• Toxicological Research
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• 제16권4호
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• pp.302-309
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• 2000

The purpose of this study is to investigate toxic effects of iso-butylalcohol (iBA) in Sprague-Dawley (SD) rats under the exposure of 6 hours a day, 5 days a week for 13 weeks by inhalation, and to evaluate the occupational safety of iBA in comparison with the permissible exposure level (PEL) stipulated by the Occupational Safety and Health Administration (OSHA). iBA did not induce any abnormal changes from the aspects of clinical signs, feed consumption, ophthalmic test, urinalysis, hematology and blood chemistry during and at the terminal of the inhalation toxicity tests. We did not find any abnormal findings in the gross and microscopic observations due to the inhalation of iBA. There was no alteration in relative organ weights by the inhalation of iBA. No observed adverse effect level (NOAEL) of iBA was considered to be more than 3,000 ppm in rats under the inhalation of 6 hours a day, 5 days a week for 13 weeks. Fifty ppm of iBA, the PEL regulated by OSHA, is too conservative for working places. As iBA showed no abnormal observations in all the experimental parameters at any concentration under this experimental condition, we suggest that 150 ppm is safe enough for the PEL of iBA in the working areas, even taking into onsideration that OSHA lowered the PEL to 50 ppm for fear of the probable risk of its skin irritation.

• Toxicological Research
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• 제34권2호
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• pp.143-150
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• 2018

It has been demonstrated that vanadate causes nephrotoxicity. Vanadate inhibits renal sodium potassium adenosine triphosphatase (Na, K-ATPase) activity and this is more pronounced in injured renal tissues. Cardiac cyclic adenosine monophosphate (cAMP) is enhanced by vanadate, while increased cAMP suppresses Na, K-ATPase action in renal tubular cells. There are no in vivo data collectively demonstrating the effect of vanadate on renal cAMP levels; on the abundance of the alpha 1 isoform (${\alpha}_1$) of the Na, K-ATPase protein or its cellular localization; or on renal tissue injury. In this study, rats received a normal saline solution or vanadate (5 mg/kg BW) by intraperitoneal injection for 10 days. Levels of vanadium, cAMP, and malondialdehyde (MDA), a marker of lipid peroxidation were measured in renal tissues. Protein abundance and the localization of renal ${\alpha}_1-Na$, K-ATPase was determined by Western blot and immunohistochemistry, respectively. Renal tissue injury was examined by histological evaluation and renal function was assessed by blood biochemical parameters. Rats treated with vanadate had markedly increased vanadium levels in their plasma, urine, and renal tissues. Vanadate significantly induced renal cAMP and MDA accumulation, whereas the protein level of ${\alpha}_1-Na$, K-ATPase was suppressed. Vanadate caused renal damage, azotemia, hypokalemia, and hypophosphatemia. Fractional excretions of all studied electrolytes were increased with vanadate administration. These in vivo findings demonstrate that vanadate might suppress renal ${\alpha}_1-Na$, K-ATPase protein functionally by enhancing cAMP and structurally by augmenting lipid peroxidation.

• Toxicological Research
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• 제34권2호
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• pp.151-162
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• 2018

Anti-diabetes activity of Catharsius molossus (Ca, a type of dung beetle) glycosaminoglycan (G) was evaluated to reduce glucose, creatinine kinase, triglyceride and free fatty acid levels in db mice. Diabetic mice in six groups were administrated intraperitoneally: Db heterozygous (Normal), Db homozygous (CON), Heuchys sanguinea glycosaminoglycan (HEG, 5 mg/kg), dung beetle glycosaminoglycan (CaG, 5 mg/kg), bumblebee (Bombus ignitus) queen glycosaminoglycan (IQG, 5 mg/kg) and metformin (10 mg/kg), for 1 month. Biochemical analyses in the serum were evaluated to determine their anti-diabetic and anti-inflammatory actions in db mice after 1 month treatment with HEG, CaG or IQG treatments. Blood glucose level was decreased by treatment with CaG. CaG produced significant anti-diabetic actions by inhiting creatinine kinase and alkaline phosphatase levels. As diabetic parameters, serum glucose level, total cholesterol and triglyceride were significantly decreased in CaG5-treated group compared to the controls. Dung beetle glycosaminoglycan, compared to the control, could be a potential therapeutic agent with anti-diabetic activity in diabetic mice. CaG5-treated group, compared to the control, showed the up-regulation of 48 genes including mitochondrial yen coded tRNA lysine (mt-TK), cytochrome P450, family 8/2, subfamily b, polypeptide 1 (Cyp8b1), and down-regulation of 79 genes including S100 calcium binding protein A9 (S100a9) and immunoglobulin kappa chain complex (Igk), and 3-hydroxy-3-methylglutaryl-CoenzymeAsynthase1 (Hmgcs1). Moreover, mitochondrial thymidine kinase (mt-TK), was up-regulated, and calgranulin A (S100a9) were down-regulated by CaG5 treatment, indicating a potential therapeutic use for anti-diabetic agent.

