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REFERENCE LINKING PLATFORM OF KOREA S&T JOURNALS
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The Korean Society of Toxicology
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Volume & Issues
Volume 12, Issue 2 - Dec 1996
Volume 12, Issue 1 - Jun 1996
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Effects of Dimethylformamide on Lipid Peroxide Level and Activity of Superoxide Dismutase in Human Serum
Toxicological Research, volume 12, issue 1, 1996, Pages 1~8
The variation in the enzyme activities of human liver usually represents the particular physiological conditions of each individuals. Thus, we investigated the variation in the activities of SOD, HR and LPO of (1) non-exposed workers (56 subjects), and (2) exposed workers to DMF (43 subjects) in synthetic leather process. Serum levels of enzyme activities of exposed workers (AST:
U/L)were slightly higher than those in nonexposed workers (AST:
U/L), but only the level of ALT was statistically significant (p< 0.05). Serum levels of LDH, TRF and CHOL in non-exposed workers were slightly higher than those of exposed workers. However, they were not statistically significant (p > 0.05). Serum levels of HR and LPO of the exposed workers appeared to be reduced, but not those of the non-exposed workers. The SOD activities of exposed workers were also slightly higher than those of non-exposed workers, but the results were not statistically significant (p > 0.05). The level of HR was increased with age, but the SOD level was not. These results suggest that the intermittent exposure to DMF at time-weighted average (TWA) level (10 ppm/
) has affected on the activities of enzymes such as AST, ALT, TRF, but not on the generation of HR, activity of SOD. However, if high dose of DMF was used, there would be severe effects for the generation of HR and LPO.
Combinatory Effects of Benzene, Toluene and Xylene on the Induction of Rat Liver Microsomal Enzymes and Their Metabolites
Toxicological Research, volume 12, issue 1, 1996, Pages 9~15
We studied the effects of a single, combined and mixed exposure of benzene, toluene and xylene on the activities of rat liver microsomal AHH, ADH and ALDH, and the excretion of their metabolites in urine. The AHH activities of the rats treated in combination and mixture were slightly higher and/or similar to those rats treated with single solvent, while the reverse effects were observed for ADH and ALDH. Similar effects were observed when the metabolites were examined in urine (p < 0.01). These results suggest that each solvent might interJkre the induction and action of ADH and ALDH, and decrease the excretion of their metabolites into urine.
Effect of Fumonisin B1 on the Bacterial Virus Multiplication
Toxicological Research, volume 12, issue 1, 1996, Pages 17~20
The effect of Fumonisin B1, a mycotoxin produced by Fusarium moniliforme on bacterial viruses P1 and Lambda, was investigated by the virus plaque assay. Fumonisin B1 inhibited the P1 viral multiplication in the concentration range from
/ml. The inhibition was Fumonisin B1 concentration-dependent. Another bacterial virus Lambda multiplication was also inhibited by lower concentration of Fumonisin B1 (
/ml). This inhibition was dependent on Fumonisin B1 and on virus-Fumonisin B1 reaction time. Sensitivity of bacteriophage Lambda to Fumonisin B1 was higher than that of P1 virus. Lambda vital DNA was treated in vitro with Fumonisin B1 at various concentration. Significant DNA fragmentation by Fumonisin 191 was observed in the agarose gel electrophoresis. Lambda viral DNA was partially digested even in the Fumonisin B1
and the level of its fragmentation was dependent on Fumonisin B1 amount up to
Inhibitory Effect of Vitamin C on Mutagenicity of 6-Sulfooxymethylbenzo[a]pyrene
Cho, Young-Sik ; Hong, Sun-Taek ; Chung, An-Sik ;
Toxicological Research, volume 12, issue 1, 1996, Pages 21~27
