effect lever for local (stomach irritation) was about 217 mg/kg bw/day. There is no evidence that disodium disulphite is genotoxic in vivo. No reproductive or developmental toxicty of disodium disulphite was observed for the period up to 2 yr and over three generation. In humans, urticaria and asthma with itching, edema, rhinitis, and nasal congestion were reported. Disodium disulphite is unlikely to induce respiratory sensitization but may enhance symptom of asthma in sensitive individuals. This chemical would be mainly transported to water compartment when released to environmental compartments since it is highly water soluble (470 g/l at 20). Low K oc (2.447) indicates disodium disulphite is so mobile in soil that it may not stay in the terrestrial compartment. The chemical has been tested in a limited number of aquatic species. hem acute toxicity test to fish, 96 hr-$LC_{50}$ was > 100 mg/1. For algae, 72 hr-$XC_{50}$ was 48.1 mg/1. For daphnid, the acute toxicity value of 48 hr-$EC_{50}$ was 88.76 mg/1, and chronic value of 21day-NOEC was > 10 mg/1. Therefore, PNEC of 0.1 mg/l for the aquatic organism was obtained from the chronic value of daphnid using the assessment factor of 100. Based on these data the disodium disulphite was recommended as low priority for further post-SIDS work in OECD.

• Food Science of Animal Resources
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• v.42 no.4
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• pp.712-722
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• 2022

In this study, we investigated the residual properties of tebuconazole-treated pigs. Twenty pigs were treated with different concentrations (0.25, 1.25, 2.5, 12.5, and 25 mg/kg bw/d) of tebuconazole for 28 d. Blood biochemistry, histology, and residual levels were analyzed using the VetTest analyzer, Masson's trichrome staining kit, and liquid chromatography-mass spectrometry, respectively. The final body weights were not significantly different between the control and treatment groups. Alkaline phosphatase, blood urea nitrogen, cholesterol, and gamma-glutamyl transpeptidase levels were significantly different from those of the control after exposure for 14 d. However, alanine aminotransferase levels showed changes only after exposure to pesticides for 28 d. The biochemical parameters were separated during the experimental period (14 d versus 28 d) by principal component analysis. Based on variable importance plots, blood urea nitrogen/creatinine ratio, blood urea nitrogen, glucose, and gamma-glutamyl transpeptidase are candidate biomarkers for tebuconazole exposure. The residual levels were observed at T4 (12.5 mg/kg bw/d) and T5 (25 mg/kg bw/d) in the liver and fat tissues, respectively. Fibrosis increased in the liver, kidney, and fat tissues, depending on the tebuconazole concentration. In conclusion, the residue limits of tebuconazole and the physiological changes caused by dietary tebuconazole in pigs provide important information for establishing maximum residue limits of pork and pork products.

• Biomolecules & Therapeutics
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• v.4 no.2
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• pp.127-137
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• 1996

This study was performed to investigate the toxicity of DA-125 in beagle dogs, an anthracycline antitumor antibiotic. The dogs were administered DA-125 i.v. at 0.0023, 0.0375, 0.15 and 0.6 mg/kg/day, 6 days/week for 26 weeks. At 0.6 mg/kg, all male and female dogs were either sacrificed moribundly or dead during the 26-week treatment. The dogs revealed inactivity, salivation, dark bloody discharge, swelling of the subcutaneous injection site, abscess, and ulceration in the abdominal wall and legs. At 0.15 mg/kg, anorexia, salivation, and swelling of the injection site were observed. The food consumption was decreased with a statistical significance at 6 and 12 weeks treatment in males of 7.6 mg/kg. At 0.0375, 0.15 and 0.6 mg/kg, body weights were decreased significantly in a dose-related fashion after 17 weeks treatment. Total white blood cell counts for male dogs at 0.6 mg/kg were lower than those of control dogs after 13 weeks treatment, which appeared mainly due to decreased neutrophils. At 0.15 mg/kg, testicular atrophy was found in all males by gross pathology and the testicular weights were significantly decreased when compared to those of control males. Microscopically, the testis showed moderate atrophy of the seminiferous tubules and marked decrease in number of spermatozoa in the epididymal tubules. At 0.6 mg/kg, petechia or echymotic hemorrhage was observed in gastrointestinal tract, heart, lungs, and other organs at the necropsy, Marked atrophy of thymus were observed in both males and females. In addition, severe testicular atrophy was noted in all males. Microscopically, gastrointestinal tract showed hemorrhage, epithelial denudation, hypermucus secretion, and atrophy of intestinal villi. Seminiferous tubules of the atrophic testis were lined with Sertoli cells only and devoid of germ cells. Severe oligospermia or aspermia was present in the epididymal tubules. Bone marrow showed marked depletion of hemopoietic cells. In addition, marked atrophy was found in the lymphoid tissue of gastrointestinal tract, various Iymph nodes, and thymus. Injection sites showed marked inflammatory response with necrosis, necrotizing vasculitis, thrombus formation, and ulceration in the skin. According to the present results, no observed effect level appeared to be 0.0375 mg/kg. At 0.15 mg/kg, testis was a target organ, while at 0.6 mg/kg hemopoietic tissue, gastrointestinal tract, and testis were considered to be target organs. At 0.6 mg/kg the test compound seems to inflict a damage on the blood vessels causing hemorrhage in the various organs and tissues.

• Journal of Food Hygiene and Safety
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• v.25 no.3
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• pp.263-268
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• 2010

This study was demonstrate a repeated oral dose toxicity of detoxication sulphur in 8-weeks-old female Sprague-Dawley (SD) rats. The rats were treated with dose of 0.2%, 1%, 5% detoxication sulphur and 1% sulphur of feed consumption administered for 13 weeks. To evaluate the safety of detoxication sulfur, we examined the body weight, the feed intake, the clinical signs, the ophthalmological test, the hematological and the serum biochemical analysis. We also observed the histopathological changes of liver and kidney in rats. As a result, no significant differences in body weight, feed intake, hematological examination and histopathological between control and detoxication sulphur treatment group were found. Serum biochemical results were not shown significant differences in 0.2% and 1% the treated groups compared with control group. But glucose level were decrease, also ALT and ALP level were increase in 5% treated group. All of these results indicate that 1% detoxication sulphur of feed consumption may be safety in SD rat.

• Journal of Food Hygiene and Safety
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• v.30 no.1
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• pp.120-125
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• 2015

The objective of this study is to investigate the effect of MSG on cognitive function and anxiety by the T-maze and elevated-plus-maze test and repeated oral dose toxicity in SD rat of MSG. The rats were treated with MSG of control group, low group (3 g/kg) and high group (5 g/kg) intragastrically for 4 weeks, respectively. We examined the body weight, the clinical signs, T-maze, Elevated-plus-maze, hematological analysis and serum biochemical analysis, we also observed the histopathological changes of liver, kidney in rats. No significant differences in body weights, biochemical analysis and histopathological observations between control and MSG treatment group were found. In the elevated plus maze (EPM), MSG-treatment group has more open arm visited than controls. MSG-treatment group has been more activated in T-maze test. These data indicate the continuous high MSG intake could be increased the anxiety and could be decreased cognitive ability. In conclusion, MSG is physiologically safety, but high MSG intake could be increased the anxiety and could be decreased cognitive ability in juvenile rat.