• Environmental Analysis Health and Toxicology
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• 제25권2호
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• pp.131-143
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• 2010

We performed the tests of acute and subchronic inhalation toxicity of methyl formate, which has limited toxicological data in spite of its widespread use and enhanced hazard consequent on its high volatility. The median lethal concentration ($LC_{50}$) was evaluated to be above 5,000ppm(12.27 mg/L). In the test with subchronic inhalation, there are no deaths, but with reduction of body weight, food intake, organ weight by exposure to 400 (0.98 mg/L) and 1,600 (3.92 mg/L) ppm, dose-dependently. There were statistical differences in some hematological and blood biochemical parameters as compared to control (e.g. neutrophile and lymphocyte in the 1,600 ppm group, calcium and A/G in 1,600 ppm group). Methyl formate under the exposure of 1,600 ppm showed the respiratory findings with nasal, it was confirmed that the chemical has respiratory hazard with 1,600 ppm inhalation exposure, induces nasal epithelial atrophy, olfactory cell degeneration/regeneration and the contraction of olfactory cells, etc. According to the notification with Ministry of Labor (No. 2009-68) for classification, labeling and MSDS of chemicals, it is suggested for methyl formate to be classified as category 4 in acute (10.0$4\leq20.0$ mg/L), category 2 (0.2$\leq$1.0 mg/L/6h, 90 days) in specific target organ-repeated exposure.

• Toxicological Research
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• 제21권4호
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• pp.309-318
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• 2005

Rhus verniciflua Stokes (RVS) has been used as a food supplement and a traditional herbal medicine. In this study, we prepared various flavonoid fractions (RS, RW1, RW2 and RWE) from a hot water extract of RVS and their influence on male reproductive organs and spermatogenesis were studied in rats which were orally administered 200 mg/kg of them for 8 weeks. All experimental groups did not show any significant changes in body weight and blood clinical chemistry for liver function. Plasma testosterone level was elevated about 3.7, 5.2 and 6.3 folds in RW1, RW2 and RWE groups, respectively. The weights of testes and epididymides tended to increase slightly without the statistical significance in RW2 and RWE. The spermatozoon motility and epididymal sperm concentration were significantly increased (P<0.05) in RWE and RW1, respectively, when compared to the control group. There was no significant difference in histology and apparent shape of testes and epididymides among the control and the experimental groups. Collectively, RWE showed effectively the elevation of plasma testosterone level, spermatozoon motility and the epididymal sperm concentration without the significant increase of testis and epidiymides weights. When the component HPLC profile among the flavonoids fractions of RVS was compared, the ratio of components were only different. These findings suggest that the Rhus flavonoid fraction, particularly RWE, can stimulate the androgen-dependent male sexual function and it can be applied to the material of functional food for enhancing the sexual function.

• Toxicological Research
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• 제20권3호
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• pp.213-223
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• 2004

This work aimed to study the effectiveness of cellular oxidative parameter (malondial-dehyde, protein carbonyl, and 8-hydroxy-2'deoxyguanosine). The experimental groups were aluminum treated rats and control rats. Aluminum treatd rats were given intraperitoneally aluminum nitrate nonahydrate ($Al^{3+}$, 0.2 mmol/kg) daily for 30 days except Sunday. Control rats were injected 1 ml of saline. After the dose, rats were decapitated and hippocampus and cerebral cortex were removed. The measured parameters were tissue malondialdehyde (MDA, index of lipid peroxidation), protein carbonyl (index of protein oxidation), 8-hydroxy-2'-deoxy-guanosine (8-OHdG, index of DNA oxidation), reduced glutathione (GSH) levels as well as glutathione reductase (GR) and catalase. AI concentrations in the tissues were also measured. All results were corrected by tissue protein levels. The results were as followed; 1. The concentrations of AI in the cortex and hippocampus were significantly higher in the AI-treated rats than in the control rats. 2. Antioxidative enzyme's activity, catalase and GR, were significantly higher in the AI-treated rats than the control rats. GSH levels were also higher in the AI-treated rats. 3. MDA, protein carbonyl, and 8-OHdG concentration of AI-treated rats were significantly higher than those of control rats. 4. The concentrations of antioxidants, and oxidative stress parameter were correlated with the concentrations of AI in hippocampus and cerebral cortex. Catalase and GR activity were also correlated with the concentration of AI. Based on these results, it can be suggested that intraperitoneally injected AI was accumulated in the brain and induced the increase of antioxidant levels and antioxidative enzyme activity. Also, the oxidative products of cellular macromolecules are significantly related to tissue AI concentration. Therefore MDA, protein carbonyl, and 8-OHdG are useful markers for oxidative stress on cellular macromolecules.