Vitamin C has been well known to be a potential chemopreventive agent for several toxic compounds. It reduced the mutation frequencies of 6-sulfooxymethylbenzo[a]pyrene (SMBP) and 6hydroxymethylbenzo[a]pyrene (HMBP) in Salmonella typhimurium TA98 and TA100, indicating that corbic acid affects both frameshift and base-pair substitution mtltations. A similar type of dose-response relationship was shown in the V79 cells, although the inhibitory effect was less dramatic compared with that in S. typhimurium. However, SMBP or HMBP binding to calf thymus DNA was not affected by the presence of vitamin C, suggesting that SMBP seems to be much more reactive to calf thymus DNA than vitamin C. This was supported by migration pattern and fluorescence intensity of SMBP-modified plasmid on the gel. These restilts were not correlated with mutation tests in bacterial and mammalian cell systems. It has been already reported that vitamin C inactivates SMBP through the formation of covalently bound addact. It was found from HPLC analysis that the reaction between vitamin C and SMBP was accomplished within just 5 min and then produced the several products. These findings indicate that the beneficiary of vitamin C is not merely derived from the covalent adducts. On the other hand, the addition of DNA to incubation mixture reduced the amounts of vitamin C adducts while the magnitude of HMBP peak increased, suggesting that DNA accelerates the SMBP hydrolysis to intercept the interaction between SMBP and vitamin C or forms rapidly complex with SMBP.
The Acute Toxicity of 1,2,4-Trichlorobenzene in Sprague-Dawley Rats Depleted of Glutathione by Treatment with Buthionine Sulfoximine
Toxicological Research, volume 12, issue 1, 1996, Pages 29~34
1,2,4-trichlorobenzene (1,2,4-TCB) is used as a dye carrier, an intermediate in the syn[hesis of herbicides, aflame retardant, and for other purpose. After a single oral administration of 1,2,4-TCB (200 mg/kg, 400 mg/kg) in rats, toxic effects were studied by means of serum biochemical and hematological analysis, and liver calcium concentration. Administration of 1,2,4-TCB resulted in dose-dependent manner liver and kidney damage being suggested by increased serum alanine aminbtransferase (ALT) activities, liver calcium concentration and blood urea nitrogen (BUN). Pretreatment with DL-buthionine sulfoximine (BSO, 2 mmol/kg, i.p.) considerably decreased liver glatathione concentration, which was accompanied by markedly elevated serum ALT activites. It is well-known that toxicity of halogenated benzene such as bromobenzene, 1,4-dichlorobenzene is increased by pretreatment of phenobarbital, and protected by pretreatment of cytochrorn P450 inhibitor including metyrapone. However, there were no obvious alterations in toxicity of 1,2,4-TCB by pretreatment of phenobarbital or metyrapone. In comparison with control group, treatment groups exhibited significant changes in some parameters of hematological analysis but all hematological values remained within normal ranges.
Development of Antitoxic Agents from Korean Medicinal Plants. Part 6. -Effects of Methanol Fraction of Lonicerae flos on the Accumulation of Cadmium in Spleen-
Toxicological Research, volume 12, issue 1, 1996, Pages 35~39
This study was conducted to investigate the antitoxic component in methanol fraction of Lonicerae fios. The results were as follows: 1. When a 500 ppm of water soluble fraction of Lonicerae flos was administered, it showed the highest antitoxic effect. 2. Generally, detoxication effects of methanol fraction of Lonicerae fios increased. 'When the ethyl acetate soluble fraction of Lonicerae fios was administered, it exhibited the highest antitoxic effect against the toxicity of cadmium in spleen.
Development of Antitoxic Agents from Korean Medicinal Plants. Part 8. -Effects of Methanol Fraction of Lonicerae flos on the Accumulation of Cadmium and Metallothionein in Rats.-
Toxicological Research, volume 12, issue 1, 1996, Pages 41~46
This study was performed to investigate the antitoxic component in methanol fraction of Lonicerae fios. The results were as follows: 1. When a 500 ppm of water soluble fraction of Lonicerae flos was administered, it showed the highest antitoxic effect. 2. Generally, detoxication effects by methanol fraction of Lonicerae fios increased. When the ethyl acetate soluble fraction of Lonicerae rios was administered, it exhibited the highest antitoxic effect against the toxicity of cadmium in Liver. 3. The combined administration of cadmium and methanol fraction of Lonicerae rios significantly increased metallothionein in liver compared to administration of cadmium only. This phenomenon was more remarkable when the ethyl acetate soluble fraction of Lonicerae fios was administered with cadmium chloride.
