• Toxicological Research
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• v.8 no.2
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• pp.217-233
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• 1992

This study was performed to determine the toxic effects of graded dose levels of SKI 2053R after repeated administration. Three groups of Sprague-Dawley rats(10M and 10F per group) were given a total of 25 i.v. injections of SKI 2053R (1.50,3.75,9.38mg/kg/day). In order to compare the toxic effects of SKI 2053R with those of cisplatin, one group of Sprague-Dawley rats (10M and 10F per group) were given a total of 25 i.v.injections of cisplatin (1.70mg/kg/day). The dosing schedule was divided into five courses of 5 consecutive days with 16-day dose-free intervals between each course. No drug-related toxicity occurred in low dose level group (1.50mg/kg/day) of SKI2053R. From the results of hematological examination, peripheral WBC counts, RBC counts and hemoglobin of high dose level group(9.38mg/kg/day)of SKI 2053R were significantly lower than those of no-treated group. Other toxicities including reduced final body weight, proteinuria and hematuria were observed in high dose level group of SKI 2053R. But, no change was detected in serum biochemical values of SKI 2053R treated groups. All of the rats in cisplatin treated group were died between 3 and 13 weeks, while rats treated with SKI2053R survived to the end except one rat of middle dose level group(3.75mg/kg/day). In histopathological examinations, rats that received cisplatin manifested severe tubular damage in kidney and hemosiderosis in spleen, but no critical pathological lesion was observed in rats of other groups. Considering the results of this study, it was concluded that non-toxic dose of SKI 2053R in this treatment schedule was estimated to be 3.75 mg/kg/day and the maximum tolerated dose was to be higher than 9.38mg/kg/day. The toxic profiles fo SKI 2053R were different from those of cisplatin, and its toxicity was considerably lower than that of cisplatin.

• Toxicological Research
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• v.8 no.2
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• pp.235-253
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• 1992

A subacute toxicity study of cis-Malonato[(4R,5R)-4,5-bis(aminomethyl)-2-isopropyl-1,3-dioxolane]platinum(II)(SKI 2053R) was carried out to obtain information on its toxicological profiles, and to determine the maximum tolerated dose in beagle dogs. Four groups of beagle dogs (2M and 2F per group, 0,0.5,1.0,2.0mg/kg/day)were given 15 i.v. injections of SKI 2053R. In order to compare the toxic effects of SKI 2053R with those of cisplatin, one group was treated with cisplatin(0.7mg/kg/day)according to the same treatment schedule. The dosing schedule was divided into 3 courses of 5 consecutive days with 23-day dose-free intervals between each course. After completion of the treatments, remaining dogs were necropsied under established guidelines. Three of four dogs in the high dose group and one of four dogs in the middle dose group treated with SKI 2053R died of hypovolemic shock secondary to hemorrhagic and ulcerative enterocolitis. No toxicity-related mortality occurred in the low dose group of SKI 2053R. No survivor was observed in the group of cisplatin. Clinical signs including vomiting, diarrhea, anorexia and loss body weight were apparent in dogs given either cisplatin or high and middle doses of SKI 2053R. Severe thrombocytopenia and leukocytopenia were observed in the high dose group of SKI 2053R and cisplatin-treatment group, while toxicities as bone marrow suppression were reversible. The significant elevation of serum ALP values in group of SKI 2053R(2.0 mg/kg/day and 1.0mg/kg/day) and cisplatin(0.7mg/kg/day)was observed. Slight proteinuria waa observed in high and middle dose level groups of SKI 2053R. In histopathological examinations, pathological alterations of liver, kidney and spleen were noted dose-dependantly in dogs treated with SKI 2053R, and there was no overt sign of toxicity in low dose group of SKI 2053R. Compared to SKI 2053R, more severe durg-related toxicities occurred in dogs treated with cisplatin. It waw estimated that maximum tolerated dose of SKI 2053R in this treatment schedule was 0.5~0.7mg/kg/day. In conclusion, overall toxic potential of SKI 2053R was approximately 3 times lower than that of cisplatin with respect of lethality.