• Toxicological Research
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• 제11권2호
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• pp.279-288
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• 1995

To apply the serum xanthine oxidase (XO) determining for the index of the toluene intoxication, the serum XO activity was compared with the other parameters, the activities of serum alanine aminotransferase(ALT), aspartate aminotransferase(AST), 5'-nucleotidase(5'-NT), alkaline phosphatase(ALP), guanase(GDA) and $\gamma$-gIutamyl transpeptidase(T-GTP). Concomitantly, the cause of increased level of serum XO was clarified in the present experimental conditions. Although the other serum enzyme activities, ALT, AST, 5'-NT, ALP, GDA and $\gamma$-GTP were respectively not found to be different between control group and toluene-treated group, the serum XO activity in toluene-treated group showed the higher levels than that in the control group. These suggested that the determination of serum XO activity could be used for monitoring the intoxication of toluene. On the other hand, the activities of XO both in the serum and liver were higher in toluene-treated or benzaldehyde-treated rats than those in each control group. In the pooled liver XO from each group, toluene-treated or benzaldehyde-treated group showed the higher $V_{max}$ value than the control group, whereas no changes were observed in liver XO activities between the control liver specimen and that preincubated with bertzaldehyde in vitro. The present results indicate that the increased level of XO in toluene-treated rats is due to the result of enzyme protein induction in liver cell by the benzaldehyde metabolized from toluene. All the more, the benzaldehyde may be acted as a substrate for XO, since the benzaldehyde induced the increased activity of both liver and serum XO, and no changes were found in purine catabolite, uric acid in serum or urine and liver purine catabolizing enzymes, adenosine deaminase, GDA, uricuse except XO in toluene-treated rats.

• Toxicological Research
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• 제18권4호
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• pp.401-409
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• 2002

Phthalate esters have possible effects on the endocrine system. Di-n-butyl phthalate (DBP) is one of the most commonly wed phthalic acid esters (PAEs). It is extensively wed as a plasticizer in elastomers, as a solvent for printing inks and resins, and as a textile lubricating agent. It is also present in the formulations of various cosmetic products. DBP has been identified as a reproductive toxicant in several animal species and also know as a endocrine disruptor. The objective of this study was to investigate the effect of DBP on developmental immune Junction wing rat pups as experimental animals. Timed-bred pregnant SD rats were orally dosed with 0, 250, 500, or 750 mg DBP/kg body weight once a day from gestational day (GD) 5 to 18 and postpartum day (PD) 3 to 18. On PD22, the dams and their pups were euthanized and examined for alteration in parameters associated to immune function. The results showed no significant changes in body weight, thymus weight, thymus and spleen cellularities, the polyclonal activation respones of splenocyte with ConA and LPS, and also the distribution of arterial blood cells and thymocyto subsets in both rat dam and pups. However DBP exposure on rat dam resulted in increases of liver weights of dam and their pups except 750 mg DBP/kg, and body and spleen weights in pups except 750 mg DBP/kg. On the other hands, distribution rates of CD8+ T cells at 500 mg DBP/kg and B cells at 750 mg DBP/kg among splenocyte subsets were significantly increased in rat pups, unlike dams. Reasons of these distribution alterations of CD8+ T cells and B cells in rat pups are under study.

• Toxicological Research
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• 제23권4호
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• pp.383-389
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• 2007

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 $1000{\mu}g/kg$. The lethal dose ($LD_{50}$) was not found in this range. Moreover, repeated dose toxicity study of 14-days period and at the doses of 50 and $200{\mu}g/kg$ (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.

• Toxicological Research
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• 제23권4호
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• pp.363-371
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• 2007

Isaria sinelairii (IS) was orally administered at doses of 0, 0.04, 0.2, and 1 g/kg/day over a 13-week period. There were no observed clinical signs or deaths related to treatment in all the groups tested. Therefore, the approximate lethal oral dose of I. sinclairii was considered to be higher than 1 g/kg in rats. Throughout the administration periods, no significant changes in diet consumption, ophthalmologic findings, organ weight, clinical pathology (hematology, clinical chemistry, coagulation, and urinalysis) or gross pathology were detected. Minor changes were found in hematological parameters for the 0.04 g/kg/day and 0.2 g/kg/day IS treated groups (triglyceride reductions of $20.1{\sim}46.6%$ and platelet increases), but all changes were within physiological range. Microscopic examination failed to identify any treatment-related histopathologic changes in the organs of the IS-treated rats other than nuclear enlargement (cellular atypia) of the tubular regions in the medulla of the kidney in the high dose group. From these results, one can conclude that the no-observed effect level (NOAEL) of I. sinclairii is less than 0.04 g/kg/day in rats.