Toxic Effects of Polygalae Radix on Rat Kidney
Yi, Eun-Young ; Park, Chae-Young ; Ma, Young ; Lim, Dong-Koo ;
Toxicological Research, volume 12, issue 1, 1996, Pages 47~52
The renal toxicity of the extract of Polygalae Radix was investigated in rats. Rats were treated with 3.5 mg/Kg of the extract, i.p., for 7 days. Changes in consumatory behavior, 24 hour-urine and the activities of urinary enzymes were determined during the administration of the extract. Significant decrease in body weight and food consumption and increase in 24 hour-urine volume were observed during the administration. However, the quantity of total creatinine in urine was decreased significantly. Those indicate that subacute treatment with the extract might induce diuresis and the ditiresis might be due to the decrease in water reabsorption. In the activities of urinary enzymes, the activities of alanine aminopejotidase (AAP) and gamma-glutamyl transpeptidase (GGT) were increased 4.3 and 3.5 times and then returned to the control. The activity of N-acetyl-
-D-glucosaminidase (NAG) was increased 7.2 times and then decreased slowly. But, it was significantly higher than that of the control evea after the last administration. The activity of factate dehydrogenase (LDH) was increased continuozlsly during the treatment. It showed 32 times higher than the control. These results suggested that the extract of Polygalae Radix had toxic effect on kidney. Furthermore, the result suggested that the subacute administration of the extract induced resistance against the toxicity of Polygalae Radix.
Eye Irritation, Skin Irritation and Skin Sensitization Tests for Aloewhite in Animals
Toxicological Research, volume 12, issue 1, 1996, Pages 53~58
Eye irritation, primary skin irritation and skin sensitization tests for Aloewhite were tested in New Zealand White rabbits and Hartley guinea pig. In primary skin irritation test of male New Zealand White rabbits, body weights were not significantly changed and Primary Irritation Index (PII) was O.47, indicating Aloewhite as mildly irritating material. In ocular irritation test, any injury on iris, conjunctival membrane, and cornea in New Zealand White rabbits was not observed. No injuries of the ocular mucous membrane were also recorded. Skin sensitization was tested in guinea pig after intradermal and epicutaneous induction and graded 1 with zero % sensitization rate. These results indicate that Aloewhite was not considered to be irritant in test organs of animals.
A Study on the Effects of Radix Menispermi Extracts Against Cadmium Chloride Sub-chronic Toxicity in Rats
Toxicological Research, volume 12, issue 1, 1996, Pages 59~68
This study was conducted to investigate the antitoxic effects of Radix Menispermi extracts against cadmium toxicity. The experimental rats were divided into 5 groups such as control group, cadmium alone treatment group and simultaneous treatment groups of cadmium and three doses of Radix Menispermi extracts. Each group was administered with different dose of Radix Menispermi extracts such as 0.55 mg, 1.10 mg, 1.65 mg/kg wet weight in pallets for 12 weeks. Cadmium Chloride
was administered by 4 mg/kg body weight. The results were summarized as follows: 1. The simultaneous administration of cadmium and Radix Menispermi significantly more decreased cadmium concentration in liver tissues compared to the administration of cadmium only (P < 0.05). 2. When blood were measured, no significantly difference in haemoglobin, haematocrit, erythrocyte values compared to the administration of cadmium only. 3. The simultaneous administration of cadmium and Radix Menispermi more increased metallothionein concentration in liver than the administration of cadmium only (P < 0.05). 4. There were the histopathological slight changes in the liver and kidney tissues of rats.