• Biomolecules & Therapeutics
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• v.2 no.2
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• pp.190-205
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• 1994

This study was conducted to investigate the repeated dose toxicity of DA-125, a new anthracycline antitumor antibiotic, in rats. Before the 13-week main study, a 4-week dose-range finding (DRF) study was carried out. The administration of DA-125 intravenously at dosage levels of 0, 0.125, 0.5, 2.0, and 8.0 mg/kg/day to rats for 4 weeks resulted in premature deaths of all animals in the 8.0 mg/kg/day group and in the deaths of 4 males and 4 females at 2.0 mg/kg/day. Body weights were markedly reduced in the 8.0 mg/kg/day group and showed dose-related decreases in all treatment groups when compared with the control group. Reductions in weight gain were slight and not significantly different at 0.125 mg/kg/day but animals receiving 0.5 mg/kg/day showed more marked decreases in gain in a clear dose-related manner Based On the results of the above DRF study, a 13-week repeated dose intravenous toxicity study in rats with DA-125 was performed at a dose level of 0, 0.012, 0.08 and 0.3 mg/kg/day. No treatment related effects were noted in behavior or body weight in all treatment groups. One male at the highest dose level died on study day 26, but the death could not be related to test article toxicity. Swelling and scabbing of the ears was present in all of the groups, including the control group. There were no treatment related changes in the hematological, biochemical or urinalysis values in all treatment groups. Thymus weights were significantly reduced ill males receiving 0.3 mg/kg/day and they were sligltly, and not significantly, reduced in females of the same group. While there were no associated histological changes. Treatment related necrosis was found in the tail vein (injection site) at 0.08 and 0.3 mg/kg/day. On the basis of these results, the no observed effect level (NOEL) was 0.012 mg/kg/day and the maximum tolerated dose (MTD) was estimated to be more than 0.3 mg/kg/day under the conditions tested.

• The Korean Journal of Pesticide Science
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• v.7 no.4
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• pp.280-287
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• 2003

To assess the risk of pesticides on earthworm, the acute toxicities of 10 pesticides were investigated and their toxicity exposure ratios(TERs) were calculated. As the TERs of paraquat dichloride and pendimethalin were more than 100, their risks were rated negligible. Risk of benfuracarb, cadusafos, chlorpyrifos-methyl, endosulfan, isazofos and parathion which have TERs of $10\sim100$ were rated low. However, risk of imidacloprid and phorate which have TER of less than 10 were estimated highly to need a reproduction study. Earthworms were exposed to twenty two pesticides including dazomet 98% GR having PECs of more than $5mg{\cdot}kg^{-1}$ in artificial soil at standard and double dose for 14 days. All the earthworms exposed to dazomet 98% GR and metam-sodium 25% SL were died to show their high risk, while no serious adverse effects were observed in the soil treated with 15 pesticides, calcite 95% WP, calcium polysulfide 36% CF, chlorothalonil 75% WP, daminozide 85% WP, dichlonil 6.7% GR, etridiazole 25% EC, fosetyl-Al 80% WP, glyphosate 41 % SL, hymexazol 30% SL, iprodione 50% WP, machine oil 95% EC, mancozeb 75% WP, propineb 70% WP, terbuthylazine 80% WP and triazophos 40% EC. In case of thiophanate-methyl 70% WP, copper hydroxide 77% WP, dimethoate 46% EC, tolclofos-methyl 50% WP and propamocarb hydrochloride 67% SL, any effect did not show clearly, suggesting an additional subchronic toxicity study. The risk of thiophanate-methyl 70% WP to earthworm was estimated high, considering its subchronic effect, while effects of copper hydroxide 77% WP, dimethoate 46% EC, tolclofos-methyl 50% WP and propamocarb hydrochloride 67% SL to earthworms were negligible, considering no adverse effects in subchronic tests.