Neurotoxicity Assessment of Methamphetamine and Cadmium Using Cultured Neuronal Cells of Long-Evans Rats
Toxicological Research, volume 12, issue 1, 1996, Pages 69~79
Primary culture of cerebellar neuronal cells derived from 8-day old Long-Evans rats was used. Pure granule cells, astrocytes or mixed cells culture systems were prepared. These cells were differentiated and developed synaptic connections. And the astrocytes were identified by immunostaining with glial fibrillary acidic protein (GFAP). Methamphetamine (MAP), which acts on dopaminergic system and cadmium (Cd), a toxic heavy metal, were applied and biochemical assays and electrophysiological studies were performed. $LC_50$ values estimated by MTT assay of MAP and Cd were 3 mM and 2$\mu M$ respectively. Cells were treated with 1 mM or 2 mM MAP and 1$\mu M$ $CdCl_2$ for 48 hour, and the incubation media were analyzed for the content of released LDH. MAP (2 mM) and Cd significantly increased the LDH release. Cell viability was decreased in both groups and some cytopathological changes like cell swelling or vacuolization were seen. The cerebellar granule cells were used for measuring membrane currents using whole-cell clamp technique. Sodium and potassium currents were not affected by MAP neither Cd, but calcium current was significantly reduced by Cd but not affected by MAP. Therefore, in vitro neurotoxicity test system using neuronaI cells and astrocytes cultures were established and can be used in screening of potential neurotoxic chemicals.
A Study on Antigenicity of Recombinant Human Interferon
(LB00013) in Mice and Guinea Pigs
Park, Jong-Il ; Jeong, Tae-Cheon ; Cha, Shin-Woo ; Shin, Ho-Chul ; Han, Sang-Seop ;
Toxicological Research, volume 12, issue 1, 1996, Pages 81~86
Antigenicity of recombinant human interferon $\beta$(LB00013), a newly developed drug for anti-cancer and anti-viral therapeutic use, was investigated in mice and guinea pigs. The following results were obtained: 1. Mice showed no production of antibodies against LB00013 sensitized with aluminum hydroxide gel (Alum) as an adjuvant, when judged by the heterologous passive cutaneous anaphylaxis (PCA) test in rats. Meanwhile, antibodies against ovalbumin (OVA) sensitized with Alum were clearly detected. 2. In guinea pigs, the sensitization of neither LB00013 only nor LB00013 with complete Freund's adjuvant (CFA) produced positive reactions in the homologous active systemic anaphylaxis (ASA) and the PCA tests. Meanwhile, the sensitization of OVA with CFA produced positive reactions in both PCA and ASA. 3. A LB00013-specific reaction was not observed in an indirect hemagglutination(IHA) assay using sera isolated from LB00013 sensitized mice. The present results suggested that LB00013 may have no antigenic potential in mice and guinea pigs.
A Study of Recombinant Human Interferon
(LB00013) for Primary Eye and Skin Irritation in Rabbits
Park, Jong-Il ; Bae, Ju-Hyun ; Suh, Jeong-Eun ; Jeong, Tae-Cheon ; Shin, Ho-Chul ; Han, Sang-Seop ;
Toxicological Research, volume 12, issue 1, 1996, Pages 87~91
LB00013, a newly developed recombinant human Interferon $\beta$, was tested for primary eye and skin irritation in male New Zealand White rabbits. In the primary eye irritation test, 0.1 ml of a solution of LB00013 was instilled into the eye. In the rinsing group, the eye was washed with water at 30 seconds after instillation. No reaction was produced at the cornea, iris and conjunctivae by LB00013. In the primary skin irritation test, LB00013 was applied to the back of rabbits for 24 hours. Primary irritation index was "0" in test and control sites of all animals. Thus LB00013 was evaluated as a non-irritant on the basis of the criteria of Draize et al. (1944).l. (1944).