• Journal of Pharmacopuncture
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• v.5 no.1 s.8
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• pp.27-42
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• 2002

Objective: The purpose of this study was to investigate the acute and subacute toxicity and sarcoma- 180 anti-cancer effects of Herbal acupuncture with Triglii Semen in mice and rats. Method: Balble mice were injected intraperitoneally with Triglii semen Herbal acupuncture for $LD_{50}$ and acute toxicity test. Sprague Dawley rats were injected intraperitoneally with Triglii semen Herbal acupuncture for subacute toxicity test. The Triglii semen Herbal acupuncture was injected on Chung-wan(CV12) of mice with S-180 cancer cell line. Results: 1. In acute toxicity test, the $LD_{50}$ value was $7.49{\times}10^3$ml, 0.30ml/kg.2. The body weights of mice treated with Triglii semen Herbal acupuncture increased during the acute toxicity test. 3. In acute toxicity test of serum biochenrical values of mice, total protein was decreased in treatment groups I, 2 and 3, albunrin was decreased in treatment groups 2 and 3 compared to the control group. GOT was increased in treatment group I and Alk. Phosphatase was increased in treatment groups 1,2 and 3 compared to the normal group(p<0.05). 4.ln subacute toxicity test, severe tissue injury was found in lung and liver. 5. In subacute toxicity test, the body weight was decreased in treatment groups I and 2 compared to the normal group and the weight of liver. lung and kidney were increased in treatment groups 1, 2 and 3 compared to the normal group.(p<0.05) 6. In subacute toxicity test, RBC, HGB and HCT were decreased in treatment groups 1 and 2 compared to the normal group. MCV was increased in treatment group1 compared to the normal group, MCH was increased in treatment groups 1 and 2 compared to the control group in complete blood count test.(p<0.05) 7. In subacute toxicity test, total protein was decreased in treatment groups 1 and 2 compared to the nonnal group, BUN was increased in treatment groups 1 and 2 compared to the nonnal group, creatinine and uric acid were decreased in treatment groups 1 and 2 compared to the normal group, glucose was increased in treatment group 2 compared to the nonnal group, triglycelide was decreased in treatment groups I and 2 compared to the normal group, total cholesterol was increased in treatment groups 1 and 2 compared to the control group. GOT was decreased in treatment group 2 compared to the normal and control group, AIk. Phosphatase was increased in treatment group 1 compared to the normal and control group.(p<0.05) 8. Median survival time was 17days in treatment group 2 for S- 180 cancer cell treated with Triglii semen Herbal acupuncture. 9. Natural killer cell activity was insignificant for S-180 cell treated with Triglii semen Herbal acupuncture.(p<0.05) 10. lnterieukin-2 productivity was decreased for S-180 cell treated with Triglii semen Herbal acupuncture compared to the normal and control group.(p<0.05) Conclusion: According to the results, we can conclude Herbal-acupuncture with Triglii semen caused toxicity, and caused no effects in S-180 cancer cell.

• Current Research on Agriculture and Life Sciences
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• v.6
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• pp.171-180
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• 1988