Fertility Study of KTC-1, a New Semisynthetic Rifamycin Derivative, in Rats.
Toxicological Research, volume 12, issue 1, 1996, Pages 93~99
The effect of KTC-1, a new semisynthetic rifamycin antituberculous drug, on general toxicity, reproductive capability and fetal development was investigated in Sprague-Dawley rats. Male rats were administered KTC-1 with mashed feed from 63 days before mating to the end of mating period, and female rats were given from 14 days before mating to day 7 of gestation at dose levels of 0, 375, 750, and 1,500 ppm. The females were sacrificed on day 21 of gestation for examination of their fetuses. At 1,500 ppm, a reduction in body weight gain and testis atrophy were observed in male rats. Histological examination revealed testicular atrophy, absence or decrease of germinal cells, and vacuolization of Sertoli cells in testis. A reduction in body weight gain, a decrease in food consumption were found in female rats. In addition, decreases in the number of corpora lutea, iraplantations, and the litter size of live fetuses were seen. Mating, fertility, and pregnancy performances were also affected. There were no external abnormalities observed by examination of fetuses. At 750 ppm, a reduction in the body weight gain of male and female rats and decreases in the number of implantations and litter size were found. At 375 ppm, no treatment-related effects were observed. The results suggest that the no-effect dose levels (NOELs) of KTC-1 are 375 ppm for males and females on general toxicity, 750 ppm for males and females on reproductive capability, and 375 ppm for fetuses on embryonic development.
Local Irritation of DA-3285, Recombinant Human Erythropoietin
Toxicological Research, volume 12, issue 1, 1996, Pages 101~111
The local irritation studies of DA-3285, recombinant human erytropoietin(rHu-EPO), were carried out in rabbits after the following treatment; single application into the conjunctival sac of the eye, single subcutaneous injection, 7-day repeated subcutaneous injection and 8-day repeated infusion into the ear vein. Also, the local irritancy of DA-3285 leaked around vein was studied in mice by single perivascular injection. The results obtained were as follows. In the result of ocular irritation test, DA-3285 could be considered as a non-irritating material. In single and 7-day repeated subcutaneous irritation test, the irritancy of DA-3285 was not so much different from that of saline. The vascular irritancy of DA3285 by 8-day repeated infusion was negligible and similar to that of saline. And the irritancy of DA3285 by perivascular injection was comparable to that of saline. These results indicate that DA-3285 has no irritating activity when injected through subcutaneous or intravenous route for clinical practice as 3.5% solution.
Three Month Subacute Toxicity Study of Ginkgo Biloba Extract(EGb 761) in Rats
Lee, Yong-Soon ; Nam, Jeong-Seok ; Che, Jeong-Hwan ; Lee, Suk-Man ; Yang, Jae-Man ; Kang, Byeong-Cheol ; Lee, Hak-Mo ; Park, Jae-Hak ; Chai, Chan-Hee ; Kang, Sung-An ;
Toxicological Research, volume 12, issue 1, 1996, Pages 113~119
Group of 40 male and 40 female Sprague-Dawley rats was given daily intravenous injections of different dosage of Ginkgo biloba extract(EGb 761), 7.5 mg/kg/day (low dosage group), 15 mg/kg/day (middle dosage group), or 30 mg/kg/day (high dosage group)for 3 month by tail vein according to Established Regulation of Korean National Institute of Safety Research (1994. 4. 14). Appearance, behavior, mortality, and food consumption of rats of treated groups were not affected during the experimental periods. No significant Ginkgo biloba extract(EGb 761)-related changes were found in urinalysis, hematology, serum chemistry, and organ weight. No histopathological lesions were seen in both control and treatment groups. Our results strongly suggest that no toxic changes were found in rat treated intravenously with Ginkgo biloba extract(EGb 761)for 3 month.
Three Month Subacute Toxicity Study of Ginkgo Biloba Extract(EGb 761) in Rabbits
Lee, Yong-Soon ; Nam, Jeong-Seok ; Che, Jeong-Hwan ; Lee, Suk-Man ; Yang, Jae-Man ; Kang, Byeong-Cheol ; Lee, Hak-Mo ; Park, Jae-Hak ; Chai, Chan-Hee ;
Toxicological Research, volume 12, issue 1, 1996, Pages 121~128
Group of 12 male and 12 female rabbits was given daily intravenous injections of different dosage of Ginkgo biloba extract(EGb 761), 7.5 mg/kg/day (low dosage group), 15 mg/kg/day (middle dosage group), or 30 mg/kg/day (high dosage group)for 3 month by ear vein according to Established Regulation of Korean National Institute of Safety Research (1994. 4. 14). Appearance, behavior, mortality, and food consumption of rabbits of treated groups were not affected during the experimental periods. No significant Ginkgo biloba extract(EGb 761)-related changes were found in urinalysis, hematology, serum chemistry, and organ weight. No histopathological lesions were seen in both control and treatment groups. Our results strongly suggest that no toxic changes should be found in rabbit treated intravenously with Ginkgo biloba extract(EGb 761)for 3 month.
Fertility and General Reproductive Ability Test of Ginkgo Biloba Extract (EGb 761) in Rats
Lee,Yong-Soon ; Nam, Jeong-Seok ; Yang, Jae-Man ; Che, Jeong-Hwan ; Kang, Byeong-Chul ; Lee, Hak-Mo ; Park, Jae-Hak ; Kim, Dai-Yong ; Kang, Sung-An ;
Toxicological Research, volume 12, issue 1, 1996, Pages 129~136
A fertility and general reproductive a. bility study was performed in Sparque-Dawley rats intravenously injected with Ginkgo biloba extract (EGb 761), a potential pharmaceutical excipient, at dose levels of 7.5, 15, and 30 mg/kg/day. Male rats were treated with Ginkgo biloba extract (EGb 761)from 14 days before mating until 21 days after delivery. Female rats received extract for 2 months prior to mating. No abnormal signs were noted in mating or fertility of the rats treated with Ginkgo biloba extract (EGb 761). No significant external, visceral, and skeletal anomalies or mental and physical development attributable to treatment was noted in any fetuses examined. The fertility of F1 generation was not affected by the treatment also. It was concluded that Ginkgo biloba extract (EGb 761) has no harmful effect on mating, fertilization, implantation, embryonic development and normal physical development.
Teratological Studies of Ginkgo biloba Extract(EGb 761) in Rabbits
Lee, Yong-Soon ; Nam, Jeong-Seok ; Che, Jeong-Hwan ; Lee, Suk-Man ; Yang, Jae-Man ; Kang, Byeong-Cheol ; Lee, Hak-Mo ; Park, Jae-Hak ; Kim, Dai-Yong ; Kang, Sung-An ;
Toxicological Research, volume 12, issue 1, 1996, Pages 137~141
A teratological study was performed using New Zealand White rabbits to examine the teratological potential of Ginkgo biloba extract(EGb 761), which is a known strong platelet activating factor antagonist. Ginkgo biloba extract(EGb 761) was administered per intravenously during the organogenesis period (day 6th to 18th of gestation) of rabbits at dose levels of 7.5, 15, and 30 mg/kg/day. All pregnant females were sacrificed on day 29 of gestation and teratological abnormalities of their fetuses was examined. No statistically significant difference of body weight change between control and treated groups during experimental periods was noted. There was no statistically signifiant difference of numbers of corpus lutes and implantations, fetal death ratio, fetal sex ratio, and placental weight between control and rabbits exposed to three different concentration ranges of Ginkgo biloba extract (EGb 761). No marked external, visceral and skeletal abnormalities related to Ginkgo biloba extract(EGb 761) were observed in the fetuses. In conclusion Ginkgo biloba extract(EGb 761) does not show any effect on implantation or embryonic development.