Parathion is widely used in agriculture, but it is highly toxic and now clear that parathion behaves like a cholinergic drug by inhibiting the enzyme cholinesterase. In order to know the effect of toxicity and cholinesterase activity in rats injected repeatedly with parathion, cholinesterase activity in plasma, whole brain and spinal cord, and the subacute toxicity after repetitive intraperitoneal injection of parathion 20 times every 3 days were investigated. The results obtained were summerized as follows ; $LD_{50}$ value of parathion given intraperitoneally to rats was 10.5mg/kg(95% confidence limits, 6.6-16.8mg/kg). In subacute toxicity test of parathion injected intraperitoneally, mortality of parathion-pretreated rats(B : 57%, C : 83%) were increased in comparison with the control(50%). Cholinesterase activities in plasma of parathion-pretreated rats(B : 0.47 U/ml, C : 0.36 U/ml, AA : 0.31 U/ml, B : 0.26 U/ml, CC : 0.17 U/ml) were significantly decreased in comparison with the control(0.58 U/ml). Cholinesterase activities in spinal cord of parathion-pretreated rats(B : 1.87 U/g, C : 1.29 U/g, AA : 1.27 U/g, BB : 0.71 U/g, CC : 0.25 U/g) were decreased in comparison with the control(2.48 U/g). Cholinesterase activities in whole brain of parathion-pretreated rats(B : 2.52 U/g, C : 1.32 U/g, AA : 2.48 U/g, BB : 1.08 U/g, CC : 0.51 U/g) were significantly inhibited in comparison with the control(4.67 U/g). However, there were no differences in the urea nitrogen and creatinine concentrations between parathion-pretreated rats and control.

• Journal of Fisheries and Marine Sciences Education
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• v.27 no.1
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• pp.41-48
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• 2015

Juvenile banded catfish(Pseudobagurus fulvidraco, mean length $10.4{\pm}0.37cm$ and mean weight $14.5{\pm}0.46g$) were exposed to several nitrite(${NO_2}^-$) concentrations for 96h at pH levels of $6.18{\pm}0.54$, $6.5{\pm}0.30$ and $7.07{\pm}0.22$. The result showed that cumulative mortalities of fish to ${NO_2}^-$ levels of 12.4, 19.8, 33.9 and 53.6 mg/L at pH levels of $6.18{\pm}0.54$ were 20, 25, 40 and 85%, respectively. At pH $6.5{\pm}0.54$, mortalities to ${NO_2}^-$ 22.4, 36.4, 45.3 and 63.2 mg/L were 25, 35, 50 and 100%, respectively. At pH $7.07{\pm}0.22$, mortalities to ${NO_2}^-$ 25.5, 45.7, 56.3 and 66.4 mg/L were 0, 55, 70 and 100%, respectively. The 96h-$LC_{50}$(median lethal concentration, $LC_{50}$) of fish to several ${NO_2}^-$ concentrations at pH levels of $6.18{\pm}0.54$, $6.5{\pm}0.30$ and $7.07{\pm}0.22$ were assessed in these experiments. 96h-$LC_{50}$ at pH levels of $6.18{\pm}0.54$, $6.5{\pm}0.30$ and $7.07{\pm}0.22$ were 32.68, 40.49 and 45.85 mg/L, respectively. It indicated that acute toxicity of ${NO_2}^-$ to juvenile banded catfish increased with low levels of pH and lengthening of exposure time to ${NO_2}^-$. In particular, smaller fish(mean weight $14.5{\pm}0.46g$) were more sensitive to ${NO_2}^-$ than larger fish(mean weight $81.7{\pm}1.42g$; not published). The 96h-$LC_{50}$ of juvenile banded catfish to ${NO_2}^-$ would be primary guideline for water quality management in the intensive culture system such as RAS and BFT.

• Korean Journal of Fisheries and Aquatic Sciences
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• v.55 no.5
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• pp.697-704
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• 2022

This study was investigated to evaluate the level of acute TAN (total ammonia nitrogen) and NO₂^--N concentrations at pH levels of 6.0, 7.0 and 8.0 for 96 h in juvenile marbled eel Anguilla marmorata (total length 209.0±22.02 mm and body weight 13.0±5.01 g). The result of the present study showed that the survival rate of juvenile eel at TAN concentrations 0, 100, 200, 300, 400, and 500 ppm at pH 6.0, pH 7.0, and pH 8.0 were 100, 100, 96.7, 74.4, 31.1, and 0%; 100, 82.2, 61.1, 36.7, 0, and 0%; and 98.9, 55.6, 8.9, 0, 0, and 0%, respectively. In addition, the survival rate of juvenile eel at NO₂^--N concentrations 0, 100, 200, 300, 400, and 500 ppm at pH 6.0, pH 7.0, and pH 8.0 were 100, 43.3, 21.7, 0, 0, and 0%; 100, 76.7, 65.0, 43.3, 21.7, and 13.3%; and 100, 100, 100, 88.3, 78.3; and 58.3% respectively. The 96h-LC₅₀ at pH 6.0, 7.0, and 8.0 were 332, 235, and 167 mg/L for TAN, and 188, 296, and 711 mg/L for NO₂^--N, respectively. The acute toxicity of TAN to juvenile eel increased exponentially with increase in pH, whereas the acute toxicity of NO₂^--N to juvenile ell increased with low levels of pH and lengthening of exposure time to NO₂^--N.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.15 no.1
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• pp.29-34
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• 2015

Citrullinemia type1 is an autosomal recessive disorder of the urea cycle characterized by neonatal or late onset of hyperammonemia caused by a deficiency of the enzyme argininosuccinate synthetase (ASS). An ASS1 deficiency demonstrates fatal clinical manifestations that are characterized by the neonatal metabolic coma and early death when untreated. It causes a broad spectrum of effects, ranging from a mild disorder to a severe mental retardation, epilepsy, neurologic deficits. An acute neonatal form is the most common. Infants are normal at birth followed by an acute illness characterized by vomiting, lethargy, seizures and coma. These medical problems are life-threatening in many cases. A later onset form is less frequent and may be milder than the neonatal form. This later-onset form is associated with severe headaches, visual dysfunction, motor dysfunction, and lack of energy. Citrullinemia type1 is caused by mutations in the ASS1 gene located on chromosome 9q34.1 that encodes argininosuccinate synthetase, the third enzyme of the urea cycle catalyzing the formation of argininosuccinic acid from citrulline and aspartic acid. The enzyme is distributed in tissues including liver and fibroblasts. This mutation leads to hyperammonemia, arginine deficiency and elevated citrulline level. In the urea cycle, argininosuccinate synthetase catalyses the conversion of citrulline and aspartate to argininosuccinate.. Here, we describe a female newborn patient with lethargy, rigidity and hyperammonemia who was diagnosed as citrullinemia type1 with a c.[421-2A>G], c.[1128-6_1188dup] mutation.

• Korean Journal of Veterinary Research
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• v.34 no.2
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• pp.361-368
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• 1994

Teratogenic and embryotoxic effects of mercury have been reported, however, there is little information about possible antidotes against mercury exposure during gestation. In order to evaluate therapeutic effects of selenium as an antidote against mercury poisoning, pregnant CD-1 mice were exposed to methylmercury chloride(20ppm) through the drinking water with treatment of sodium selenite (1.0mg, 2.0mg or 3.0mg/kg b.w., subcutaneously) or BAL(5.0mg/kg b.w., subcutaneously) under the single or combination base as the therapeutic agents from day 6 to 15 of gestation. Fetal growth parameters such as body weight and crown-rump length in the mice exposed to mercury, were reduced as was placental weight compared to those in the control. Treatment of selenium(alone, combination with BAL) reduced the harmful effects induced by mercury on the fetal growth parameters even though no specific relationship between dose and therapeutic effect. The incidence of dead fetuses/resorptions and malformed fetuses(especially cleft palate) was also increased in the mercury only treated group. Selenium treatment demonostrated reduced the incidence of abnormal fetuses under the exposure of mercury. Relative maternal organ weights(liver, kidney, spleen) were increased significantly but relative brain weight was decreased as evidenced by decreased in the mercury treated mice compared to that in the control. A subtle indication of maternal mercury toxicity evidenced by changes of relative maternal organ weights, decreased water and feed consumption were also prevented efficiently by selenium treatment. The present study suggests that methylmercuric chloride is embrytoxic and teratogenic in CD-1 mice when exposured during organogenesis and that selenium administration may have therapeutic application for the treatment of mercury poisoning although more applicable study in human should be performed with caution in the future.